Cost-effectiveness of a reactive oral cholera immunization campaign using Shanchol™ in Malawi.

BACKGROUND: Oral cholera vaccines (OCV) have been recommended as additional measures for the prevention of cholera. However, little is known about the cost-effectiveness of OCV use in sub-Saharan Africa, particularly in reactive outbreak contexts. This study aimed to investigate the cost-effectiveness of the use of OCV Shanchol in response to a cholera outbreak in the Lake Chilwa area, Malawi. METHODS: The Excel-based Vaccine Introduction Cost-Effectiveness model was used to assess the cost-effectiveness ratios with and without indirect protection. Model input parameters were obtained from cost evaluations and epidemiological studies conducted in Malawi and published literature. One-way sensitivity and threshold analyses of cost-effectiveness ratios were performed. RESULTS: Compared with the reference scenario i.e. treatment of cholera cases, the immunization campaign would have prevented 636 and 1 020 cases of cholera without and with indirect protection, respectively. The cost-effectiveness ratios were US$19 212 per death, US$500 per case, and US$738 per DALY averted without indirect protection. They were US$10 165 per death, US$264 per case, and US$391 per DALY averted with indirect protection. The net cost per DALY averted was sensitive to four input parameters, including case fatality rate, duration of immunity (vaccine's protective duration), discount rate and cholera incidence. CONCLUSION: Relative to the Malawi gross domestic product per capita, the reactive OCV campaign represented a cost-effective intervention, particularly when considering indirect vaccine effects. Results will need to be assessed in other settings, e.g., during campaigns implemented directly by the Ministry of Health rather than by international partners.

Mapping the burden of cholera in sub-Saharan Africa and implications for control: an analysis of data across geographical scales.

BACKGROUND: Cholera remains a persistent health problem in sub-Saharan Africa and worldwide. Cholera can be controlled through appropriate water and sanitation, or by oral cholera vaccination, which provides transient (∼3 years) protection, although vaccine supplies remain scarce. We aimed to map cholera burden in sub-Saharan Africa and assess how geographical targeting could lead to more efficient interventions. METHODS: We combined information on cholera incidence in sub-Saharan Africa (excluding Djibouti and Eritrea) from 2010 to 2016 from datasets from WHO, Médecins Sans Frontières, ProMED, ReliefWeb, ministries of health, and the scientific literature. We divided the study region into 20 km × 20 km grid cells and modelled annual cholera incidence in each grid cell assuming a Poisson process adjusted for covariates and spatially correlated random effects. We combined these findings with data on population distribution to estimate the number of people living in areas of high cholera incidence (>1 case per 1000 people per year). We further estimated the reduction in cholera incidence that could be achieved by targeting cholera prevention and control interventions at areas of high cholera incidence. FINDINGS: We included 279 datasets covering 2283 locations in our analyses. In sub-Saharan Africa (excluding Djibouti and Eritrea), a mean of 141 918 cholera cases (95% credible interval [CrI] 141 538-146 505) were reported per year. 4·0% (95% CrI 1·7-16·8) of districts, home to 87·2 million people (95% CrI 60·3 million to 118·9 million), have high cholera incidence. By focusing on the highest incidence districts first, effective targeted interventions could eliminate 50% of the region's cholera by covering 35·3 million people (95% CrI 26·3 million to 62·0 million), which is less than 4% of the total population. INTERPRETATION: Although cholera occurs throughout sub-Saharan Africa, its highest incidence is concentrated in a small proportion of the continent. Prioritising high-risk areas could substantially increase the efficiency of cholera control programmes. FUNDING: The Bill & Melinda Gates Foundation.

Oral cholera vaccination in hard-to-reach communities, Lake Chilwa, Malawi.

OBJECTIVE: To evaluate vaccination coverage, identify reasons for non-vaccination and assess satisfaction with two innovative strategies for distributing second doses in an oral cholera vaccine campaign in 2016 in Lake Chilwa, Malawi, in response to a cholera outbreak. METHODS: We performed a two-stage cluster survey. The population interviewed was divided in three strata according to the second-dose vaccine distribution strategy: (i) a standard strategy in 1477 individuals (68 clusters of 5 households) on the lake shores; (ii) a simplified cold-chain strategy in 1153 individuals (59 clusters of 5 households) on islands in the lake; and (iii) an out-of-cold-chain strategy in 295 fishermen (46 clusters of 5 to 15 fishermen) in floating homes, called zimboweras. FINDING: Vaccination coverage with at least one dose was 79.5% (1153/1451) on the lake shores, 99.3% (1098/1106) on the islands and 84.7% (200/236) on zimboweras. Coverage with two doses was 53.0% (769/1451), 91.1% (1010/1106) and 78.8% (186/236), in the three strata, respectively. The most common reason for non-vaccination was absence from home during the campaign. Most interviewees liked the novel distribution strategies. CONCLUSION: Vaccination coverage on the shores of Lake Chilwa was moderately high and the innovative distribution strategies tailored to people living on the lake provided adequate coverage, even among hard-to-reach communities. Community engagement and simplified delivery procedures were critical for success. Off-label, out-of-cold-chain administration of oral cholera vaccine should be considered as an effective strategy for achieving high coverage in hard-to-reach communities. Nevertheless, coverage and effectiveness must be monitored over the short and long term.

Use of Vibrio cholerae vaccine in an outbreak in Guinea.

BACKGROUND: The use of vaccines to prevent and control cholera is currently under debate. Shanchol is one of the two oral cholera vaccines prequalified by the World Health Organization; however, its effectiveness under field conditions and the protection it confers in the first months after administration remain unknown. The main objective of this study was to estimate the short-term effectiveness of two doses of Shanchol used as a part of the integrated response to a cholera outbreak in Africa. METHODS: We conducted a matched case-control study in Guinea between May 20 and October 19, 2012. Suspected cholera cases were confirmed by means of a rapid test, and controls were selected among neighbors of the same age and sex as the case patients. The odds of vaccination were compared between case patients and controls in bivariate and adjusted conditional logistic-regression models. Vaccine effectiveness was calculated as (1-odds ratio)×100. RESULTS: Between June 8 and October 19, 2012, we enrolled 40 case patients and 160 controls in the study for the primary analysis. After adjustment for potentially confounding variables, vaccination with two complete doses was associated with significant protection against cholera (effectiveness, 86.6%; 95% confidence interval, 56.7 to 95.8; P=0.001). CONCLUSIONS: In this study, Shanchol was effective when used in response to a cholera outbreak in Guinea. This study provides evidence supporting the addition of vaccination as part of the response to an outbreak. It also supports the ongoing efforts to establish a cholera vaccine stockpile for emergency use, which would enhance outbreak prevention and control strategies. (Funded by Médecins sans Frontières.).

Prevention of Rebleeding From Esophageal Varices in Patients With Cirrhosis Receiving Small-Diameter Stents Versus Hemodynamically Controlled Medical Therapy.

BACKGROUND & AIMS: Patients with cirrhosis and variceal hemorrhage have a high risk of rebleeding. We performed a prospective randomized trial to compare the prevention of rebleeding in patients given a small-diameter covered stent vs those given hepatic venous pressure gradient (HVPG)-based medical therapy prophylaxis. METHODS: We performed an open-label study of patients with cirrhosis (92% Child class A or B, 70% alcoholic) treated at 10 medical centers in Germany. Patients were assigned randomly more than 5 days after variceal hemorrhage to groups given a small covered transjugular intrahepatic portosystemic stent-shunt (TIPS) (8 mm; n = 90), or medical reduction of portal pressure (propranolol and isosorbide-5-mononitrate; n = 95). HVPG was determined at the time patients were assigned to groups (baseline) and 2 weeks later. In the medical group, patients with an adequate reduction in HVPG (responders) remained on the drugs whereas nonresponders underwent only variceal band ligation. The study was closed 10 months after the last patient was assigned to a group. The primary end point was variceal rebleeding. Survival, safety (adverse events), and quality of life (based on the Short Form-36 health survey) were secondary outcome measures. RESULTS: A significantly smaller proportion of patients in the TIPS group had rebleeding within 2 years (7%) than in the medical group (26%) (P = .002). A slightly higher proportion of patients in the TIPS group experienced adverse events, including encephalopathy (18% vs 8% for medical treatment; P = .05). Rebleeding occurred in 6 of 23 patients (26%) receiving medical treatment before hemodynamic control was possible. Per-protocol analysis showed that rebleeding occurred in a smaller proportion of the 32 responders (18%) than in nonresponders who received variceal band ligation (31%) (P = .06). Fifteen patients from the medical group (16%) underwent TIPS placement during follow-up evaluation, mainly for refractory ascites. Survival time and quality of life did not differ between both randomized groups. CONCLUSIONS: Placement of a small-diameter, covered TIPS was straightforward and prevented variceal rebleeding in patients with Child A or B cirrhosis more effectively than drugs, which often required step-by-step therapy. However, TIPS did not increase survival time or quality of life and produced slightly more adverse events. Clinical Trial no: ISRCTN 16334693.

Cholera outbreaks in Africa.

During the current seventh cholera pandemic, Africa bore the major brunt of global disease burden. More than 40 years after its resurgence in Africa in 1970, cholera remains a grave public health problem, characterized by large disease burden, frequent outbreaks, persistent endemicity, and high CFRs, particularly in the region of the central African Great Lakes which might act as reservoirs for cholera. There, cases occur year round with a rise in incidence during the rainy season. Elsewhere in sub-Saharan Africa, cholera occurs mostly in outbreaks of varying size with a constant threat of widespread epidemics. 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. The number of cholera cases is possibly much higher than what is reported to the WHO due to the variation in modalities, completeness, and case definition of national cholera data. One source on country specific incidence rates for Africa, adjusting for underreporting, estimates 1,341,080 cases and 160,930 deaths (52.6 % of 2,548,227 estimated cases and 79.6 % of 209,216 estimated deaths worldwide). Another estimates 1,411,453 cases and 53,632 deaths per year, respectively (50 % of 2,836,669 estimated cases and 58.6 % of 91,490 estimated deaths worldwide). Within Africa, half of all cases between 1970 and 2011 were notified from only seven countries: Angola, Democratic Republic of the Congo, Mozambique, Nigeria, Somalia, Tanzania, and South Africa. In contrast to a global trend of decreasing case fatality ratios (CFRs), CFRs have remained stable in Africa at approximately 2 %. Early propagation of cholera outbreaks depends largely on the extent of individual bacterial shedding, host and organism characteristics, the likelihood of people coming into contact with an infectious dose of Vibrio cholerae and on the virulence of the implicated strain. Cholera transmission can then be amplified by several factors including contamination of human water- or food sources; climate and extreme weather events; political and economic crises; high population density combined with poor quality informal housing and poor hygiene practices; spread beyond a local community through human travel and animals, e.g., water birds. At an individual level, cholera risk may increase with decreasing immunity and hypochlorhydria, such as that induced by Helicobacter pylori infection, which is endemic in much of Africa, and may increase individual susceptibility and cholera incidence. Since contaminated water is the main vehicle for the spread of cholera, the obvious long-term solution to eradicate the disease is the provision of safe water to all African populations. This requires considerable human and financial resources and time. In the short and medium term, vaccination may help to prevent and control the spread of cholera outbreaks. Regardless of the intervention, further understanding of cholera biology and epidemiology is essential to identify populations and areas at increased risk and thus ensure the most efficient use of scarce resources for the prevention and control of cholera.

Cholera surveillance in Uganda: an analysis of notifications for the years 2007-2011.

INTRODUCTION: Cholera outbreaks have occurred periodically in Uganda since 1971. The country has experienced intervals of sporadic cases and localized outbreaks, occasionally resulting in prolonged widespread epidemics. METHODS: Cholera surveillance data reported to the Uganda Ministry of Health from 2007 through 2011 were reviewed to determine trends in annual incidence and case fatality rate. Demographic characteristics of cholera cases were analyzed from the national line list for 2011. Cases were analyzed by district and month of report to understand the geographic distribution and identify any seasonal patterns of disease occurrence. RESULTS: From 2007 through 2011, Uganda registered a total of 7615 cholera cases with 181 deaths (case fatality rate = 2.4%). The absolute number of cases and incidence per 100 000 varied from year to year with the highest incidence occurring in 2008 following heavy rainfall and flooding in eastern Uganda. For 2011, cholera cases occurred in 1.6 times more males than females. The geographical areas affected by the outbreaks shifted each year, with the exception of a few endemic districts. No clear seasonal trends in cholera occurrence were identified for this time period. CONCLUSIONS: We observed an overall decline in cases reported during the 5 years under review. During this period, concerted efforts were made by the Ugandan government and development partners to educate communities on proper sanitation and hygiene and provide safe water and timely treatment. Mechanisms to ensure timely and complete cholera surveillance data are reported to the national level should continue to be strengthened.

Elimination of cholera in the democratic Republic of the Congo: the new national policy.

We evaluated published and unpublished data on cholera cases and deaths reported from clinical care facilities in the 56 health districts of the Democratic Republic of Congo to the National Ministry of Health during 2000-2011. Cholera incidence was highest in the eastern provinces bordering lakes and epidemics primarily originated in this region. Along with a strong seasonal component, our data suggest a potential Vibrio cholerae reservoir in the Rift Valley lakes and the possible contribution of the lakes' fishing industry to the spread of cholera. The National Ministry of Health has committed to the elimination-rather than control-of cholera in DRC and has adopted a new national policy built on improved alert, response, case management, and prevention. To achieve this goal and implement all these measures it will require strong partners in the international community with a similar vision.

VKORC1-dependent pharmacokinetics of intravenous and oral phylloquinone (vitamin K1) mixed micelles formulation.

OBJECTIVE: The pharmacokinetics of phylloquinone (vitamin K1) were evaluated in healthy human adult volunteers (15 male and 15 female) following oral and intravenous administration of a mixed micelles formulation (Konakion MM 2 mg) in an open label study design. The subjects were allocated to one of three genotype-specific groups (n = 10 in each group) in terms of VKORC1 promoter polymorphism c.-1639 G > A to explore the relationship between genotype and pharmacokinetic parameters. METHODS: Blood samples were collected for up to 24 h after administration. Phylloquinone serum levels were determined by reversed phase HPLC with fluorometric detection after post-column zinc reduction. Pharmacokinetic evaluation was performed using non-compartmental analysis. RESULTS: Pharmacokinetic analysis of serum phylloquinone concentration versus time profiles revealed significant differences in the main pharmacokinetic parameters between groups. Upon oral administration, VKORC1 AG carriers showed 41 % higher mean bioavailability (p = 0.01) compared with homozygous AA individuals. Furthermore, AG subjects exhibited 30 % (p = 0.042) and 36 % (p = 0.021) higher mean AUC compared with GG and AA respectively. Terminal half-life was 32 % and 27 % longer for AG carriers in comparison to GG (p = 0.004) and AA (p = 0.015) genotypes respectively. CONCLUSION: Pharmacokinetic differences indicated significant inter-individual variance of vitamin K fate in the human body. The influence of the VKORC1 promoter polymorphism c.-1639 G > A on the pharmacokinetic properties of phylloquinone could be demonstrated in humans. To gain deeper insight in other potential genetic determinants of systemic vitamin K exposure, further correlation of the phenotype-genotype relationship of different players in vitamin K turnover has to be gained.

Epidemiology of cholera.

Cholera is an ancient disease that remains a public health problem in many impoverished locations around the world. Seven pandemics of cholera have been recorded since the first pandemic in 1817, the last of which is on going. Overcrowding, poverty, insufficient water and sanitation facilities increase the risk for cholera outbreaks. The epidemiology of cholera in the areas in Asia, Africa and the Americas where the disease occurs continues to evolve.

Oral cholera vaccine coverage during a preventive door-to-door mass vaccination campaign in Nampula, Mozambique.

BACKGROUND: In addition to improving water, sanitation and hygiene (WASH) measures and optimal case management, the introduction of Oral cholera vaccine (OCV) is a complementary strategy for cholera prevention and control for vulnerable population groups. In October 2016, the Mozambique Ministry of Health implemented a mass vaccination campaign using a two-dose regimen of the Shanchol™ OCV in six high-risk neighborhoods of Nampula city, in Northern Mozambique. Overall 193,403 people were targeted by the campaign, which used a door-to-door strategy. During campaign follow-up, a population survey was conducted to assess: (1) OCV coverage; (2) frequency of adverse events following immunization; (3) vaccine acceptability and (4) reasons for non-vaccination. METHODOLOGY/PRINCIPAL FINDINGS: In the absence of a household listing and clear administrative neighborhood delimitations, we used geospatial technology to select households from satellite images and used the support of community leaders. One person per household was randomly selected for interview. In total, 636 individuals were enrolled in the survey. The overall vaccination coverage with at least one dose (including card and oral reporting) was 69.5% (95%CI: 51.2-88.2) and the two-dose coverage was 51.2% (95%CI: 37.9-64.3). The campaign was well accepted. Among the 185 non-vaccinated individuals, 83 (44.6%) did not take the vaccine because they were absent when the vaccination team visited their houses. Among the 451 vaccinated individuals, 47 (10%) reported minor and non-specific complaints, and 78 (17.3%) mentioned they did not receive any information before the campaign. CONCLUSIONS/SIGNIFICANCE: In spite of overall coverage being slightly lower than expected, the use of a mobile door-to-door strategy remains a viable option even in densely-populated urban settings. Our results suggest that campaigns can be successfully implemented and well accepted in Mozambique in non-emergency contexts in order to prevent cholera outbreaks. These findings are encouraging and complement the previous Mozambican experience related to OCV.

Innovative vaccine delivery strategies in response to a cholera outbreak in the challenging context of Lake Chilwa. A rapid qualitative assessment.

A reactive campaign using two doses of Shanchol Oral Cholera Vaccine (OCV) was implemented in 2016 in the Lake Chilwa Region (Malawi) targeting fish dependent communities. Three strategies for the second vaccine dose delivery (including delivery by a community leader and self-administration) were used to facilitate vaccine access. This assessment collected vaccine perceptions and opinions about the OCV campaign of 313 study participants, including: fishermen, fish traders, farmers, community leaders, and one health and one NGO officer. Socio-demographic surveys were conducted, In Depth Interviews and Focus Group Discussions were conducted before and during the campaign. Some fishermen perceived the traditional delivery strategy as reliable but less practical. Delivery by traditional leaders was acceptable for some participants while others worried about traditional leaders not being trained to deliver vaccines or beneficiaries taking doses on their own. A slight majority of beneficiaries considered the self-administration strategy practical while some beneficiaries worried about storing vials outside of the cold chain or losing vials. During the campaign, a majority of participants preferred receiving oral vaccines instead of injections given ease of intake and lack of pain. OCV was perceived as efficacious and safe. However, a lack of information on how sero-protection may be delayed and the degree of sero-protection led to loss of trust in vaccine potency among some participants who witnessed cholera cases among vaccinated individuals. OCV campaign implementation requires accompanying communication on protective levels, less than 100% vaccine efficacy, delays in onset of sero-protection, and out of cold chain storage.

A rapid qualitative assessment of oral cholera vaccine anticipated acceptability in a context of resistance towards cholera intervention in Nampula, Mozambique.

INTRODUCTION: While planning an immunization campaign in settings where public health interventions are subject to politically motivated resistance, designing context-based social mobilization strategies is critical to ensure community acceptability. In preparation for an Oral Cholera Vaccine campaign implemented in Nampula, Mozambique, in November 2016, we assessed potential barriers and levers for vaccine acceptability. METHODS: Questionnaires, in-depth interviews, and focus group discussions, as well as observations, were conducted before the campaign. The participants included central and district level government informants (national immunization program, logistics officers, public health directors, and others), community leaders and representatives, and community members. RESULTS: During previous well chlorination interventions, some government representatives and health agents were attacked, because they were believed to be responsible for spreading cholera instead of purifying the wells. Politically motivated resistance to cholera interventions resurfaced when an OCV campaign was considered. Respondents also reported vaccine hesitancy related to experiences of problems during school-based vaccine introduction, rumors related to vaccine safety, and negative experiences following routine childhood immunization. Despite major suspicions associated with the OCV campaign, respondents' perceived vulnerability to cholera and its perceived severity seem to override potential anticipated OCV vaccine hesitancy. DISCUSSION: Potential hesitancy towards the OCV campaign is grounded in global insecurity, social disequilibrium, and perceived institutional negligence, which reinforces a representation of estrangement from the central government, triggering suspicions on its intentions in implementing the OCV campaign. Recommendations include a strong involvement of community leaders, which is important for successful social mobilization; representatives of different political parties should be equally involved in social mobilization efforts, before and during campaigns; and public health officials should promote other planned interventions to mitigate the lack of trust associated with perceived institutional negligence. Successful past initiatives include public intake of purified water or newly introduced medication by social mobilizers, teachers or credible leaders.

Temporo-spatial dynamics and behavioural patterns of 2012 cholera epidemic in the African mega-city of Conakry, Guinea.

BACKGROUND: Cholera is endemic in Guinea, having suffered consecutive outbreaks from 2004 to 2008 followed by a lull until the 2012 epidemic. Here we describe the temporal-spatial and behavioural characteristics of cholera cases in Conakry during a three-year period, including the large-scale 2012 epidemic. METHODS: We used the national and African Cholera Surveillance Network (Africhol) surveillance data collected from every cholera treatment centre in Conakry city from August 2011 to December 2013. The prevalence of suspect and confirmed cholera cases, the case fatality ratio (CFR), and the factors associated with suspected cholera were described according to three periods: pre-epidemic (A), epidemic 2012 (B) and post epidemic (C). Weekly attack rates and temporal-spatial clustering were calculated at municipality level for period B. Cholera was confirmed by culture at the cholera national reference laboratory. RESULTS: A total of 4559 suspect cases were reported: 66, 4437, and 66 suspect cases in periods A, B and C, respectively. Among the 204 suspect cases with culture results available, 6%, 60%, and 70% were confirmed in periods A, B, and C, respectively. With 0.3%, the CFR was significantly lower in period B than in periods A (7.6%) and C (7.1%). The overall attack rate was 0.28% in period B, ranging from 0.17% to 0.31% across municipalities. Concomitantly, a cluster of cases was identified in two districts in the northern part of Conakry. At 14%, rice water stools were less frequent in period A than in period B and C (78% and 84%). Dehydration (31% vs 94% and 89%) and coma (0.4% vs 3.1% and 2.9%) were lower during period B than in periods A and C. The treatment of drinking water was less frequent in period A, while there were more reports of recent travel in period C. CONCLUSIONS: The epidemic dynamic and the sociological description of suspect cases before, during, and after the large-scale epidemic revealed that the Vibrio cholerae was already present before the epidemic. However, it appeared that infected individuals reacted differently in terms of disease severity as well as their access to treated water and travel habits. Such an in-depth description of cholera epidemics should be systematically carried out in cholera endemic settings in order to prioritize higher risk areas, identify transmission factors, and optimize preventive interventions.

Sensitivity, Specificity, and Public-Health Utility of Clinical Case Definitions Based on the Signs and Symptoms of Cholera in Africa.

During 2014, Africa reported more than half of the global suspected cholera cases. Based on the data collected from seven countries in the African Cholera Surveillance Network (Africhol), we assessed the sensitivity, specificity, and positive and negative predictive values of clinical cholera case definitions, including that recommended by the World Health Organization (WHO) using culture confirmation as the gold standard. The study was designed to assess results in real-world field situations in settings with recent cholera outbreaks or endemicity. From June 2011 to July 2015, a total of 5,084 persons with suspected cholera were tested for Vibrio cholerae in seven different countries of which 35.7% had culture confirmation. For all countries combined, the WHO case definition had a sensitivity = 92.7%, specificity = 8.1%, positive predictive value = 36.1%, and negative predictive value = 66.6%. Adding dehydration, vomiting, or rice water stools to the case definition could increase the specificity without a substantial decrease in sensitivity. Future studies could further refine our findings primarily by using more sensitive methods for cholera confirmation.

Cholera prevention and control in Asian countries.

Cholera remains a major public health problem in many countries. Poor sanitation and inappropriate clean water supply, insufficient health literacy and community mobilization, absence of national plans and cross-border collaborations are major factors impeding optimal control of cholera in endemic countries. In March 2017, a group of experts from 10 Asian cholera-prone countries that belong to the Initiative against Diarrheal and Enteric Diseases in Africa and Asia (IDEA), together with representatives from the World Health Organization, the US National Institutes of Health, International Vaccine Institute, Agence de médecine préventive, NGOs (Save the Children) and UNICEF, met in Hanoi (Vietnam) to share progress in terms of prevention and control interventions on water, sanitation and hygiene (WASH), surveillance and oral cholera vaccine use. This paper reports on the country situation, gaps identified in terms of cholera prevention and control and strategic interventions to bridge these gaps.

Cost-of-illness of cholera to households and health facilities in rural Malawi.

Cholera remains an important public health problem in many low- and middle-income countries. Vaccination has been recommended as a possible intervention for the prevention and control of cholera. Evidence, especially data on disease burden, cost-of-illness, delivery costs and cost-effectiveness to support a wider use of vaccine is still weak. This study aims at estimating the cost-of-illness of cholera to households and health facilities in Machinga and Zomba Districts, Malawi. A cross-sectional study using retrospectively collected cost data was undertaken in this investigation. One hundred patients were purposefully selected for the assessment of the household cost-of-illness and four cholera treatment centres and one health facility were selected for the assessment conducted in health facilities. Data collected for the assessment in households included direct and indirect costs borne by cholera patients and their families while only direct costs were considered for the assessment conducted in health facilities. Whenever possible, descriptive and regression analysis were used to assess difference in mean costs between groups of patients. The average costs to patients' households and health facilities for treating an episode of cholera amounted to US$65.6 and US$59.7 in 2016 for households and health facilities, respectively equivalent to international dollars (I$) 249.9 and 227.5 the same year. Costs incurred in treating a cholera episode were proportional to duration of hospital stay. Moreover, 52% of households used coping strategies to compensate for direct and indirect costs imposed by the disease. Both households and health facilities could avert significant treatment expenditures through a broader use of pre-emptive cholera vaccination. These findings have direct policy implications regarding priority investments for the prevention and control of cholera.

Oral cholera vaccine coverage in hard-to-reach fishermen communities after two mass Campaigns, Malawi, 2016.

CONTEXT: From December 2015 to August 2016, a large epidemic of cholera affected the fishermen of Lake Chilwa in Malawi. A first reactive Oral Cholera Vaccines (OCV) campaign was organized, in February, in a 2km radius of the lake followed by a preemptive one, conducted in November, in a 25km radius. We present the vaccine coverage reached in hard-to-reach population using simplified delivery strategies. METHOD: We conducted two-stage random-sampling cross-sectional surveys among individuals living in a 2km and 25km radius of Lake Chilwa (islands and floating homes included). Individuals aged 12months and older from Machinga and Zomba districts were sampled: 43 clusters of 14 households were surveyed. Simplified strategies were used for those living in islands and floating homes: self- delivery and community-supervised delivery of the second dose. Vaccine coverage (VC) for at-least-two-doses was estimated taking into account sampling weights and design effects. RESULTS: A total of 1176 households were surveyed (2.7% of non-response). Among the 2833 individuals living in the 2km radius of Lake and the 2915 in the 25km radius: 457 (16.1%) and 239 (8.2%) lived in floating homes or on islands at some point in the year, respectively. For the overall population, VC was 75.6% and 54.2%, respectively. In the 2km radius, VC was 92.2% for those living on the lake at some point of the year: 271 (64.8%) used the simplified strategies. The main reasons for non-vaccination were absence during the campaign and vaccine shortage. Few adverse events occurring in the 24h following vaccination was reported. CONCLUSIONS: We reached a high two-dose coverage of the most at-risk population using simplified delivery strategies. Because of the high fishermen mobility, regular catch-up campaigns or another strategy specifically targeting fishermen need to be assessed for more efficient vaccines use.