A Holistic Strategy of Mother and Child Health Care to Improve the Coverage of Routine and Polio Immunization in Pakistan: Results from a Demonstration Project.

BACKGROUND: The eradication of poliovirus and improving routine immunization (RI) coverage rates present significant challenges in Pakistan. There is a need for interventions that focus on strengthening community engagement to improve routine immunization coverage. Our primary objective is to assess the impact of an integrated strategy designed to enhance community engagement and maternal and child health immunization campaigns on immunization coverage in Pakistan's high-risk union councils of polio-endemic districts. METHOD: We implemented an integrated approach for routine immunization and maternal and child health in the polio-endemic district of Pakistan. This approach involved setting up health camps and actively engaging and mobilizing the local community. An independent team conducted surveys at three key points: baseline, midline, and endline, to evaluate immunization coverage among children under the age of five. The primary outcome measures for the study were coverage of OPV, IPV, and changes in the proportion of unvaccinated and fully vaccinated children. To select clusters and eligible households in each cluster, we utilized a 30 × 15 cluster sampling technique. Multivariable associations between socio-demographic factors and changes in the proportion of fully vaccinated children at the UC level were assessed using hierarchical linear regression models. RESULTS: A total of 256,946 children under the age of five (122,950 at baseline and 133,996 at endline) were enrolled in the study. By the endline, full immunization coverage had increased to 60% or more in all three study areas compared to the baseline. Additionally, there was a significant increase in the coverage of both OPV and IPV across all three provinces at the endline. The full immunization rates were assessed on three levels of the framework: the distal, intermediate (access and environment), and proximal level (camp attendance and effectiveness). At the distal level, on multivariate analysis, family size was found to be a significant predictor of change in immunity within the families (ß = 0.68; p ≤ 0.0001). At the intermediate level, the likelihood of full immunization decreased with the decrease in knowledge about vaccination (ß = -0.38; p = 0.002), knowledge about polio vaccine (ß = -0.25; p = 0.011), and knowledge about IPV (ß = -0.06; p = 0.546). Perceived obstacles to vaccination were fear of adverse events (ß = -0.4; p ≤ 0.0001) and lack of education (ß = 0.23; p = 0.031), which were found to be significant in bivariate and multivariate analyses. At the proximal level, community mobilization (ß = 0.26; p = 0.008) and attendance at health camp (ß = 0.21; p ≤ 0.0001) were found to enhance full immunization coverage. On the other hand, the most prominent reason for not attending health camp included no need to attend the health camp as the child was not ill (ß = -0.13; p = 0.008). CONCLUSIONS: This study found that community mobilization and attendance at health camps significantly enhanced full immunization coverage. The findings highlight the importance of community engagement and targeted interventions in improving immunization coverage and addressing barriers to healthcare seeking.

Exploring the long-term seroprevalence of SARS-CoV-2 antibodies in infants born to women with clinical or laboratory-confirmed COVID-19.

INTRODUCTION: Infants are at a higher risk of severe illness with COVID-19 infection compared to older children. While COVID-19 vaccination is not recommended for young infants, they can acquire maternally-derived anti-SARS-CoV-2 antibodies passively through the placenta and breastmilk. We described the persistence of infection-induced maternal antibodies in infant circulation at 9-12 months of age. METHODOLOGY: This was a cross-sectional study nested within the INTERCOVID multinational cohort study. For each COVID positive pregnant woman, two unmatched consecutive COVID negative pregnant women were enrolled between April and September 2020. Women with a positive PCR test, radiographic signs consistent with COVID-19, or at least 2 predefined symptoms of COVID-19 were considered as COVID positive. For this nested cross-sectional study, all COVID positive and either one of the COVID negative participants recruited from the Aga Khan University, Pakistan were approached 9-12 months after delivery, and maternal and infant sera were collected for antibody detection. RESULTS: Altogether, 83 mothers provided consent, of whom 32 (38.6 %) were COVID positive and 51 (61.4 %) were COVID negative during pregnancy. Anti-SARS-CoV-2 antibodies were present in 13 (41 %) infants born to COVID positive and 19 (39 %) infants born to COVID negative mothers (p = 0.87). The presence of reactive antibodies in infants at follow-up was associated with maternal antibodies at follow-up (OR:9.50, 95 % CI:2.03-44.42; p = 0.004). COVID infection occurred in 3 (6 %) infants born to COVID negative mothers while no infant born to a COVID positive mother had a history of infection (p = 0.27). CONCLUSION: The presence of reactive anti-SARS-CoV-2 antibodies in infants at 9-12 months of age is associated with maternal seropositivity 9-12 months after delivery rather than maternal infection during pregnancy. Further studies are required to validate these findings and assess whether passive immunity in infants is protective against COVID-19 infection.

Does IPV Boost Intestinal Immunity among Children under Five Years of Age? An Experience from Pakistan.

The oral poliovirus vaccine (OPV) has been the mainstay of polio eradication, especially in low-income countries, and its use has eliminated wild poliovirus type 2. However, the inactivated poliovirus vaccine (IPV) is safer than OPV, as IPV protects against paralytic poliomyelitis without producing adverse reactions. The present study compared mucosal and humoral responses to poliovirus vaccines administered to previously OPV-immunized children to assess the immunity gap in children in areas of high poliovirus transmission. A cluster-randomized trial was implemented in three high-risk districts of Pakistan-Karachi, Kashmore, and Bajaur-from June 2013 to May 2014. This trial was community-oriented and included three arms, focusing on healthy children below five years of age. The study involved the randomization of 387 clusters, of which 360 were included in the final analysis. The control arm (A) received the routine polio program bivalent poliovirus vaccine (bOPV). The second arm (B) received additional interventions, including health camps providing routine vaccinations and preventive maternal and child health services. In addition to the interventions in arm B, the third arm (C) was also provided with IPV. Blood and stool samples were gathered from children to evaluate humoral and intestinal immunity. The highest levels of poliovirus type 1 serum antibodies were observed in Group C (IPV + OPV). The titers for poliovirus type 2 (P2) and poliovirus type 3 (P3) were noticeably higher in those who had received a routine OPV dose than in those who had not across all study groups and visits. Providing an IPV booster after at least two OPV doses could potentially fill immunity gaps in regions where OPV does not show high efficacy. However, IPV only marginally enhances humoral immunity and fails to offer intestinal immunity, which is critical to stop the infection and spread of live poliovirus in populations that have not been exposed before.

Determinants of Stunting among Children under Five in Pakistan.

INTRODUCTION: Child stunting remains a public health concern. It is characterized as poor cognitive and physical development in children due to inadequate nutrition during the first 1000 days of life. Across south Asia, Pakistan has the second-highest prevalence of stunting. This study assessed the most recent nationally representative data, the National Nutrition Survey (NNS) 2018, to identify the stunting prevalence and determinants among Pakistani children under five. METHODS: The NNS 2018, a cross-sectional household-level survey, was used to conduct a secondary analysis. Data on malnutrition, dietary practices, and food insecurity were used to identify the prevalence of stunting among children under five years in terms of demographic, socioeconomic, and geographic characteristics. The prevalence of stunting was calculated using the World Health Organization (WHO) height for age z-score references. Univariate and multivariable logistic regressions were conducted to identify the factors associated with child stunting. RESULTS: The analysis showed that out of 52,602 children under five, 40.0% were found to be stunted. Male children living in rural areas were more susceptible to stunting. Furthermore, stunting was more prevalent among children whose mothers had no education, were between 20 and 34, and were employed. In the multivariable logistic regression, male children (AOR = 1.08, 95% CI [1.04-1.14], p < 0.001) from rural areas (AOR = 1.07, 95% CI [1.01-1.14], p = 0.014), with the presence of diarrhea in the last two weeks (AOR = 1.15, 95% CI [1.06-1.25], p < 0.001) and mothers who had no education (AOR = 1.57, 95% CI [1.42-1.73], p < 0.001) or lower levels of education (primary: AOR = 1.35, 95% CI [1.21-1.51], p < 0.001; middle: AOR = 1.29, 95% CI [1.15-1.45], p < 0.001), had higher odds of stunting. Younger children aged < 6 months (AOR = 0.53, 95% CI [0.48-0.58], p < 0.001) and 6-23 months (AOR = 0.89, 95% CI [0.84-0.94], p < 0.001), with mothers aged 35-49 years (AOR = 0.78, 95% CI [0.66-0.92], p = 0.003), had lower odds of stunting. At the household level, the odds of child stunting were higher in lower-income households (AOR = 1.64, 95% CI [1.46-1.83], p < 0.001) with ≥ 7 members (AOR = 1.09, 95% CI [1.04-1.15], p < 0.001), with no access to improved sanitation facilities (AOR = 1.14, 95% CI [1.06-1.22], p < 0.001) and experiencing severe food insecurity (AOR = 1.07, 95% CI [1.01-1.14], p = 0.02). CONCLUSION: Child stunting in Pakistan is strongly associated with various factors, including gender, age, diarrhea, residence, maternal age and education, household size, food and wealth status, and access to sanitation. To address this, interventions must be introduced to make locally available food and nutritious supplements more affordable, improve access to safe water and sanitation, and promote female education for long-term reductions in stunting rates.

Exploring Knowledge and Perceptions of Polio Disease and Its Immunization in Polio High-Risk Areas of Pakistan.

Pakistan is one of the few countries where poliovirus transmission still persists, despite intensive efforts to eradicate the disease. Adequate vaccination coverage is essential to achieve polio eradication, but misconceptions about polio vaccines have hindered vaccination efforts. To address this issue, we conducted a mixed-methods study to explore knowledge and perceptions regarding polio disease and immunization in high-risk areas of Pakistan. We collected quantitative data from 3780, 1258, and 2100 households in Karachi, Bajaur, and Pishin, respectively, and supplemented this with qualitative data from focus group discussions and in-depth interviews. Our findings reveal a high level of awareness about polio and its immunization; however, misperceptions about the polio vaccine persist, leading to refusal for both polio vaccines and routine immunizations. Our study provides up-to-date data on knowledge and perceptions of polio and its immunization and identifies critical gaps. These findings can inform the development of future strategies and innovative approaches to improve the success of the polio program in Pakistan.

Factors Associated with Vaccine Refusal (Polio and Routine Immunization) in High-Risk Areas of Pakistan: A Matched Case-Control Study.

BACKGROUND: Pakistan has subpar childhood immunization rates and immunization activities have faced several challenges over the past years. We evaluated the social-behavioral and cultural barriers and risk factors for refusal of polio, Routine Immunization (RI), or both in high-risk areas of poliovirus circulation. METHODS: A matched case-control study was conducted from April to July 2017 in eight super high-risk Union Councils of five towns in Karachi, Pakistan. A total of 3 groups, each with 250 cases, including refusals for the Oral Polio Vaccine (OPV) in campaigns (national immunization days and supplementary immunization activities), RI, and both, were matched with 500 controls and identified using surveillance records. Sociodemographic characteristics, household information, and immunization history were assessed. Study outcomes included social-behavioral and cultural barriers and reasons for vaccine refusal. Data were analyzed in STATA using conditional logistic regression. RESULTS: RI refusal was associated with illiteracy and fear of the vaccine's adverse effects, while OPV refusals were linked to the mother's decision authority and the assumption that the OPV caused infertility. Conversely, higher socioeconomic status (SES) and knowledge of and willingness to vaccinate with Inactivated Polio Vaccine (IPV) were inversely associated with RI; and lower SES, walking to the vaccination point, knowledge of IPV, and an understanding of contracting polio were inversely associated with OPV refusals, with the latter two also inversely associated with complete vaccine refusal. CONCLUSION: Education, knowledge and understanding of vaccines, and socioeconomic determinants influenced OPV and RI refusals among children. Effective interventions are needed to address knowledge gaps and misconceptions among parents.

Risk factors for acute diarrhoea in children between 0 and 23 months of age in a peri-urban district of Pakistan: a matched case-control study.

BACKGROUND: Diarrhoea is a leading cause of preventable childhood morbidity and mortality worldwide. Unfortunately, Pakistan has the third-highest burden of diarrhoea-related deaths in children <5 y of age. Therefore we aimed to evaluate factors associated with diarrhoea among Pakistani children. METHODS: A retrospective 1:2 matched case-control study nested in a baseline cross-sectional survey was conducted from October to December 2018 in Taluka Kotri, a two-thirds urban locality in the Jamshoro district. Children between the ages of 0 and 23 months with a history of diarrhoea in the 2 weeks preceding the survey were labelled as cases. Age-matched controls were children without symptoms of diarrhoea. Univariate and multivariable conditional logistic regression was performed to identify diarrhoea-related factors. RESULTS: A total of 1558 cases were matched with 3116 controls. Factors significantly associated with lower odds of diarrhoea in the multivariate analysis included increasing maternal age (odds ratio [OR] 0.78 [95% confidence interval {CI} 0.67 to 0.90]), breastfeeding (OR 0.77 [95% CI 0.66 to 0.90]), higher paternal education (OR 0.79 [95% CI 0.65 to 0.97]) and belonging to the rich (OR 0.66 [95% CI 0.54 to 0.80]) and richest quintiles (OR 0.54 [95% CI 0.44 to 0.66]). CONCLUSIONS: This study identifies risk factors associated with diarrhoea in children <23 months of age, including younger maternal age, higher paternal education, not breastfeeding and poverty, which has implications for developing preventive programs and strategies that target populations with a higher risk of diarrhoea.

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.

Eradicating polio in Pakistan: a systematic review of programs and policies.

Introduction: Established in 1994, Pakistan's polio program demonstrated early success. However, despite over 120 supplementary immunization activities in the last decade, polio eradication efforts in Pakistan have been unable to achieve their objective of halting polio transmission. Variable governance, and inconsistent leadership and accountability have hindered the success of the polio program and the quality of the campaigns. Insecurity and terrorism has interrupted polio activities, and community fears and misbeliefs about polio vaccinations continue to persist.Areas covered: The article consists of a systematic review of the barriers and facilitators associated with the delivery of polio eradication activities in Pakistan. We also provide a comprehensive review of the policy and programmatic decisions made by the Pakistan Polio Programme since 1994. Searches were conducted on Embase and Medline databases and 25 gray literature sources.Expert opinion: Polio eradication efforts must be integrated with other preventive health services, particularly immunization services. Addressing the underlying causes of polio refusals including underdevelopment and social exclusion will help counteract resistance to polio vaccination. Achieving polio eradication will require building health systems that provide comprehensive community-centered care, and improving governance and systems of accountability.

Specialized Nutritious Food Combined With Cash Transfers and Social and Behavior Change Communication to Prevent Stunting Among Children Aged 6 to 23 Months in Pakistan: Protocol for a Cluster Randomized Controlled Trial.

BACKGROUND: In Pakistan, the prevalence of stunting in children younger than 5 years has remained above global critical levels over the past two decades, with the stunting rate being 40.2% in 2018. Children living in rural areas and in the poorest households suffer the most from stunting across the country-43.2% in rural areas and 51.4% in the lowest wealth quintile. As a continuing public health concern, it is essential that stunting prevention is a national priority in order to ensure human capital development, especially among the poorest households. OBJECTIVE: The primary objective of this study is to determine the effect of a medium quantity of a lipid-based nutrient supplement (LNS) combined with unconditional cash transfers and social and behavior change communication (SBCC) on reduction of stunting in children aged 6 to 23 months. METHODS: A 5-arm cluster randomized controlled trial will be conducted in the district of Rahim Yar Khan in Punjab, Pakistan. The intervention packages will be (1) cash only, (2) cash with LNS, (3) cash with SBCC, and (4) cash with SBCC and LNS. The control arm will receive routine standard of care. We will enroll children at 6 months of age and follow up on a monthly basis up to 24 months of age. A total of 2000 children, 400 in each arm, will be enrolled to detect a 20% reduction in the prevalence of stunting among children aged 24 months. Length, weight, food intake, compliance to interventions, morbidities, and other relevant data will be collected at enrollment and on a monthly basis over the period of 18 months. The process evaluation will assess acceptability of the interventions and potential barriers to implementation through focus group discussions and in-depth interviews with the target population and relevant stakeholders. Furthermore, a cost analysis will be conducted to assess the cost-effectiveness of each intervention package. RESULTS: The study protocol was approved by the Ethics Review Committee of Aga Khan University in Pakistan on January 4, 2017. Data collection began in May 2017 and was completed in July 2019. Data analyses are yet to be completed. This study will explore the effectiveness of intervention packages comprised of cash transfers from Benazir Income Support Programme with or without additional LNS and SBCC in preventing childhood stunting. We expect the results to be published in peer-reviewed journals by autumn of 2020. CONCLUSIONS: The findings of this trial will provide robust evidence as to which intervention packages can have significant effects on linear growth of children and design effective intervention packages to prevent stunting in children aged 6 to 23 months. TRIAL REGISTRATION: ClinicalTrials.gov NCT03299218; https://clinicaltrials.gov/ct2/show/NCT03299218. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/19001.

Immunity and field efficacy of type 2-containing polio vaccines after cessation of trivalent oral polio vaccine: A population-based serological study in Pakistan.

BACKGROUND: In Pakistan and other countries using oral polio vaccine (OPV), immunity to type 2 poliovirus is now maintained by a single dose of inactivated polio vaccine (IPV) in routine immunization, supplemented in outbreak settings by monovalent OPV type 2 (mOPV2) and IPV. While well-studied in clinical trials, population protection against poliovirus type 2 achieved in routine and outbreak settings is generally unknown. METHODS: We conducted two phases of a population-based serological survey of 7940 children aged 6-11 months old, between November 2016 and October 2017 from 13 polio high-risk locations in Pakistan. RESULTS: Type 2 seroprevalence was 50% among children born after trivalent OPV (tOPV) withdrawal (April 2016), with heterogeneity across survey areas. Supplementary immunization activities (SIAs) with mOPV2 followed by IPV improved population immunity, varying from 89% in Pishin to 64% in Killa Abdullah, with little observed marginal benefit of subsequent campaigns. In the other high-risk districts surveyed, a single SIA with IPV was conducted and appeared to improve immunity to 57% in Karachi to 84% in Khyber. CONCLUSIONS: Our study documents declining population immunity following trivalent OPV withdrawal in Pakistan, and wide heterogeneity in the population impact of supplementary immunization campaigns. Differences between areas, attributable to vaccination campaign coverage, were far more important for type 2 humoral immunity than the number of vaccination campaigns or vaccines used. This emphasizes the importance of immunization campaign coverage for type 2 outbreak response in the final stages of polio eradication. Given the declining type 2 immunity in new birth cohorts it is also recommended that 2 or more doses of IPV should be introduced in the routine immunization program of Pakistan.

Prevalence and determinants of iron deficiency anemia among non-pregnant women of reproductive age in Pakistan.

BACKGROUND AND OBJECTIVES: Iron deficiency Anemia (IDA) in women of reproductive age is a recognized public health concern that impairs health and well-being in women and is associated with adverse reproductive outcomes. In Pakistan there is a dearth of up-to-date information on the prevalence and predictors of IDA. This study sought to investigate IDA in Pakistani women. METHODS AND STUDY DESIGN: Secondary analysis was performed using the National Nutrition Survey in Pakistan 2011- 2012. We used a pre-structured instrument to collect socio demographic, reproductive and nutritional data on women. We also collected anthropometric measurements and blood samples for micronutrient deficiencies. Univariate and multivariate logistic regression were used to analyse the data. RESULTS: A total of 7491 non-pregnant women aged between 15-49 years were included in the analysis. The prevalence of IDA was 18.1%. In the multivariate regression analysis; not using iron folic acid supplementation during the last pregnancy adjusted odds ratio (AOR) (95% CI) 1.31 (1.05, 1.64), a history of four or more pregnancies AOR (95% CI) 1.30 (1.04, 1.60), birth interval of <24 months AOR (95% CI) 1.27 (1.06, 1.71), household food insecurity AOR (95% CI) 1.42 (1.23, 1.63) and presence of clinical anemia AOR (95% CI) 5.82 (4.82, 7.02) were significantly associated with increased odds of IDA while with obesity AOR (95% CI) 0.60 (0.4, 0.88) showed a protective effect on IDA. CONCLUSION: To reduce IDA in Pakistani women, the country needs a multifaceted approach that incorporates iron supplementation, food fortification, improved family planning services and efforts to reduce food insecurity.

Prevalence and determinants of unintended pregnancies amongst women attending antenatal clinics in Pakistan.

BACKGROUND: Unintended pregnancies are a global public health concern and contribute significantly to adverse maternal and neonatal health, social and economic outcomes and increase the risks of maternal deaths and neonatal mortality. In countries like Pakistan where data for the unintended pregnancies is scarce, studies are required to estimate its accurate prevalence and predictors using more specific tools such as the London Measure of Unplanned Pregnancies (LMUP). METHODS: We conducted a hospital based cross sectional survey in two tertiary care hospitals in Pakistan. We used a pre tested structured questionnaire to collect the data on socio-demographic characteristics, reproductive history, awareness and past experience with contraceptives and unintended pregnancies using six item the LMUP. We used Univariate and multivariate analysis to explore the association between unintended pregnancies and predictor variables and presented the association as adjusted odds ratios. We also evaluated the psychometric properties of the Urdu version of the LMUP. RESULTS: Amongst 3010 pregnant women, 1150 (38.2%) pregnancies were reported as unintended. In the multivariate analysis age < 20 years (AOR 3.5 1.1-6.5), being illiterate (AOR 1.9 1.1-3.4), living in a rural setting (1.7 1.2-2.3), having a pregnancy interval of = < 12 months (AOR 1.7 1.4-2.2), having a parity of >2 (AOR 1.4 1.2-1.8), having no knowledge about contraceptive methods (AOR 3.0 1.7-5.4) and never use of contraceptive methods (AOR 2.3 1.4-5.1) remained significantly associated with unintended pregnancy. The Urdu version of the LMUP scale was found to be acceptable, valid and reliable with the Cronbach's alpha of 0.85. CONCLUSIONS: This study explores a high prevalence of unintended pregnancies and important factors especially those related to family planning. Integrated national family program that provides contraceptive services especially the modern methods to women during pre-conception and post-partum would be beneficial in averting unintended pregnancies and their related adverse outcomes in Pakistan.

Community engagement and integrated health and polio immunisation campaigns in conflict-affected areas of Pakistan: a cluster randomised controlled trial.

BACKGROUND: Pakistan faces huge challenges in eradicating polio due to widespread poliovirus transmission and security challenges. Innovative interventions are urgently needed to strengthen community buy-in, to increase the coverage of oral polio vaccine (OPV) and other routine immunisations, and to enhance immunity through the introduction of inactivated polio vaccine (IPV) in combination with OPV. We aimed to evaluate the acceptability and effect on immunisation coverage of an integrated strategy for community engagement and maternal and child health immunisation campaigns in insecure and conflict-affected polio-endemic districts of Pakistan. METHODS: We did a community-based three-arm cluster randomised trial in healthy children aged 1 month to 5 years that resided within the study sites in three districts of Pakistan at high risk of polio. Clusters were randomly assigned by a computer algorithm using restricted randomisation in blocks of 20 by an external statistician (1:1:1) to receive routine polio programme activities (control, arm A), additional interventions with community outreach and mobilisation using an enhanced communication package and provision of short-term preventive maternal and child health services and routine immunisation (health camps), including OPV (arm B), or all interventions of arm B with additional provision of IPV delivered at the maternal and child health camps (arm C). An independent team conducted surveys at baseline, endline, and after each round of supplementary immunisation activity for acceptability and effect. The primary outcome measures for the study were coverage of OPV, IPV, and routine extended programme on immunisation vaccines and changes in the proportion of unvaccinated and fully vaccinated children. This trial is registered with ClinicalTrials.gov, number NCT01908114. FINDINGS: Between June 4, 2013, and May 31, 2014, 387 clusters were randomised (131 to arm A, 127 to arm B, and 129 to arm C). At baseline, 28 760 children younger than 5 years were recorded in arm A, 30 098 in arm B, and 29 126 in arm C. 359 clusters remained in the trial until the end (116 in arm A, 120 in arm B, and 123 in arm C; with 23 334 children younger than 5 years in arm A, 26 110 in arm B, and 25 745 in arm C). The estimated OPV coverage was 75% in arm A compared with 82% in arm B (difference vs arm A 6·6%; 95% CI 4·8-8·3) and 84% in arm C (8·5%, 6·8-10·1; overall p<0·0001). The mean proportion of routine vaccine doses received by children younger than 24 months of age was 43% in arm A, 52% in arm B (9%, 7-11) and 54% in arm C (11%, 9-13; overall p<0·0001). No serious adverse events requiring hospitalisation were reported after immunisation. INTERPRETATION: Despite the challenges associated with the polio end-game in high-risk, conflict-affected areas of Pakistan, a strategy of community mobilisation and targeted community-based health and immunisation camps during polio immunisation campaigns was successful in increasing vaccine coverage, including polio vaccine coverage. FUNDING: Bill & Melinda Gates Foundation.

A mixed methods study to assess the effectiveness of food-based interventions to prevent stunting among children under-five years in Districts Thatta and Sujawal, Sindh Province, Pakistan: study protocol.

BACKGROUND: Maternal and child malnutrition is widely prevalent in low and middle income countries. In Pakistan, widespread food insecurity and malnutrition are the main contributors to poor health, low survival rates and the loss of human capital development. The nutritional status trends among children exhibit a continuous deteriorating with rates of malnutrition exceeding the WHO critical threshold. With the high prevalence of maternal and child malnutrition, it is important to identify effective preventative approaches, especially for reducing stunting in children under-five years of age. The primary aim of this study is to assess the effectiveness of food-based interventions to prevent stunting in children under-five years. METHODS: A mixed methods study design will be conducted to evaluate the effectiveness of food-based interventions to prevent stunting among children under-five years in districts Thatta and Sujawal, Sindh Province, Pakistan. The study will include cross sectional surveys, a community-based cluster randomized controlled trial and a process evaluation. The study participants will be pregnant women, lactating mothers and children under-five years. The cross-sectional surveys will be conducted with 7360 study participants at baseline and endline. For the randomized control trial, 5000 participants will be recruited and followed monthly for compliance of food-based supplements, dietary diversity, pregnancy outcomes, and maternal and child morbidity and mortality. Anthropometric measurements and hemoglobin levels will be measured at baseline, quarterly and at endline. The interventions will consist of locally produced lipid-based nutrient supplement (Wawamum) for children 6-23 months, micronutrient powders for children 24-59 months, and wheat soya blends for pregnant and lactating mothers. Government lady health workers will deliver interventions to participants. The effectiveness of the project will be measured in terms of the impact of the proposed interventions on stunting, nutritional status, micronutrient deficiencies, and other key indicators of the participants. The process evaluation will assess the acceptability, feasibility and potential barriers of project implementation through focus group discussions, key informant interviews and household surveys. Data analysis will be conducted using STATA version 12. DISCUSSION: There is considerable evidence on the effectiveness of food-based interventions in managing stunting in developing countries. However, these studies do not account for the local environmental factors and widespread nutrient deficiencies in Pakistan. These studies are often conducted in controlled environments, where the results cannot be generalized to programs operating under field conditions. The findings of this study will provide sufficient evidence to develop policies and programs aimed to prevent stunting in children 6-59 months and to improve maternal and child health and growth outcomes in poor resource settings. TRIAL REGISTRATION: NCT02422953 . Registered on April 15, 2015.

Knowledge and perceptions of polio and polio immunization in polio high-risk areas of Pakistan.

Pakistan and Afghanistan remain the only countries where polio is endemic, and Pakistan reports the most cases in the world. Although the rate is lower than in previous years, the situation remains alarming. We conducted a mixed methods study in high-risk areas of Pakistan to identify knowledge, attitudes, and practices of target populations about polio vaccine and its eradication, and to estimate coverage of routine immunization and oral polio vaccine. We surveyed 10,685 households in Karachi, 2522 in Pishin, and 2005 in Bajaur. Some knowledge of polio is universal, but important misconceptions persist. The findings of this study carry strategic importance for program direction and implementation.

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.

Prevalence and Predictors of Iron Deficiency Anemia in Children under Five Years of Age in Pakistan, A Secondary Analysis of National Nutrition Survey Data 2011-2012.

BACKGROUND: Iron deficiency Anemia (IDA) in children is a recognized public health problem that impacts adversely on child morbidity, mortality and impairs cognitive development. In Pakistan information on the true prevalence and predictors of IDA is limited. This study sought to investigate IDA in children under five years of age using data from a nationally representative stratified cross-sectional survey. METHODS: Secondary analysis was performed on the National Nutrition Survey in Pakistan 2011-2012. We used a pre-structured instrument to collect socio demographic and nutritional data on mothers and children. We also collected Anthropometric measurements and blood samples for micronutrient deficiencies. IDA was defined as having both haemoglobin levels of <110 g/L and ferritin levels of < 12 µg/L. Data analysis was performed by applying univariate and multivariate techniques using logistic regression through SPSS. FINDINGS: A total of 7138 children aged between 6-59 months were included in the analysis. The prevalence of IDA was 33.2%. In multivariate regression analysis adjusted odds ratios (AOR) were calculated. Age < 24 months (AOR 1.40, 95% CI 1.18-1.55 p <0.05), stunting (AOR 1.42 CI 1.23-1.63 p<0.05), presence of clinical anemia (AOR 5.69 CI 4.93-6.56 p<0.05), having a mother with IDA (AOR 1.72 CI 1.47-2.01 p<0.05) and household food insecurity (AOR 1.20 CI 1.10-1.40 P<0.05) were associated with IDA. Living in a rural area (AOR 0.77 CI 0.65-0.90 p<0.05) and being a female child (AOR 0.87 CI 0.76-0.98 p<0.05) were associated with reduced odds of IDA. CONCLUSION: The prevalence of IDA amongst Pakistani children represents a moderate burden that disproportionately affects the youngest, growth retarded children, affected children are more likely to have mothers with IDA and live in areas where food security is lacking. National efforts to alleviate the burden of IDA should involve both short term vertical programs such as iron supplementation and long term horizontal programs including wheat flour fortification.

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.

A comparison of disease caused by Shigella and Campylobacter species: 24 months community based surveillance in 4 slums of Karachi, Pakistan.

Despite the efforts of the international community diarrheal diseases still pose a major threat to children in children less than five years of age. Bacterial diarrhea has also emerged as a public health concern due to the proliferation of drug resistant species in many parts of the world. There is a paucity of population-based data about the incidence of shigellosis and Campylobacter infections in Pakistan. We report country specific results for Shigella diarrhea that were derived from a multicenter study conducted in six Asian countries. Disease surveillance was conducted over a 24 month period in urban slums of Karachi, Pakistan, a city with a population of 59,584. Cases were detected through passive detection in study treatment centers. Stool specimens or rectal swabs were collected from all consenting patients. Between January 2002 and December 2003 10,540 enteric infection cases were detected. The incidence rate of treated diarrhea in children under 5 was 488/1000/year. In children, 5 years and older, the diarrhea rate was 22/1000/year. 576 (7%) Campylobacter isolates were detected. The pre-dominant Campylobacter species was C. jenuni with an increase of 29/1000 year in children under 5 years. Shigella species were isolated from 394 of 8032 children under 5 years of age. Shigella flexneri was the dominant species (10/1000/year in children under 5 years) followed by Shigella sonnei (3.9/1000/year), Shigella boydii (2.0/1000/year) and Shigella dysenteriae (1.3/1000/year). Shigellosis and Campylobacter infection rates peaked during the second year of life. The incidence rate of shigellosis increased in old age but such a trend was not observed in Campylobacter infections. Of 394 shigellosis patients 123 (31%) presented with dysentery in contrast to only 54 (9%) of 576 patients with Campylobacter infections (p<0.001). Both Campylobacter infections and shigellosis are common in community settings of Pakistan but shigellosis presented more frequently with abdominal pain and dysentery than Campylobacter infections indicating that shigellosis may be a more severe illness than Campylobacter infections. Due to the increased and disease severity, drug resistant shigella have become a significant health problem; moreover it is a disease of poor and impoverished people who do not have the access to standard water and sanitary conditions, health care services or optimal treatment. In the face of these facts it is empirically important to develop a low cost effective vaccine that can protect these populations for a longer duration.