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Best allocation protocol for limited cholera vaccines – Fred Hutch News Service

Fred Hutch, Seattle Cancer Care Alliance, and UW Medicine Complete Restructure of Partnership
The diarrheal disease, cholera, is caused by the bacterium, Vibrio cholerae, and is transmitted by the fecal-oral route. This means that fecal contamination of water, food or living spaces can create hot spots for transmission of V. cholerae. To limit bacterial spread, access to clean water and proper sanitation are required but not always accessible. For example, in October of 2010 a catastrophic earthquake resulted in the displacement of over a million people in Haiti (CDC). This event was followed by an outbreak of cholera, at a time when there was limited access to clean water and proper sanitation for an extended time. While this event received extensive press coverage, cholera outbreaks are ongoing in several countries in Africa and Asia with between 100-100,000 confirmed cases per country in 2022 alone (ECDC). In the event of natural disasters or occurrences in which large populations of people are displaced to generate cholera hot-spots, vaccination against V. cholerae would aid in limiting disease and death due to cholera. The oral cholera vaccine has minimal single-dose efficacy rates for children under 5 years old (~8%) and moderate efficacy rates for those over 5 years old (>50%). For two-doses, the vaccine efficacy rates for children under 5 approach single-dose rates for those over 5 (>40%) and individuals over 5 years old have higher efficacy rates than single-dose recipients (>70%). This significant difference between single and double dose vaccination efficacies for children under 5 is challenging, especially when oral cholera vaccine stockpiles are limited. Drs. Tiffany Leung and Laura Matrajt from Fred Hutchinson Cancer Center in collaboration with Dr. Julie Eaton from the University of Washington addressed this challenge of how to allocate limited oral cholera vaccines to optimally reduce disease burden. Their findings were published recently in PLoS Neglected Tropical Diseases.
The standard vaccination regimen in most circumstances is to give two-dose vaccinations, irrespective of age. “When vaccine supply is limited, it has previously been suggested to give a single dose of vaccine to twice as many people. In fact, some countries have successfully carried out single-dose vaccination campaigns,” stated Dr. Matrajt. Yet, the challenges of limited cholera vaccine efficacy for children under 5 and vaccine supply shortages provide conflicting pressures on the decision to conduct single- versus double-vaccine campaigns. “In this study, we used mathematical models paired with optimization algorithms to determine when is optimal to use single-dose or full-dose [two-dose] vaccines,” explained Dr. Matrajt.
The models developed were based on past vaccine allocation data from three “scenarios where large cholera outbreaks have occurred: a refugee camp in Thailand, a highly populated city in Chad, and a region torn by a natural disaster, Haiti,” commented Dr. Matrajt. For the refugee camp, the model included in-migration and out-migration variables as people enter and exit the camp to alter transmission. In the case of Chad, the outbreak in the highly populated city occurred during the rainy season which may impact sanitation of the water reservoir. Thus, rainfall was added as a variable for this setting. The third setting modeled cholera in Haiti following a catastrophic earthquake. Prior to the earthquake, Haiti did not have V. cholerae, but after this natural disaster, the introduction of V. cholerae to Haiti resulted in endemic V. cholerae. This model of post-natural disaster and pre-endemic V. cholerae setting included migration through two modes, road and river networks, and changes between dry and rainy season. These setting-specific variables were combined with two age groups to model the best method of dose allocation with the lowest disease burden.
“We found that in the short term (1 year) when there is limited vaccine supply, it is optimal to vaccinate individuals over five years old with one dose and young children under five years old with two doses.” This strategy would offer moderate vaccine efficacy rates (>40%) for all vaccinated individuals and would remain effective for 2 or 4 years depending on single or double dosage, respectively. However, the model for the Haiti setting did differ from the other two models in the timing of vaccinations for those under 5 years old. One explanation for this difference was that in Haiti there was delayed vaccination until cholera was widespread, while the other two settings employed timely vaccination campaigns. Therefore, the differences in V. cholerae spread altered the optimal modeled timing of vaccination of those under and over 5 years old to occur concurrently as opposed to first vaccinating those over 5 years old.
“Our optimal strategies prevented the most cases, save the most lives, and avert 1.2 to 1.8 times as many cases and deaths as the standard two-dose untargeted strategy for all the scenarios considered.” Using this vaccination strategy, deaths averted were 87%, 55% and 25% for the refugee camp in Thailand, highly populated city in Chad, and natural disaster struck Haiti, respectively. The strategy of using modeling has provided insight into how vaccination strategies are employed for cholera and support a single-dose vaccination regimen for most except those under 5 years old. Additionally, these models highlighted several important variables relevant to cholera transmission that may be relevant to other communicable diseases. Dr. Matrajt is currently extending this modeling strategy to other public health interventions to evaluate the effectiveness of these standard approaches on limiting other disease burdens.
The spotlighted research was funded by the UK Foreign, Commonwealth and Development Office, and Wellcome.
Leung T, Eaton J, Matrajt L. 2022. Optimizing one-dose and two-dose cholera vaccine allocation in outbreak settings: A modeling study. PLoS Negl Trop Dis. 16(4):e0010358.
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