Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. Non-diarrheal stool samples (N=22,846) from 1253 children from multiple sites were evaluated for a panel of 40 enteropathogens and fecal concentrations of myeloperoxidase, alpha-1-antitrypsin, and neopterin. Among these same children, urinary lactulose:mannitol (L:M) (N=6363) and plasma alpha-1-acid glycoprotein (AGP) (N=2797) were also measured. The temporal sampling design was used to create a directed acyclic graph of proposed mechanistic pathways between enteropathogen detection in non-diarrheal stools, biomarkers of intestinal permeability and inflammation, systemic inflammation and change in length- and weight- for age in children 0-2years of age. Children in these populations had frequent enteric infections and high levels of both intestinal and systemic inflammation. Higher burdens of enteropathogens, especially those categorized as being enteroinvasive or causing mucosal disruption, were associated with elevated biomarker concentrations of gut and systemic inflammation and, via these associations, indirectly associated with both reduced linear and ponderal growth. Evidence for the association with reduced linear growth was stronger for systemic inflammation than for gut inflammation; the opposite was true of reduced ponderal growth. Although Giardia was associated with reduced growth, the association was not mediated by any of the biomarkers evaluated. The large quantity of empirical evidence contributing to this analysis supports the conceptual model of EE. The effects of EE on growth faltering in young children were small, but multiple mechanistic pathways underlying the attribution of growth failure to asymptomatic enteric infections had statistical support in the analysis. The strongest evidence for EE was the association between enteropathogens and linear growth mediated through systemic inflammation. Bill & Melinda Gates Foundation.

Introduction: Anemia remains a global public health problem, especially in developing countries. It affects primarily children under five (CU5), women of reproductive age (WRA), and pregnant women due to their higher need for iron. The most common form of anemia is iron-deficiency anemia (IDA). IDA is estimated to cause half of all anemia cases and one million deaths per year worldwide. However, there remains a lack of well-documented and biochemically assessed prevalence of IDA based on the representative population-based samples globally and regionally. In this study, we aimed to assess the National Nutrition Survey (NNS) 2018 to identify the prevalence and risk factors of IDA in Pakistani CU5 and WRA. Methods: Secondary analysis was conducted on the NNS 2018, a cross-sectional survey, which collected data on dietary practices, malnutrition, and food insecurity. Anemia was defined as hemoglobin levels < 11.0 g/dL in children and 12.0 g/dL in women. IDA was defined as low hemoglobin and low ferritin (<12 ng/mL) levels, adjusted for inflammation using AGP and CRP biomarkers in CU5 and WRA. Univariate and multivariable logistic regressions were conducted using Stata statistical software (version 16). We also compared the IDA rates of NNS 2018 and 2011. Results: A total of 17,814 CU5 and 22,114 WRA were included in the analysis. Of the CU5, 28.9% had IDA, while 18.4% of WRA reported to experience IDA. Among the CU5, IDA was most prevalent among male children aged 6–23 months living in rural areas and with the presence of diarrhea and fevers in the last 2 weeks. Children whose mothers had no education, were aged 20–34 years, and employed, had a higher prevalence of IDA. Married WRA, who are employed, living in rural areas, and with no education, had a higher prevalence of IDA. In the multivariable logistic regression, children aged 6–23 months (AOR = 1.19, 95% CI [1.08–1.33], p < 0.001) and with the presence of diarrhea in the last 2 weeks (AOR = 1.32, 95% CI [1.13–1.54], p < 0.001) or fever (AOR = 1.16, 95% CI [1.02–1.32], p = 0.02) had higher odds of IDA. At the household level, the odds of IDA among CU5 were higher in the poorest households (AOR = 1.27, 95% CI [1.08–1.50], p = 0.005), with ≥5 CU5 (AOR = 1.99, 95% CI [1.28–3.11], p = 0.002), and with no access to improved sanitation facilities (AOR = 1.17, 95% CI [1.02–1.34], p = 0.026). For WRA, the multivariable logistic regression found that the odds of IDA were higher among women with vitamin A deficiency (Severe: AOR = 1.26, 95% CI [1.05–1.52], p = 0.013; Mild: AOR = 1.36, 95% CI [1.23–1.51], p < 0.001), zinc deficiency (AOR = 1.42, 95% CI [1.28–1.57], p < 0.001), no education (AOR = 1.53, 95% CI [1.30–1.81], p < 0.001), and from severely food insecure households (AOR = 1.20, 95% CI [1.07–1.34], p = 0.001). The odds of IDA were lower among women whose body mass index was overweight (AOR = 0.77, 95% CI [0.69–0.86], p < 0.001) or obese (AOR = 0.71, 95% CI [0.62–0.81], p < 0.001). Conclusions: The child’s age, presence of diarrhea or fever, place of residence, household size, wealth status, and access to sanitation facilities were significantly associated with IDA among CU5 in Pakistan. For WRA, education, body mass index, vitamin A and zinc status, household food security status, wealth status, and access to sanitation facilities were significantly associated with IDA. Large, well-established, government-funded programmes focused on micronutrient supplementation, food fortification, the diversification of food supplies, and the treatment and prevention of infectious and parasitic diseases are needed to prevent IDA and all forms of anemia among children and women in Pakistan.

Typhoid remains a major cause of morbidity and mortality in endemic countries. This review analyzed typhoid burden changes in Pakistan and its association with contextual factors. A retrospective cohort study on blood culture–positive typhoid and antibiotic resistance was conducted from three tertiary hospitals and contextual factor data obtained from primary household surveys. Salmonella Typhi/Paratyphi positivity rates were estimated and trend analysis was carried out using positive cases out of total number of blood cultures performed. Contextual factors’ associations were determined through bivariate correlation analysis, using STATA (SataCorp, College Station, TX). We report a total of 17,387 S. Typhi–positive and 8,286 S. Paratyphi A and B–positive specimens from 798,137 blood cultures performed. The results suggest an overall decline in typhoid incidence as S. Typhi positivity rates declined from 6.42% in 1992 to 1.32% in 2015 and S. Paratyphi (A and B) from 1.29% to 0.39%. Subgroup analysis suggests higher S. Typhi prevalence in adults older than 18 years, whereas S. Paratyphi is greater in children aged 5–18 years. The relative contribution of S. Paratyphi to overall confirmed cases increased from 16.8% in 1992 to 23% in 2015. The analysis suggests high burden of fluoroquinolone resistance and multidrug-resistant S. Typhi strains. Statistically significant associations of water, sanitation indicators, and literacy rates were observed with typhoid positivity. Despite some progress, typhoid remains endemic and a strong political will is required for targeted typhoid control strategies. A multipronged approach of improving water, sanitation and hygiene in combination with large-scale immunization in endemic settings of Pakistan could help reduce burden and prevent epidemics.

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.

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.

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. 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. 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 %. 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.