Recent Cholera Publications on PubMed

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Accumulating evidence suggests that some waterbird species are potential vectors of Vibrio cholerae.

January 16, 2020
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Accumulating evidence suggests that some waterbird species are potential vectors of Vibrio cholerae.

PLoS Pathog. 2019 08;15(8):e1007814

Authors: Laviad-Shitrit S, Izhaki I, Halpern M

Abstract
Vibrio cholerae is the causative agent of cholera, a life-threatening diarrheal disease. Cholera causes epidemics and pandemics, but the ways this disease spreads worldwide is still unclear. This review highlights a relatively new hypothesis regarding the way V. cholerae can be globally dispersed. Copepods and chironomids are natural reservoirs of V. cholerae and are part of different fish species' diet. Furthermore, V. cholerae inhabits marine and freshwater fish species. Waterbird species feed on fish or on small invertebrates such as copepods and chironomids. Waterbirds have also been found to carry living copepods and/or chironomids internally or externally from one waterbody to another. All of the above points to the fact that some waterbird species might be vectors of V. cholerae. Indeed, we and others have found evidence for the presence of V. cholerae non-O1 as well as O1 in waterbird cloacal swabs, feces, and intestine samples. Moreover, hand-reared cormorants that were fed on tilapia, a fish that naturally carries V. cholerae, became infected with this bacterial species, demonstrating that V. cholerae can be transferred to cormorants from their fish prey. Great cormorants as well as other waterbird species can cover distances of up to 1,000 km/day and thus may potentially transfer V. cholerae in a short time across and between continents. We hope this review will inspire further studies regarding the understanding of the waterbirds' role in the global dissemination of V. cholerae.

PMID: 31437258 [PubMed - indexed for MEDLINE]

Molecular characterization of NDM-1-producing Klebsiella pneumoniae ST29, ST347, ST1224, and ST2558 causing sepsis in neonates in a tertiary care hospital of North-East India.

January 16, 2020
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Molecular characterization of NDM-1-producing Klebsiella pneumoniae ST29, ST347, ST1224, and ST2558 causing sepsis in neonates in a tertiary care hospital of North-East India.

Infect Genet Evol. 2019 04;69:166-175

Authors: Mukherjee S, Bhattacharjee A, Naha S, Majumdar T, Debbarma SK, Kaur H, Dutta S, Basu S

Abstract
Geographical differences can manifest in different spectra of microorganisms and patterns of antibiotic resistance. Considering this, Enterobacteriacae isolated from septicemic neonates from a tertiary care centre in Agartala, India were studied with focus on carbapenem resistance. Two hundred non-duplicate Enterobacteriaceae, of which 12 NDM-1-producing Klebsiella pneumoniae were recovered. Antibiotic susceptibility tests and detection of ESBLs and carbapenemases were performed for all Enterobacteriaceae. For NDM-1-producing isolates, plasmid-mediated quinolone resistance genes, addiction systems, genetic environment of blaNDM-1 and virulence genes was investigated by PCR. Bacterial clonal relatedness was established using REP-PCR, PFGE, and multi-locus sequence typing (MLST). Transferability of blaNDM-1 was tested by conjugation and transconjugants were characterized. K. pneumoniae was the primary organism causing sepsis in neonates. Resistance to different antimicrobials was high except for aminoglycosides and carbapenems. blaCTX-M was present in all isolates. All carbapenem-resistant isolates harboured blaNDM-1 as the only carbapenemase. blaCTX-M-15 and qnrS1 were detected in all NDM-1-producing isolates. Plasmid analysis of transconjugants revealed that blaNDM-1 along with blaCTX-M-15, qnrS1, qnrB1, aac(6')-Ib, aac(6')-Ib-cr and ccdAB or vagCD addiction systems were carried on large IncFIIK conjugative plasmids of varied sizes. blaNDM-1 was associated with ISAba125 or ISEc33 element at its 5'-end. In addition, isolates also harboured wabG, uge, fimH, mrkD, and entB virulence genes. The NDM-1-producing K. pneumoniae belonged to four distinct clones and were distributed in 4 STs (ST347, ST29, ST2558, and ST1224), of which ST347 was predominant. The association of blaNDM-1 with diverse STs in K. pneumoniae from neonates indicates the promiscuity of the gene and its widespread dissemination.

PMID: 30677535 [PubMed - indexed for MEDLINE]

Risk and Protective Factors for Cholera Deaths during an Urban Outbreak-Lusaka, Zambia, 2017-2018.

January 15, 2020
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Risk and Protective Factors for Cholera Deaths during an Urban Outbreak-Lusaka, Zambia, 2017-2018.

Am J Trop Med Hyg. 2020 Jan 13;:

Authors: Mutale LS, Winstead AV, Sakubita P, Kapaya F, Nyimbili S, Mulambya NL, Nanzaluka FH, Gama A, Mwale V, Kim S, Ngosa W, Yard E, Sinyange N, Mintz E, Brunkard J, Mukonka V

Abstract
The Republic of Zambia declared a cholera outbreak in Lusaka, the capital, on October 6, 2017. By mid-December, 20 of 661 reported cases had died (case fatality rate 3%), prompting the CDC and the Zambian Ministry of Health through the Zambia National Public Health Institute to investigate risk factors for cholera mortality. We conducted a study of cases (cholera deaths from October 2017 to January 2018) matched by age-group and onset date to controls (persons admitted to a cholera treatment center [CTC] and discharged alive). A questionnaire was administered to each survivor (or relative) and to a family member of each decedent. We used univariable exact conditional logistic regression to calculate matched odds ratios (mORs) and 95% CIs. In the analysis, 38 decedents and 76 survivors were included. Median ages for decedents and survivors were 38 (range: 0.5-95) and 25 (range: 1-82) years, respectively. Patients aged > 55 years and those who did not complete primary school had higher odds of being decedents (matched odds ratio [mOR] 6.3, 95% CI: 1.2-63.0, P = 0.03; mOR 8.6, 95% CI: 1.8-81.7, P < 0.01, respectively). Patients who received immediate oral rehydration solution (ORS) at the CTC had lower odds of dying than those who did not receive immediate ORS (mOR 0.1, 95% CI: 0.0-0.6, P = 0.02). Cholera prevention and outbreak response should include efforts focused on ensuring access to timely, appropriate care for older adults and less educated populations at home and in health facilities.

PMID: 31933465 [PubMed - as supplied by publisher]

Outbreak of Cholera Due to Cyclone Kenneth in Northern Mozambique, 2019.

January 14, 2020
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Outbreak of Cholera Due to Cyclone Kenneth in Northern Mozambique, 2019.

Int J Environ Res Public Health. 2019 08 15;16(16):

Authors: Cambaza E, Mongo E, Anapakala E, Nhambire R, Singo J, Machava E

Abstract
Cyclone Kenneth was the strongest in the recorded history of the African continent. It landed in the Cabo Delgado province in northern Mozambique on 25 April 2019, causing 45 deaths, destroying approximately 40,000 houses, and leaving 374,000 people in need for assistance, most at risk of acquiring waterborne diseases such as cholera. This short article aims to explain how the resulting cholera outbreak occurred and the response by the government and partner organizations. The outbreak was declared on 2 May 2019, after 14 cases were recorded in Pemba city (11 cases) and the Mecúfi district (3 cases). The disease spread to Metuge, and by the 12th of May 2019, there were 149 cases. Aware of the risk of an outbreak of cholera, the government and partners took immediate action as the cyclone ended, adapting the Cholera Response Plan for Beira, revised after the experience with cyclone Idai (4-21 March 2019). The response relevant to cholera epidemics consisted of social mobilization campaigns for prevention, establishment of treatment centers and units, coordination to improve of water, sanitation and hygiene, and surveillance. By 26 May 2019, 252,448 people were immunized in the area affected by cyclone Kenneth. The recovery process is ongoing but the number of new cases has been reducing, seemingly due to an efficient response, support of several organizations and collaboration of the civil society. Future interventions shall follow the same model of response but the government of Mozambique shall keep a contingency fund to manage disasters such as cyclone Idai and Kenneth. The unlikeliness of two cyclones (Idai and Kenneth) within two months after decades without such kind of phenomena points towards the problem of climate change, and Mozambique needs to prepare effective, proven response plans to combat outbreaks of waterborne diseases due to cyclones.

PMID: 31443180 [PubMed - indexed for MEDLINE]

Simple Visualized Detection Method of Virulence-Associated Genes of Vibrio cholerae by Loop-Mediated Isothermal Amplification.

January 11, 2020
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Simple Visualized Detection Method of Virulence-Associated Genes of Vibrio cholerae by Loop-Mediated Isothermal Amplification.

Front Microbiol. 2019;10:2899

Authors: Xu M, Fu H, Chen D, Shao Z, Zhu J, Alali WQ, Chen L

Abstract
Vibrio cholerae is a leading waterborne pathogenic bacterium worldwide. It can cause human cholera that is still pandemic in developing nations. Detection of V. cholerae contamination in drinking water and aquatic products is imperative for assuring food safety. In this study, a simple, sensitive, specific, and visualized method was developed based on loop-mediated isothermal amplification (LAMP) (designated sssvLAMP) to detect virulence-associated (ctxA, tcpA, hapA, mshA, pilA, and tlh) and species-specific (lolB) genes of V. cholerae. Three pairs of oligonucleotide primers (inner, outer, and loop primers) were designed and or synthesized to target each of these genes. The optimal conditions of the sssvLAMP method was determined, and one-step sssvLAMP reaction was performed at 65°C for 40 min. Positive results were simply read by the naked eye via color change (from orange to light green) under the visible light, or by the production of green fluorescence under the UV light (260 nm). The sssvLAMP method was more efficient in detecting 6.50 × 101-6.45 × 104-fold low number of V. cholerae cells, and more sensitive in V. cholerae genomic DNA (1.36 × 10-2-4.42 × 10-6 ng/reaction) than polymerase chain reaction (PCR) method. Among 52 strains of V. cholerae and 50 strains of non-target species (e.g., other Vibrios and common pathogens) examined, the sensitivity and specificity of the sssvLAMP method were 100% for all the target genes. Similar high efficiency of the method was observed when tested with spiked samples of water and aquatic products, as well as human stool specimens. Water from various sources and commonly consumed fish samples were promptly screened by this simple and efficient visualized method and diversified variation in the occurrence of the target genes was observed. V. cholerae strains could be mostly detected by the presence of hapA and tlh alone or in combination with other genes, indicating a variable risk of potentially pathogenic non-O1/O139 strains in edible food products. This novel LAMP method can be a promising tool to address the increasing need of food safety control of aquatic products.

PMID: 31921074 [PubMed]

Prevention and control of cholera with household and community water, sanitation and hygiene (WASH) interventions: A scoping review of current international guidelines.

January 9, 2020

Prevention and control of cholera with household and community water, sanitation and hygiene (WASH) interventions: A scoping review of current international guidelines.

PLoS One. 2020;15(1):e0226549

Authors: D'Mello-Guyett L, Gallandat K, Van den Bergh R, Taylor D, Bulit G, Legros D, Maes P, Checchi F, Cumming O

Abstract
INTRODUCTION: Cholera remains a frequent cause of outbreaks globally, particularly in areas with inadequate water, sanitation and hygiene (WASH) services. Cholera is spread through faecal-oral routes, and studies demonstrate that ingestion of Vibrio cholerae occurs from consuming contaminated food and water, contact with cholera cases and transmission from contaminated environmental point sources. WASH guidelines recommending interventions for the prevention and control of cholera are numerous and vary considerably in their recommendations. To date, there has been no review of practice guidelines used in cholera prevention and control programmes.
METHODS: We systematically searched international agency websites to identify WASH intervention guidelines used in cholera programmes in endemic and epidemic settings. Recommendations listed in the guidelines were extracted, categorised and analysed. Analysis was based on consistency, concordance and recommendations were classified on the basis of whether the interventions targeted within-household or community-level transmission.
RESULTS: Eight international guidelines were included in this review: three by non-governmental organisations (NGOs), one from a non-profit organisation (NPO), three from multilateral organisations and one from a research institution. There were 95 distinct recommendations identified, and concordance among guidelines was poor to fair. All categories of WASH interventions were featured in the guidelines. The majority of recommendations targeted community-level transmission (45%), 35% targeted within-household transmission and 20% both.
CONCLUSIONS: Recent evidence suggests that interventions for effective cholera control and response to epidemics should focus on case-centred approaches and within-household transmission. Guidelines did consistently propose interventions targeting transmission within households. However, the majority of recommendations listed in guidelines targeted community-level transmission and tended to be more focused on preventing contamination of the environment by cases or recurrent outbreaks, and the level of service required to interrupt community-level transmission was often not specified. The guidelines in current use were varied and interpretation may be difficult when conflicting recommendations are provided. Future editions of guidelines should reflect on the inclusion of evidence-based approaches, cholera transmission models and resource-efficient strategies.

PMID: 31914164 [PubMed - in process]

Impact of a Large-Scale Handwashing Intervention on Reported Respiratory Illness: Findings from a Cluster-Randomized Controlled Trial.

January 8, 2020
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Impact of a Large-Scale Handwashing Intervention on Reported Respiratory Illness: Findings from a Cluster-Randomized Controlled Trial.

Am J Trop Med Hyg. 2019 03;100(3):742-749

Authors: Najnin N, Leder K, Forbes A, Unicomb L, Winch PJ, Ram PK, Nizame FA, Arman S, Begum F, Biswas S, Cravioto A, Luby SP

Abstract
We assessed the impact of handwashing promotion on reported respiratory illness as a secondary outcome from among > 60,000 low-income households enrolled in a cluster-randomized trial conducted in Bangladesh. Ninety geographic clusters were randomly allocated into three groups: cholera-vaccine-only; vaccine-plus-behavior-change (handwashing promotion and drinking water chlorination); and control. Data on respiratory illness (fever plus either cough or nasal congestion or breathing difficulty within previous 2 days) and intervention uptake (presence of soap and water at handwashing station) were collected through monthly surveys conducted among a different subset of randomly selected households during the intervention period. We determined respiratory illness prevalence across groups and used log-binomial regression to examine the association between respiratory illness and presence of soap and water in the handwashing station. Results were adjusted for age, gender, wealth, and cluster-randomized design. The vaccine-plus-behavior-change group had more handwashing stations with soap and water present than controls (45% versus 25%; P < 0.001). Reported respiratory illness prevalence was similar across groups (vaccine-plus-behavior-change versus control: 2.8% versus 2.9%; 95% confidence interval [CI]: -0.008, 0.006; P = 0.6; cholera-vaccine-only versus control: 3.0% versus 2.9%; 95% CI: -0.006, 0.009; P = 0.4). Irrespective of intervention assignment, respiratory illness was lower among people who had soap and water present in the handwashing station than among those who did not (risk ratioadjusted: 0.82; 95% CI: 0.69-0.98). With modest uptake of the handwashing intervention, we found no impact of this large-scale intervention on respiratory illness. However, those who actually had a handwashing station with soap and water had less illness. This suggests improving the effectiveness of handwashing promotion in achieving sustained behavior change could result in health benefits.

PMID: 30608050 [PubMed - indexed for MEDLINE]

The Cholera Phone: Diarrheal Disease Surveillance by Mobile Phone in Bangladesh.

January 7, 2020
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The Cholera Phone: Diarrheal Disease Surveillance by Mobile Phone in Bangladesh.

Am J Trop Med Hyg. 2019 03;100(3):510-516

Authors: Carstensen LS, Tamason CC, Sultana R, Tulsiani SM, Phelps MD, Gurley ES, Jensen PKM

Abstract
Existing methodologies to record diarrheal disease incidence in households have limitations due to a high-episode recall error outside a 48-hour window. Our objective was to use mobile phones for reporting diarrheal episodes in households to provide real-time incidence data with minimum resource consumption and low recall error. From June 2014 to June 2015, we enrolled 417 low-income households in Dhaka, Bangladesh, and asked them to report diarrheal episodes to a call center. A team of data collectors then visited persons reporting the episode to collect data. In addition, each month, the team conducted in-home surveys on diarrhea incidence for a preceding 48-hour period. The mobile phone surveillance reported an incidence of 0.16 cases per person-year (95% CI: 0.13-0.19), with 117 reported diarrhea cases, and the routine in-home survey detected an incidence of 0.33 cases per person-year (95% CI: 0.18-0.60), the incidence rate ratio was 2.11 (95% CI: 1.08-3.78). During focus group discussions, participants reported a lack in motivation to report diarrhea by phone because of the absence of provision of intervening treatment following reporting. Mobile phone technology can provide a unique tool for real-time disease reporting. The phone surveillance in this study reported a lower incidence of diarrhea than an in-home survey, possibly because of the absence of intervention and, therefore, a perceived lack of incentive to report. However, this study reports the untapped potential of mobile phones in monitoring infectious disease incidence in a low-income setting.

PMID: 30693862 [PubMed - indexed for MEDLINE]

Lessons Learned from Enhancing Sentinel Surveillance for Cholera in Post-Earthquake Nepal in 2016.

January 7, 2020
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Lessons Learned from Enhancing Sentinel Surveillance for Cholera in Post-Earthquake Nepal in 2016.

Am J Trop Med Hyg. 2019 03;100(3):494-496

Authors: Sekine K, Roskosky M

Abstract
A major earthquake in 2015 that struck Nepal created a favorable environment for the rapid spread of infectious diseases. In anticipation of a cholera outbreak in 2016, UNICEF, Johns Hopkins University, and the Group for Technical Assistance, Nepal, collaborated to assist the government of Nepal to strengthen early warning surveillance, laboratory-based diagnosis, and field investigation. This article outlines the challenges and lessons learned in cholera prevention and control based on the authors' experiences in 2016. Priorities for the future plan should include sustaining the enhanced surveillance system for acute gastroenteritis and cholera, rolling out a rapid diagnostic test, and ensuring rapid and systematic epidemiological investigation and environmental testing.

PMID: 30652658 [PubMed - indexed for MEDLINE]

Modelling cholera transmission dynamics in the presence of limited resources.

January 3, 2020
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Modelling cholera transmission dynamics in the presence of limited resources.

BMC Res Notes. 2019 Aug 01;12(1):475

Authors: Nyabadza F, Aduamah JM, Mushanyu J

Abstract
OBJECTIVES: We study the transmission dynamics of cholera in the presence of limited resources, a common feature of the developing world. The model is used to gain insight into the impact of available resources of the health care system on the spread and control of the disease. A deterministic model that includes a nonlinear recovery rate is formulated and rigorously analyzed. Limited treatment is described by inclusion of a special treatment function. Center manifold theory is used to show that the model exhibits the phenomenon of backward bifurcation. Matlab has been used to carry out numerical simulations to support theoretical findings.
RESULTS: The model analysis shows that the disease free steady state is locally stable when the threshold [Formula: see text]. It is also shown that the model has multiple equilibria and the model exhibits the phenomenon of backward bifurcation whose implications to cholera infection are discussed. The results are useful for the public health planning in resource allocation for the control of cholera transmission.

PMID: 31370867 [PubMed - indexed for MEDLINE]

Epidemiology of Cholera in Bangladesh: Findings From Nationwide Hospital-based Surveillance, 2014-2018.

January 1, 2020
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Epidemiology of Cholera in Bangladesh: Findings From Nationwide Hospital-based Surveillance, 2014-2018.

Clin Infect Dis. 2019 Dec 31;:

Authors: Khan AI, Rashid MM, Islam MT, Afrad MH, Salimuzzaman M, Hegde ST, Zion MMI, Khan ZH, Shirin T, Habib ZH, Khan IA, Begum YA, Azman AS, Rahman M, Clemens JD, Flora MS, Qadri F

Abstract
BACKGROUND: Despite advances in prevention, detection, and treatment, cholera remains a major public health problem in Bangladesh and little is known about cholera outside of limited historical sentinel surveillance sites. In Bangladesh, a comprehensive national cholera control plan is essential, although national data are needed to better understand the magnitude and geographic distribution of cholera.
METHODS: We conducted systematic hospital-based cholera surveillance among diarrhea patients in 22 sites throughout Bangladesh from 2014 to 2018. Stool specimens were collected and tested for Vibrio cholerae by microbiological culture. Participants' socioeconomic status and clinical, sanitation, and food history were recorded. We used generalized estimating equations to identify the factors associated with cholera among diarrhea patients.
RESULTS: Among 26 221 diarrhea patients enrolled, 6.2% (n = 1604) cases were V. cholerae O1. The proportion of diarrhea patients positive for cholera in children <5 years was 2.1% and in patients ≥5 years was 9.5%. The proportion of cholera in Dhaka and Chittagong Division was consistently high. We observed biannual seasonal peaks (pre- and postmonsoon) for cholera across the country, with higher cholera positivity during the postmonsoon in western regions and during the pre-monsoon season in eastern regions. Cholera risk increased with age, occupation, and recent history of diarrhea among household members.
CONCLUSIONS: Cholera occurs throughout a large part of Bangladesh. Cholera-prone areas should be prioritized to control the disease by implementation of targeted interventions. These findings can help strengthen the cholera-control program and serve as the basis for future studies for tracking the impact of cholera-control interventions in Bangladesh.

PMID: 31891368 [PubMed - as supplied by publisher]

Estimating effectiveness of case-area targeted response interventions against cholera in Haiti.

December 31, 2019
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Estimating effectiveness of case-area targeted response interventions against cholera in Haiti.

Elife. 2019 Dec 30;8:

Authors: Michel E, Gaudart J, Beaulieu S, Bulit G, Piarroux M, Boncy J, Dely P, Piarroux R, Rebaudet S

Abstract
Case-area targeted interventions (CATIs) against cholera are conducted by rapid response teams, and may include various activities like water, sanitation, hygiene measures. However, their real-world effectiveness has never been established. We conducted a retrospective observational study in 2015-2017 in the Centre department of Haiti. Using cholera cases, stool cultures and CATI records, we identified 238 outbreaks that were responded to. After adjusting for potential confounders, we found that a prompt response could reduce the number of accumulated cases by 76% (95% confidence interval, 59 to 86) and the outbreak duration by 61% (41 to 75) when compared to a delayed response. An intense response could reduce the number of accumulated cases by 59% (11 to 81) and the outbreak duration by 73% (49 to 86) when compared to a weaker response. These results suggest that prompt and repeated CATIs were significantly effective at mitigating and shortening cholera outbreaks in Haiti.

PMID: 31886768 [PubMed - as supplied by publisher]

Mapping cholera outbreaks and antibiotic resistant Vibrio cholerae in India: An assessment of existing data and a scoping review of the literature.

December 31, 2019
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Mapping cholera outbreaks and antibiotic resistant Vibrio cholerae in India: An assessment of existing data and a scoping review of the literature.

Vaccine. 2019 Dec 26;:

Authors: Chatterjee P, Kanungo S, Bhattacharya SK, Dutta S

Abstract
Although fluid and electrolyte replenishment remains the mainstay of clinical management of cholera, antibiotics are an important component of the strategy for clinical management of moderate to severe cases of cholera. The emergence of antibiotic resistance (ABR) in Vibrio cholerae has led to difficulties in case management. The past decade has also seen the development of cheap and effective oral cholera vaccines (OCVs). In addition to the two-dose strategy for widespread immunization, OCVs have also been shown to be effective in containing outbreaks using a single-dose schedule. In this scoping review we map the states and union territories (SUTs) of India which are prone to cholera outbreaks followed by a scoping review of peer-reviewed publications about ABR outbreaks of cholera employing the Arksey and O'Malley framework. Using the data reported by the Integrated Disease Surveillance Program (IDSP), we identified 559 outbreaks of cholera between 2009 and 2017, affecting 27 SUTs. We defined SUTs which had reported outbreaks in at least three out of the last five years (2012-2016) or had experienced two or more outbreaks in the same year in at least two of the last five years to be outbreak-prone. The scoping review identified 62 ABR outbreaks, with four SUTs accounting for two-thirds of them: West Bengal (14), Maharashtra (10), Odisha (10) and Delhi (7). Overall, this scoping review suggests that there is an increasing trend of ABR in Vibrio cholerae isolated from outbreaks in India. This opens up avenues for exploring the role of antibiotic stewardship in the clinical management of diarrhea, the institution of vaccination as an infection prevention intervention to reduce selection pressure, and the deployment of high quality surveillance systems which report accurate, real-time data allowing appropriate and timely public health responses. It is crucial to counter the issue of ABR in cholera before it assumes a menacing magnitude.

PMID: 31883807 [PubMed - as supplied by publisher]

Diarrhoeal disease and subsequent risk of death in infants and children residing in low-income and middle-income countries: analysis of the GEMS case-control study and 12-month GEMS-1A follow-on study.

December 23, 2019

Diarrhoeal disease and subsequent risk of death in infants and children residing in low-income and middle-income countries: analysis of the GEMS case-control study and 12-month GEMS-1A follow-on study.

Lancet Glob Health. 2019 Dec 18;:

Authors: Levine MM, Nasrin D, Acácio S, Bassat Q, Powell H, Tennant SM, Sow SO, Sur D, Zaidi AKM, Faruque ASG, Hossain MJ, Alonso PL, Breiman RF, O'Reilly CE, Mintz ED, Omore R, Ochieng JB, Oundo JO, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ahmed S, Qureshi S, Quadri F, Hossain A, Das SK, Antonio M, Saha D, Mandomando I, Blackwelder WC, Farag T, Wu Y, Houpt ER, Verweiij JJ, Sommerfelt H, Nataro JP, Robins-Browne RM, Kotloff KL

Abstract
BACKGROUND: The Global Enteric Multicenter Study (GEMS) was a 3-year case-control study that measured the burden, aetiology, and consequences of moderate-to-severe diarrhoea (MSD) in children aged 0-59 months. GEMS-1A, a 12-month follow-on study, comprised two parallel case-control studies, one assessing MSD and the other less-severe diarrhoea (LSD). In this report, we analyse the risk of death with each diarrhoea type and the specific pathogens associated with fatal outcomes.
METHODS: GEMS was a prospective, age-stratified, matched case-control study done at seven sites in Africa and Asia. Children aged 0-59 months with MSD seeking care at sentinel health centres were recruited along with one to three randomly selected matched community control children without diarrhoea. In the 12-month GEMS-1A follow-on study, children with LSD and matched controls, in addition to children with MSD and matched controls, were recruited at six of the seven sites; only cases of MSD and controls were enrolled at the seventh site. We compared risk of death during the period between enrolment and one follow-up household visit done about 60 days later (range 50-90 days) in children with MSD and LSD and in their respective controls. Approximately 50 pathogens were detected using, as appropriate, classic bacteriology, immunoassays, gel-based PCR and reverse transcriptase PCR, and quantitative real-time PCR (qPCR). Specimens from a subset of GEMS cases and controls were also tested by a TaqMan Array Card that compartmentalised probe-based qPCR for 32 enteropathogens.
FINDINGS: 223 (2·0%) of 11 108 children with MSD and 43 (0·3%) of 16 369 matched controls died between study enrolment and the follow-up visit at about 60 days (hazard ratio [HR] 8·16, 95% CI 5·69-11·68, p<0·0001). 12 (0·4%) of 2962 children with LSD and seven (0·2%) of 4074 matched controls died during the follow-up period (HR 2·78, 95% CI 0·95-8·11, p=0·061). Risk of death was lower in children with dysenteric MSD than in children with non-dysenteric MSD (HR 0·20, 95% CI 0·05-0·87, p=0·032), and lower in children with LSD than in those with non-dysenteric MSD (HR 0·29, 0·14-0·59, p=0·0006). In children younger than 24 months with MSD, infection with typical enteropathogenic Escherichia coli, enterotoxigenic E coli encoding heat-stable toxin, enteroaggregative E coli, Shigella spp (non-dysentery cases), Aeromonas spp, Cryptosporidium spp, and Entamoeba histolytica increased risk of death. Of 61 deaths in children aged 12-59 months with non-dysenteric MSD, 31 occurred among 942 children qPCR-positive for Shigella spp and 30 deaths occurred in 1384 qPCR-negative children (HR 2·2, 95% CI 1·2-3·9, p=0·0090), showing that Shigella was strongly associated with increased risk of death.
INTERPRETATION: Risk of death is increased following MSD and, to a lesser extent, LSD. Considering there are approximately three times more cases of LSD than MSD in the population, more deaths are expected among children with LSD than in those with MSD. Because the major attributable LSD-associated and MSD-associated pathogens are the same, implementing vaccines and rapid diagnosis and treatment interventions against these major pathogens are rational investments.
FUNDING: Bill & Melinda Gates Foundation.

PMID: 31864916 [PubMed - as supplied by publisher]

Comparing alternative cholera vaccination strategies in Maela refugee camp: using a transmission model in public health practice.

December 23, 2019

Comparing alternative cholera vaccination strategies in Maela refugee camp: using a transmission model in public health practice.

BMC Infect Dis. 2019 Dec 21;19(1):1075

Authors: Havumaki J, Meza R, Phares CR, Date K, Eisenberg MC

Abstract
BACKGROUND: Cholera is a major public health concern in displaced-person camps, which often contend with overcrowding and scarcity of resources. Maela, the largest and longest-standing refugee camp in Thailand, located along the Thai-Burmese border, experienced four cholera outbreaks between 2005 and 2010. In 2013, a cholera vaccine campaign was implemented in the camp. To assist in the evaluation of the campaign and planning for subsequent campaigns, we developed a mathematical model of cholera in Maela.
METHODS: We formulated a Susceptible-Infectious-Water-Recovered-based transmission model and estimated parameters using incidence data from 2010. We next evaluated the reduction in cases conferred by several immunization strategies, varying timing, effectiveness, and resources (i.e., vaccine availability). After the vaccine campaign, we generated case forecasts for the next year, to inform on-the-ground decision-making regarding whether a booster campaign was needed.
RESULTS: We found that preexposure vaccination can substantially reduce the risk of cholera even when <50% of the population is given the full two-dose series. Additionally, the preferred number of doses per person should be considered in the context of one vs. two dose effectiveness and vaccine availability. For reactive vaccination, a trade-off between timing and effectiveness was revealed, indicating that it may be beneficial to give one dose to more people rather than two doses to fewer people, given that a two-dose schedule would incur a delay in administration of the second dose. Forecasting using realistic coverage levels predicted that there was no need for a booster campaign in 2014 (consistent with our predictions, there was not a cholera epidemic in 2014).
CONCLUSIONS: Our analyses suggest that vaccination in conjunction with ongoing water sanitation and hygiene efforts provides an effective strategy for controlling cholera outbreaks in refugee camps. Effective preexposure vaccination depends on timing and effectiveness. If a camp is facing an outbreak, delayed distribution of vaccines can substantially alter the effectiveness of reactive vaccination, suggesting that quick distribution of vaccines may be more important than ensuring every individual receives both vaccine doses. Overall, this analysis illustrates how mathematical models can be applied in public health practice, to assist in evaluating alternative intervention strategies and inform decision-making.

PMID: 31864298 [PubMed - in process]

Emergence of Vibrio cholerae O1 Sequence Type 75 in Taiwan.

December 20, 2019
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Emergence of Vibrio cholerae O1 Sequence Type 75 in Taiwan.

Emerg Infect Dis. 2020 Jan;26(1):164-166

Authors: Tu YH, Chen BH, Hong YP, Liao YS, Chen YS, Liu YY, Teng RH, Wang YW, Chiou CS

Abstract
We investigated the epidemiology of cholera in Taiwan during 2002-2018. Vibrio cholerae sequence type (ST) 75 clone emerged in 2009 and has since become more prevalent than the ST69 clone from a previous pandemic. Closely related ST75 strains have emerged in 4 countries and may now be widespread in Asia.

PMID: 31855545 [PubMed - in process]

Cholera control and anti-Haitian stigma in the Dominican Republic: from migration policy to lived experience.

December 19, 2019
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Cholera control and anti-Haitian stigma in the Dominican Republic: from migration policy to lived experience.

Anthropol Med. 2019 Aug;26(2):123-141

Authors: Keys HM, Kaiser BN, Foster JW, Freeman MC, Stephenson R, Lund AJ, Kohrt BA

Abstract
As cholera spread from Haiti to the Dominican Republic, Haitian migrants, a largely undocumented and stigmatized population in Dominican society, became a focus of public health concern. Concurrent to the epidemic, the Dominican legislature enacted new documentation requirements. This paper presents findings from an ethnographic study of anti-Haitian stigma in the Dominican Republic from June to August 2012. Eight focus group discussions (FGDs) were held with Haitian and Dominican community members. Five in-depth interviews were held with key informants in the migration policy sector. Theoretical frameworks of stigma's moral experience guided the analysis of how cholera was perceived, ways in which blame was assigned and felt and the relationship between documentation and healthcare access. In FGDs, both Haitians and Dominicans expressed fear of cholera and underscored the importance of public health messages to prevent the epidemic's spread. However, health messages also figured into experiences of stigma and rationales for blame. For Dominicans, failure to follow public health advice justified the blame of Haitians and seemed to confirm anti-Haitian sentiments. Haitians communicated a sense of powerlessness to follow public health messages given structural constraints like lack of safe water and sanitation, difficulty accessing healthcare and lack of documentation. In effect, by making documentation more difficult to obtain, the migration policy undermined cholera programs and contributed to ongoing processes of moral disqualification. Efforts to eliminate cholera from the island should consider how policy and stigma can undermine public health campaigns and further jeopardize the everyday 'being-in-the-world' of vulnerable groups.

PMID: 29058456 [PubMed - indexed for MEDLINE]

Increase in Reported Cholera Cases in Haiti Following Hurricane Matthew: An Interrupted Time Series Model.

December 18, 2019
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Increase in Reported Cholera Cases in Haiti Following Hurricane Matthew: An Interrupted Time Series Model.

Am J Trop Med Hyg. 2019 02;100(2):368-373

Authors: Hulland E, Subaiya S, Pierre K, Barthelemy N, Pierre JS, Dismer A, Juin S, Fitter D, Brunkard J

Abstract
Matthew, a category 4 hurricane, struck Haiti on October 4, 2016, causing widespread flooding and damage to buildings and crops, and resulted in many deaths. The damage caused by Matthew raised concerns of increased cholera transmission particularly in Sud and Grand'Anse departments, regions which were hit most heavily by the storm. To evaluate the change in reported cholera cases following Hurricane Matthew on reported cholera cases, we used interrupted time series regression models of daily reported cholera cases, controlling for the impact of both rainfall, following a 4-week lag, and seasonality, from 2013 through 2016. Our results indicate a significant increase in reported cholera cases after Matthew, suggesting that the storm resulted in an immediate surge in suspect cases, and a decline in reported cholera cases in the 46-day post-storm period, after controlling for rainfall and seasonality. Regression models stratified by the department indicate that the impact of the hurricane was regional, with larger surges in the two most highly storm-affected departments: Sud and Grand'Anse. These models were able to provide input to the Ministry of Health in Haiti on the national and regional impact of Hurricane Matthew and, with further development, could provide the flexibility of use in other emergency situations. This article highlights the need for continued cholera prevention and control efforts, particularly in the wake of natural disasters such as hurricanes, and the continued need for intensive cholera surveillance nationally.

PMID: 30594260 [PubMed - indexed for MEDLINE]

The projected impact of geographic targeting of oral cholera vaccination in sub-Saharan Africa: A modeling study.

December 12, 2019
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The projected impact of geographic targeting of oral cholera vaccination in sub-Saharan Africa: A modeling study.

PLoS Med. 2019 Dec;16(12):e1003003

Authors: Lee EC, Azman AS, Kaminsky J, Moore SM, McKay HS, Lessler J

Abstract
BACKGROUND: Cholera causes an estimated 100,000 deaths annually worldwide, with the majority of burden reported in sub-Saharan Africa. In May 2018, the World Health Assembly committed to reducing worldwide cholera deaths by 90% by 2030. Oral cholera vaccine (OCV) plays a key role in reducing the near-term risk of cholera, although global supplies are limited. Characterizing the potential impact and cost-effectiveness of mass OCV deployment strategies is critical for setting expectations and developing cholera control plans that maximize the chances of success.
METHODS AND FINDINGS: We compared the projected impacts of vaccination campaigns across sub-Saharan Africa from 2018 through 2030 when targeting geographically according to historical cholera burden and risk factors. We assessed the number of averted cases, deaths, and disability-adjusted life years and the cost-effectiveness of these campaigns with models that accounted for direct and indirect vaccine effects and population projections over time. Under current vaccine supply projections, an approach optimized to targeting by historical burden is projected to avert 828,971 (95% CI 803,370-859,980) cases (equivalent to 34.0% of projected cases; 95% CI 33.2%-34.8%). An approach that balances logistical feasibility with targeting historical burden is projected to avert 617,424 (95% CI 599,150-643,891) cases. In contrast, approaches optimized for targeting locations with limited access to water and sanitation are projected to avert 273,939 (95% CI 270,319-277,002) and 109,817 (95% CI 103,735-114,110) cases, respectively. We find that the most logistically feasible targeting strategy costs US$1,843 (95% CI 1,328-14,312) per DALY averted during this period and that effective geographic targeting of OCV campaigns can have a greater impact on cost-effectiveness than improvements to vaccine efficacy and moderate increases in coverage. Although our modeling approach does not project annual changes in baseline cholera risk or directly incorporate immunity from natural cholera infection, our estimates of the relative performance of different vaccination strategies should be robust to these factors.
CONCLUSIONS: Our study suggests that geographic targeting substantially improves the cost-effectiveness and impact of oral cholera vaccination campaigns. Districts with the poorest access to improved water and sanitation are not the same as districts with the greatest historical cholera incidence. While OCV campaigns can improve cholera control in the near term, without rapid progress in developing water and sanitation services or dramatic increases in OCV supply, our results suggest that vaccine use alone is unlikely to allow us to achieve the 2030 goal.

PMID: 31825965 [PubMed - in process]

Epidemicity thresholds for water-borne and water-related diseases.

December 4, 2019
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Epidemicity thresholds for water-borne and water-related diseases.

J Theor Biol. 2018 06 14;447:126-138

Authors: Mari L, Casagrandi R, Rinaldo A, Gatto M

Abstract
Determining the conditions that favor pathogen establishment in a host community is key to disease control and eradication. However, focusing on long-term dynamics alone may lead to an underestimation of the threats imposed by outbreaks triggered by short-term transient phenomena. Achieving an effective epidemiological response thus requires to look at different timescales, each of which may be endowed with specific management objectives. In this work we aim to determine epidemicity thresholds for some prototypical examples of water-borne and water-related diseases, a diverse family of infections transmitted either directly through water infested with pathogens or by vectors whose lifecycles are closely associated with water. From a technical perspective, while conditions for endemicity are determined via stability analysis, epidemicity thresholds are defined through generalized reactivity analysis, a recently proposed method that allows the study of the short-term instability properties of ecological systems. Understanding the drivers of water-borne and water-related disease dynamics over timescales that may be relevant to epidemic and/or endemic transmission is a challenge of the utmost importance, as large portions of the developing world are still struggling with the burden imposed by these infections.

PMID: 29588168 [PubMed - indexed for MEDLINE]

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