Abdul Momin Kazi

Impact of Withholding Breastfeeding at the Time of Vaccination on the Immunogenicity of Oral Rotavirus Vaccine—A Randomized Trial

Background Breast milk contains anti-rotavirus IgA antibodies and other innate immune factors that inhibit rotavirus replication in vitro. These factors could diminish the immunogenicity of oral rotavirus vaccines, particularly if breastfeeding occurs close to the time of vaccine administration. Methods Between April 2011 and November 2012, we conducted an open label, randomized trial to compare the immunogenicity of Rotarix (RV1) in infants whose breastfeeding was withheld one hour before through one hour after vaccination with that in infants breastfed at the time of vaccination. The trial was conducted in the peri-urban area of Ibrahim Hyderi in Karachi, Pakistan. Both groups received three doses of RV1 at 6, 10 and 14 weeks of age. Seroconversion (anti-rotavirus IgA antibodies ≥20 U/mL in subjects seronegative at 6 weeks of age) following three vaccine doses (6, 10 and 14 weeks) was determined at 18 weeks of age (primary objective) and seroconversion following two doses (6 and 10 weeks) was determined at 14 weeks of age (secondary objective). Results Four hundred eligible infants were randomly assigned in a 1:1 ratio between the withholding breastfeeding and immediate breastfeeding arms. Overall, 353 (88.3%) infants completed the study according to protocol; 181 in the withholding breastfeeding group and 172 in the immediate breastfeeding group. After three RV1 doses, anti-rotavirus IgA antibody seroconversion was 28.2% (95% CI: 22.1; 35.1) in the withholding arm and 37.8% (95% CI: 30.9; 45.2) in the immediate breastfeeding arm (difference: -9.6% [95% CI: -19.2; 0.2] p=0.07). After two doses of RV1, seroconversion was 16.6% (95% CI: 11.9; 22.7) in the withholding arm and 29.1% (95% CI: 22.8, 36.3) in the immediate breastfeeding arm (difference: -12.5% [95% CI: -21.2,-3.8] p=0.005). Conclusions Withholding breastfeeding around the time of RV1 vaccine administration did not lead to increased anti-rotavirus IgA seroconversion compared with that seen with a breastfeed at the time of vaccination. On the contrary, IgA seroconversion in infants immediately breastfed tended to be higher than in those withheld from a feeding. Our findings suggest that breastfeeding should be continued adlib around the time of rotavirus vaccination and withholding breastfeeding at that time is unlikely to improve the vaccine immunogenicity. Trial Registration ClinicalTrials.gov NCT01199874

Impact of Different Dosing Schedules on the Immunogenicity of the Human Rotavirus Vaccine in Infants in Pakistan - a Randomized Trial

BACKGROUND Current oral rotavirus vaccines perform suboptimally in resource-poor settings. We investigated the effect of an additional dose and later schedule on the immunogenicity of monovalent rotavirus vaccine (RV1) in a developing country. METHODS Infants received RV1 at 6 and 10, 10 and 14, or 6, 10, and 14 weeks of age. The primary objective was to compare antirotavirus immunoglobulin A (IgA) seroconversion at 18 weeks in the 6/10/14 arm to the cumulative seroconversion (highest result at 14 or 18 weeks) in the 6/10 arm. RESULTS Overall, 480 (76.2%) of 630 randomized infants completed the trial per protocol. Seroconversion in the 6/10/14 arm was 36.7% (95% CI, 29.8, 44.2) compared to 36.1% (CI, 29.0, 43.9) in the 6/10 arm, (P=1.0); the result from the 10/14 arm was 38.5% (CI, 31.2, 46.3). Seroconversion in the 6/10 arm at 14 weeks (post hoc) was lower at 29.7% (CI, 23.1, 37.3). CONCLUSIONS In Pakistani infants, the immunogenicity of RV1 did not increase significantly with 3 doses at 6, 10, and 14 weeks compared to 2 doses at 6 and 10 weeks. Additional strategies should be evaluated for improving rotavirus vaccine immunogenicity in high burden countries.

Infection Surveillance Protocol for a Multicountry Population-based Study in South Asia to Determine the Incidence Etiology and Risk Factors for Infections Among Young Infants of 0 to 59 Days Old.

Background: Insufficient knowledge of the etiology and risk factors for community-acquired neonatal infection in low-income countries is a barrier to designing appropriate intervention strategies for these settings to reduce the burden and treatment of young infant infection. To address these gaps, we are conducting the Aetiology of Neonatal Infection in South Asia (ANISA) study among young infants in Bangladesh, India and Pakistan. The objectives of ANISA are to establish a comprehensive surveillance system for registering newborns in study catchment areas and collecting data on bacterial and viral etiology and associated risk factors for infections among young infants aged 0–59 days. Methods: We are conducting active surveillance in 1 peri-urban and 4 rural communities. During 2 years of surveillance, we expect to enroll an estimated 66,000 newborns within 7 days of their birth and to follow-up them until 59 days of age. Community health workers visit each young infant in the study area 3 times in the first week of life and once a week thereafter. During these visits, community health workers assess the newborns using a clinical algorithm and refer young infants with signs of suspected infection to health care facilities where study physicians reassess them and provide care if needed. On physician confirmation of suspected infection, blood and respiratory specimens are collected and tested to identify the etiologic agent. Conclusions: ANISA is one of the largest initiatives ever undertaken to understand the etiology of young infant infection in low-income countries. The data generated from this surveillance will help guide evidence-based decision making to improve health care in similar settings.

Secretor and Salivary ABO Blood Group Antigen Status Predict Rotavirus Vaccine Take in Infants

Histo-blood group antigens (HBGAs) expressed on enterocytes are proposed receptors for rotaviruses and can be measured in saliva. Among 181 Pakistani infants in a G1P[8] rotavirus vaccine trial who were seronegative at baseline, anti-rotavirus immunoglobulin A seroconversion rates after 3 vaccine doses differed significantly by salivary HBGA phenotype, with the lowest rate (19%) among infants who were nonsecretors (ie, who did not express the carbohydrate synthesized by FUT2), an intermediate rate (30%) among secretors with non-blood group O, and the highest rate (51%) among secretors with O blood group. Differences in HBGA expression may be responsible for some of the discrepancy in the level of protection detected for the current rotavirus vaccines in low-income versus high-income settings.

Assessing acceptability of hypertensive/diabetic patients towards mobile health based behavioral interventions in Pakistan: A pilot study.

INTRODUCTION Diabetes and hypertension are prevalent chronic diseases among the general population of Pakistan with an exponential progress expected over the upcoming years. Mobile Health services can be an efficient method of helping curtail this rise and improve quality of life of such patients as proven in developed countries. We aim to assess the acceptability of using Mobile Health services among diabetic and hypertensive patients in Pakistan. METHODS A total of 100 patients were approached in a large tertiary care Government Hospital of Karachi, Pakistan, using a nonprobability convenient sampling technique. Co-authors conducted an interview based sampling of a modified questionnaire to each participant after consent. All data was recorded and analyzed on SPSS 16. RESULTS A total of 100 patients participated in our study with 66 (66%) males and 34 (34%) females having a mean prevalence age of 54.27. All the 100 participants had easy access to cell phones with 88% participants (88/100) stating that they would be willing to participate in Mobile Health based interventions. A statistically significant number (p=0.014) of them preferred receiving phone calls (85.2%) rather than SMS (14.8%) reminders for these interventions. 85% of the participants even agreed to participate in such intervention on cash incentives. CONCLUSION The use of phone call reminders or SMS reminders seems like an acceptable and favorable option among hypertensive and diabetic patients. This can greatly improve their self-management and help curtail this rise in the future.

Sentinel Hospital-Based Surveillance for Assessment of Burden of Rotavirus Gastroenteritis in Children in Pakistan

Objectives To determine the burden and molecular epidemiology of rotavirus gastroenteritis in children hospitalized with severe acute watery diarrhea in Pakistan prior to introduction of rotavirus vaccine. Methods A cross-sectional study was carried out over a period of two years from 2006 – 2008 at five sentinel hospitals in the cities of Karachi, Lahore, Rawalpindi, and Peshawar. Stool samples collected from children under five years of age hospitalized with severe acute watery diarrhea were tested for rotavirus antigen via enzyme immunoassay (EIA) (IDEA REF K6020 Oxoid Ltd (Ely), Cambridge, United Kingdom). A subset of EIA positive stool samples were further processed for genotyping. Results 6679 children were enrolled and stool specimens of 2039 (30.5%) were positive for rotavirus. Rotavirus positivity ranged from 16.3% to 39.4% in the 5 hospitals with highest positivity in Lahore. 1241 (61%) of all rotavirus cases were in infants under one year of age. Among the strains examined for G-serotypes, the occurrence of G1, G2, G9 and G4 strains was found to be 28%, 24%, 14% and 13%, respectively. Among P-types, the most commonly occurring strains were P6 (31.5%) followed by P8 (20%) and P4 (12%). Prevalent rotavirus genotype in hospitalized children of severe diarrhea were G1P[8] 11.6% (69/593), followed by G2P[4] 10.4% (62/593), and G4P[6] 10.1% (60/593). Conclusions Approximately one third of children hospitalized with severe gastroenteritis in urban centers in Pakistan have rotavirus. Introduction of rotavirus vaccine in Pakistans national immunization program could prevent many severe episodes and diarrheal deaths.

Implementation of the ANISA Study in Karachi, Pakistan: Challenges and Solutions.

Background: Aetiology of Neonatal Infection in South Asia (ANISA) is a multicenter study in Bangladesh, India and Pakistan exploring the incidence and etiology of neonatal infections. A periurban site in Karachi was selected for its representativeness of the general population in neonatal health indicators. An established demographic surveillance system and other infrastructure needed for conducting the study already existed at this site. ANISA presents a unique challenge because of the need to capture every birth outcome in the community within a few hours of delivery to reliably estimate the incidence and etiology of early-onset sepsis in a setting where home births and deaths are common. Contextual Challenges: Major challenges at the Karachi site are related to early birth reporting and newborn assessment for births outside the catchment areas, parental refusal to participate, diverse ethnicity of the population, collection of biological specimens from healthy controls, political instability and crime, power outages and blood culture contamination. Some of the remedial actions taken include prolonging working hours; developing counseling skills of field workers; hiring staff with different linguistic abilities from within the study community; liaising with health facilities, key community informants, Lady Health Workers and traditional birth attendants; hiring community mobilizers; enhancing community sensitization; developing contingency plans for field work interruptions and procuring backup generators. The specimen contamination rate has decreased through training, supervision and video monitoring of blood collection procedures with individualized counseling of phlebotomists. Conclusion: ANISA offers lessons for successful implementation of complex study protocols in areas of high child mortality and challenging social environments.

Effect of Mobile Phone Text Message Reminders on Routine Immunization Uptake in Pakistan: Randomized Controlled Trial

Background Improved routine immunization (RI) coverage is recommended as the priority public health strategy to decrease vaccine-preventable diseases and eradicate polio in Pakistan and worldwide. Objective The objective of this study was to ascertain whether customized, automated, one-way text messaging (short message service, SMS) reminders delivered to caregivers via mobile phones when a child is due for an RI visit can improve vaccination uptake and timelines in Pakistan. Methods This was a randomized controlled trial, conducted in an urban squatter settlement area of Karachi, Pakistan. Infants less than 2 weeks of age with at least one family member who had a valid mobile phone connection and was comfortable receiving and reading SMS text messages were included. Participants were randomized to the intervention (standard care + one-way SMS reminder) or control (standard care) groups. The primary outcome was to compare the proportion of children immunized up to date at 18 weeks of age. Vaccine given at 6, 10, and 14 weeks schedule includes DPT-Hep-B-Hib vaccine (ie, diphtheria, pertussis, and tetanus; hepatitis B; and Haemophilus influenza type b) and oral poliovirus vaccine (OPV). Data were analyzed using chi-square tests of independence and tested for both per protocol (PP) and intention-to-treat (ITT) analyses. Results Out of those approached, 84.3% (300/356) of the participants were eligible for enrollment and 94.1% (318/338) of the participants had a working mobile phone. Only children in the PP analyses, who received an SMS reminder for vaccine uptake at 6 weeks visit, showed a statistically significant difference (96.0%, 86/90 vs 86.4%, 102/118; P=.03).The immunization coverage was consistently higher in the intervention group according to ITT analyses at the 6 weeks scheduled visit (76.0% vs 71.3%, P=.36). The 10 weeks scheduled visit (58.7% vs 52.7%, P=.30) and the 14 weeks scheduled visit (31.3% vs 26.0%, P=.31), however, were not statistically significant. Conclusions Automated simple one-way SMS reminders in local languages might be feasible for improving routine vaccination coverage. Whether one-way SMS reminders alone can have a strong impact on parental attitudes and behavior for improvement of RI coverage and timeliness needs to be further evaluated by better-powered studies and by comparing different types and content of text messages in low-and middle-income countries (LMICs). Trial Registration ClinicalTrials.gov NCT01859546; https://clinicaltrials.gov/ct2/show/NCT01859546 (Archived by WebCite at http://www.webcitation.org/6xFr57AOc)