Early child health in Lahore, Pakistan: XII. Milestones

Psychomotor development was assessed in 1476 infants from four different levels of urbanization in and around Lahore, Pakistan. Development was assessed monthly at birth to 24 months of age by using a set of 10 milestones selected from the Denver Developmental Screening Test and the Developmental Screening Inventory. The psychomotor development of children in the upper middle (Um) class was consistent with reference population groups in Europe and North America, hence this group was used as control. There was significant delay in the psychomotor development of infants belonging to the poorer areas compared to the Um class. There was no sex difference in the development of the milestones in any study area, except for girls in the Um class who were earlier for about one month than boys in talking. Infants in the poorer areas were, on average about 3 months, delayed in their walking and fine motor activity (building a tower of 3 cubes) in comparison with the Um class. Observed disturbance in psychomotor development at an early age may affect the abilities and achievements in later life.     

Prevalence of non-vision-impairing conditions in a village in Chakwal district,Punjab, Pakistan

purpose To determine the prevalence of non-vision-impairing ocular conditions (NVIC) and estimate the number of primary eye care treatments per 1000 population per month. methods A cross-sectional study in a random sample of 1670 people was done to determine the load of NVIC in a village in Chakwal district. results The prevalence of NVIC was 30.6% (306 per 1000 population). NVIC with the exclusion of presbyopia accounted for 14.6%. The main NVIC were allergic conjunctivitis (3.7%), bacterial conjunctivitis (3.5%), pterygium/pinguicula (2.6%) and acute/chronic dacryocystitis (1%). The average Complaint Frequency (CF) per month/1000 population was 55, excluding complaints of near vision and watery eyes. conclusions The foundation of a comprehensive district eye care strategy in the light of VISION 2020 - the Right to Sight - remains an effective primary eye care service whose elements are treatment of NVIC, detection and referral of cataracts and refractive errors, and promotion of eye health.     

DFNB79: reincarnation of a nonsyndromic deafness locus on chromosome 9q34.3

Genetic analysis of an inbred Pakistani family PKDF280, segregating prelingual severe to profound sensorineural hearing loss, provided evidence for a DFNB locus on human chromosome 9q34.3. Co-segregation of the deafness trait with marker D9SH159 was determined by a two-point linkage analysis (LOD score 9.43 at θ=0). Two additional large families, PKDF517 and PKDF741, co-segregate recessive deafness with markers linked to the same interval. Haplotype analyses of these three families refined the interval to 3.84 Mb defined by D9S1818 (centromeric) and D9SH6 (telomeric). This interval overlaps with the previously reported DFNB33 locus whose chromosomal map position has been recently revised and assigned to a new position on chromosome 10p11.23–q21.1. The nonsyndromic deafness locus on chromosome 9q segregating in family PKDF280 was designated DFNB79. We are currently screening the 113 candidate DFNB79 genes for mutations and have excluded CACNA1B, EDF1, PTGDS, EHMT1, QSOX2, NOTCH1, MIR126 and MIR602.     

Epidemiology of Van der Woude syndrome from mutational analyses in affected patients from Pakistan

Malik S, Kakar N, Hasnain S, Ahmad J, Wilcox ER, Naz S. Epidemiology of Van der Woude syndrome from mutational analyses in affected patients from Pakistan. Mutations in IRF6 cause Van der Woude syndrome (VWS), one of the most common syndromes associated with cleft lip (CL) with or without cleft palate (CP). The presence of pits on the lower lip of patients is the most characteristic feature of the syndrome. We have identified three novel and seven previously reported IRF6 mutations in 12 of 16 unrelated families segregating VWS from Pakistan. The three newly identified mutations include a frameshift (c.568delG) and two missense mutations c.295G>A (p.G99S) and c.1219T>C (p.S407P). Recent functional studies on IRF6 and the three‐dimensional structure of IRF5 carboxy (C) terminus, a protein encoded by a paralog of IRF6, shed light on the p.S407P substitution. Additionally, the identification of the same mutations responsible for VWS in Pakistan, as reported in other global populations worldwide, marks these residues as mutational hotspots and indicates their essential role in structural stability or function of IRF6. This is the first study of VWS in Pakistan and we estimate that 1 in 100 patients with CL with or without CP (CL/P) are affected in the Pakistani population predominantly from the Punjab area.     

Mapping of three novel loci for non‐syndromic autosomal recessive mental retardation (NS‐ARMR) in consanguineous families from Pakistan

Rafiq MA, Ansar M, Marshall CR, Noor A, Shaheen N, Mowjoodi A, Khan MA, Ali G, Amin‐ud‐Din M, Feuk L, Vincent JB, Scherer SW. Mapping of three novel loci for non‐syndromic autosomal recessive mental retardation (NS‐ARMR) in consanguineous families from Pakistan. To date, of 13 loci with linkage to non‐syndromic autosomal recessive mental retardation (NS‐ARMR), only six genes have been established with associated mutations. Here we present our study on NS‐ARMR among the Pakistani population, where people are traditionally bound to marry within the family or the wider clan. In an exceptional, far‐reaching genetic survey we have collected more than 50 consanguineous families exhibiting clinical symptoms/phenotypes of NS‐ARMR. In the first step, nine families (MR2‐9 and MR11) with multiple affected individuals were selected for molecular genetic studies. Two families (MR3, MR4) showed linkage to already know NS‐ARMR loci. Fifteen affected and 10 unaffected individuals from six (MR2, MR6, MR7, MR8, MR9 and MR11) families were genotyped by using Affymetrix 5.0 or 6.0 single‐nucleotide polymorphism (SNP) microarrays. SNP microarray data was visually inspected by dChip and genome‐wide homozygosity analysis was performed by HomozygosityMapper. Additional mapping was performed (to exclude false‐positive regions of homozygosity called by HomozygosityMapper and dChip) on all available affected and unaffected members in seven NS‐ARMR families, using microsatellite markers. In this manner we were able to map three novel loci in seven different families originating from different areas of Pakistan. Two families (MR2, MR5) showed linkage on chromosome 2p25.3‐p25.2. Three families (MR7, MR8, and MR9) that have been collected from the same village and belong to the same clan were mapped on chromosome 9q34.3. MR11 maps to a locus on 9p23‐p13.3. Analysis of MR6 showed two positive loci, on chromosome 1q23.2‐q23.3 and 8q24.21‐q24.23. Genotyping in additional family members has so far narrowed, but not excluded the 1q locus. In summary, through this study we have identified three new loci for NS‐ARMR, namely MRT14, 15 and 16.     

Localization of a novel autosomal recessive nonsyndromic hearing impairment locus DFNB65 to chromosome 20q13.2–q13.32

Autosomal recessive nonsyndromic hearing impairment (ARNSHI) is the most frequent form of prelingual hereditary hearing loss in humans. Between 75 and 80% of all nonsyndromic deafness is inherited in an autosomal recessive pattern. Using linkage analysis, we have mapped a novel gene responsible for this form of nonsyndromic hearing impairment, DFNB65, in a consanguineous family from the Azad Jammu and Kashmir regions, which border Pakistan and India. A maximum multipoint LOD score of 3.3 was obtained at marker D20S840. The three-unit support interval is contained between markers D20S902 and D20S430, while the region of homozygosity is flanked by markers D20S480 and D20S430. The novel locus maps to a 10.5-cM region on chromosome 20q13.2–q13.32 and corresponds to a physical map distance of 4.3 Mb. DFNB65 represents the first ARNSHI locus to map to chromosome 20.     

Evidence-based training of frontline health workers for door-to-door health promotion: a pilot randomized controlled cluster trial with Lady Health Workers in Sindh Province, Pakistan

OBJECTIVE: Demonstrate the effective use of community-based evidence for health promotion by Lady Health Workers (LHWs) in Sindh, Pakistan. METHODS: A baseline study on mothers and children provided local evidence for risk communication tools designed and tested by LHWs. The communities were randomized to intervention and control. LHWs visited women before and after childbirth to discuss safe practices in pregnancy, in the intervention group LHW using the new tools and in the control group using their standard procedures. A household survey and focus groups permitted assessment of the impact of the intervention. RESULTS: Women in the intervention communities were more likely to attend prenatal checkups, to stop routine heavy work during pregnancy, to give colostrum to newborn babies, and to maintain exclusive breastfeeding for four months. Community focus groups confirmed a positive reaction to the tools. CONCLUSION: Discussion by lay health workers of local evidence underlying safe motherhood messages improved uptake of protective health practices. PRACTICE IMPLICATIONS: Door-to-door health promotion based on culturally appropriate interaction around relevant evidence can have a positive impact on health practices. Engaging health workers from the onset builds capacities, improves dialogue within the health system and performance of frontline health workers.     

Human infection with avian influenza virus, Pakistan, 2007

Human infection with avian influenza (H5N1) virus raises concern for the possibility of a pandemic. We report 20 cases, which ranged from asymptomatic to fatal, in Pakistan in 2007. These cases indicate human-to-human-to-human transmission of this virus, and the number of cases may be higher than realized.     

Health sector decentralization and local decision-making: Decision space, institutional capacities and accountability in Pakistan

Health sector decentralization has been widely adopted to improve delivery of health services. While many argue that institutional capacities and mechanisms of accountability required to transform decentralized decision-making into improvements in local health systems are lacking, few empirical studies exist which measure or relate together these concepts. Based on research instruments administered to a sample of 91 health sector decision-makers in 17 districts of Pakistan, this study analyzes relationships between three dimensions of decentralization: decentralized authority (referred to as "decision space"), institutional capacities, and accountability to local officials. Composite quantitative indicators of these three dimensions were constructed within four broad health functions (strategic and operational planning, budgeting, human resources management, and service organization/delivery) and on an overall/cross-function basis. Three main findings emerged. First, district-level respondents report varying degrees of each dimension despite being under a single decentralization regime and facing similar rules across provinces. Second, within dimensions of decentralization-particularly decision space and capacities-synergies exist between levels reported by respondents in one function and those reported in other functions (statistically significant coefficients of correlation ranging from ρ=0.22 to ρ=0.43). Third, synergies exist across dimensions of decentralization, particularly in terms of an overall indicator of institutional capacities (significantly correlated with both overall decision space (ρ=0.39) and accountability (ρ=0.23)). This study demonstrates that decentralization is a varied experience-with some district-level officials making greater use of decision space than others and that those who do so also tend to have more capacity to make decisions and are held more accountable to elected local officials for such choices. These findings suggest that Pakistan's decentralization policy should focus on synergies among dimensions of decentralization to encouraging more use of de jure decision space, work toward more uniform institutional capacity, and encourage greater accountability to local elected officials.