Karachi, Pakistan
Karachi, Pakistan

The Aga Khan University , is a private research university located in Karachi, Sindh, Pakistan. Founded in 1983, the university was named for its famed benefactor and philanthropist, Aga Khan IV. The university holds the unique distinction of being one of the first private-sector universities in Pakistan.The Aga Khan University maintains its central campus in Pakistan; teaching hospitals in countries in the African Great Lakes; and the United Kingdom. The university offers various academic programmes for undergraduate, post-graduate studies in biological and medical science. It is organized into five undergraduate and four post-graduate programmes on two main campuses— Pakistan and Tanzania. The University is a member of the Association of Commonwealth Universities of the United Kingdom.It consistently maintained its high ranking position and currently ranked as one of the top institutions in "medical school" category by the HEC as of 2013. In addition, the university secured its ranking among the 250 Asian universities ranking by the British Quacquarelli Symonds. Agha Khan pioneers the concept of modern medical science research in Pakistan and overall ranked its research in top on the global impact of its research. Wikipedia.

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Aboud F.E.,McGill University | Yousafzai A.K.,Aga Khan University
Annual Review of Psychology | Year: 2015

Health and nutritional risks co-occur in the lives of children under the age of 2 years who live in developing countries. We review evidence showing how these risks, in addition to inadequate psychosocial stimulation, prevent children from developing expected cognitive and language abilities. A systematic review and meta-analysis of 21 interventions aimed at enhancing stimulation and 18 interventions that provided better nutrition-all conducted since 2000-revealed that stimulation had a medium effect size of 0.42 and 0.47 on cognitive and language development, respectively, whereas nutrition by itself had a small effect size of 0.09. The implementation processes of these interventions are described and compared. A number of unresolved issues are outlined and discussed, including ways to maximize parental health behavior change, assess mediators that account for intervention effects, and expand the assessment of young children's brain functions that underlie language and cognition and are affected by nutrition and stimulation. © 2015 by Annual Reviews. All rights reserved.

Imdad A.,Aga Khan University
Cochrane database of systematic reviews (Online) | Year: 2010

Vitamin A deficiency (VAD) is a major public health problem in low and middle income countries affecting 190 million children under 5. VAD can lead to many adverse health consequences, including death. To evaluate the effect of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged 6 months to 5 years. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2010 Issue 2),  MEDLINE (1950 to April Week 2 2010), EMBASE (1980 to 2010 Week 16), Global Health (1973 to March 2010), Latin American and Caribbean Health Sciences (LILACS), metaRegister of Controlled Trials and African Index Medicus (27 April 2010). Randomised controlled trials (RCTs) and cluster RCTs evaluating the effect of synthetic VAS in children aged 6 months to 5 years living in the community. We excluded studies concerned with children in hospital and children with disease or infection. We excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods or beta-carotene supplementation. Two review authors independently assessed studies for inclusion. Data were double abstracted and discrepancies were resolved by discussion. Meta-analyses were performed for outcomes including all-cause and cause-specific mortality, disease, vision, and side-effects. 43 trials involving 215,633 children were included. A meta-analysis for all-cause mortality included 17 trials comprising 194,795 children with 3536 deaths in both groups. At follow-up, there was a 24% observed reduction in the risk of all-cause mortality for Vitamin A compared with Control (Relative risk (RR) = 0.76 [95% confidence interval (CI) 0.69, 0.83]). Seven trials reported diarrhoea mortality and a 28% overall reduction for VAS (RR = 0.72 [0.57, 0.91]). There was no significant effect of VAS on cause specific mortality of measles, respiratory disease and meningitis. VAS reduced incidence of diarrhoea (RR = 0.85 [0.82, 0.87]) and measles morbidity (RR = 0.50 [0.37, 0.67]); however, there was no significant effect on incidence of respiratory disease or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR = 2.75 [1.81, 4.19]). VAS is effective in reducing all-cause mortality by about 24% compared to no treatment. In our opinion, given the evidence that VAS causes considerable reduction in child mortality, further placebo-controlled trials of VAS in children between 6 months and 5 years of age are not required. There is a need for further studies comparing different doses and delivery mechanisms (for example, fortification).

Objective: To estimate the effects of chlorhexidine vaginal and baby wipes on fetal and neonatal mortality, respectively, and infection-related morbidity. Methods: We performed a placebo-controlled, randomized trial of chlorhexidine vaginal and neonatal wipes to reduce neonatal sepsis and mortality in three hospitals in Pakistan. The primary study outcome was a composite of neonatal sepsis or 7-day perinatal mortality. Results: From 2005 to 2008, 5,008 laboring women and their neonates were randomly assigned to receive either chlorhexidine wipes (n=2,505) or wipes with a saline placebo (n=2,503). The primary outcome was similar in the chlorhexidine and control groups (3.1% compared with 3.4%; relative risk 0.91, 95% confidence interval 0.67-1.24) as was the composite rate of neonatal sepsis or 28-day perinatal mortality (3.8% compared with 3.9%, relative risk 0.96, 95% confidence interval 0.73-1.27). At day 7, the chlorhexidine group had a lower rate of neonatal skin infection (3.3% compared with 8.2%, P<.001). With the exception of less frequent 7-day hospitalization in the chlorhexidine group, there were no significant differences in maternal outcomes between the groups. Conclusion: Using maternal chlorhexidine vaginal wipes during labor and neonatal chlorhexidine wipes does not reduce maternal and perinatal mortality or neonatal sepsis. The finding of reduced superficial skin infections on day 7 without change in sepsis or mortality suggests that this difference, although statistically significant, may not be of major importance. © 2010 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins.

Khoja S.,Aga Khan University
Journal of medical Internet research | Year: 2012

eHealth is widely used as a tool for improving health care delivery and information. However, distinct policies and strategies are required for its proper implementation and integration at national and international levels. To determine the scope of policy issues faced by individuals, institutions, or governments in implementing eHealth programs. We conducted a structured review of both peer-reviewed and gray literature from 1998-2008. A Medline search for peer-reviewed articles found 40 papers focusing on different aspects of eHealth policy. In addition, a Google search found 20 national- and international-level policy papers and documents. We reviewed these articles to extract policy issues and solutions described at different levels of care. The literature search found 99 policy issues related to eHealth. We grouped these issues under the following themes: (1) networked care, (2) interjurisdictional practice, (3) diffusion of eHealth/digital divide, (4) eHealth integration with existing systems, (5) response to new initiatives, (6) goal-setting for eHealth policy, (7) evaluation and research, (8) investment, and (9) ethics in eHealth. We provide a list of policy issues that should be understood and addressed by policy makers at global, jurisdictional, and institutional levels, to facilitate smooth and reliable planning of eHealth programs.

Lassi Z.S.,Aga Khan University
The Cochrane database of systematic reviews | Year: 2013

During pregnancy, fetal growth causes an increase in the total number of rapidly dividing cells, which leads to increased requirements for folate. Inadequate folate intake leads to a decrease in serum folate concentration, resulting in a decrease in erythrocyte folate concentration, a rise in homocysteine concentration, and megaloblastic changes in the bone marrow and other tissues with rapidly dividing cells To assess the effectiveness of oral folic acid supplementation alone or with other micronutrients versus no folic acid (placebo or same micronutrients but no folic acid) during pregnancy on haematological and biochemical parameters during pregnancy and on pregnancy outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2012) and we contacted major organisations working in micronutrient supplementation, including UNICEF Nutrition Section, World Health Organization (WHO) Maternal and Reproductive Health, WHO Nutrition Division, and National Center on Birth defects and Developmnetal Disabilities, US Centers for Disease Control and Prevention (CDC). All randomised, cluster-randomised and cross-over controlled trials evaluating supplementation of folic acid alone or with other micronutrients versus no folic acid (placebo or same micronutrients but no folic acid) in pregnancy. Two review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. Data were checked for accuracy. Thirty-one trials involving 17,771 women are included in this review. This review found that folic acid supplementation has no impact on pregnancy outcomes such as preterm birth (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.73 to 1.38; three studies, 2959 participants), and stillbirths/neonatal deaths (RR 1.33, 95% CI 0.96 to 1.85; three studies, 3110 participants). However, improvements were seen in the mean birthweight (mean difference (MD) 135.75, 95% CI 47.85 to 223.68). On the other hand, the review found no impact on improving pre-delivery anaemia (average RR 0.62, 95% CI 0.35 to 1.10; eight studies, 4149 participants; random-effects), mean pre-delivery haemoglobin level (MD -0.03, 95% CI -0.25 to 0.19; 12 studies, 1806 participants), mean pre-delivery serum folate levels (standardised mean difference (SMD) 2.03, 95% CI 0.80 to 3.27; eight studies, 1250 participants; random-effects), and mean pre-delivery red cell folate levels (SMD 1.59, 95% CI -0.07 to 3.26; four studies, 427 participants; random-effects). However, a significant reduction was seen in the incidence of megaloblastic anaemia (RR 0.21, 95% CI 0.11 to 0.38, four studies, 3839 participants). We found no conclusive evidence of benefit of folic acid supplementation during pregnancy on pregnancy outcomes.

Pathogenic free living amoeba like Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris are known to cause fatal "amoebic meningoencephalitis" (AME) by acquiring different route of entries to the brain. The host immune response to these protist pathogens differs from each another, as evidenced by the postmortem gross and microscopic findings from the brains of the affected patients. Cited with the expression of 'brain eating amoeba' when the infection is caused by Naegleria fowleri, this expression is making its way into parasitology journals and books. The impression that it imparts is, as if the brain damage is substantially due to the enzymes and toxins produced by this amoeba.A detailed review of the literature, analysis of archived specimens and with our experimental assays, here we establish that with Naegleria fowleri, Acanthamoeba and Balamuthia spp., the infections result in an extensive brain damage that in fact is substantially caused by the host immune response rather than the amoebas. Due to the comparatively larger sizes of these pathogens and the prior exposure of the amoebal antigen to the human body, the host immune system launches an amplified response that not only breaches the blood brain barrier (BBB), but also becomes the major cause of brain damage in AME. It is our understanding that for Naegleria fowleri the host immune response is dominated by acute inflammatory cytokines and that, in cases of Acanthamoeba and Balamuthia spp., it is the type IV hypersensitivity reaction that fundamentally not only contributes to disruption and leakiness of the BBB, but also causes the neuronal damage. The further intensification of brain damage as expected does comes from the toxins and enzymes secreted by the amoeba, which causes the irreversible brain damage, a phenomenon, which could very well continue even after the death of the patient. © 2015 Elsevier B.V.

Vitamins and minerals are essential for growth and metabolism. The World Health Organization estimates that more than 2 billion people are deficient in key vitamins and minerals. Groups most vulnerable to these micronutrient deficiencies are pregnant and lactating women and young children, given their increased demands. Food fortification is one of the strategies that has been used safely and effectively to prevent vitamin and mineral deficiencies. A comprehensive search was done to identify all available evidence for the impact of fortification interventions. Studies were included if food was fortified with a single, dual or multiple micronutrients and impact of fortification was analyzed on the health outcomes and relevant biochemical indicators of women and children. We performed a meta-analysis of outcomes using Review Manager Software version 5.1. Our systematic review identified 201 studies that we reviewed for outcomes of relevance. Fortification for children showed significant impacts on increasing serum micronutrient concentrations. Hematologic markers also improved, including hemoglobin concentrations, which showed a significant rise when food was fortified with vitamin A, iron and multiple micronutrients. Fortification with zinc had no significant adverse impact on hemoglobin levels. Multiple micronutrient fortification showed non-significant impacts on height for age, weight for age and weight for height Z-scores, although they showed positive trends. The results for fortification in women showed that calcium and vitamin D fortification had significant impacts in the post-menopausal age group. Iron fortification led to a significant increase in serum ferritin and hemoglobin levels in women of reproductive age and pregnant women. Folate fortification significantly reduced the incidence of congenital abnormalities like neural tube defects without increasing the incidence of twinning. The number of studies pooled for zinc and multiple micronutrients for women were few, though the evidence suggested benefit. There was a dearth of evidence for the impact of fortification strategies on morbidity and mortality outcomes in women and children. Fortification is potentially an effective strategy but evidence from the developing world is scarce. Programs need to assess the direct impact of fortification on morbidity and mortality.

Lassi Z.S.,Aga Khan University
Cochrane database of systematic reviews (Online) | Year: 2010

While maternal, infant and under-five child mortality rates in developing countries have declined significantly in the past two to three decades, newborn mortality rates have reduced much more slowly. While it is recognised that almost half of the newborn deaths can be prevented by scaling up evidence-based available interventions such as tetanus toxoid immunisation to mothers; clean and skilled care at delivery; newborn resuscitation; exclusive breastfeeding; clean umbilical cord care; management of infections in newborns, many require facility based and outreach services. It has also been stated that a significant proportion of these mortalities and morbidities could also be potentially addressed by developing community-based packages interventions which should also be supplemented by developing and strengthening linkages with the local health systems. Some of the recent community-based studies of interventions targeting women of reproductive age have shown variable impacts on maternal outcomes and hence it is uncertain if these strategies have consistent benefit across the continuum of maternal and newborn care. To assess the effectiveness of community-based intervention packages in reducing maternal and neonatal morbidity and mortality; and improving neonatal outcomes. We searched The Cochrane Pregnancy and Childbirth Group's Trials Register (January 2010), World Bank's JOLIS (12 January 2010), BLDS at IDS and IDEAS database of unpublished working papers (12 January 2010), Google and Google Scholar (12 January 2010). All prospective randomised and quasi-experimental trials evaluating the effectiveness of community-based intervention packages in reducing maternal and neonatal mortality and morbidities; and improving neonatal outcomes. Two review authors independently assessed trial quality and extracted the data. The review included 18 cluster-randomised/quasi-randomised trials, covering a wide range of interventional packages, including two subsets from one trial. We incorporated data from these trials using generic inverse variance method in which logarithms of risk ratio estimates were used along with the standard error of the logarithms of risk ratio estimates. Our review did not show any reduction in maternal mortality (risk ratio (RR) 0.77; 95% confidence interval (CI) 0.59 to 1.02, random-effects (10 studies, n = 144,956), I2 39%, P value 0.10. However, significant reduction was observed in maternal morbidity (RR 0.75; 95% CI 0.61 to 0.92, random-effects (four studies, n = 138,290), I2 28%; neonatal mortality (RR 0.76; 95% CI 0.68 to 0.84, random-effects (12 studies, n = 136,425), I2 69%, P value < 0.001), stillbirths (RR 0.84; 95% CI 0.74 to 0.97, random-effects (11studies, n = 113,821), I2 66%, P value 0.001) and perinatal mortality (RR 0.80; 95% CI 0.71 to 0.91, random-effects (10 studies, n = 110,291), I2 82%, P value < 0.001) as a consequence of implementation of community-based interventional care packages. It also increased the referrals to health facility for pregnancy related complication by 40% (RR 1.40; 95% CI 1.19 to 1.65, fixed-effect (two studies, n = 22,800), I2 0%, P value 0.76), and improved the rates of early breastfeeding by 94% (RR 1.94; 95% CI 1.56 to 2.42, random-effects (six studies, n = 20,627), I2 97%, P value < 0.001). We assessed our primary outcomes for publication bias, but observed no such asymmetry on the funnel plot. Our review offers encouraging evidence of the value of integrating maternal and newborn care in community settings through a range of interventions which can be packaged effectively for delivery through a range of community health workers and health promotion groups. While the importance of skilled delivery and facility-based services for maternal and newborn care cannot be denied, there is sufficient evidence to scale up community-based care through packages which can be delivered by a range of community-based workers.

BACKGROUND: Stimulation and nutrition delivered through health programmes at a large scale could potentially benefit more than 200 million young children worldwide who are not meeting their developmental potential. We investigated the feasibility and effectiveness of the integration of interventions to enhance child development and growth outcomes in the Lady Health Worker (LHW) programme in Sindh, Pakistan.METHODS: We implemented a community-based cluster-randomised effectiveness trial through the LHW programme in rural Sindh, Pakistan, with a 2 × 2 factorial design. We randomly allocated 80 clusters (LHW catchments) of children to receive routine health and nutrition services (controls; n=368), nutrition education and multiple micronutrient powders (enhanced nutrition; n=364), responsive stimulation (responsive stimulation; n=383), or a combination of both enriched interventions (n=374). The allocation ratio was 1:20 (ie, 20 clusters per intervention group). The data collection team were masked to the allocated intervention. All children born in the study area between April, 2009, and March, 2010, were eligible for enrolment if they were up to 2·5 months old without signs of severe impairments. Interventions were delivered by LHWs to families with children up to 24 months of age in routine monthly group sessions and home visits. The primary endpoints were child development at 12 and 24 months of age (assessed with the Bayley Scales of Infant and Toddler Development, Third Edition) and growth at 24 months of age. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT007159636.FINDINGS: 1489 mother-infant dyads were enrolled into the study, of whom 1411 (93%) were followed up until the children were 24 months old. Children who received responsive stimulation had significantly higher development scores on the cognitive, language, and motor scales at 12 and 24 months of age, and on the social-emotional scale at 12 months of age, than did those who did not receive the intervention. Children who received enhanced nutrition had significantly higher development scores on the cognitive, language, and social-emotional scales at 12 months of age than those who did not receive this intervention, but at 24 months of age only the language scores remained significantly higher. We did not record any additive benefits when responsive stimulation was combined with nutrition interventions. Responsive stimulation effect sizes (Cohen's d) were 0·6 for cognition, 0·7 for language, and 0·5 for motor development at 24 months of age; these effect sizes were slightly smaller for the combined intervention group and were low to moderate for the enhanced nutrition intervention alone. Children exposed to enhanced nutrition had significantly better height-for-age Z scores at 6 months (p<0·0001) and 18 months (p=0·02) than did children not exposed to enhanced nutrition. Longitudinal analysis showed a small benefit to linear growth from enrolment to 24 months (p=0·026) in the children who received the enhanced nutrition intervention.INTERPRETATION: The responsive stimulation intervention can be delivered effectively by LHWs and positively affects development outcomes. The absence of a major effect of the enhanced nutrition intervention on growth shows the need for further analysis of mediating variables (eg, household food security status) that will help to optimise future nutrition implementation design.UNICEF. Copyright © 2014 Elsevier Ltd. All rights reserved.

Agency: GTR | Branch: MRC | Program: | Phase: Research Grant | Award Amount: 839.93K | Year: 2014

Pneumonia is a major cause of illness and death in children in low-income countries. With a view to decreasing death from pneumonia, the World Health Organization and UNICEF developed the the Integrated Management of Childhood Illness (IMCI) algorithm which simplifies management of common childhood illnesses such as pneumonia and diarrhoea into different levels of severity for determining the most appropriate case management by primary healthcare providers. Many pneumonia cases are categorized as non-severe pneumonia (defined as fast breathing above the specified age cut-off for respiratory rates). As there is incomplete information regarding the cause of this type of pneumonia from primary care settings, treatment guidelines by WHO are dictated by culture information from hospital pneumonia cases which are different in severity and cause. Current WHO guidelines advocate the use of oral antibiotics for non-severe pneumonia. However, it is postulated that most non severe pneumonia not requiring hospitalization is of viral aetiology, thus does not require antibiotic treatment. The cost of antibiotic treatment for all children with pneumonia is high; an estimated US$ 200 million in South Asia & sub Saharan Africa alone. Since more than 60% of pneumonia is classified as non-severe, this puts a strain on already under-sourced programmes in low-income countries. Giving antibiotics where they confer no benefit also puts the child at risk of side effects and increases the risk of antimicrobial resistance in the community. This uncertainty forms the basis of the proposed study. We propose to show in a clinical trial that the outcome of children diagnosed with WHO defined non severe pneumonia is similar regardless of whether they receive antibiotics or not. This study will be conducted in five primary health care centres located in low income communities of Karachi, Pakistan, with extensive trial experience. Children identified to have fast breathing without any danger signs will be randomized to receive either three days of the WHO recommended oral antibiotic (Amoxicillin 45mg/kg/day divided twice daily) or matching placebo (a drug that will taste and look like the amoxicillin but will not have an active ingredient) by a study physician working at the primary health centre. The assignment of the antibiotic amoxicillin or placebo to a child will be done using a computer generated randomization list in a manner that at the end of the trial, there are equal numbers of children in both arms of the trial. Based on the statistical calculations for sample size, we will need to assign 521 children to receive amoxicillin and the same number of children to receive placebo. All children will receive the antibiotic or placebo under supervision of the primary health care physician in the morning. Evening doses will be delivered by locally hired Community Health Workers (CHWs) visiting the children at their home. All children will be assessed again on day 3 by a study physician to see if the childs presenting sign of high respiratory rate has resolved or not. All children with persistently high respiratory rate and/or development of a new clinical sign indicating illness progression will be labelled a treatment failure. There will invariably be some children with treatment failure in both the treatment arms; we hypothesize that there will be equal number of treatment failures in both the groups i.e. around 7%. If we are able to show with the help of this trial that there is no added advantage of prescribing antibiotics to children with non-severe pneumonia we will develop an evidence base to revise the current WHO guidelines and thus reduce the financial burden on an already resource constrained health system and also decrease out of pocket expenses for families. In the long term this will have implications for decreasing global antimicrobial resistance to antibiotics.

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