Trials and tribulations of conducting interventional studies in urban slums of a developing country: Experiences from Kolkata, India.

Experimental studies involving human subjects provide most internally valid evidences in epidemiological research due to their robust methodology. While conducting population-based interventional studies, to achieve external validity, inclusion of information from vulnerable groups like urban slum-dwellers of the developing world, in the epidemiological estimates is of paramount importance. The challenges faced while conducting 2 consecutive large-scale, community-based vaccine trials in urban slums of Kolkata, India are presented in this article. Interventions in these communities often get constrained by issues pertaining to human rights and benefits, socio-cultural factors, political environment, methodological shortcomings in addition to the challenges in ensuring community participation. While conducting these trials although we intermittently faced obstacles, by virtue of having a long term and robust surveillance system and developing a trusted relationship between the researchers, community leaders and residents we were able to come up with a commendable community participation which culminated into the success of the interventions. Bridging the gap between research and field operations by incorporating knowledge gathered from interventional studies and making strategies to improve health conditions of these informal settlers is a major unfulfilled agenda. We believe the lessons learnt during our research will help researchers while developing efficient interventions in similar setting.

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.

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

Flexibility of oral cholera vaccine dosing-a randomized controlled trial measuring immune responses following alternative vaccination schedules in a cholera hyper-endemic zone.

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.