SummaryBackground Newborn deaths account for 57% of deaths in children younger than 5 years in Pakistan. Although a large programme of trained lady health workers (LHWs) exists, the eff ectiveness of this training on newborn outcomes has not been studied. We aimed to evaluate the eff ectiveness of a community-based intervention package, principally delivered through LHWs working with traditional birth attendants and community health committees, for reduction of perinatal and neonatal mortality in a rural district of Pakistan. Interpretation Our results support the scale-up of preventive and promotive maternal and newborn interventions through community health workers and emphasise the need for attention to issues of programme management and coverage for such initiatives to achieve maximum potential. Methods

To determine the prevalence and routes of transmission of hepatitis C virus (HCV) infection in Hafizabad, Pakistan, we collected sera in 1993 from a geographically based random sample of residents, and in 1994 identified 15 HCV-infected individuals (cases) and 67 age and sex matched uninfected individuals (controls). Initially we approached 504 households, and collected serum from a randomly selected household member in 309 (64%). Twenty persons (6·5%) had anti-HCV antibody; 31% percent had hepatitis B core antibodies, and 4·3% had hepatitis B surface antigen. In the case-control study, persons who received more therapeutic injections (categorized as averaging 1, 2–4, 5–9 or >10 injections per year in the previous 10 years) were more likely to be infected with HCV (odds ratio 0, 1·5, 2·5 and 6·9 respectively, P=0·008) compared to persons averaging 0 injections per year. Efforts to limit therapeutic injections to only those that are medically indicated and that use sterile equipment are essential in order to prevent transmission of HCV.

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BackgroundPostpartum anxiety and depression has detrimental effects on the overall mental development of children. This study aims to assess the impact of postpartum anxiety and depression on children’s mental development on all sub-scales in a Pakistani population.MethodsA quasi-experimental study was conducted in two peri-urban communities of Karachi, a mega city of Pakistan, to assess the impact of postpartum anxiety and depression on children’s growth and mental development. A total of 420 women were enrolled, who had given consent out of 651 pregnant women identified, during February 2004 to December 2005. Data for socio-demographic, home environment and family relationship variables were collected between 36 weeks of pregnancy and within 10 days of childbirth. Mother’s levels of anxiety and depression were assessed at 1, 2, 6, 12, 18, 24, and 30 months of childbirth. An indigenous, validated screening instrument- Aga Khan University Anxiety and Depression scale was used and diagnostic confirmation was done through a psychologist’s interview, based on DSM IV criteria. Children’s growth and development was monitored in the same sequence using an Early Childhood Development tool that consists of five subscales; socio emotional, language, cognitive, gross motor and fine motor development. Physical growth was monitored by measuring height and weight of the child. Data was analyzed using SAS 9.2. Multivariable Generalized Estimating Equations (GEE) logistic regression was conducted to identify association of postpartum anxiety and depression with each early childhood development indicator, adjusting for parental and child factors.ResultsA significant association of postpartum anxiety and depression with delayed development on all five subscales of children’s mental development was found in our study. Interestingly, our study found that higher maternal age had adverse effects on child’s emotional whereas positive impact on child’s cognitive development. Children’s stunting had an adverse impact on all five subscales of children’s development. Male children were at higher risk for delayed language and gross motor development relative to female children.ConclusionsOur study found that postpartum anxiety and depression is associated with adverse outcomes regarding children’s mental development on all sub-scales. The impact was accentuated by low family income or child’s increasing age.

The purpose of this paper is to summarize the formative research findings of newborn care practices in poor and rural districts of Bangladesh, Nepal, and Pakistan and to explain how these findings were used to design behavior change communication elements of newborn care programs. In-depth interviews and focus group discussions regarding newborn care practices were conducted with mothers, mothers-in-law, delivery attendants, health care providers, husbands/fathers, male and female community leaders, religious leaders and elderly influential persons between 2002-2003 in three countries supported by Save the Children's Saving Newborn Lives program. Key findings from each country are summarized according to time periods and care-seeking practices: antenatal care, birth and emergency preparedness/care-seeking, postnatal care and care-seeking for newborn illness. All country reports indicated cultural and religious barriers to seeking care as well as limited societal knowledge about the importance of care-seeking and recognition of maternal and newborn danger signs. Routine care-seeking, especially during the postnatal period, was universally low. When families did seek care, they preferred remedies from traditional healers rather than skilled health workers because of cultural and religious beliefs, poor access to health facilities, and financial barriers. Findings from the country reports were used to design behavior change communication strategies that addressed the underlying reasons why newborn care practices were sub-optimal. Cultural and religious barriers, though strong, were not insurmountable in implementing effective behavior change communication strategies. Formative research from South Asian countries has proved crucial to program approaches to improve care-seeking for maternal and newborn care, increasing availability and access of key services, and expanding family and community knowledge and demand for these services.

Protection of the brain from viral infections involves the type I interferon (IFN-I) system, defects in which renders humans susceptible to herpes simplex encephalitis (HSE). However, excessive cerebral IFN-I levels leads to pathologies, suggesting the need for tight regulation of responses. Based on data from mouse models, human HSE cases, and primary cell culture systems, we here show that microglia and other immune cells undergo apoptosis in the HSV-1-infected brain through a mechanism dependent on the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, but independent of IFN-I. HSV-1 infection of microglia induced cGAS-dependent apoptosis at high viral doses, while lower viral doses led to IFN-I responses. Importantly, inhibition of caspase activity prevented microglial cell death and augmented IFN-I responses. Accordingly, HSV-1-infected organotypic brain slices, or mice treated with caspase inhibitor, exhibited lower viral load and improved outcome of infection. Collectively, we identify an activation-induced apoptosis program in brain immune cells which down-modulates local immune responses.

Background First dose oral cotrimoxazole and referral is the recommended treatment for WHO-defined severe pneumonia. Difficulties with referral compliance are reported from many low resource settings resulting in low access to appropriate treatment. Methods In a cluster-randomized equivalence trial in Haripur District, Pakistan 28 clusters were randomized equally to intervention and control clusters. In 14 intervention clusters children 2-59 months of age with severe pneumonia were treated with oral amoxicillin by community-based Lady Health Workers (LHW). In 14 control clusters LHWs gave first dose of oral cotrimoxazole and referred to a health facility for appropriate treatment, which was standard of care. The objective was to determine whether community case-management (CCM) of severe pneumonia by LHW using oral amoxicillin was equivalent to current standard of care. Primary outcome was treatment failure on day 6 of treatment. Participants, care givers, and assessors were not blinded to study therapy. Per-protocol analysis was conducted adjusting for clustering within arms using generalized estimating equations. Findings 1995 children were randomized to intervention and 1477 to control clusters. We analysed 1857 children randomized to intervention and 1354 randomized to control clusters. They were similar in sex, age, and clinical characteristics. Treatment failure was 8·9% (165/1857) in intervention and 17·8% (241/1354) in control clusters. Cluster adjusted failure rates, the primary outcome, were significantly reduced in intervention clusters (risk difference (RD) -8·9%; 95% CI:-12.4% to -5.4%) by day 6. Further adjusting for baseline covariates made little difference (RD: -7·3%, CI: -10·1% to -4·5%). Three deaths occurred, only one in the intervention arm. Two deaths were before day 6, while one occurred between day 6 and 14. Most reduction in risk was in fever and lower chest indrawing on day 3 (RD -6·38%; 95% CI: -8·3% to -4·5%). Age, gender and very fast breathing were predictive of treatment failure. Interpretation CCM of severe pneumonia by LHWs resulted in reduced treatment failure versus current standard of care. CCM could result in standardized therapy for severe pneumonia, reduce delay in treatment initiation and costs for families and health systems. Funding United States Agency for International Development.