A study to evaluate the acceptability, feasibility and impact of packaged interventions ("Diarrhea Pack") for prevention and treatment of childhood diarrhea in rural Pakistan.

BACKGROUND: Diarrhea remains one of the leading public health issues in developing countries and is a major contributor in morbidity and mortality in children under five years of age. Interventions such as ORS, Zinc, water purification and improved hygiene and sanitation can significantly reduce the diarrhea burden but their coverage remains low and has not been tested as packaged intervention before. This study attempts to evaluate the package of evidence based interventions in a "Diarrhea Pack" through first level health care providers at domiciliary level in community based settings. This study sought to evaluate the acceptability, feasibility and impact of diarrhea Pack on diarrhea burden. METHODS: A cluster randomized design was used to evaluate the objectives of the project a union council was considered as a cluster for analysis, a total of eight clusters, four in intervention and four in control were included in the study. We conducted a baseline survey in all clusters followed by the delivery of diarrhea Pack in intervention clusters through community health workers at domiciliary level and through sales promoters to health care providers and pharmacies. Four quarterly surveillance rounds were conducted to evaluate the impact of diarrhea pack in all clusters by an independent team of Field workers. RESULTS: Both the intervention and control clusters were similar at the baseline but as the study progress we found a significant increase in uptake of ORS and Zinc along with the reduction in antibiotic use, diarrhea burden and hospitalization in intervention clusters when compared with the control clusters. We found that the Diarrhea Pack was well accepted with all of its components in the community. CONCLUSION: The intervention was well accepted and had a productive impact on the uptake of ORS and zinc and reduction in the use of antibiotics. It is feasible to deliver interventions such as diarrhea pack through community health workers in community settings. The intervention has the potential to be scaled up at national level.

Effect of bovine lactoferrin on seroconversion following polio vaccine administration in children: protocol for a double-blinded randomised controlled trial.

INTRODUCTION: The oral polio vaccine (OPV) has substantial results in eliminating wild poliovirus and the vaccine of choice in polio eradication. However, the mucosal immunity induced by the OPV is still uncertain. Literature has shown that bovine lactoferrin (BLF) is a safe and useful protein found in cow's milk with extraordinary antimicrobial, antiviral, antiinflammatory and immune-modulatory functions that help children's gut to fight against micro-organisms like poliovirus. However, limited data exist regarding the effect of BLF on polio vaccine immune response. The primary objective is to evaluate the effect of BLF in enhancing mucosal and humoral immunity in children following the administration of oral and inactivated polio vaccines. METHODS AND ANALYSIS: This is a two-arm double-blinded randomised controlled trial comparing 462 neonates (231 in both groups) receiving either BLF or placebo with breast milk. The intervention is administered from day 1 till 6 weeks of age to a full-term healthy singleton newborn born at the Aga Khan University Hospitals, Karachi, Pakistan. The primary outcome is the seroconversion, 1 month after the receipt of two doses of OPV (at 10 weeks). For descriptive statistical analysis, Stata will be used, the frequency with percentages will be reported to describe baseline characteristics of the participants. A χ2 test will be used to compare categorical variables and a simple t test to compare continuous variables. The proportion of seroconversion and shedding will be compared using χ2 test or Fisher's exact test. ETHICS AND DISSEMINATION: The Ethics approval has been granted by the Ethics Review Committee (ERC) of Aga Khan University for the proposed trial (ID: 2019-1955-5013). Furthermore, the National Bioethics Committee (NBC) of Pakistan has also approved the study for human subject research (ID: 4-87/NBC-443/19/669). Study findings will be disseminated through presentations at scientific conferences and educational practice workshops and will be published in an international peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: NCT04432935; ClinicalTrials.gov.

Understanding Perceptions and Practices for Designing an Appropriate Community-Based Kangaroo Mother Care Implementation Package: Qualitative Exploratory Study.

BACKGROUND: Low birth weight (LBW) is a common outcome of preterm birth, which increases the risk of an infant's morbidity and mortality. Approximately 20 million infants are born with LBW globally per year. Since a significant number of births in Pakistan take place at home, it is important to focus on the use of kangaroo mother care (KMC), the practice of skin-to-skin contact, in communities to prevent neonatal mortality and morbidity. OBJECTIVE: We employed a formative research approach to understand the context of communities and facilities with regard to neonatal care and KMC practice. The broader aims were to inform the design and delivery of culturally appropriate platforms to introduce KMC in communities, and develop effective recruitment and retention strategies of KMC in rural areas of the Dadu district in the Sindh province of Pakistan. METHODS: We conducted focus group discussions, in-depth interviews, and key informant interviews with families of LBW babies, community members, health care providers, and hospital administrators to identify barriers, enablers, and a knowledge base for KMC interventions. RESULTS: Newborn care practices in communities were found to be suboptimal. The community was generally unaware of the KMC intervention for the care of LBW babies. However, facility health care providers, the community, and family members were willing to provide KMC to improve outcomes. We found significant support from the community members and health care providers for KMC practices. Mothers were also ready to provide intermittent KMC. The administrative staff at the hospitals accepted the introduction of KMC practices for LBW babies. CONCLUSIONS: KMC as a method of treating LBW babies is widely accepted in the community. This formative research provides strategically valuable information that will be helpful for developing effective implementation strategies by identifying common community practices for LBW babies, along with identifying the barriers and enablers to KMC practice.

Effect of Community-Based Kangaroo Mother Care Package on Neonatal Mortality Among Preterm and Low Birthweight Infants in Rural Pakistan: Protocol for a Cluster Randomized Controlled Trial.

BACKGROUND: Neonatal mortality due to preterm birth and low birthweight remains a significant challenge in Pakistan. Kangaroo mother care (KMC) is a unique, low-cost intervention proven to reduce neonatal mortality and morbidity and increase exclusive breastfeeding rates. However, KMC has not been attempted in community settings in Pakistan. We aim to implement and evaluate the effectiveness of a community-based KMC package to reduce neonatal morbidity and mortality among preterm and low birthweight (LBW) infants, which will provide evidence for policy development and the large-scale implementation of KMC across the country. OBJECTIVE: The primary objective of this trial is to reduce neonatal mortality among preterm and LBW infants. The secondary objectives are growth (measured as weight gain), reduced incidence of possible serious bacterial infection, and increased exclusive breastfeeding and continued breastfeeding practices. METHODS: We designed a community-based cluster randomized controlled trial in one rural district of Pakistan. Stable, LBW babies (weighing 1200 grams to 2500 grams) are included in the study. The community KMC package, consisting of the KMC kit, information and counseling material, and community mobilization through KMC champions (village volunteers), was designed after preliminary research in the same geographical location and implemented in intervention clusters. The standard essential newborn care is offered in the control clusters. Infants are recruited and followed up by independent teams of data collectors. Data are collected on the duration of skin-to-skin contact, growth, breastfeeding practices, morbidities, neonatal mortality, and neurodevelopment status. Data analysis will be conducted based on the intention to treat principle. The Cox regression model will be used to assess the primary outcome of neonatal mortality. The secondary outcomes will be evaluated using linear or logistic regression. RESULTS: The Ethics Review Committee of Aga Khan University, Pakistan, approved the study protocol in February 2017. Data collection began in August 2019 and will be completed in December 2021. Data analyses are yet to be completed. CONCLUSIONS: This intervention may be effective in preventing sepsis and subsequently improve survival in LBW newborns in Pakistan and other low-income and middle-income countries worldwide. TRIAL REGISTRATION: clinicaltrials.gov NCT03545204; https://clinicaltrials.gov/ct2/show/NCT03545204. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28156.

Effect of booster doses of poliovirus vaccine in previously vaccinated children, Clinical Trial Results 2013.

BACKGROUND: Considering the current polio situation Pakistan needs vaccine combinations to reach maximum population level immunity. The trial assessed whether inactivated poliovirus vaccine (IPV) can be used to rapidly boost immunity among children in Pakistan. METHODS: A five-arm randomized clinical trial was conducted among children (6-24months, 5-6years and 10-11years). Children were randomized in four intervention arms as per the vaccines they received (bOPV, IPV, bOPV+vitamin A, and bOPV+IPV) and a control arm which did not receive any vaccine. Baseline seroprevalence of poliovirus antibodies and serological immune response 28days after intervention were assessed. RESULTS: The baseline seroprevalence was high for all serotypes and the three age groups [PV1: 97%, 100%, 96%, PV2: 86%, 100%, 99%, PV3: 83%, 95%, 87% for the three age groups respectively]. There was significantly higher rate of immune response observed in the study arms which included IPV (95-99%) compared with bOPV only arms (11-43%), [p<0.001]; Vitamin A was not associated with improved immune response. Immune response rates in the IPV only arm and IPV+bOPV arm were similar [p>0.5]. CONCLUSION: IPV has shown the ability to efficiently close existing immunity gaps in a vulnerable population of children in rural Pakistan.