Increasing rates of Salmonella Paratyphi A and the current status of its vaccine development

Sahastrabuddhe, S.,Carbis, R.,Wierzba, T.F.,Ochiai, R.L. Expert Reviews 2013 Expert review of vaccines Vol.12 No.9

Strategy, Demand, Management, and Costs of an International Cholera Vaccine Stockpile

Maskery, Brian,DeRoeck, Denise,Levin, Ann,Kim, Young Eun,Wierzba, Thomas F.,Clemens, John D. Oxford University Press 2013 The Journal of infectious diseases Vol.208 No.suppl1

<P>In this article, we review the feasibility of mass vaccination against cholera and estimate the global population at risk for epidemic cholera. We then examine the cost of establishing and managing a cholera vaccine stockpile and summarize published mathematical models of the estimated impact of reactive vaccination campaigns developed for the current Haitian outbreak and a recent outbreak in Zimbabwe. On the basis of these evaluations, we recommend a stockpile that starts at 2 million doses, with an estimated annual cost of $5.5–$13.9 million in 2013, and grows to 10 million doses per year by 2017, with an annual cost of $27–$51 million. We believe that the stockpile can enhance efforts to mitigate future cholera outbreaks by guaranteeing the availability of cholera vaccines and, through use of the stockpile, by revealing knowledge about the efficient use of cholera vaccines during and after crises.</P>

Community Management of Acute Malnutrition in the Developing World

Se-Eun Park,Sungtae Kim,Cyprian Ouma,Mesfin Loha,Thomas F Wierzba,Nam Seon Beck 대한소아소화기영양학회 2012 Pediatric gastroenterology, hepatology & nutrition Vol.15 No.4

Globally, acute malnutrition triggers more than 50% of childhood mortality in children under 5 years old, which implies that about 3.5 million children die of malnutrition each year. Prior to the advent of ready-to-use therapeutic food (RUTF), the management of acute malnutrition was limited to hospitals, resulting in low coverage rates with high mortality, as malnourished cases were indentified at later stages often plagued with complications. However, current availability of RUTF has enabled malnourished children to be treated at communities. Further, because RUTF is dehydrated and sealed, it has the added advantage of a lower risk of bacterial contamination, thereby prolonging its storage life at room temperature. Recent data indicate that Community Management of Acute Malnutrition (CMAM) is as cost effective as other high-impact public health measures such as oral rehydration therapy for acute diarrheal diseases, vitamin A supplementation, and antibiotic treatment for acute respiratory infections. Despite the high efficacy of CMAM programs, CMAM still draws insufficient attention for global implementation, suggesting that CMAM programs should be integrated into local or regional routine health systems. Knowledge gaps requiring further research include: the definition of practical screening criteria for malnourished children at communities, the need for systematic antibiotic therapy during malnutrition treatment, and the dietary management of severe malnutrition in children below 6 months of age.

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

Qadri, Firdausi,Ali, Mohammad,Lynch, Julia,Chowdhury, Fahima,Khan, Ashraful Islam,Wierzba, Thomas F,Excler, Jean-Louis,Saha, Amit,Islam, Md Taufiqul,Begum, Yasmin A,Bhuiyan, Taufiqur R,Khanam, Farhana Elsevier 2018 LANCET INFECTIOUS DISEASES Vol.18 No.6

<P><B>Summary</B></P> <P><B>Background</B></P> <P>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.</P> <P><B>Methods</B></P> <P>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 <I>Vibrio cholerae</I> O1 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 ClinicalTrials.gov, number NCT02027207.</P> <P><B>Findings</B></P> <P>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).</P> <P><B>Interpretation</B></P> <P>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.</P> <P><B>Funding</B></P> <P> <ce:grant-sponsor id='gs3' sponsor-id='http://dx.doi.org/10.13039/100000865' xlink:type='simple' xlink:role='http://www.elsevier.com/xml/linking-roles/grant-sponsor'>Bill & Melinda Gates Foundation</ce:grant-sponsor> to the International Vaccine Institute.</P>

Validity of the estimates of oral cholera vaccine effectiveness derived from the test-negative design

Ali, M.,You, Y.A.,Sur, D.,Kanungo, S.,Kim, D.R.,Deen, J.,Lopez, A.L.,Wierzba, T.F.,Bhattacharya, S.K.,Clemens, J.D. Butterworths ; Elsevier Science Ltd 2016 Vaccine Vol.34 No.4

Background: The test-negative design (TND) has emerged as a simple method for evaluating vaccine effectiveness (VE). Its utility for evaluating oral cholera vaccine (OCV) effectiveness is unknown. We examined this method's validity in assessing OCV effectiveness by comparing the results of TND analyses with those of conventional cohort analyses. Methods: Randomized controlled trials of OCV were conducted in Matlab (Bangladesh) and Kolkata (India), and an observational cohort design was used in Zanzibar (Tanzania). For all three studies, VE using the TND was estimated from the odds ratio (OR) relating vaccination status to fecal test status (Vibrio cholerae O1 positive or negative) among diarrheal patients enrolled during surveillance (VE= (1-OR)x100%). In cohort analyses of these studies, we employed the Cox proportional hazard model for estimating VE (=1-hazard ratio)x100%). Results: OCV effectiveness estimates obtained using the TND (Matlab: 51%, 95% CI:37-62%; Kolkata: 67%, 95% CI:57-75%) were similar to the cohort analyses of these RCTs (Matlab: 52%, 95% CI:43-60% and Kolkata: 66%, 95% CI:55-74%). The TND VE estimate for the Zanzibar data was 94% (95% CI:84-98%) compared with 82% (95% CI:58-93%) in the cohort analysis. After adjusting for residual confounding in the cohort analysis of the Zanzibar study, using a bias indicator condition, we observed almost no difference in the two estimates. Conclusion: Our findings suggest that the TND is a valid approach for evaluating OCV effectiveness in routine vaccination programs.

Herd Protection by a Bivalent Killed Whole-Cell Oral Cholera Vaccine in the Slums of Kolkata, India

Ali, Mohammad,Sur, Dipika,You, Young Ae,Kanungo, Suman,Sah, Binod,Manna, Byomkesh,Puri, Mahesh,Wierzba, Thomas F.,Donner, Allan,Nair, G. Balakrish,Bhattacharya, Sujit K.,Dhingra, Mandeep Singh,Deen, J Oxford University Press 2013 Clinical infectious diseases Vol.56 No.8

<P>We evaluated the herd protection conferred by the bivalent killed oral cholera vaccine. The vaccine conferred significant herd protection, suggesting that significant public health impact in cholera control may be achieved even with modest vaccination coverage.</P>

Uptake during an oral cholera vaccine pilot demonstration program, Odisha, India.

Kar, Shantanu K,Pach, Alfred,Sah, Binod,Kerketta, Anna S,Patnaik, Bikash,Mogasale, VijayaLaxmi,Kim, Yang Hee,Rath, Shyam Bandhu,Shin, Sunheang,Khuntia, Hemant K,Bhattachan, Anuj,Puri, Mahesh K,Wierzba Landes Bioscience 2014 Human Vaccines & Immunotherapeutics Vol.10 No.10

<P>Approximately 30% of reported global cholera cases occur in India. In 2011, a household survey was conducted 4 months after an oral cholera vaccine pilot demonstration project in Odisha India to assess factors associated with vaccine up-take and exposure to a communication and social mobilization campaign. Nine villages were purposefully selected based on socio-demographics and demonstration participation rates. Households were stratified by level of participation and randomly selected. Bivariate and ordered logistic regression analyses were conducted. 517/600 (86%) selected households were surveyed. At the household level, participant compared to non-participant households were more likely to use the local primary health centers for general healthcare (P < 0.001). Similarly, at the village level, higher participation was associated with use of the primary health centers (P < 0.001) and private clinics (p = 0.032). Also at the village level, lower participation was associated with greater perceived availability of effective treatment for cholera (p = 0.013) and higher participation was associated with respondents reporting spouse as the sole decision-maker for household participation in the study. In terms of pre-vaccination communication, at the household level verbal communication was reported to be more useful than written communication. However written communication was perceived to be more useful by respondents in low-participating villages compared to average-participating villages (p = 0.007) These data on participation in an oral cholera vaccine demonstration program are important in light of the World Health Organization's (WHO) recommendations for pre-emptive use of cholera vaccine among vulnerable populations in endemic settings. Continued research is needed to further delineate barriers to vaccine up-take within and across targeted communities in low- and middle-income countries.</P>

An Open Label Non-inferiority Trial Assessing Vibriocidal Response of a Killed Bivalent Oral Cholera Vaccine Regimen following a Five Year Interval in Kolkata, India

Kanungo, Suman,Desai, Sachin N.,Saha, Jayanta,Nandy, Ranjan Kumar,Sinha, Anuradha,Kim, Deok Ryun,Bannerjee, Barnali,Manna, Byomkesh,Yang, Jae Seung,Ali, Mohammad,Sur, Dipika,Wierzba, Thomas F. Public Library of Science 2015 PLoS neglected tropical diseases Vol.9 No.5

<▼1><P><B>Background</B></P><P>The bivalent killed oral cholera vaccine (OCV) provides 65% cumulative protection over five years. It remains unknown whether a boosting regimen can maintain protection in previously immunized populations. This study examines the immunogenicity and safety of an OCV regimen given five years following initial dosing.</P><P><B>Methodology/Principal Findings</B></P><P>An open label controlled trial was conducted in 426 healthy Indian participants previously enrolled in a large efficacy trial. To assess whether an OCV regimen given after five years can elicit an antibody response equal to that of a primary series, we compared vibriocidal antibody titers in previously immunized participants receiving a two dose booster regimen to participants receiving a primary two dose immunization series. Among participants receiving a two dose primary series of OCV (n = 186), 69% (95% CI 62%-76%) seroconverted. In the intervention arm (n = 184), 66% (95% CI 59%-73%) seroconverted following a two dose boosting schedule given five years following the initial series. Following a single boosting dose, 71% (95% CI 64%-77%) seroconverted. Children demonstrated 79% (95% CI 69%-86%) and 82% (95% CI 73%-88%) seroconversion after primary and boosting regimens, respectively.</P><P><B>Conclusions/Significance</B></P><P>Administration of an OCV boosting regimen elicits an immune response similar to those receiving a primary series in endemic areas. Though a single boosting dose induces a strong immune response, further investigations are needed to measure if these findings translate to clinical protection.</P></▼1><▼2><P><B>Author Summary</B></P><P>The five year efficacy results of the bivalent, killed whole cell oral cholera vaccine (WC OCV) was shown to offer 65% protection in cholera endemic Kolkata. Further search strategies focused on natural boosting of immunity, since this trial assessed protection in a population that has endemic cholera at high rates every year. The efficacy demonstrated in this project reflected both vaccine and naturally induced immunity. Though efficacy is maintained for five years, no formal recommendations on a boosting regimen exist. This study suggests that a boosting regimen of killed OCV can elicit vibriocidal titers similar to those levels produced by a primary series in adults and children residing in endemic areas. A boosting recommendation could help to ease logistical challenges faced in maintaining protection in cholera endemic areas. These immunogenicity findings provide initial evidence to support the use of an OCV boosting regimen five years following the primary series, with consideration of a shorter interval for children under the age of 5 years due to a lower observed efficacy in field trials.</P></▼2>

An Estimation of Private Household Costs to Receive Free Oral Cholera Vaccine in Odisha, India

Mogasale, Vittal,Kar, Shantanu K.,Kim, Jong-Hoon,Mogasale, Vijayalaxmi V.,Kerketta, Anna S.,Patnaik, Bikash,Rath, Shyam Bandhu,Puri, Mahesh K.,You, Young Ae,Khuntia, Hemant K.,Maskery, Brian,Wierzba, Public Library of Science 2015 PLoS neglected tropical diseases Vol.9 No.9

<▼1><P><B>Background</B></P><P>Service provider costs for vaccine delivery have been well documented; however, vaccine recipients’ costs have drawn less attention. This research explores the private household out-of-pocket and opportunity costs incurred to receive free oral cholera vaccine during a mass vaccination campaign in rural Odisha, India.</P><P><B>Methods</B></P><P>Following a government-driven oral cholera mass vaccination campaign targeting population over one year of age, a questionnaire-based cross-sectional survey was conducted to estimate private household costs among vaccine recipients. The questionnaire captured travel costs as well as time and wage loss for self and accompanying persons. The productivity loss was estimated using three methods: self-reported, government defined minimum daily wages and gross domestic product per capita in Odisha.</P><P><B>Findings</B></P><P>On average, families were located 282.7 (SD = 254.5) meters from the nearest vaccination booths. Most family members either walked or bicycled to the vaccination sites and spent on average 26.5 minutes on travel and 15.7 minutes on waiting. Depending upon the methodology, the estimated productivity loss due to potential foregone income ranged from $0.15 to $0.29 per dose of cholera vaccine received. The private household cost of receiving oral cholera vaccine constituted 24.6% to 38.0% of overall vaccine delivery costs.</P><P><B>Interpretation</B></P><P>The private household costs resulting from productivity loss for receiving a free oral cholera vaccine is a substantial proportion of overall vaccine delivery cost and may influence vaccine uptake. Policy makers and program managers need to recognize the importance of private costs and consider how to balance programmatic delivery costs with private household costs to receive vaccines.</P></▼1><▼2><P><B>Author Summary</B></P><P>The price of vaccine and the costs of its delivery are two important economic measures considered by governments and various international organizations in their decisions on the use of a new vaccine. However, the costs to the vaccine recipients resulting from their travel, time and wage loss are hardly considered and rarely documented. Even if the vaccine is provided for free, the costs borne by vaccine recipients could be sufficient enough to be a hurdle for taking vaccine. We elucidate this less explored angle of “vaccine recipient cost” in the context of oral cholera vaccine mass campaign in Odisha, India. Our research shows that the potential loss of income for individuals for receiving oral cholera vaccine ranged from 25% to 38% of overall vaccine delivery costs. We believe our findings have global implications on future decisions and policy making on vaccine introduction in balancing programmatic delivery costs with private household costs to receive vaccines.</P></▼2>