A commensal-encoded genotoxin drives restriction of Vibrio cholerae colonization and host gut microbiome remodeling.

SignificanceIn a polymicrobial battlefield where different species compete for nutrients and colonization niches, antimicrobial compounds are the sword and shield of commensal microbes in competition with invading pathogens and each other. The identification of an Escherichia coli-produced genotoxin, colibactin, and its specific targeted killing of enteric pathogens and commensals, including Vibrio cholerae and Bacteroides fragilis, sheds light on our understanding of intermicrobial interactions in the mammalian gut. Our findings elucidate the mechanisms through which genotoxins shape microbial communities and provide a platform for probing the larger role of enteric multibacterial interactions regarding infection and disease outcomes.

Descriptive epidemiology of cholera outbreak in Nigeria, January-November, 2018: implications for the global roadmap strategy.

BACKGROUND: The cholera outbreak in 2018 in Nigeria reaffirms its public health threat to the country. Evidence on the current epidemiology of cholera required for the design and implementation of appropriate interventions towards attaining the global roadmap strategic goals for cholera elimination however seems lacking. Thus, this study aimed at addressing this gap by describing the epidemiology of the 2018 cholera outbreak in Nigeria. METHODS: This was a retrospective analysis of surveillance data collected between January 1st and November 19th, 2018. A cholera case was defined as an individual aged 2 years or older presenting with acute watery diarrhoea and severe dehydration or dying from acute watery diarrhoea. Descriptive analyses were performed and presented with respect to person, time and place using appropriate statistics. RESULTS: There were 43,996 cholera cases and 836 cholera deaths across 20 states in Nigeria during the outbreak period, with an attack rate (AR) of 127.43/100,000 population and a case fatality rate (CFR) of 1.90%. Individuals aged 15 years or older (47.76%) were the most affected age group, but the proportion of affected males and females was about the same (49.00 and 51.00% respectively). The outbreak was characterised by four distinct epidemic waves, with higher number of deaths recorded in the third and fourth waves. States from the north-west and north-east regions of the country recorded the highest ARs while those from the north-central recorded the highest CFRs. CONCLUSION: The severity and wide-geographical distribution of cholera cases and deaths during the 2018 outbreak are indicative of an elevated burden, which was more notable in the northern region of the country. Overall, the findings reaffirm the strategic role of a multi-sectoral approach in the design and implementation of public health interventions aimed at preventing and controlling cholera in Nigeria.

Cholera Epidemics of the Past Offer New Insights Into an Old Enemy.

Background: Although cholera is considered the quintessential long-cycle waterborne disease, studies have emphasized the existence of short-cycle (food, household) transmission. We investigated singular Danish cholera epidemics (in 1853) to elucidate epidemiological parameters and modes of spread. Methods: Using time series data from cities with different water systems, we estimated the intrinsic transmissibility (R0). Accessing cause-specific mortality data, we studied clinical severity and age-specific impact. From physicians' narratives we established transmission chains and estimated serial intervals. Results: Epidemics were seeded by travelers from cholera-affected cities; initial transmission chains involving household members and caretakers ensued. Cholera killed 3.4%-8.9% of the populations, with highest mortality among seniors (16%) and lowest in children (2.7%). Transmissibility (R0) was 1.7-2.6 and the serial interval was estimated at 3.7 days (95% confidence interval, 2.9-4.7 days). The case fatality ratio (CFR) was high (54%-68%); using R0 we computed an adjusted CFR of 4%-5%. Conclusions: Short-cycle transmission was likely critical to early secondary transmission in historic Danish towns. The outbreaks resembled the contemporary Haiti outbreak with respect to transmissibility, age patterns, and CFR, suggesting a role for broader hygiene/sanitation interventions to control contemporary outbreaks.

Anti-Vibriocholerae IgY Antibody Inhibits Mortality in Suckling Mice Model.

BACKGROUND: Regarding to the importance of cholera in Iran and the potential advantages of egg yolk antibody (IgY) for immunotherapy, the aim of this study was to produce IgY antibody against V. cholerae Lipopolysaccharide (LPS) and determine its potential for V. cholerae treatment. METHODS: LPS was prepared, and the Anti-V. cholerae LPS IgY was purified from egg yolk and serially diluted in phosphate-buffered saline (PBS), mixed with V. cholerae and then gavaged into several groups of suckling mice. RESULTS: The yield of Anti-LPS IgY extraction was 40 mg/Egg yolk. The results demonstrated that up to approximately 75 ng of IgY can detect specifically V. cholerae. The lowest protective dose of anti-V. cholerae LPS IgY was 2.5 µg. CONCLUSIONS: The produced anti-Vibrio LPS specific IgY showed a good reactivity with its specific antigen and it may use as a complimentary oral immunotherapy for cholera disease.

Cholera Mortality during Urban Epidemic, Dar es Salaam, Tanzania, August 16, 2015-January 16, 20161.

In 2015, a cholera epidemic occurred in Tanzania; most cases and deaths occurred in Dar es Salaam early in the outbreak. We evaluated cholera mortality through passive surveillance, burial permits, and interviews conducted with decedents' caretakers. Active case finding identified 101 suspected cholera deaths. Routine surveillance had captured only 48 (48%) of all cholera deaths, and burial permit assessments captured the remainder. We interviewed caregivers of 56 decedents to assess cholera management behaviors. Of 51 decedents receiving home care, 5 (10%) used oral rehydration solution after becoming ill. Caregivers reported that 51 (93%) of 55 decedents with known time of death sought care before death; 16 (29%) of 55 delayed seeking care for >6 h. Of the 33 (59%) community decedents, 20 (61%) were said to have been discharged from a health facility before death. Appropriate and early management of cholera cases can reduce the number of cholera deaths.

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.

Cholera surveillance during the Haiti epidemic--the first 2 years.

BACKGROUND: In October 2010, nearly 10 months after a devastating earthquake, Haiti was stricken by epidemic cholera. Within days after detection, the Ministry of Public Health and Population established a National Cholera Surveillance System (NCSS). METHODS: The NCSS used a modified World Health Organization case definition for cholera that included acute watery diarrhea, with or without vomiting, in persons of all ages residing in an area in which at least one case of Vibrio cholerae O1 infection had been confirmed by culture. RESULTS: Within 29 days after the first report, cases of V. cholerae O1 (serotype Ogawa, biotype El Tor) were confirmed in all 10 administrative departments (similar to states or provinces) in Haiti. Through October 20, 2012, the public health ministry reported 604,634 cases of infection, 329,697 hospitalizations, and 7436 deaths from cholera and isolated V. cholerae O1 from 1675 of 2703 stool specimens tested (62.0%). The cumulative attack rate was 5.1% at the end of the first year and 6.1% at the end of the second year. The cumulative case fatality rate consistently trended downward, reaching 1.2% at the close of year 2, with departmental cumulative rates ranging from 0.6% to 4.6% (median, 1.4%). Within 3 months after the start of the epidemic, the rolling 14-day case fatality rate was 1.0% and remained at or below this level with few, brief exceptions. Overall, the cholera epidemic in Haiti accounted for 57% of all cholera cases and 53% of all cholera deaths reported to the World Health Organization in 2010 and 58% of all cholera cases and 37% of all cholera deaths in 2011. CONCLUSIONS: A review of NCSS data shows that during the first 2 years of the cholera epidemic in Haiti, the cumulative attack rate was 6.1%, with cases reported in all 10 departments. Within 3 months after the first case was reported, there was a downward trend in mortality, with a 14-day case fatality rate of 1.0% or less in most areas.

A retrospective analysis of oral cholera vaccine use, disease severity and deaths during an outbreak in South Sudan.

OBJECTIVE: To determine whether pre-emptive oral cholera vaccination reduces disease severity and mortality in people who develop cholera disease during an outbreak. METHODS: The study involved a retrospective analysis of demographic and clinical data from 41 cholera treatment facilities in South Sudan on patients who developed cholera disease between 23 April and 20 July 2014 during a large outbreak, a few months after a pre-emptive oral vaccination campaign. Patients who developed severe dehydration were regarded as having a severe cholera infection. Vaccinated and unvaccinated patients were compared and multivariate logistic regression analysis was used to identify factors associated with developing severe disease or death. FINDINGS: In total, 4115 cholera patients were treated at the 41 facilities: 1946 (47.3%) had severe disease and 62 (1.5%) deaths occurred. Multivariate analysis showed that patients who received two doses of oral cholera vaccine were 4.5-fold less likely to develop severe disease than unvaccinated patients (adjusted odds ratio, aOR: 0.22; 95% confidence interval, CI: 0.11-0.44). Moreover, those with severe cholera were significantly more likely to die than those without (aOR: 4.76; 95% CI: 2.33-9.77). CONCLUSION: Pre-emptive vaccination with two doses of oral cholera vaccine was associated with a significant reduction in the likelihood of developing severe cholera disease during an outbreak in South Sudan. Moreover, severe disease was the strongest predictor of death. Two doses of oral cholera vaccine should be used in emergencies to reduce the disease burden.

Cross-protection against Vibrio cholerae infection by monoclonal antibodies against Vibrio vulnificus RtxA1/MARTXVv.

Gram-negative Vibrio species secrete multifunctional autoprocessing repeats-in-toxin (MARTX) toxins associated with bacterial pathogenesis. Here, the cross-reactivity and cross-protectivity of mAbs against V. vulnificus RtxA1/MARTXVv was evaluated. Passive administration of any of these mAbs (21RA, 24RA, 46RA, 47RA and 50RA) provided strong protection against lethal V. cholerae infection. Interestingly, 24RA and 46RA, which map to the cysteine protease domain of V. cholerae MARTXVc , inhibited CPD autocleavage in vitro; this process is involved in V. cholerae pathogenesis. These results generate new insight into the development of broadly protective mAbs and/or vaccines against Vibrio species with MARTX toxins.

The mortality rates and the space-time patterns of John Snow's cholera epidemic map.

BACKGROUND: Snow's work on the Broad Street map is widely known as a pioneering example of spatial epidemiology. It lacks, however, two significant attributes required in contemporary analyses of disease incidence: population at risk and the progression of the epidemic over time. Despite this has been repeatedly suggested in the literature, no systematic investigation of these two aspects was previously carried out. Using a series of historical documents, this study constructs own data to revisit Snow's study to examine the mortality rate at each street location and the space-time pattern of the cholera outbreak. METHODS: This study brings together records from a series of historical documents, and prepares own data on the estimated number of residents at each house location as well as the space-time data of the victims, and these are processed in GIS to facilitate the spatial-temporal analysis. Mortality rates and the space-time pattern in the victims' records are explored using Kernel Density Estimation and network-based Scan Statistic, a recently developed method that detects significant concentrations of records such as the date and place of victims with respect to their distance from others along the street network. The results are visualised in a map form using a GIS platform. RESULTS: Data on mortality rates and space-time distribution of the victims were collected from various sources and were successfully merged and digitised, thus allowing the production of new map outputs and new interpretation of the 1854 cholera outbreak in London, covering more cases than Snow's original report and also adding new insights into their space-time distribution. They confirmed that areas in the immediate vicinity of the Broad Street pump indeed suffered from excessively high mortality rates, which has been suspected for the past 160 years but remained unconfirmed. No distinctive pattern was found in the space-time distribution of victims' locations. CONCLUSIONS: The high mortality rates identified around the Broad Street pump are consistent with Snow's theory about cholera being transmitted through contaminated water. The absence of a clear space-time pattern also indicates the water-bourne, rather than the then popular belief of air bourne, nature of cholera. The GIS data constructed in this study has an academic value and would cater for further research on Snow's map.

Biological and Cultural Causes of Seasonality of Deaths in Historical Populations From Poland.

Seasonal fluctuations in mortality and their causes in the nineteenth century Polish rural populations: wealthy, agriculturally and economically advanced populations from Wielkopolska, and poor populations from Silesia and Galicia (southern Poland) were described. Data-sources included parish death registers from the Roman Catholic parish of Dziekanowice in the region of Wielkopolska, Prussian statistical yearbooks for the Pozna Province as well as information from previous publications regarding Silesia and Galicia. The 19th century patterns were compared with those in present-day Poland. The occurrence of seasonality of deaths was assessed with: the Chi-squared test, the Kolmogorov-Smirnov test, and the Autoregressive Integrated Moving Average Models (ARIMA). In all populations there was a winter maximum of the number of deaths, while the minimum occurred in early summer. In the poor populations of Silesia and Galicia another statistically significant increase in the incidence of deaths was observed in the early spring. In the rich and modern villages of Wielkopolska there was no spring increase in the number of deaths, however, in all populations of Wielkopolska, irrespective of a particular pattern, a secondary mortality peak occurred in the late summer and autumn. Statistical tests used in this study did not show any clear differences in the distribution of the seasonality of deaths between the populations of Wielkopolska on the one hand, and the populations from Galicia and Silesia, on the other hand. The statistical significance of differences was, however, evident between populations representing the two distinguished by secondary peaks death seasonality patterns. Seasonal death increase split the populations under study into two groups according to the criterion of wealth.

Analysis of fatality due to cholera epidemics in Tuliszków parish in 1852.

INTRODUCTION: Little is known about the correlation between age, gender-distribution and fatality rate during cholera epidemics. AIM: To analyze the change in the fatality rate with regard to age and gender during cholera epidemics in 1852 in Tuliszków Parish. MATERIAL AND METHODS: Data for the present study were retrieved from the archives. Information on fatal cases was obtained from the records of Tuliszków Parish - The Register of Deaths (1851-1879). Age, gender of the deceased and place of residence in Tuliszków Parish were analyzed. Data from the year in which the epidemic occurred (1852) and year preceding it (1851) were compared using Pearson's χ2 test. RESULTS: A total of 3200 persons lived in the Roman Catholic Parish of Tuliszków during cholera epidemic in 1852. Having compared to the control year (1851), fatality rate distribution changed statistically significantly in the epidemic year (1852); (χ2=27.5665, p=0.0011). In particular, it applied to males (χ2=28.9476, p=0.0007). Irrespective of the gender, the highest increase of the fatality rate was observed in the 10-25 age group (χ2=5.0375, p=0.0248) while infant fatality rate decreased (χ2=19.2789, p=0.0000). CONCLUSIONS: Cholera epidemic resulted in a significant change of fatality rate in infants, males and the youth. Death of both parents aged up to 45 years old contributed to an increase in the number of orphans.

Descriptive characterization of the 2010 cholera outbreak in Nigeria.

BACKGROUND: In 2010, 18 States of Nigeria reported cholera outbreaks with a total of 41,787 cases including 1,716 deaths (case-fatality rate [CFR]: 4.1%). This exceeded the mean overall CFR of 2.4% reported in Africa from 2000-2005 and the WHO acceptable rate of 1%. We conducted a descriptive analysis of the 2010 cholera outbreak to determine its epidemiological and spatio-temporal characteristics. METHODS: We conducted retrospective analysis of line lists obtained from 10 of the 18 states that submitted line lists to the Federal Ministry of Health (FMOH). We described the outbreak by time, place and person and calculated the attack rates by state as well as the age- and sex-specific CFR from cholera cases for whom information on age, sex, place of residence, onset of symptoms and outcome were available. RESULTS: A total of 21,111 cases were reported with an overall attack rate and CFR of 47.8 cases /100,000 population and 5.1%, respectively. The CFR ranged in the states between 3.8% and 8.9%. The age-specific CFR was highest among individuals 65 years and above (14.6%). The epidemiological curve showed three peaks with increasing number of weekly reported cases. A geographical clustering of LGAs reporting cholera cases could be seen in all ten states. During the third peak which coincided with flooding in five states the majority of newly affected LGAs were situated next to LGAs with previously reported cholera cases, only few isolated outbreaks were seen. CONCLUSION: Our study showed a cholera outbreak that grew in magnitude and spread to involve the whole northern part of the country. It also highlights challenges of suboptimal surveillance and response in developing countries as well as potential endemicity of cholera in the northern part of Nigeria. There is the need for a harmonized, coordinated approach to cholera outbreaks through effective surveillance and response with emphasis on training and motivating front line health workers towards timely detection, reporting and response. Findings from the report should be interpreted with caution due to the high number of cases with incomplete information, and lack of data from eight states.

Kabrit ki gen twòp mèt: understanding gaps in WASH services in Haiti's IDP camps.

Despite the enormous infusion of post-quake aid to Haiti, cholera had killed more than 8,000 people by January 2013. Based on two mixed-method studies of a random sample of 108 internally displaced person (IDP) camps and 168 interviews with agency representatives and recipients, this article examines the prevalence of factors that have proven most relevant to the rapid spread of cholera, particularly the provision of water and sanitation services in IDP camps. The study reveals that 30% of IDP camps had no toilets and 40% had no access to water before the outbreak, with only minimal progress after three months. Using bivariate and multivariate statistical analyses, this article explores patterns in the gaps of services with a range of variables such as NGO camp management, municipality and land-owners. It offers several theoretical and policy explanations for low level of services, concluding with a series of recommendations for better coordination and management.

Traveling wave solutions for epidemic cholera model with disease-related death.

Based on Codeço's cholera model (2001), an epidemic cholera model that incorporates the pathogen diffusion and disease-related death is proposed. The formula for minimal wave speed c (∗) is given. To prove the existence of traveling wave solutions, an invariant cone is constructed by upper and lower solutions and Schauder's fixed point theorem is applied. The nonexistence of traveling wave solutions is proved by two-sided Laplace transform. However, to apply two-sided Laplace transform, the prior estimate of exponential decrease of traveling wave solutions is needed. For this aim, a new method is proposed, which can be applied to reaction-diffusion systems consisting of more than three equations.

National surveillance data on the epidemiology of cholera in Cameroon.

Background. The cholera burden in Cameroon has increased during the past 2 decades. During 2010 and 2011, the largest number of cholera cases in Cameroon since February 1971 were reported. This article describes cholera outbreaks during 2010-2011. Methods. Data received from the national surveillance system from 2010 and 2011 were compiled and analyzed. Results. The first suspected cholera cases were reported in the Far North region on 6 May 2010. In 2010, 10 759 cholera cases were reported by 8 of the 10 regions in the country, with 657 deaths (case-fatality ratio [CFR], 6.1%). In 2011, through September 22, 17 121 suspected cholera cases, including 636 deaths (CFR, 3.7%), were reported all over the country. During 2010, the Far North region accounted for 87.6% of cases (9421/10 759) and 91.6% of deaths (602/657) recorded. By contrast, during 2011, 5 regions (Far North, North, Center, Southwest, and Littoral) accounted for 90.6% of cases (15 511/17 121) and 84.0% of deaths recorded. Vibrio cholerae was identified in 525 stool specimens, and all organisms were serogroup O1. Conclusions. The ongoing cholera outbreak in Cameroon increased in intensity and geographic spread from 2010 to 2011. Nevertheless, the overall CFR decreased during this period. Strengthening the early warning system and enhancing water, sanitation, and hygiene interventions and sensitization should be considered in addressing cholera outbreaks.

A national cholera epidemic with high case fatality rates--Kenya 2009.

BACKGROUND: Cholera remains endemic in sub-Saharan Africa. We characterized the 2009 cholera outbreaks in Kenya and evaluated the response. METHODS: We analyzed surveillance data and estimated case fatality rates (CFRs). Households in 2 districts, East Pokot (224 cases; CFR = 11.7%) and Turkana South (1493 cases; CFR = 1.0%), were surveyed. We randomly selected 15 villages and 8 households per village in each district. Healthcare workers at 27 health facilities (HFs) were surveyed in both districts. RESULTS: In 2009, cholera outbreaks caused a reported 11 425 cases and 264 deaths in Kenya. Data were available from 44 districts for 6893 (60%) cases. District CFRs ranged from 0% to 14.3%. Surveyed household respondents (n = 240) were aware of cholera (97.5%) and oral rehydration solution (ORS) (87.9%). Cholera deaths were reported more frequently from East Pokot (n = 120) than Turkana South (n = 120) households (20.7% vs. 12.3%). The average travel time to a HF was 31 hours in East Pokot compared with 2 hours in Turkana South. Fewer respondents in East Pokot (9.8%) than in Turkana South (33.9%) stated that ORS was available in their village. ORS or intravenous fluid shortages occurred in 20 (76.9%) surveyed HFs. CONCLUSIONS: High CFRs in Kenya are related to healthcare access disparities, including availability of rehydration supplies.

Recurrent epidemic cholera with high mortality in Cameroon: persistent challenges 40 years into the seventh pandemic.

Cameroon has experienced recurrent cholera epidemics with high mortality rates. In September 2009, epidemic cholera was detected in the Far North region of Cameroon and the reported case-fatality rate was 12%. We conducted village-, healthcare facility- and community-level surveys to investigate reasons for excess cholera mortality. Results of this investigation suggest that cholera patients who died were less likely to seek care, receive rehydration therapy and antibiotics at a healthcare facility, and tended to live further from healthcare facilities. Furthermore, use of oral rehydration salts at home was very low in both decedents and survivors. Despite the many challenges inherent to delivering care in Cameroon, practical measures could be taken to reduce cholera mortality in this region, including the timely provision of treatment supplies, training of healthcare workers, establishment of rehydration centres, and promotion of household water treatment and enhanced handwashing with soap.

Antibiotics for the treatment of Cholera, Shigella and Cryptosporidium in children.

BACKGROUND: Diarrhea is a major contributor to the burden of morbidity and mortality in children; it accounts for a median of 11% of all deaths among children aged less than 5 years, amounting to approximately 0.8 million deaths per year. Currently there is a dearth of literature exploring the effectiveness of antibiotics for diarrhea due to Cholera, Shigella and cryptosporidiosis in children. METHODS: We reviewed the literature reporting the effect of antibiotics for the treatment of diarrhea due to Cholera, Shigella and Cryptosporidium in children under five years. We used a standardized abstraction and grading format and performed meta-analyses to determine the effect of the treatment with various antibiotics on mortality and rates of clinical and bacteriological/parasitological failure. The CHERG Standard Rules were applied to determine the final effect of treatment with antibiotics on diarrhea morbidity and mortality. RESULTS: For Cholera; the evidence was weak to recommend any effect on mortality. For Shigella; there was no data on mortality; either all-cause or cause specific, hence we used clinical failure rates as a proxy for Shigella deaths and propose that treatment of Shigella dysentery with antibiotics can result in a 82% reduction in diarrhea mortality due to Shigella. For cryptosporidiosis; there was data on all-cause mortality but the evidence was weak hence we used clinical failure rates as a proxy for mortality to estimate that antimicrobial treatment of diarrhea due to cryptosporidiosis can result in a 54% reduction in mortality. CONCLUSIONS: There is evidence to recommend antibiotic use for reduction of morbidity and mortality due to Cholera, Shigella and Cryptosporidium. We recommend that more clinical trials should be conducted to evaluate the efficacy and safety of first- and second- line drugs currently in use for treatment for diarrhea and dysentery in both developing and developed countries.

[The cholera epidemic in Latin America: reemergence, morbidity, and mortality]. / La epidemia de cólera en América Latina: reemergencia y morbimortalidad.

OBJECTIVE: To determine morbidity and mortality from cholera during different segments of the period 1991-2011 in the countries of Latin America. METHODS: Using information sources from a nonsystematic literature search for works on cholera epidemics, a mixed ecological study was conducted aimed at a time series analysis of morbidity, mortality, and case-fatality in cholera-related health events between 1991 and 2011 in 18 Latin American countries. RESULTS: During the period 1991-2011, 1 839 037 cases of cholera were reported in Latin America, with 19 538 deaths and a case fatality rate of 1.06%. The most affected countries were Peru between 1991 and 2002-with a maximum annual cumulative incidence of 1 452.72 cases per 100 000 population but a low case fatality rate (0.72%)-and Haiti between 2010 and 2011, with a maximum annual cumulative incidence of 3 319.13 per 100 000 population and a case fatality rate of 1.32%. CONCLUSIONS: The cholera epidemic has resulted in high morbidity, mortality, and case fatality in some Latin American countries, due largely to basically socioeconomic and climatic factors. The reemergence of this disease and the many factors related to how cholera outbreaks evolve call for the development and strengthening of regional prevention and control strategies in the countries as well as a study on the determinants that influence the emergence and reemergence of infectious diseases in Latin America.