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BackgroundBiannual vitamin A supplementation is a well-established survival tool for preschool children 6 months and older in vitamin A deficient populations but this schedule misses the opportunity to intervene on most young infant deaths. Randomised trials of neonatal vitamin A supplementation (NVAS) in the first few days of life to assess its impact on under 6-month mortality in low/middle-income countries have had varying results.MethodsInvestigators of 11 published randomised placebo-controlled NVAS trials (n=163 567 children) reanalysed their data according to an agreed plan and pooled the primary outcomes of mortality from supplementation through 6 and 12 months of age using random effects models and meta-regression. One investigator withdrew but allowed use of the data.FindingsOverall there was no effect of NVAS on infant survival through 6 (risk ratio (RR) 0.97; 95% CI 0.89 to 1.06) or 12 months of age (RR 1.00; 95% CI 0.93 to 1.08) but results varied by study population characteristics.NVAS significantly reduced 6-month mortality among the trials conducted in Southern Asia (RR 0.87; 95% CI 0.77 to 0.98), in contexts with moderate or severe vitamin A deficiency (defined as 10% or higher proportion of women with serum retinol 32% mothers had no schooling (RR 0.88; 95% CI 0.80 to 0.96). NVAS did not reduce mortality in the first 6 months of life in trials conducted in Africa, in contexts characterised by a low prevalence of vitamin A deficiency, lower rates of infant mortality and where maternal education was more prevalent. There was a suggestion of increased infant mortality in trials conducted in Africa (RR 1.07; 95% CI 1.00 to 1.15).Individual-level characteristics such as sex, birth weight, gestational age and size, age at dosing, parity, time of breast feeding initiation, maternal education and maternal vitamin A supplementation did not modify the impact of NVAS.ConclusionNVAS reduced infant mortality in South Asia, in contexts where the prevalence of maternal vitamin A deficiency is moderate to severe and early infant mortality is high; but it had no beneficial effect on infant survival in Africa, in contexts where the prevalence of maternal vitamin A deficiency is lower, early infant mortality is low.

BACKGROUND: Pakistan is one of the 3 remaining wild poliovirus endemic countries. We collected sera from children to assess the prevalence of poliovirus antibodies in selected high-risk areas for poliovirus transmission. METHODS: Children in 2 age groups (6–11 and 36–48 months) were randomly selected between November 2015 and March 2016 in 6 areas of Pakistan (Sindh Province: Karachi and Kashmore; Khyber Pakhtunkhwa Province: Peshawar, Bannu and Nowshera; Punjab Province: Faisalabad). After obtaining informed consent, basic demographic and vaccination history data were collected, 1 peripheral venipuncture was obtained, and assays to detect poliovirus (PV)–neutralizing antibodies were performed. RESULTS: A total of 1301 children were enrolled and had peripheral blood drawn that analyzed. Study subjects were evenly distributed among survey sites and age groups. Anti-polio seroprevalence differed significantly among geographic areas (P < 0.001); in the 6–11 months group, it ranged between 89% and 98%, 58% and 95%, and 74% and 96% for PV serotypes 1, 2 and 3, respectively; in 36–48 months group, it ranged between 99% and 100%, 95% and 100%, and 92% and 100% for PV 1, 2, and 3, respectively. Having received inactivate poliovirus vaccine, malnourishment (stunting) and educational level of parents were found to be associated with presence of anti-polio antibodies. CONCLUSION: The polio eradication program achieved overall high serologic protection; however, immunity gaps in young children in the high polio risk areas remain. These gaps enable sustained circulation of wild poliovirus type 1, and pose risk for emergence of vaccine-derived polioviruses. Focusing on the lowest socioeconomic strata of society, where malnutrition is most prevalent, could accelerate poliovirus eradication.

Summary Background Progress in reproductive, maternal, newborn, and child health (RMNCH) in Kenya has been inconsistent over the past two decades, despite the global push to foster accountability, reduce child mortality, and improve maternal health in an equitable manner. Although several cross-sectional assessments have been done, a systematic analysis of RMNCH in Kenya was needed to better understand the push and pull factors that govern intervention coverage and influence mortality trends. As such, we aimed to determine coverage and impact of key RMNCH interventions between 1990 and 2015. Methods We did a comprehensive, systematic assessment of RMNCH in Kenya from 1990 to 2015, using data from nationally representative Demographic Health Surveys done between 1989 and 2014. For comparison, we used modelled mortality estimates from the UN Inter-Agency Groups for Child and Maternal Mortality Estimation. We estimated time trends for key RMNCH indicators, as defined by Countdown to 2015, at both the national and the subnational level, and used linear regression methods to understand the determinants of change in intervention coverage during the past decade. Finally, we used the Lives Saved Tool (LiST) to model the effect of intervention scale-up by 2030. Findings After an increase in mortality between 1990 and 2003, there was a reversal in all mortality trends from 2003 onwards, although progress was not substantial enough for Kenya to achieve Millennium Development Goal targets 4 or 5. Between 1990 and 2015, maternal mortality declined at half the rate of under-5 mortality, and changes in neonatal mortality were even slower. National-level trends in intervention coverage have improved, although some geographical inequities remain, especially for counties comprising the northeastern, eastern, and northern Rift Valley regions. Disaggregation of intervention coverage by wealth quintile also revealed wide inequities for several health-systems-based interventions, such as skilled birth assistance. Multivariable analyses of predictors of change in family planning, skilled birth assistance, and full vaccination suggested that maternal literacy and family size are important drivers of positive change in key interventions across the continuum of care. LiST analyses clearly showed the importance of quality of care around birth for maternal and newborn survival. Interpretation Intensified and focused efforts are needed for Kenya to achieve the RMNCH targets for 2030. Kenya must build on its previous progress to further reduce mortality through the widespread implementation of key preventive and curative interventions, especially those pertaining to labour, delivery, and the first day of life. Deliberate targeting of the poor, least educated, and rural women, through the scale-up of community-level interventions, is needed to improve equity and accelerate progress. Funding US Fund for UNICEF, Bill & Melinda Gates Foundation.

Since 2001 substantial resources have been allocated to the reproductive, maternal, newborn and child health sector (RMNCH) in Pakistan. Many new programmes have been started and coverage of some existing programmes has been extended to un-served and rural areas. Despite these efforts the Millennium Development Goals (MDGs) 4 and 5 were not achieved (2000-15). Maternal Mortality Ratio was reduced to 170 per 100 000 live births (target 100) by 2013 at an annual reduction rate of 3.6% (1990-2013). Against the target of 46 per 1000 live births, the Under Five Mortality Rate was reduced to 81 per 1000 live births by 2015 at an annual reduction rate of 2.1% (1990-2015). We evaluated the comparative expenditures for the RMNCH sector and analysed impact of public expenditures on the use of the public facilities for the RMNCH services. Expenditure on RMNCH increased by 181% (2000-10), reaching PKR 628.79 billion (US$9.67 billion). The Share of the RMNCH expenditure in the total health expenditure increased from 16 to 21% (2005-10). The share of official development assistance for the RMNCH increased from 36 to 51% (2003-10). Equity was modestly achieved with a greater proportion of the poor using public facilities for the childhood diarrhoea (Concentration Index -0.06 in 2001-02 to - 0.11 in 2010-11) and reduction in the proportion of the rich using the public health facilities for institutional births (Concentration Index 0.30 in 2001-02 to 0.25 in 2010-11). Overall the RMNCH disease control programmes focused on vertical primary health approach and targeted the district health system in the un-served areas. Our findings confirm that diseconomies of scale, donor dependence and supply side perspective could only result in a modest progress towards achieving the MDGs. We call for urgent attention of the policy makers for the integration of the vertical and the routine primary health care and reliance on indigenous sustainable healthcare financing. We also recommend acknowledging economic perspective on health policy and health programmes.

BackgroundDespite evidence for the benefits of vitamin A supplementation (VAS) among children 6 to 59 months of age, the feasibility of introduction and potential benefit of VAS in the neonatal period in public health programmes is uncertain.ObjectiveThe primary objective was to evaluate the feasibility and effectiveness of early neonatal VAS (single dose of 50 000 international units within 48–72 hours after birth) delivered through the public sector Lady Health Worker (LHW) programme in rural Pakistan and to document its association with a reduction in mortality at 6 months of age.MethodsA community-based, cluster randomised, placebo-controlled trial was undertaken in two districts of rural Pakistan. LHWs dispensed vitamin A/placebo in identical capsules to newborn infants within 48–72 hours of birth. Follow-up visits were undertaken at 1 week of age and every 4 weeks thereafter until 6 months of age.ResultsOf a total of 15 433 consecutive pregnancies among eligible women of reproductive age, 13 225 pregnancies were registered, 12 218 live births identified and 11 028 newborn infants reached by LHWs. Of these, 5380 (49%) received neonatal VAS and 5648 (51%) placebo. The LHWs successfully delivered the capsules to 79% of newborns within 72 hours of birth with no significant adverse effects. Although the proportion of days observed with symptoms of fever, diarrhoea or rapid breathing were lower with neonatal VAS, these differences were not statistically significant. Mortality rates in the two groups were comparable at 6 months of age.ConclusionsWhile our study demonstrated that neonatal VAS was safe and could be feasibly delivered by LHWs in Pakistan as part of their early postnatal visits, the overall lack of benefit on neonatal and 6-month morbidity and mortality in our population suggests the need for further evaluation of this intervention in populations at risk.Trial registration numberClinicalTrials.gov NCT00674089.

Summary Background After the fall of the Taliban in 2001, Afghanistan experienced a tumultuous period of democracy overshadowed by conflict, widespread insurgency, and an inflow of development assistance. Although there have been several cross-sectional assessments of health gains over the last decade, there has been no systematic analysis of progress and factors influencing maternal and child health in Afghanistan. Methods We undertook a comprehensive, systematic assessment of reproductive, maternal, newborn, and child health in Afghanistan over the last decade. Given the paucity of high-quality data before 2001, we relied mainly on 11 nationally representative surveys conducted between 2003 and 2013. We estimated national and subnational time trends for key reproductive, maternal, and child health indicators, and used linear regression methods to determine predictors of change in health-care service use. All analyses were weighted for sampling and design effects. Additional information was collated and analysed about health system performance from third party surveys and about human resources from the Afghan Ministry of Public Health. Findings Between 2003 and 2015, Afghanistan experienced a 29% decline in mortality of children younger than 5 years. Although definite reductions in maternal mortality remain uncertain, concurrent improvements in essential maternal health interventions suggest parallel survival gains in mothers. In a little over a decade (2003–13 inclusive), coverage of several maternal care interventions increased—eg, for antenatal care (16% to 53%), skilled birth attendance (14% to 46%), and births in a health facility (13% to 39%). Childhood vaccination coverage rates for the basic vaccines from the Expanded Programme of Immunisation (eg, BCG, measles, diphtheria-tetanus-pertussis, and three doses of polio) doubled over this period (about 40% to about 80%). Between 2005 and 2013, the number of deployed facility and community-based health-care professionals also increased, including for nurses (738 to 5766), midwives (211 to 3333), general physicians (403 to 5990), and community health workers (2682 to 28 837). Multivariable analysis of factors contributing to overall changes in skilled birth attendance and facility births suggests independent contributions of maternal literacy, deployment of community midwives, and proximity to a facility. Interpretation Despite conflict and poverty, Afghanistan has made reasonable progress in its reproductive, maternal, newborn, and child health indicators over the last decade based on contributions of factors within and outside the health sector. However, equitable access to health care remains a challenge and present delivery models have high transactional costs, affecting sustainability. To maintain and further accelerate health and development gains, future strategies in Afghanistan will need to focus on investments in improving social determinants of health and targeted cost-effective interventions to address major causes of maternal and newborn mortality. Funding US Fund for UNICEF under the Countdown to 2015 for Maternal, Newborn, and Child Survival grant from the Bill & Melinda Gates Foundation, and from the Government of Canada, Foreign Affairs, Trade and Development Canada. Additional direct and in-kind support was received from the UNICEF Country Office Afghanistan, the Centre for Global Child Health, the Hospital for Sick Children, Toronto, the Aga Khan University, and Mother and Child Care Trust (Pakistan).

Objective To estimate the cost-effectiveness of price subsidies on fortified packaged complementary foods (FPCF) in reducing iodine deficiency, iron-deficiency anaemia and Vitamin A deficiency in Pakistani children.Design The study proceeded in three steps: (i) we determined the current lifetime costs of the three micronutrient deficiencies with a health economic model; (ii) we assessed the price sensitivity of demand for FPCF with a market survey in two Pakistani districts; (iii) we combined the findings of the first two steps with the results of a systematic review on the effectiveness of FPCF in reducing micronutrient deficiencies. The cost-effectiveness was estimated by comparing the net social cost of price subsidies with the disability-Adjusted life years (DALY) averted.Setting Districts of Faisalabad and Hyderabad in Pakistan.Subjects Households with 6-23-month-old children stratified by socio-economic strata.Results The lifetime social costs of iodine deficiency, iron-deficiency anaemia and Vitamin A deficiency in 6-23-month-old children amounted to production losses of US 209 million and 175 000 DALY. Poor households incurred the highest costs, yet even wealthier households suffered substantial losses. Wealthier households were more likely to buy FPCF. The net cost per DALY of the interventions ranged from a return per DALY averted of US 783 to US 65. Interventions targeted at poorer households were most cost-effective.Conclusions Price subsidies on FPCF might be a cost-effective way to reduce the societal costs of micronutrient deficiencies in 6-23-month-old children in Pakistan. Interventions targeting poorer households are especially cost-effective., Public Health Nutrition, 21 (15), ISSN:1368-9800, ISSN:1475-2727

Reaching high population immunity against polioviruses (PV) is essential to achieving global polio eradication. Efficacy of oral poliovirus vaccine (OPV) varies and is lower among children living in tropical areas with impoverished environments. Malnutrition found as a risk factor for lower serological protection against PV. We compared whether inactivated polio vaccine (IPV) can be used to rapidly close the immunity gap among chronically malnourished (stunted) infants in Pakistan who will not be eligible for the 14 week IPV dose in routine EPI schedule. A phase 3, multicenter 4-arm randomized controlled trial conducted at five Primary Health Care (PHC) centers in Karachi, Pakistan. Infants, 9–12 months were stratified by length for age Z score into chronically malnourished and normally nourished. Infants were randomized to receive one dose of either bivalent OPV (bOPV) alone or bOPV + IPV. Baseline seroprevalence of PV antibodies and serum immune response to study vaccine dose were assessed by neutralization assay. Vaccine PV shedding in stool was evaluated 7 days after a bOPV challenge dose. Sera and stool were analyzed from 852/928 (92%) enrolled children. At baseline, the seroprevalence was 85.6% (n = 386), 73.6% (n = 332), and 70.7% (n = 319) in malnourished children against PV types 1, 2 and 3 respectively; and 94.1% (n = 448), 87.0% (n = 441) and 83.6% (n = 397) in the normally nourished group (p

Summary: Background: Undernutrition is a pervasive condition in Afghanistan, and prevalence is among the highest in the world. We aimed to comprehensively assess district-level geographical disparities and determinants of nutritional status (stunting, wasting, or underweight) among women and children in Afghanistan. Methods: The study used individualised data from the recent Afghanistan National Nutrition Survey 2013. Outcome variables were based on growth and weight anthropometry data, which we analysed linearly as Z scores and as dichotomous categories. We analysed data from a total of almost 14 000 index mother–child pairs using Bayesian spatial and generalised least squares regression models accounting for the complex survey design. Findings: We noted that childhood stunting, underweight, and combined stunting and wasting were consistently highest in districts in Farah, Nangarhar, Nuristan, Kunar, Paktia, and Badakhshan provinces. District prevalence ranged from 4% to 84% for childhood stunting and 5% to 66% for underweight. Child wasting exceeded 20% in central and high-conflict regions that bordered Pakistan including east, southeast, and south. Among mothers, dual burden of underweight and overweight or obesity existed in districts of north, northeast, central, and central highlands (prevalence of 15–20%). Linear growth and weight of children were independently associated with household wealth, maternal literacy, maternal anthropometry, child age, food security, geography, and improved hygiene and sanitation conditions. The mother's body-mass index was determined by many of the same factors, in addition to ethnolinguistic status and parity. Younger mothers (

Food and Nutrition Bulletin, 38 (4), ISSN:0379-5721, ISSN:1564-8265

The Pakistan study site of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study is located in Molhan union council of Naushahro Feroze district in the Sindh province. The study site is located in a rural district, where the majority of the population has an agrarian livelihood. Most families are nuclear families and the average household has 7 persons. More than half the women in the region have no formal education, and the median parity is 6. Only 48%-61% of the households across the district, province, and country have access to an improved toilet facility. Similar to the provincial and national estimates, the district has a low rate of exclusive breastfeeding at 6 months, and the prevalence of prelacteal feeding is high. There is also a high proportion of malnourished children. In addition, the acute respiratory infection and diarrheal illness burden and the mortality rates in children

This survey study evaluates associations of conflict severity with improvement of health system performance, use of health services, and child nutrition outcomes in Afghanistan during the 2003 to 2018 reconstruction period., Key Points Question Is conflict severity associated with the performance of health systems and population health outcomes in Afghanistan during the 2003 to 2018 reconstruction period? Findings In this survey study of 64 815 women in Afghanistan, notable health and health system improvements were made despite increasing conflict after 2010. However, regions with greater conflict had lower gains in contraceptive use, skilled birth attendance, and child vaccination and increased child wasting, as well as poor health facility infrastructure, client background and physical assessments, and health care professionals’ knowledge level. Meaning These findings suggest that efforts to improve contraceptive use, measles vaccination, and functioning health service infrastructure should be prioritized in provinces of Afghanistan that experience severe conflict., Importance Current studies examining the effects of Afghanistan’s conflict transition on the performance of health systems, health service delivery, and health outcomes are outdated and small in scale and do not span all essential reproductive, maternal, newborn, and child health interventions. Objective To evaluate associations of conflict severity with improvement of health system performance, use of health services, and child nutrition outcomes in Afghanistan during the 2003 to 2018 reconstruction period. Design, Setting, and Participants This population-based survey study included a sequential cross-sectional analysis of individual-level panel data across 2 periods (2003-2010 and 2010-2018) and a difference-in-differences design. Surveys included the 2003 to 2004 and 2010 to 2011 Multiple Indicator Cluster Surveys and the 2018 Afghanistan Health Survey. Afghanistan’s 2013 National Nutrition Survey was used to assess nutritional outcomes, and the annual Balanced Scorecard data sets were used to evaluate health system performance. Participants included girls and women aged 12 to 49 years and children younger than 5 years who completed nationally representative household surveys. All analyses were conducted from January 1 through April 30, 2019. Exposures Provinces were categorized as experiencing minimal-, moderate-, and severe-intensity conflict using battle-related death data from the Uppsala Conflict Data Program. Main Outcomes and Measures Health intervention coverage was examined using 10 standard indicators: contraceptive method (any or modern); antenatal care by a skilled health care professional; facility delivery; skilled birth attendance (SBA); bacille Calmette-Guérin vaccination (BCG); diphtheria, pertussis, and tetanus vaccination (DPT3) or DPT3 plus hepatitis B and poliomyelitis (penta); measles vaccination; care-seeking for acute respiratory infection; oral rehydration therapy for diarrhea; and the Composite Coverage Index. The health system performance was analyzed using the following standard Balanced Scorecard composite domains: client and community, human resources, physical capacity, quality of service provision, management systems, and overall mission. Child stunting, wasting, underweight, and co-occurrence of stunting and wasting were estimated using World Health Organization growth reference cutoffs. Results Responses from 64 815 women (mean [SD] age, 31.0 [8.5] years) were analyzed. Provinces with minimal-intensity conflict had greater gains in contraceptive use (mean annual percentage point change [MAPC], 1.3% vs 0.5%; P

The South Asian Association for Regional Cooperation (SAARC) is an organization of eight countries--Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, Sri Lanka and Afghanistan. The major objectives of this review are to examine trends and progress in newborn and neonatal health care in the region. A landscape analysis of the current state of neonatal mortality, stillbirths and trends over the years for each country and the effective interventions to reduce neonatal mortality and stillbirths was undertaken. A modelling exercise using the Lives Saved Tool (LiST) was also undertaken to determine the impact of scaling up a set of essential interventions on neonatal mortality and stillbirths. The findings demonstrate that there is an unacceptably high and uneven burden of neonatal mortality and stillbirths in the region which together account for 39% of global neonatal deaths and 41% of global stillbirths. Progress is uneven across countries in the region, with five of the eight SAARC countries having reduced their neonatal mortality rate by more than 50% since 1990, while India (43%), Afghanistan (29%) and Pakistan (25%) have made slower progress and will not reach their MDG4 targets. The major causes of neonatal mortality are intrapartum-related deaths, preterm birth complications and sepsis which account for nearly 80% of all deaths. The LiST analysis shows that a gradual increase in coverage of proven available interventions until 2020 followed by a uniform scale-up to 90% of all interventions until 2030 could avert 52% of neonatal deaths (0.71 million), 29% of stillbirths (0.31 million) and achieve a 31% reduction in maternal deaths (0.25 million). The analysis demonstrates that the Maldives and Sri Lanka have done remarkably well while other countries need greater attention and specific focus on strategies to improve neonatal health.

Summary Background Pakistan has one of the highest levels of child and maternal undernutrition worldwide, but little information about geographical and socioeconomic inequalities is available. We aimed to analyse anthropometric indicators for childhood and maternal nutrition at a district level in Pakistan and assess the association of nutritional status with food security and maternal and household socioeconomic factors. Methods We used data from the 2011 Pakistan National Nutrition Survey, which included anthropometric measurements for 33 638 children younger than 5 years and 24 826 women of childbearing age. We estimated the prevalences of stunting, wasting, and underweight among children and of underweight, overweight, and obesity in women for all 143 districts of Pakistan using a Bayesian spatial technique. We used a mixed-effect linear model to analyse the association of nutritional status with individual and household sociodemographic factors and food security. Findings Stunting prevalence in Pakistan's districts ranged between 22% (95% credible interval 19–26) and 76% (69–83); the lowest figures for wasting and underweight were both less than 2·5% and the highest were 42% (34–50) for wasting and 54% (49–59) for underweight. In 106 districts, more women were overweight than were underweight; in 49 of these districts more women were obese than were underweight. Children were better nourished if their mothers were taller or had higher weight, if they lived in wealthier households, and if their mothers had 10 or more years of education. Severe food insecurity was associated with worse nutritional outcomes for both children and women. Interpretation We noted large social and geographical inequalities in child and maternal nutrition in Pakistan, masked by national and provincial averages. Pakistan is also beginning to face the concurrent challenge of high burden of childhood undernutrition and overweight and obesity among women of reproductive age. Planning, implementation, and evaluation of programmes for food and nutrition should be based on district-level needs and outcomes. Funding Bill & Melinda Gates Foundation, Grand Challenges Canada, UK Medical Research Council.

Background Globally, clinical certification of the cause of neonatal death is not commonly available in developing countries. Under such circumstances it is imperative to use available WHO verbal autopsy tool to ascertain causes of death for strategic health planning in countries where resources are limited and the burden of neonatal death is high. The study explores the diagnostic accuracy of WHO revised verbal autopsy tool for ascertaining the causes of neonatal deaths against reference standard diagnosis obtained from standardized clinical and supportive hospital data. Methods All neonatal deaths were recruited between August 2006 –February 2008 from two tertiary teaching hospitals in Province Sindh, Pakistan. The reference standard cause of death was established by two senior pediatricians within 2 days of occurrence of death using the International Cause of Death coding system. For verbal autopsy, trained female community health worker interviewed mother or care taker of the deceased within 2–6 weeks of death using a modified WHO verbal autopsy tool. Cause of death was assigned by 2 trained pediatricians. The performance was assessed in terms of sensitivity and specificity. Results Out of 626 neonatal deaths, cause-specific mortality fractions for neonatal deaths were almost similar in both verbal autopsy and reference standard diagnosis. Sensitivity of verbal autopsy was more than 93 % for diagnosing prematurity and 83.5 % for birth asphyxia. However the verbal autopsy didn’t have acceptable accuracy for diagnosing the congenital malformation 57 %. The specificity for all five major causes of neonatal deaths was greater than 90 %. Conclusion The WHO revised verbal autopsy tool had reasonable validity in determining causes of neonatal deaths. The tool can be used in resource limited community-based settings where neonatal mortality rate is high and death certificates from hospitals are not available.

Summary Background Supplementary immunisation activities with oral poliovirus vaccines (OPVs) are usually separated by 4 week intervals; however, shorter intervals have been used in security-compromised areas and for rapid outbreak responses. We assessed the immunogenicity of monovalent type-1 oral poliovirus vaccine (mOPV1) given at shorter than usual intervals in Karachi, Pakistan. Methods This was a multicentre, randomised, controlled, four-arm, open-label, non-inferiority trial done at five primary health-care centres in low-income communities in and around Karachi, Pakistan. Eligible participants were healthy newborn babies with a birthweight of at least 2·5 kg, for whom informed consent was provided by their parent or guardian, and lived less than 30 km from the study clinic. After receiving a birth dose of trivalent OPV, we enrolled and randomly assigned newborn babies (1:1:1:1) to receive two doses of mOPV1 with an interval of 1 week (mOPV1–1 week), 2 weeks (mOPV1–2 weeks), or 4 weeks (mOPV1–4 weeks) between doses, or two doses of bivalent OPV (bOPV) with an interval of 4 weeks between doses (bOPV–4 weeks). We gave the first study dose of OPV at age 6 weeks. We did the randomisation with a centrally generated, computerised allocation sequence with blocks of 16; participants' families and study physicians could not feasibly be masked to the allocations. Trial participants were excluded from local supplementary immunisation activities during the study period. The primary outcome was non-inferiority (within a 20% margin) between groups in seroconversion to type-1 poliovirus. The primary and safety analyses were done in the per-protocol population of infants who received all three doses of vaccine. This trial is registered with ClinicalTrials.gov, number NCT01586572, and is closed to new participants. Findings Between March 1, 2012, and May 31, 2013, we enrolled 1009 newborn babies, and randomly assigned 829 (82%) to treatment. 554 (67%) of the 829 babies were included in the per-protocol analysis. Proportions of seroconversion to type-1 poliovirus were 107/135 (79%, 95% CI 72·4–86·1) with mOPV1–1 week, 108/135 (80%, 73·2–86·8) with mOPV1–2 weeks, 129/148 (87%, 80·9–92·0) with mOPV1–4 weeks, and 107/136 (79%, 71·8–85·6) with bOPV–4 weeks. Non-inferiority was shown between groups and no significant differences were noted. Ten participants died during the trial. Seven of these deaths occurred during the lead-in period before randomisation (two from diarrhoea, five from unknown causes). Three infants died from sepsis after random assignment. No deaths were attributed to the procedures or vaccines. Additionally, we noted no events of vaccine-associated paralysis. Interpretation We identified no significant differences in responses to mOPV1 given with shorter intervals between doses than with the standard 4 week intervals. The short-interval strategy could be particularly beneficial when temporary windows of opportunity for safe access can be granted in areas of conflict—eg, during cease-fire periods. In such situations, we recommend shortening the interval between OPV doses to 7 days. Funding World Health Organization.

Adequacy of zinc intake from breast milk alone becomes marginal in relation to infant requirements by around 6 mo of age. Simple and cost-effective strategies are needed at the population level to ensure adequate intakes of zinc in infants and toddlers in populations at risk of zinc deficiency. We determined the amount of absorbed zinc (AZ) from a micronutrient powder (MNP) without and with 10 mg of zinc (MNP+Zn) added to local complementary foods used in Pakistan and the impact on the exchangeable zinc pool (EZP) size. As a nested study within a large, prospective, cluster randomized trial, 6-mo-old infants were randomly assigned to receive MNP or MNP+Zn. Stable isotope methodology was applied after ∼3 and 9 mo of use to measure AZ from MNP-fortified test meals of rice-lentils (khitchri) and EZP. Nineteen infants per group completed the first metabolic studies and 14 and 17 infants in the MNP and MNP+Zn groups, respectively, completed the follow-up studies. AZs were (mean ± SD) 0.1 ± 0.1 and 1.2 ± 0.5 mg at the first point for the MNP and MNP+Zn groups, respectively (P < 0.001); results were nearly identical at the follow-up measurement. EZP did not differ between groups at the first measurement but was less in the MNP group (3.7 ± 0.6 mg/kg) than in the MNP+Zn group (4.5 ± 1.0 mg/kg) at the second measurement (P = 0.01). These data confirm that the MNP+Zn in khitchri were well absorbed and after 1 y of home fortification, zinc status assessed by EZP was significantly better for the MNP+Zn group. Additional field studies may be necessary to ascertain the adequacy of this dose for infants at high risk of deficiency. This trial was registered at ClinicalTrials.gov as NCT00705445.

Diarrhea causes 16% of all child deaths in Pakistan. We assessed patterns of healthcare use among caretakers of a randomly selected sample of 959 children ages 0–59 months in low-income periurban settlements of Karachi through a cross-sectional survey. A diarrheal episode was reported to have occurred in the previous 2 weeks among 298 (31.1%) children. Overall, 280 (80.3%) children sought care. Oral rehydration solution and zinc were used by 40.8% and 2%, respectively; 11% were admitted or received intravenous rehydration, and 29% sought care at health centers identified as sentinel centers for recruiting cases of diarrhea for a planned multicenter diarrheal etiology case-control study. Odds ratios for independent predictors of care-seeking behavior were lethargy, 4.14 (95% confidence interval = 1.45–11.77); fever, 2.67 (1.27–5.59); and stool frequency more than six per day, 2.29 (1.03–5.09). Perception of high cost of care and use of home antibiotics were associated with reduced care seeking: odds ratio = 0.28 (0.1–0.78) and 0.29 (0.11–0.82), respectively. There is a need for standardized, affordable, and accessible treatment of diarrhea as well as community education regarding appropriate care in areas with high diarrheal burden.

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