Modalities and preferred routes of geographic spread of cholera from endemic areas in eastern Democratic Republic of the Congo.

Cholera is endemic along the Great Lakes Region, in eastern Democratic Republic of the Congo (DRC). From these endemic areas, also under perpetual conflicts, outbreaks spread to other areas. However, the main routes of propagation remain unclear. This research aimed to explore the modalities and likely main routes of geographic spread of cholera from endemic areas in eastern DRC. We used historical reconstruction of major outbreak expansions of cholera since its introduction in eastern DRC, maps of distribution and spatiotemporal cluster detection analyses of cholera data from passive surveillance (2000-2017) to describe the spread dynamics of cholera from eastern DRC. Four modalities of geographic spread and their likely main routes from the source areas of epidemics to other areas were identified: in endemic eastern provinces, and in non-endemic provinces of eastern, central and western DRC. Using non-parametric statistics, we found that the higher the number of conflict events reported in eastern DRC, the greater the geographic spread of cholera across the country. The present study revealed that the dynamics of the spread of cholera follow a fairly well-defined spatial logic and can therefore be predicted.

Vibrio cholerae was found in cultured bullfrog.

Bullfrog is one of the most important economic aquatic animals in China that is widely cultured in southern China and is a key breed recommended as an industry of poverty alleviation in China. During recent years, a fatal bacterial disease has often been found in cultured bullfrogs. The clinical manifestations of the diseased bullfrogs were severe intestinal inflammation and an anal prolapse. A bacterial pathogen was isolated from the diseased bullfrog intestines. The bacterium was identified as Vibrio cholerae using morphological, biochemical and 16S rRNA phylogenetic analysis. In this study, V. cholerae was isolated and identified in diseased bullfrogs for the first time, providing a basis for the diagnosis and control of the disease. Therefore, attention should be paid to the modes of transmission of V. cholerae from bullfrog and formulate reasonable safety measures.

Case-area targeted preventive interventions to interrupt cholera transmission: Current implementation practices and lessons learned.

BACKGROUND: Cholera is a major cause of mortality and morbidity in low-resource and humanitarian settings. It is transmitted by fecal-oral route, and the infection risk is higher to those living in and near cholera cases. Rapid identification of cholera cases and implementation of measures to prevent subsequent transmission around cases may be an efficient strategy to reduce the size and scale of cholera outbreaks. METHODOLOGY/PRINCIPLE FINDINGS: We investigated implementation of cholera case-area targeted interventions (CATIs) using systematic reviews and case studies. We identified 11 peer-reviewed and eight grey literature articles documenting CATIs and completed 30 key informant interviews in case studies in Democratic Republic of Congo, Haiti, Yemen, and Zimbabwe. We documented 15 outbreaks in 12 countries where CATIs were used. The team composition and the interventions varied, with water, sanitation, and hygiene interventions implemented more commonly than those of health. Alert systems triggering interventions were diverse ranging from suspected cholera cases to culture confirmed cases. Selection of high-risk households around the case household was inconsistent and ranged from only one case to approximately 100 surrounding households with different methods of selecting them. Coordination among actors and integration between sectors were consistently reported as challenging. Delays in sharing case information impeded rapid implementation of this approach, while evaluation of the effectiveness of interventions varied. CONCLUSIONS/SIGNIFICANCE: CATIs appear effective in reducing cholera outbreaks, but there is limited and context specific evidence of their effectiveness in reducing the incidence of cholera cases and lack of guidance for their consistent implementation. We propose to 1) use uniform cholera case definitions considering a local capacity to trigger alert; 2) evaluate the effectiveness of individual or sets of interventions to interrupt cholera, and establish a set of evidence-based interventions; 3) establish criteria to select high-risk households; and 4) improve coordination and data sharing amongst actors and facilitate integration among sectors to strengthen CATI approaches in cholera outbreaks.

JMM Profile: Vibrio cholerae: an opportunist of human crises.

Vibrio cholerae O1 is the aetiological agent of the severe diarrhoeal disease cholera. Annually, there are an estimated 1-4 million cholera cases worldwide and over 140 000 deaths. The primary mode of disease transmission is through the consumption of water or food contaminated with the bacterium. Although cholera patients can be treated effectively using rehydration therapy, the disease remains a major scourge in areas with limited access to clean water and proper sanitation. Its continued prevalence highlights the failure of socioeconomic policies leading to wealth disparities, fragile and dated public infrastructure, and lack of appropriate health surveillance.

Mathematical Modeling of Endemic Cholera Transmission.

Mathematical modeling can be used to project the impact of mass vaccination on cholera transmission. Here, we discuss 2 examples for which indirect protection from mass vaccination needs to be considered. In the first, we show that nonvaccinees can be protected by mass vaccination campaigns. This additional benefit of indirect protection improves the cost-effectiveness of mass vaccination. In the second, we model the use of mass vaccination to eliminate cholera. In this case, a high population level of immunity, including contributions from infection and vaccination, is required to reach the "herd immunity" threshold needed to stop transmission and achieve elimination.

Spread and Endemicity of Cholera in India: Factors Beyond the Numbers.

Cholera outbreaks currently account for 1.3 to 4.0 million cases and cause between 21 000 and 143 000 deaths worldwide. Cholera is preventable by proper sanitization and immunization; however, in many developing nations such as India, cholera disease is endemic. The surveillance system in India does not adequately capture the actual number of cases. As a result, it is important to utilize limited public health resources correctly in India and other developing counties more effectively to reach vulnerable communities. In this study, we analyze how studies make sense of cholera transmission and spread in India from 1996 to 2015. Furthermore, we analyze how a more sensitive surveillance system can contribute to cholera eradication by giving rise to outbreak preparedness.

Household Disinfection Interventions to Prevent Cholera Transmission: Facilitators, Barriers, Training, and Evidence Needs.

There are two common household disinfection interventions to prevent interhousehold transmission of cholera: household spraying, whereby a team disinfects cholera patients' households, and household disinfection kits (HDKs), whereby cleaning materials are provided to cholera patients' family members. Currently, both interventions lack evidence, and international agencies recommend HDK distribution; however, household spraying remains widely implemented. To understand this disconnect, we conducted 14 key informant interviews with international and national responders and a study in Haiti assessing HDK efficacy using two training modules including 20 household surveys and 327 surfaces samples before and after cleaning. During interviews, 80% of the international-level informants discussed evidence gaps for both interventions, and 60% preferred HDKs. Conversely, no national-level informants knew what an HDK was; therefore, they all preferred spraying. Informants discussed behavior changes, bleach perceptions, and implementation as facilitators and/or barriers to implementing both interventions. In households, training with demonstrations regarding the use of HDK led to increased reductions of Escherichia coli (P < 0.001) and Vibrio spp. (P < 0.001) on surfaces after participants cleaned the household compared with a hygiene promotion session only. These results emphasize the gap between the current international-level policy and the realities of cholera response programs, highlight the need for evidence to align household disinfection recommendations, and underscore the importance of the dissemination and training of responders and affected populations regarding methods to prevent intrahousehold cholera transmission.

Regional sequencing collaboration reveals persistence of the T12 Vibrio cholerae O1 lineage in West Africa.

Background: Despite recent insights into cholera transmission patterns in Africa, regional and local dynamics in West Africa-where cholera outbreaks occur every few years-are still poorly understood. Coordinated genomic surveillance of Vibrio cholerae in the areas most affected may reveal transmission patterns important for cholera control. Methods: During a regional sequencing workshop in Nigeria, we sequenced 46 recent V. cholerae isolates from Cameroon, Niger, and Nigeria (37 from 2018 to 2019) to better understand the relationship between the V. cholerae bacterium circulating in these three countries. Results: From these isolates, we generated 44 whole Vibrio cholerae O1 sequences and analyzed them in the context of 1280 published V. cholerae O1 genomes. All sequences belonged to the T12 V. cholerae seventh pandemic lineage. Conclusions: Phylogenetic analysis of newly generated and previously published V. cholerae genomes suggested that the T12 lineage has been continuously transmitted within West Africa since it was first observed in the region in 2009, despite lack of reported cholera in the intervening years. The results from this regional sequencing effort provide a model for future regionally coordinated surveillance efforts. Funding: Funding for this project was provided by Bill and Melinda Gates Foundation OPP1195157.

Three transmission events of Vibrio cholerae O1 into Lusaka, Zambia.

BACKGROUND: Cholera has been present and recurring in Zambia since 1977. However, there is a paucity of data on genetic relatedness and diversity of the Vibrio cholerae isolates responsible for these outbreaks. Understanding whether the outbreaks are seeded from existing local isolates or if the outbreaks represent separate transmission events can inform public health decisions. RESULTS: Seventy-two V. cholerae isolates from outbreaks in 2009/2010, 2016, and 2017/2018 in Zambia were characterized using multilocus variable number tandem repeat analysis (MLVA) and whole genome sequencing (WGS). The isolates had eight distinct MLVA genotypes that clustered into three MLVA clonal complexes (CCs). Each CC contained isolates from only one outbreak. The results from WGS revealed both clustered and dispersed single nucleotide variants. The genetic relatedness of isolates based on WGS was consistent with the MLVA, each CC was a distinct genetic lineage and had nearest neighbors from other East African countries. In Lusaka, isolates from the same outbreak were more closely related to themselves and isolates from other countries than to isolates from other outbreaks in other years. CONCLUSIONS: Our observations are consistent with i) the presence of random mutation and alternative mechanisms of nucleotide variation, and ii) three separate transmission events of V. cholerae into Lusaka, Zambia. We suggest that locally, case-area targeted invention strategies and regionally, well-coordinated plans be in place to effectively control future cholera outbreaks.

Historical and contemporary views on cholera transmission: are we repeating past discussions? Can lessons learned from cholera be applied to COVID-19?

Cholera, a devastating diarrheal disease that caused several global pandemics in the last centuries, may share some similarities with the new COVID-19. Cholera has affected many populations in history and still remains a significant burden in developing countries. The main transmission route was thought to be predominantly through contaminated drinking water. However, revisiting the historical data collected during the Copenhagen 1853 cholera outbreak allowed us to re-evaluate the role of drinking-water transmission in a city-wide outbreak and reconsider some critical transmission routes, which have been neglected since the time of John Snow. Recent empirical and cohort data from Bangladesh also strengthened the dynamic potentiality of other transmission routes (food, fomite, fish, flies) for transmitting cholera. Analyzing this particular nature of the cholera disease transmission, this paper will describe how the pattern of transmission routes are similar to COVID-19 and how the method of revisiting old data can be used for further exploration of new and known diseases.

Sensor-based localization of epidemic sources on human mobility networks.

We investigate the source detection problem in epidemiology, which is one of the most important issues for control of epidemics. Mathematically, we reformulate the problem as one of identifying the relevant component in a multivariate Gaussian mixture model. Focusing on the study of cholera and diseases with similar modes of transmission, we calibrate the parameters of our mixture model using human mobility networks within a stochastic, spatially explicit epidemiological model for waterborne disease. Furthermore, we adopt a Bayesian perspective, so that prior information on source location can be incorporated (e.g., reflecting the impact of local conditions). Posterior-based inference is performed, which permits estimates in the form of either individual locations or regions. Importantly, our estimator only requires first-arrival times of the epidemic by putative observers, typically located only at a small proportion of nodes. The proposed method is demonstrated within the context of the 2000-2002 cholera outbreak in the KwaZulu-Natal province of South Africa.

Highly targeted spatiotemporal interventions against cholera epidemics, 2000-19: a scoping review.

Globally, cholera epidemics continue to challenge disease control. Although mass campaigns covering large populations are commonly used to control cholera, spatial targeting of case households and their radius is emerging as a potentially efficient strategy. We did a Scoping Review to investigate the effectiveness of interventions delivered through case-area targeted intervention, its optimal spatiotemporal scale, and its effectiveness in reducing transmission. 53 articles were retrieved. We found that antibiotic chemoprophylaxis, point-of-use water treatment, and hygiene promotion can rapidly reduce household transmission, and single-dose vaccination can extend the duration of protection within the radius of households. Evidence supports a high-risk spatiotemporal zone of 100 m around case households, for 7 days. Two evaluations separately showed reductions in household transmission when targeting case households, and in size and duration of case clusters when targeting radii. Although case-area targeted intervention shows promise for outbreak control, it is critically dependent on early detection capacity and requires prospective evaluation of intervention packages.

Mathematical Analyses on the Effects of Control Measures for a Waterborne Disease Model with Socioeconomic Conditions.

Waterborne diseases are present major health problems to humanity especially in rural communities where many individuals belong to the lower socioeconomic classes (SECs). The impacts of introducing waterborne disease control measures for such communities are investigated by considering a waterborne disease model. The model is extended by introducing treatment of infected individuals and water purification as control measures. The possible benefits of considering these control measures for the various SECs are investigated. Further analyses show how different degrees of control impact the rate at which waterborne diseases are spread across SECs. The disease control model is validated by using it to study the cholera outbreak in Haiti.

A prolonged cholera outbreak caused by drinking contaminated stream water, Kyangwali refugee settlement, Hoima District, Western Uganda: 2018.

BACKGROUND: On 23 February 2018, the Uganda Ministry of Health (MOH) declared a cholera outbreak affecting more than 60 persons in Kyangwali Refugee Settlement, Hoima District, bordering the Democratic Republic of Congo (DRC). We investigated to determine the outbreak scope and risk factors for transmission, and recommend evidence-based control measures. METHODS: We defined a suspected case as sudden onset of watery diarrhoea in any person aged ≥ 2 years in Hoima District, 1 February-9 May 2018. A confirmed case was a suspected case with Vibrio cholerae cultured from a stool sample. We found cases by active community search and record reviews at Cholera Treatment Centres. We calculated case-fatality rates (CFR) and attack rates (AR) by sub-county and nationality. In a case-control study, we compared exposure factors among case- and control-households. We estimated the association between the exposures and outcome using Mantel-Haenszel method. We conducted an environmental assessment in the refugee settlement, including testing samples of stream water, tank water, and spring water for presence of fecal coliforms. We tested suspected cholera cases using cholera rapid diagnostic test (RDT) kits followed by culture for confirmation. RESULTS: We identified 2122 case-patients and 44 deaths (CFR = 2.1%). Case-patients originating from Demographic Republic of Congo were the most affected (AR = 15/1000). The overall attack rate in Hoima District was 3.2/1000, with Kyangwali sub-county being the most affected (AR = 13/1000). The outbreak lasted 4 months, which was a multiple point-source. Environmental assessment showed that a stream separating two villages in Kyangwali Refugee Settlement was a site of open defecation for refugees. Among three water sources tested, only stream water was feacally-contaminated, yielding > 100 CFU/100 ml. Of 130 stool samples tested, 124 (95%) yielded V. cholerae by culture. Stream water was most strongly associated with illness (odds ratio [OR] = 14.2, 95% CI: 1.5-133), although tank water also appeared to be independently associated with illness (OR = 11.6, 95% CI: 1.4-94). Persons who drank tank and stream water had a 17-fold higher odds of illness compared with persons who drank from other sources (OR = 17.3, 95% CI: 2.2-137). CONCLUSIONS: Our investigation demonstrated that this was a prolonged cholera outbreak that affected four sub-counties and two divisions in Hoima District, and was associated with drinking of contaminated stream water. In addition, tank water also appears to be unsafe. We recommended boiling drinking water, increasing latrine coverage, and provision of safe water by the District and entire High Commission for refugees.

Parameter and State Estimation in a Cholera Model with Threshold Immunology: A Case Study of Senegal.

It is often impossible to measure all states affecting spread of a disease. In cholera, asymptomatic and cholera pathogen densities are not practically measurable despite playing a big role in its transmission. They are referred to as inaccessible states of the model and can only be manipulated using the measurable states of the given model. Our interest lies in estimating such states and the parameters catalyzing the spread. A mathematical model for cholera dynamics consisting of five compartments (susceptible, symptomatic, asymptomatic, recovered and bacteria population) with a minimum infection dose (MID) is considered. A method based on observer (from modern control theory) is proposed to estimate the state variables not accessible to measurement and the time-dependent parameters from real data of Senegal. We suppose that the total population of Senegal, the monthly reported cholera-induced deaths and the monthly recovered individuals are known inputs obtainable from real data, and the monthly new cholera cases the system output. An auxiliary system is used, an observer whose solutions converge exponentially to those of an original system and solely utilize known inputs and output of the model. Thus, the estimation of the unmeasured state variables like the pathogen density and the yearly asymptomatic population within the human community playing an important role in the spread of cholera is possible. We derive the expressions for time-dependent infection rate, induced cholera death rate and symptomatic recovery rate and their estimations done using real data. Numerical simulations are then performed for the validation of estimation results. The system together with the observer designed is detectable but is not observable. The observer delivered estimates reflect a close trend already ascertained by other researchers. They indicate the existence of bacteria and asymptomatic individuals in the population of Senegal at any single time for the duration of collection of the data. The ever existence of cholera pathogen explains the endemicity of Cholera in Senegal and other sub-Saharan-African countries owing to role played by the asymptomatic individual in the bacteria density. As such, the heath authorities in Senegal need to educate the general public on hygiene irrespective of observable symptoms to lower the possible number of new infections. We have analytically showed and numerically confirmed the exponential convergence to zero of the estimation errors resulting from the observer model hence the high quality of the estimates.

Water, sanitation and hygiene risk factors for the transmission of cholera in a changing climate: using a systematic review to develop a causal process diagram.

Cholera is a severe diarrhoeal disease affecting vulnerable communities. A long-term solution to cholera transmission is improved access to and uptake of water, sanitation and hygiene (WASH). Climate change threatens WASH. A systematic review and meta-analysis determined five overarching WASH factors incorporating 17 specific WASH factors associated with cholera transmission, focussing upon community cases. Eight WASH factors showed lower odds and six showed higher odds for cholera transmission. These results were combined with findings in the climate change and WASH literature, to propose a health impact pathway illustrating potential routes through which climate change dynamics (e.g. drought, flooding) impact on WASH and cholera transmission. A causal process diagram visualising links between climate change dynamics, WASH factors, and cholera transmission was developed. Climate change dynamics can potentially affect multiple WASH factors (e.g. drought-induced reductions in handwashing and rainwater use). Multiple climate change dynamics can influence WASH factors (e.g. flooding and sea-level rise affect piped water usage). The influence of climate change dynamics on WASH factors can be negative or positive for cholera transmission (e.g. drought could increase pathogen desiccation but reduce rainwater harvesting). Identifying risk pathways helps policymakers focus on cholera risk mitigation, now and in the future.

What are the drivers of recurrent cholera transmission in Nigeria? Evidence from a scoping review.

BACKGROUND: The 2018 cholera outbreak in Nigeria affected over half of the states in the country, and was characterised by high attack and case fatality rates. The country continues to record cholera cases and related deaths to date. However, there is a dearth of evidence on context-specific drivers and their operational mechanisms in mediating recurrent cholera transmission in Nigeria. This study therefore aimed to fill this important research gap, with a view to informing the design and implementation of appropriate preventive and control measures. METHODS: Four bibliographic literature sources (CINAHL (Plus with full text), Web of Science, Google Scholar and PubMed), and one journal (African Journals Online) were searched to retrieve documents relating to cholera transmission in Nigeria. Titles and abstracts of the identified documents were screened according to a predefined study protocol. Data extraction and bibliometric analysis of all eligible documents were conducted, which was followed by thematic and systematic analyses. RESULTS: Forty-five documents met the inclusion criteria and were included in the final analysis. The majority of the documents were peer-reviewed journal articles (89%) and conducted predominantly in the context of cholera epidemics (64%). The narrative analysis indicates that social, biological, environmental and climatic, health systems, and a combination of two or more factors appear to drive cholera transmission in Nigeria. Regarding operational dynamics, a substantial number of the identified drivers appear to be functionally interdependent of each other. CONCLUSION: The drivers of recurring cholera transmission in Nigeria are diverse but functionally interdependent; thus, underlining the importance of adopting a multi-sectoral approach for cholera prevention and control.

Direct transmission via households informs models of disease and intervention dynamics in cholera.

While several basic properties of cholera outbreaks are common to most settings-the pathophysiology of the disease, the waterborne nature of transmission, and others-recent findings suggest that transmission within households may play a larger role in cholera outbreaks than previously appreciated. Important features of cholera outbreaks have long been effectively modeled with mathematical and computational approaches, but little is known about how variation in direct transmission via households may influence epidemic dynamics. In this study, we construct a mathematical model of cholera that incorporates transmission within and between households. We observe that variation in the magnitude of household transmission changes multiple features of disease dynamics, including the severity and duration of outbreaks. Strikingly, we observe that household transmission influences the effectiveness of possible public health interventions (e.g. water treatment, antibiotics, vaccines). We find that vaccine interventions are more effective than water treatment or antibiotic administration when direct household transmission is present. Summarizing, we position these results within the landscape of existing models of cholera, and speculate on its implications for epidemiology and public health.

Prevention and control of cholera with household and community water, sanitation and hygiene (WASH) interventions: A scoping review of current international guidelines.

INTRODUCTION: Cholera remains a frequent cause of outbreaks globally, particularly in areas with inadequate water, sanitation and hygiene (WASH) services. Cholera is spread through faecal-oral routes, and studies demonstrate that ingestion of Vibrio cholerae occurs from consuming contaminated food and water, contact with cholera cases and transmission from contaminated environmental point sources. WASH guidelines recommending interventions for the prevention and control of cholera are numerous and vary considerably in their recommendations. To date, there has been no review of practice guidelines used in cholera prevention and control programmes. METHODS: We systematically searched international agency websites to identify WASH intervention guidelines used in cholera programmes in endemic and epidemic settings. Recommendations listed in the guidelines were extracted, categorised and analysed. Analysis was based on consistency, concordance and recommendations were classified on the basis of whether the interventions targeted within-household or community-level transmission. RESULTS: Eight international guidelines were included in this review: three by non-governmental organisations (NGOs), one from a non-profit organisation (NPO), three from multilateral organisations and one from a research institution. There were 95 distinct recommendations identified, and concordance among guidelines was poor to fair. All categories of WASH interventions were featured in the guidelines. The majority of recommendations targeted community-level transmission (45%), 35% targeted within-household transmission and 20% both. CONCLUSIONS: Recent evidence suggests that interventions for effective cholera control and response to epidemics should focus on case-centred approaches and within-household transmission. Guidelines did consistently propose interventions targeting transmission within households. However, the majority of recommendations listed in guidelines targeted community-level transmission and tended to be more focused on preventing contamination of the environment by cases or recurrent outbreaks, and the level of service required to interrupt community-level transmission was often not specified. The guidelines in current use were varied and interpretation may be difficult when conflicting recommendations are provided. Future editions of guidelines should reflect on the inclusion of evidence-based approaches, cholera transmission models and resource-efficient strategies.

An optimal control problem for carrier dependent diseases.

In developing countries, several diseases spread in human population due to the abundance of houseflies (a kind of carrier). The main reason behind the spread of these diseases is the lack of awareness among peoples regarding the sanitation practices and economic constraints. To understand the dynamics of the spread and control of these diseases, in this paper, we propose a mathematical model by considering logistic growth of houseflies. In the model formulation, it is assumed that houseflies transport the bacteria responsible for the disease transmission from the environment to the edibles of human population. To reduce the density of houseflies and number of infected individuals, an optimization problem is also formulated and analyzed. Numerical simulations are performed to support analytically obtained results.