CHOLERA STRIKES AGAIN: RESPONSE STRATEGIES TAKE CENTER STAGE

In strange new patterns, cholera cases are making rounds in different parts of the world after the acute diarrheal illness was thought to be on the verge of eradication. According to the World Health Organization (WHO), Africa is currently experiencing an exponential rise in cholera cases and cholera-associated deaths. The trend is expected to continue into this year without strong interventions.

A major concern with cholera is its high rate of fatalities. The average case fatality ratio is currently almost at 3%, above the 2.3% reached in 2022, and far exceeding the acceptable level of below 1%. Since January 2023, the World Health Organization estimates that about 26,000 cases and 660 deaths were recorded in 10 African countries, including Malawi, Mozambique, Zambia, Burundi, Cameroon, the Democratic Republic of the Congo (DRC), Nigeria, Ethiopia, Kenya, and Somalia.

The resurgence of cholera is characterized by the number, size, and concurrence of multiple outbreaks around the world, the spread to areas free of cholera for decades, and alarming high mortality rates. Here's what you should know about the latest epidemic of cholera on the African continent and how health experts are trying to keep the water-borne disease under control.

Cholera is easily treatable but remains an anover present risk in many developing nations. In 2022, nearly 80,000 cases and 1,863 deaths were recorded from 15 affected countries across Africa. The caseload has increased by more than 30% in the first month of 2023 compared to the whole of 2022. The United Nations (UN) attributed the sharp rise in cases to conflicts, concurrent epidemics, inadequate levels of access to health care, poor drinking water, hygienic and sanitary conditions, and population movements between the affected areas and neighboring countries.

The ongoing armed conflict in the province of North Kivu in the Democratic Republic of the Congo is a case in point. In 2022, the UN Office for the Coordination of Humanitarian Affairs estimates that DRC reported 17,355 suspected cases including 285 deaths. It is unsettling that poor people living in disadvantaged neighborhoods, lacking adequate sanitation and safe drinking water are at an increased risk of becoming severely ill from diarrhoeal diseases.

Although it has sickened people from Central Africa to Eastern Africa, cholera has had particularly dramatic effects in Malawi: since last March nearly 37,000 cholera cases and 1,210 deaths have been reported in all 29 districts. More than 600 Malawians are estimated to contract the disease, or have symptoms of cholera, daily. It is the costliest cholera outbreak in Malawi's history, with the case fatality ratio near 3.1%. The nation is experiencing an outbreak of unprecedented scale, outpacing hospitals' ability to keep up with the volume of new patients.

In a disheartening twist, countries that share land borders with cholera-affected countries are at risk. The epidemic has spread to neighboring South Africa, Botswana, Mozambique, and Zambia. Grappling with severe storms brought on by Tropical Cyclone Freddy, Mozambique too is facing a multi-layer crisis, with a cumulative total of 5,237 suspected cases and 37 deaths reported in 29 districts from six out of 11 provinces in the country. All six cholera-affected provinces are flood-prone areas, and WHO anticipates that more areas will be affected as the rainy season continues.

In Zimbabwe, the dreaded disease has killed 783 people and more than 16,000 people have been affected by the latest outbreak of cholera. Since the beginning of the year, up to 15 March, cholera has claimed the lives of nearly 818 people and more than 40,563 have been affected by the disease outbreaks in 13 African countries. Other countries facing cholera outbreaks include South Africa, Haiti, Lebanon, India, Pakistan, the Philippines, Turkey, and Syria.

In some parts of the African continent, the cholera outbreak is being driven by civil unrest, mass displacement, the collapse of essential public health services, and malnutrition. Caused by comma-shaped bacteria known as Vibrio or Spirillum cholerae, which dwell in sewagecontaminated water, cholera causes a particular type of acute watery diarrhoea that leads to rapid loss of fluids. Flooding and heavy rainfalls can spread the bacteria and contaminate water sources. For instance, Nigeria is experiencing an uptick in cholera infections following extensive flooding amid the Boko Haram insurgency.

Notably, heavy flooding due to seasonal rains and tropical cyclones in Southern Africa has led to a spike in malaria cases and increased the risk of cholera outbreaks. New United Nations Children's Fund estimates show that millions of children are at risk in the face of a potential increase in cholera cases in Malawi and Mozambique in the aftermath of Tropical Cyclone Freddy. Across Malawi, an estimated 4.8 million children – "one in two children in the country" –need humanitarian assistance.

Because the incubation period of cholera is short (2 hours to 5 days), the number of cases can rise quickly and multiple deaths can occur, creating an acute public health problem. The disease risk is considerably heightened in humanitarian emergencies- large-scale displacement is often accompanied by a deterioration in hygiene and sanitation. Unsurprisingly, a combination of water scarcity and food crisis leads to the proliferation of severe malnutrition and a high risk of serious waterborne diseases.

An estimated more than 16.2 million people cannot access enough water for drinking, cooking, and cleaning across the Horn of Africa, including 8.2 million in Ethiopia, 3.9 million in Somalia, and 4.1 million in Kenya. Drought decreases the available amount of clean water, forcing people to use contaminated water. Water vulnerability makes children 11 times more likely to die from water-borne diseases than those who are well nourished, according to the current publicly available data from UNICEF. The worst drought in the region in 60 years has spurred the spread of cholera and made stopping it substantially harder. The frequent disruption of access to healthcare services and unequal distribution of health resources across impoverished areas makes access to treatment even more challenging. Communities in these drought-affected areas are in dire need of humanitarian assistance to avert a looming crisis, threatening the lives of hundreds of thousands of adults and children.

Outbreaks of water-borne disease surge globally amid climate change chaos. Shifts in climate patterns can lead to variations in water availability, rainfall, and temperature, which can create conditions favorable for the growth and spread of Vibrio cholerae. While the host for the agent of cholera is an integral part of the environment, the consequences of Vibrio-related diseases due to climate change are worsening, hampering efforts to eliminate the silent illness.

Between 1970 and 2011, African countries reported 3,221,050 suspected cholera cases to the World Health Organization, representing 46 % of all cases reported globally. Excluding the Haitian epidemic, sub-Saharan Africa accounted for 86 % of reported cases and 99 % of deaths worldwide in 2011. In 2021, Africa experienced its highest-ever reported numbers – more than 137,000 cases and 4,062 deaths in 19 countries. The global disease prevalence is now higher than previous WHO estimates, nearly 1 billion people in 43 countries face the threat of cholera infections.

Extreme weather events, including heatwaves, hurricanes, and floods, fuelled by climate change have resulted in a higher incidence of waterborne infections like cholera. These climate-related events are critical contributing factors to the breakdown of an already limited healthcare infrastructure, compromised sanitation systems and access to clean water, and ultimately, increasing vulnerability to cholera epidemics in low-resource environments.

The State of the Climate 2021 Report, a multiagency publication coordinated by the UN World Meteorological Organization (WMO), reveals that high water stress is estimated to affect about 250 million people in Africa and displace up to 700 million individuals by 2030. What's worse, four out of five African countries are unlikely to have sustainably managed water resources by 2030. Africa, despite its low contribution to greenhouse gas emissions, remains the most vulnerable continent. Climate-related hazards continue to be a major driver of new displacement in the continent, the UN agency warns.

Population density is also a critical driver of cholera spread. With hundreds of people from Somalia arriving each week in Kenya's Dadaab

Refugee Complex, living conditions in camps hosting over 233,000 refugees and thousands of new arrivals since January are worsening, according to the latest Médecins Sans Frontières (MSF) analysis. 1,875 cholera cases have so far been recorded in Dadaab camp which is hosting hundreds of thousands of refugees and asylum seekers in three camps: Dagahaley, Ifo, and Hagadera.

The number of cholera cases is rising at an alarming rate in these overcrowded camps in the context of inadequate access to clean water, waste collection, and proper toilets. In response, MSF called on relevant health stakeholders to enhance cholera prevention measures, including vaccination campaigns, to prevent large-scale outbreaks and save lives. The call to action comes after Kenya issued a cholera alert following confirmation of 61 cases reported across six counties in October 2022.

The oral cholera vaccine (OCV) has been recommended as an additional public health tool in conjunction with the safe Water, Sanitation, and Hygiene (WASH) technique as a measure to eliminate the preventable disease. Following the explosion of cholera outbreaks worldwide, WHO and its partners recommended in October 2022 that countries temporarily switch to using a single dose of the cholera vaccine instead of two to "counter" the ongoing supply shortage. The three WHO pre-qualified oral cholera vaccines, Dukoral, Shanchol, and Euvichol-Plus, have proven to be effective in controlling cholera during outbreaks by targeting critical populations in hotspots. Although the single-dose approach offers shortterm protection, the new strategy will ensure a more proactive response in containing the deadly outbreaks in endemic areas and humanitarian crises.

As attested by WHO, the pivot in strategy will allow for the doses to be used in more countries, at a time of an unprecedented rise in cholera outbreaks worldwide. The suspension of the two-dose regime is a timely response to help prevent active transmission of cholera infections as many African countries lack immediate access to vaccines. Of the total 36 million doses forecast to be produced in 2022, 24 million have already been shipped for preventive (17%) and reactive (83%) campaigns and an additional 8 million doses were approved by the International Coordinating Group for the second round for emergency vaccination in 4 countries. Illustrating the short supply of the vaccines, only 37 million doses are available in 2023.

A number of vaccines, funded by Gavi, the Vaccine Alliance, were sourced from the global stockpile and are being used to carry out major campaigns in Zambia, Nigeria, Malawi, Mozambique, and Kenya. As of February 2023, Kenya's Ministry of Health rolled out the first-ever cholera vaccination campaign in the country, targeting 2.2 million people in affected counties. MSF collaborated with the Ministry of Health and its partners to coordinate the cholera vaccination campaign reaching 122,832 people in the Dagahaley camp. Also, Malawi has conducted two oral cholera vaccination campaigns in 21

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NUMBER OF CHOLERA VACCINE DOSES AVAILABLE IN 2023 affected districts while Mozambique has kicked off a cholera vaccination drive targeting around 720,000 people in eight districts. WHO also disbursed US$6 million to kick-start emergency cholera response in Malawi, Kenya, and Mozambique, through the ICG.

To increase vaccine access, the Africa Centers for Disease Control and Prevention chief is in advanced talks with local manufacturers to explore opportunities for collaboration, particularly repurposing their facilities to meet the growing local demand for cholera vaccines. In November 2022, South Africa-based Biovac Institute inked a licensing and technology transfer pact with the International Vaccine Institute (IVI) to develop, manufacture, and deploy oral cholera vaccine doses for the African and global markets. According to Gavi, the burden of cholera could get worse unless governments put measures in place to control and prevent outbreaks. In 2015, it was estimated that over one million cases in 44 African countries resulted in an economic burden of US$130 million from cholera-related illness and its treatment. African leaders have been urged to address water and hygiene infrastructure, alongside community engagement in concerted efforts to attain the long-term goal of ending Cholera by 2030.

Apart from concerted vaccination campaigns in cholera-affected areas, the spread of the disease can be checked by educating communities about sanitation, hygiene, and food preparation. According to the Centers for Disease Control and Prevention, sustainable WASH solutions is a critical step to reducing Africa's cholera burden. The WASH strategy has been adopted in some countries of Africa, which are making up the bulk of the new cholera cases on the continent. This strategy will contribute to improvements in water supply, sanitation, food safety, and community awareness of preventive measures before outbreaks occur.

A shining example is Malawi which has launched the Malawi Cholera Flash Appeal which aims to address the most immediate needs of people impacted by the current outbreak through an integrated response that brings together health and water, sanitation and hygiene. These campaigns are usually effective particularly in mild cholera cases where victims are treated with an oral or intravenous solution of fluids and electrolytes - to replace those violently expelled by cholera's main symptom, diarrhoea. The survival rate is usually 99%.

Besides addressing the near-term risk of cholera, there is a dire need for a greater supply of vaccines and rapid progress in developing safely managed water and sanitation services to achieve the targets of the Sustainable Development Goals. More investments in socioeconomic conditions are critical to curbing the growing incidences of cholera, acute watery diarrhoea, dysentery, and other diarrheal diseases. Prevention is key at a time when nearly half the world lacks access to safely managed sanitation. Efforts for an integrated approach to cholera control are vital to tackle cross-border transmission and persistence of cholera outbreaks.

According to WHO, cholera surveillance should be part of an integrated disease surveillance system that includes feedback at the local level and information-sharing at the global level. A concerted action of all relevant government ministries is needed to realize access to safe drinking water and sanitation, which are internationally recognized human rights. To successfully eliminate cholera by 2030, national, regional, and international bodies should also be empowered to coordinate the implementation of joint interventions addressing health inequities and human-related determinants

USA — Medical technology company Stryker has launched Mako Total Knee 2.0, the latest advancement in its Mako SmartRobotics system at the AAOS 2023 Annual Meeting.

Leveraging the strengths of the Mako SmartRobotics system, including 3D CT-based planning, AccuStop haptic technology, and insightful data analytics, the new system promises better patient outcomes compared to manual surgery for total knee, total hip, and partial knee procedures.

Mako Total Knee 2.0 includes a new, intuitive design with customizable workflows and other features, such as a digital tensioner for assessing knee stability during total knee arthroplasty. The system began a limited release in August 2022 and will roll out in phases in 2023. Stryker also plans to launch two additional Mako systems, Mako Spine and Mako Shoulder, in the near future.

USA — Bruker, a leading life science research and diagnostics solutions provider headquartered in the US, has unveiled a range of cuttingedge diagnostic solutions specifically designed for routine clinical microbiology and infection diagnostics laboratories.

These solutions include the nextgeneration MALDI Biotyper IVD Software, MBT Mycobacteria IVD Kit, MBT HT Filamentous Fungi IVD Module, and LiquidArray Gastrointestinal PCR Assay.

Bruker’s innovative MALDI Biotyper (MBT) platform employs a molecular approach based on proteomic fingerprinting to enable swift identification and classification of bacteria, yeasts, and fungi.

According to the company, the platform delivers rapid and reliable results, thus facilitating timely decisionmaking for better patient outcomes.

The MALDI Biotyper (MBT) system, offers rapid sample target exchange and can analyze up to 600 samples per hour.

Moreover, this system covers over 4,600 species in the reference library, making it a versatile and reliable tool for microbial identification.

The MBT system now comes equipped with the new IDealTune, which offers fully automated tuning of MALDI-TOF parameters within a sample run, delivering consistent data quality without requiring any user intervention.

Wolfgang Pusch, the President of Bruker’s Microbiology and Infection Diagnostics Division, stated that the company’s new diagnostic solutions, such as IVD workflows, kits, software, and reference libraries for mycobacteria and fungi, are expanding the applications of their established MALDI Biotyper platform.

Pusch also highlighted that the new LiquidArray Gastrointestinal is a nextgeneration syndromic panel that offers amazing pathogen coverage and is ideal for laboratories that require a broad screening approach to detect most pathogens in one run.

USA — Cardiawave, a medical device manufacturer, has been granted three US patents for its Valvosoft ultrasound device used in treating aortic stenosis, the most common heart valve disease in adults.

The patents cover the device's ultrasound imaging and therapy system, detection and monitoring of cavitation bubbles that create the therapeutic effect generated by the focused ultrasound, and the entire apparatus for treating deep vein thrombosis.

Cardiawave's device aims to provide a safe and effective non-invasive alternative to surgical interventions, such as transcatheter aortic valve replacement, and address the unmet medical need in treating severe symptomatic aortic stenosis in patients, particularly those who do not undergo treatment.