start 81 cholera vx annotated bibliography...

ANNOTATED BIBLIOGRAPHY FOR A LITERATURE REVIEW ON ORAL CHOLERA VACCINES SINCE SEPTEMBER 1, 2009

UNIVERSITY OF WASHINGTON GLOBAL HEALTH START PROGRAM REPORT TO THE BILL AND MELINDA GATES FOUNDATION DECEMBER 9, 2015

PRODUCED BY: FARLEY JM, HWANG P, NEWCOMB P, DUERR A

WO45R81 Cholera Vaccine, START Program December 2015 2

TABLE OF CONTENTS BY FIRST AUTHOR

1. The First Use of the Global Oral Cholera Vaccine Emergency Stockpile: Lessons from South Sudan. ...................................................................................................................................................................................... 5 o Abubakar et al., 2015

2. Natural Cholera Infection-‐Derived Immunity in an Endemic Setting ..................................................... 6 o Ali et al., 2011

3. The Global Burden of Cholera .................................................................................................................................. 7 o Ali et al., 2012

4. Herd Protection by a Bivalent Killed Whole-‐Cell Oral Cholera Vaccine in the Slums of Kolkata, India ......................................................................................................................................................................................... 8 o Ali et al., 2013

5. Antigen-‐Specific Memory T Cell Responses after Vaccination with an Oral Killed Cholera Vaccine in Bangladeshi Children and Comparison to Responses in Patients with Naturally Acquired Cholera ................................................................................................................................................................ 9 o Arifuzzaman et al., 2012

6. 5 Year Efficacy of a Bivalent Killed Whole-‐Cell Oral Cholera Vaccine in Kolkata, India: A Cluster-‐Randomised, Double-‐Blind, Placebo-‐Controlled Trial. .................................................................... 10 o Bhattacharya et al., 2013

7. Immunogenicity of a Killed Bivalent (O1 and O139) Whole Cell Oral Cholera Vaccine, Shanchol, in Haiti. ............................................................................................................................................................. 11 o Charles et al., 2014

8. Feasibility of Mass Vaccination Campaign with Oral Cholera Vaccines in Response to an Outbreak in Guinea .......................................................................................................................................................... 12 o Ciglenecki et al., 2013

9. Impact on Human Health of Climate Changes ................................................................................................. 13 o Franchini and Mannucci, 2015

10. Safety of the Recombinant Cholera Toxin B Subunit, Killed Whole-‐Cell (rBS-‐WC) Oral Cholera Vaccine in Pregnancy ...................................................................................................................................................... 14 o Hashim et al., 2012

11. Use of Oral Cholera Vaccine in Haiti: A Rural Demonstration Project ............................................... 15 o Ivers et al., 2013

12. Immunogenicity of the Bivalent Oral Cholera Vaccine Shanchol in Haitian Adults With HIV Infection. .............................................................................................................................................................................. 16


o Ivers et al., 2015

13. Cost-‐Benefit Comparisons of Investments in Improved Water Supply and Cholera Vaccination Programs .................................................................................................................................................... 17 o Jeuland and Whittington, 2009

14. Environmental Factors Influencing Epidemic Cholera ............................................................................ 18 o Jutla et al., 2013

15. Safety and Immunogenicity of a Live Oral Recombinant Cholera Vaccine VA1.4: A Randomized, Placebo Controlled Trial in Healthy Adults in a Cholera Endemic Area in Kolkata, India. ...................................................................................................................................................................................... 19 o Kanungo et al., 2014

16. Flexibility of Oral Cholera Vaccine Dosing-‐A Randomized Controlled Trial Measuring Immune Responses Following Alternative Vaccination Schedules in a Cholera Hyper-‐Endemic Zone. ....................................................................................................................................................................................... 20 o Kanungo et al., 2015

17. Mass Vaccination with a New, Less Expensive Oral Cholera Vaccine Using Public Health Infrastructure in India: The Odisha Model ............................................................................................................ 21 o Kar et al., 2014

18. Coverage and Cost of a Large Oral Cholera Vaccination Program in a High-‐Risk Cholera Endemic Urban Population in Dhaka, Bangladesh ............................................................................................ 22 o Khan et al., 2013

19. Effectiveness of an Oral Cholera Vaccine in Zanzibar: Findings from a Mass Vaccination Campaign and Observational Cohort Study .......................................................................................................... 23 o Khatib et al., 2012

20. Potential Impact of Reactive Vaccination in Controlling Cholera Outbreaks: An Exploratory Analysis Using a Zimbabwean Experience ............................................................................................................ 24 o Kim et al., 2011

21. Memory B Cell and Other Immune Responses in Children Receiving Two Doses of an Oral Killed Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh .......................................................................................................................................................................... 25 o Leung et al., 2012

22. Effectiveness of the WC/rBS Oral Cholera Vaccine in the Prevention of Traveler’s Diarrhea 26 o López-‐Gigosos et al., 2013

23. Feasibility of a Preventive Mass Vaccination Campaign with Two Doses of Oral Cholera Vaccine during a Humanitarian Emergency in South Sudan. ........................................................................ 27 o Porta et al., 2014


24. Feasibility and Effectiveness of Oral Cholera Vaccine in an Urban Endemic Setting in Bangladesh: a Cluster-‐Randomised Open-‐Label Trial. ........................ 28 o Qadri et al., 2015

25. Peru-‐15 (Choleragarde(®)), a Live Attenuated Oral Cholera Vaccine, is Safe and Immunogenic in Humanimmunodeficiency Virus (HIV)-‐Seropositive Adults in Thailand. ................................................................................................................................ 29 o Ratanasuwan et al., 2015

26. Safety and Immunogenicity Study of a Killed Bivalent (O1 and O139) Whole-‐Cell Oral Cholera Vaccine Shanchol, in Bangladeshi Adults and Children as Young as 1 Year of Age. ........... 30 o Saha et al., 2011

27. Using Mobile Health (mHealth) and Geospatial Mapping Technology in a Mass Campaign for Reactive Oral Cholera Vaccination in Rural Haiti. .............................................................................................. 31 o Teng et al., 2014

28. Randomized, Double-‐Blind, Placebo-‐Controlled Trial to Evaluate the Safety and Immunogenicity of Live Oral Cholera Vaccine 638 in Cuban Adults. ........................................................ 32 o Valera et al., 2009

Appendix: PubMed Search Terms ............................................................................................................................. 33


1. THE FIRST USE OF THE GLOBAL ORAL CHOLERA VACCINE EMERGENCY STOCKPILE: LESSONS FROM SOUTH SUDAN.

Abubakar A, Azman AS, Rumunu J, Ciglenecki I, Helderman T, West H et al.

PLoS Med. 2015. 12(11): e1001901.

PMID: 26576044

ABSTRACT

SUMMARY POINTS

• A global oral cholera vaccine (OCV) stockpile was established in 2012 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 stock-‐ pile 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 alterative dosing regimens and targeting specific subpopulations.

WEB: http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001901

IMPACT FACTOR: 14.43

UW EDITORIAL COMMENT: This first use of the global oral vaccine stockpile is an important milestone in the control of endemic cholera, and shows the type of coordination needed between different organizations for successful implementation. Figure 1 shows a timeline of the vaccination campaign.


2. NATURAL CHOLERA INFECTION-‐DERIVED IMMUNITY IN AN ENDEMIC SETTING

Ali M, Emch M, Park JK, Yunus M, Clemens J.

J Infect Dis. 2011 Sep 15;204(6):912-‐8.

PMID: 21849288

ABSTRACT

BACKGROUND: Live oral cholera vaccines may protect against cholera in a manner similar to natural cholera infections. However, information on which to base these vaccines is limited.

METHODS: The study was conducted in a cholera-‐endemic population in Bangladesh. Patients with cholera (index patients) detected between 1991 and 2000 were age-‐matched to 4 cholera-‐free controls and then followed up during the subsequent 3 years.

RESULTS: El Tor cholera was associated with a 65% (95% confidence interval [CI], 37%-‐81%; P < .001) lower risk of a subsequent El Tor episode. Reduction of the risk of subsequent El Tor cholera was similar for children < 5 years and for older persons and was sustained during all 3 years of follow-‐up. Having El Tor Inaba cholera was associated with lower risks of both El Tor Inaba and El Tor Ogawa cholera, but having El Tor Ogawa cholera was associated only with a reduced risk of El Tor Ogawa cholera. O139 cholera was associated with a 63% (95% CI, -‐61% to 92%; P = .18) lower risk of subsequent O139 cholera, but there was no evidence of cross-‐protection between the O1 and O139 serogroups

CONCLUSIONS: Live oral cholera vaccines designed to protect against the O1 and O139 serogroups should contain at least the Inaba serotype and strains of both serogroups.

WEB: http://dx.doi.org/10.1093/infdis/jir416

IMPACT FACTOR: 6.00

UW EDITORIAL COMMENT: This study has implications for the design, development, and evaluation of live oral vaccines against cholera. It also informs the development of future inactivated oral vaccines against cholera by serotypes and serogroups.


3. THE GLOBAL BURDEN OF CHOLERA

Ali M, Lopez AL, You AE, Kim YE, Sah B, Maskery B, Clemens J.

Bull World Health Organ. 2012 Mar 1;90(3):209-‐18A.

PMID: 22461716

ABSTRACT

OBJECTIVE: To estimate the global burden of cholera using population-‐based incidence data and reports. METHODS: Countries with a recent history of cholera were classified as endemic or non-‐endemic, depending on whether they had reported cholera cases in at least three of the five most recent years. The percentages of the population in each country that lacked access to improved sanitation were used to compute the populations at risk for cholera, and incidence rates from published studies were applied to groups of countries to estimate the annual number of cholera cases in endemic countries. The estimates of cholera cases in non-‐endemic countries were based on the average numbers of cases reported from 2000 to 2008. Literature-‐based estimates of cholera case-‐fatality rates (CFRs) were used to compute the variance-‐weighted average cholera CFRs for estimating the number of cholera deaths. FINDINGS: About 1.4 billion people are at risk for cholera in endemic countries. An estimated 2.8 million cholera cases occur annually in such countries (uncertainty range: 1.4-‐4.3) and an estimated 87 000 cholera cases occur in non-‐endemic countries. The incidence is estimated to be greatest in children less than 5 years of age. Every year about 91 000 people (uncertainty range: 28 000 to 142 000) die of cholera in endemic countries and 2500 people die of the disease in non-‐endemic countries. CONCLUSION: The global burden of cholera, as determined through a systematic review with clearly stated assumptions, is high. The findings of this study provide a contemporary basis for planning public health interventions to control cholera.

WEB: http://dx.doi.org/10.2471/BLT.11.093427

IMPACT FACTOR: 5.09

UW EDITORIAL COMMENT: Study showed that the global burden of cholera is large, particularly in developing countries. Estimates were based on a framework using available endemic cholera incidence rates, identification of endemic countries based on WHO crtieria and, for Bangladesh, interviews with in-‐country experts.


4. HERD PROTECTION BY A BIVALENT KILLED WHOLE-‐CELL ORAL CHOLERA VACCINE IN THE SLUMS OF KOLKATA, INDIA

Ali M, Sur D, You YA, Kanungo S, Sah B, Manna B, et al.

Clin Infect Dis. 2013 April;56(8):1123-‐31.

PMID: 23362293

ABSTRACT

BACKGROUND: We evaluated the herd protection conferred by an oral cholera vaccine using 2 approaches: cluster design and geographic information system (GIS) design.

METHODS: Residents living in 3933 dwellings (clusters) in Kolkata, India, were cluster-‐randomized to receive either cholera vaccine or oral placebo. Non-‐pregnant residents aged≥1 year were invited to participate in the trial. Only the first episode of cholera detected for a subject between 14 and 1095 days after a second dose was considered. In the cluster design, indirect protection was assessed by comparing the incidence of cholera among nonparticipants in vaccine clusters vs those in placebo clusters. In the GIS analysis, herd protection was assessed by evaluating association between vaccine coverage among the population residing within 250 m of the household and the occurrence of cholera in that population.

RESULTS: Among 107 347 eligible residents, 66 990 received 2 doses of either cholera vaccine or placebo. In the cluster design, the 3-‐year data showed significant total protection (66% protection, 95% confidence interval [CI], 50%-‐78%, P<.01) but no evidence of indirect protection. With the GIS approach, the risk of cholera among placebo recipients was inversely related to neighborhood-‐level vaccine coverage, and the trend was highly significant (P<.01). This relationship held in multivariable models that also controlled for potentially confounding demographic variables (hazard ratio, 0.94 [95% CI, .90-‐.98]; P<.01).

CONCLUSIONS: Indirect protection was evident in analyses using the GIS approach but not the cluster design approach, likely owing to considerable transmission of cholera between clusters, which would vitiate herd protection in the cluster analyses.

WEB: http://dx.doi.org/10.1093/cid/cit009

IMPACT FACTOR: 8.89

UW EDITORIAL COMMENT: This study was the first report of the herd protection conferred by the bivalent killed whole-‐cell OCV in an urban slum setting. Analysis included data from 3 years of surveillance to indicate that herd protection may be sustained for 3 years after receipt of the vaccine.


5. ANTIGEN-‐SPECIFIC MEMORY T CELL RESPONSES AFTER VACCINATION WITH AN ORAL KILLED CHOLERA VACCINE IN BANGLADESHI CHILDREN AND COMPARISON TO RESPONSES IN PATIENTS WITH NATURALLY ACQUIRED CHOLERA

Arifuzzaman M, Rashu R, Leung DT, Hosen MI, Bhuiyan TR, Bhuiyan MS, et al.

Clin Vaccine Immunol. 2012 Aug;19(8):1304-‐11.

PMID: 22739692

ABSTRACT

Young children, older children, and adults develop comparable levels and durations of immunity following cholera. In comparison, young children receiving oral killed cholera vaccines (OCV) develop a lower level and shorter duration of protection than those of older children and adults. The reasons for this are unclear. We investigated OCV-‐induced memory T cell responses in younger and older children and compared responses to those in children with cholera. We found that patients with cholera developed significant levels of toxin-‐specific effector memory T cells (T(EM)) with follicular helper and gut-‐homing characteristics. Older children (6 to 14 years of age) receiving two doses of OCV containing recombinant cholera toxin B subunit (rCTB) had more modest T(EM) responses with follicular helper and gut-‐homing characteristics, but younger vaccinees (24 to 71 months of age) did not develop T(EM) responses. The T(EM) response correlated positively with subsequent IgG memory B cell responses specific to rCTB in older vaccinees. Cytokine analyses indicated that cholera patients developed significant Th1, Th17, and Th2 responses, while older children receiving vaccine developed more modest increases in Th1 and Th17 cells. Younger vaccinees had no increase in Th1 cells, a decrease in Th17 cells, and an increase in regulatory T (Treg) cells. Our findings suggest that T cell memory responses are markedly diminished in children receiving OCV, especially young children, compared to responses following naturally acquired cholera, and that these differences affect subsequent development of memory B cell responses. These findings may explain the lower efficacy and shorter duration of protection afforded by OCV in young children.

WEB: http://dx.doi.org/10.1128/CVI.00196-‐12

IMPACT FACTOR: 2.47

UW EDITORIAL COMMENT: This study was the first to describe the T helper memory characteristics in children receiving an oral cholera vaccine.


6. 5 YEAR EFFICACY OF A BIVALENT KILLED WHOLE-‐CELL ORAL CHOLERA VACCINE IN KOLKATA, INDIA: A CLUSTER-‐RANDOMISED, DOUBLE-‐BLIND, PLACEBO-‐CONTROLLED TRIAL.

Bhattacharya SK, Sur D, Ali M, Kanungo S, You YA, Manna B et al.

Lancet Infect Dis. 2013 Dec;13(12):1050-‐6. Epub 2013 Oct 18.

PMID: 24140390

ABSTRACT

BACKGROUND: Efficacy and safety of a two-‐dose regimen of bivalent killed whole-‐cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-‐term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India.

METHODS: In our double-‐blind, cluster-‐randomised, placebo-‐controlled trial, we assessed incidence of cholera in non-‐pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-‐cell cholera vaccine or heat-‐killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-‐generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-‐confirmed Vibrio cholerae o1 diarrhoea severe enough for patients to seek treatment in a health-‐care facility. We identified culture-‐confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-‐protocol population of participants who had completely ingested two doses of assigned study treatment.

FINDINGS: 69 of 31 932 recipients of vaccine and 219 of 34 968 recipients of placebo developed cholera during 5 year follow-‐up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% ci 52-‐74; p<0·0001), and point estimates by year of follow-‐up suggested no evidence of decline in protective efficacy.

INTERPRETATION: Sustained protection for 5 years at the level we reported has not been noted previously with other oral cholera vaccines. Established long-‐term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings.

WEB: http://dx.doi.org/10.1016/S1473-‐3099(13)70273-‐1


UW EDITORIAL COMMENT: Figure 1 shows the trial design of vaccine and placebo groupings, while Tables 2 and 3 show efficacy by age at vaccination and by year of the trial. Results suggest that oral cholera vaccines are an effective tool to use in conjunction with improved treatment services and water and sanitation improvements to control cholera in endemic settings.


7. IMMUNOGENICITY OF A KILLED BIVALENT (O1 AND O139) WHOLE CELL ORAL CHOLERA VACCINE, SHANCHOL, IN HAITI.

Charles RC, Hilaire IJ, Mayo-‐Smith LM, Teng JE, Jerome JG, Franke MF et al.

PLoS Negl Trop Dis. 2014 May 1;8(5):e2828. eCollection 2014.

PMID: 24786645

ABSTRACT

BACKGROUND: Studies of the immunogenicity of the killed bivalent whole cell oral cholera vaccine, Shanchol, have been performed in historically cholera-‐endemic areas of Asia. There is a need to assess the immunogenicity of the vaccine in Haiti and other populations without historical exposure to Vibrio cholerae.

METHODOLOGY/PRINCIPAL FINDINGS: We measured immune responses after administration of Shanchol, in 25 adults, 51 older children (6-‐17 years), and 47 younger children (1-‐5 years) in Haiti, where cholera was introduced in 2010. A≥4-‐fold increase in vibriocidal antibody titer against V. cholerae o1 Ogawa was observed in 91% of adults, 74% of older children, and 73% of younger children after two doses of Shanchol; similar responses were observed against the inaba serotype. A≥2-‐fold increase in serum o-‐antigen specific polysaccharide IgA antibody levels against V. cholerae o1 Ogawa was observed in 59% of adults, 45% of older children, and 61% of younger children; similar responses were observed against the Inaba serotype. We compared immune responses in Haitian individuals with age-‐ and blood group-‐matched individuals from Bangladesh, a historically cholera-‐endemic area. The geometric mean vibriocidal titers after the first dose of vaccine were lower in Haitian than in Bangladeshi vaccinees. However, the mean vibriocidal titers did not differ between the two groups after the second dose of the vaccine.

CONCLUSIONS/SIGNIFICANCE: A killed bivalent whole cell oral cholera vaccine, Shanchol, is highly immunogenic in Haitian adults and children. A two-‐dose regimen may be important in Haiti, and other populations lacking previous repeated exposures to V. cholerae.

WEB: http://dx.doi.org/10.1371/journal.pntd.0002828

IMPACT FACTOR: 4.45

UW EDITORIAL COMMENT: This study offers important information on vaccine immunogenicity across regions and age groups. The authors note that immunogenicity is still an imperfect measure of protection in real-‐world settings.


8. FEASIBILITY OF MASS VACCINATION CAMPAIGN WITH ORAL CHOLERA VACCINES IN RESPONSE TO AN OUTBREAK IN GUINEA

Ciglenecki I, Sakoba K, Luquero FJ, Heile M, Itama C, Mengel M et al.

PLoS Med. 2013;10(9):e1001512. Epub 2013 Sep 10.

PMID: 24058301

ABSTRACT

SUMMARY POINTS

• Oral cholera vaccines are safe and effective, and in 2010 were added to WHO recommendations for cholera outbreak control. However, doubts about feasibility, timeliness, and acceptability by the population, and the fear of diverting resources from other preventive interventions, have discouraged their use during epidemics.

• We report on the first large-‐scale use of oral cholera vaccine as an outbreak control measure in Africa; this was also the first time Shanchol vaccine was used in Africa.

• We administered 312,650 doses of vaccine during two vaccination rounds in two coastal districts in Guinea. The feasibility, timeliness of implementation, and delivery cost were similar to those of other mass vaccination campaigns.

• The campaign was well accepted by the population, and high vaccination coverage was achieved despite the short time available for preparation, the two-‐dose schedule, the remote rural setting, and the highly mobile population.

• Oral cholera vaccines are a promising new tool in the arsenal of cholera control measures, alongside efforts to improve provision of safe water and sanitation and access to cholera treatment.

WEB: http://dx.doi.org/10.1371/journal.pmed.1001512


UW EDITORIAL COMMENT: This campaign was successful despite being implemented in hard-‐to-‐reach areas and being the first of its kind in Africa. It achieved 92% and 71% at least one dose coverage and 68% and 51% two-‐dose coverage in respective study areas in a six-‐week period It was also cost-‐effective; Table 1 shows the direct costs of the vaccination campaign.


9. IMPACT ON HUMAN HEALTH OF CLIMATE CHANGES

Franchini M, Mannucci PM.

Eur J Intern Med. 2015 Jan;26(1):1-‐5. Epub 2015 Jan 10.

PMID: 25582074

ABSTRACT

There is increasing evidence that climate is rapidly changing. These changes, which are mainly driven by the dramatic increase of greenhouse gas emissions from anthropogenic activities, have the potential to affect human health in several ways. These include a global rise in average temperature, an increased frequency of heat waves, of weather events such as hurricanes, cyclones and drought periods, plus an altered distribution of allergens and vector-‐borne infectious diseases. The cardiopulmonary system and the gastrointestinal tract are particularly vulnerable to the adverse effects of global warming. Moreover, some infectious diseases and their animal vectors are influenced by climate changes, resulting in higher risk of typhus, cholera, malaria, dengue and West Nile virus infection. On the other hand, at mid latitudes warming may reduce the rate of diseases related to cold temperatures (such as pneumonia, bronchitis and arthritis), but these benefits are unlikely to rebalance the risks associated to warming.

WEB: http://dx.doi.org/10.1016/j.ejim.2014.12.008

IMPACT FACTOR: 2.89

UW EDITORIAL COMMENT: This article provides an overview of climate-‐sensitive infectious diseases. Cholera bacteria in particular can multiply more rapidly in warmer water; this is a cause for concern as mean global temperatures rise.


10. SAFETY OF THE RECOMBINANT CHOLERA TOXIN B SUBUNIT, KILLED WHOLE-‐CELL (rBS-‐WC) ORAL CHOLERA VACCINE IN PREGNANCY

Hashim R, Khatib RM, Enwere G, Park JK, Reyburn R, Ali M, et al.

PLoS Negl Trop Dis. 2012;6(7):e1743.

PMID: 22848772

ABSTRACT

BACKGROUND: Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-‐cell oral cholera (rBS-‐WC) vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine.

METHODS/PRINICPAL FINDINGS: From January to February 2009, a mass rBS-‐WC vaccination campaign of persons over two years of age was conducted in an urban and a rural area (population 51,151) in Zanzibar. Pregnant women were advised not to participate in the campaign. More than nine months after the last dose of the vaccine was administered, we visited all women between 15 and 50 years of age living in the study area. The outcome of pregnancies that were inadvertently exposed to at least one oral cholera vaccine dose and those that were not exposed was evaluated. 13,736 (94%) of the target women in the study site were interviewed. 1,151 (79%) of the 1,453 deliveries in 2009 occurred during the period when foetal exposure to the vaccine could have occurred. 955 (83%) out of these 1,151 mothers had not been vaccinated; the remaining 196 (17%) mothers had received at least one dose of the oral cholera vaccine. There were no statistically significant differences in the odds ratios for birth outcomes among the exposed and unexposed pregnancies.

CONCLUSIONS: We found no statistically significant evidence of a harmful effect of gestational exposure to the rBS-‐WC vaccine. These findings, along with the absence of a rational basis for expecting a risk from this killed oral bacterial vaccine, are reassuring but the study had insufficient power to detect infrequent events


IMPACT FACTOR: 4.45

UW EDITORIAL COMMENT: Insufficient power in this study to rule out the possibility that rBS-‐WC vaccine could cause adverse events during pregnancy, but does provide reassurance that such events are not common. Overall, findings supported current recommendation that killed OCV is not contraindicated during pregnancy.


11. USE OF ORAL CHOLERA VACCINE IN HAITI: A RURAL DEMONSTRATION PROJECT

Ivers LC, Teng JE, Lascher J, Raymond M, Weigel J, Victor N, et al.

Am J Trop Med Hyg. 2013 Oct;89(4):617-‐24.

PMID: 24106187

ABSTRACT

A cholera epidemic has claimed the lives of more than 8,000 Haitians and sickened 650,000 since the outbreak began in October 2010. Early intervention in the epidemic focused on case-‐finding, treatment, and water and sanitation interventions for prevention of transmission. Use of oral cholera vaccine (OCV) as part of a complementary set of control activities was considered but initially rejected by policymakers. In December 2011, the Minister of Health of Haiti called for a demonstration of the acceptability and feasibility of the use of OCV in urban and rural Haiti. This paper describes the collaborative activity that offered OCV to one region of the Artibonite Department of rural Haiti in addition to other ongoing treatment and control measures. Despite logistics and cold chain challenges, 45,417 persons were successfully vaccinated with OCV in the region, and 90.8% of these persons completed their second dose.

WEB: http://dx.doi.org/10.4269/ajtmh.13-‐0183

IMPACT FACTOR: 2.70

UW Editorial Comment: This article provided a brief introduction to the cholera outbreak in Haiti. It was mainly focused on the use of OCVs in a rural vaccination campaign to demonstrate acceptability and feasibility (e.g., logistics) of such a campaign.


12. IMMUNOGENICITY OF THE BIVALENT ORAL CHOLERA VACCINE SHANCHOL IN HAITIAN ADULTS WITH HIV INFECTION.

Ivers LC, Charles RC, Hilaire IJ, Mayo-‐Smith LM, Teng JE, Jerome JG et al.

J Infect Dis. 2015 Sep 1;212(5):779-‐83. Epub 2015 Feb 26.

PMID: 25722294

ABSTRACT

We evaluated immune responses following bivalent oral cholera vaccination (Shanchol [Shantha Biotechnics]; BivWC) in a cohort of 25 human immunodeficiency virus (HIV)-‐infected adults in Haiti. Compared with adults without HIV infection, vaccination in HIV-‐infected individuals resulted in lower vibriocidal responses against Vibrio cholerae O1, and there was a positive relationship between the CD4(+) T-‐cell count and vibriocidal responses following vaccination. Nevertheless, seroconversion occurred at a rate of 65% against the Ogawa serotype and 74% against the Inaba serotype in adults with HIV infection. These results suggest that the vaccine retains substantial immunogenicity in adults with HIV infection and may benefit this population by protecting against cholera.

WEB: http://dx.doi.org/10.1093/infdis/jiv108

IMPACT FACTOR: 6.00

UW EDITORIAL COMMENT: This article augments the limited literature on susceptibility to Vibrio cholerae and different immune responses to OCV among HIV positive adults. Table 1 shows demographic characteristics and OCV responses among study participants.


13. COST-‐BENEFIT COMPARISONS OF INVESTMENTS IN IMPROVED WATER SUPPLY AND CHOLERA VACCINATION PROGRAMS

Jeuland M, Whittington D.

Vaccine. 2009 May 18;27(23):3109-‐20.

PMID: 19428925

ABSTRACT

This paper presents the first cost-‐benefit comparison of improved water supply investments and cholera vaccination programs. Specifically, we compare two water supply interventions -‐-‐ deep wells with public hand pumps and biosand filters (an in-‐house, point-‐of-‐use water treatment technology) -‐-‐ with two types of cholera immunization programs with new-‐generation vaccines -‐-‐ general community-‐based and targeted and school-‐based programs. In addition to these four stand-‐alone investments, we also analyze five combinations of water and vaccine interventions: (1) borehole+hand pump and community-‐based cholera vaccination, (2) borehole+hand pump and school-‐based cholera vaccination, (3) biosand filter and community-‐based cholera vaccination, (4) biosand filter and school-‐based cholera vaccination, and (5) biosand filter and borehole+hand pump. Using recent data applicable to developing country locations for parameters such as disease incidence, the effectiveness of vaccine and water supply interventions against diarrheal diseases, and the value of a statistical life, we construct cost-‐benefit models for evaluating these interventions. We then employ probabilistic sensitivity analysis to estimate a frequency distribution of benefit-‐cost ratios for all four interventions, given a wide variety of possible parameter combinations. Our results demonstrate that there are many plausible conditions in developing countries under which these interventions will be attractive, but that the two improved water supply interventions and the targeted cholera vaccination program are much more likely to yield attractive cost-‐benefit outcomes than a community-‐based vaccination program. We show that implementing community-‐based cholera vaccination programs after borehole+hand pump or biosand filters have already been installed will rarely be justified. This is especially true when the biosand filters are already in place, because these achieve substantial cholera risk reductions on their own. On the other hand, implementing school-‐based cholera vaccination programs after the installation of boreholes with hand pump is more likely to be economically attractive. Also, if policymakers were to first invest in cholera vaccinations, then subsequently investing in water interventions is still likely to yield positive economic outcomes. This is because point-‐of-‐use water treatment delivers health benefits other than reduced cholera, and deep boreholes+hand pumps often yield non-‐health benefits such as time savings. However, cholera vaccination programs are much cheaper than the water supply interventions on a household basis. Donors and governments with limited budgets may thus determine that cholera vaccination programs are more equitable than water supply interventions because more people can receive benefits with a given budget… [text not shown]

WEB: http://dx.doi.org/10.1016/j.vaccine.2009.02.104

IMPACT FACTOR: 3.62

UW EDITORIAL COMMENT: This modeling analysis showed that the net benefits of sector-‐level interventions typically presented in the literature are misleading. For the vaccination interventions, the value of a statistical life, baseline disease incidence, the case-‐fatality rate, and the marginal cost of vaccination were all more important parameters for the cost-‐benefit calculations than the parameters describing the effectiveness of the vaccine (duration, herd protection, and efficacy).


14. ENVIRONMENTAL FACTORS INFLUENCING EPIDEMIC CHOLERA

Jutla A, Whitcombe E, Hasan N, Haley B, Akanda A, Huq A et al.

Am J Trop Med Hyg. 2013 Sep;89(3):597-‐607. Epub 2013 Jul 29.

PMID: 23897993

ABSTRACT

Cholera outbreak following the earthquake of 2010 in Haiti has reaffirmed that the disease is a major public health threat. Vibrio cholerae is autochthonous to aquatic environment, hence, it cannot be eradicated but hydroclimatology-‐based prediction and prevention is an achievable goal. Using data from the 1800s, we describe uniqueness in seasonality and mechanism of occurrence of cholera in the epidemic regions of Asia and Latin America. Epidemic regions are located near regional rivers and are characterized by sporadic outbreaks, which are likely to be initiated during episodes of prevailing warm air temperature with low river flows, creating favorable environmental conditions for growth of cholera bacteria. Heavy rainfall, through inundation or breakdown of sanitary infrastructure, accelerates interaction between contaminated water and human activities, resulting in an epidemic. This causal mechanism is markedly different from endemic cholera where tidal intrusion of seawater carrying bacteria from estuary to inland regions, results in outbreaks.

WEB: http://dx.doi.org/10.4269/ajtmh.12-‐0721

IMPACT FACTOR: 2.70

UW EDITORIAL COMMENT: This article explores the historical relationship between cholera, precipitation, and temperature. Figure 6 shows a schematic of these three variables, as well as water and sanitation access.


15. SAFETY AND IMMUNOGENICITY OF A LIVE ORAL RECOMBINANT CHOLERA VACCINE VA1.4: A RANDOMIZED, PLACEBO CONTROLLED TRIAL IN HEALTHY ADULTS IN A CHOLERA ENDEMIC AREA IN KOLKATA, INDIA.

Kanungo S, Sen B, Ramamurthy T, Sur D, Manna B, Pazhani GP, et al.

PLoS One. 2014 Jul 1;9(7):e99381. eCollection 2014.

PMID: 24983989

ABSTRACT

BACKGROUND: A live oral cholera vaccine VA 1.4 developed from a non-‐toxigenic Vibrio cholerae O1 El Tor strain using ctxB gene insertion was further developed into a clinical product following cGMP and was evaluated in a double-‐blind randomized placebo controlled parallel group two arm trial with allocation ratio of 1∶1 for safety and immunogenicity in men and women aged 18-‐60 years from Kolkata, India.

METHOD: A lyophilized dose of 1.9×109 CFU (n = 44) or a placebo (n = 43) reconstituted with a diluent was administered within 5 minutes of drinking 100 ml of a buffer solution made of sodium bicarbonate and ascorbic acid and a second dose on day 14.

RESULT: The vaccine did not elicit any diarrhea related adverse events. Other adverse events were rare, mild and similar in two groups. One subject in the vaccine group excreted the vaccine strain on the second day after first dose. The proportion of participants who seroconverted (i.e. had 4-‐folds or higher rise in reciprocal titre) in the vaccine group were 65.9% (95% CI: 50.1%-‐79.5%) at both 7 days (i.e. after 1st dose) and 21 days (i.e. after 2nd dose). None of the placebo recipients seroconverted. Anti-‐cholera toxin antibody was detected in very few recipients of the vaccine.

CONCLUSION: This study demonstrates that VA 1.4 at a single dose of 1.9×109 is safe and immunogenic in adults from a cholera endemic region. No additional benefit after two doses was seen.

WEB: http://dx.doi.org/10.1371/journal.pone.0099381

IMPACT FACTOR: 3.23

UW EDITORIAL COMMENT: This article details safety and immunogenicity trial results in adults of a live oral cholera vaccine under development; VA 1.4.


16. FLEXIBILITY OF ORAL CHOLERA VACCINE DOSING-‐A RANDOMIZED CONTROLLED TRIAL MEASURING IMMUNE RESPONSES FOLLOWING ALTERNATIVE VACCINATION SCHEDULES IN A CHOLERA HYPER-‐ENDEMIC ZONE.

Kanungo S, Desai SN, Nandy RK, Bhattacharya MK, Kim DR, Sinha A et al.

PLoS Negl Trop Dis. 2015 Mar 12;9(3):e0003574. eCollection 2015.

PMID: 24516675

ABSTRACT

BACKGROUND: A bivalent killed whole cell oral cholera vaccine has been found to be safe and efficacious for five years in the cholera endemic setting of Kolkata, India, when given in a two dose schedule, two weeks apart. A randomized controlled trial revealed that the immune response was not significantly increased following the second dose compared to that after the first dose. We aimed to evaluate the impact of an extended four week dosing schedule on vibriocidal response.

METHODOLOGY/PRINCIPAL FINDINGS: In this double blind randomized controlled non-‐inferiority trial, 356 Indian, non-‐pregnant residents aged 1 year or older were randomized to receive two doses of oral cholera vaccine at 14 and 28 day intervals. We compared vibriocidal immune responses between these schedules. Among adults, no significant differences were noted when comparing the rates of seroconversion for V. cholerae O1 Inaba following two dose regimens administered at a 14 day interval (55%) vs the 28 day interval (58%). Similarly, no differences in seroconversion were demonstrated in children comparing the 14 (80%) and 28 day intervals (77%). Following 14 and 28 day dosing intervals, vibriocidal response rates against V. cholerae O1 Ogawa were 45% and 49% in adults and 73% and 72% in children respectively. Responses were lower for V. cholerae O139, but similar between dosing schedules for adults (20%, 20%) and children (28%, 20%).

CONCLUSIONS/SIGNIFICANCE: Comparable immune responses and safety profiles between the two dosing schedules support the option for increased flexibility of current OCV dosing. Further operational research using a longer dosing regimen will provide answers to improve implementation and delivery of cholera vaccination in endemic and epidemic outbreak scenarios.


IMPACT FACTOR: 4.45

UW EDITORIAL COMMENT: Preliminary research is presented here to suggest that an alternate dosing schedule of oral cholera vaccine does not yield different immune responses. Given the challenges to vaccine delivery in many endemic and outbreak settings, the possibility of greater flexibility in dosing has many implications.


17. MASS VACCINATION WITH A NEW, LESS EXPENSIVE ORAL CHOLERA VACCINE USING PUBLIC HEALTH INFRASTRUCTURE IN INDIA: THE ODISHA MODEL

Kar SK, Sah B, Patnaik B, Kim YH, Kerketta AS, Shin S, et al.

PLoS Negl Trop Dis. 2014 Feb 6;8(2):e2629.

PMID: 24516675

ABSTRACT

BACKGROUND: The substantial morbidity and mortality associated with recent cholera outbreaks in Haiti and Zimbabwe, as well as with cholera endemicity in countries throughout Asia and Africa, make a compelling case for supplementary cholera control measures in addition to existing interventions. Clinical trials conducted in Kolkata, India, have led to World Health Organization (WHO)-‐prequalification of Shanchol, an oral cholera vaccine (OCV) with a demonstrated 65% efficacy at 5 years post-‐vaccination. However, before this vaccine is widely used in endemic areas or in areas at risk of outbreaks, as recommended by the WHO, policymakers will require empirical evidence on its implementation and delivery costs in public health programs. The objective of the present report is to describe the organization, vaccine coverage, and delivery costs of mass vaccination with a new, less expensive OCV (Shanchol) using existing public health infrastructure in Odisha, India, as a model.

METHODS: All healthy, non-‐pregnant residents aged 1 year and above residing in selected villages of the Satyabadi block (Puri district, Odisha, India) were invited to participate in a mass vaccination campaign using two doses of OCV. Prior to the campaign, a de jure census, micro-‐planning for vaccination and social mobilization activities were implemented. Vaccine coverage for each dose was ascertained as a percentage of the censused population. The direct vaccine delivery costs were estimated by reviewing project expenditure records and by interviewing key personnel.

RESULTS: The mass vaccination was conducted during May and June, 2011, in two phases. In each phase, two vaccine doses were given 14 days apart. Sixty-‐two vaccination booths, staffed by 395 health workers/volunteers, were established in the community. For the censused population, 31,552 persons (61% of the target population) received the first dose and 23,751 (46%) of these completed their second dose, with a drop-‐out rate of 25% between the two doses. Higher coverage was observed among females and among 6-‐17 year-‐olds. Vaccine cost at market price (about US$1.85/dose) was the costliest item. The vaccine delivery cost was $0.49 per dose or $1.13 per fully vaccinated person.

CONCLUSION: This is the first undertaken project to collect empirical evidence on the use of Shanchol within a mass vaccination campaign using existing public health program resources. Our findings suggest that mass vaccination is feasible but requires detailed micro-‐planning. The vaccine and delivery cost is affordable for resource poor countries. Given that the vaccine is now WHO pre-‐qualified, evidence from this study should encourage oral cholera vaccine use in countries where cholera remains a public health problem.


IMPACT FACTOR: 4.45

UW EDITORIAL COMMENT: Table 2 provided a comprehensive description of micro-‐planning for a vaccination campaign. Table 4 outlined public sector costs. This analysis was limited by lack of cholera incidence data.


18. COVERAGE AND COST OF A LARGE ORAL CHOLERA VACCINATION PROGRAM IN A HIGH-‐RISK CHOLERA ENDEMIC URBAN POPULATION IN DHAKA, BANGLADESH

Khan IA, Saha A, Chowdhury F, Khan AI, Uddin MJ, Begum YA et al.

Vaccine. 2013 Dec 9;31(51):6058-‐64. Epub 2013 Oct 22..

PMID: 24161413

ABSTRACT

A feasibility study of an oral cholera vaccine was carried out to test strategies to reach high-‐risk populations in urban Mirpur, Dhaka, Bangladesh. The study was cluster randomized, with three arms: vaccine, vaccine plus safe water and hand washing practice, and no intervention. High risk people of age one year and above (except pregnant woman) from the two intervention arms received two doses of the oral cholera vaccine, Shanchol™. Vaccination was conducted between 17th February and 16th April 2011, with a minimum interval of fourteen days between two doses. Interpersonal communication preceded vaccination to raise awareness amongst the target population. The number of vaccine doses used, the population vaccinated, left-‐out, drop out, vaccine wastage and resources required were documented. Fixed outreach site vaccination strategy was adopted as the mode of vaccine delivery. Additionally, mobile vaccination sites and mop-‐up activities were carried out to reach the target communities. Of the 172,754 target population, 141,839 (82%) and 123,666 (72%) received complete first and second doses of the vaccine, respectively. Dropout rate from the first to the second dose was 13%. Two complete doses were received by 123,661 participants. Vaccine coverage in children was 81%. Coverage was significantly higher in females than in males (77% vs. 66%, P<0.001). Vaccine wastage for delivering the complete doses was 1.2%. The government provided cold-‐chain related support at no cost to the project. Costs for two doses of vaccine per-‐person were US$3.93, of which US$1.63 was spent on delivery. Cost for delivering a single dose was US$0.76. We observed no serious adverse events. Mass vaccination with oral cholera vaccine is feasible for reaching high risk endemic population through the existing national immunization delivery system employed by the government.


IMPACT FACTOR: 3.62

UW EDITORIAL COMMENT: To the authors’ knowledge, this was the largest feasibility study to-‐date looking at two-‐dose OCV immunization in an endemic urban setting. Further strategies are suggested in particular to reach adults working in the garment industry, such as early-‐morning mobile sessions and immunizations on holidays.


19. EFFECTIVENESS OF AN ORAL CHOLERA VACCINE IN ZANZIBAR: FINDINGS FROM A MASS VACCINATION CAMPAIGN AND OBSERVATIONAL COHORT STUDY

Khatib AM, Ali M, von Seidlein L, Kim DR, Hashim R, Reyburn R, et al.

Lancet Infect Dis. 2012 Nov;12(11):837-‐44.

PMID: 22954655

ABSTRACT

BACKGROUND: Zanzibar, in east Africa, has been severely and repeatedly affected by cholera since 1978. We assessed the effectiveness of oral cholera vaccination in high-‐risk populations in the archipelago to estimate the indirect (herd) protection conferred by the vaccine and direct vaccine effectiveness.

METHODS: We offered two doses of a killed whole-‐cell B-‐subunit cholera vaccine to individuals aged 2 years and older in six rural and urban sites. To estimate vaccine direct protection, we compared the incidence of cholera between recipients and non-‐recipients using generalised estimating equations with the log link function while controlling for potential confounding variables. To estimate indirect effects, we used a geographic information systems approach and assessed the association between neighbourhood-‐level vaccine coverage and the risk for cholera in the non-‐vaccinated residents of that neighbourhood, after controlling for potential confounding variables. This study is registered with ClinicalTrials.gov, number NCT00709410.

FINDINGS: Of 48,178 individuals eligible to receive the vaccine, 23,921 (50%) received two doses. Between February, 2009, and May, 2010, there was an outbreak of cholera, enabling us to assess vaccine effectiveness. The vaccine conferred 79% (95% CI 47-‐92) direct protection against cholera in participants who received two doses. Indirect (herd) protection was shown by a decrease in the risk for cholera of non-‐vaccinated residents within a household's neighbourhood as the vaccine coverage in that neighbourhood increased.

CONCLUSIONS: Our findings suggest that the oral cholera vaccine offers both direct and indirect (herd) protection in a sub-‐Saharan African setting. Mass oral cholera immunisation campaigns have the potential to provide not only protection for vaccinated individuals but also for the unvaccinated members of the community and should be strongly considered for wider use. Because this is an internationally-‐licensed vaccine, we could not undertake a randomised placebo-‐controlled trial, but the absence of vaccine effectiveness against non-‐cholera diarrhoea indicates that the noted protection against cholera could not be explained by bias.



UW EDITORIAL COMMENT: Results are particularly applicable for policymakers who have to deal with cholera in settings where the infrastructure for safe water supply and adequate sanitation cannot be established in a reasonable timeframe. Study suggested that mass vaccination campaigns are likely to reach high levels of coverage in communities that are at-‐risk for cholera.


20. POTENTIAL IMPACT OF REACTIVE VACCINATION IN CONTROLLING CHOLERA OUTBREAKS: AN EXPLORATORY ANALYSIS USING A ZIMBABWEAN EXPERIENCE

Kim SY, Choi Y, Mason PR, Rusakanika S, Goldie SJ.

S Afr Med J. 2011 Sep 5;101(9):659-‐64.

PMID: 21920160

ABSTRACT

BACKGROUND: To contain ongoing cholera outbreaks, the World Health Organization has suggested that reactive vaccination should be considered in addition to its previous control measures.

METHODS: This was a retrospective cost-‐effectiveness analysis calculating the health and economic burden of the cholera outbreak in Zimbabwe with and without reactive vaccination. The primary outcome measure was incremental cost per disability-‐adjusted life year (DALY) averted.

RESULTS: Under the base-‐case assumptions (assuming 50% coverage among individuals aged ≥2 years), reactive vaccination could have averted 1,320 deaths and 23,650 DALYs. Considering herd immunity, the corresponding values would have been 2,920 deaths and 52,360 DALYs averted. The total vaccination costs would have been ~$74 million and ~$21 million, respectively, with per-‐dose vaccine price of US$5 and $1. The incremental costs per DALY averted of reactive vaccination were $2,770 and $370, respectively, for vaccine price set at $5 and $1. Assuming herd immunity, the corresponding cost was $980 with vaccine price of $5, and the program was cost-‐saving with a vaccine price of $1. Results were most sensitive to case-‐fatality rate, per-‐dose vaccine price, and the size of the outbreak.

CONCLUSION: Reactive vaccination has the potential to be a cost-‐effective measure to contain cholera outbreaks in countries at high risk. However, the feasibility of implementation should be further evaluated, and caution is warranted in extrapolating the findings to different settings in the absence of other in-‐depth studies.

WEB: http://www.ncbi.nlm.nih.gov/pubmed/21920160

IMPACT FACTOR: 1.63

UW EDITORIAL COMMENT: Analysis was exploratory by design, and provided insights into the practical challenges that might be associated with reactive vaccination and the potential value of the intervention. Findings should be carefully interpreted when considered for different settings, since some parameter values may be specific to the size and severity of the Zimbabwe outbreak and demographics (i.e., age-‐specific life expectancy).


21. MEMORY B CELL AND OTHER IMMUNE RESPONSES IN CHILDREN RECEIVING TWO DOSES OF AN ORAL KILLED CHOLERA VACCINE COMPARED TO RESPONSES FOLLOWING NATURAL CHOLERA INFECTION IN BANGLADESH

Leung DT, Rahman MA, Mohasin M, Patel SM, Aktar A, Khanam F, et al.

Clin Vaccine Immunol. 2012 May;19(5):690-‐8.

PMID: 22441386

ABSTRACT

Current oral cholera vaccines induce lower protective efficacy and shorter duration of protection against cholera than wild-‐type infection provides, and this difference is most pronounced in young children. Despite this, there are limited data comparing immune responses in children following wild-‐type disease versus vaccination, especially with regard to memory responses associated with long-‐term immunity. Here, we report a comparison of immune responses in young children (2 to 5 years of age; n = 20) and older children (6 to 17 years of age; n = 20) given two doses of an oral killed cholera vaccine containing recombinant cholera toxin B subunit (CtxB) 14 days apart and compare these responses to those induced in similarly aged children recovering from infection with Vibrio cholerae O1 Ogawa in Bangladesh. We found that the two vaccine groups had comparable vibriocidal and lipopolysaccharide (LPS)-‐specific plasma antibody responses. Vaccinees developed lower levels of IgG memory B cell (MBC) responses against CtxB but no significant MBC responses against LPS. In contrast, children recovering from natural cholera infection developed prominent LPS IgG and IgA MBC responses, as well as CtxB IgG MBC responses. Plasma LPS IgG, IgA, and IgM responses, as well as vibriocidal responses, were also significantly higher in children following disease than after vaccination. Our findings suggest that acute and memory immune responses following oral cholera vaccination in children are significantly lower than those observed following wild-‐type disease, especially responses targeting LPS. These findings may explain, in part, the lower efficacy of oral cholera vaccination in children.

WEB: http://dx.doi.org/10.1128/CVI.05615-‐11

IMPACT FACTOR: 2.47

UW EDITORIAL COMMENT: Effect of zinc supplementation, small bowel bacterial overgrowth, and anti-‐parasitic drug treatment on immune response to OCV in young children was not assessed between different age groups. Sample size was limited by difficulties in recruiting child participants, especially those less than 4 years of age.


22. EFFECTIVENESS OF THE WC/RBS ORAL CHOLERA VACCINE IN THE PREVENTION OF TRAVELER’S DIARRHEA

Lopez-‐Gigosos R, Campins M, Calvo RJ, Perez-‐Hoyos S, Diez-‐Domingo J, Salleras L, et al.

Hum Vaccin Immunother. 2013 Mar;9(3):692-‐8.

PMID: 23324573

ABSTRACT

OBJECTIVE: Traveler's diarrhea (TD) is the most frequent disease among people from industrialized countries who travel to less developed ones, especially sub-‐Saharan Africa, Southern Asia and South America. The most common bacteria causing TD is enterotoxigenic Escherichia coli (ETEC). The WC/rBS cholera vaccine (Dukoral) has been shown to induce cross-‐protection against ETEC by means of the B subunit of the cholera toxin. The aim of the study was to evaluate the effectiveness of the WC/rBS cholera vaccine in preventing TD.

METHODS: Between May 1 and September 30 (2007), people seeking pre-‐travel advice in ten Spanish international vaccination centers were included in a prospective cohort study of travelers to cholera risk countries. The incidence rates of TD were adjusted for variables whose frequencies were statistically different (entry point 0.10) between the vaccinated and non-‐vaccinated cohorts.

FINDINGS: The vaccinated cohort (n = 544 travelers) included people vaccinated with the WC/rBS cholera vaccine, and the non-‐vaccinated cohort (n = 530 travelers) by people not vaccinated. The cumulative incidence rate of TD was 1.69 in vaccinated and 2.14 in non-‐vaccinated subjects. The adjusted relative risk of TD in vaccinated travelers was 0.72 (95% CI: 0.58-‐0.88) and the adjusted vaccination effectiveness was 28% (95% CI: 12-‐42).

CONCLUSIONS: The WC/rBS cholera vaccine prevents TD in 2 out of 7 travelers (preventive fraction: 28%). The number needed to vaccinate (NNV) to prevent 1 case of TD is 10.

WEB: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891730/

IMPACT FACTOR: 2.37

UW EDITORIAL COMMENT: Although the effectiveness of the WC/rBS vaccine against TD was low compared to other vaccines typically administered to travelers such as yellow fever or hepatitis A, the high frequency of the disease justified vaccination of travelers as the protective potential in terms of cases of TD was substantial.


23. FEASIBILITY OF A PREVENTIVE MASS VACCINATION CAMPAIGN WITH TWO DOSES OF ORAL CHOLERA VACCINE DURING A HUMANITARIAN EMERGENCY IN SOUTH SUDAN.

Porta MI, Lenglet A, de Weerdt S, Crestani R, Sinke R, Frawley MJ, et al.

Trans R Soc Trop Med Hyg. 2014 Dec;108(12):810-‐5. Epub 2014 Oct 13.

PMID: 25311798

ABSTRACT

BACKGROUND: As an adjunct to cholera prevention measures, WHO advises the use of oral cholera vaccine through mass vaccination campaigns in high-‐risk areas and for vulnerable population groups. We assessed the feasibility and acceptability of a mass vaccination campaign using 1) a predominantly fixed and 2) a mobile door-‐to-‐door strategy.

METHODS: Vaccination included administration of two doses (given 2 weeks apart) of oral cholera vaccine to individuals older than 1 year of age, in four refugee camps: Jamam, Doro, Batil and Gendrassa, and the host population in Maban County, South Sudan, from December 2012 to February 2013.

RESULTS: A total of 258 832 doses were administered to a population of 166 000 (126 000 refugees and 40 000 host population). The first round coverage for the refugees was above 84% for Doro, Jamam and Batil and 104% for Gendrassa. The second dose reached the same coverage as the first dose. For the host population, the coverage for the first dose was above 90% in Doro and Jamam and 53% in Gendrassa and Batil. For the second round, the coverage was above 79% in Doro and Jamam and above 70% in Batil and Gendrassa.

CONCLUSIONS: The vaccination of a large population in an emergency context proved to be feasible and acceptable and achieved high coverage. This is encouraging and is a way forward for reducing cholera related morbidity and mortality among vulnerable populations.

WEB: http://dx.doi.org/10.1093/trstmh/tru153

IMPACT FACTOR: 1.84

UW EDITORIAL COMMENT: While the predominantly fixed and mobile door-‐to-‐door immunization strategies differed in terms of implementation, the two strategies ultimately had no significant differences in terms of coverage or campaign speed. The use of community health workers and the high thermostability of Shanchol also contributed to the success of this campaign.


24. FEASIBILITY AND EFFECTIVENESS OF ORAL CHOLERA VACCINE IN AN URBAN ENDEMIC SETTING IN BANGLADESH: A CLUSTER-‐RANDOMISED OPEN-‐LABEL TRIAL.

Qadri F, Ali M, Chowdhury F, Khan AI, Saha A, Khan IA, et al.

Lancet. 2015 Oct 3;386(10001):1362-‐71. Epub 2015 Jul 9.

PMID: 26164097

ABSTRACT

BACKGROUND: Cholera is endemic in Bangladesh with epidemics occurring each year. The decision to use a cheap oral killed whole-‐cell cholera vaccine to control the disease depends on the feasibility and effectiveness of vaccination when delivered in a public health setting. We therefore assessed the feasibility and protective effect of delivering such a vaccine through routine government services in urban Bangladesh and evaluated the benefit of adding behavioural interventions to encourage safe drinking water and hand washing to vaccination in this setting.

METHODS: We did this cluster-‐randomised open-‐label trial in Dhaka, Bangladesh. We randomly assigned 90 clusters (1:1:1) to vaccination only, vaccination and behavioural change, or no intervention. The primary outcome was overall protective effectiveness, assessed as the risk of severely dehydrating cholera during 2 years after vaccination for all individuals present at time of the second dose. This study is registered with ClinicalTrials.gov, number NCT01339845.

FINDINGS: Of 268,896 people present at baseline, we analysed 267,270: 94,675 assigned to vaccination only, 92,539 assigned to vaccination and behavioural change, and 80,056 assigned to non-‐intervention. Vaccine coverage was 65% in the vaccination only group and 66% in the vaccination and behavioural change group. Overall protective effectiveness was 37% (95% CI lower bound 18%; p=0·002) in the vaccination group and 45% (95% CI lower bound 24%; p=0·001) in the vaccination and behavioural change group. We recorded no vaccine-‐related serious adverse events.

INTERPRETATION: Our findings provide the first indication of the effect of delivering an oral killed whole-‐cell cholera vaccine to poor urban populations with endemic cholera using routine government services and will help policy makers to formulate vaccination strategies to reduce the burden of severely dehydrating cholera in such populations.



UW EDITORIAL COMMENT: The percentage of participants in this study who migrated out of clusters was 58%. The authors suggest that this may have diluted the vaccinated clusters and contaminated the control cluster, therefore the estimates of vaccine efficacy presented in the results may be lower than actual protection.


25. PERU-‐15 (CHOLERAGARDE(®)), A LIVE ATTENUATED ORAL CHOLERA VACCINE, IS SAFE AND IMMUNOGENIC IN HUMANIMMUNODEFICIENCY VIRUS (HIV)-‐SEROPOSITIVE ADULTS IN THAILAND.

Ratanasuwan W, Kim YH, Sah BK, Suwanagool S, Kim DR, Anekthananon A, et al.

Vaccine. 2015 Sep 11;33(38):4820-‐6. Epub 2015 Aug 1.

PMID: 26241948

ABSTRACT

BACKGROUND: Many areas with endemic and epidemic cholera report significant levels of HIV transmission. According to the World Health Organization (WHO), over 95% of reported cholera cases occur in Africa, which also accounts for nearly 70% of people living with HIV/AIDS globally.Peru-‐15, a promising single dose live attenuated oral cholera vaccine (LA-‐OCV), was previously found to be safe and immunogenic in cholera endemic areas. However, no data on the vaccine's safety among HIV-‐seropositive adults had been collected.

METHODS: This study was a double-‐blinded, individually randomized, placebo-‐controlled trial enrolling HIV-‐seropositive adults, 18-‐45 years of age, conducted in Bangkok, Thailand, to assess the safety of Peru-‐15 in a HIV-‐seropositive cohort.

RESULTS: 32 HIV infected subjects were randomized to receive either a single oral dose of the Peru-‐15 vaccine with a buffer or a placebo (buffer only). No serious adverse events were reported during the follow-‐up period in either group. The geometric mean fold (GMF) rise in V. cholerae O1 El Tor specific antibody titers between baseline and 7 days after dosing was 32.0 (p<0.001) in the vaccine group compared to 1.6 (p<0.14) in the placebo group. Among the 16 vaccinees, 14 vaccinees (87.5%) had seroconversion compared to 1 of 16 placebo recipients (6.3%). V. cholerae was isolated from the stool of one vaccinee, and found to be genetically identical to the Peru-‐15 vaccine strain. There were no significant changes in HIV viral load or CD4 T-‐cell counts between vaccine and placebo groups.

CONCLUSION: Peru-‐15 was shown to be safe and immunogenic in HIV-‐seropositive Thai adults.


IMPACT FACTOR: 3.62

UW EDITORIAL COMMENT: Table 2 outlines adverse effects following dosing, while Table 3 shows vibriocidal antibody response at baseline and 7 days. Figure 2 shows a boxplot of Cd4 lymphocytes counts at screening and day 90.


26. SAFETY AND IMMUNOGENICITY STUDY OF A KILLED BIVALENT (O1 AND O139) WHOLE-‐CELL ORAL CHOLERA VACCINE SHANCHOL, IN BANGLADESHI ADULTS AND CHILDREN AS YOUNG AS 1 YEAR OF AGE.

Saha A, Chowdhury MI, Khanam F, Bhuiyan MS, Chowdhury F, Khan AI, et al.

Vaccine. 2011 Oct 26;29(46):8285-‐92. Epub 2011 Sep 9.

PMID: 21907255

ABSTRACT

BACKGROUND: Safety and immunogenicity study of an oral, killed, bivalent whole-‐cell, cholera vaccine, Shanchol was carried out in Bangladeshi participants. This study was conducted prior to initiating a feasibility study in Bangladesh.

STUDY PARTICIPANTS: The double-‐blind, randomized placebo controlled study was carried out in adults (18-‐45 years), toddlers (2-‐5 years) and younger children (12-‐23 months). Two doses of the vaccine/placebo were given 14 days apart.

RESULTS: Shanchol did not elicit major adverse events in any age group. Vibriocidal antibody responses in adults were 60% against Vibrio cholerae O1 Inaba, 72% against V. cholerae O1 Ogawa and 21% against V. cholerae O139. In toddlers, responses were 84%, 75% and 64% and in younger children it was 74%, 78% and 54% against Inaba, Ogawa and O139 serotypes. The responses in all ages were higher in vaccinees compared to pre-‐immune titers or to responses in placebo recipients (P<0.001). Plasma IgA antibody response to O1 Inaba LPS was seen in 61%, 73% and 45% of adults, toddlers and younger children, respectively.

CONCLUSIONS: The safety and immunogenicity data for Shanchol is promising and warrants future use in large scale trial in cholera endemic areas, high risk Bangladeshi population and in other countries in the region.


IMPACT FACTOR: 3.62

UW EDITORIAL COMMENT: This is the first study to report on the safety and immunogenicity of Shanchol in Bangladesh, and therefore has many implications for future use of Shanchol as a cholera control measure in the country. Table 3 shows vibriocidal antibody response to Vibrio cholerae O139 bacteria, by age.


27. USING MOBILE HEALTH (MHEALTH) AND GEOSPATIAL MAPPING TECHNOLOGY IN A MASS CAMPAIGN FOR REACTIVE ORAL CHOLERA VACCINATION IN RURAL HAITI.

Teng JE, Thomson DR, Lascher JS, Raymond M, Ivers LC.

PLoS Negl Trop Dis. 2014 Jul 31;8(7):e3050. eCollection 2014.

PMID: 25078790

ABSTRACT

BACKGROUND: In mass vaccination campaigns, large volumes of data must be managed efficiently and accurately. In a reactive oral cholera vaccination (OCV) campaign in rural Haiti during an ongoing epidemic, we used a mobile health (mHealth) system to manage data on 50,000 participants in two isolated communities.

METHODS: Data were collected using 7-‐inch tablets. Teams pre-‐registered and distributed vaccine cards with unique barcodes to vaccine-‐eligible residents during a census in February 2012. First stored on devices, data were uploaded nightly via Wi-‐fi to a web-‐hosted database. During the vaccination campaign between April and June 2012, residents presented their cards at vaccination posts and their barcodes were scanned. Vaccinee data from the census were pre-‐loaded on tablets to autopopulate the electronic form. Nightly analysis of the day's community coverage informed the following day's vaccination strategy. We generated case-‐finding reports allowing us to identify those who had not yet been vaccinated.

RESULTS: During 40 days of vaccination, we collected approximately 1.9 million pieces of data. A total of 45,417 people received at least one OCV dose; of those, 90.8% were documented to have received 2 doses. Though mHealth required up-‐front financial investment and training, it reduced the need for paper registries and manual data entry, which would have been costly, time-‐consuming, and is known to increase error. Using Global Positioning System coordinates, we mapped vaccine posts, population size, and vaccine coverage to understand the reach of the campaign. The hardware and software were usable by high school-‐educated staff.

CONCLUSION: The use of mHealth technology in an OCV campaign in rural Haiti allowed timely creation of an electronic registry with population-‐level census data, and a targeted vaccination strategy in a dispersed rural population receiving a two-‐dose vaccine regimen. The use of mHealth should be strongly considered in mass vaccination campaigns in future initiatives.


IMPACT FACTOR: 4.45

UW EDITORIAL COMMENT: The uses of mHealth applications in an outbreak setting were explored in this study. Given the success of this pilot, the authors recommend this strategy particularly for time-‐sensitive campaigns where data needs to be created and recorded quickly.


28. RANDOMIZED, DOUBLE-‐BLIND, PLACEBO-‐CONTROLLED TRIAL TO EVALUATE THE SAFETY AND IMMUNOGENICITY OF LIVE ORAL CHOLERA VACCINE 638 IN CUBAN ADULTS.

Valera R1, García HM, Jidy MD, Mirabal M, Armesto MI, Fando R, et al.

Vaccine. 2009 Nov 5;27(47):6564-‐9. Epub 2009 Aug 29.

PMID: 19720365

ABSTRACT

A randomized, double-‐blind, placebo-‐controlled clinical trial was conducted to evaluate the safety, reactogenicity and the immunogenicity of a 2 x 10(9)CFU dose of the 638 lyophilized live attenuated cholera vaccine for oral administration, formulated and produced at Finlay Institute, City of Havana, Cuba. Thirty-‐six healthy female and male adult volunteers from 18 to 40 years old were involved, clinically examined and laboratory tested after the informed consent signature. Adverse events were monitored and seroconversion rates and geometrical mean titer (GMT) of vibriocidal antibodies were tested in volunteer's sera samples. Neither serious adverse events nor other damages to the volunteers due to vaccine or placebo feeding were reported during the clinical follow-‐up period of this study; none of the adverse events registered within the first 72 h after inoculation were life-‐threatening for volunteers. Neither severe nor moderate adverse events were reported. Sixty-‐one percent of subjects showed mild expected adverse events in an interval lower than 24h up to the first 72 h, 75% of these in the vaccinated group and 18% in the placebo group. Fourteen days after inoculation the GMT of vibriocidal antibodies in the vaccine group significantly increased in comparison to the placebo group. All subjects in the vaccine group (24) seroconverted (100%). Results show that this vaccine is safe, well tolerated and immunogenic in healthy female and male volunteers.


IMPACT FACTOR:

UW EDITORIAL COMMENT: Table 4 shows the vibrocidal antibody responses among participants. The authors recommend further phase I-‐II clinical trials in children and adults in cholera-‐endemic areas.


APPENDIX: PUBMED SEARCH TERMS

((oral cholera vaccine) AND (cholera) AND (English[LA]) AND ("2009/09/01"[PDAT] : "2015/12/07"[PDAT])), humans only

*On December 7, 2015, this search of English language articles published between September 1, 2009 and December 7, 2015 and indexed by the US National Library of Medicine resulted in 158 unique manuscripts.

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