BackgroundA major limitation to understanding the etiopathogenesis of environmental enteric dysfunction (EED) is the lack of a comprehensive, reproducible histologic framework for characterizing the small bowel lesions. We hypothesized that the development of such a system will identify unique histology features for EED, and that some features might correlate with clinical severity. Data Availability Statement: All relevant analyses are within the manuscript and its Supporting was assessed. The histology index was further used to identify within-and between-child variations as well as features common across and unique to each cohort, and those that correlated with host phenotype. ResultsEight of the 11 histologic scoring parameters showed useful degrees of variation. The overall concordance across all parameters was 96% weighted agreement, kappa 0.70, and Gwet's AC 0.93. Zambian and Pakistani tissues shared some histologic features with GSE, but most features were distinct, particularly abundance of intraepithelial lymphocytes in the Pakistani cohort, and marked villous destruction and loss of secretory cell lineages in the Zambian cohort. ConclusionsWe propose the first EED histology index for interpreting duodenal biopsies. This index should be useful in future clinical and translational studies of this widespread, poorly understood, and highly consequential disorder, which might be caused by multiple contributing processes, in different regions of the world. Author summaryThe study of EED has been limited by the lack of a rigorously tested, reproducible histology index that can provide insight to the pathogenesis of this entity. In this study we report the first duodenal histology index that was developed using an unbiased approach, with excellent inter-observer reproducibility, for the study of EED. The EED histology index readily identified histologic features that are common or unique to cohorts of distinct geographic locations. Incorporating the histology index into future clinical studies will provide useful insight into the pathogenesis and for intervention strategy development.

BackgroundMore than 450 newborns die every hour worldwide, before they reach the age of four weeks (neonatal period) and over 500,000 women die from complications related to childbirth. The major direct causes of neonatal death are infections (36%), Prematurity (28%) and Asphyxia (23%). Pakistan has one of the highest perinatal and neonatal mortality rates in the region and contributes significantly to global neonatal mortality. The high mortality rates are partially attributable to scarcity of trained skilled birth attendants and paucity of resources. Empowerment of health care providers with adequate knowledge and skills can serve as instrument of change.MethodsWe carried out training needs assessment analysis in the public health sector of Pakistan to recognize gaps in the processes and quality of MNCH care provided. An assessment of Knowledge, Attitude, and Practices of Health Care Providers on key aspects was evaluated through a standardized pragmatic approach. Meticulously designed tools were tested on three tiers of health care personnel providing MNCH in the community and across the public health care system. The Lady Health Workers (LHWs) form the first tier of trained cadre that provides MNCH at primary care level (BHU) and in the community. The Lady Health Visitor (LHVs), Nurses, midwives) cadre follow next and provide facility based MNCH care at secondary and tertiary level (RHCs, Taluka/Tehsil, and DHQ Hospitals). The physician/doctor is the specialized cadre that forms the third tier of health care providers positioned in secondary and tertiary care hospitals (Taluka/Tehsil and DHQ Hospitals). The evaluation tools were designed to provide quantitative estimates across various domains of knowledge and skills. A priori thresholds were established for performance rating.ResultsThe performance of LHWs in knowledge of MNCH was good with 30% scoring more than 70%. The Medical officers (MOs), in comparison, performed poorly in their knowledge of MNCH with only 6% scoring more than 70%. All three cadres of health care providers performed poorly in the resuscitation skill and only 50% were able to demonstrate steps of immediate newborn care. The MOs performed far better in counselling skills compare to the LHWs. Only 50 per cent of LHWs could secure competency scale in this critical component of skills assessment.ConclusionsAll three cadres of health care providers performed well below competency levels for MNCH knowledge and skills. Standardized training and counselling modules, tailored to the needs and resources at district level need to be developed and implemented. This evaluation highlighted the need for periodic assessment of health worker training and skills to address gaps and develop targeted continuing education modules. To achieve MDG4 and 5 goals, it is imperative that such deficiencies are identified and addressed.

ObjectiveTo determine the prevalence and possible factors associated with anaemia, and vitamin B12 and folate deficiencies in women of reproductive age (WRA) in Pakistan.MethodsA secondary analysis was conducted on data collected through the large-scale National Nutrition Survey in Pakistan in 2011. Anaemia was defined as haemoglobin levels <12 g/dL, vitamin B12 deficiency as serum vitamin B12 levels of <203 pg/mL (150 pmol/L) and folate deficiency as serum folate levels <4 ng/mL (10 nmol/L).ResultsA total of 11 751 blood samples were collected and analysed. The prevalence of anaemia, vitamin B12 deficiency and folate deficiency was 50.4%, 52.4% and 50.8%, respectively. After adjustment, the following factors were positively associated with anaemia: living in Sindh province (RR 1.07; 95% CI 1.04 to 1.09) P<0.00, food insecure with moderate hunger (RR 1.03; 95% CI 1.00 to 1.06) P=0.02, four or more pregnancies (RR 1.03; 95% CI 1.01 to 1.05) P<0.00, being underweight (RR 1.03; 95% CI 1.00 to 1.05) P=0.02, being overweight or obese (RR 0.95; 95% CI 0.93 to 0.97) P<0.00 and weekly intake of leafy green vegetables (RR 0.98; 95% CI 0.95 to 1.00) P=0.04. For vitamin B12 deficiency, a positive association was observed with rural population (RR 0.81; 95% CI 0.66 to 1.00) P=0.04, living in Khyber Pakhtunkhwa province (RR 1.25; 95% CI 1.11 to 1.43) P<0.00 and living in Azad Jammu and Kashmir (RR 1.50; 95% CI 1.08 to 2.08) P=0.01. Folate deficiency was negatively associated with daily and weekly intake of eggs (RR 0.89; 95% CI 0.81 to 0.98) P=0.02 and (RR 0.88; 95% CI 0.78 to 0.99) P=0.03.ConclusionsIn Pakistan, anaemia, and vitamin B12 and folate deficiencies are a severe public health concern among WRA. Our findings suggest that further research is needed on culturally appropriate short-term and long-term interventions within communities and health facilities to decrease anaemia, and vitamin B12 and folate deficiencies among Pakistani women.

Environmental Enteric Dysfunction (EED), a syndrome characterized by chronic gut inflammation, contributes towards stunting and poor response to enteric vaccines in children in developing countries. In this study, we evaluated major putative biomarkers of EED using growth faltering as its clinical proxy. Newborns (n = 380) were enrolled and followed till 18 months with monthly anthropometry. Biomarkers associated with gut and systemic inflammation were assessed at 6 and 9 months. Linear mixed effects model was used to determine the associations of these biomarkers with growth faltering between birth and 18 months. Fecal myeloperoxidase (neutrophil activation marker) at 6 months [β = −0.207, p = 0.005], and serum GLP 2 (enterocyte proliferation marker) at 6 and 9 months [6M: β = −0.271, p = 0.035; 9M: β = −0.267, p = 0.045] were associated with decreasing LAZ score. Ferritin at 6 and 9 months was associated with decreasing LAZ score [6M: β = −0.882, p < 0.0001; 9M: β = −0.714, p < 0.0001] and so was CRP [β = −0.451, p = 0.039] and AGP [β = −0.443, p = 0.012] at 9 months. Both gut specific and systemic biomarkers correlated negatively with IGF-1, but only weakly correlated, if at all with each other. We therefore conclude that EED may be contributing directly towards growth faltering, and this pathway is not entirely through the pathway of systemic inflammation.

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