Achievements and challenges for the use of killed oral cholera vaccines in the global stockpile era.

Cholera remains an important but neglected public health threat, affecting the health of the poorest populations and imposing substantial costs on public health systems. Cholera can be eliminated where access to clean water, sanitation, and satisfactory hygiene practices are sustained, but major improvements in infrastructure continue to be a distant goal. New developments and trends of cholera disease burden, the creation of affordable oral cholera vaccines (OCVs) for use in developing countries, as well as recent evidence of vaccination impact has created an increased demand for cholera vaccines. The global OCV stockpile was established in 2013 and with support from Gavi, has assisted in achieving rapid access to vaccine in emergencies. Recent WHO prequalification of a second affordable OCV supports the stockpile goals of increased availability and distribution to affected populations. It serves as an essential step toward an integrated cholera control and prevention strategy in emergency and endemic settings.

Mortality Rates during Cholera Epidemic, Haiti, 2010-2011.

The 2010 cholera epidemic in Haiti was one of the largest cholera epidemics ever recorded. To estimate the magnitude of the death toll during the first wave of the epidemic, we retrospectively conducted surveys at 4 sites in the northern part of Haiti. Overall, 70,903 participants were included; at all sites, the crude mortality rates (19.1-35.4 deaths/1,000 person-years) were higher than the expected baseline mortality rate for Haiti (9 deaths/1,000 person-years). This finding represents an excess of 3,406 deaths (2.9-fold increase) for the 4.4% of the Haiti population covered by these surveys, suggesting a substantially higher cholera mortality rate than previously reported.

Geographic distribution and mortality risk factors during the cholera outbreak in a rural region of Haiti, 2010-2011.

BACKGROUND: In 2010 and 2011, Haiti was heavily affected by a large cholera outbreak that spread throughout the country. Although national health structure-based cholera surveillance was rapidly initiated, a substantial number of community cases might have been missed, particularly in remote areas. We conducted a community-based survey in a large rural, mountainous area across four districts of the Nord department including areas with good versus poor accessibility by road, and rapid versus delayed response to the outbreak to document the true cholera burden and assess geographic distribution and risk factors for cholera mortality. METHODOLOGY/PRINCIPAL FINDINGS: A two-stage, household-based cluster survey was conducted in 138 clusters of 23 households in four districts of the Nord Department from April 22nd to May 13th 2011. A total of 3,187 households and 16,900 individuals were included in the survey, of whom 2,034 (12.0%) reported at least one episode of watery diarrhea since the beginning of the outbreak. The two more remote districts, Borgne and Pilate were most affected with attack rates up to 16.2%, and case fatality rates up to 15.2% as compared to the two more accessible districts. Care seeking was also less frequent in the more remote areas with as low as 61.6% of reported patients seeking care. Living in remote areas was found as a risk factor for mortality together with older age, greater severity of illness and not seeking care. CONCLUSIONS/SIGNIFICANCE: These results highlight important geographical disparities and demonstrate that the epidemic caused the highest burden both in terms of cases and deaths in the most remote areas, where up to 5% of the population may have died during the first months of the epidemic. Adapted strategies are needed to rapidly provide treatment as well as prevention measures in remote communities.

Evaluation of a rapid test for the diagnosis of cholera in the absence of a gold standard.

BACKGROUND: Early detection and confirmation of cholera outbreaks are crucial for rapid implementation of control measures. Because cholera frequently affects regions with limited laboratory resources, rapid diagnostic tests (RDT) designed for field conditions are important to enhance rapid response. Stool culture remains the "gold standard" for cholera diagnosis; however, its lack of sensitivity may lead to underestimation of test specificity. We evaluated the Crystal VC® immunochromatographic test (Span Diagnostics, India) for cholera diagnosis using a modified reference standard that combines culture-dependent and independent assays, or a Bayesian latent class model (LCM) analysis. METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted during a cholera epidemic in 2008, in Lubumbashi, Democratic Republic of Congo. Stools collected from 296 patients were used to perform the RDT on site and sent to Institut Pasteur, Paris, for bacterial culture. In comparison with culture as the gold standard, the RDT showed good sensitivity (92.2%; 95% CI: 86.8%-95.9%) but poor specificity when used by a trained laboratory technician (70.6%; 95% CI: 60.7%-79.2%) or by clinicians with no specific test training (60.4%, 95% CI: 50.2%-70.0%). The specificity of the test performed by the laboratory technician increased to 88.6% (95% CI: 78.7-94.9) when PCR was combined with culture results as the reference standard, and to 85.0% (95% CI: 70.4-99.2), when the Bayesian LCM analysis was used for performance evaluation. In both cases, the sensitivity remained high. CONCLUSION: Using an improved reference standard or appropriate statistical methods for diagnostic test evaluations in the absence of a gold standard, we report better performance of the Crystal VC® RDT than previously published. Our results confirm that this test can be used for early outbreak detection or epidemiological surveillance, key components of efficient global cholera control. Our analysis also highlights the importance of improving evaluations of RDT when no reliable gold standard is available.

Use of filter paper as a transport medium for laboratory diagnosis of cholera under field conditions.

Confirmation of a cholera epidemic is based on bacteriological identification of the agent and requires the sending of samples to a culture laboratory, often in countries with limited resources. Comparison of the use of filter paper with the use of Cary-Blair reference medium for stool transport showed that this simple transport medium is appropriate for the recovery of Vibrio cholerae.

Violence against civilians and access to health care in North Kivu, Democratic Republic of Congo: three cross-sectional surveys.

BACKGROUND: The province of North Kivu in the Democratic Republic of Congo has been afflicted by conflict for over a decade. After months of relative calm, offences restarted in September 2008. We did an epidemiological study to document the impact of violence on the civilian population and orient pre-existing humanitarian aid. METHODS: In May 2009, we conducted three cross-sectional surveys among 200 000 resident and displaced people in North Kivu (Kabizo, Masisi, Kitchanga). The recall period covered an eight month period from the beginning of the most recent offensives to the survey date. Heads of households provided information on displacement, death, violence, theft, and access to fields and health care. RESULTS: Crude mortality rates (per 10 000 per day) were below emergency thresholds: Kabizo 0.2 (95% CI: 0.1-0.4), Masisi 0.5 (0.4-0.6), Kitchanga 0.7 (0.6-0.9). Violence was the reported cause in 39.7% (27/68) and 35.8% (33/92) of deaths in Masisi and Kitchanga, respectively. In Masisi 99.1% (897/905) and Kitchanga 50.4% (509/1020) of households reported at least one member subjected to violence. Displacement was reported by 39.0% of households (419/1075) in Kitchanga and 99.8% (903/905) in Masisi. Theft affected 87.7% (451/514) of households in Masisi and 57.4% (585/1019) in Kitchanga. Access to health care was good: 93.5% (359/384) of the sick in Kabizo, 81.7% (515/630) in Masisi, and 89.8% (651/725) in Kitchanga received care, of whom 83.0% (298/359), 87.5% (451/515), and 88.9% (579/651), respectively, did not pay. CONCLUSIONS: Our results show the impact of the ongoing war on these civilian populations: one third of deaths were violent in two sites, individuals are frequently subjected to violence, and displacements and theft are common. While humanitarian aid may have had a positive impact on disease mortality and access to care, the population remains exposed to extremely high levels of violence.

Reactive vaccination as an effective tool for measles outbreak control in measles mortality reduction settings, Democratic Republic of Congo, 2005-2006.

New WHO guidelines for measles outbreak response in measles mortality reduction settings now include reactive vaccination for outbreaks. Here we used surveillance data and vaccine coverage surveys following two mass vaccine campaigns in the Democratic Republic of Congo, to show the impact of reactive vaccination on reducing cases during outbreaks. The number of measles cases reported was collected via the national surveillance system. Following vaccination campaigns, two-stage cluster sampling surveys were used to evaluate pre and post campaign coverage. In Matadi, 1035 cases were reported from 24 October 2005 to 19 February 2006 and in Mbuji Mayi, 4734 cases were reported from 3 October 2005 to 30 April 2006. Following the mass vaccination campaign, coverage rose from 87.5% (95% CI 87.2-87.8) to 97.1% (95% CI 96.9-97.3) in Matadi and from 74.0% (95% CI 70.9-77.0) to 96.5% (95% CI: 95.7-97.2) in Mbuji Mayi. Weekly reported cases reduced respectively by 89.3% and 68.9% in the 3 weeks following the mass vaccination campaigns. The introduction of reactive vaccination for measles outbreak control provides an additional tool to help reduce the impact of outbreaks. Our experience shows that this type of intervention is feasible and effective even when baseline vaccination coverage is > 70%.

Malaria epidemics and interventions, Kenya, Burundi, southern Sudan, and Ethiopia, 1999-2004.

Quantitative data on the onset and evolution of malaria epidemics are scarce. We review case studies from recent African Plasmodium falciparum epidemics (Kisii and Gucha Districts, Kenya, 1999; Kayanza Province, Burundi, 2000-2001; Aweil East, southern Sudan, 2003; Gutten and Damot Gale, Ethiopia, 2003-2004). We highlight possible epidemic risk factors and review delays in epidemic detection and response (up to 20 weeks), essentially due to poor case reporting and analysis or low use of public facilities. Epidemics lasted 15-36 weeks, and patients' age profiles suggested departures from classical notions of epidemic malaria everywhere but Burundi. Although emergency interventions were mounted to expand inpatient and outpatient treatment access, we believe their effects were lessened because of delays, insufficient evaluation of disease burden, lack of evidence on how to increase treatment coverage in emergencies, and use of ineffective drugs.