Estimating #cholera #incidence with cross-sectional #serology (Sci Transl Med., abstract)

[Source: Science Translational Medicine, full page: (LINK). Abstract, edited.]

Estimating cholera incidence with cross-sectional serology

Andrew S. Azman1,*, Justin Lessler1, Francisco J. Luquero2,3, Taufiqur Rahman Bhuiyan4, Ashraful Islam Khan4, Fahima Chowdhury4, Alamgir Kabir4, Marc Gurwith5, Ana A. Weil6,7, Jason B. Harris6,8,9, Stephen B. Calderwood6,7, Edward T. Ryan6,7,10, Firdausi Qadri4 and Daniel T. Leung11,12

1 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. 2 Epicentre, Paris 75012, France. 3 Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. 4 Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka 1212, Bangladesh. 5 PaxVax Inc., Redwood City, CA 94065, USA. 6 Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA . 7 Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. 8 Division of Global Health, Massachusetts General Hospital, Boston, MA 02114, USA. 9 Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. 10 Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. 11 Division of Infectious Diseases, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. 12 Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.

*Corresponding author. Email:

Science Translational Medicine  20 Feb 2019: Vol. 11, Issue 480, eaau6242 / DOI: 10.1126/scitranslmed.aau6242


Estimating the true prevalence of cholera

Successful development of anti-cholera measures requires accurate estimates of infection incidence. Reporting of cholera cases, however, typically relies on clinical assessment at the time of patient presentation and can be problematized by lack of access to health care and variable, nonspecific symptomatology. Combining a small number of serological markers with machine learning methods, Azman et al. were able to accurately detect individuals who had had cholera infections within the previous year. Simulated serosurveys showed that this simple antibody-based approach could potentially be used as an alternative method to estimate cholera incidence in a population.



The development of new approaches to cholera control relies on an accurate understanding of cholera epidemiology. However, most information on cholera incidence lacks laboratory confirmation and instead relies on surveillance systems reporting medically attended acute watery diarrhea. If recent infections could be identified using serological markers, cross-sectional serosurveys would offer an alternative approach to measuring incidence. Here, we used 1569 serologic samples from a cohort of cholera cases and their uninfected contacts in Bangladesh to train machine learning models to identify recent Vibrio cholerae O1 infections. We found that an individual’s antibody profile contains information on the timing of V. choleraeO1 infections in the previous year. Our models using six serological markers accurately identified individuals in the Bangladesh cohort infected within the last year [cross-validated area under the curve (AUC), 93.4%; 95% confidence interval (CI), 92.1 to 94.7%], with a marginal performance decrease using models based on two markers (cross-validated AUC, 91.0%; 95% CI, 89.2 to 92.7%). We validated the performance of the two-marker model on data from a cohort of North American volunteers challenged with V. cholerae O1 (AUC range, 88.4 to 98.4%). In simulated serosurveys, our models accurately estimated annual incidence in both endemic and epidemic settings, even with sample sizes as small as 500 and annual incidence as low as two infections per 1000 individuals. Cross-sectional serosurveys may be a viable approach to estimating cholera incidence.

Keywords: Vibrio cholerae; Cholera; Serology.


#Global #Disease #Outbreaks Associated with the 2015–2016 #ElNiño Event (Sci Rep., abstract)

[Source: Scientific Reports, full page: (LINK). Abstract, edited.]

Article | OPEN | Published: 13 February 2019

Global Disease Outbreaks Associated with the 2015–2016 El Niño Event

Assaf Anyamba, Jean-Paul Chretien, Seth C. Britch, Radina P. Soebiyanto, Jennifer L. Small, Rikke Jepsen, Brett M. Forshey, Jose L. Sanchez, Ryan D. Smith, Ryan Harris, Compton J. Tucker, William B. Karesh & Kenneth J. Linthicum

Scientific Reports, volume 9, Article number: 1930 (2019)



Interannual climate variability patterns associated with the El Niño-Southern Oscillation phenomenon result in climate and environmental anomaly conditions in specific regions worldwide that directly favor outbreaks and/or amplification of variety of diseases of public health concern including chikungunya, hantavirus, Rift Valley fever, cholera, plague, and Zika. We analyzed patterns of some disease outbreaks during the strong 2015–2016 El Niño event in relation to climate anomalies derived from satellite measurements. Disease outbreaks in multiple El Niño-connected regions worldwide (including Southeast Asia, Tanzania, western US, and Brazil) followed shifts in rainfall, temperature, and vegetation in which both drought and flooding occurred in excess (14–81% precipitation departures from normal). These shifts favored ecological conditions appropriate for pathogens and their vectors to emerge and propagate clusters of diseases activity in these regions. Our analysis indicates that intensity of disease activity in some ENSO-teleconnected regions were approximately 2.5–28% higher during years with El Niño events than those without. Plague in Colorado and New Mexico as well as cholera in Tanzania were significantly associated with above normal rainfall (p < 0.05); while dengue in Brazil and southeast Asia were significantly associated with above normal land surface temperature (p < 0.05). Routine and ongoing global satellite monitoring of key climate variable anomalies calibrated to specific regions could identify regions at risk for emergence and propagation of disease vectors. Such information can provide sufficient lead-time for outbreak prevention and potentially reduce the burden and spread of ecologically coupled diseases.

Keywords: ENSO; Extreme weather; Chikungunya fever; Plague; Cholera; Global Health.


#Niche #adaptation limits #bacteriophage #predation of #Vibrio cholerae in a nutrient-poor aquatic #environment (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Niche adaptation limits bacteriophage predation of Vibrio cholerae in a nutrient-poor aquatic environment

Cecilia A. Silva-Valenzuela and Andrew Camilli

PNAS published ahead of print January 11, 2019 / DOI:

Edited by Lucia B. Rothman-Denes, The University of Chicago, Chicago, IL, and approved December 11, 2018 (received for review June 13, 2018)



Virulent phages can reduce populations of bacteria and help shape bacterial evolution. Here, we used three virulent phages to understand their equilibrium with V. cholerae in nutrient-limiting aquatic microcosms. It has been proposed that phages quench cholera outbreaks, but no direct evidence of phage predation in aquatic environments had been established. Here, we show that different phages possess varied abilities to infect in certain niches or stages of the host bacterial life cycle. Unveiling the phage/bacterial interactions in their natural setting is important to the understanding of cholera outbreaks and could be ultimately used to help develop a method for outbreak prediction and/or control.



Vibrio cholerae, the causative agent of cholera, has reservoirs in fresh and brackish water where it interacts with virulent bacteriophages. Phages are the most abundant biological entity on earth and coevolve with bacteria. It was reported that concentrations of phage and V. cholerae inversely correlate in aquatic reservoirs and in the human small intestine, and therefore that phages may quench cholera outbreaks. Although there is strong evidence for phage predation in cholera patients, evidence is lacking for phage predation of V. choleraein aquatic environments. Here, we used three virulent phages, ICP1, ICP2, and ICP3, commonly shed by cholera patients in Bangladesh, as models to understand the predation dynamics in microcosms simulating aquatic environments. None of the phages were capable of predation in fresh water, and only ICP1 was able to prey on V. cholerae in estuarine water due to a requirement for salt. We conclude that ICP2 and ICP3 are better adapted for predation in a nutrient rich environment. Our results point to the evolution of niche-specific predation by V. cholerae-specific virulent phages, which complicates their use in predicting or monitoring cholera outbreaks as well as their potential use in reducing aquatic reservoirs of V. cholerae in endemic areas.

Vibrio cholerae – cholera – bacteriophage – aquatic reservoir – environment



1 To whom correspondence should be addressed. Email:

Author contributions: C.A.S.-V. and A.C. designed research; C.A.S.-V. and A.C. performed research; C.A.S.-V. contributed new reagents/analytic tools; C.A.S.-V. and A.C. analyzed data; and C.A.S.-V. and A.C. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at

Published under the PNAS license.

Keywords: Vibrio cholerae; Cholera; Bacteriophages.


1818, 1918, 2018: Two #Centuries of #Pandemics (Health Secur., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Health Secur. 2018 Dec 4. doi: 10.1089/hs.2018.0083. [Epub ahead of print]

1818, 1918, 2018: Two Centuries of Pandemics.

Snyder MR1,2, Ravi SJ1,2.

Author information: 1 Michael R. Snyder, MALD, is an Analyst, and Sanjana J. Ravi, MPH, is a Senior Analyst, both at the Johns Hopkins Center for Health Security. 2 Both are Research Associates at the Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.



2018 marks the centennial of the 1918 influenza pandemic, widely acknowledged as one of the deadliest infectious disease crises in human history. As public health and medical communities of practice reflect on the aftermath of the influenza pandemic and the ways in which it has altered the trajectory of history and informed current practices in health security, it is worth noting that the Spanish flu was preceded by a very different 100-year threat: the first Asiatic cholera pandemic of 1817 to 1824. In this commentary, we offer a historical analysis of the common socioeconomic, political, and environmental factors underlying both pandemics, consider the roles of cholera and Spanish flu in shaping global health norms and modern public health practices, and examine how strategic applications of soft power and broadening the focus of health security to include sustainable development could help the world prepare for pandemics of the future.

PMID: 30511884 DOI: 10.1089/hs.2018.0083

Keywords: Pandemics; Pandemic preparedness; Influenza A; Cholera; Society.


Efficacy of a single-dose regimen of inactivated whole-cell oral #cholera #vaccine: results from 2 years of follow-up of a randomised trial (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

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

Firdausi Qadri, PhD, Mohammad Ali, PhD, Julia Lynch, MD, Fahima Chowdhury, MPH, Ashraful Islam Khan, PhD, Thomas F Wierzba, PhD, Jean-Louis Excler, MD, Amit Saha, MMed, Md Taufiqul Islam, MPH, Yasmin A Begum, PhD, Taufiqur R Bhuiyan, PhD, Farhana Khanam, MSc, Mohiul I Chowdhury, MPH, Iqbal Ansary Khan, MPH, Alamgir Kabir, MSc, Prof Baizid Khoorshid Riaz, MPH, Afroza Akter, MPH, Arifuzzaman Khan, MBBS, Muhammad Asaduzzaman, MPH, Deok Ryun Kim, MSc, Ashraf U Siddik, MSS, Nirod C Saha, MSc, Prof Alejandro Cravioto, PhD, Ajit P Singh, MD, Prof John D Clemens, MD

Published: 14 March 2018 / Open Access  / DOI:

© 2018 The Author(s). Published by Elsevier Ltd.




A single-dose regimen of inactivated whole-cell oral cholera vaccine (OCV) is attractive because it reduces logistical challenges for vaccination and could enable more people to be vaccinated. Previously, we reported the efficacy of a single dose of an OCV vaccine during the 6 months following dosing. Herein, we report the results of 2 years of follow-up.


In this placebo-controlled, double-blind trial done in Dhaka, Bangladesh, individuals aged 1 year or older with no history of receipt of OCV were randomly assigned to receive a single dose of inactivated OCV or oral placebo. The primary endpoint was a confirmed episode of non-bloody diarrhoea for which the onset was at least 7 days after dosing and a faecal culture was positive for Vibrio choleraeO1 or O139. Passive surveillance for diarrhoea was done in 13 hospitals or major clinics located in or near the study area for 2 years after the last administered dose. We assessed the protective efficacy of the OCV against culture-confirmed cholera occurring 7–730 days after dosing with both crude and multivariable per-protocol analyses. This trial is registered at, number NCT02027207.


Between Jan 10, 2014, and Feb 4, 2014, 205 513 people were randomly assigned to receive either vaccine or placebo, of whom 204 700 (102 552 vaccine recipients and 102 148 placebo recipients) were included in the per-protocol analysis. 287 first episodes of cholera (109 among vaccine recipients and 178 among placebo recipients) were detected during the 2-year follow-up; 138 of these episodes (46 in vaccine recipients and 92 in placebo recipients) were associated with severe dehydration. The overall incidence rates of initial cholera episodes were 0·22 (95% CI 0·18 to 0·27) per 100 000 person-days in vaccine recipients versus 0·36 (0·31 to 0·42) per 100 000 person-days in placebo recipients (adjusted protective efficacy 39%, 95% CI 23 to 52). The overall incidence of severe cholera was 0·09 (0·07 to 0·12) per 100 000 person-days versus 0·19 (0·15 to 0·23; adjusted protective efficacy 50%, 29 to 65). Vaccine protective efficacy was 52% (8 to 75) against all cholera episodes and 71% (27 to 88) against severe cholera episodes in participants aged 5 years to younger than 15 years. For participants aged 15 years or older, vaccine protective efficacy was 59% (42 to 71) against all cholera episodes and 59% (35 to 74) against severe cholera. The protection in the older age groups was sustained throughout the 2-year follow-up. In participants younger than 5 years, the vaccine did not show protection against either all cholera episodes (protective efficacy −13%, −68 to 25) or severe cholera episodes (−44%, −220 to 35).


A single dose of the inactivated whole-cell OCV offered protection to older children and adults that was sustained for at least 2 years. The absence of protection of young children might reflect a lesser degree of pre-existing natural immunity in this age group.


Bill & Melinda Gates Foundation to the International Vaccine Institute.

Keywords: Cholera; Vaccines.


Mapping the #burden of #cholera in #subSaharan #Africa and implications for control: an analysis of data across geographical scales (Lancet, abstract)

[Source: The Lancet, full page: (LINK). Abstract, edited.]

Mapping the burden of cholera in sub-Saharan Africa and implications for control: an analysis of data across geographical scales

Justin Lessler, PhD†, , Sean M Moore, PhD†, Francisco J Luquero, PhD, Heather S McKay, PhD, Rebecca Grais, PhD, Myriam Henkens, MD, Martin Mengel, MD, Jessica Dunoyer, MSc, Maurice M’bangombe, MSc, Elizabeth C Lee, PhD, Mamoudou Harouna Djingarey, MD, Bertrand Sudre, MD, Didier Bompangue, MD, Robert S M Fraser, BMeEng, Abdinasir Abubakar, MD, William Perea, MD, Dominique Legros, MD, Andrew S Azman, PhD

†Contributed equally

Published: 01 March 2018 / Open Access  / DOI:

© 2018 The Author(s). Published by Elsevier Ltd.




Cholera remains a persistent health problem in sub-Saharan Africa and worldwide. Cholera can be controlled through appropriate water and sanitation, or by oral cholera vaccination, which provides transient (∼3 years) protection, although vaccine supplies remain scarce. We aimed to map cholera burden in sub-Saharan Africa and assess how geographical targeting could lead to more efficient interventions.


We combined information on cholera incidence in sub-Saharan Africa (excluding Djibouti and Eritrea) from 2010 to 2016 from datasets from WHO, Médecins Sans Frontières, ProMED, ReliefWeb, ministries of health, and the scientific literature. We divided the study region into 20 km × 20 km grid cells and modelled annual cholera incidence in each grid cell assuming a Poisson process adjusted for covariates and spatially correlated random effects. We combined these findings with data on population distribution to estimate the number of people living in areas of high cholera incidence (>1 case per 1000 people per year). We further estimated the reduction in cholera incidence that could be achieved by targeting cholera prevention and control interventions at areas of high cholera incidence.


We included 279 datasets covering 2283 locations in our analyses. In sub-Saharan Africa (excluding Djibouti and Eritrea), a mean of 141 918 cholera cases (95% credible interval [CrI] 141 538–146 505) were reported per year. 4·0% (95% CrI 1·7–16·8) of districts, home to 87·2 million people (95% CrI 60·3 million to 118·9 million), have high cholera incidence. By focusing on the highest incidence districts first, effective targeted interventions could eliminate 50% of the region’s cholera by covering 35·3 million people (95% CrI 26·3 million to 62·0 million), which is less than 4% of the total population.


Although cholera occurs throughout sub-Saharan Africa, its highest incidence is concentrated in a small proportion of the continent. Prioritising high-risk areas could substantially increase the efficiency of cholera control programmes.


The Bill & Melinda Gates Foundation.

Keywords: Cholera; Africa Region.


#Cholera #epidemics of the past offer new insights into an old enemy (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Cholera epidemics of the past offer new insights into an old enemy

Matthew Phelps, Mads Linnet Perner,  Virginia E Pitzer, Viggo Andreasen, Peter K M Jensen, Lone Simonsen

The Journal of Infectious Diseases, jix602,

Published: 20 November 2017 – Received: 04 September 2017

Citation: Matthew Phelps, Mads Linnet Perner, Virginia E Pitzer, Viggo Andreasen, Peter K M Jensen, Lone Simonsen; Cholera epidemics of the past offer new insights into an old enemy, The Journal of Infectious Diseases, , jix602,

© 2017 Oxford University Press




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 (1853) to elucidate epidemiological parameters and modes of spread.


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, age-specific impact. From physicians’ narratives we established transmission chains and estimated serial intervals.


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% CI: 2.9 – 4.7). The case fatality ratio (CFR) was high (54%-68%); using R0 we computed an adjusted CFR of 4-5%.


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.

Issue Section: Major Article

© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (, which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact

Keywords: Cholera.