Culture-confirmed Cholera Research Articles

Identifying clustering of cholera cases using geospatial analysis in Kolkata and surrounding districts: data from patients at tertiary care referral hospitals

Cholera cases have increased globally across the Eastern Mediterranean, Africa, Southeast Asia, and parts of Europe since early 2024. This study aims to identify cholera hotspots and understand the spatial distribution of cholera in Kolkata and surrounding regions, a key cholera reservoir. Additionally, we examine sociodemographic factors and aspects related to water, sanitation, and hygiene (WASH). Cholera clusters were detected using kernel density estimation and spatial autocorrelation through Global Moran's-I statistics, with local cluster patterns examined using Local Moran's-I statistics. Cholera cases from August 2021 to December 2023, treated at two tertiary care facilities in Kolkata: Infectious Diseases and Beleghata General Hospital and Dr. B C Roy Post Graduate Institute of Paediatric Sciences Hospital were included. Additionally, through a case-control study, 196 culture-confirmed cholera cases and 764 age/sex-matched neighborhood controls were enrolled, to investigate cholera risk factors. Spatial analysis revealed a concentration of 196 cholera cases in Kolkata and its surrounding regions of Howrah, Hooghly, and North and South 24 Parganas. Hotspot analysis showed significant clustering in several Kolkata wards (31, 33, 56, 46, 57, 58, 59, 61, 66, 71, and 107), particularly in the northern, central, and east Kolkata wetlands areas (Global Moran's I statistic=0.14, p<0.001). These clusters had proximity between cases, with a median distance of 187.7m, and 25.5% of cases as close as 73.9m apart, suggesting localized transmission. Hotspots were identified with an average distance of 1600m between them. Local Moran's I analysis found dense "high-high" clusters in these areas (p<0.01), with a mean Moran's I index of 0.3, (range 0.1-4.6). The case-control study revealed that males were more likely to contract cholera, with an adjusted odds ratio of 2.4 (p<0.01). There was no significant association found between cholera infection and sociodemographic factors or various WASH practices. The findings emphasize the importance of targeted interventions, especially in identified hotspots, to mitigate cholera transmission. Addressing Socio-economic, and environmental factors especially improvement in WASH practices may further enhance prevention effects. The author KK, received funding from the program of the Japan Initiative for Global Research Network on Infectious Diseases, (grant id: JP23wm0125004), from the Ministry of Education, Culture, Sports, Science and Technology in Japan, and Japan Agency for Medical Research and Development.

Individual and household exposures associated with cholera transmission in case-control studies: a systematic review.

Uncertainty persists regarding cholera transmission routes. We conducted a structured review of case-control studies on cholera transmission and provide a qualitative summary of reported exposures in order to inform public health efforts and future cholera research. We searched two electronic databases for published case-control studies that investigated risk factors for cholera and included any publications that did not match our exclusion criteria. From the included studies, we grouped exposures using two parameters, whether transmission domain was public or domestic, and also on the vehicle of transmission. We extracted data on study location, method of case and control inclusion, type of statistical analysis performed and which exposures were included. Additionally, two parallel subgroup analyses were performed. The first included the subgroup of all studies that used culture-confirmed cholera cases, and the second included the subgroup of all studies employing a multivariate analysis. In the second analysis, we calculated the population attributable risk (PAR). Our search yielded 2347 peer-reviewed publications, of which 65 did not match our exclusion criteria, comprising 69 individual studies. Water-based exposures were investigated in 97% of these studies, of which 70% found a significant association with cholera infection. Food-based exposures were investigated in 75% of studies, of which 63% found a significant association with risk of cholera infection. Close personal contact with cholera cases was investigated in 30% of studies, of which 52% found a significant association with risk of cholera infection. Hygiene-related exposures were investigated in 51% of studies, of which 63% found a significant association with cholera transmission. Among studies that examined at least one exposure related to the domestic domain, 76% found a significant association with cholera infection vs. 71% of studies investigating at least one public domain exposure. The subgroup analyses produced similar results. Despite strong evidence for cholera transmission via foodborne-, hygiene-, waterborne- and close personal contact-related pathways in both domestic and public domains, we found that non-waterborne-related factors are understudied. Future cholera case-control studies would benefit from investigating all transmission vehicles and transmission domains.

Efficacy of a single-dose regimen of inactivated whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial

A single-dose regimen of inactivated whole-cell oral cholera vaccine (OCV) is attractive because it reduces logistical challenges for vaccination and could enable more people to be vaccinated. Previously, we reported the efficacy of a single dose of an OCV vaccine during the 6 months following dosing. Herein, we report the results of 2 years of follow-up. In this placebo-controlled, double-blind trial done in Dhaka, Bangladesh, individuals aged 1 year or older with no history of receipt of OCV were randomly assigned to receive a single dose of inactivated OCV or oral placebo. The primary endpoint was a confirmed episode of non-bloody diarrhoea for which the onset was at least 7 days after dosing and a faecal culture was positive for Vibrio cholerae O1 or O139. Passive surveillance for diarrhoea was done in 13 hospitals or major clinics located in or near the study area for 2 years after the last administered dose. We assessed the protective efficacy of the OCV against culture-confirmed cholera occurring 7-730 days after dosing with both crude and multivariable per-protocol analyses. This trial is registered at ClinicalTrials.gov, number NCT02027207. Between Jan 10, 2014, and Feb 4, 2014, 205 513 people were randomly assigned to receive either vaccine or placebo, of whom 204 700 (102 552 vaccine recipients and 102 148 placebo recipients) were included in the per-protocol analysis. 287 first episodes of cholera (109 among vaccine recipients and 178 among placebo recipients) were detected during the 2-year follow-up; 138 of these episodes (46 in vaccine recipients and 92 in placebo recipients) were associated with severe dehydration. The overall incidence rates of initial cholera episodes were 0·22 (95% CI 0·18 to 0·27) per 100 000 person-days in vaccine recipients versus 0·36 (0·31 to 0·42) per 100 000 person-days in placebo recipients (adjusted protective efficacy 39%, 95% CI 23 to 52). The overall incidence of severe cholera was 0·09 (0·07 to 0·12) per 100 000 person-days versus 0·19 (0·15 to 0·23; adjusted protective efficacy 50%, 29 to 65). Vaccine protective efficacy was 52% (8 to 75) against all cholera episodes and 71% (27 to 88) against severe cholera episodes in participants aged 5 years to younger than 15 years. For participants aged 15 years or older, vaccine protective efficacy was 59% (42 to 71) against all cholera episodes and 59% (35 to 74) against severe cholera. The protection in the older age groups was sustained throughout the 2-year follow-up. In participants younger than 5 years, the vaccine did not show protection against either all cholera episodes (protective efficacy -13%, -68 to 25) or severe cholera episodes (-44%, -220 to 35). A single dose of the inactivated whole-cell OCV offered protection to older children and adults that was sustained for at least 2 years. The absence of protection of young children might reflect a lesser degree of pre-existing natural immunity in this age group. Bill & Melinda Gates Foundation to the International Vaccine Institute.

Household and Individual Risk Factors for Cholera among Cholera Vaccine Recipients in Rural Haiti.

.Oral cholera vaccination was used as part of cholera control in Haiti, but the vaccine does not provide complete protection. We conducted secondary data analyses of a vaccine effectiveness study in Haiti to evaluate risk factors for cholera among cholera vaccine recipients. Individuals vaccinated against cholera that presented with acute watery diarrhea and had a stool sample positive for Vibrio cholerae O1 were included as cases. Up to four vaccinated individuals who did not present for treatment of diarrhea were included as controls for each case, and matched by location of residence, enrollment time, and age. We evaluated sociodemographic characteristics and risk factors for cholera. Univariable and multivariable logistic regression were performed to identify risk factors for cholera among vaccinees. Thirty-three vaccine recipients with culture-confirmed cholera were included as cases. One-hundred-and-seventeen of their matched controls reported receiving vaccine and were included as controls. In a multivariable analysis, self-reporting use of branded household water disinfection products as a means of treating water (adjusted relative risk [aRR] = 44.3, 95% confidence interval [CI] = 4.19–468.05, P = 0.002), and reporting having a latrine as the main household toilet (aRR = 4.22, 95% CI = 1.23–14.43, P = 0.02), were independent risk factors for cholera. Self-reporting always treating water (aRR = 0.09, 95% CI = 0.01–0.57, P = 0.01) was associated with protection against cholera. The field effectiveness of water, sanitation, and hygiene interventions used in combination with cholera vaccination in cholera control should be measured and monitored over time to identify and remediate shortcomings, and ensure successful impact on disease control.

Clinical Features of Human Immunodeficiency Virus-Infected Patients Presenting with Cholera in Port-au-Prince, Haiti.

Human immunodeficiency virus (HIV) infection has been postulated to alter the natural history of cholera, including increased susceptibility to infection, severity of illness, and chronic carriage of Vibrio cholerae Haiti has a generalized HIV epidemic with an adult HIV prevalence of 1.9% and recently suffered a cholera epidemic. We conducted a prospective study at the cholera treatment center (CTC) of GHESKIO in Haiti to characterize the coinfection. Adults admitted at the CTC for acute diarrhea were invited to participate in the study. Vital signs, frequency, and volume of stools and/or vomiting were monitored, and single-dose doxycycline was administered. After counseling, participants were screened for HIV by enzyme-linked immunosorbent assay and for cholera by culture. Of 729 adults admitted to the CTC, 99 (13.6%) had HIV infection, and 457 (63%) had culture-confirmed cholera. HIV prevalence was three times higher in patients without cholera (23%, 63/272) than in those with culture-confirmed cholera (7.9%, 36/457). HIV prevalence in patients with culture-confirmed cholera (7.9%) was four times higher than the adult prevalence in Port-au-Prince (1.9%). Of the 36 HIV-infected patients with cholera, 25 (69%) had moderate/severe dehydration versus 302/421 (72%) in the HIV negative. Of 30 HIV-infected patients with weekly stool cultures performed after discharge, 29 (97%) were negative at week 1. Of 50 HIV-negative patients with weekly stool cultures, 49 (98%) were negative at week 1. In countries with endemic HIV infection, clinicians should consider screening patients presenting with suspected cholera for HIV coinfection.

Cholera Incidence and Mortality in Sub-Saharan African Sites during Multi-country Surveillance.

BackgroundCholera burden in Africa remains unknown, often because of weak national surveillance systems. We analyzed data from the African Cholera Surveillance Network (www.africhol.org).Methods/ Principal findingsDuring June 2011–December 2013, we conducted enhanced surveillance in seven zones and four outbreak sites in Togo, the Democratic Republic of Congo (DRC), Guinea, Uganda, Mozambique and Cote d’Ivoire. All health facilities treating cholera cases were included. Cholera incidences were calculated using culture-confirmed cholera cases and culture-confirmed cholera cases corrected for lack of culture testing usually due to overwhelmed health systems and imperfect test sensitivity. Of 13,377 reported suspected cases, 34% occurred in Conakry, Guinea, 47% in Goma, DRC, and 19% in the remaining sites. From 0–40% of suspected cases were aged under five years and from 0.3–86% had rice water stools. Within surveillance zones, 0–37% of suspected cases had confirmed cholera compared to 27–38% during outbreaks. Annual confirmed incidence per 10,000 population was <0.5 in surveillance zones, except Goma where it was 4.6. Goma and Conakry had corrected incidences of 20.2 and 5.8 respectively, while the other zones a median of 0.3. During outbreaks, corrected incidence varied from 2.6 to 13.0. Case fatality ratios ranged from 0–10% (median, 1%) by country.Conclusions/SignificanceAcross different African epidemiological contexts, substantial variation occurred in cholera incidence, age distribution, clinical presentation, culture confirmation, and testing frequency. These results can help guide preventive activities, including vaccine use.

Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh

BackgroundA single-dose regimen of the current killed oral cholera vaccines that have been prequalified by the World Health Organization would make them more attractive for use against endemic and epidemic cholera. We conducted an efficacy trial of a single dose of the killed oral cholera vaccine Shanchol, which is currently given in a two-dose schedule, in an urban area in which cholera is highly endemic.MethodsNonpregnant residents of Dhaka, Bangladesh, who were 1 year of age or older were randomly assigned to receive a single dose of oral cholera vaccine or oral placebo. The primary outcome was vaccine protective efficacy against culture-confirmed cholera occurring 7 to 180 days after dosing. Prespecified secondary outcomes included protective efficacy against severely dehydrating culture-confirmed cholera during the same interval, against cholera and severe cholera occurring 7 to 90 versus 91 to 180 days after dosing, and against cholera and severe cholera according to age at baseline.ResultsA total of 101 episodes of cholera, 37 associated with severe dehydration, were detected among the 204,700 persons who received one dose of vaccine or placebo. The vaccine protective efficacy was 40% (95% confidence interval [CI], 11 to 60%; 0.37 cases per 1000 vaccine recipients vs. 0.62 cases per 1000 placebo recipients) against all cholera episodes, 63% (95% CI, 24 to 82%; 0.10 vs. 0.26 cases per 1000 recipients) against severely dehydrating cholera episodes, and 63% (95% CI, −39 to 90%), 56% (95% CI, 16 to 77%), and 16% (95% CI, −49% to 53%) against all cholera episodes among persons vaccinated at the age of 5 to 14 years, 15 or more years, and 1 to 4 years, respectively, although the differences according to age were not significant (P=0.25). Adverse events occurred at similar frequencies in the two groups.ConclusionsA single dose of the oral cholera vaccine was efficacious in older children (≥5 years of age) and in adults in a setting with a high level of cholera endemicity. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02027207.)

Effectiveness of Oral Cholera Vaccine in Haiti: 37-Month Follow-Up.

The first oral cholera vaccine (OCV) campaign, since its prequalification by the World Health Organization, in response to an ongoing cholera epidemic (reactive vaccination) was successfully conducted in a poor urban slum of approximately 70,000 inhabitants in Port-au-Prince, Haiti, in 2012. Vaccine coverage was 75% of the target population. This report documents the impact of OCV in reducing the number of culture-confirmed cases of cholera admitted to the Groupe Haïtien d'Etude du Sarcome de Kaposi et des Infections Opportunistes (GHESKIO) cholera treatment center from that community in the 37 months postvaccination (April 2012-April 30, 2015). Of 1,788 patients with culture-confirmed cholera, 1,770 (99%) were either from outside the vaccine area (1,400 cases) or from the vaccinated community who had not received OCV (370 cases). Of the 388 people from the catchment area who developed culture-confirmed cholera, 370 occurred among the 17,643 people who had not been vaccinated (2.1%) and the remaining 18 occurred among the 52,357 people (0.034%) who had been vaccinated (P < 0.001), for an efficacy that approximates 97.5%. Despite not being designed as a randomized control trial, the very high efficacy is a strong evidence for the effectiveness of OCV as part of an integrated package for the control of cholera in outbreak settings.

5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial

Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India. In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment. 69 of 31 932 recipients of vaccine and 219 of 34 968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; p<0·0001), and point estimates by year of follow-up suggested no evidence of decline in protective efficacy. Sustained protection for 5 years at the level we reported has not been noted previously with other oral cholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings. Bill & Melinda Gates Foundation and the governments of South Korea and Sweden.

Costs of illness due to endemic cholera.

Economic analyses of cholera immunization programmes require estimates of the costs of cholera. The Diseases of the Most Impoverished programme measured the public, provider, and patient costs of culture-confirmed cholera in four study sites with endemic cholera using a combination of hospital- and community-based studies. Families with culture-proven cases were surveyed at home 7 and 14 days after confirmation of illness. Public costs were measured at local health facilities using a micro-costing methodology. Hospital-based studies found that the costs of severe cholera were US$32 and US$47 in Matlab and Beira. Community-based studies in North Jakarta and Kolkata found that cholera cases cost between US$28 and US$206, depending on hospitalization. Patients' cost of illness as a percentage of average monthly income were 21% and 65% for hospitalized cases in Kolkata and North Jakarta, respectively. This burden on families is not captured by studies that adopt a provider perspective.

Prevalence of cholera in pediatric patients with acute dehydrating diarrhea

To estimate the prevalence of culture-confirmed cholera in patients with acute dehydrating diarrhea, at a tertiary care center in north India, during a 6-month period from March to August, 2006. We studied 145 children, who presented to the pediatric emergency services of a tertiary care teaching hospital in north India with acute dehydrating diarrhea. Each patient had his/her stool sample collected for Vibrio cholerae culture and hanging drop preparation for darting motility. The stool specimen for hanging drop analysis was immediately transported to the emergency laboratory, where a trained technician prepared the slides and examined them for darting motility characteristic of Vibrio cholerae. V. cholerae was isolated in 36 (24.8%) patients. Forty-nine (33.7%) patients had a positive hanging drop examination. Hanging drop examination had a sensitivity and specificity of 85.8% and 81.7%, respectively. Severe dehydration (OR 4.3; P<0.01) and hanging drop positivity (OR 12.42; P<0.001) were associated with higher odds of cholera after adjustment for other risk factors. Cholera is an important cause of acute watery diarrhea in pediatric patients in urban north India and should be ruled out in all children presenting with acute dehydrating diarrhea, particularly those with severe dehydration. Hanging drop test is useful for diagnosis in the emergency setting.

Antigen-Specific Memory B-Cell Responses to Vibrio cholerae O1 Infection in Bangladesh

Cholera, caused by Vibrio cholerae, is a noninvasive dehydrating enteric disease with a high mortality rate if untreated. Infection with V. cholerae elicits long-term protection against subsequent disease in countries where the disease is endemic. Although the mechanism of this protective immunity is unknown, it has been hypothesized that a protective mucosal response to V. cholerae infection may be mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue. To characterize memory B-cell responses to cholera, we enrolled a cohort of 39 hospitalized patients with culture-confirmed cholera and evaluated their immunologic responses at frequent intervals over the subsequent 1 year. Memory B cells to cholera antigens, including lipopolysaccharide (LPS), and the protein antigens cholera toxin B subunit (CTB) and toxin-coregulated pilus major subunit A (TcpA) were enumerated using a method of polyclonal stimulation of peripheral blood mononuclear cells followed by a standard enzyme-linked immunospot procedure. All patients demonstrated CTB, TcpA, and LPS-specific immunoglobulin G (IgG)and IgA memory responses by day 90. In addition, these memory B-cell responses persisted up to 1 year, substantially longer than other traditional immunologic markers of infection with V. cholerae. While the magnitude of the LPS-specific IgG memory B-cell response waned at 1 year, CTB- and TcpA-specific IgG memory B cells remained significantly elevated at 1 year after infection, suggesting that T-cell help may result in a more durable memory B-cell response to V. cholerae protein antigens. Such memory B cells could mediate anamnestic responses on reexposure to V. cholerae.

Helicobacter pylori-associated chronic atrophic gastritis involving the gastric body and severe disease by Vibrio cholerae

Evidence has associated chronic infection by Helicobacter pylori with chronic gastritis, low gastric acid production and an increased risk of life-threatening cholera. However, the relationship of specific patterns of histological damage in the gastric mucosa associated with H. pylori infection and the occurrence of cholera has not been described. The purpose of this study was to compare the gastric pH and histopathological findings in gastric biopsies taken from patients with severe diarrhoeal disease due to Vibrio cholerae with those taken from a control (cholera-negative) population. Thirty-five H. pylori-positive patients who had severe dehydration from culture-confirmed cholera (cases) and 40 patients with H. pylori but with no history of cholera (controls) were recruited. Gastric pH was measured and multiple biopsies were taken from the gastric antrum and body for histopathological examination. The results revealed that patients with severe cholera had a significantly higher prevalence of hypochlorhydria at endoscopy compared with controls. Furthermore, cases had significantly more chronic atrophic gastritis (45.7% vs. 12.5%; P=0.002) and intestinal metaplasia (37.1% vs. 2.5%; P<0.01) in the gastric body than controls. Our findings suggest that the nature and location of these gastric lesions may predispose a subset of H. pylori-infected individuals to severe disease by V. cholerae.

Effectiveness of Mass Oral Cholera Vaccination in Beira, Mozambique

New-generation, orally administered cholera vaccines offer the promise of improved control of cholera in sub-Saharan Africa. However, the high prevalence of human immunodeficiency virus (HIV) infection in many cholera-affected African populations has raised doubts about the level of protection possible with vaccination. We evaluated a mass immunization program with recombinant cholera-toxin B subunit, killed whole-cell (rBS-WC) oral cholera vaccine in Beira, Mozambique, a city where the seroprevalence of HIV is 20 to 30 percent. From December 2003 to January 2004, we undertook mass immunization of nonpregnant persons at least two years of age, using a two-dose regimen of rBS-WC vaccine in Esturro, Beira (population 21,818). We then assessed vaccine protection in a case-control study during an outbreak of El Tor Ogawa cholera in Beira between January and May 2004. To estimate the level of vaccine protection, antecedent rates of vaccination were compared between persons with culture-confirmed cholera severe enough to have prompted them to seek treatment and age- and sex-matched neighborhood controls without treated diarrhea. We assessed the effectiveness of the vaccine in 43 persons with cholera and 172 controls. Receipt of one or more doses of rBS-WC vaccine was associated with 78 percent protection (95 percent confidence interval, 39 to 92 percent; P=0.004). The vaccine was equally effective in children younger than five years of age and in older persons. A concurrently conducted case-control study designed to detect bias compared persons with treated, noncholeraic diarrhea and controls without diarrhea in the same population and found no protection associated with receipt of the rBS-WC vaccine. The rBS-WC vaccine was highly effective against clinically significant cholera in an urban sub-Saharan African population with a high prevalence of HIV infection.

Epidemiologic Study of Vibrio cholerae O1 and O139 in Thailand: At the Advancing Edge of the Eighth Pandemic

Vibrio cholerae O139 Bengal emerged on the Indian subcontinent in late 1992 and was first recognized in Thailand in 1993. To characterize the epidemiology of this disease, a hospital-based case-control study was conducted in Samutsakorn, a port city 30 km southwest of Bangkok. Between November 15, 1993, and June 3, 1994, 366 patients were confirmed to have cholera by culture, including 165 (45%) with O139 Bengal, 191 (52%) with O1 Ogawa, and 10 (3%) with both serogroups. During the same time period the previous year, 319 culture-confirmed cholera cases occurred, all serogroup O1. Questionnaires were obtained from 105 patients with O139 Bengal and 103 with O1 infections; for each case patient, two asymptomatic age- and sex-matched control persons were selected. Of the patients with O139 Bengal infections, 93% were adults (> or = 15 years) compared with 92% of patients with O1 infections. Risk factors for cholera identified by case-control comparisons were similar for the two serogroups and included consumption of untreated water, uncooked seafood, and food served at group gatherings. V. cholerae O139 Bengal has emerged in Thailand as a cause of endemic cholera, with epidemiologic features and incidence similar to those of the preexisting O1 strain.