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

Mahapatra, Tanmay,Mahapatra, Sanchita,Pal, Debottam,Saha, Jayanta,Lopez, AnnaLena,Ali, Mohammad,Bannerjee, Barnali,Manna, Byomkesh,Sur, Dipika,Bhattacharya, Sujit,Kanungo, Suman TaylorFrancis 2016 Human vaccines & immunotherapeutics Vol.12 No.1

<P>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.</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>

Flexibility of Oral Cholera Vaccine Dosing—A Randomized Controlled Trial Measuring Immune Responses Following Alternative Vaccination Schedules in a Cholera Hyper-Endemic Zone

Kanungo, Suman,Desai, Sachin N.,Nandy, Ranjan Kumar,Bhattacharya, Mihir Kumar,Kim, Deok Ryun,Sinha, Anuradha,Mahapatra, Tanmay,Yang, Jae Seung,Lopez, Anna Lena,Manna, Byomkesh,Bannerjee, Barnali,Ali, Public Library of Science 2015 PLoS neglected tropical diseases Vol.9 No.3

<▼1><P><B>Background</B></P><P>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.</P><P><B>Methodology/Principal Findings</B></P><P>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 <I>V</I>. <I>cholerae O1 Inaba</I> 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 <I>V</I>. <I>cholerae</I> O1 Ogawa were 45% and 49% in adults and 73% and 72% in children respectively. Responses were lower for <I>V</I>. <I>cholerae</I> O139, but similar between dosing schedules for adults (20%, 20%) and children (28%, 20%).</P><P><B>Conclusions/Significance</B></P><P>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.</P></▼1><▼2><P><B>Author Summary</B></P><P>The five year efficacy results of the bivalent, killed whole cell oral cholera vaccine was shown to offer 65% protection in cholera endemic Kolkata. Currently, two oral cholera vaccines (OCV) are prequalified by the World Health Organization: the whole cell recombinant cholera toxin B subunit vaccine (Dukoral), and the bivalent killed whole cell only OCV (Shanchol). Shanchol, which is less expensive and possibly associated with longer protection, is recommended in a two dose schedule to be given at two weeks apart. Large scale cholera outbreaks often affect vulnerable populations with limited access to care. Strict dosing schedules can create further logistical barriers, hindering proper vaccine delivery to affected residents returning for their second OCV dose. In this study, 356 participants aged 1 year or older were randomized to receive two doses of OCV at 14 or 28 day intervals, for which vibriocidal immune responses were compared. Similar immune responses were demonstrated between a two and four week OCV dosing schedule, which can increase flexibility when offered as part of a targeted vaccination program. This can further serve to increase adherence and completion of the recommended dosing regimen, as well as providing a platform to increase coverage of other beneficial non-vaccine interventions.</P></▼2>