Is home environment associated with child fluid reasoning abilities in middle childhood in high-risk settings? findings from a cross-sectional study in Pakistan.

BACKGROUND: Evidence from low- and middle-income countries (LMIC) suggests that home environment is associated with early childhood development outcomes. However, studies from LMIC that have examined how the home environment during middle childhood is associated with intellectual abilities are scarce. The objective of the study was to explore the association between different aspects of the home environment at 7-8 years and fluid reasoning abilities in a rural, high-risk cohort in Pakistan. METHODS: We employed a cross-sectional research design to examine 1172 children between 7 and 8 years and their families, utilizing the Home Observation for Measurement of Environment for Middle Childhood (HOME-MC) to evaluate various aspects of the home environment and the Fluid Reasoning Index (FRI) of the Wechsler Intelligence for Children (WISC)-5th edition to assess the fluid reasoning abilities of the children. Multivariable regression analyses were used to examine the association between different components of HOME-MC (scored as indices) and FRI scores. FINDINGS: Learning materials and opportunities (ß = 1.74, 95% CI = 1.15, 2.33) and Responsivity (ß = 1.73, 95% CI = 1.07, 2.38) indices had the strongest association with FRI score followed by Family companionship index (ß = 1.27, 95% CI = 0.63, 1.90). The eight different indices of the HOME-DC explained 22% of the total variation in FRI scores. CONCLUSION: We conclude that concurrent learning opportunities, parental responsivity and family companionship at home are associated with fluid reasoning abilities during middle childhood which is comparable to what has been found in early childhood years.

A dyadic approach to depression, resilience and quality of life on marital adjustment among infertile couples in Karachi, Pakistan: A cross-sectional study.

BACKGROUND: Infertility is a major reproductive health problem in Pakistan. It has the potential to cause serious negative impact on a couple's marital life and psychological health. AIM: This study aimed to assess the factors associated with maladjustment among infertile couples. METHOD: An analytical cross-sectional design was employed. Validated scales were used to assess marital adjustment, depression, resilience and quality of life among infertile couples. Purposive sampling was employed to enrol 334 infertile couples from a private infertility medical centre, of Karachi, Pakistan. RESULTS: Among couples, marital adjustment scores were comparable, but resilience and quality of life were significantly low among wives whereas depression was significantly high among wives compared with husbands. Wives' marital adjustment was positively correlated with husband's resilience and quality of life and negatively related with his depression. After employing adjusted actor-partner interdependence modelling, wives' own depression and resilience had significant effect on their marital adjustment and their partner's resilience, depression and quality of life did not have any impact on their outcome. On the contrary, wives' resilience had a significant effect in increasing the marital adjustment of their husband. CONCLUSION: This study highlights the need to promote psychological support (resilience building skills) or couples' therapy to all those couples undergoing infertility treatment.

Outcomes of preterm neonates with patent ductus arteriosus: A retrospective review from a tertiary care hospital.

The management of patent ductus arteriosus (PDA) in preterm neonates remains controversial. A retrospective review was conducted to determine the outcomes in preterm neonates with PDA. Data of neonates admitted to the Aga Khan University Hospital from January 2012 to December 2016 were retrieved from patient records. Of the 208 neonates included in the study, 143 (68.7%) received no treatment, while 65 (31.2%) underwent pharmacotherapy and/or surgical ligation for PDA closure. PDA closure was spontaneous in 109 (52.4%) neonates. The mean ±SD gestational age (GA) of neonates with spontaneous ductal closure was greater as compared to those who required some form of treatment [33±3.3 vs 29.7±3.1weeks, p=0.001]. Apnoea (OR:4.47; 95% CI:1.21-16.44), sepsis (OR:3.81; 95% CI:1.33-10.87), pulmonary haemorrhage (OR:4.88; 95% CI:1.24-19.19), and lower APGAR (OR:0.69; 95% CI:0.54-0.90) were associated with higher odds of mortality in our cohort. Our findings demonstrate that PDA resolves spontaneously in most preterm neonates and provide evidence that conservative treatment is not associated with mortality.

Evaluating motor performance with the Bruininks-Oseretsky Test of motor proficiency in impoverished Pakistani children.

OBJECTIVE: To evaluate the sensitivity of the modified Brief Form of Bruininks Oseretsky Test in identifying motor differences secondary to malnutrition and poverty. METHODS: This longitudinal cohort study was conducted at Nowshero Feroze, Sindh from 2013 to 2014 and comprised data drawn from children who participated in a randomised controlled trial, that assessed responsive stimulation and nutrition interventions in the first two years of life. Outcome measures included motor development assessed using Brief Form of Bruininks Oseretsky Test, child anthropometry and household economic and demographic information. Data was analysed using SPSS 15 and STATA 12. RESULTS: Of the 1058 children, 570(53%) were boys. Moderate-severe stunting was reported in 171(16.12%) subjects, while moderate-severe underweight was reported in 117(11.1%). Also, 591(56%) subjects belonged to poor families, 343(32%) had illiterate mothers, and 392(37%) were food-insecure. Malnutrition, socio-economic status and maternal literacy were significantly associated with a 6-item motor composite of the Brief Form of Bruininks Oseretsky Test (p<0.05). CONCLUSIONS: The 6-item motor composite of the Brief Form of Bruininks Oseretsky Test was found to be a reliable tool to measure motor performance in Pakistani pre-school children.

Factors associated with low birthweight in term pregnancies: a matched case-control study from rural Pakistan.

Low birthweight (LBW) remains a significant public health problem in Pakistan and further understanding of factors associated with LBW is required. We conducted a hospital-based matched case control study to identify risk factors associated with LBW in a rural district of Pakistan. We found that illiteracy (AOR: 2.68; 95% CI: 1.59 - 4.38), nulliparity (AOR: 1.82; 95% CI: 1.26-2.44), having a previous miscarriage/abortion (AOR: 1.22; 95% CI: 1.06-2.35), having < 2 antenatal care (ANC) visits during last pregnancy (AOR: 2.43; 95% CI: 1.34-2.88), seeking ANC in third trimester (AOR: 3.62; 95% CI : 2.14-5.03), non-use of iron folic acid during last pregnancy (AOR: 2.72; 95% CI: 1.75-3.17), having hypertension during last pregnancy (AOR: 1.42; 95% CI: 1.13-2.20), being anemic (AOR: 2.67; 95% CI: 1.65-5.24) and having postpartum weight of <45 kg (AOR: 3.30; 95% CI : 1.97-4.52) were significantly associated with an increased odds of having a LBW baby. Our study identifies modifiable risk factors requiring immediate commitment from the health authorities.

The predictive validity of Bayley Scales of Infant and Toddler Development-III at 2 years for later general abilities: Findings from a rural, disadvantaged cohort in Pakistan.

Using data from a rural cohort in Pakistan (N = 1298), the study examined the predictive validity of the Bayley Scales of Infant and Toddler Development (BSID) 3rd edition on later tests of general abilities. The BSID III subscales (cognitive, language and motor) were administered at 2 years; general ability was assessed using the Verbal, Performance and Full-Scale score from the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) III at 4 years, and the Fluid Reasoning Index (FRI) from the Wechsler Intelligence Scale for Children (WISC) V at 8 years. The combined BSID subscales explained 15% of the variation of the WPPSI III full scale, 16% of the Verbal scale, 7% of the Performance scale and 1% of the FRI. BSID III scores at 24 months should be used with caution to predict future intellectual abilities.

Referral Profile of Developmental Disabilities at a Tertiary Care Hospital in a Resource-limited Country.

The burden and the spectrum of neuro-developmental disabilities are well-established in the developed countries, however, they continue to be a challenge in the Low Middle-Income Countries. The aim of this study was to present the referral profile and trends of developmental disabilities in the child development centre of The Agha khan University, from 2012 to 2021. All children (1 month to 18 years), who had undergone diagnostic evaluations for suspected neurodevelopmental disabilities were included. A total of 1340 children were evaluated at the centre. The mean age of the children at the presentation was 5.4 ± 3.0 years. Male to female ratio was 3:1. Autism Spectrum Disorder (ASD) was the most common diagnosis (n=446, 33.3%). This study highlights a considerable burden and an increasing trend of children being referred for suspected developmental disabilities in Pakistan. Key Words: Developmental disabilities, Referral, Pakistan, Autism spectrum disorder.

Differential associations between body composition indices and neurodevelopment during early life in term-born infants: findings from the Pakistan cohort: Multi-Center Body Composition Reference Study.

OBJECTIVE: We examined associations between fat free mass (FFM) and fat mass (FM) accretion during the first 1000 days of life and neurodevelopment in term-born, low-risk infants from Karachi, Pakistan. DESIGN: Prospective, observational study nested within the larger Multi-Center Body Composition Reference Study. FFM, FM, and fat% were estimated using measured deuterium dilution method. Neurodevelopmental outcomes were assessed at 24 months on the INTER-NDA (INTERGROWTH-21st Project Neurodevelopment Assessment) (n = 132). RESULTS: Children with gross motor delays had significantly lower FFM at 18 months (8.01 ± 0.97 kg vs. 7.55 ± 0.20 kg). Children with positive and negative behavior problems had significantly higher fat% at 24 months (20.62 ± 4.30% vs. 18.23 ± 5.46%) and 20.89 ± 4.24% vs. 18.54 ± 5.38%). No associations remained significant after adjusting for covariates. Trajectory modeling showed that between 12 and 18 months, negative behavior scores changed by 13.8 points for every standard deviation change in fat accretion. CONCLUSIONS: Our findings highlight the importance of balancing neurodevelopment and metabolic risk when designing nutritional interventions for young children.

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.

Practices and predictors of menstrual hygiene management material use among adolescent and young women in rural Pakistan: A cross-sectional assessment.

Background: In low- and middle-income countries (LMICs), women often use inappropriate materials to manage menstruation, which can threaten their health. Improper practices can also have critical downstream consequences beyond physiologic health, including restricting adolescent girls' access to academic pursuits. Methods: We used cross-sectional data collected through a structured questionnaire from the menstruating adolescents and young women 15-23 years of age living in rural Pakistan (n = 25 305). We aimed to describe menstrual hygiene management (MHM) practices and generate a predictive model of the socioeconomic and demographic factors related to the use of MHM materials. Beliefs and barriers around MHM were also summarized. The outcome variable included: those who practiced appropriate and inappropriate MHM practices. Logistic regression was used to generate the predictive model, with results presented as odds ratios (OR) and 95% confidence interval (CI). Results: Inappropriate MHM practices were reported by 75% (n = 19 006) of participants. The majority 61.9% (n = 15 667) reported using old cloths, 12.6% (n = 3191) used nothing, and 0.5% (n = 136) used old cloth with a sanitary pad. One-fourth of participants reported appropriate MHM material use, including 16.2% (n = 4087) sanitary pads, 8.6% (n = 2167) new cloth, and a few reported using sanitary pads with new cloth 0.2% (n = 45). Inappropriate MHM practices were more common in lowest wealth quintile (OR = 4.41; 95% CI = 2.77-7.01, P < 0.0001), followed by those with no education (OR = 3.9; 95% CI = 3.36-4.52, P < 0.0001). Conclusions: The study indicates the need for multi-sectoral efforts to introduce MHM-specific and MHM-sensitive interventions to improve MHM practices, ranging from the availability of low-cost MHM materials to the inclusion of MHM education in school curriculums and within the community platforms.

Prevalence and risk factors of Severe Acute Respiratory Syndrome Coronavirus 2 infection in women and children in peri-urban communities in Pakistan: A prospective cohort study.

Background: Population-based seroepidemiological surveys provide accurate estimates of disease burden. We compare the COVID-19 prevalence estimates from two serial serological surveys and the associated risk factors among women and children in a peri-urban area of Karachi, Pakistan. Methods: The AMANHI-COVID-19 study enrolled women and children between November 2020 and March 2021. Blood samples were collected from March to June 2021 (baseline) and September to December 2021 (follow-up) to test for anti-SARS-CoV-2 antibodies using ROCHE Elecsys®. Participants were visited or called weekly during the study for recording symptoms of COVID-19. We report the proportion of participants with anti-SARS-CoV-2 antibodies and symptoms in each survey and describe infection risk factors using step-wise binomial regression analysis. Results: The adjusted seroprevalence among women was 45.3% (95% confidence interval (CI) = 42.6-47.9) and 82.3% (95% CI = 79.9-84.4) at baseline and follow-up survey, respectively. Among children, it was 18.4% (95% CI = 16.1-20.7) and 57.4% (95% CI = 54.3-60.3) at baseline and follow-up, respectively. Of the women who were previously seronegative, 404 (74.4%) tested positive at the follow-up survey, as did 365 (50.4%) previously seronegative children. There was a high proportion of asymptomatic infection. At baseline, being poorest and lacking access to safe drinking water lowered the risk of infection for both women (risk ratio (RR) = 0.8, 95% CI = 0.7-0.9 and RR = 1.2, 95% CI = 1.1-1.4, respectively) and children (RR = 0.7, 95% CI = 0.5-1.0 and RR = 1.4, 95% CI = 1.0-1.8, respectively). At the follow-up survey, the risk of infection was lower for underweight women and children (RR = 0.4, 95% CI = 0.3-0.7 and RR = 0.7, 95% CI = 0.5-0.8, respectively) and for women in the 30-39 years age group and children who were 24-36 months of age (RR = 0.6, 95% CI = 0.4-0.9 and RR = 0.7, 95% CI = 0.5-0.9, respectively). In both surveys, paternal employment was an important predictor of seropositivity among children (RR = 0.7, 95% CI = 0.6-0.9 and RR = 0.8, 95% CI = 0.7-1.0, respectively). Conclusion: There was a high rate of seroconversion among women and children. Infection was generally mild. Parental education plays an important role in protection of children from COVID-19.

Global variation of COVID-19 mortality rates in the initial phase.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused devastation in over 200 countries. Italy, Spain, and the United States (US) were most severely affected by the first wave of the pandemic. The reasons why some countries were more strongly affected than others remain unknown. We identified the most-affected and less-affected countries and states and explored environmental, host, and infrastructure risk factors that may explain differences in the SARS-CoV-2 mortality burden. METHODS: We identified the top 10 countries/US states with the highest deaths per population until May 2020. For each of these 10 case countries/states, we identified 6 control countries/states with a similar population size and at least 3 times fewer deaths per population. We extracted data for 30 risk factors from publicly available, trusted sources. We compared case and control countries/states using the non-parametric Wilcoxon rank-sum test, and conducted a secondary cluster analysis to explore the relationship between the number of cases per population and the number of deaths per population using a scalable EM (expectation-maximization) clustering algorithm. RESULTS: Statistically significant differences were found in 16 of 30 investigated risk factors, the most important of which were temperature, neonatal and under-5 mortality rates, the percentage of under-5 deaths due to acute respiratory infections (ARIs) and diarrhea, and tuberculosis incidence (p < 0.05). CONCLUSION: Countries with a higher burden of baseline pediatric mortality rates, higher pediatric mortality from preventable diseases like diarrhea and ARI, and higher tuberculosis incidence had lower rates of coronavirus disease 2019-associated mortality, supporting the hygiene hypothesis.

Psychometric Analysis for fear of COVID-19 Scale (FCV-19S) and its association with depression in patients with diabetes: A cross sectional study from a Tertiary Care Centre in Karachi, Pakistan.

BACKGROUND AND AIMS: To assess the psychometric properties of the Fear of COVID-19 (FCV-19S) scale and to determine its associated factors among the Pakistani patients with diabetes. METHODS: This observational study was conducted in 24-h helpline service, a department of Baqai Institute of Diabetology and Endocrinology (BIDE). Study duration was from August to September 2020. The target population was registered adult patients with type 2 diabetes aged >16 years. Baseline demographic details were obtained from hospital management system of BIDE. Forward-backward translation method was used to translate the existing Fear scale (FCV-19S). Symptoms of depressive disorder were assessed through Patient Health Questionnaire (PHQ9). RESULTS: Total of 380 participants with mean age 51.93 ± 12.03 years contributed in the study. Three factors loading and item correlation of fear COVID-19 explained 96% of total variance having unidimensional Cronbach's alpha of 0.881. All demographic indicators that showed significance in univariate model were included in multivariate model. Females had more fear for COVID-19 compared to males (OR = 1.73, 95% CI (1.15-2.6)), whereas current smokers had also showed 4 times more fear than non-smokers (OR = 4.19, 95% CI (1.18-14.83). Depression assessed by PHQ9 showed maximum fear of COVID-19 in participants with moderate depression. CONCLUSION: FCV-19S had adequate psychometric properties for assessing effects of pandemic in people with diabetes attending tertiary care center.

Impact evaluation of the efficacy of different doses of vitamin D supplementation during pregnancy on pregnancy and birth outcomes: a randomised, controlled, dose comparison trial in Pakistan.

BACKGROUND: Vitamin D deficiency during pregnancy is a public health problem in Pakistan and is prevalent among most women of reproductive age in the country. Vitamin D supplementation during pregnancy is suggested to prevent adverse pregnancy outcomes and vitamin D deficiency in both the mother and her newborn. METHODS: We conducted a double-blinded, randomised controlled trial in Karachi, Pakistan to evaluate the effect of different doses of vitamin D supplementation during pregnancy on biochemical markers (serum 25(OH)D, calcium, phosphorus and alkaline phosphatase) in women and neonates, and on pregnancy and birth outcomes (gestational diabetes, pre-eclampsia, low birth weight, preterm births and stillbirths). RESULTS: Pregnant women (N=350) in their first trimester were recruited and randomised to three treatment groups of vitamin D supplementation: 4000 IU/day (group A, n=120), 2000 IU/day (group B, n=115) or 400 IU/day (group C, n=115). Women and their newborn in group A had the lowest vitamin D deficiency at endline (endline: 75.9%; neonatal: 64.9%), followed by group B (endline: 84.9%; neonatal: 73.7%) and then the control group (endline: 90.2%; neonatal: 91.8%). Vitamin D deficiency was significantly lower in group A than in group C (p=0.006) among women at endline and lower in both groups A and B than in the control group (p=0.001) in neonates. Within groups, serum 25(OH)D was significantly higher between baseline and endline in group A and between maternal baseline and neonatal levels in groups A and B. Participant serum 25(OH)D levels at the end of the trial were positively correlated with those in intervention group A (4000 IU/day) (ß=4.16, 95% CI 1.6 to 6.7, p=0.002), with food group consumption (ß=0.95, 95% CI 0.01 to 1.89, p=0.047) and with baseline levels of serum 25(OH)D (ß=0.43, 95% CI 0.29 to 0.58, p<0.0001). CONCLUSION: The evidence provided in our study indicates that vitamin D supplementation of 4000 IU/day was more effective in reducing vitamin D deficiency among pregnant women and in improving serum 25(OH)D levels in mothers and their neonates compared with 2000 IU/day and 400 IU/day. Trial registration number NCT02215213.

Determinants of infant and young complementary feeding practices among children 6-23 months of age in urban Pakistan: a multicenter longitudinal study.

BACKGROUND: Suboptimal feeding practices have a negative impact on children's health and growth in the first 2 years of life and increase their risk of undernutrition, morbidity, and mortality. The aim of the study was to assess the factors that influence infant and young child feeding practices among urban mothers in a hospital setting at Karachi, Pakistan. METHODS: A longitudinal multi-center cohort study was conducted in four countries, MULTICENTER BODY COMPOSITION REFERENCE STUDY (MBCRS) to produce normal body composition reference data in healthy infants from 3 months to 24 months of age. Repeated anthropometric (weight, length and head circumference) and body composition measurements using "deuterium dilution method" along with 24-h dietary recall questionnaires were performed on 250 healthy term infants at 3, 6, 9, 12, 18, and 24 months of age. The 24-h dietary recall data from this study was used to assess the breastfeeding and complementary feeding practices in children aged 6-24 months. RESULTS: A total of 250 healthy infants were enrolled in the study. A majority of newborns (75.4%) were exclusively breastfed till 3 months of age; however, by 6 months of age, only 30.2% of infants were exclusively breastfed. Only 44.1% of children aged 6-24 months achieved minimum dietary diversity (MDD), 84.7% achieved minimum meal frequency (MMF), and 44.1% achieved a minimum acceptable diet (MAD). 71.4% achieved MDD and MAD and 100% achieved MMF at 24 months. The bivariate analysis found that breastfed children (OR 3.93, 95% CI 2.72-5.68), with employed mothers (OR 1.55, 95% CI 1.06-2.27) who had graduated from secondary school (OR 1.45, 95% CI 1.08-1.94) were more likely to meet minimum dietary diversity. The multivariable analysis showed that only the child's age was significantly associated with MDD (p value< 0.0001), with the likelihood of meeting MDD increasing as the children aged; 9 months (OR 18.96, 95% CI 6.63-54.19), 12 months (OR 40.25, 95% CI 14.14-114.58), 18 months (OR 90.02, 95% CI 30.84-262.77) and 24 months (OR 82.14, 95% CI 27.23-247.83). CONCLUSION: Our study revealed that Infant and young child feeding practices are significantly associated with maternal education, employment, and the child's age. Therefore, it is essential that investments be made towards protective breastfeeding and complementary feeding policies and legislations, emphasis on female education and ensuring the availability of affordable nutritious and diverse foods.

Adult congenital heart disease: frequency, risk factors and outcomes of acute kidney injury in postoperative period.

BACKGROUND: Acute kidney injury (AKI) after surgery for congenital heart disease (CHD) in adults is poorly studied despite being well-recognized as a postoperative complication after cardiac surgery in adults. The primary aim of our study was to determine the frequency of AKI in adults undergoing surgery for CHD. We also aimed to determine risk factors and predictors of AKI in this patient population, and to explore outcomes in terms of duration of mechanical ventilation, intensive care unit (ICU) stay, and hospital stay. METHODS: This retrospective cross-sectional study included all adult patients (18 years) who underwent cardiac surgery with cardiopulmonary bypass for their congenital heart problems from January 2011 to December 2016 in a tertiary-care private hospital. RESULTS: A total of 166 patients with a mean age of 32.05 ± 12.11 years were included in this study. The postoperative course was complicated by AKI in 29.5% of patients. Thirty-two percent of these patients had moderate-to-severe kidney disease. Two patients (4%) developing AKI required renal replacement therapy in the form of transient hemodialysis. All patients in our study showed complete resolution of AKI, with no mortalities in the postoperative period. On univariable analysis, (Risk adjusted classification for congenital heart surgery-1) RACHS-1 category 2 and 3, aortic valve replacement, preoperative creatinine clearance, ventricular septal defect closure, cardiopulmonary bypass time, aortic cross-clamp time, intra-operative excessive blood loss, intra-operative ionotropic score, and postoperative hypotension were found to be significant predictors for the development of AKI. On age-adjusted multivariable analysis, RACHS-1 category 2 (OR = 3.49; CI = 1.22-9.95) and category 3 (OR = 3.28 = 1.15-9.36), and intra-operative excessive blood loss (OR = 2.9; CI = 1.07-7.85) were significant predictors of AKI development in the postoperative period. Moreover, development of AKI postoperatively was a predictor of a significantly longer cardiac intensive care unit (CICU) stay (OR = 1.21; CI = 1.08-1.37). CONCLUSION: We found that preoperative creatinine clearance, ACC time, intraoperative excessive blood loss, and RACHS-1Category 2 and 3 are potential risk factors for postoperative AKI development. Moreover, patients who develop AKI are likely to have a significantly longer CICU stay. Our study has tried to fill the lacunae with regard to AKI in adults undergoing surgery for CHD. However, there is a need for more studies with larger cohorts involving more complex surgeries to truly estimate the incidence and potential risk factors for AKI in this group of patients.

Antibody-Secreting Cells To Diagnose Mycobacterium tuberculosis Infection in Children in Pakistan.

Reliance on microbiologic methods to diagnose Mycobacterium tuberculosis infection is a suboptimal approach for children due in part to the paucibacillary nature of the disease. A blood-based biomarker assay, such as the mycobacterial-antibody-secreting cell (MASC) assay, could be a major advance for the field of study of pediatric tuberculosis (TB). Children <15 years of age with clinical concern for TB and age-matched children with no concern for TB were enrolled from outpatient clinics in Karachi, Pakistan. MASC, ferritin, and C-reactive protein (CRP) assays were performed, and results were compared among cases and controls, as well as among children with a case definition of "confirmed TB," "probable TB," or "possible TB." MASC responses were significantly higher among children with TB than among controls (0.41 optical density [OD] versus 0.28 OD, respectively, P < 0.001), and the differences were largely driven by the data from children with confirmed TB (P = 0.002). Ferritin and CRP values were significantly higher among those with confirmed TB than among those with the other disease states and controls (P = 0.004 and P = 0.019, respectively). The use of the MASC assay as a blood-based biomarker for TB disease shows some promise among children with microbiologically confirmed disease; however, the performance characteristics for the majority of young children with unconfirmed TB were suboptimal in this cohort.IMPORTANCE Tuberculosis (TB) in children represents a missed opportunity for diagnosis and preventive therapy. The magnitude or burden of disease in children is not fully understood due to our limitations with respect to exploring sensitive diagnostic algorithms. In a setting of TB endemicity in Pakistan, we carried out a proof-of-concept study to evaluate for the first time the performance of B cell analyses by the use of well-defined diagnostic criteria and NIH consensus guidelines as "culture-confirmed," "probable," and "possible" TB groups. In contrast to detection of serum antibody, we focused on mycobacterial-antibody-secreting cell (MASC) detection as a marker of active disease in children with a strong suspicion of TB. Further work exploring a larger panel of inflammatory biomarkers and enrichment of B cells with the objective of increasing the sensitivity of the current MASC assay would lead to the development of a field-friendly assay for timely diagnosis of childhood TB.

Epidemiology of Shigella infections and diarrhea in the first two years of life using culture-independent diagnostics in 8 low-resource settings.

Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (<10 years, RR: 1.14, 95% CI: 1.03, 1.26), initiating complementary foods before 3 months (RR: 1.10, 95% CI: 1.01, 1.20), and malnutrition (RR: 0.91, 95% CI: 0.88, 0.95 per unit increase in weight-for-age z-score) were risk factors for Shigella. There was a linear dose-response between Shigella quantity and myeloperoxidase concentrations. The burden of Shigella varied widely across sites, but uniformly increased through the second year of life and was associated with intestinal inflammation. Culture missed most clinically relevant cases of severe diarrhea and dysentery.

Optimized health care for subjects with type 1 diabetes in a resource constraint society: A three-year follow-up study from Pakistan.

BACKGROUND: Inadequate health infrastructure and poverty especially in rural areas are the main hindrance in the optimal management of subjects with type 1 diabetes (T1D) in Pakistan. AIM: To observe effectiveness of diabetes care through development of model clinics for subjects with T1D in the province of Sindh Pakistan. METHODS: A welfare project with name of "Insulin My Life", was started in province of Sindh, Pakistan. This was collaborative work of Baqai Institute of Diabetology and Endocrinology, World Diabetes Foundation and Baqai Medical University between February 2010 to February 2013. Under this project thirty-four T1D clinics were established. Electronic database was designed for demographic, biochemical, anthropometric and medical examination. Monthly consultation was part of the standardized diabetes care. All the recruited subjects with T1D were provided free insulins and related materials. RESULTS: Out of 1428 subjects, 795 (55.7%) were males and 633 (44.3%) were females. Subjects were categorized into ≤ 5 years of age 103 (7.2%), between 6-12 years 323 (22.6%), between 13-18 years 428 (29.7%) and ≥ 19 years of age 574 (40.2%) groups. Glycemic control as assessed by HbA1c was significantly improved (P < 0.0001) at three years follow up as compared to baseline in all age groups. Decreasing trends of mean self-monitoring blood glucose were observed at different meal timings in all age groups. No significant change was found in the frequency of neuropathy, nephropathy and retinopathy during the study period (P > 0.05). CONCLUSION: This study gives us long-term longitudinal data of people with T1D in a resource constraint society. With provision of standardized and comprehensive care significant improvement in glycemic control without any change in the frequency of microvascular complications was observed over 3 years.

Effectiveness of a youth-led early childhood care and education programme in rural Pakistan: A cluster-randomised controlled trial.

BACKGROUND: The United Nation's Sustainable Development Goals encompass lifelong learning from birth to youth to adulthood (Goal 4) and economic opportunities for young people (Goal 8). The targets include improving access to quality early childhood care and education (ECCE) as well as learning and training opportunities for adolescents and youth. Cross-generational models for young children and youth may offer opportunities to address the interconnections between goals and targets for the next generation. We investigated whether an ECCE programme for young children (3.5-6.5 years) delivered by female youth (18-24 years) in rural Pakistan would be effective on children's school readiness. METHODS: In partnership with the National Commission for Human Development in Pakistan, we implemented the 'Youth Leaders for Early Childhood Assuring Children are Prepared for School' (LEAPS) programme to train female youth to deliver ECCE. The effectiveness of the LEAPS programme on children's school readiness was evaluated in a cluster-randomised controlled trial. We randomly allocated five clusters (villages) to receive the intervention (n = 170 children) and five clusters to control (n = 170 children). Children's school readiness was assessed after nine months of intervention exposure using the International Development and Early Learning Assessment tool. Analyses was by intention-to-treat. The trial is registered with ClinicalTrials.gov, number NCT02645162. FINDINGS: At endline, the intervention group had significantly higher school readiness scores (n = 166, mean percentage score 59.4, 95% CI 52.7 to 66.2) compared with the control group (n = 168, mean percentage score 45.5, 95% CI 38.8 to 52.3). The effect size (Cohen's d) was 0.3. CONCLUSION: Trained female youth delivered an ECCE programme that was effective in benefitting young children's school readiness. The cross-generational model is a promising approach to support early child development; however, further evaluation of the model is needed to assess the specific benefits to youth including their skills and economic development.