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Introduction Enterotoxigenic Escherichia coli (ETEC) is a major cause of infectious diarrhea in the developing world (1, 2). These organisms are estimated to be responsible for millions of infections and [...], Enterotoxigenic Escherichia coli (ETEC) infections are highly prevalent in developing countries, where clinical presentations range from asymptomatic colonization to severe cholera-like illness. The molecular basis for these varied presentations, which may involve strain-specific virulence features as well as host factors, has not been elucidated. We demonstrate that, when challenged with ETEC strain H10407, originally isolated from a case of cholera-like illness, blood group A human volunteers developed severe diarrhea more frequently than individuals from other blood groups. Interestingly, a diverse population of ETEC strains, including H10407, secrete the EtpA adhesin molecule. As many bacterial adhesins also agglutinate red blood cells, we combined the use of glycan arrays, biolayer inferometry, and noncanonical amino acid labeling with hemagglutination studies to demonstrate that EtpA is a dominant ETEC blood group A-specific lectin/ hemagglutinin. Importantly, we have also shown that EtpA interacts specifically with glycans expressed on intestinal epithelial cells from blood group A individuals and that EtpA-mediated bacterial-host interactions accelerate bacterial adhesion and effective delivery of both the heat-labile and heat-stable toxins of ETEC. Collectively, these data provide additional insight into the complex molecular basis of severe ETEC diarrheal illness that may inform rational design of vaccines to protect those at highest risk.

In December 2013, violence erupted in Juba, South Sudan, and quickly spread throughout the country. By the end of 2014, one in five persons within the country had been displaced, [...]

Severe cholera without adequate rehydration kills up to half of affected persons (1). The World Health Organization estimates that 3-5 million cholera cases occur worldwide each year (2). Studies have [...]

In South Asia and Africa, an estimated 88.5 million diarrhea episodes are attributed to Shigella infections annually (1). Shigellosis occurs most often in children < 5 years of age (2,3). [...]

Introduction Cholera continues to be a threat in many countries. Cases and deaths continue in Hispaniola, Africa and Asia. Each year, the WER provides an update of these numbers as [...]

Introduction Vibrio cholerae O1 and O139 causes severe diarrhoea and the main strategies to prevent the disease are to promote hygiene and to ensure safe water and sanitation. These basic [...], Objective To describe and analyse the characteristics of oral cholera vaccination campaigns; Including location, target population, logistics, vaccine coverage and delivery costs. Methods We searched PubMed, the World Health Organization (WHO) website and the Cochrane database with no date or language restrictions. We contacted public health personnel, experts In the field and in ministries of health and did targeted web searches. Findings A total of 33 documents were included In the analysis. One country, Viet Nam, incorporates oral cholera vaccination into its public health programme and has administered approximately 10.9 million vaccine doses between 1997 and 2012. In addition, over 3 million doses of the two WHO pre-qualified oral cholera vaccines have been administered in more than 16 campaigns around the world between 1997 and 2014. These campaigns have either been pre-emptive or reactive and have taken place under diverse conditions, such as in refugee camps or natural disasters. Estimated two-dose coverage ranged from 46 to 88% of the target population. Approximate delivery cost per fully immunized person ranged from 0.11-3.99 United States dollars. Conclusion Experience with oral cholera vaccination campaigns continues to Increase. Public health officials may draw on this experience and conduct oral cholera vaccination campaigns more frequently. Objectif Decrire et analyser les caracteristiques des campagnes de vaccination orale contre le cholera; y compris le site, la population cible, la logistique, la couverture vaccinale et les couts de distribution. Methodes Nous avons effectue des recherches dans PubMed, le site Internet de l'Organisation mondiale de la Sante (OMS) et la base de donnees Cochrane sans aucune restriction de date ou de langue. Nous avons contacte des membres du personnel de la sante publique, des experts travaillant dans le domaine et dans les ministeres de la Sante et nous avons cible les recherches sur Internet. Resultats Nous avons inclus 33 documents au total dans l'analyse. Un seul pays, le Viet Nam, inclut la vaccination orale anticholerlque dans son programme de sante publique et a administre environ 10,9 millions de doses de vacclns entre 1997 et 2012. En outre, plus de 3 millions de doses des deux vaccins oraux anticholeriques prequalifies de I'OMS ont ete administres dans plus de 16 campagnes de vaccination dans le monde entier entre 1997 et 2014. Ces campagnes ont ete menees en prevention ou en reaction et ont eu lieu dans diverses conditions, comme dans des camps de refugies ou lors de catastrophes naturelles. La couverture estimee des deux doses etait comprise entre 46 et 88% de la population cible. Les frais de distribution approximatifs par personne entierement vaccinee sont compris entre 0,11 et 3,99 dollars. Conclusion L'experience avec les campagnes de vaccination orale contre le cholera continue a se developper. Les responsables de la sante publique peuvent tirer profit de cette experience et mener plus frequemment des campagnes de vaccination orale contre le cholera. Objetivo Describir y analizar las caracteristicas de las campanas de vacunacion oral contra el colera, incluyendo la ubicacion, la poblacion objetivo, la logistica, los costes de cobertura y la entrega de vacunas. Metodos Realizamos busquedas en PubMed, la pagina web de la Organizacion Mundial de la salud (OMS) y la base de datos Cochrane sin restricciones de fechas ni idioma. Nos pusimos en contacto con el personal de salud publica, expertos del sector y los ministerios de salud, y realizamos busquedas especificas en la web. Resultados Se incluyo un total de 33 documentos en el analisis. Un pais, Viet Nam, incorpora vacunas orales contra el colera en su programa de salud publica y ha administrado aproximadamente 10,9 millones de dosis de vacunas entre 1997 y 2012. Ademas, se han administrado mas 3 de millones de dosis de las dos vacunas orales contra el colera orales que cumplen con los requisitos de la OMS en mas de 16 campanas en todo el mundo realizadas entre 1997 y 2014. Estas campanas han sido preventivas o reactivas, y se han llevado a cabo en diversas condiciones, como en campamentos de refugiados o desastres naturales. La cobertura estimada de dos dosis oscilo entre el 46 y 88% de la poblacion objetivo. El coste aproximado del suministro por persona completamente inmunizada oscilo entre 0,11 y 3,99 dolares de los Estados Unidos. Conclusion La experiencia con las campanas de vacunacion oral contra el colera sigue aumentando. Los funcionarios de salud publica pueden aprovechar esta experiencia y realizar campanas de vacunacion orales contra el colera con mayor frecuencia.

In many areas of the world, cholera remains a major public health problem; it affects millions of persons each year and causes a substantial number of deaths (1,2). In Bangladesh, [...]

In 1999, Kotloff et al. reviewed the literature to estimate the global incidence of shigellosis. On the basis of studies published during 1966-1997, they estimated million shigellosis-related deaths annually, resulting [...]

Author(s): K. Zaman 1, David A. Sack 2, Kathleen M. Neuzil 3, Mohammad Yunus 1, Lawrence H. Moulton 2, Jonathan D. Sugimoto 4, Jessica A. Fleming 3, Ilias Hossain 1, [...], Background Rotavirus vaccines are now globally recommended by the World Health Organization (WHO), but in early 2009 WHO&apos;s Strategic Advisory Group of Experts on Immunization reviewed available data and concluded that there was no evidence for the efficacy or effectiveness of a two-dose schedule of the human rotavirus vaccine (HRV; Rotarix) given early at 6 and 10 wk of age. Additionally, the effectiveness of programmatic rotavirus vaccination, including possible indirect effects, has not been assessed in low-resource populations in Asia. Methods and findings In Bangladesh, we cluster-randomized (1:1) 142 villages of the Matlab Health and Demographic Surveillance System to include two doses of HRV with the standard infant vaccines at 6 and 10 wk of age or to provide standard infant vaccines without HRV. The study was initiated November 1, 2008, and surveillance was conducted concurrently at Matlab Diarrhoea Hospital and two community treatment centers to identify children less than 2 y of age presenting with acute rotavirus diarrhea (ARD) through March 31, 2011. Laboratory confirmation was made by enzyme immunoassay detection of rotavirus antigen in stool specimens. Overall effectiveness of the HRV vaccination program (primary objective) was measured by comparing the incidence rate of ARD among all children age-eligible for vaccination in villages where HRV was introduced to that among such children in villages where HRV was not introduced. Total effectiveness among vaccinees and indirect effectiveness were also evaluated. In all, 6,527 infants were age-eligible for vaccination in 71 HRV villages, and 5,791 in 71 non-HRV villages. In HRV villages, 4,808 (73.7%) infants received at least one dose of HRV. The incidence rate of ARD was 4.10 cases per 100 person-years in non-HRV villages compared to 2.8 per 100 person-years in HRV villages, indicating an overall effectiveness of 29.0% (95% CI, 11.3% to 43.1%). The total effectiveness of HRV against ARD among vaccinees was 41.4% (95% CI, 23.2% to 55.2%). The point estimate for total effectiveness was higher against ARD during the first year of life than during the second (45.2% versus 28.9%), but estimates for the second year of life lacked precision and did not reach statistical significance. Indirect effects were not detected. To check for bias in presentation to treatment facilities, we evaluated the effectiveness of HRV against acute diarrhea associated with enterotoxigenic Escherichia coli; it was 4.0% (95% CI, -46.5% to 37.1%), indicating that bias likely was not introduced. Thirteen serious adverse events were identified among recipients of HRV, but none were considered related to receipt of study vaccine. The main limitation of this study is that it was an open-label study with an observed-only control group (no placebo). Conclusions The two-dose HRV rotavirus vaccination program significantly reduced medically attended ARD in this low-resource population in Asia. Protection among vaccinees was similar to that in other low-resource settings. In low-resource populations with high rotavirus incidence, large-scale vaccination across a wide population may be required to obtain the full benefit of rotavirus vaccination, including indirect effects. Trial registration ClinicalTrials.gov NCT00737503

Vibrio cholerae persists in aquatic environments predominantly in a nonculturable state. In this study coccoid, nonculturable V. cholerae O1 in biofilms maintained for 495 days in Mathbaria, Bangladesh, pond water became culturable upon animal passage. Culturability, biofilm formation, and the wbe, ctxA, and rstR2 genes were monitored by culture, direct fluorescent antibody (DFA), and multiplex PCR. DFA counts were not possible after formation of biofilm. Furthermore, wbe, but not ctxA, were amplifiable0 even after incubation for 54 and 68 days at room temperature ([approximately equal to]25[degrees]C) and 4[degrees]C, respectively, when no growth was detectable. Slower biofilm formation and extended culturability were observed for cultures incubated at 4[degrees]C, compared with [approximately equal to]25[degrees]C, suggesting biofilm production to be temperature dependent and linked to loss of culturability. Small colonies appearing after incubation in microcosms for 54 and 68 days at 25[degrees]C and 4[degrees]C, respectively, were wbe positive and ctxA and rstR2 negative, indicating loss of bacteriophage CTX[PHI]. The coccoid V. cholerae O1 observed as free cells in microcosms incubated for 495 days could not be cultured, but biofilms in the same microcosms yielded culturable cells. It is concluded that biofilms can act as a reservoir for V. cholerae O1 between epidemics because of its long-term viability in biofilms. In contrast to biofilms produced in Mathbaria pond water, V. cholerae O1 in biofilms present in cholera stools and incubated under identical conditions as the Mathbaria pond water biofilms could not be cultured after 2 months, indicating that those V. cholerae cells freshly discharged into the environment are significantly less robust than cells adapted to environmental conditions. Bangladesh | bacteriophage CTX[PHI] | DFA | multiplex-PCR | ctxA

Approximately 20,000 stool specimens from patients with diarrhea visiting 1 urban and 1 rural hospital in Bangladesh during January 2001-May 2006 were tested for group A rotavirus antigen, and 4,712 [...]

The rates of symptomatic hyponatremia were measured during treatment of patients with diarrhea with reduced osmolarity oral rehydration solution (ORS), as recommended by the World Health Organization on changing the formulation of the ORS in use to one with a reduced osmolarity. It was found that the risk of symptoms associated with hyponatremia in patients treated with the reduced osmolarity ORS was minimal and did not increase with the change in formulation.

Shigella is a major cause of morbidity, mortality, and growth retardation for children in developing countries. Emergence of antibiotic resistance among Shigellae demands the development of effective medicines. Previous studies found that the endogenous antimicrobial peptide LL-37 is down-regulated in the rectal epithelium of patients during shigellosis and that butyrate upregulates the expression of LL-37 in colonic epithelial cells in vitro and decreases severity of inflammation in experimental shigellosis. In this study, Shigella-infected dysenteric rabbits were treated with butyrate (0.14 mmol/kg of body weight) twice daily for 3 days, and the expression levels of the rabbit homologue to LL-37, CAP-18, were monitored in the colon. Butyrate treatment resulted in (i) reduced clinical illness, severity of inflammation in the colon, and bacterial load in the stool, (ii) significant up-regulation of CAP-18 in the surface epithelium, and (iii) disappearance of CAP-18-positive cells in lamina propria. The active CAP-18 peptide was released in stool from its proform by butyrate treatment. In healthy controls, CAP-18 expression was localized predominantly to the epithelial surface of the colon. In infected rabbits, CAP-18 expression was localized to immune and inflammatory cells in the colon, whereas the ulcerated epithelium was devoid of CAP-18 expression. The combination of CAP-18 and butyrate was more efficient in killing Shigella in vitro than CAP-18 alone. Our findings indicate that oral butyrate treatment in shigellosis may be of clinical value because of induction of the endogenous cathelicidin CAP-18 in the colonic epithelium, stimulation of the release of the active peptide CAP-18, and promoting elimination of Shigella. antimicrobial peptides | CAP-18 | cathelicidin | colon | Shigella

A study of epidemiology and ecology of Vibrio cholerae O1 and O139 was carried out in two coastal areas, Bakerganj and Mathbaria, Bangladesh where cholera occurs seasonally. The results of bi-weekly clinical study employing culture methods, direct and enrichment culture, colony blot hybridization and direct fluorescent-antibody methods showed that cholera is endemic in both Bakerganj and Mathbaria and that V. cholerae O1, O139, and nonO1/nonO139 are autochthonous to aquatic environment.

The factors that enhance the waterborne spread of bacterial epidemics and sustain the epidemic strain in nature are unclear. Although the epidemic diarrheal disease cholera is known to be transmitted by water contaminated with pathogenic Vibrio cholerae, routine isolation of pathogenic strains from aquatic environments is challenging. Here, we show that conditionally viable environmental cells (CVEC) of pathogenic V. cholerae that resist cultivation by conventional techniques exist in surface water as aggregates (biofilms) of partially dormant cells. Such CVEC can be recovered as fully virulent bacteria by inoculating the water into rabbit intestines. Furthermore, when V. cholerae shed in stools of cholera patients are inoculated in environmental water samples in the laboratory, the cells exhibit characteristics similar to CVEC, suggesting that CVEC are the infectious form of V. cholerae in water and that CVEC in nature may have been derived from human cholera stools. We also observed that stools from cholera patients contain a heterogenous mixture of biofilm-like aggregates and free-swimming planktonic cells of V. cholerae. Estimation of the relative infectivity of these different forms of V. cholerae cells suggested that the enhanced infectivity of V. cholerae shed in human stools is largely due to the presence of clumps of cells that disperse in vivo, providing a high dose of the pathogen. The results of this study support a model of cholera transmission in which in vivo-formed biofilms contribute to enhanced infectivity and environmental persistence of pathogenic V. cholerae. cholera epidemic | Vibrio cholerae | conditionally viable environmental cells | waterborne disease

A study was conducted to understand the effect of transporting environmental samples at the ambient air temperature on isolation and enumeration of Vibrio cholerae. The findings indicate that holding samples isolated from a freshwater ecosystem at ambient temperatures ranging from 31 degree Celsius to 35 degree Celsius for 20 hours did not have deleterious effects but rather facilitated the growth of the total heterotrophic bacteria.

Flooding in Dhaka in July 2004 caused epidemics of diarrhea. Enterotoxigenic Escherichia coil (ETEC) was almost as prevalent as Vibrio cholerae O1 in diarrheal stools. ETEC that produced heat-stable enterotoxin [...]

Phage predation of Vibrio cholerae has recently been reported to be a factor that influences seasonal epidemics of cholera in Bangladesh. To understand more about this phenomenon, we studied the dynamics of the V. cholerae-phage interaction during a recent epidemic in Dhaka. Because the outbreak strain causing this epidemic was resistant to multiple antibiotics, including streptomycin, we used a selective medium containing streptomycin to monitor accurately the abundance of this strain in the environment. The changing prevalence in the environment of the epidemic V. cholerae O1 strain and a particular lytic cholera phage (JSF4) to which it was sensitive was measured every 48-72 h for 17 weeks. We also monitored the incidence of phage excretion in stools of 387 cholera patients during the epidemic. The peak of the epidemic was preceded by high V. cholerae prevalence in the environment and was followed by high JSF4 phage levels as the epidemic ended. The buildup to the phage peak in the environment coincided with increasing excretion of the same phage in the stools of cholera patients. These results suggest that patients toward the end of the epidemic ingested both JSF4 phage and the outbreak V. cholerae strain. Host-mediated phage amplification during the cholera epidemic likely contributed to increased environmental phage abundance, decreased load of environmental V. cholerae and, hence, the collapse of the epidemic. Thus, in vivo phage amplification in patients and subsequent phage predation in the environment may explain the self-limiting nature of seasonal cholera epidemics in Bangladesh. Vibrio cholerae | vibriophage

The relationship among (i) the local incidence of cholera, (ii) the prevalence in the aquatic environment of Vibrio cholerae, and (iii) bacterial viruses that attack potentially virulent O1 and O139 serogroup strains of this organism (cholera phages) was studied in Dhaka, Bangladesh. Over nearly a 3-year period, we found that significantly more environmental water samples contained either a phage or a phage-susceptible V. cholerae strain than both (P < 0.00001). The number of cholera patients varied seasonally during this period and frequently coincided with the presence of pathogenic V. cholerae strains in water samples that otherwise lacked detectable cholera phages. Interepidemic periods were characterized by water samples containing cholera phages but no viable bacteria. Our data support the conclusion that cholera phages can influence cholera seasonality and may also play a role in emergence of new V. cholerae pandemic serogroups or clones. bacteriophage | seasonality | epidemiology | emergence | lysogeny

To understand the evolutionary events and possible selection mechanisms involved in the emergence of pathogenic Vibrio cholerae, we analyzed diverse strains of V. cholerae isolated from environmental waters in Bangladesh by direct enrichment in the intestines of adult rabbits and by conventional laboratory culture. Strains isolated by conventional culture were mostly (99.2%) negative for the major virulence gene clusters encoding toxin-coregulated pilus (TCP) and cholera toxin (CT) and were nonpathogenic in animal models. In contrast, all strains selected in rabbits were competent for colonizing infant mice, and 56.8% of these strains carried genes encoding TCP alone or both TCP and CT. Ribotypes of toxigenic O1 and O139 strains from the environment were similar to pandemic strains, whereas ribotypes of non-O1 non-O139 strains and [TCP.sup.-] nontoxigenic O1 strains diverged widely from the seventh pandemic O1 and the O139 strains. Results of this study suggest that (i) the environmental V. cholerae population in a cholera-endemic area is highly heterogeneous, (ii) selection in the mammalian intestine can cause enrichment of environmental strains with virulence potential, (iii) pathogenicity of V. cholerae involves more virulence genes than currently appreciated, and (iv) most environmental V. cholerae strains are unlikely to attain a pandemic potential by acquisition of TCP and CT genes alone. Because most of the recorded cholera pandemics originated in the Ganges Delta region, this ecological setting presumably favors extensive genetic exchange among V. cholerae strains and thus promotes the rare, multiple-gene transfer events needed to assemble the critical combination of genes required for pandemic spread.

During March and April 2002, a resurgence of Vibrio cholerae O139 occurred in Dhaka and adjoining areas of Bangladesh with an estimated 30,000 cases of cholera. Patients infected with O139 [...]

The emergence of Vibrio cholerae O139 Bengal during 1992-1993 was associated with large epidemics of cholera in India and Bangladesh and, initially, with a total displacement of the existing V. cholerae 01 strains. However, the 01 strains reemerged in 1994 and initiated a series of disappearance and reemergence of either of the two serogroups that was associated with temporal genetic and phenotypic changes sustained by the strains. Since the initial emergence of the 0139 vibrios, new variants of the pathogen derived from multiple progenitors have been isolated and characterized. The clinical and epidemiological characteristics of these strains have been studied. Rapid genetic reassortment in 0139 strains appears to be a response to the changing epidemiology of V. cholerae 01 and also a strategy for persistence in competition with strains of the 01 serogroup. The emergence of V. cholerae 0139 has provided a unique opportunity to witness genetic changes in V. cholerae that may be associated with displacement of an existing serogroup by a newly emerging one and, thus, provide new insights into the epidemiology of cholera. The genetic changes and natural selection involving both environmental and host factors are likely to influence profoundly the genetics, epidemiology, and evolution of toxigenic V. cholerae, not only in the Ganges Delta region of India and Bangladesh, but also in other areas of endemic and epidemic cholera.

The cholera toxin genes of Vibrio cholerae are encoded by the filamentous phage, CTX[PHI]. Chromosomal CTX[PHI] prophage DNA is often found flanked by copies of a related genetic element designated RS1, and RS1 DNA can be packaged into filamentous phage particles (designated RS1[PHI]) by using the CTX[PHI] morphogenesis genes. RS1[PHI] is a satellite phage that further controls expression and dissemination of CTX[PHI]. Here we describe a CTX[PHI]-independent mechanism for production of RS1[PHI]. A nontoxigenic environmental V. cholerae strain (55V71) was identified that supports production of RS1[PHI]. However, newly infected CTX-negative strains did not produce RS1[PHI], indicating that additional 55V71 genes were involved in production of RS1[PHI]. Analysis of nucleic acids from phage preparations of 55V71 revealed a 7.5-kb single-stranded DNA, whose corresponding replicative form was found in plasmid preparations. This DNA likely corresponds to the genome of a new filamentous phage, which we have designated KSF-1[PHI]. The replicative form DNA of KSF-1[PHI] was cloned into pUC18, and the resulting construct pKSF-1.1 supported the production of RS1[PHI] particles by CTX-negative V. cholerae strains. RS1[PHI] particles produced in this way infect recipient V. cholerae strains by a mechanism that is independent of the CTX[PHI] receptor, the toxin-coregulated pilus. Thus, KSF-1[PHI] is capable of facilitating the transfer of the RS1 element to strains that do not express toxin coregulated pilus. Given that RS1[PHI] can enhance coproduction of CTX[PHI] particles, KSF-1[PHI]-mediated dissemination of RS1 may indirectly promote the spread of toxin genes among V. cholerae strains. This study also shows that filamentous phages can package diverse DNA elements and thus may play a role in horizontal transfer of more genes than previously appreciated.

Based on results of ecological studies demonstrating that Vibrio cholerae, the etiological agent of epidemic cholera, is commensal to zooplankton, notably copepods, a simple filtration procedure was developed whereby zooplankton, most phytoplankton, and particulates >20 [micro]m were removed from water before use. Effective deployment of this filtration procedure, from September 1999 through July 2002 in 65 villages of rural Bangladesh, of which the total population for the entire study comprised [approximately equal to] 133,000 individuals, yielded a 48% reduction in cholera (P < 0.005) compared with the control.

Research has been conducted on the environmental Shigella isolates. The use of molecular techniques in genetical characterization of these isolates and the comparison of the isolates with the clinical isolates carried out in the attempt to understand the pathological potential and the origin of environmental Shigella isolates are discussed.

Author(s): Mohammad Ali 1, Amanda K. Debes 1, Francisco J. Luquero 1, Deok Ryun Kim 2, Je Yeon Park 2, Laura Digilio 2, Byomkesh Manna 3, Suman Kanungo 3, Shanta [...], Introduction Vaccinating a buffer of individuals around a case (ring vaccination) has the potential to target those who are at highest risk of infection, reducing the number of doses needed to control a disease. We explored the potential vaccine effectiveness (VE) of oral cholera vaccines (OCVs) for such a strategy. Methods and Findings This analysis uses existing data from a cluster-randomized clinical trial in which OCV or placebo was given to 71,900 participants in Kolkata, India, from 27 July to 10 September 2006. Cholera surveillance was then conducted on 144,106 individuals living in the study area, including trial participants, for 5 y following vaccination. First, we explored the risk of cholera among contacts of cholera patients, and, second, we measured VE among individuals living within 25 m of cholera cases between 8 and 28 d after onset of the index case. For the first analysis, individuals living around each index case identified during the 5-y period were assembled using a ring to define cohorts of individuals exposed to cholera index cases. An index control without cholera was randomly selected for each index case from the same population, matched by age group, and individuals living around each index control were assembled using a ring to define cohorts not exposed to cholera cases. Cholera attack rates among the exposed and non-exposed cohorts were compared using different distances from the index case/control to define the rings and different time frames to define the period at risk. For the VE analysis, the exposed cohorts were further stratified according to the level of vaccine coverage into high and low coverage strata. Overall VE was assessed by comparing the attack rates between high and low vaccine coverage strata irrespective of individuals&apos; vaccination status, and indirect VE was assessed by comparing the attack rates among unvaccinated members between high and low vaccine coverage strata. Cholera risk among the cohort exposed to cholera cases was 5-11 times higher than that among the cohort not exposed to cholera cases. The risk gradually diminished with an increase in distance and time. The overall and indirect VE measured between 8 and 28 d after exposure to a cholera index case during the first 2 y was 91% (95% CI 62%-98%) and 93% (95% CI 44%-99%), respectively. VE persisted for 5 y after vaccination and was similar whether the index case was a young child ( Conclusions These findings suggest that high-level protection can be achieved if individuals living close to cholera cases are living in a high coverage ring. Since this was an observational study including participants who had received two doses of vaccine (or placebo) in the clinical trial, further studies are needed to determine whether a ring vaccination strategy, in which vaccine is given quickly to those living close to a case, is feasible and effective. Trial registration ClinicalTrials.gov NCT00289224

Both monovalent and tetravalent rhesus rotavirus vaccines may safely and effectively reduce the rate of rotavirus disease in children. Rotavirus infection causes inflammation of the stomach and intestines and diarrhea. Researchers administered three doses of oral vaccines to 898 infants. Of these, 297 received a monovalent rotavirus vaccine, 305 received a tetravalent vaccine, and 296 received a placebo. At the two-year follow-up, the monovalent vaccine was 40% effective and the trivalent vaccine was 57% effective. Both vaccines were more than 70% effective against severe rotavirus infection and reduced the number of medical visits for rotavirus disease by more than 65%. Children in the tetravalent vaccine group were more likely to develop a mild fever than placebo-recipients after one vaccine dose, although the rate of other adverse reactions did not differ according to vaccination group., Objective. - To determine the safety and relative efficacy of two reassortant rhesus rotavirus vaccines over two rotavirus seasons. Design. - A prospective, double-masked, placebo-controlled trial. Setting. - Twenty-three centers in the United States. Participants. - A total of 1006 healthy infants between 4 and 26 weeks of age were enrolled, and 898 received three doses of vaccine or placebo. Main Outcome Measures. - Reactogenicity was determined by comparing the incidence of fever, diarrhea, and/or vomiting for 5 days after each dose of vaccine. Rotavirus IgA and neutralizing antibody to rhesus rotavirus and four rotavirus serotypes were measured in a subset of subjects. Relative efficacy was determined by comparing the incidence of rotavirus gastroenteritis after three doses of vaccine or placebo over two rotavirus seasons. Results. - Adverse reactions were mild and limited to a small but significant increase in the incidence of fever after the first dose of tetravalent but not monovalent vaccine. The relative efficacy against rotavirus disease over the 2 years of observation was 40% (98.3% confidence interval, 7% to 62%) for the monovalent and 57% (98.3% confidence interval, 29% to 74%) for the tetravalent vaccine. In post hoc analyses, the relative efficacy against very severe rotavirus gastroenteritis was 73% and 82% for monovalent and tetravalent vaccine recipients, respectively. Also, a 67% and 78% reduction in medical visits for rotavirus gastroenteritis was observed. Both vaccines protected against disease caused by serotype 1 rotavirus, but only the tetravalent vaccine reduced the incidence of disease caused by non-serotype 1 rotavirus infection detected in the second season. It is unclear, however, whether this result represents serotype-specific protection or a difference in the duration of protection. Conclusions. - Vaccination with both vaccines was safe and significantly reduced the incidence of rotavirus gastroenteritis, but only the tetravalent vaccine provided protection against disease caused by non-serotype 1 rotaviruses during the second year of follow-up.

Background In December 2013, violence erupted in South Sudan's capital, Juba, and quickly spread throughout the country. The crisis exacerbated an already dire humanitarian situation in the youngest and one [...], * A global oral cholera vaccine (OCV) stockpile was established in 2013 to improve rapid access to the vaccine in outbreaks and emergencies in which cholera risk is high. The first deployment from the global OCV stockpile was to South Sudan in 2014 because of high cholera risk from massive population displacements within the civil war. * 256,700 doses of OCV were delivered, with high coverage, throughout the country as part of a comprehensive cholera prevention strategy by multiple agencies, some of which had little to no previous experience with this vaccine. * A cholera epidemic began during vaccination, and a basic comparison of epidemic curves in vaccinated and unvaccinated areas suggests little to no transmission occurred in vaccinated areas, though more in depth analysis is needed. * This deployment highlights the feasibility of effective deployments from the OCV stockpile and the importance of strong coordination between governmental and nongovernmental agencies in cholera prevention and control planning from the assessment of cholera risk to the deployment of the vaccines. * A larger global supply of OCV is urgently needed to cover those most in need. With limited vaccine availability now and likely in the upcoming years, more work is needed on deciding how to most efficiently use the vaccine, which may include alternative dosing regimens and targeting specific subpopulations.

Introduction Despite years of control efforts, cholera remains a major killer worldwide, causing an estimated 2 to 3 million cases and 100,000 deaths each year [1]. Recently, large outbreaks in [...], Background In 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both. Methods and Findings Using mathematical models we determined the minimum relative single-dose efficacy (MRSE) at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%-56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%). This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%-88%) for two doses and 44% (95% CI -27% to 76%) for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%-88%), which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval Π 55,943-86,205) cases in Zimbabwe, 78,317 (95% PI 57,435-100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490-3,170) cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture uncertainty due to imperfect surveillance data and uncertainty about the transmission dynamics of cholera in each setting. Conclusions Reactive vaccination campaigns using a single dose of OCV may avert more cases and deaths than a standard two-dose campaign when vaccine supplies are limited, while at the same time reducing logistical complexity. These findings should motivate consideration of the trade-offs between one- and two-dose campaigns in resource-constrained settings, though further field efficacy data are needed and should be a priority in any one-dose campaign.

Infection by Haemophilus influenzae type b bacteria can lead to a variety of serious complications, including meningitis, in which the membranes that surround the brain and spinal cord become inflamed. Some population groups, including certain Native American tribes, have infection rates several times higher than the general population. To evaluate the effectiveness of a new vaccine among Navajo infants, a controlled study was carried out. Infants aged between 42 and 90 days were randomly assigned to receive either the vaccine (2,588 subjects), a conjugate of H. influenzae type b capsular polysaccharide and parts of the outer-membrane protein complex (OMPC) of Neisseria meningitidis serogroup B, or a placebo (2,602 subjects), an inactive substance. Second injections were given between the ages of 70 and 146 days. Blood samples were obtained at different points during the study and analyzed to determine the infants' levels (titers) of antibodies against H. influenzae; the safety and efficacy of the vaccine were also monitored. The study began in July 1988; by August 1990, after 23 cases of H. influenzae infection had occurred, it was decided to stop the study. The group that had received the vaccine had far fewer cases than the placebo group (1 case versus 22 cases) by the age of 18 months. Thirteen of the 22 placebo cases developed meningitis. No infections occurred in the vaccine group between the first and second doses of vaccine; eight occurred in the placebo group. Antibody levels did not increase noticeably after the second vaccination, but the vaccine was effective up until 18 months of age. The overall efficacy of the H. influenzae type b OMPC vaccine was more than 90 percent in this population. This was much higher than the efficacy reported for another conjugate vaccine in another study of Native Americans in Alaska. Use of this vaccine should eliminate H. influenzae type b infection. (Consumer Summary produced by Reliance Medical Information, Inc.)