Sajid Soofi

Implementing community-based perinatal care: results from a pilot study in rural Pakistan

OBJECTIVE This pilot study investigated the feasibility of delivering a package of community-based interventions for improving perinatal care using lady health workers (LHWs) and traditional birth attendants (Dais) in rural Pakistan. METHODS The intervention was implemented in four of eight village clusters (315 villages, total population 138,600), while four served as a comparison group. The LHWs in intervention clusters received additional training focused on essential maternal and newborn care, conducted community education group sessions, and were encouraged to link up with local Dais. The intervention was delivered within the regular government LHW programme and was supported by the creation of voluntary community health committees. FINDINGS In intervention villages, there were significant reductions from baseline in stillbirth (from 65.9 to 43.1 per 1000 births, P < 0.001) and neonatal mortality rates (from 57.3 to 41.3 per 1000 live births, P < 0.001). The proportion of deliveries conducted by skilled attendants at public sector facilities also increased, from 18% at baseline to 30%, while the proportion of home births decreased from 79% to 65%. A household survey indicated a higher frequency of key behaviours (e.g. early and exclusive breastfeeding, delayed bathing and cord care) in intervention villages. CONCLUSION The improved stillbirth and neonatal mortality rates observed indicate that community health workers (i.e. LHWs and Dais) can be effective in implementing a community and outreach package that leads to improved home care practices by families, increased care-seeking behaviour and greater utilization of skilled care providers. These preliminary observations require confirmation in an adequately powered trial.

Improvement of perinatal and newborn care in rural Pakistan through community-based strategies: a cluster-randomised effectiveness trial

BACKGROUND 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 effectiveness of this training on newborn outcomes has not been studied. We aimed to evaluate the effectiveness 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. METHODS We undertook a cluster randomised trial between February, 2006, and March, 2008, in Hala and Matiari subdistricts, Pakistan. Catchment areas of primary care facilities and all affiliated LHWs were used to define clusters, which were allocated to intervention and control groups by restricted, stratified randomisation. The intervention package delivered by LHWs through group sessions consisted of promotion of antenatal care and maternal health education, use of clean delivery kits, facility births, immediate newborn care, identification of danger signs, and promotion of careseeking; control clusters received routine care. Independent data collectors undertook quarterly household surveillance to capture data for births, deaths, and household practices related to maternal and newborn care. Data collectors were masked to cluster allocation; those analysing data were not. The primary outcome was perinatal and all-cause neonatal mortality. Analysis was by intention to treat. This trial is registered, ISRCTN16247511. FINDINGS 16 clusters were assigned to intervention (23,353 households, 12,391 total births) and control groups (23,768 households, 11,443 total births). LHWs in the intervention clusters were able to undertake 4428 (63%) of 7084 planned group sessions, but were only able to visit 2943 neonates (24%) of a total 12,028 livebirths in their catchment villages. Stillbirths were reduced in intervention clusters (39·1 stillbirths per 1000 total births) compared with control (48·7 per 1000; risk ratio [RR] 0·79, 95% CI 0·68-0·92; p=0·006). The neonatal mortality rate was 43·0 deaths per 1000 livebirths in intervention clusters compared with 49·1 per 1000 in control groups (RR 0·85, 0·76-0·96; p=0·02). 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. FUNDING WHO; Saving Newborn Lives Program of Save the Children USA, funded by the Bill & Melinda Gates Foundation.

Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: a cluster-randomised trial.

BACKGROUND Powders containing iron and other micronutrients are recommended as a strategy to prevent nutritional anaemia and other micronutrient deficiencies in children. We assessed the effects of provision of two micronutrient powder formulations, with or without zinc, to children in Pakistan. METHODS We did a cluster randomised trial in urban and rural sites in Sindh, Pakistan. A baseline survey identified 256 clusters, which were randomly assigned (within urban and rural strata, by computer-generated random numbers) to one of three groups: non-supplemented control (group A), micronutrient powder without zinc (group B), or micronutrient powder with 10 mg zinc (group C). Children in the clusters aged 6 months were eligible for inclusion in the study. Powders were to be given daily between 6 and 18 months of age; follow-up was to age 2 years. Micronutrient powder sachets for groups B and C were identical except for colour; investigators and field and supervisory staff were masked to composition of the micronutrient powders until trial completion. Parents knew whether their child was receiving supplementation, but did not know whether the powder contained zinc. Primary outcomes were growth, episodes of diarrhoea, acute lower respiratory tract infection, fever, and incidence of admission to hospital. This trial is registered with ClinicalTrials.gov, number NCT00705445. RESULTS The trial was done between Nov 1, 2008, and Dec 31, 2011. 947 children were enrolled in group A clusters, 910 in group B clusters, and 889 in group C clusters. Micronutrient powder administration was associated with lower risk of iron-deficiency anaemia at 18 months compared with the control group (odds ratio [OR] for micronutrient powder without zinc=0·20, 95% CI 0·11-0·36; OR for micronutrient powder with zinc=0·25, 95% CI 0·14-0·44). Compared with the control group, children in the group receiving micronutrient powder without zinc gained an extra 0·31 cm (95% CI 0·03-0·59) between 6 and 18 months of age and children receiving micronutrient powder with zinc an extra 0·56 cm (0·29-0·84). We recorded strong evidence of an increased proportion of days with diarrhoea (p=0·001) and increased incidence of bloody diarrhoea (p=0·003) between 6 and 18 months in the two micronutrient powder groups, and reported chest indrawing (p=0·03). Incidence of febrile episodes or admission to hospital for diarrhoea, respiratory problems, or febrile episodes did not differ between the three groups. INTERPRETATION Use of micronutrient powders reduces iron-deficiency anaemia in young children. However, the excess burden of diarrhoea and respiratory morbidities associated with micronutrient powder use and the very small effect on growth recorded suggest that a careful assessment of risks and benefits must be done in populations with malnourished children and high diarrhoea burdens. FUNDING Bill & Melinda Gates Foundation.

Topical application of chlorhexidine to neonatal umbilical cords for prevention of omphalitis and neonatal mortality in a rural district of Pakistan: a community-based, cluster-randomised trial

BACKGROUND Umbilical cord infection (omphalitis) is a risk factor for neonatal sepsis and mortality in low-resource settings where home deliveries are common. We aimed to assess the effect of umbilical-cord cleansing with 4% chlorhexidine (CHX) solution, with or without handwashing with antiseptic soap, on the incidence of omphalitis and neonatal mortality. METHODS We did a two-by-two factorial, cluster-randomised trial in Dadu, a rural area of Sindh province, Pakistan. Clusters were defined as the population covered by a functional traditional birth attendant (TBA), and were randomly allocated to one of four groups (groups A to D) with a computer-generated random number sequence. Implementation and data collection teams were masked to allocation. Liveborn infants delivered by participating TBAs who received birth kits were eligible for enrolment in the study. One intervention comprised birth kits containing 4% CHX solution for application to the cord at birth by TBAs and once daily by family members for up to 14 days along with soap and educational messages promoting handwashing. One intervention was CHX solution only and another was handwashing only. Standard dry cord care was promoted in the control group. The primary outcomes were incidence of neonatal omphalitis and neonatal mortality. The trial is registered with ClinicalTrials.gov, number NCT00682006. FINDINGS 187 clusters were randomly allocated to one of the four study groups. Of 9741 newborn babies delivered by participating TBAs, factorial analysis indicated a reduction in risk of omphalitis with CHX application (risk ratio [RR]=0·58, 95% CI 0·41-0·82; p=0·002) but no evidence of an effect of handwashing (RR=0·83, 0·61-1·13; p=0·24). We recorded strong evidence of a reduction in neonatal mortality in neonates who received CHX cleansing (RR=0·62, 95 % CI 0·45-0·85; p=0·003) but no evidence of an effect of handwashing promotion on neonatal mortality (RR=1·08, 0·79-1·48; p=0·62). We recorded no serious adverse events. INTERPRETATION Application of 4% CHX to the umbilical cord was effective in reducing the risk of omphalitis and neonatal mortality in rural Pakistan. Provision of CHX in birth kits might be a useful strategy for the prevention of neonatal mortality in high-mortality settings. FUNDING The United States Agency for International Development.

Effectiveness of community case management of severe pneumonia with oral amoxicillin in children aged 2–59 months in Matiari district, rural Pakistan: a cluster-randomised controlled trial

BACKGROUND Pneumonia is a leading global cause of morbidity and mortality in children younger than 5 years. In Pakistan, the proportion of deaths due to pneumonia is higher in rural areas than it is in urban areas, with a substantial proportion of individuals dying at home because referral for care is problematic in such areas. We aimed to establish whether community case identification and management of severe pneumonia by oral antibiotics delivered through community health workers has the potential to reduce the number of infants dying at home. METHODS We did a cluster-randomised controlled trial in Matiari district of rural Sindh, Pakistan. Public-sector lady health workers (LHWs) undertook community case management of WHO-defined severe pneumonia. The children in intervention clusters with suspected pneumonia were screened by LHWs and those diagnosed with severe pneumonia were prescribed oral amoxicillin syrup (90 mg/kg per day in two doses) for 5 days at home. Children in control clusters were given one dose of oral co-trimoxazole and were referred to their nearest health facility for admission and intravenous antibiotics, as per government policy. In both groups, follow-up visits at home were done at days 2, 3, 6, and 14 by LHW. The primary outcome was treatment failure by day 6 after enrolment. We matched and randomly allocated 18 clusters (union councils, the smallest administrative unit of the district) to either intervention and control using a computer-generated randomisation scheme. Analyses were done per-protocol. This trial is registered with ClinicalTrials.gov, number NCT01192789. FINDINGS 2341 children in intervention clusters and 2069 children in control clusters participated in the study, enrolled between Feb 13, 2008, and March 15, 2010. We recorded 187 (8%) treatment failures by day 6 in the intervention group and 273 (13%) in the control group. After adjusting for clustering, the risk difference for treatment failure was -5·2% (95% CI -13·7% to 3·3%). We recorded three deaths, two by day 6 and one between days 7 and 14. We recorded no serious adverse events. INTERPRETATION Public sector LHWs in Pakistan were able to satisfactorily diagnose and treat severe pneumonia at home in rural Pakistan. This strategy might effectively reach children with pneumonia in settings where referral is difficult, and it could be a key component of community detection and management strategies for childhood pneumonia. FUNDING US Agency for International Development through grants to John Snow Incorporation and Boston University, USA.

Immunogenicity and safety of the Vi-CRM197 conjugate vaccine against typhoid fever in adults, children, and infants in south and southeast Asia: results from two randomised, observer-blind, age de-escalation, phase 2 trials

BACKGROUND Typhoid vaccination is a public health priority in developing countries where young children are greatly affected by typhoid fever. Because present vaccines are not recommended for children younger than 2 years, the Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM197) for infant immunisation. We aimed to assess the immunogenicity and safety of Vi-CRM197 in participants of various ages in endemic countries in south and southeast Asia. METHODS We did two randomised, observer-blind, age de-escalation, phase 2 trials at two sites in Pakistan and India (study A), and at one site in the Philippines (study B), between March 2, 2011, and Aug 9, 2012. Adults aged 18-45 years, children aged 24-59 months, older infants aged 9-12 months, and infants aged 6-8 weeks were randomly assigned (1:1) with a computer-generated randomisation list (block size of four) to receive either 5 μg Vi-CRM197 or 25 μg Vi-polysaccharide vaccine (or 13-valent pneumococcal conjugate vaccine in children younger than 2 years). Both infant populations received Vi-CRM197 concomitantly with vaccines of the Expanded Programme on Immunization (EPI), according to WHO schedule. With the exception of designated study site personnel responsible for vaccine preparation, study investigators, those assessing outcomes, and data analysts were masked to treatment allocation. We specified no a-priori null hypothesis for the immunogenicity or safety objectives and all analyses were descriptive. Analyses were by modified intention-to-treat. These studies are registered with ClinicalTrials.gov, numbers NCT01229176 and NCT01437267. FINDINGS 320 participants were enrolled and vaccinated in the two trials: 200 in study A (all age groups) and 120 in study B (children and infants only), of whom 317 (99%) were included in the modified intention-to-treat analysis. One dose of Vi-CRM197 significantly increased concentrations of anti-Vi antibody in adults (from 113 U/mL [95% CI 67-190] to 208 U/mL [117-369]), children (201 U/mL [138-294] to 368 U/mL [234-580]), and older infants (179 U/mL [129-250] to 249 U/mL [130-477]). However, in children and older infants, a second dose of conjugate vaccine had no incremental effect on antibody titres and, at all ages, concentrations of antibodies increased substantially 6 months after vaccination (from 55 U/mL [33-94] to 63 U/mL [35-114] in adults, from 23 U/mL [15-34] to 51 U/mL [34-76] in children, and from 21 U/mL [14-31] to 22 U/mL [14-33] in older infants). Immune response in infants aged 6-8 weeks was lower than that in older participants and, 6 months after third vaccination, antibody concentrations were significantly higher than pre-vaccination concentrations in Filipino (21 U/mL [16-28] vs 2.88 U/mL [1.95-4.25]), but not Pakistani (3.76 U/mL [2.77-5.08] vs 2.77 U/mL [2.1-3.66]), infants. Vi-CRM197 was safe and well tolerated and did not induce any significant interference with EPI vaccines. No deaths or vaccine-related serious adverse events were reported throughout the studies. INTERPRETATION Vi-CRM197 is safe and immunogenic in endemic populations of all ages. Given at 9 months of age, concomitantly with measles vaccine, Vi-CRM197 shows a promise for potential inclusion in EPI schedules of countries endemic for typhoid. An apparent absence of booster response and a reduction in antibody titres 6 months after immunisation should be further investigated, but data show that an immunogenic typhoid vaccine can be safely delivered to infants during EPI visits recommended by WHO. FUNDING Sclavo Vaccines Association and Regione Toscana.

A comparative evaluation of multiple micronutrient and iron-folic acid supplementation during pregnancy in Pakistan: Impact on pregnancy outcomes

Background Maternal micronutrient deficiencies are widespread in Pakistan and are potentially associated with maternal undernutrition and intrauterine growth retardation. Intervention strategies largely consist of administration of iron–folic acid supplements during pregnancy. Objective We evaluated the acceptability of multiple micronutrient supplementation and its potential benefits on pregnancy outcomes and maternal micronutrient status in a cohort of pregnant women in rural and urban Sindh through a cluster-randomized design. Methods We randomly assigned 2,378 pregnant women to receive either iron–folic acid or multiple micronutrient supplements. The supplements were administered fortnightly by community health workers who performed home visits to assess tolerance and observe the mothers. Results The women in both groups consumed about 75% of the supplements provided, and few reported adverse effects such as vomiting, abdominal pain, etc. There was a small (70 g) but significant increase in birthweight among infants of mothers receiving multiple micronutrients as compared with infants of mothers receiving iron–folic acid supplements (2.95 ± 0.6 vs. 2.88 ± 0.5 kg, p = .01). This translated into a 10% reduction (p < 0.17) in the proportion of low-birthweight infants among infants of mothers receiving multiple micronutrients. Although stillbirth rates were comparable in the two groups, the early neonatal mortality rate in the group receiving multiple micronutrients was higher, although not significantly, than that in the group receiving iron– folic acid (43.2 vs. 23.5 deaths per 1,000 live births; RR = 1.64; 95% CI, 0.94 to 2.87). Comparable reductions in anemia (hemoglobin < 11 g/dL) were observed, although the proportion with low iron stores (assessed by serum ferritin) was lower in the iron–folic acid group in the postnatal period. Although the proportion of women with subclinical vitamin A deficiency after supplementation did not differ between the two groups, the iron–folic acid group had a higher proportion with lower serum zinc levels in the immediate postpartum period. Conclusions These data suggest that multiple micronutrient supplements are well tolerated during pregnancy, but the effect on birthweight is modest. The observed effect on early neonatal mortality suggests the need for further studies and careful assessment of the intervention in health system settings.

Evaluation of health workforce competence in maternal and neonatal issues in public health sector of Pakistan: an Assessment of their training needs.

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.

Effectiveness of Vi capsular polysaccharide typhoid vaccine among children: a cluster randomized trial in Karachi, Pakistan

BACKGROUND Typhoid fever is endemic in Karachi, with an incidence among children ranging from 170 to 450 per 100,000 child-years. Vaccination strategies are important for prevention, and the Vi capsular polysaccharide (ViCPS) vaccine has been shown to be effective in reducing the burden of typhoid fever. METHODS A cluster randomized trial was conducted in three low socioeconomic urban squatter settlements in Karachi, Pakistan between 2002 and 2007. Subsamples were followed up for assessment of immune response and adverse events after vaccination. RESULTS The study participants were similar in a wide variety of socio-demographic and economic characteristics at baseline. A total of 27,231 individuals of the total target population of 51,965 in 120 clusters either received a ViCPS vaccine (13,238 [52% coverage]) or the control Hepatitis A vaccine (13,993 [53%]). Typhoid fever was diagnosed in 30 ViCPS vaccine recipients and 49 Hepatitis A vaccine recipients with an adjusted total protective effectiveness of 31% (95%CI: -28%, 63%). The adjusted total vaccine protective effectiveness was -38% (95%CI: -192%, 35%) for children aged 2-5 years and 57% (95%CI: 6%, 81%) for children 5-16 years old. CONCLUSION The ViCPS vaccine did not confer statistically significant protection to children in the study areas, and there was a decline in antibody response 2 years post-vaccination. However, the ViCPS vaccine showed significant total protection in children 5-16 years of age, which is consistent with other studies of ViCPS vaccine conducted in India, Nepal, China and South Africa. These findings suggest that ViCPS vaccination of school-aged children will protect the children of urban, typhoid endemic areas against typhoid fever.

Geographical and socioeconomic inequalities in women and children's nutritional status in Pakistan in 2011: an analysis of data from a nationally representative survey

Summary Background Pakistan has one of the highest levels of child and maternal undernutrition worldwide, but little information about geographical and socioeconomic inequalities is available. We aimed to analyse anthropometric indicators for childhood and maternal nutrition at a district level in Pakistan and assess the association of nutritional status with food security and maternal and household socioeconomic factors. Methods We used data from the 2011 Pakistan National Nutrition Survey, which included anthropometric measurements for 33 638 children younger than 5 years and 24 826 women of childbearing age. We estimated the prevalences of stunting, wasting, and underweight among children and of underweight, overweight, and obesity in women for all 143 districts of Pakistan using a Bayesian spatial technique. We used a mixed-effect linear model to analyse the association of nutritional status with individual and household sociodemographic factors and food security. Findings Stunting prevalence in Pakistans districts ranged between 22% (95% credible interval 19–26) and 76% (69–83); the lowest figures for wasting and underweight were both less than 2·5% and the highest were 42% (34–50) for wasting and 54% (49–59) for underweight. In 106 districts, more women were overweight than were underweight; in 49 of these districts more women were obese than were underweight. Children were better nourished if their mothers were taller or had higher weight, if they lived in wealthier households, and if their mothers had 10 or more years of education. Severe food insecurity was associated with worse nutritional outcomes for both children and women. Interpretation We noted large social and geographical inequalities in child and maternal nutrition in Pakistan, masked by national and provincial averages. Pakistan is also beginning to face the concurrent challenge of high burden of childhood undernutrition and overweight and obesity among women of reproductive age. Planning, implementation, and evaluation of programmes for food and nutrition should be based on district-level needs and outcomes. Funding Bill & Melinda Gates Foundation, Grand Challenges Canada, UK Medical Research Council.