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SAN FRANCISCO MEDICINE J O U R NA L O F T H E S A N F R A N C I S C O M E D I CA L S O C I E T Y

Infectious Disease Adult Vaccine Controversies Drug Resistance Update HIV at Year 30 Is There an End in Sight?

California’s Vaccine Registry Curtailing Antibiotic Overuse Nathan Wolfe on Viral Threats to Modern Humanity

VOL. 85 NO. 7 September 2012


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IN THIS ISSUE

SAN FRANCISCO MEDICINE

September 2012 Volume 85, Number 7

Infectious Disease FEATURE ARTICLES

MONTHLY COLUMNS

12 Stalking the Wild Pathogen: Nathan Wolfe on Viral Threats to Modern Humanity Steve Heilig, MPH

4

Membership Matters

6

Ask the SFMS

9

President’s Message Peter J. Curran, MD

13 15

The AIDS Epidemic at Year 30: Is There an End in Sight? Mike McCune, MD, PhD No Shot Left Behind: Increasing the Use of California’s Vaccine Registry Kaitlyn Bailey, MD, and Andrew Resignato, MS

17 Bad Bugs, from Farm to Us: Curtailing Antibiotic Overuse in Agriculture Steve Heilig, MPH; Philip R. Lee, MD; and Lester Breslow, MD 19 Infections in Hospitals: Preventive Measures in California Elaine M. Dekker, BSN, CIC, and Lisa G. Winston, MD

10 SFMS Advocacy Activities 11 Editorial Gordon Fung, MD, PhD 32 Hospital News

34 In Memoriam Nancy Thomson, MD

21 Drug Resistance: An Update on Cephalosporin Resistance in Neisseria Gonorrhoeae Mark W. Pandori, PhD, HCLD (ABB), and Susan S. Philip, MD, MPH 23 Viral Hepatitis: An Overview of Strands A through E Francis Yao, MD 25 HPV Vaccine: It’s Not Just for Girls Anymore Charles Wibbelsman, MD

27 Pertussis Prevention: All Health Care Providers Play a Role Lisa Tanisawa, MPH 29 Adult Vaccine Controversies: Pneumococcal and Varicella Vaccines Roger Paul Baxter, MD 31 No Reason Not to Test: HIV Testing Continues to Matter Stephen Follansbee, MD

Editorial and Advertising Offices: 1003 A O’Reilly Ave., San Francisco, CA 94129 Phone: (415) 561-0850 e-mail: adenz@sfms.org Web: www.sfms.org Advertising information is available by request.


MEMBERSHIP MATTERS Activities and Actions of Interest to SFMS Members

SFMS Career Fair

Membership Desktop Reference

Calling all residents, fellows, and employers! SFMS will be hosting its third annual Career Fair on October 25. The event runs from 5:00 p.m. until 8:00 p.m. and is complimentary to residents and fellows from the four San Francisco-based residency programs.  This is an excellent opportunity for physicians looking to practice in the Bay Area to network with representatives from a variety of practice types and settings, and for employers to connect with physician job seekers. As part of an effort to make participation accessible to all, we are offering a tiered pricing structure for employers, ranging from $100 to $400; solo/small-group physician member practices can exhibit free of charge. For event details or to inquire about exhibiting, contact the Membership Department at (415) 561-0850 or visit http://www.sfms.org/Events.aspx.

The 2012–2013 SFMS Membership Directory and Physician Desk Reference has been mailed out to all active physician members. The annual Directory is one of the most valued benefits of membership and is the only pictorial directory of physicians in San Francisco. This resource is complimentary to all SFMS physician members currently practicing medicine and is used throughout the year by physicians and their staff. For questions or information about the Directory, please contact Lauren Estrada at (415) 561-0850 extension 200 or lestrada@sfms.org.

Anthem Blue Cross Announces New Reimbursement Policies Changes

Anthem Blue Cross notified physicians of upcoming changes to ClaimsXten, the insurer’s reimbursement policies and claims-editing software. Most changes will go into effect on December 8, 2012, with a few exceptions that go live on January 1, 2013. Physicians may notice a difference in how certain codes and code pairs are adjudicated as a result of these changes. Updates include frequency edits on certain codes, restrictions on payment for prolonged services codes 99354 and 99355, and denial of certain screening services when billed with preventive or problem-focused evaluation and management codes. For detailed information, please visit the SFMS blog at http://bit.ly/MZlSIu. If you are a SFMS member experiencing problems with reimbursement and claims issues, please contact our toll-free member reimbursement helpline at (888) 401-5911.

Foster the Next Generation of Physicians: Volunteer Teaching Opportunities at UCSF

Make a lasting impression on future physicians by precepting a first- or second-year medical student in your practice setting. Please consider signing up for a volunteer teaching opportunity at UCSF. There’s a need for primary care and emergency medicine physician preceptors, but all San Francisco physicians are eligible to participate. Time commitment ranges from a few hours to a few weeks. Please visit http://www.sfms.org/ForPhysicians/ ProfessionalDevelopment.aspx for more information or contact Christina Cicoletti at Cicoletti@medsch.ucsf.edu. 4 5

San Francisco Medicine September 2012

San Francisco Hospital Update

Dignity Health and UCSF Medical Center have signed a memorandum of understanding to integrate operations at their San Francisco hospitals. The plan would integrate operations at UCSF’s Parnassus, Mount Zion, and Mission Bay campuses with Dignity’s Saint Francis Memorial and St. Mary’s hospitals. UCSF and Dignity officials did not unveil further details of the integration plan but said it would not involve a merger or an acquisition. UCSF and Dignity have worked on past projects, and officials said the goal of the new integrated system would be to lower costs and boost the quality of care.

SFMS Supports Bills to Reinstate Healthy Families Program

SFMS/CMA support SB 301 (DeSaulnier) and AB 826 (Swanson), which would reinstate the Medi-Cal Managed Care Organization (MCO) Tax and the Healthy Families Program. Both bills have support from Republicans and Democrats in both houses. In June, Governor Brown signed the proposal to transition all of the children currently enrolled in Healthy Families to Medi-Cal. If approved by the CMS, the move would have an enormously negative impact on the 900,000 children that rely on Healthy Families for heath care coverage. “The proposal signed in June puts the health of millions of California’s children at risk, as Medi-Cal already faces serious challenges in providing access to care for its enrollees,” said CMA President James T. Hay, MD. “SB 301 and AB 826 will ensure that California’s children have access to the care they need and deserve.” When the MCO Tax was created in 2009, it was to address persistent funding shortfalls that plagued the Healthy Families Program. Since the creation of the tax, Healthy Families has been stable and successful in providing care for the nearly 900,000 children it serves. www.sfms.org


Save the Date: CMA President’s Reception and Awards Gala CMA and the CMA Foundation invite all SFMS members to attend the 2012 President’s Reception and Awards Gala. This annual awards dinner is hosted in conjunction with the CMA’s House of Delegates meeting to honor leaders in both organizations. This event hosts more than 600 California physician leaders and key staff from both the CMA and CMAF, the national and state health care stakeholders. Please visit http://bit.ly/ KGrsbN for event details and registration.

Complimentary Webinars for SFMS Members

CMA offers a number of excellent webinars that are free to SFMS members. Members can register at www.cmanet.org/events. October 3: Protecting Your Practice from Payor Abuse • 12:15 p.m. to 1:15 p.m. October 17: Establishing Expectations for High Performance from Medical Staff • 12:15 p.m. to 1:15 p.m.

10/19 SFMS Seminar: “MBA” for Physicians and Office Managers

Gain critical business skills in the areas of strategic planning, finance, operations, marketing, and personnel management at SFMS’ popular “MBA” for Physicians and Office Managers session. Join Debra Phairas for this one-day seminar on October 19 from 9:00 a.m. to 5:00 p.m. $225 for SFMS/CMA members and their staff ($200 each for additional attendees from same office); $325 for nonmembers. Contact Posi Lyon, plyon@ sfms.org or (415) 561-0850 extension 260 for more information.

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September 2012 Volume 85, Number 7 Editor Gordon Fung, MD, PhD Managing Editor Amanda Denz, MA Copy Editor Mary VanClay

EDITORIAL BOARD Editor Gordon Fung, MD, PhD Obituarist Nancy Thomson, MD Stephen Askin, MD Erica Goode, MD, MPH Toni Brayer, MD Shieva Khayam-Bashi, MD Linda Hawes Clever, MD Arthur Lyons, MD Peter J. Curran, MD Stephen Walsh, MD Sashi Amara, MD SFMS OFFICERS President Peter J. Curran, MD President-Elect Shannon Udovic-Constant, MD Secretary Jeffrey Beane, MD Treasurer Lawrence Cheung, MD Immediate Past President George A. Fouras, MD SFMS STAFF Executive Director Mary Lou Licwinko, JD, MHSA Assistant Executive Director Steve Heilig, MPH Associate Executive Director for Membership Development Jessica Kuo, MBA Director of Administration Posi Lyon Membership Coordinator Lauren Estrada

BOARD OF DIRECTORS Term: Jan 2012-Dec 2014 Andrew F. Calman, MD Edward T. Melkun, MD Roger S. Eng, MD Kimberly Newell, MD John Maa, MD Richard A. Podolin, MD Elizabeth K. Ziemann, MD

Term: Jan 2010-Dec 2012 Gary L. Chan, MD Donald C. Kitt, MD Cynthia A. Point, MD Adam Rosenblatt, MD Lily M. Tan, MD Willim T. Prey, MD Joseph Woo, MD

Term: Jan 2011-Dec 2013 Jennifer H. Do, MD Benjamin C.K. Lau, MD Man-Kit Leung, MD Keith E. Loring, MD Terri-Diann Pickering, MD Adam Schickedanz, MD Rachel H.C. Shu, MD

CMA Trustee Robert J. Margolin, MD AMA Representatives H. Hugh Vincent, MD, Delegate Robert J. Margolin, MD, Alternate Delegate

September 2012 San Francisco Medicine

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SFMS experts answer practice-related questions

Our new Ask the SFMS column, published here and on our website, connects SFMS members with experts who answer questions on a wide variety of topics related to practicing medicine. Topics include practice management, patient education, EHR assistance, health policy, legal/malpractice issues, financial management, and more. Each month the column answers a selection of commonly asked questions from physicians. For the full archive of Q & As, or to access extensive information and additional resources relating to each topic, visit our member-only Ask the SFMS section at www.sfms.org If you would like to submit a question for our experts, email info@sfms.org.

How long do I need to keep medical records after I retire?

The Medical Board of California website confirms that there is no general law requiring a physician to maintain medical records for a specific period of time. Most physicians have heard seven years, but that pertains only to licensed medical clinics. The best answer is to check with your own medical malpractice carrier for their current recommendations. Many recommend longer time frames due to the California Statute of Limitations regarding minors and tolling the statute of limitations with alteration of records, fraud, or discovery of a foreign object after surgery many years later than the three years’ usual time limit to file a malpractice claim. Unfortunately, the physician or the physician’s estate— should a physician die—must retain the medical records for the time period the carrier recommends. The best option is to sell your practice or, if you cannot, arrange for another physi6

San Francisco Medicine September 2012

cian to become the legal custodian of records. The sale of the practice should always contain the provision that the buyer will retain the medical records for the recommended period of time and make them available to the seller, particularly in the event of a malpractice claim. Malpractice carriers typically suggest destroying a patient record three years after the patient’s death. If you do not sell the practice or arrange for a custodian of records, the retiring physician or estate will be responsible for release of information. The physician owns the medical record as his or her “work product.” The patient only has rights to copies. This physician responsibility can present a storage and copying burden after leaving practice, so the best course of action is to transfer your records to another physician with a legal document that requires the custodian to secure, maintain, and store the records, and to make them available to you if needed. Debra Phairas is the president of Practice & Liability Consultants, LLC, a firm specializing in practice management and malpractice prevention. Contact her at dphairas@practiceconsultants.net or (415) 764-4800.

Can I bill my Medi-Medi patient for the 20 percent co-pay after Medicare pays? Generally speaking, the answer is no. A physician who bills the Medicare program for services provided to a patient also eligible for benefits under the Medicaid program must do so on an assignment basis. Additionally, Section 1902(n)(3) (B) of the Social Security Act, as modified by section 4714 of the Balanced Budget Act of 1997, prohibits Medicare providers from “balance billing” Medicare beneficiaries who have www.sfms.org


secondary coverage under a state Medicaid plan. If a physician knowingly and willfully violates the law, he or she faces the possibility of exclusion for five years from all programs that receive federal funding. This means physicians could lose their ability see patients covered under Medicare, Tricare, Medi-Cal, Medicare Advantage (managed care) programs, and Federal Workers’ Compensation. In addition to exclusion, the federal government may impose civil monetary penalties. Physicians who are not currently enrolled in the Medi-Cal program may enroll as Medi-Medi-only providers.

cover your tax bill and could result in owing additional taxes and penalties when filing your return. You’ll want to involve your tax and legal advisors along with your financial advisor to implement a number of strategies to help you reduce or avoid these new taxes. Keep in mind these ideas should not be based on tax planning alone, as you will want to consider the effects on your overall investment plan as you weigh these strategies.

How will the Affordable Care Act affect me in my personal finances?

WHY I’M A MEMBER: “ The SFMS provides an open platform for physicians to discuss pertinent issues and policy affecting medical practice and offering a means to present a unified voice.”–Mark Edmunds, MD, Assistant Medical Director at the Blood Centers of the Pacific

Center for Economic Services is staffed by experts with a combined experience of more than 125 years in medical practice operations. SFMS members may access the reimbursement helpline at (888) 401-5911 or economicservices@cmanet.org

The 2010 health care reform act includes two key tax provisions that will go into effect in 2013, impacting higherincome taxpayers. The first is a 0.9% increase in Medicare tax on earned income (including self-employment income) above $200,000 for individuals or $250,000 for joint filers. The second tax is a 3.8% Medicare tax on investment income if your modified adjusted gross income (MAGI) exceeds those same thresholds. The amount your respective employer withholds may not

www.sfms.org

Boys Georgiadis Financial Strategies Group of Wells Fargo Advisors. William X. Georgiadis, CFP®, senior vice president of investments can be reached at William.georgiadis@wellsfargoadvisors.com, (415) 291-1246. Wells Fargo Advisors, LLC, member SIPC is a registered broker-dealer and separate nonbank affiliate of Wells Fargo & Company. CAR 0812-02682.

September 2012 San Francisco Medicine

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San Francisco Medicine September 2012

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PRESIDENT’S MESSAGE Peter J. Curran, MD

Burden of Proof Before this column is published, the verdict will be in for my malpractice lawsuit in San Francisco civil court. The timing of this article is not coincidental; I wanted there to be no prejudicial treatment of potential jurors or perception of personal sour grapes in the event of a negative verdict. Having lived through the experience for almost three years, I decided to share with fellow members what I’ve learned. Once you receive the notice of an actual suit (usually handdelivered by a courier while you have a waiting room full of patients) and get over the realization that opening unwanted mail takes on new meaning for the next few years, the first thing you do is call your insurance carrier to find a company representative and, more important, an attorney who will represent you. Before agreeing to work with anyone, make sure that they have actually been in a courtroom and don’t spend all their time negotiating early settlements. This needs to be regarded as a long-term relationship from day one, and, unlike in marriage, there is no honeymoon period with an attorney. Other than having a compatible and trial-worthy attorney, the next most critical period in the life of a malpractice lawsuit is selection of expert witnesses. You will need at least two in a wrongful death case to address standard of care and causation. Weighing in on the selection of witnesses should not be left solely to the discretion of the attorney, even if they have had a positive experience with a witness in a prior case. The medical knowledge of attorneys is limited to a few buzz words at best, and too much importance is placed on the resume, particularly as it relates to academic appointments and publications, and less on what really matters in front of a jury. You want somebody who comes across as knowledgeable and approachable to the lay person. Again, previous trial experience cannot be discounted. As the “discovery” period (disclosure of expert witnesses) draws to a close, usually after several months to a year or more, there will be talk of settlement. You may even hear the term “mandatory settlement conference.” I am not saying that settlement is necessarily a bad thing for the defense, but the early settlement is mostly the friend of the plaintiff’s attorney, working for a contingent fee under the constraints of MICRA (Medical Injury Compensation Reform Act) limits on noneconomic damages. Either you stay in or you get out, but do not settle before you hear the testimony of all disclosed witnesses in deposition. When the trial date approaches and there are no more continuances (delays) due to requests of either side or court scheduling conflicts, plan on two to three weeks away from the office. Your insurance carrier should help cover costs while you are focused on your defense. Regardless of what your atwww.sfms.org

torney suggests, approach the trial weeks as final board exam preparation: Do your homework by rereading pertinent medical records and deposition transcripts, sitting in on all the various phases of courtroom and judge assignment, motions, jury selection, and then crunch time. Also plan on after- hours’ time prepping with your attorney. You cannot just show up at opening statements and think that you will know the idiosyncrasies of the opposing lawyer or the pace of the judge. Your own attorney will appreciate your input at the end of the day. Finally, and most important, never underestimate the importance of MICRA. Other than your own performance in the trial process, there is no greater deterrent to malpractice lawsuits than MICRA’s cap on pain and suffering damages. Despite the statistics that report that nearly half of all physicians, and three-quarters of all specialists, are involved in a medical malpractice case during their careers, you often feel alone going through the ordeal. It is never fun being on display for a less-than-desired outcome. I hope my experience and observations will prove helpful to the next physician involved in a malpractice lawsuit. Dr. Peter Curran is a cardiologist at Breall & Associates and is director of Cardiovascular Rehabilitation at St. Mary’s Medical Center.

September 2012 San Francisco Medicine

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SFMS Advocacy Activities A PROFESSIONAL VOICE FOR COMMUNITY HEALTH SINCE 1868 The San Francisco Medical Society (SFMS) has been involved in community health issues since the 1868. As the only medical association in San Francisco representing the full range of medical specialties and interests, SFMS health advocacy has been broad. Via policy-making efforts with state and national medical and political leaders and an award-winning journal, SFMS has often been influential far beyond the city. The SFMS agenda and activities continue to focus on the community and the following areas of involvement: • Forming HealthShare Bay Area (see below) to improve patient care and reduce costs • Working with the physician community to promote the adoption of electronic health records to better serve patients • Advocating against cuts to Medi-Cal and Medicare reimbursement to provide continued access to care for all San Franciscans • Preserving the health care safety net and public health programs in times of severe budget cuts • Supporting antitobacco legislation and San Francisco’s law banning the sale of tobacco in pharmacies, and smoking in restaurants and other businesses, and eliminating tax credits for films showing smoking • Supporting the Healthy San Francisco program and participating in legal defenses to preserve the program, while helping to monitor the program’s progress • Providing physicians for medical consultation for San Francisco schools and for volunteer care at community clinics • Working on legislation to allow minors, without parental consent, to receive vaccines to prevent STIs; to prevent bans on medical procedures such as circumcision; and more • Cosponsorship of the Hep B Free program in San Francisco • Advocacy for improving end-of-life care in the Bay Area via new policies, use of new advance directives (such as POLST), and educational outreach to physicians and patients  

HOW SFMS SERVES THE COMMUNITY

HEALTHSHARE BAY AREA Working under the auspices of

the SFMS Community Service Foundation and guided by a diverse board of San Francisco and Bay Area health care industry professionals, the SFMS worked to develop HealthShare Bay Area to provide the infrastructure for a unified electronic health record system. The project originally targeted San Francisco but now includes partners from the East Bay. This service allows providers to have access to secure community-wide patient data. It also permits patients to gain a complete view of their medical records, irrespective of where individual records may reside. HSBA will launch in 2012.

UNIVERSAL ACCESS TO CARE SFMS leaders have long advocated that every San Franciscan should have access to quality medical care. Recent SFMS participation in this effort has included the Mayor’s Health Care Reform Task Force, the San Francisco Health Care Services Master Plan Task Force, and the Mayoral Task Force, which designed the Healthy San Francisco program. SFMS also joined in the lawsuits to preserve that program. SFMS has advo10 San 11 SanFrancisco FranciscoMedicine Medicine September September2012 2012

cated for community clinics since the founding of the original HaightAshbury Free Clinics in the 1960s.

MEDICAL LIABILITY PROTECTION The CMA and SFMS were

instrumental in passing MICRA, which saves virtually every doctor many thousands of dollars in liability premiums annually and saves hospitals and health systems much more. We have successfully defeated repeated attacks on MICRA by trial lawyers through the years.

REBUILDING/PRESERVING SAN FRANCISCO GENERAL HOSPITAL SFMS spokespersons took a lead in advocating for full

funding of the seismic rebuild and in advising, as members of the Mayoral committee, where and how that would occur.

HIV PREVENTION AND TREATMENT The SFMS was at the center of medical advocacy for solid responses to the AIDS epidemic, being among the first to push for legalized syringe exchange programs, adequate funding, and more.

SCHOOL AND TEEN HEALTH SFMS helped establish and staff a citywide school health education and condom program, removed questionable drug education efforts from high schools, worked on improving school nutritional standards, and provides medical consultation to the SFUSD school health service.

ENVIRONMENTAL HEALTH SFMS established a nationwide educational network on scientific approaches to environmental factors in human health; has advocated on reducing mercury, lead, and air pollution exposures; and much more. REPRODUCTIVE HEALTH AND RIGHTS SFMS has been a state and national advocate for reproductive health and choice.

BLOOD SUPPLY SFMS has long been a partner of the Blood Centers of the Pacific and seeks to help increase donations.

ORGAN DONATION SFMS has been a leader in seeking improved

donation of organs to decrease waiting lists, via education and new polices regarding consent and incentives for organ donation.

OPERATION ACCESS SFMS is a founding sponsor of this local organization providing free surgical services to the uninsured and has provided office space, volunteers, and funds. DRUG POLICY SFMS has been a leader in exploring and advocat-

ing new and sound approaches to treating drug abuse, including some of the first policies regarding syringe exchange, medical cannabis, and treatment instead of incarceration.

MEDICAL ETHICS SFMS has developed and promulgated for-

ward-looking policies and approaches regarding end-of-life care, patient directives, physician-assisted dying, and other topics of interest to patients, physicians, policy makers, and the general public. www.sfms.org


EDITORIAL Gordon Fung, MD, PhD

Infectious Disease The specialty of infectious disease is the focus of this month’s issue—certainly not the entire field of infectious diseases, but some of the hot topics facing today’s clinicians. Like all subspecialties in internal medicine (and pediatrics), a basic understanding of the principles of infection, along with diagnosis and management, has been considered part of the core knowledge of every physician, from surgeon to general practitioner. The first step in beginning to think about infections is that the disease has to obey Koch’s postulates. What are they? From the Canadian Phytopathological Society (http://phytopath.ca/education/kochpostulates.html): Three rules for experimental proof of the pathogenicity of an organism were presented in 1883 by the German bacteriologist Robert Koch; a fourth was appended by E. F. Smith (1905). Briefly, these rules state: (1) The suspected causal organism must be constantly associated with the disease. (2) The suspected causal organism must be isolated from an infected plant and grown in pure culture. (3) When a healthy susceptible host is inoculated with the pathogen from pure culture, symptoms of the original disease must develop. (4) The same pathogen must be reisolated from plants infected under experimental conditions. Historically, once the diagnosis was made and the organism that met these criteria was identified, then treatment was dependent on having the correct antibiotics that could, ideally, kill the organism as the patient recovered from the damage caused by the infecting agent. At times surgery was needed to remove dead or damaged tissue to allow the healthy tissue to regenerate or repair the damage. The challenges, then, were making the diagnosis and having a drug that could do the job. For the most part, there were two types of antibiotics: those that actually killed the organisms, and those that just stopped the growth and multiplication of the bacteria or infection. For the most part, viruses did not have effective treatments and usually only caused short-term illnesses, like colds and flus. But there was a host of other infections, such as parasites, fungi, and amoeba. Not only that, but infections could spread by contact and via vectors including insects, dirty water, rodents, contaminated food, and dust particles. Prior to the specialty of ID, most infections were treated by primary doctors—family and general practice physicians and pediatricians, or public health physicians who monitored all the infections, especially contagious ones in the community. Before the era of antibiotics, the concept of prevention was the best management strategy, rather than allowing the infection to happen and then try to treat it. This was the origin of sterile technique in the operating room, including hand washing before and after seeing each patient in the hospital or in the clinic. Some of the major successes in ID have been the eradication of diseases such as smallpox and rheumatic fever. These successwww.sfms.org

es required the development of successful vaccines and public health approaches to vaccinate whole populations (as in the case of polio) and developing rapid response systems to identify and source epidemic outbreaks and control the spread locally and internationally (as with SARS). As the bacteria and infecting agents got smarter and mutated or gained resistances, the development of many different kinds of antibiotics followed. A critical mass of knowledge grew, sufficient to form a specialty to address the world of infectious diseases. One of the major challenges in this specialty is the management of viral infections in a patient when there is no real cure but, as with a chronic disease state, the infection can be controlled with constant monitoring. This is addressed here in articles by Mike McCune and Francis Yao. Another major issue in ID is the need for testing of occult diseases that have a long phase of growth (incubation), remaining asymptomatic in the host until the disease is full-blown. Steve Follansbee discusses this issue with regard to HIV testing. A long-standing question for ID and the public health community has been the issue of vaccinations for target populations or the public at large. Charles Wibbelsman discusses vaccinations for the HPV vaccine for boys and girls. Roger Baxter presents the current controversies concerning pneumococcal and varicella vaccines for adults. Lisa Tanisawa writes about pertussis prevention. Kaitlyn Bailey and Andrew Resignato present the use of vaccine registries. A problem that the San Francisco Medical Society has been a leader in bringing to the CMA and AMA has been antibiotic overuse in agriculture. Philip Lee, Lester Breslow, and Steve Heilig give the latest update on where we are with this issue. As a medical center-based physician, I am particularly interested in the topics of hospital infections and drug resistance. These two topics are updated by Elaine Dekker, Lisa Winston, Mark Pandori, and Susan Philip, respectively. Finally, Steve Heilig records an excellent interview with virologist Nathan Wolfe on viral threats to modern humanity in a piece entitled “Stalking the Wild Pathogen.” September 2012 San Francisco Medicine

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Infectious Disease

Stalking the wild pathogen Nathan Wolfe on Viral Threats to Modern Humanity Steve Heilig, MPH In our ongoing battle to stay at least one step ahead of the many infective pathogens bedeviling humankind, our species has benefitted much from “dumb

luck,” says Nathan Wolfe, author of the recent book The Viral Storm: The Dawn of a New Pandemic Age. He warns that “microbial threats will grow in coming years in their ability to plague us, kill people, destroy regional economies, and threaten humanity in ways more severe than the worst imaginable volcanoes, hurricanes, or earthquakes.”  This is no mere speculation. Note that, as the New York Times just observed in an article about a new influenza strain spreading from birds to seals, “Four times in the past century, a new strain of flu has emerged that can spread quickly in humans. One of those strains, which emerged in 1918, killed an estimated 50 million people.” In the past few weeks, there has been an outbreak of ebola virus in central Africa, a cluster of a new flu infection linked to contact with pigs in some American states—and then there’s malaria, H1N1, SARS, HIV, BSE, anthrax, and uncountable others, for, as Wolfe admits, “We know very little about what’s out there.”  Wolfe is a Stanford human biology professor whose academic and professional pedigree includes Harvard, Oxford, Johns Hopkins, the CDC, field research around the globe, a Fulbright, Science, Nature, Scientific American, The Economist, and much more. He is founder and CEO of Metabiota, a forprofit company that specializes in microbiological research, products, and services; and founder and chairman of Global Viral, a nonprofit that promotes understanding, exploration, and stewardship of the microbial world.   SFMS: Your book is both scary and optimistic. To start, please distill your message about the current risk of serious pandemics.   Wolfe: We live in this moment in history when the level of interconnectivity between human and animal populations is certainly higher than it’s ever been, and when we can move from one country to another in the course of hours, with high population density of both humans and animals in many areas. So we’ve created an environment that can be 12 13

San Francisco Medicine September 2012

thought of as a viral mixing vessel worldwide, and any agent that is in animals has the potential to enter humans and go global. And the vast majority of important pandemics of the past emerged from animal populations. So today something that emerges anywhere in the world has the potential to quickly impact us anywhere else.

As we speak, the international HIV conference is occurring in Washington. What has HIV taught us about emerging pathogens?  HIV is a good model in the sense that it is a chimpanzee virus that crossed to humans in Central Africa and then spread around the world in a dramatic way, so even though it existed for many decades in Africa, the first place we detected it was in places like Los Angeles and New York. It demonstrated how a spillover of a single agent into humans could be launched globally. And although it continues to be devastating, it could have been much worse, given the way that HIV transmission rates compare to, say, HPV. That has a much higher capacity for transmission and infects, on average, 25 to 35 percent of sexually active adults. So had HIV been a little bit more transmissible, we could have hundreds of millions of infected individuals instead of tens of millions.   You write of the kinds of “threats that keep you awake at night.” What might those be?  Yes, there are a couple of categories, such as a virus with a long latency between transmission and the appearance of symptoms—again, like HIV, but with higher transmission, such as via air. The other might be viruses that are distinct from what we’ve seen in the past so that none of our techniques identify them. And although we have a general sense that we now really know most of what forms of life exist on our planet, that is definitely not the case with respect to viruses or microorganisms in general, where most of such life remains relatively unknown.    In terms of doing something about these risks, you refer to the “Holy Grail of public health” being some new prevention measures.  If we again think of this moment in history with respect to how we interact with animals and how we transport both animals and humans, posing unprecedented risk, it also presents some interventions. We now have new techniques for surveillance and communications—cell phones, novel sequencing technologies that allow us to identify unknown agents without having to culture them, and so forth. I should say that I lead two organizations in this respect: Metabiota,

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Infectious Disease

The aids epidemic at year 30 Is There an End in Sight?

When the International AIDS Conference was last held on U.S. soil more than twenty years ago, an

optimistic view might have foreseen the focus of the most recent conference on prevention, diagnosis, and treatment of HIV disease and AIDS (see Havlir and Beyrer, NEJM, July 18, 2012). It would have been totally surprising, however, to look forward then and find that we would also now be talking about a “cure” for HIV. The pressing need for and path toward a “cure” have been made more palpable by a number of conceptual, scientific, and practical advances over the intervening years. First, although it is clear that illness can be prevented or reversed by early diagnosis and treatment with antiretroviral therapy (ART), it will be difficult to provide such treatment to all in need. Even with the funds provided by the President’s Emergency Plan for AIDS Relief and other similar programs, more people are being newly infected than newly treated; it is also not clear whether and for how much longer the treatment programs can be sustained. Second, even if we assume that all of those who need treatment can receive it and continue to take it indefinitely, it is also now more evident that good health is not always obtained with the use of “effective” ART (i.e., by reducing the circulating virus to undetectable levels). It is estimated, by example, that those on such treatment regimens live ten years less than do age-matched, uninfected controls and that they are often suffer from a higher frequency of non-HIV diseases (e.g., atherosclerosis, cancer, dementia) before they die. It is conjectured that these problems arise in part because of previous damage caused by the virus, because of the presence of persistent virus even in the presence of “effective” ART, and possibly even because of the adverse effects of chronically administered ART. Third, the science of HIV disease has moved forward at an astonishing pace. We now know much more about how the virus might be able to persist in the tissues of treated hosts; this knowledge, in turns, prompts hypotheses about ways in which such persistence can be curtailed. Finally, and not less compellingly, an adult with HIV disease (the “Berlin patient”) has been effectively “cured” of his HIV disease upon provision of CCR5-negative bone marrow transplants and has been off ART for the past five years. This case, juxtaposed with earlier reports of viral clearance in newborns, raises the hope that a cure may also be achievable in others. Given such hope and the indefatigable efforts of the late Martin Delaney (the founder of San Francisco’s Project Inform), the National Institutes of Health has recently estabwww.sfms.org

Mike McCune, MD, PhD

lished the Martin Delaney Collaboratory to understand how such cures might be extended to more HIVinfected individuals (see http:// www.nih.gov/news/health/ jul2011/niaid-11.htm). These multidisciplinary efforts have engaged labs around the world to address the following questions: might the example of the “Berlin patient” be replicated using currently available tools of gene therapy, modifying hematopoietic stem cells so that they and their progeny are resistant to HIV? Is it possible to eliminate long-lived cells that harbor latent HIV genomes? And might the persistence of HIV be due to continued replication and spread in tissues and, if so, how might this process be stopped? The Collaboratory hopes to answer these questions within the very short timeline of four to five years. At that point, there will hopefully be a prioritized list of potential “cure” interventions that might be carried, alone or in combination, into more definitive and extensive analyses in HIV-infected individuals. The ultimate goal would be to manage HIV disease in the same way that many cancers are now handled: Diagnose early, treat aggressively with ART to reduce the virus load, provide one or more “cure” interventions for a period of time to remove most if not all persistent virus, and then stop therapy altogether. The effectiveness of a given “cure” regimen would then be assessed by measuring the duration of virus-free survival. For this goal to be achieved, there needs to be a heightened level of awareness, especially among potential donors around the world, that the AIDS epidemic has not gone away and that additional resources will be required to eradicate it. The science must move forward with wise strategies, effective collaboration, and—not least—good luck. We must find “cure” interventions (as well as ART regimens) that can be made readily accessible to all in need, wherever they may be. No less important, it will be necessary to summon the financial means and the societal will to bring these interventions to all. Although these are all formidable problems, it is perhaps

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The AIDS Epidemic at Year 30 Continued from previous page . . . the last that is the most vexing: How, in the setting of a forprofit business economy, does one distribute curative regimens to millions around the world (including in the States) who cannot afford to pay for them and/or who are not part of a health care system in which the regimens can be provided? The enormity of the epidemic has galvanized many to work feverishly to improve the lot of those affected by HIV. In so doing, there have been many collateral benefits for those with other diseases. Perhaps if we can answer this question for curative regimens against HIV, we can do so in the setting of other chronic diseases that afflict many around the world as well. Mike McCune, MD, PhD, is a professor of medicine and chief of the Division of Experimental Medicine at the University of California, San Francisco (UCSF). He has worked as an HIV care provider since 1982, first as a medical resident and then (since 1986) as a staff member at the SFGH AIDS Clinic (Ward 86). His research led to the formation of two biotechnology companies (SyStemix and Progenesis) aimed at developing hematopoietic stem cell-based therapies, including gene therapy for HIV disease, and he currently helps lead the UCSF-based DARE Collaboratory aimed at eradicating HIV. In 2006, he was the founding PI of the UCSF Clinical and Translational Science Institute.

Stalking the Wild Pathogen Continued from page 12 . . . a for-profit group devoted to creating new surveillance systems for governments and corporations around the world; and Global Viral, a nonprofit that develops leaders and exploration of the microbial world. Both are devoted to exploring risks and opportunities with respect to microbial threats and working with universities, governments, and businesses to improve that.   How would crowdsourcing, using cell phones and digital surveillance, work?  There is some fascinating work done in this area, such as a demonstration project called Flu Trends, conducted by folks at Google—the hypothesis being that when people feel ill, they often search their symptoms online. Flu Trends aggregated a massive amount of search data and showed they could monitor influenza via search patterns in a way that was as accurate, and faster, than the CDC’s reported measurements. The question for groups like ours is how many new such approaches there will be—new, inexpensive diagnostics at point of care and so on.   Those are the things that lead to your more optimistic notes.   Yes. Certainly there will be major epidemics that harm the human population. But I also think that if we continue to invest in the next generation of surveillance tactics, we have the potential to get ahead of some of the pandemics that wouldn’t have been identified until much later.   Beyond that technological optimism, do you think lead14 15

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ers and political and financial constraints will continue to hinder such progress? Public health programs are being cut around the world, and some politicians want to cut things even more drastically.   There definitely are challenges. NIH, for example, has had budget cuts, but on the other hand some newer organizations have emerged. There are wonderful foundations like Skoll Global Threats Fund and others who support this kind of work, and a recognition in both public and private sectors about emerging infectious diseases. There are huge numbers of scientists, including young ones, involved in this. That said, yes, it would be terrible to cut basic safety mechanisms even though times are tough. There are things we need to stay on top of no matter what, as the risks are just going to get more intense, not less.   Prevention has long been shortchanged.   Right, but if you look back a few decades at things like cancer or heart disease, there are much more robust communities of scientists and organizations focusing on prevention than before. The real challenge is to move that forward on the population level for pandemic prediction and prevention— the techniques are coming online, and what we really do need now is a sort of “global immune system” in this dramatically more linked-in world.   In your book, you envision a sort of idealized “global control room” monitoring the planet for threats with what you call “digital epidemiology.” Is that a real possibility?   This is the exciting part, where we see everything we know and can do being linked in to monitor and respond with tracking, diagnostics, and treatment interventions, all much faster than now. This might be run by governments, independent organizations, or a combination, and be decentralized or not, but we have a sense there will be an inevitable change and improvement in how we respond to and prevent the threats.   What did you think of the big epidemiological Hollywood film of last year, Contagion?  It was done by an incredibly smart group that pulled in a large group of experts to make sure it was accurate scientifically—I played a small role as one of the technical advisors. And they reached many, many people. I think it helped to remind people, in a way that would be entertaining, that you have a risk of contagious diseases that hasn’t disappeared at all. It’s an example of how to deal in a contemporary way with difficult, complex problems, not necessarily through oldfashioned approaches—and perhaps to help ensure that the public understands the need for systems to protect us from such disasters.   You seem to be always on the go. Do you still enjoy the fieldwork and hassles of travel?  Yes, very much. It’s about the people—being able to interact with people around the world who are trying to get together to do something useful and important. That makes it all worthwhile. www.sfms.org


Infectious Disease

no shot left behind Increasing the Use of California’s Vaccine Registry Kaitlyn Bailey, MD, and Andrew Resignato, MS More than 2 million children in the United States lack the immunizations recommended to protect them

against infectious diseases that cause serious illness and death.1 This problem extends throughout California, and San Francisco ranks 35 out of 58 California counties in its pediatric immunization coverage.2 Low immunization rates are largely attributable to mobile pediatric populations and the challenges providers face in obtaining vaccination records for these patients. Immunization information systems (IIS) allow efficient transfer of vaccine information between providers, facilitating timely immunization and reducing administrative costs. For these reasons, increased use of the California Immunization Registry would greatly benefit health care providers both in San Francisco and throughout the state of California.

Benefits of Immunization Information Systems

Immunization information systems, also known as immunization registries, are secure electronic databases designed to store and facilitate access to vaccination records. Health care providers, WIC offices, child care centers, school systems, and foster care agencies can access immunization registries after signing a confidentiality agreement and receiving training. Use of an IIS is cost-free and requires only Internet access. In addition to storing immunization records, many registries are capable of other helpful functions, such as providing vaccination reminders, tracking allergies and adverse reactions, expediting inventory processes, and alerting providers of recalls. Immunization registries promote timely childhood immunization and reduce medical errors.3,4 They achieve cost savings by decreasing unnecessary vaccinations and increasing administrative efficiency.5 Given the numerous benefits of immunization registries, their use is supported by the CDC, the American Academy of Pediatrics, and the U.S. Department of Health and Human Services.

Use of the California Immunization Registry

At present, nearly all U.S. states have some form of electronic immunization registry. Registry participation is defined as the proportion of the pediatric population with at least two immunizations entered into the registry. Although there is significant variance in registry participation, the majority of state registries have at least 80 percent enrollment.6 The California Immunization Registry (CAIR) ranks 43 out of 50 states in registry participation, with only half of resident children having two immunizations entered into CAIR.6 These low rates are due to poor provider participation.6 www.sfms.org

With the current poor and inconsistent usage of CAIR, it cannot be trusted by medical providers as an accurate and complete immunization record. There are two key reasons for the poor provider usage of CAIR. First, the software currently used by CAIR is unable to perform all functions critical to an efficient immunization registry. The software also fails to meet requirements for HL7 meaningful use. The California Department of Health is working to solve this issue by rolling out CAIR 2.0, a new HL7-compliant version of the CAIR software that will satisfy meaningful use criteria. Although some funding for CAIR 2.0 has been secured from the federal government, the state of California’s funding commitment is low. Without this support, it will be difficult to improve our statewide immunization infrastructure. The second challenge faced by CAIR is an issue of incentive. Whereas all providers (and patients) would benefit from a complete registry, it is in the best interest of each individual provider to access the system as needed without having to expend effort uploading his or her own records. Therefore, no provider has an incentive to upload to the registry. This conundrum is a classic collective action failure—a public policy term describing situations wherein society benefits from a specific action but no individual party has an incentive to participate. One common example of a collection action failure is pollution regulation. Every member of society benefits from breathing cleaner air; however, no individual person or company has an incentive to invest in technological changes to reduce emissions. Emissions laws mandate societal action, providing benefit to the global community and solving the collective action failure.

Argument for Mandated Reporting to the California Immunization Registry

Similar to other collective action failures, an effective way to increase use of CAIR would be the enactment of a legislative mandate requiring health care professionals to upload their immunization records. This strategy was successful in Arizona, a state that shares the immunization challenges of a mobile pediatric population. As a result of the frustration of Arizona’s medical providers in obtaining timely and complete immunization records for their patients, the Arizona Medical Association lobbied the state legislature for an IIS reporting mandate. The regulation, enacted in 1998, resulted in drastic increases in the immunization registry use.4 Simultaneously, toddler immunization rates increased from 62 percent premandate to 77 percent in 2003.7 Secondary benefits of the mandate included improved school atten-

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No Shot Left Behind Continued from previous page . . .

dance and decreased absenteeism of parents from work.4 The Nevada mandate is another success story. In 2008, Nevada had poor enrollment in its immunization registry, with only 43 percent participation.6 In 2009, a legal mandate was passed to require provider reporting of immunizations to the registry. With the passage of this law, enrollment has increased to 85 oercent in two years.8 With increased registry use, Nevada pediatricians will have easy access to reliable immunization records, and rates of timely immunization are likely to improve. Legal mandates are not limited to these two U.S. states. They exist in fifteen of the thirty-one states with governmentsanctioned vaccine registries, including such populous states as New York and Texas.9 Mean registry participation rates approximate 88 percent in these states. With the exception of Maryland (whose mandate is limited to public providers), all of these states have higher rates of registry participation than California’s.6 These high levels of reporting and enrollment have been achieved with no use of sanctions levied on health care providers.10

Call to Action

Immunization registries are one of few health care interventions that simultaneously decrease costs and improve patient care. In order to improve their usage, San Francisco health care providers and public health officials should discuss methods to improve registry use, including lobbying the state government for funding to support software improvements. Given that immunization registries are most likely to be effective when government legislation mandates vaccination reporting, providers both in San Francisco and throughout the state of California should discuss the potential benefits and implications of such a policy. On the local level, a policy supported by the San Francisco Department of Public Health or a municipal legislative mandate may be a good first step. The time is right for health care providers to revisit our systems for immunizing children and thereby protecting them from serious infectious diseases. San Francisco physicians should consider lobbying government officials for CAIR funding and promoting a mandated electronic immunization registry wherein no shot is left behind. Kaitlyn Bailey, MD, is a pediatrics resident in the UCSF Pediatric Leadership for the Underserved (PLUS) program. Her passion is to improve access to health care services for all children. As a medical student at the University of North Carolina, she designed a research and community service project to improve the health of Mexican immigrant women. She also volunteered extensively and held leadership roles at her medical school’s community clinic, at a domestic violence shelter, and internationally in Peru and Mexico. Bailey is currently working to improve childhood immunization rates and to address the needs of local children with developmental delays. Andrew J. Resignato, MS, was born in Brooklyn, NYC. He received a bachelor’s degree in business management from Stock16 17

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ton College of New Jersey and a master’s in economics from Florida State University. Resignato has worked in the public health field for more than nineteen years. He has been the director of the San Francisco Immunization Coalition since November 2002. He also has experience as a college instructor, economist, reporter, caseworker, filmmaker, public information representative, music performer, and producer. He presents regularly across the country on immunization and vaccine-preventable diseases.

References 1. Smith PJ, Chu SY, Barker LE. Children who have received no vaccines: Who are they and where do they live? Pediatrics. 2004; 114(1):187-195. 2. Kidsdata.org. Immunizations: Kindergarteners with all required immunizations. http://www.kidsdata.org/data/topic/ table/immunizations-kindergarteners.aspx. 2010; cited 2012 July 3. 3. Every Child by Two. About registries (immunization information systems). http://www.ecbt.org/registries. 2012; cited 2012 Feb 20. 4. American Immunization Registry Association. How immunization registries can make a difference: Advocacy at your state and local level. http://www.immregistries.org/pubs/. Cited 2012 Feb 20. 5. National Vaccine Advisory Committee. Development of community- and state-based immunization registries. http:// www.hhs.gov/nvpo/report071100.pdf. 1999 Jan 12; cited 2012 Feb 20. 6. Centers for Disease Control and Prevention. IISAR data participation rates table. National Center for Immunization and Respiratory Diseases. www.cdc.gov/vaccines/programs/ iis/rates/data-rates.htm. 2010 Dec 7; cited 2012 Feb 20. 7. Morrison Institute for Public Policy. Arizona indicators: Immunization rates. http://arizonaindicators.org/health/ immunization-rates. Cited 2012 Feb 21. 8. Nevada Department of Health and Human Services, Nevada State Health Division. Nevada WebIZ—Our statewide immunization information system. http://health.nv.gov/Immunization_WebIZ_Info.htm 2006; updated 2012 Feb 20; cited 2012 Feb 20. 9. Centers for Disease Control and Prevention. Survey of state immunization information system legislation. National Center of Immunization and Respiratory Diseases. http:// www.cdc.gov/vaccines/programs/iis/privacy/legsurv.htm. 2010 June 17; reviewed 2011 Feb 9; cited 2012 Feb 20. 10. Horlick GA, Beeler SF, Linkins RW. A review of state legislation related to immunization registries. Am J Prev Med. 2001; 20(3):208-213.

www.sfms.org


Infectious Disease

Bad Bugs, From Farm to Us Curtailing Antibiotic Overuse in Agriculture Steve Heilig, MPH; Philip R. Lee, MD; and Lester Breslow, MD Editor’s Note: With ever-increasing microbial resistance to our ever-challenged arsenal of antibiotics, clearly we need to do everything possible to stay ahead in the Darwinian race between bacterial pathogens and humanity. One intervention, increasingly indicated by research and supported by many reputable health organizations, is to decrease the massive prophylactic and growth-promoting use of antibiotics in the production of food, primarily meat. Ten years ago, the SFMS brought policy to the CMA and then to the AMA urging more careful and curtailed use of antibiotics in food production. We also hosted a daylong invitational conference on this topic, cochaired by two living legends of public health, Phil Lee, MD (a longtime SFMS member, UCSF chancellor emeritus, Stanford medical professor and former United States Assistant Secretary of Health), and Lester Breslow, MD (dean emeritus of the UCLA School of Public Health, former California state health director, and past-president of the American Public Health Association), along with then-SFMS President George Susens, MD. This meeting resulted in a new network of advocates working to preserve antibiotics, as well as an editorial in the Western Journal of Medicine (then edited by SFMS member Linda Clever, MD). This piece, reprinted below, has become one of the most-cited articles on this topic, no doubt due to the stature of Lee and Breslow. Breslow died in April of this year at age 97, prompting extensive tributes, from the New York Times to many professional forums. Breslow said he saw himself as “a political activist for disadvantaged people”— which, with respect to microbes, could include anybody. This reprint is offered as one more thanks—and, sadly, it remains all too relevant. *****

Antibiotics are arguably the single most important and widely used medical intervention of our era. Almost every medical specialty uses antibiotic therapy at some point. These drugs have prevented incalculable suffering and death and are perhaps still the closest medications we have to a “magic bullet.” Of course, bad bugs can bite back, and bacterial adaptation and resistance were reported soon after antibiotics were first used. The struggle to stay one step ahead of pathogens has been widely described and debated. Correcting the overuse of antibiotics in human medicine has gradually become a priority, with slow but heartening progress being gained in this Darwinian race. Still, the rise of multidrug resistance and the ready transfer of resistant traits among pathogens require www.sfms.org

heightened action if we are to prevent increasing outbreaks of infections that become more difficult, or even impossible, to treat. One essential course of action is to minimize any and all causes and reservoirs of antibiotic resistance. Besides medical use in humans, there is the troubling issue of use in agriculture, specifically in livestock production. Antibiotics have long been routinely used not only for the treatment of infections but also as a means of getting animals to market faster by growth promotion. Controversies about these practices have resulted in numerous reports, dating back decades, urging more caution or outright bans on the practice. The World Health Organization and other leading medical and public health bodies have advised that animals not be dosed with antibiotics used in humans—to little avail here in the United States to date, even though our own Food and Drug Administration took this position as far back as 1972.1 Still, many longtime observers of the issue were surprised—or even shocked—to learn the true extent of antibiotic use on farms; estimates are that upward of 70 percent of all antibiotics manufactured are used in agricultural settings.2  Although the exact percentages are uncertain, agricultural antibiotic use is apparently more substantial than previously thought. And the type of use is worrisome because it involves continual, subtherapeutic doses that would seem to provide ideal environments for the selection of resistant pathogens. The introduction of new molecular epidemiologic tools has heightened the worry because these tools have been used to show that resistant bacteria originating on farms are finding their way into humans.3-10 The extent of this epidemiologic “spillover” to date is uncertain—assertions of the extent of bacterial resistance arising from farms vary widely—and this needs to be a higher research priority. But there is no question that the phenomenon does exist. Recognizing this risk, the American Medical Association’s House of Delegates adopted a policy that “nontherapeutic use of antimicrobials in animals that are also used in humans should be terminated or phased out based on scientifically sound risk assessments.”11  Reaction from the pharmaceutical industry, in the guise of a trade association of manufacturers of animal drugs, was swift. The Animal Health Institute erroneously claimed “The assertion that there is increasing evidence that resistance developed in animals is spreading to humans is not true,” and it went on to oppose any further restriction on agricultural use.12 As a case study of such profit-motivated opposition,

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Infectious Disease

Infections in Hospitals Preventive Measures in California Elaine M. Dekker, BSN, CIC, and Lisa G. Winston, MD Infection prevention and control programs emerged in the United States in the early 1970s. However, over the last decade, efforts to prevent health careassociated infections have developed a much higher profile, gaining the attention of the public and the executive staffs of health care organizations. For many years, the individuals in charge of these programs worked largely in single-person departments and requested assistance from their organizations’ leaders in putting together strong programs to keep patients, employees, and visitors safe. With new federal guidelines and state legislation, the scope of infection-prevention activities is now much broader. For acute care settings, the State of California has enacted three separate laws that specifically address health careassociated infections: Hospital Infectious Disease Control Program (SB 739, 2006), Patient Safety and Infection Control (SB 158, 2008), and Nile’s Law (SB 1058, 2008). Each of these laws details specific components that must be included in the infection prevention and control programs, though there are some areas of overlap. As a result of state laws, additional state regulatory oversight, and Joint Commission mandates, many of the activities of hospital infection control and prevention programs are now prescribed. While these components are generally in accordance with Centers for Disease Control and Prevention (CDC) and the national Association for Professionals in Infection Control and Epidemiology (APIC) guidelines, facilities have less flexibility to make judgments based on their own risk-assessment processes. Senate Bill 739 defines what must be included in the infection control program. It establishes the requirement for a triannual written report that must include certain data elements, with annual updates and revisions as necessary. It emphasizes prevention measures for central-line-associated bloodstream infection, ventilator-associated pneumonia, and surgical site infections. It also requires the public reporting of certain measures, e.g., central-line insertion practices. This law sets minimum standards for addressing influenza prevention measures, which include respiratory hygiene programs, isolation of influenza patients, and no-cost influenza immunization for employees. The legislation additionally mandates antimicrobial stewardship programs that are jointly monitored by quality improvement and other appropriate committees. SB 158 compels the establishment of a formal patient safety program, including a specific patient safety plan, a committee to oversee it, and a process that allows staff to report patient safety concerns without fear of retribution. Prevention of health care-associated infections (HAI) is noted to be www.sfms.org

one of the key components of the patient safety program, and a facility-wide hand hygiene program must be implemented. It also lists educational requirements for the physician in charge of the infection control program, all clinical staff, and environmental services personnel on an initial and annual basis. SB 1058 restates some of the above components and then targets methicillin-resistant Staphylococcus aureus (MRSA) as an organism of special concern. It establishes a mandatory MRSA screening process for patients readmitted to the hospital, patients admitted from skilled nursing facilities, dialysis patients, patients admitted to an intensive care unit, and other patients who are at increased risk for MRSA infection (not otherwise specified). There is a requirement for the attending physician to follow up with and educate those patients who test positive, whether colonized or infected. The law also requires surveillance and public reporting of certain health care-acquired infections, including central-lineassociated bloodstream infections, bloodstream infections due to MRSA or vancomycin-resistant enteroccoci, and Clostridium difficile infections. Deep and organ-space infections for all clean and clean-contaminated surgical procedures must also be reported. HAIs are the most common complication of hospital care and are listed among the top ten leading causes of death in the United States. The CDC has estimated that each year there are more than 1.7 million infections, 99,000 deaths, and $3.1 billion dollars in excess health care costs in U.S. acute care hospitals. Based on these data, the California Department of Public Health estimated that approximately 200,000 HAIs occur in California each year, with an annual cost of about $600 million to $1.6  billion. Preventing health care-associated infections is a major public health concern, as these infections pose a tremendous burden with respect to mortality, morbidity, and expense. The California state laws and other new regulations have had a significant impact on the operations at acute care facilities. Clearly, the new requirements have brought hospital staff from all levels to the table to discuss infection prevention efforts. There are some signs nationwide that certain health care-associated infections, such as central-line-associated bloodstream infections, are decreasing. However, the overall impacts for patients in California have yet to be determined. A number of the mandates are controversial, due to limited scientific evidence and/or conflicting data with regard to their effectiveness. These are unfunded mandates, so the costs of implementing them are borne by the institutions. For some facilities, such as public hospitals, this may result in difficult budgeting decisions. There may be unintended consequences

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Infections in Hospitals Continued from previous page . . . with respect to health care-associated infections, as infection control and prevention departments shift limited time and resources to the detailed tasks that are now required. In addition, infection-prevention measures may not always be benign. For example, data suggest that patients placed in isolation may receive fewer doctor and nurse visits, experience increased falls, and have lower patient satisfaction scores. Additional information may be found at the California Department of Public Health Healthcare Associated Infections Program website at http://www.cdph.ca.gov/programs/hai/ Pages/default.aspx. Public reporting results for acute care hospitals are listed here. The following websites show the complete requirements of the three recently enacted California laws: http://www.dhcs.ca.gov/provgovpart/initiatives/nqi/ Documents/SB739.pdf http://www.cdph.ca.gov/services/boards/Documents/ SB1058chaptered09_25_08.pdf http://www.cdph.ca.gov/services/boards/Documents/ SB158chaptered09_25_08.pdf Elaine M. Dekker, BSN, CIC, has fifteen years of experience as an infection control practitioner. She currently serves as the Infection Prevention and Control Program Manager for San Francisco General Hospital.  Lisa G. Winston, MD, is an associate professor in the Department of Medicine, Divisions of Infectious Diseases and Hospital Medicine at the University of California, San Francisco. She is primarily based at San Francisco General Hospital, where she serves as the vice chief of Inpatient Medical Services and as the hospital epidemiologist.

Bad Bugs, from Farm to Us Continued from page 17. . . Bayer Corporation vigorously contested the FDA’s proposal to withdraw a widely used class of antimicrobials, fluoroquinolones, from agricultural use. These medications are used to combat some of the same bacterial pathogens that are treated with the same drugs in human medicine. Hence there is a high risk of resistant strains finding their way from animals to humans.13  Abbot Laboratories, the other major manufacturer of fluoroquinolones, showed admirable scientific judgment and corporate responsibility in agreeing to the FDA’s request. Unfortunately, judging from the Animal Health Institute’s response to the AMA, we fear the drug industry’s reactions may more closely mirror Bayer’s shortsighted approach. But, notably, even some forward-thinking agricultural leaders are now questioning the wisdom of such stonewalling.14 Admittedly, we tend to give more credibility to those who do not have any financial interest in the status quo. Leading experts unequivocally state that our current practices of feeding antibiotics to animals go against “a strong scientific consensus that it is a bad idea” and that the long stalemate on this issue constitutes a “struggle between strong science and bad politics.”15  The intentional obfuscation of the issue by those 20 San 21 SanFrancisco FranciscoMedicine Medicine September September2012 2012

with profit in mind is an uncomfortable reminder of the long and ongoing battle to regulate the tobacco industry, with similar dismaying exercises in political and public relations lobbying and even scandal.16 As with tobacco control, science and health concerns should take precedence over profit in regulating the overuse of antibiotics in the production of meat and other agricultural products. Antibiotics do have a place on farms, but the benefits of their use can likely be preserved while minimizing harm. We need to learn more about the extent of risk, but the delay tactic of allowing current practices to continue while “more research” is conducted is unacceptable. Enough is already known to justify a more cautious, preventive approach.17 Other nations are ahead of the United States in this regard and have banned routine agricultural use, with demonstrable benefit in reduced bacterial resistance.18 We call on the FDA or legislators to, in the coming year, ban the nontherapeutic agricultural use of antibiotics. This ban should be lifted only if it is scientifically proved, in unbiased studies, that this use does not contribute to bacterial resistance in humans. Producers of agricultural antibiotics should be required to submit data on the specific antibiotics used, in sufficient detail to track usage and resistance trends. Finally, individual and business consumers of meat should begin to demand that the meat they purchase be grown without the routine use of antibiotics. The need to preserve the efficacy and supply of our antibiotic tools becomes even more crucial. It is time for our government to act in the public interest on this important issue.   For information on the growing campaign surrounding this issue, including the AMA-endorsed Preservation of Antibiotics for Medical Treatment Act (PAMTA, H.R. 965/S. 1211), see www. keepantibioticsworking.com. For a recent update on how Denmark is leading on this issue, see Pig out: If farmers do not rein in the use of antibiotics for livestock, people will be severely affected. Nature 486, 440. 28 June 2012.  Originally published: West J Med. 2002 January; 176(1):9–11. For a full list of references, please see www.sfms.org.

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Infectious Disease

Drug Resistance An Update on Cephalosporin Resistance in Neisseria Gonorrhoeae Mark W. Pandori, PhD, HCLD (ABB), and Susan S. Philip, MD, MPH The causative agent Neisseria gonorrhoeae has demonstrated significant adaptive capability to resist pharmacological agents. Since the 1940s, ev-

ery agent that has been recommended as monotherapy for N. gonorrhoeae infection has eventually met with a strain of the organism capable of resisting that agent. Moreover, the accumulation of resistances has been for some strains cumulative, resulting in the creation of multidrug-resistant strains of the organism.1 The remaining recommended oral compounds for the treatment of gonorrhea, cephalosporins, have been associated with multiple treatment failures in Asia since the early 2000s, and more recently in Europe. 2,3,4,5 The availability of an oral compound given as a single dose to treat a sexually transmitted disease such as gonorrhea is of utmost importance from the public health point of view, as it facilitates treatment completion of not only infected individuals but also their sex partners in order to decrease ongoing transmission. Even more troubling, recent reports from Asia and Europe have documented isolates associated with treatment failure to ceftriaxone, the more potent injectable form of cephalosporin. 5,6 The strains of N. gonorrhoeae associated with both the oral and injectable cephalosporin failures were found in each case to be multidrug resistant. Efforts to stave off cephalosporin- (and multidrug-) resistant N. gonorrhoeae in the United States have proceeded. The Centers for Disease Control and Prevention have warned the medical community of the impending issue. 1,7 Additionally, the CDC made new treatment recommendations in 2010 that included the simultaneous use of two drugs of different classes for the treatment of gonorrhea (ceftriaxone 250 mg IM plus either azithromycin 1 g single dose orally or doxycycline 100 mg a day for seven days). 8 The CDC also continues its ongoing surveillance of drug susceptibility for the organism. This program, in place at multiple health departments in the United States, including the San Francisco Department of Public Health, is termed GISP (Gonococcal Isolate Surveillance Project), relies on the live culture of the organism, and provides resistance data on isolates (collected locally and tested regionally) about four to eight weeks after the collection of the specimen. Given the turnaround time, GISP is not considered a real-time interventional strategy but instead functions as a surveillance tool. In San Francisco, concern about the arrival and dissemination of cephalosporin-resistant N. gonorrhoeae is very high. Previous patterns of the spread of drug resistance in this organism have shown that within the United States, California is often hit first and hardest by drug resistance. 9 San Francisco has been shown previously to harbor high rates of drug-resiswww.sfms.org

tant gonorrhea, and a variety of multidrug-resistant strains of N. gonorrhoeae have been shown to exist within the city. 9,10 In 2007 and 2008, the CDC GISP program did not include oral cephalosporins as a surveyed drug. At that time, resistance to oral cephalosporins had been shown to be widely disseminated in Japan. Noting this, in 2008, the San Francisco Department of Public Health (SFDPH) Laboratory sought to characterize its jurisdiction’s stored gonococcal isolates for decreased susceptibility to oral cephalosporins. The standard method of assessing drug susceptibility in N. gonorrhoeae requires the live culture of the organism, which can take several days to accomplish in the laboratory for even a single specimen. Hence the analysis of nearly an entire year’s worth of cultures would be time consuming and onerous. To surmount this, the SFDPH Laboratory used DNAbased testing to survey isolates for resistance. Since virtually all microbial drug resistance has a genetic basis, potential resistance can be detected by rapid analysis of genes rather than phenotypes (for example, the ability of the organism to grow in the presence of an antibiotic). Typically, DNA-based methods such as PCR can be used to analyze hundreds of organisms in a day. The same number of organisms analyzed by culture-based methods would take more labor and weeks to perform. Note that such genetic analyses are not unheard of in microbiology: For drug susceptibility testing of Mycobacterium tuberculosis, PCR and DNA sequencing at reference laboratories is not uncommon. The use of DNA sequencing for assessment of resistance to antiviral compounds has become routine for HIV diagnoses. It therefore seemed logical to adopt a similar strategy for gonorrhea—especially since drug resistance has been such a practical and continuous problem for this disease. Early studies in Japan on cephalosporin resistance had identified a significant genetic alteration in the penA gene of N. gonorrhoeae that is easily detectable by the method of PCR (polymerase chain reaction). 11 Using PCR and subsequent DNA sequencing, the SFDPH Laboratory screened all of its 2008 isolates and was able to determine that 6 out of 186 harbored a penA gene that possessed a significantly altered version of the gene (now termed allele XXXIV). This alteration was highly similar to those found in isolates of N. gonorrhoeae that were associated with treatment failures to oral cephalosporins in Japan from 2000 to 2008. 12 In a recent report, allele XXXIV has been associated with a pharyngeal gonorrhea treatment failure to an injectable cephalosporin in Slovenia 5. Another method of genetic analysis that allows for the categorization of N. gonorrhoeae into distinct genetic families called

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Drug Resistance Continued from previous page. . . NG-MAST showed that the 2008 San Francisco isolates possessed strain type 1407. This was the same strain type seen in cases of cephalosporin treatment failures in France and Slovenia, and it has been associated with decreased susceptibility to oral cephalosporins in Canada and Great Britain. 4,5,13,14 The 2008 San Francisco isolates were also evaluated by classical culture methods to determine their ability to grow in the presence of cephalosporins. The SF isolates of type 1407 and penA allele XXXIV were found to have significantly decreased susceptibility to oral cephalosporins, with minimum inhibitory concentrations (MIC) of the drug cefpodoxime for these isolates ranging from 0.5 to 1.0 mg/L, when 0.015 mg/L is typical.12 When the CDC GISP program resumed the usage of oral cephalosporins in its surveillance efforts in 2009, the program began to identify, nationally, several instances of isolates with “alert” levels (an MIC of greater than or equal to 0.250 mg/L) of decreased susceptibility to cefixime and cefpodoxime. Additionally in 2009, the SFDPH Laboratory used PCR and DNA sequencing to rapidly screen 400 gonococcal isolates collected nationwide for a different study in 2007. That analysis revealed 11 isolates that possessed allele XXXIV and were type 1407. Those 11 isolates came from the following locations: Seattle, Portland, San Francisco, Los Angeles, San Diego, and Orange County—exclusively West Coast population centers. At the SFDPH Laboratory, screening by both genetic and phenotypic means has become standard since 2008. The use of genetic testing has provided considerable dexterity to screening for resistance, both prospectively and retrospectively. Isolates (100 specimens) tested from San Francisco in 2006 revealed no presence of type1407 or penA allele XXXIV in San Francisco. However, each of the years from 2009 to 2012 has revealed isolates of type 1407 with decreased susceptibility to cephalosporins (both oral and injectable) that also possess the penA XXXIV. These data indicate that N. gonorrhoeae with a decreased susceptibility to cephalosporins and with genetics previously associated with treatment failures to these drugs internationally are circulating in San Francisco and in other locations within the U.S. and that their arrival may have occurred in or after 2006. While no overt treatment failures to cephalosporins have been documented in the U.S. to date, it is possible that subclinical failures have occurred and have gone undetected, as routine follow-up of patients with gonococcal infections is not yet standard practice. Moreover, such infections can be asymptomatic, making it difficult to elicit subsequent testing from individuals. San Francisco clinicians are urged to use current recommended dual treatment for gonorrhea as detailed above, to maintain a high index of suspicion for possible treatment failure, and to contact the Department of Health’s STD Prevention and Control Section with any questions about clinical management of these cases. What we may be learning through the surveillance experience in San Francisco, however, is the potential value of DNA-based methods in screening for resistant organisms. These methods have proven to be faster and more informa22 23

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tive than traditional culture-based methods. They can be used to evaluate large numbers of either cultured isolates or clinical specimens with very short turnaround times. Genetic methods facilitate two additional potentialities: one is the use of genetic tests to guide treatment at the time of diagnosis; the other is the rapid, real-time gathering of population-level surveillance data to inform treatment policies. The geneticbased testing used to evaluate cephalosporin resistance in San Francisco has been demonstrative of these possibilities, but it has also allowed the Department of Public Health to see the problem of impending resistance within a national and international context. DNA-based laboratory techniques such as PCR and DNA sequencing are easy to develop or modify, giving laboratories and health departments powerful weapons when dealing with highly adaptable organisms. This is of great significance because the continuous battle between human beings and microbial drug resistance is, at its roots, genetic and evolutionary warfare. And the time during which humans continue to be the victors in this conflict is perhaps nearing an end. Dr. Mark Pandori obtained his bachelor’s of science degree in genetics from U.C. Berkeley and a PhD in biomedical science from U.C. San Diego. He performed postdoctoral work and was an instructor of medicine at Harvard Medical School. He is currently director of the Public Health Laboratory in  San Francisco  and associate clinical professor of laboratory medicine at U.C. San Francisco. He is California state certified in public health microbiology and is board certified as a high-complexity laboratory director with the American Board of Bioanalysis. Dr. Pandori grew up in San Jose, California, and resides in San Francisco’s Sunset District. Susan Philip completed medical school at Washington University in St. Louis, following with a residency in internal medicine at the University of Chicago and a fellowship in infectious diseases at the University of California, San Francisco. She has also obtained an MPH at the Harvard School of Public Health. Currently, she serves as president of the California STD Controllers Association and is on the board of directors of the National Coalition of STD Directors. Dr. Philip is an assistant clinical professor of medicine in the Division of Infectious Diseases at UCSF and sees HIV primary care patients at San Francisco City Clinic.

References 1. Del Rio C, Hall G, Hook EW, Whittington WLH, Kirkcaldy RD, Papp JR, Weinstock H, Murray EL. Cephalosporin susceptibility among Neisseria gonorrhoeae isolates—United States, 2000–2010. Morb Mortal Weekly Rep. 2011; 60(26): 873. 2. Barry P, Klausner J. The use of cephalosporins for gonorrhea: The impending problem of resistance. Expert Opin Pharmacother. 2009; 10(4):555-577. 3. Unemo M, Golparian D, Syversen G, Vesterjeo DF, Moi H. Two cases of verified clinical failures using internationally recommended first-line cefixime for gonorrhoea treatment, Norway, 2010. Euro Surveill. 2010; 15(47):pii-19721. 4. Unemo M, Golparian D, Nicholas R, Ohnishi M, Gallay

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Infectious Disease

Viral hepatitis An Overview of Strands A through E Francis Yao, MD Viral hepatitis is a major health problem in the United States. There are five known hepatitis viruses, hepatitis A to hepatitis E, that have been confirmed to cause liver disease in humans.

Hepatitis A

A causes acute hepatitis that is typically transmitted by the fecal-oral route, either by person-to-person contact or by ingestion of contaminated food or water. Acute hepatitis A is usually self-limited. However, 10 to 15 percent of patients experience prolonged or relapsing disease for up to six months. About 1 percent of acute hepatitis A may be severe and cause acute liver failure, with an overall case fatality rate of about 0.5 percent. The currently licensed hepatitis A vaccine is highly effective with two doses given six to twelve months apart. The Centers for Disease Control (CDC) recommends hepatitis A vaccination for all children at age one year and for those at increased risk for acquiring hepatitis A and those at increased risk for complications of hepatitis A, including those with chronic liver disease from other causes. The Advisory Committee on Immunization Practices (ACIP) has amended its guidelines for hepatitis A vaccination for travelers to endemic areas. One dose of single-antigen hepatitis A vaccine administered at any time before departure may provide adequate protection for most healthy individuals.

Hepatitis B

B is transmitted by exposure (percutaneous or mucous membrane) to infected blood or body fluids. Vertical transmission from an infected mother to the newborn is the major risk factor for acquiring hepatitis B in endemic areas such as Asia. In nonendemic areas, major risk factors include unprotected sex with an infected partner or with more than one partner, men having sex with other men, a history of other sexually transmitted disease, and use of illegal injected drugs. Universal hepatitis B vaccination in all newborns has dramatically reduced the hepatitis B carrier rate and its complications. Patients at increased risk for hepatitis B infection should undergo serologic testing; and positive hepatitis B surface antigen in the blood defines infection. Markers for viral replication, including hepatitis B e antigen and hepatitis B DNA, should be tested in chronically infected patients. Patients with chronic hepatitis B are at risk for cirrhosis and its complications, including hepatocellular carcinoma. Patients with chronic hepatitis B infection can be classified into different subgroups. The “inactive carrier” group has normal liver chemistries, negative hepatitis B e antigen, undetectable or low levels of hepatitis B DNA, and does not www.sfms.org

require antiviral therapy. The other two major subgroups are the “wild type” with positive hepatitis B e antigen, and the hepatitis B e antigen-negative group due to precore or corepromoter mutation. Recommended criteria for treatment in these two subgroups depend on the level of hepatitis B DNA and liver enzymes and vary slightly among different practice guidelines. In general, the currently available oral antiviral agents are highly effective in suppressing virologic and inflammatory activities, with minimal side effects. Among them, the first-line agents are entecavir and tenofovir, primarily because they’re also associated with low risks for drug resistance in the long term. In general, these antiviral agents are only suppressive, and most patients require long-term, indefinite therapy. Interferon is an alternative therapy with shorter treatment duration, but the side effects are substantial and sustained long-term response occurs in only about 20 to 40 percent of patients. There is still a need for new and effective treatment regimens that are potentially curative and require only finite treatment duration.

Hepatitis C

C is transmitted primarily by parenteral exposure to infected blood. The most common risk factors for hepatitis C infection include a history of injection drug use and blood transfusions before 1992. An estimated 75 to 85 percent of patients with acute hepatitis C will become chronically infected, and that 5 to 20 percent of patients will eventually develop cirrhosis over an average of twenty years. The overall prevalence of hepatitis C is estimated to be about 2 percent in the United States. Hepatitis C is currently the most common disease indication for liver transplantation and is the leading cause of hepatocellular carcinoma in the United States. Among the hepatitis C subtypes (genotype 1 to 6), genotype 1 is the most common in the United States, and it is also the most difficult to treat. Until recently, treatment of chronic hepatitis C using a combination of pegylated interferon and ribavirin resulted in a sustained response rate of less than 50 percent for patients with genotype 1 infection. In May 2011, the two protease inhibitors, boceprevir and telaprevir, were approved by the FDA for treatment of hepatitis C genotype 1 infection in combination with pegylated interferon and ribavirin. The sustained response rate with “triple” therapy has improved to 70 to 80 percent for previously untreated patients. The response rate in patients who did not respond to previous interferon treatment varies according to the different subgroups classified as prior nonresponders, partial responders, or relaps-

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Viral Hepatitis Continued from previous page . . .

Drug Resistance Continued from page 22 . . .

ers. The current treatment for hepatitis C is limited by poor patient tolerance and is labor intensive due to the need for monitoring and management of the many serious side effects of treatment. Research is ongoing in developing an effective oral combination of “direct-acting antivirals” (DAA), including protease or polymerase inhibitors without interferon in the treatment of hepatitis C.

A, Sednaoui P. High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: Novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother. 2012; 56(3):1273-80. Epub 2011 Dec 12. 5. Unemo M, Golparian D, Potočnik M, Jeverica S. Treatment failure of pharyngeal gonorrhoea with internationally recommended first-line ceftriaxone verified in Slovenia, September 2011. Euro Surveill. 2012 Jun 21; 17(25). 6. Ohnishi M, Golparian D, Shimuta K, Saika T, Hoshina S, Iwasaku K, Nakayama S, Kitawaki J, Unemo M. Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea? Detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrob. Agents Chemother. 2011; 3538-3545. 7. Bolan GA, Sparling PF, Wasserheit JN. The emerging threat of untreatable gonococcal infection. N Engl J Med. 2012 Feb 9; 366(6):485-7. 8. Workowski KA, Berman S, Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010 Dec 17; 59(RR-12):1-110. 9. Centers for Disease Control and Prevention (CDC). 2010 STD surveillance report. 10. Buono S, Wu A, Hess DC, Carlson JS, Rauch L, Philip SS, Barry P, Bernstein K, Klausner JD, Pandori MW. Using the Neisseria gonorrhoeae multiantigen sequence-typing method to assess strain diversity and antibiotic resistance in San Francisco, California. Microb Drug Resist. 2012 Jun 11. 11. Ochiai S, Ishiko H, Yasuda M, Deguchi T. Rapid detection of the mosaic structure of the Neisseria gonorrhoeae penA gene, which is associated with decreased susceptibilities to oral cephalosporins. Journal of Clinical Microbiology. 2008; 1804-1810. 12. Pandori M, Barry PM, Wu A, Ren A, Whittington WLH, Liska S, Klausner JD. Mosaic penicillin-binding protein 2 in Neisseria gonorrhoeae isolates collected in 2008 in San Francisco, California. Antimicrob Agents and Chemother. 2009; 53(9). 13. Martin I, Sawatzky P, Allen V, Hoang L, Lefebvre B, Mina N, Wong T, Gilmour M. Emergence and characterization of Neisseria gonorrhoeae isolates with decreased susceptibilities to ceftriaxone and cefixime in Canada: 2001-2010. Sex Transm Dis. 2012; 39(4):316-23. 14. Chisholm SA, Alexander S, Desouza-Thomas L, Maclure-Webster E, Anderson J, Nichols T, Lowndes CM, Ison CA, GRASP Collaborative Group. Emergence of a Neisseria gonorrhoeae clone showing decreased susceptibility to cefixime in England and Wales. J Antimicrob Chemother. 2011; 66(11):2509-12. Epub 2011 Aug 16.

Hepatitis D

D or “delta” virus is a defective virus that requires the helper function of hepatitis B to replicate, and therefore it only occurs in patients who are infected with hepatitis B. The prevalence of hepatitis D is highest in South America, Africa, and the Mediterranean. It is relatively uncommon in the United States. It can be acquired either as a “coinfection” with hepatitis B or as “super-infection” in patients with chronic hepatitis B infection. There is no vaccine for hepatitis D, but it can be prevented in individuals who are not already hepatitis B infected by hepatitis B vaccination. Hepatitis D can cause serious chronic liver disease and tends to progress more rapidly to cirrhosis than chronic hepatitis B alone. Interferon is the only treatment available for hepatitis D infection, but the treatment response rate is low. The oral antiviral agents used for hepatitis B infection are ineffective against hepatitis D.

Hepatitis E

E has previously been considered rare and largely confined to travelers returning from endemic areas. This notion has recently been challenged. Hepatitis E may be more common than previously recognized as a cause of hepatitis in the United States and developed countries, and it is thought to be transmitted mainly by ingestion of raw meat or other infected food products. Hepatitis E vaccination is not available in the United States. Although acute hepatitis E is usually self-limited, it can lead to more severe, acute liver disease or even fulminant liver failure in pregnant women or in patients with underlying liver diseases. There is also growing evidence that hepatitis E not only causes acute hepatitis but may also result in chronic liver disease mainly in immunosuppressed individuals (e.g., organ transplant recipients). Diagnosis in these patients requires testing for hepatitis E RNA. Patients with unexplained hepatitis should be tested for hepatitis E, regardless of their travel history. Francis Yao, MD, is a professor of clinical medicine and surgery and medical director of liver transplantation at the University of California, San Francisco.

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Infectious Disease

HPV Vaccine It’s Not Just for Girls Anymore Charles Wibbelsman, MD On June 8, 2006, the Food and Drug Administration licensed the first vaccine developed to prevent cervical cancer and other diseases in females caused

by certain types of genital human papilloma virus (HPV). Later in June of 2006, the Advisory Committee on Immunization Practices (ACIP) voted to recommend use of this vaccine in females ages 9–26 years of age. In May of 2010, the CDC published updated HPV vaccine recommendations from the ACIP recommending the routine administration of the three-dose vaccine to all females ages 11–12 years, as well as females ages 13–26 years who were not previously vaccinated. Indeed, after the hepatitis B vaccine, which was licensed in the early 1980s (though marketed primarily as a vaccine to prevent hepatitis B infection and not hepatic cancer), the HPV vaccine is now the second vaccine that prevents cancer. In the U.S., thousands of adolescent females and young adults have received this vaccine series. By focusing on the target age of 11–12 years of age, many adolescent females received this as the “triad of vaccines” prior to entering the teen years: the three-dose series of the HPV vaccine, the Tdap booster, and the meningococcal conjugate vaccine Menactra. Over the past six years there have been many challenges to administering the HPV vaccine to adolescent females. For many primary care physicians, convincing parents to immunize their daughters against a virus that can cause cervical cancer has been understood by some parents that, since HPV is a sexually transmitted infection, giving this vaccine is licensing an adolescent to engage in sex. Many parents still are hesitant to consent to this vaccine, stating that it is “too new.” In October of 2009 the FDA approved the use of the quadrivalent HPV vaccine for males aged 9–26 years for the prevention of genital warts caused by HPV types 6 and 11. The ACIP followed later in May of 2010, recommending only “permissive administration” of the quadrivalent HPV vaccine for males. This recommendation did not give clinicians strong support in their clinical practices for endorsing this vaccine series. As a consequence, many physicians only administered the vaccine if the patient or parents specifically requested it. The epidemiologic evidence of cervical cancer being transmitted sexually from male to female still did not prevail to warrant immunizing males who transmitted the human papilloma virus. However, in the past year, more and more disease reporting has indicated that other types of cancer caused by HPV in males were being reported: oral and throat cancers as well as anal and penile cancers. A National Cancer Institute study released in 2011 found that throat and oral cancers linked to HPV increased more than 200 percent between 1988 and www.sfms.org

2004, from 0.8 occurrences per 100,000 people to 2.8 per 100,000; this increase was observed mostly in men. However, it was not until December of 2011 that the CDC issued a definite recommendation for males that those aged 11 or 12 years of age routinely receive a three-dose series of quadrivalent HPV vaccine. This recommendation has now been further expanded to include a catch-up for males ages 13–21 who have not initiated or completed the full vaccine series. HPV vaccine may be given to males age 21–26 years and should be given to high-risk males, such as men having sex with men, through age 26. In my own clinical experience practicing adolescent medicine, since the CDC recommendation late last year I have offered the HPV vaccine to all adolescent males and have observed the refusal rate by parents to be much less than for their daughters. I wonder if this reflects a different parental view on sexual activity in males. Finally, I must remind all clinicians that with AB 499 becoming law as of January 1 of this year, adolescent males and females ages 12–17 now can provide their own consent to prevention measures against sexually transmitted infection, including the HPV vaccine series. Charles J. Wibbelsman, MD, is chief of the Teenage Clinic at Kaiser Permanente San Francisco. He is chair of Adolescent Medicine Subspecialists for Kaiser Permanente Northern California and president of Chapter 1, district IX for the American Academy of Pediatrics. He is a longtime member of the SFMS and is a past president. He is also on the board of directors for Larkin Street Youth Services.

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“Resources and respect: two of the reasons I’m at Saint Francis.” David Duong, MD, Urologist and Trustee, Saint Francis Memorial Hospital

Saint Francis is led by physicians like Dr. David Duong: urologist, Vietnamese refugee, and Yale graduate who earned his MD at Vanderbilt and completed his residency at Stanford. What brings talented physicians like Dr. Duong to Saint Francis? First-class facilities, advanced technology, and an abiding respect for the professionalism of physicians and the dignity of patients. Saint Francis: Physician founded. Physician led.

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Infectious Disease

Pertussis Prevention All Health Care Providers Play a Role Lisa Tanisawa, MPH

The San Francisco Department of Public Health (SFDPH) conducts an Expanded Kindergarten Retrospective Survey (EKRS) every three years to determine how

well immunized two-year-olds are in San Francisco. The results are used by health care providers, community organizations, and advocacy groups to improve opportunities for and systems pertaining to pediatric immunizations. Being up to date at two years old indicates the child is protected from dangerous diseases, has had regular checkups, and has had regular communication with a provider. The 2011 EKRS analyzed 1,766 kindergarten students from 18 public and 19 private schools (25% of the City’s schools). The overall up-to-date (UTD) rate for 4DTaP (diphtheria, tetanus, pertussis), 3polio, and 1MMR (measles, mumps, rubella) at 24 months was 79.3%, which was the same result as the 2008 EKRS. For 3- and 4-year-olds, however, results were more positive, with UTD rates of 86.4% and 89.3% respectively. Among coverage rates for the individual DTaP, polio, and MMR vaccines, the proportion of children UTD at 24 months appears lowest for the DTaP vaccine (84.4% with 95%CI 80.1‐88.8) compared to polio (92.3% with 95%CI 87.9‐96.9) and MMR (89.6% with 95%CI 85.3‐94.2). In light of the recent pertussis epidemic in California, ensuring that San Francisco children are up to date with their DTaP immunizations is an important step toward decreasing pertussis incidence. In 2010, during the California pertussis epidemic, the incidence of pertussis in San Francisco increased almost sevenfold compared to 2009 (2010: 17.0 cases per 100,000 residents, 95% CI 14.3-20.1; 2009: 2.5 cases per 100,000 residents, 95% CI 1.53.8). The highest rates of pertussis were observed among infants less than 1 year of age, followed by those ages 5–14 (78.1 cases per 100,000 residents, 95% CI 57.8-103.0).1 While pertussis incidence rates have decreased in 2012, cases continue to be reported in infants, children, and adults in San Francisco. Furthermore, pertussis is endemic, with epidemic cycles every three to four years. It is vital that we continue cocooning efforts in order to reduce incidence.2 Cocooning is the act of vaccinating everyone around an infant, forming a cocoon of protection from pertussis. Anyone who anticipates close contact with an infant aged less than 12 months should receive at least a single dose of Tdap or the full pediatric series of DTaP vaccines. This includes siblings, parents, grandparents, and child care and health care providers. Additionally, pregnancy is not a contraindication to the Tdap vaccine. Use Tdap to proactively vaccinate pregnant women in their third trimester. In this regard, most all types of providers—pediatricians, those in internal medicine, obstetricians/gynecologists, and even emergency room physicians—play a role in helping prevent pertussis. As has been cited in all related health alerts (http://www.sfcdcp.org/ www.sfms.org

healthalerts.html), clinicians should also continue to keep pertussis in mind for any patient presenting with a persistent cough. The 2010 pertussis epidemic prompted the California legislature to pass AB 354, which requires all students entering seventh grade for the 2012–2013 school year, and all future school years, to be immunized against pertussis with a Tdap booster. Remember that when immunizing sixth graders with Tdap, other vaccines are recommended as well, including meningococcal, HPV, flu, and any vaccine they may have missed during childhood. Childhood immunizations are primarily administered in pediatrician and family practice offices. But in this current landscape in which questions of vaccine safety have become part of the social discourse, it is important that conversations about immunizations occur with expecting parents prior to their baby’s birth. As the primary providers for expecting parents, the obstetrician and gynecologist community should be included in immunization education and outreach in order to initiate these conversations with patients. The complete EKRS report and a one-page summary are available at www.sfcdcp.org/izchildren.html. SFDPH also has recommended websites and materials to assist any provider in discussing with and offering vaccines to their patients. Call (415) 554-2830 for more information or visit www.sfcdcp.org/izs.html. Lisa Tanisawa, MPH, is the pediatric and adolescent immunization coordinator for the San Francisco Department of Public Health. She has also worked on public health projects related to HIV prevention among prisoners and conducted qualitative research on veterans returning home from the Iraq and Afghanistan wars.

References 1. Communicable Disease Control & Prevention Section. Annual report of communicable diseases in San Francisco, 2010. San Francisco, California: SFDPH 2012 May. Available from http://www.sfcdcp.org. 2. California Department of Public Health. Vaccine preventable diseases and immunization coverage in California, 2001–2006. Available from http://ww2.cdph.ca.gov/ programs/immunize/Pages/VaccinePreventableDisease.aspx.

September 2012 San Francisco Medicine

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Infectious Disease

Adult Vaccine Controversies Pneumococcal and Varicella Vaccines Roger Paul Baxter, MD There are a number of controversies and unanswered questions about vaccines in adults. This article will address two of them.

What Vaccine Is Best to Prevent Pneumococcal Infections In Adults?

Pneumovax®, the 23-valent pneumococcal polysaccharide vaccine (PPV23), has been used for years in adults over 60 and in younger persons who are immunocompromised or medically ill. There is a recommendation for a second dose for people who may have a worse response to the vaccine, but there has always been confusion around who gets a booster, and why. Partly this is because PPV23 does not actually boost. Polysaccharide vaccines stimulate the B-cells to produce antibodies but are not effective at initiating a cell-mediated T-cell response. This means that PPV23 produces short-lived antibodies and no memory cells. A second shot does not produce any actual boost and, in fact, the response to the second shot may be less than to the first. This phenomenon is called hyporesponsiveness, and it can lead to a poor response to all subsequent pneumococcal vaccines, both polysaccharide and conjugate. In other words, the vaccine effect is short-lived, and there’s no help with a boost. But newer polysaccharide-conjugate vaccines, such as Prevnar 13® (PNCV13), produce a more balanced Th1/Th2 response, leading to T-cell activation with generation of plasma and memory cells. A second shot after maturation of the memory cells (about six months later) leads to boosting, generation of much higher and prolonged antibodies, and much better immune protection. In infants and children, the conjugate vaccine has made fantastic reductions in invasive disease and has even been shown to decrease colonization. So why don’t we give the better vaccine to adults? PNCV13 has recently been licensed for all adults over 50, but, as yet, the Advisory Committee on Immunization Practices (ACIP), which directs our recommendations that come from CDC, has not given a recommendation to replace PPV23 with PNCV13. Of course, PPV23 contains more antigens, but good activity against most strains would seem better than poor activity against more strains. Unfortunately, studies to date have not shown convincing evidence that PNCV13 is actually more protective, though results of large-scale trials in South America are underway. So at this time it’s premature to replace all PPV23 with PNCV13, but we may be changing direction with prevention of this infection in the near future. In the meantime, many vaccine experts recommend at least changing over to PNCV13 for all persons at high risk for pneumococcal disease, e.g., splenectomized patients or those with few or ineffective immunoglobulins, such as hypogammaglobulinemia or myeloma. www.sfms.org

The Shingles Vaccine after Shingles

Zostavax®, though containing the same live attenuated virus as Varivax®, the children’s chicken pox vaccine, is different from other vaccines. Instead of being formulated to prevent infection, this vaccine’s purpose is to prevent reactivation of varicella. Therefore, it targets the T-cell (cell-mediated) wing of the immune system. Although the vaccine is clearly beneficial, its effectiveness is lower than that of some vaccines, in the range of 60–70% for those 60–70 years of age and less than 50% for those over 80 years of age. This would be expected, as the immune system weakens with age. This is not controversial. The vaccine works and is now licensed for anyone over 50. As with PNCV13, ACIP has not made a firm recommendation for ages 50–59, but the reason for this is that Merck, the vaccine manufacturer, has not been able to keep up with demand and shortages have occurred, leading ACIP to hold off on its recommendation. But the controversy lies in ACIP’s decision to include individuals with prior shingles as candidates for vaccination. Will Zostavax help someone after they’ve had shingles, to prevent them from getting another case? Interestingly, it is often an episode of shingles that prompts a person to come in for the vaccine, so this is an important distinction. Clearly, shingles is not always a one-time occurrence. Studies show that rates of recurrence may be as high as first-time episodes. This should not be unexpected, as prevention of reactivation requires constant immune activation and surveillance, while waning of immunity, whether from aging, medications, or medical conditions, allows release and reactivation of the varicella virus. As our population ages and is increasingly on immunosuppressive medications, we can expect to see more recurrences of zoster. So boosting the immune system to prevent it is a good idea. However, on a practical level, the vaccine has only been studied and licensed for a one-time dose, so why waste it? If you or your patient has recently had an episode of shingles, this has produced the same or perhaps better immune activation as the vaccine. So wouldn’t it make sense to allow this newfound immunity to wane a bit before trying to boost again? Because of this, most vaccine experts recommend that recent zoster victims not be immediately vaccinated; rather wait five to ten years (depending on the expert, not the patient) to vaccinate and help prevent the next episode. Roger Paul Baxter, MD, is codirector of the Kaiser Permanente Vaccine Study Center. He is currently principal investigator for many ongoing studies of vaccines, biologics, and epidemiology of infectious diseases; he has also published extensively on vaccine safety and effectiveness.

September 2012 San Francisco Medicine

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Artwork copyright © 2012 Dan Harding www.sfms.org


Infectious Disease

No Reason Not to Test HIV Testing Continues to Matter Stephen Follansbee, MD An article from the June 22, 2012, Morbidity and Mortality Weekly Report (MMWR) points out important information for clinicians. Adults who had their

first-ever HIV test were more likely to develop AIDS within the next six months, compared to adults who had been previously tested. At particularly high risk for being diagnosed late during HIV infection are persons > 50 years, blacks/African Americans, and persons whose risk factor for acquisition appeared to be heterosexual contact or intravenous drug use.

Why Should We Care?

This MMWR report reminds us to offer HIV testing for everyone at least once and to offer it again, at least annually, for persons whose lifestyles may place them at ongoing risk for acquisition of HIV. This recommendation is particularly important for people who may not be accessing health care regularly. Thus, even though testing for HIV or hepatitis C may not be related to the presenting problem, clinicians in the emergency room and urgent care settings have as much responsibility for testing as those clinicians seeing their “regular” patients.

Dr. Follansbee is head of Infectious Disease at Kaiser Permanente San Francisco. He is a longtime member of the SFMS and is a past president. Reference: Previous HIV Testing Among Adults and Adolescents Newly Diagnosed with HIV Infection—National HIV Surveillance System, 18 Jurisdictions, United States, 2006–2009. MMWR June 22, 2012 / 61(24);441-445.

First, diagnosing HIV earlier in infection is much more effective in improving outcome. Those individuals who are younger and started on combination antiretroviral treatment (cART) with higher CD4 cell counts have improved immune reconstitution compared to those diagnosed later in age or with more advanced disease. Second, people not diagnosed with HIV are more likely to spread HIV. The XIX International AIDS Conference in Washington, D.C., July 22–27, 2012, was themed “Turning the Tide.” In developed and developing countries around the The Epic-powered EHR solution world, access to HIV treatment has markfor your independent practice edly improved longevity and, importantly, has helped to decrease the pandemic imComprehensive pact of new infections. The most potent example of this is the marked improveEHR and practice management applications ment in maternal-to-child transmission Certified of HIV in communities where pregnant CCHIT Certified; Compliant to meet Meaningful Use women have access to HIV testing and perinatal treatment. However, if we are to Integrated truly turn the tide on this pandemic, more with Sutter Health’s clinical data repository people have to be diagnosed with HIV earlier in their infection, and they have to For a limited time, Sutter Health will make have access to cART. a donation to help offset the costs of implementing It is clear that many older people an EHR system for eligible physicians. with HIV infection acquired it many years before, from activities that are long historical. Many of these adults do not want to discuss these risk behaviors with their doctors, for a variety of reasons. Signifiwww.suttercommunityconnect.org or call (855) 426-7117 cantly, they do not want the history as part of their medical record or do not consider their often “brief” episodes of Powered by such behavior as being inconsequential. Not only HIV but also hepatitis C can be clinically asymptomatic for many years.

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HOSPITAL NEWS KAISER

Veteran’s

CPMC

Robert Mithun, MD

Diana Nicoll, MD, PhD, MPA

Michael Rokeach, MD

At Kaiser Permanente San Francisco, we realize that working in partnership with other health care organizations and the San Francisco Department of Public Health (SFDPH) is the most effective approach to controlling infectious diseases. Whether collaborating on projects to treat and prevent HIV/AIDS or working with tuberculosis control, our highly skilled teams of physicians, nurses, researchers, and allied staff are an integral part of the city’s infectious disease program. As the second-largest provider of outpatient HIV care in the city, we provide comprehensive services to more than 2,400 patients in our specialty clinic within the Department of Medicine at the medical center. All staff selected to work in the clinic have extensive experience treating those patients who are HIV positive as well as those with AIDS. In addition to treating those affected by the illness, we have a firm commitment to HIV prevention through such efforts as prenatal testing programs, nonoccupational post-exposure prophylaxis for HIV, and piloting pre-exposure prophylaxis for patients who are at high risk of acquiring HIV. Additionally, we offer a comprehensive travel medicine program that provides chemoprophylaxis (medicines), immunoprophylaxis (vaccinations), and travel advice for those traveling outside the United States. With the increasing frequency of travel to areas with high incidence of such infectious diseases as malaria, typhoid, and yellow fever, the need to have current disease data and prophylaxis protocol is essential. Our infectious diseases program also includes research. We have studies involving novel treatment options for HIV, hepatitis B, and hepatitis C. In addition, we attempt to provide up-to-date information on clinical trial research opportunities at other sites throughout the Bay Area. We give our patients contact information and the opportunity to obtain more details on a variety of research opportunities. As providers, we encourage patients to forward us questions or concerns about these research projects.

The fifth annual conference of the Brain at War was recently held in San Francisco at the Marines’ Memorial Club and Hotel. This leading national conference on the neurocognitive consequences of combat is presented each year by the Northern California Institute for Research and Education (NCIRE): The Veterans Health Research Institute. The conference offers a unique opportunity for researchers, clinicians, service members, veterans, policy makers, and others to meet and discuss the latest information on traumatic brain injury and posttraumatic stress (PTS). An important focus at this gathering was the impact of PTS on military members as they return from war. Although the stigma of PTS still exists and trauma may be difficult to measure, today’s technology has led to better understanding of the brain. Advances in digital imaging, brain mapping, and DNA research have allowed researchers to identify the effects of PTS. Kristine Yaffe, MD, chief of geriatric psychiatry at the San Francisco VA Medical Center (SFVAMC), reviewed her research on the long-term risks of neurodegenerative disease associated with traumatic brain injury and posttraumatic stress.  Director of SFVAMC’s Stress and Health Research Program Dr. Thomas Neylan, along with mental health researchers Aoife O’Donovan, PhD, and Sabra Inslicht, PhD, provided an overview of unique health issues facing active-duty women and female veterans. Featured speaker Karen Kelly spoke of her experiences as a Gold Star parent: her husband and two sons are in the U.S. Marine Corps, serving on multiple combat deployments to Afghanistan and Iraq. Community partners were recognized in the Veterans Outreach Program at City College of San Francisco and the Veterans Health Integration Program, supported by a donation from the American pop and blues rock musician John Mayer. For more information about the annual Brain at War conference and NCIRE, visit www. ncire.org.

32 33

San Francisco Medicine September 2012

CPMC’s Breast Health Center recently launched a new program at the California Campus called Breast CARE (Cancer Assessment of Risk and Education). It is for women who may be at high risk for developing breast cancer, want to learn more about their options, and want to be proactive about their breast health. The program can help women take steps to identify breast cancer early and possibly even prevent it. This free service is a great example of how CPMC continues to grow its outpatient services. One of CPMC’s long-standing community partnerships has been with the Lions Eye Foundation. Since 1959, we have worked together to provide free eye surgery, treatment, and medication to community members who don’t have insurance or have limited incomes. From 2009 to 2011, CPMC provided an estimated $15.7 million in free eye care as part of this program. Many of the patients would have gone blind if these services had not been made available. CPMC is being recognized with the American Heart Association/American Stroke Association’s Mission Lifeline Silver Receiving Award. This award recognizes hospitals for achieving 85 percent or higher composite adherence to all Mission: Lifeline STEMI Receiving Center performance achievement indicators for consecutive twelve-month intervals and 75 percent or higher compliance on all Mission: Lifeline STEMI Receiving Center quality measures to improve the quality of care for STEMI patients. California Pacific Medical Center has been recognized as a “Leader in LGBT Healthcare Equality” in Healthcare Equality Index 2012, the report of an annual survey conducted by the Human Rights Campaign (HRC) Foundation, the educational arm of the country’s largest lesbian, gay, bisexual, transgender (LGBT) organization. CPMC earned top marks for its commitment to equitable, inclusive care for LGBT patients and their families, who can face challenges in accessing adequate health care. CPMC was one of a select group of 234 health care facilities nationwide to be named Leaders in Healthcare Equality. www.sfms.org


HOSPITAL NEWS St. Mary’s

Saint Francis

Francis Charlton, MD

Patricia Galamba, MD

National and State Vaccination Coverage Among Adolescents Aged 13–17 Years —United States, 2011 From the MMWR Weekly, August 31, 2012 / 61(34);671-677

Summary The treatment of infectious diseases has evolved at a dizzying pace, especially in the last thirty-five years since ID began to boom as a specialty. Of course, this coincided with the onset of the HIV epidemic, which had San Francisco at its epicenter. What was once an ominous, certain, and frighteningly quick death sentence now has become an eminently treatable chronic condition when promptly diagnosed and properly treated with the most advanced agents using the latest protocols. In fact, HIV prevention has taken leaps forward with the prophylactic use of Truvada, in conjunction with barrier precautions. The best strategy regarding infectious diseases has always clearly been to not get infected in the first place. The recent push to increase immunization rates has certainly had a favorable impact against many diseases: influenza, pneumococcus, hepatitis A and B, meningococcus, varicella, pertussis, measles, mumps, rubella, polio, cholera, yellow fever, and typhoid. Smallpox has been eliminated. The greatest killer worldwide, however, is malaria, against which we have no vaccine. Certainly there are effective prophylactic and therapeutic antibiotics to prevent and treat malaria, but an ounce of prevention beats a pound of cure any day. We do have effective and affordable, albeit underused, prophylaxis against this scourge in the form of insecticidetreated mosquito nets. The World Health Organization shamefully endorses only the expensive nets produced by the companies owned by members of their board of directors. St. Mary’s ID specialist, Dr. Helen Gunthorpe, has spent much of her time and energy over the last decade developing BusinessKind, a nonprofit organization that empowers and employs disenfranchised third-world HIVinfected women to sew below-cost, locally produced insecticide-treated mosquito nets. This project not only saves innumerable lives but stimulates the blighted economy in parts of the world that need it the most.

www.sfms.org

In no other field of medicine is the disparity in health care as evident as in infectious disease. Infectious diseases that have been all but eradicated in wealthier nations continue to kill millions of the poorest people on the planet: malaria, HIV, diarrheal illnesses, and tuberculosis as well as measles, the flu, varicella, and hundreds of others. In third-world countries, these infections are the primary cause of death. Looking at infections more locally, at Saint Francis in particular, we are still able to see a microcosm of this disparity in wealth, opportunity, and access to health care as we are positioned between Nob Hill, the financial district, and the Tenderloin. Some of our local patients are facing similar difficulties as our third-world counterparts. We at Saint Francis, as a participating member of Dignity Health, continue to strive to provide care to all. But looking forward as we embrace new presidential elections, Obamacare, and our own locally grown Healthy San Francisco plan along with the local transitions to the Foundation model of care, the challenges are huge. But access to delivery of health care to address infections is not our only challenge. The era of multidrug resistance, aka the “superbugs,” is upon us. In our own Bothin Burn Center (Saint Francis’s nationally recognized center dedicated to the treatment and recovery of burn patients from all over Northern California), we have been battling a strain of multidrug resistant Acinetobacter since March 2011. Through a collaboration of efforts of infection control, pharmacy, nursing, physicians, environmental services, and even incorporating the patients’ families (yes, yellow gowns everywhere!), we were able to eradicate it from our burn unit in March of 2012. In addition, MRSA has been on the rise and has had rising MIC values, making it less responsive to our tried-and-true Vancomycin. Our yeasts have also shifted in epidemiology to more resistant isolates. All of this combined has made treating patients that much more challenging, costly, and complicated. I want to thank our infectious disease specialist Kathleen Jordan, MD, for sharing her thoughts on this column. Dr. Jordan is a great addition to our team!

What is already known on this topic? Since 2006, vaccination coverage with routinely recommended vaccines among U.S. adolescents has increased; but coverage with vaccines recommended at 11 or 12 years of age still remains below target levels, especially for human papillomavirus (HPV) vaccine.

What is added by this report? From 2010 to 2011, vaccination coverage among U.S. adolescents increased for ≥1 dose of tetanus, diphtheria, acellular pertussis (Tdap) vaccine to 78.2%, ≥1 dose of meningococcal conjugate (MenACWY) vaccine to 70.5%, and ≥1 dose and ≥3 doses of HPV vaccine among females to 53.0% and 34.8%, respectively. The increase in HPV 1-dose coverage among females (4.3 percentage points) was half the increase in Tdap and MenACWY vaccination (7.8– 9.5 percentage points) for the third consecutive year. What are the implications for public health practice? Although coverage with routine adolescent vaccines is increasing, the increase in HPV coverage among adolescent females is lagging, with only one half initiating the HPV series and the proportion of adolescent females protected from HPV-related cancers by the complete series ranging by state from 56.8% to as low as 15.5%. Stronger health-care provider recommendations for HPV vaccination, implementation of reminder/recall systems, elimination of missed opportunities for vaccination, and education of parents of adolescents regarding the risk for HPV infection and the benefits of vaccination are needed to protect adolescents from HPV-related cancers. http://www.cdc.gov/mmwr/ preview/mmwrhtml/mm6134a3. htm?s_cid=mm6134a3_w

September 2012 San Francisco Medicine

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IN MEMORIAM Frederick Margolin, MD Frederick Margolin, MD, was born in New York on March 11, 1936, to Gloria and Henry Margolin. He attended Miami Beach High School and the University of Florida, and he graduated from the University of Miami Medical School in 1960. He married his college sweetheart, Myrna Ross, in 1958 and interned at L.A. County Hospital. He served two years in Germany as an Air Force medical officer and, on return, completed a residency in radiology at UCSF. He practiced radiology at California Pacific Medical Center from 1968 to 2007 and served as chairman of the Department of Radiology from 1978 to 1992. He was founder and medical director of the Breast Health Center from 1984 to 2007. Fred’s many awards and honors included Fellow of the American College of Radiology and Fellow of the Society of Breast Imaging. In 2001 he was selected as one of America’s Best Doctors for Breast Care. Fred and Myrna traveled the world, often on cruises with close friends. He took his children and grandchildren to Mexico every year, cherishing the time he spent with them. He never lost his passion for learning and lived life to the fullest. Unfortunately, he developed ALS in 2009 and passed away in Greenbrae, May 10, 2012, surrounded by his family and friends. His survivors include his devoted wife of fifty-four years, Myrna, his two daughters and one son, their spouses, and seven grandsons. He will be deeply missed and fondly remembered by his family, many good friends, and colleagues. A memorial service was held at the Childrens’ Campus of CPMC on June 27.

Richard Coopersmith, MD

Richard C. Coopersmith, a psychiatrist in private practice for more than fifty-two years, was born in Chicago on May 1, 1929, and died in San Francisco on January 10, 2012, at the age of 83. He entered the University of Chicago at age 15, continued his education at the University of Illinois in Champaign/Urbana, and, like his father, received his medical degree at the State University of New York College of Medicine at Syracuse. He completed internships at Northwestern University College of Medicine and the Veterans Administration Hospital at Downey, Illinois. He was a resident at Albert Einstein College of Medicine and the Bronx Municipal Hospital Center in New York and received his certification from the American Board of Psychiatry and Neurology. As a captain in the U.S. Air Force, he served as chief of the Mental Hygiene Clinic at Wright-Patterson Air Force Base in Dayton, Ohio. He began a private practice in New York, where he served as psychiatrist-in-chief of the Mental Hygiene Clinic of the Riverside Mental Health Association and as a school psychiatrist for the New York City Board of Education. He relocated to San Francisco in 1965 and joined the Medical Society in 1970. He loved teaching and, in addition to his private practice, he served for thirty-five years as assistant clinical professor, Department of Psychiatry at UCSF, supervising residents at Langley Porter, Mount Zion Hospital, CPMC, and San Francisco General Hospital. He was on the staff of Saint Francis Hospital as well, and he served on committees at various hospitals. He had a passion for books, building a sizable collection of Californiana, and he enjoyed his 34

San Francisco Medicine September 2012

Nancy Thomson, MD

membership in the Roxburghe Club and the Book Club of California. He is survived by his wife, Nancy; his children, Peter (Cherie), Eloise, and Benjamin; and five grandchildren.

Ilse K. Wheelis, MD

Ilse K. Wheelis, a San Francisco psychiatrist and psychoanalyst who only retired from her clinical practice in 2011, died peacefully at home on January 9. She was 96. She was born Ilse Kaulbach in 1915 in Vienna, the only child of Richard Kaulbach, an obstetrician, and Sofie Fuchs. One of only three women in her medical school class, she was forced to interrupt her studies in 1938 when she left Austria. Arriving in New York, she supported herself by working as a governess for the children of a New York surgeon. At first thwarted in her efforts to return to medical school, she pursued a degree in social work. She married microbiologist Ernest Jawetz, a fellow Viennese whom she helped to get out of Austria, and moved to San Francisco. Ultimately granted full credit for her coursework in Austria, she completed her medical studies at Stanford Medical School graduating in 1949 with both academic honors and clinical distinction. Known professionally as Dr. Jawetz, she started her psychiatric residency at the Langley Porter clinic at the University of California, San Francisco and then finished her training at the Austen Riggs Center in Stockbridge, Massachusetts. Subsequently she returned to the Bay Area where she completed her psychoanalytic training at the San Francisco Psychoanalytic Institute. In addition to the robust private practice she maintained as a training and supervising psychoanalyst in San Francisco for more than fifty years, she was also much admired and sought after for her teaching and supervision at the SF Psychoanalytic Institute, UCSF Langley Porter, and Mount Zion Hospital. She was a member of the SFMS for over fifty years. Her marriage to Ernest Jawetz ended in divorce. In 1954 she married Allen Wheelis, also a psychiatrist/psychoanalyst and a well-known author who died in 2007. Her survivors include their daughter Joan Wheelis, a psychiatrist and psychoanalyst in Cambridge, Massachusetts; two stepchildren, Mark Wheelis, a microbiologist at U.C. Davis, and Seattle author Victoria Jenkins; one grandchild and several step-grandchildren and great-grand-children.

www.sfms.org


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