Epidemiologist, Kenya Field Epidemiology and Laboratory Training Program (K-FELTP) | Ministry of Health Kenya
Waqo Boru at Johns Hopkins University
Mr. Waqo Boru, BSc, MSc is an Epidemiologist with the Field Epidemiology and Laboratory Training Program at the Ministry of Health in Kenya. When asked what piqued his interest in cholera, Waqo rattles off a list of questions he hoped his research would be able to answer: “Why is this outbreak (that began in 2014) different from others? Where is cholera coming from, and what makes it unique? Are there environmental factors that contribute to its transmission? Is there a genetic mutation, or several, contributing to the current outbreak?”
In a recent interview with Brittany Goetsch, a Program Officer on the Delivering Oral Cholera Vaccine Effectively (DOVE) Project, Waqo described his collaboration with the DOVE Project, his work in cholera, and how he hopes his research will inform response efforts—including to the current cholera outbreak in Kenya with 17,597 cases reported between December 2014 and July 2017.1
According to Waqo, “The outbreak popped up out of nowhere and affected many counties in Kenya within a short amount of time,” after no recorded cases of cholera in the country between 2011 and 2014.
Recently Waqo traveled to Baltimore, Maryland to conduct research with the DOVE Project—funded by the Bill and Melinda Gates Foundation and led by the Johns Hopkins Bloomberg School of Public Health. The DOVE Project works to strengthen research and surveillance capacity to understand cholera transmission and inform response efforts at the country level. Under the project, DOVE hosts visiting researchers to work alongside DOVE scientists to support critical research and capacity development in cholera surveillance and laboratory techniques.
Waqo and DOVE scientists sought to better understand the particular genomes of the cholera strains present in the current outbreak and where each genome is present through multiple-locus variable number tandem repeat analysis (MLVA). Determining which genotypes of cholera are present in each geographic area helps scientists understand how the virus is spread within and outside of countries. It also helps identify when and if a strain of cholera has mutated and what this might mean for treatment efforts. Together, the team identified multiple genotypes of cholera within Kenya, and determined that multiple genotypes are present in the same area. As Waqo explains it, “This could be why [they’re] having protracted cholera outbreaks.”
Waqo’s work also includes the development of hotspot maps that use water and sanitation and surveillance data to visualize the geographic characteristics of a cholera outbreak, including the number of reported cases, the number of reported deaths, and the spread of cholera over time. This allows countries to geographically target their response efforts. Waqo expressed the frustration that, “it’s always discouraging when you put in a lot of effort and still find the same problem recurring in the country.” But he feels hopeful that recent research efforts, including hotspot mapping and identifying genome markers of the current cholera strain, can greatly impact the cholera response by facilitating more targeted response efforts.
Waqo has seen firsthand what quality data can do to guide outbreak response efforts. In response to an outbreak in 2015, his team was able to determine that the cholera cases were occurring around a specific river that runs through the county. They did this by tracking active cases, following up with patients who completed treatment, and creating case maps. He was able to tell the response team to focus their efforts on the areas surrounding the river, and attempt to implement chlorination. Due to this guidance, cases in the county decreased significantly. “It is cases like that that really excite me about what is going on in the field,” he says. Waqo believes being ahead of the response teams is critical, and hopes his work with the DOVE Project is able to inform current response efforts.
Listen to Waqo discuss how data is used in cholera responses.
Senior Laboratory Technologist/Microbiologist, Head of Molecular Microbiology Laboratory at the National Health Laboratory and Diagnostic Services | Ministry of Health Uganda
Francis Ongole at Johns Hopkins University
Francis Ongole describes himself as the type of person who wants to learn everything. This desire for knowledge led him first to the field of microbiology and public health then to the field of cholera, where he has been working for the last four years in Uganda to understand cholera epidemiology, outbreaks investigation and laboratory confirmation using both rapid diagnostic tests (RDTs) and the gold standard of culture and sensitivity.
"In Uganda, we have districts that have been ear-marked as cholera hot spots where year after year you would expect cholera disease outbreaks. These are mainly along Lake Albert. Due to porous borders, most of the cholera is imported and affected communities are mainly the refugees in refugee camps.” Francis is a Senior Laboratory Technologist/Microbiologist at the Uganda National Health Laboratory Services, previously known as the Central Public Health Laboratories at the Ministry of Health. He is based in the Department of Disease Surveillance and Outbreak Investigation (National Microbiology Reference Laboratory) and is responsible for analyzing disease outbreak samples to confirm outbreaks, conduct surveillance and direct response efforts.
Through a long-established collaboration between the Delivering Oral Cholera Vaccine (DOVE) Project, the Ministry of Health in Uganda, and Makerere University (based in Kampala), Francis has worked with the DOVE Project in strengthening laboratory capacity in Uganda and conducting cholera research through in-country and remote trainings. He recently traveled to Baltimore, Maryland to increase his familiarity with new technologies and equipment use in molecular characterization of Vibrio cholerae.
The DOVE Project, funded by the Bill and Melinda Gates Foundation and led by the Johns Hopkins Bloomberg School of Public Health, works to strengthen research and surveillance capacity to understand cholera transmission and inform response efforts at the country level. Under the project, DOVE hosts visiting researchers to work alongside DOVE scientists to support critical research and capacity development in cholera surveillance and laboratory techniques.
In a recent interview with Brittany Goetsch, a Program Officer on the DOVE Project, Francis discussed his work in cholera, strengthening laboratory capacities, and the importance of communication in cholera modes of transmission, prevention and control.
Francis worked alongside DOVE team members to conduct research using several analysis techniques, including NanoDrop. The NanoDrop quantifies the amount of DNA present in a sample prior to analysis in order to minimize wasted reagents and time spent on samples with insignificant amount of DNA. As Francis explained, “The NanoDrop, which I didn’t have in my lab, was something new, and through that I’ve managed to find out the concentration of DNA in the various samples I analyzed.” This has implications for the sensitivity of testing. A negative result could be correlated to a low DNA concentration in a sample. The ability to accurately identify cholera samples is critical in confirming the presence of cholera disease outbreaks and directing response efforts, and can be impacted significantly by the quality of samples and use of standard operating procedures.
Through his time in Baltimore with DOVE, Francis appreciated the importance of adherence to standard operating procedures in test performance, best practices and observance of safety issues, especially when it comes to disposals of generated wastes (e.g. gels) used in analysis, as well as the potential possibility for contamination in both molecular and microbiology labs. According to Francis, “molecular and microbiology lab processes are very sensitive when it comes to contaminations, and one has to follow the standard operating procedures.” Francis commented on how he observed an extensive protocol of how to dispose of waste, and separate materials being thrown away based on chemical composition to reduce potential exposures. He is excited to return to Uganda and share with his colleagues about how it is “paramount to look at every step,” and adhere to standard operating procedures, including infection control and waste disposal. Francis also discussed important aspects of cholera prevention, including ensuring that people understand the prevention measures.
Francis mentioned how cholera is a preventable disease, but that in order for prevention to be effective, people need to understand the messages that are being communicated. He commented that “[as scientists] we might use our scientific, very complicated words, but this communication needs to be simplified to the simplest way so that anybody can understand, practice, and use it.” The engagement of communities is important so that “each family is playing their part to mobilize their neighbors.” Francis commented that the “cases we’re hearing about are not within communities where vaccination has been done, but from newcomers (refugees) and those that perhaps have not received the vaccination, so to me, a knowledge gap, poor hygiene practices and unimplemented WASH programs have been a major challenge.” As he says, “Knowledge is power, knowledge is strength,” and filling that knowledge gap and empowering the community will impact cholera morbidity and mortality in Uganda.
Research Fellow | Centre for Infectious Disease Research in Zambia (CIDRZ)
John Mwaba in the Johns Hopkins University Lab.
This is the question that prompted John Mwaba, a Research Fellow at the Centre for Infectious Disease Research in Zambia (CIDRZ), to enter into the field of medical microbiology, and ultimately led him to the field of cholera.
Each year, around 2.8 million people suffer from cholera and about 91,000 die from this preventable disease.1
Cholera is “one of the biggest challenges the world is facing,” John noted in a recent interview, and an estimated 1.3 billion people are at risk. According to John, if we do nothing, the number might double in the next five to 10 years.
Recently, John’s work on cholera outbreaks and oral cholera vaccine in Zambia took him to the United States to work with the Delivering Oral Vaccine Effectively (DOVE) Project, funded by the Bill and Melinda Gates Foundation and led by the Johns Hopkins Bloomberg School of Public Health.
In a recent interview with Brittany Goetsch, a Program Officer on the DOVE Project, John discussed his work in cholera, his collaboration with the DOVE Project, and where he sees the future of cholera research and response efforts.
To support capacity development in cholera surveillance and laboratory techniques, DOVE hosts visiting researchers to travel to Baltimore, Maryland and work alongside DOVE scientists at the Johns Hopkins Bloomberg School of Public Health. During the several weeks John spent in Baltimore, he and DOVE scientists further explored the effectiveness of oral cholera vaccines in providing immunity—research that will inform national cholera control plans and cholera response efforts in Zambia. Their research focused on immunological assays—not currently available in Zambia—that allow for the testing of immunity among blood samples from people who received oral cholera vaccine. Together, they assessed if the same cholera strains are causing recent and past cholera outbreaks by analyzing V. cholerae isolates from 2009, 2010, 2016, and 2017 using multiple-locus variable-number tandem-repeat analysis (MLVA). This analysis will impact our understanding of how cholera spreads across and within countries, and the potential for closer collaboration with neighboring countries in combating cholera outbreaks. “Having this kind of knowledge will help in policy formulation at both country levels as well as regional levels,” noted John, which is critical to cholera response.
Additionally, during his time in the U.S. John worked closely with DOVE Scientist Dr. Mohamed Ali on hotspot mapping. Hotspot mapping is the process by which areas at a high risk of disease are identified through data from current and past outbreak surveillance, demographics, and water and sanitation infrastructure. According to John, identifying areas at high risk of cholera is important to guide response efforts and effectively implement campaigns. The DOVE Project works in conjunction with in-country researchers and health experts to develop hotspot maps in several countries in order to inform cholera surveillance and response efforts. John and Dr. Ali developed hotspot maps for several districts within Zambia, analyzing retrospective data from cholera outbreaks, water and sanitation infrastructure indicators, and demographics from 2008 to 2017. John hopes to use this information in coordination with the Ministry of Health for cholera prevention and control measures. “If every person knows how cholera is transmitted, how cholera is spread, they will be in a position to better protect themselves from catching cholera.”
Looking to the future, in 10 years, John hopes to see a reduction in the number of people at risk, and that research finds the “ways and means of sustaining the reduction.” However, despite achievements in limiting the spread of cholera and preventing outbreaks, John notes that failure to maintain these measures could mean that the number of cases begins to rise again.
Listen to John discuss what he wishes people knew about cholera, and where he sees cholera in the next 10 years.
Director, Public Relations and Marketing | Johns Hopkins Center for Communication Programs
This post, written by Stephanie Desmon, originally appeared on Johns Hopkins Center for Communication Programs' website.
Without clean water and proper sanitation, many Zambian fishermen and their families are at serious risk for cholera. A joint research study between the Delivering Oral Vaccine Effectively (DOVE) project and the Centre for Infectious Disease Research in Zambia aims to find better ways to protect them.
Led by the Johns Hopkins Bloomberg School of Public Health and funded by the Bill & Melinda Gates Foundation, DOVE works globally to distribute oral cholera vaccine to the people most in need. The Johns Hopkins Center for Communication Programs supports these efforts.
This spring, photographer Karen Kasmauski traveled to Zambia to document the lives of those involved in the study—and to demonstrate how challenging it is for the fishermen and their families to drink and bathe in clean water.
The internationally-licensed killed oral cholera vaccines (OCV): Dukoral, Shanchol, and Euvichol are recommended as two-dose regimens given one to two weeks apart. However, delivery of two doses can be challenging during emergency situations, especially when vaccine supplies are limited.
Under certain circumstances, a one-dose campaign, where a larger number of people receive OCV may be better than a two-dose strategy, where half as many people are vaccinated. The recommended two-dose regimen provides at least 64 percent protection during the third year after vaccination but in emergency situations, the shortened duration of outbreaks after just one OCV dose is given could make the extended protection conferred by a second dose less urgent .
Recently, we published a review on single-dose killed OCV . We included both immunity and protection data since a vaccine-induced increase in immune response in the blood has been linked (although imperfectly) with protection, and because there are relatively few studies that document protection conferred by single-dose killed OCV against cholera. In the pooled analysis of immunogenicity studies, over 70 percent of participants who receive an OCV dose developed an immune response detectable in their blood. We combined available data on protection from one randomized trial in Bangladesh  and five observational studies [4-8]. Single-dose protection is greatest soon after vaccination and wanes over time; from 87 percent at two months decreasing to 33 percent at two years. Since publication of our review, additional data has become available. For example, an observational study in Zambia showed single-dose protection of 89 percent at seven weeks , and the two-year follow-up of the Bangladesh trial showed 39 percent vaccine efficacy, as shown in the red font and circles in the Figure below . Importantly, the randomized trial in Bangladesh found no significant protective effect in children younger than five years [3, 10], but a single OCV dose conferred 57 percent protection in older children and adults at two years of follow-up.
Although single-dose OCV provides lower protection of shorter duration compared to two doses, this may be sufficient to reduce short-term risk in outbreaks or other high-risk settings. Aside from the studies described above, there is increasing experience with single-dose OCV campaigns. In 2016, during a resurgence of cholera cases after Hurricane Matthew, Haiti launched a large emergency campaign when more than 700,000 people received a single dose of OCV [11, 12]. In 2017, during mass vaccinations of Rohingya refugees in Bangladesh, one dose of OCV was given to more than 700,000 people, while a second dose was given to children between the ages of one and five .
Overall, we found that protection from a single-dose of killed OCV may be sufficient to reduce short-term risk during outbreaks or other high-risk settings, especially when vaccine supply is limited. However, a second dose should be given as soon as circumstances allow to ensure longer and more robust protection.
Figure: Estimated single-dose oral cholera vaccine protection (95% confidence intervals), by study site and month of follow-up [3-10]
Azman AS, Luquero FJ, Ciglenecki I, Grais RF, Sack DA, Lessler J. The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study. PLoS Med. 2015;12(8):e1001867. doi: 10.1371/journal.pmed.1001867. PubMed PMID: 26305226; PubMed Central PMCID: PMC4549326.
Lopez AL, Deen J, Azman AS, Luquero FJ, Kanungo S, Dutta S, et al. Immunogenicity and protection from a single dose of internationally available killed oral cholera vaccine: a systematic review and meta-analysis. Clin Infect Dis. 2017. doi: 10.1093/cid/cix1039. PubMed PMID: 29177437.
Qadri F, Wierzba TF, Ali M, Chowdhury F, Khan AI, Saha A, et al. Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh. N Engl J Med. 2016;374(18):1723-32. doi: 10.1056/NEJMoa1510330. PubMed PMID: 27144848.
Azman AS, Parker LA, Rumunu J, Tadesse F, Grandesso F, Deng LL, et al. Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study. The Lancet Global health. 2016;4(11):e856-e63.
Luquero FJ, Grout L, Ciglenecki I, Sakoba K, Traore B, Heile M, et al. Use of Vibrio cholerae vaccine in an outbreak in Guinea. N Engl J Med. 2014;370(22):2111-20. doi: 10.1056/NEJMoa1312680. PubMed PMID: 24869721.
Khatib AM, Ali M, von Seidlein L, Kim DR, Hashim R, Reyburn R, et al. Effectiveness of an oral cholera vaccine in Zanzibar: findings from a mass vaccination campaign and observational cohort study. The Lancet Infectious diseases. 2012;12(11):837-44. doi: 10.1016/S1473-3099(12)70196-2. PubMed PMID: 22954655.
Ivers LC, Hilaire IJ, Teng JE, Almazor CP, Jerome JG, Ternier R, et al. Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis. The Lancet Global health. 2015;3(3):e162-8. doi: 10.1016/S2214-109X(14)70368-7. PubMed PMID: 25701994; PubMed Central PMCID: PMC4384694.
Wierzba TF, Kar SK, Mogasale VV, Kerketta AS, You YA, Baral P, et al. Effectiveness of an oral cholera vaccine campaign to prevent clinically-significant cholera in Odisha State, India. Vaccine. 2015;33(21):2463-9. doi: 10.1016/j.vaccine.2015.03.073. PubMed PMID: 25850019.
Ferreras E, Chizema-Kawesha E, Blake A, Chewe O, Mwaba J, Zulu G, et al. Single-Dose Cholera Vaccine in Response to an Outbreak in Zambia. N Engl J Med. 2018;378(6):577-9. doi: 10.1056/NEJMc1711583. PubMed PMID: 29414267.
Qadri F, Ali M, Lynch J, Chowdhury F, Khan AI, Wierzba TF, et al. Efficacy of a single-dose regimen of inactivated whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial. The Lancet Infectious diseases. 2018. doi: 10.1016/S1473-3099(18)30108-7. PubMed PMID: 29550406.