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Background: In Pakistan the rate of consanguineous marriages is high, thus, the chance of incidence of autosomal recessive disorders is likely to be high. The aim of this study is to investigate the clinical characteristics and genetics of spinal muscular atrophy (SMA) in children who presented to Aga Khan University, Karachi. Materials and Methods: This study was a retrospective review of the medical charts of children (neonate: 15 years) with discharge diagnosis of SMA during last 10 years. Demographic features, consanguinity, and diagnostic analysis (including genetic analysis) were noted. Results: During the study period 67 children had a discharge diagnosis of SMA. Werdnig Hoffman disease (SMA type I) was the commonest variant seen in 37 (56%) children. Overall 68% were infants. High parental consanguinity was observed in 68% of the study cohort. The history of delayed development and undiagnosed early death was observed in the families of 19 children. Genetic testing was performed in 22 (33%) children. Survival motor neuron (SMN) 1 gene deletion was found in 19 (86%) of the 22 patients in whom the gene analysis was done and 13 (68%) were also positive for neuronal apoptosis inhibitory proteins (NAIP) deletion. Conclusion: SMA is not an uncommon neurodegenerative disorder in Pakistan and SMA type I was the most common type. SMN1 gene deletion was the most common genetic deletion found in this study. In addition, family history of developmental delay and frequent early deaths highlights the need for implementation of prenatal diagnosis for early detection, effective control, and management of this disorder in Pakistan. [ABSTRACT FROM AUTHOR]

Introduction: Iron deficiency anaemia (IDA) and dental caries are prevalent diseases among Pakistani children. Limited research has been done to explore their association with permanent teeth. Given the caries susceptibility of permanent first molars and their role in the development of ideal occlusion, this study aimed to estimate caries frequency in these molars and assess its association with IDA in 7-12 year-old children., Methods and Analysis: This analytical cross-sectional study will include 141 children aged 7-12 years visiting physicians in the paediatric OPD of Dr. Ruth K.M. Pfau, Civil Hospital Karachi. Using consecutive sampling, children who met initial screening criteria were further evaluated to determine eligibility for the study. Data collection will involve physical examinations (including weight and height), oral examinations (including the relevant oral hygiene and caries assessments) and laboratory examinations (including the prescribed tests). In addition, questions will be asked about sociodemographic characteristics, history of IDA, oral hygiene habits, smokeless tobacco use and the frequency of cariogenic dietary consumption. Exposure variable will include the presence of IDA, assessed using complete blood count, C-reactive protein and ferritin tests and treated as a dichotomous variable. Outcome variable will include dental caries in at least one permanent first molar, assessed using the Decayed, Missing, and Filled Teeth index and also treated as a dichotomous variable. Analysis will include Poisson regression with robust variance, reporting prevalence ratios with 95% CIs for the association of IDA and dental caries in the permanent first molars. Frequency of children with carious permanent first molars with 95% CIs will also be reported., Ethics and Dissemination: This research has been approved by ethical review committee of Aga Khan University (Reference number: 2024-9692-30593) and the institutional review board of Dow University of Health Sciences (IRB Reference: IRB-3556/DUHS/Approval/2024/196) before participant recruitment. Results will be disseminated through seminars and peer-reviewed publications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Objective: Healthcare workers are at a higher risk of burnout. The aim of the study was to explore the professional quality of life (QOL) i.e. {Compassion Satisfaction (CS), Burnout (BO) and Secondary Traumatic Stress (STS)} and association of different trainee factors on QOL amongst Pediatric specialty trainees at a private tertiary care hospital in Karachi, Pakistan., Methods: By using a mixed methods explanatory design, pediatric trainees experience of the prior year was measured in 2019 and 2020 through a predefined scale at Aga Khan University Hospital, Professional Quality of Life (ProQOL), followed by focused group discussions. Mean sums of CS, BO and STS were the primary measures assessed and the associations of different trainee factors were to explore experiences of Pediatric trainees towards the residency program, themes and subthemes were created after focused group discussions., Results: We surveyed a total of 118 pediatric responses (n=60 and n=58) during two years.Trainees from both years showed similar moderate level for mean sum of scores for all three components; CS, BO and STS. No significant association was observed with gender, place of living or year of residency. Opinions and perceptions of the trainees in qualitative analysis revealed both positive and negative impacts on the quality of life of the trainees., Conclusion: This study delves into the professional quality of life and offers valuable understanding into the specific events encountered by trainees., (Copyright: © Pakistan Journal of Medical Sciences.)

This study assesses poliovirus type 1 (PV1) immunity in children to inform the contribution of mucosal immunity in and prevention of poliovirus circulation. A community-based study was conducted in periurban Karachi, Pakistan. Randomly selected children (0-15 years of age) received oral poliovirus vaccine (OPV) challenge dose. Blood and stool samples were collected at several time points and evaluated for polio-neutralizing antibodies and serotype-specific poliovirus, respectively. Eighty-one of 589 (14%) children excreted PV1 7 days post-OPV challenge; 70 of 81 (86%) were seropositive at baseline. Twelve of 610 (2%) were asymptomatic wild poliovirus type 1 (WPV1) excretors. Most poliovirus excretors had humoral immunity, suggesting mucosal immunity in these children likely waned or never developed. Without mucosal immunity, they are susceptible to poliovirus infection, shedding, and transmission. Asymptomatic WPV1 excretion suggests undetected poliovirus circulation within the community., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: We aimed to determine the burden of respiratory disease by examining clinical profiles and associated predictors of morbidity and mortality of patients admitted to a Pediatric Intensive Care Unit (PICU) in Pakistan, a resource limited country. We also stratified the respiratory diseases as defined by the Pediatric Advanced Life Support (PALS) Classification., Methods: A retrospective study was conducted on children aged 1 month to 18 years who were diagnosed with respiratory illness at the PICU in a tertiary hospital in Karachi, Pakistan. Demographics, essential clinical details including immunization status, and the outcome in terms of mortality or survival were recorded. Predictors of mortality and morbidity including prolonged intubation and mechanical ventilation in the PICU were analyzed using the chi-square test or Fischer's exact test as appropriate., Results: 279 (63.8% male; median age 9 months, IQR 4-36 months) patients were evaluated of which 44.2% were malnourished and 23.3% were incompletely immunized. The median length of stay in the PICU was 3 days (IQR 2-5 days). Pneumonia was the principal diagnosis in 170 patients (62%) and accounted for most deaths. 76/279 (27.2%) were ventilated, and 67/279(24.0%) needed inotropic support. A high Pediatric Risk of Mortality (PRISM) III score, pneumothorax, and lower airway disease were significantly associated with ventilation support. The mortality rate of patients was 14.3%. Predictors of mortality were a high PRISM III score (OR 1.179; 95% CI 1.024-1.358, P =0.022) and a positive blood culture (OR 4.305; 95% CI 1.062-17.448, P =0.041)., Conclusion: Pneumonia is a significant contributor of respiratory diseases in the PICU in Pakistan and is the leading cause of morbidity and mortality. A high PRISM III score, pneumothorax, and lower airway disease were predictors for ventilation support. A high PRISM III score and a positive blood culture were predictors of patient mortality in our study., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Sidra Ishaque et al.)

Background: Growth faltering is well-recognized during acute childhood illness and growth acceleration during convalescence, with or without nutritional therapy, may occur. However, there are limited recent data on growth after hospitalization in low- and middle-income countries., Methods: We evaluated growth following hospitalization among children aged 2-23 months in sub-Saharan Africa and South Asia. Between November 2016 and January 2019, children were recruited at hospital admission and classified as: not-wasted (NW), moderately-wasted (MW), severely-wasted (SW), or having nutritional oedema (NO). We describe earlier (discharge to 45-days) and later (45- to 180-days) changes in length-for-age [LAZ], weight-for-age [WAZ], mid-upper arm circumference [MUACZ], weight-for-length [WLZ] z-scores, and clinical, nutritional, and socioeconomic correlates., Findings: We included 2472 children who survived to 180-days post-discharge: NW, 960 (39%); MW, 572 (23%); SW, 682 (28%); and NO, 258 (10%). During 180-days, LAZ decreased in NW (-0.27 [-0.36, -0.19]) and MW (-0.23 [-0.34, -0.11]). However, all groups increased WAZ (NW, 0.21 [95% CI: 0.11, 0.32]; MW, 0.57 [0.44, 0.71]; SW, 1.0 [0.88, 1.1] and NO, 1.3 [1.1, 1.5]) with greatest gains in the first 45-days. Of children underweight (<-2 WAZ) at discharge, 66% remained underweight at 180-days. Lower WAZ post-discharge was associated with age-inappropriate nutrition, adverse caregiver characteristics, small size at birth, severe or moderate anaemia, and chronic conditions, while lower LAZ was additionally associated with household-level exposures but not with chronic medical conditions., Interpretation: Underweight and poor linear growth mostly persisted after an acute illness. Beyond short-term nutritional supplementation, improving linear growth post-discharge may require broader individual and family support., Funding: Bill & Melinda Gates FoundationOPP1131320; National Institute for Health ResearchNIHR201813., Competing Interests: Members of the writing group declare having received support from the Bill and Melinda Gates Foundation (BMGF) for staff and research activities directly linked to this project which was paid to their universities or institutions (JAB, JLW, RHJB). Reimbursement for travel directly related to this project was also provided by BMGF and paid through the universities (JLW, JAB). JAB participated in a leadership role for the Commonwealth Association for Paediatic Gastroenterology & Nutrition (CAPGAN) and on a Data Safety Monitoring Board (DSMB) for a study regarding vitamin D., (© 2024 The Authors.)

Objectives: This study evaluated the prevalence and correlates of guideline non-adherence for common childhood illnesses in low-resource settings., Design and Setting: We used secondary cross-sectional data from eight healthcare facilities in six Asian and African countries., Participants: A total of 2796 children aged 2-23 months hospitalised between November 2016 and January 2019 with pneumonia, diarrhoea or severe malnutrition (SM) and without HIV infection were included in this study., Primary Outcome Measures: We identified children treated with full, partial or non-adherent initial inpatient care according to site-specific standard-of-care guidelines for pneumonia, diarrhoea and SM within the first 24 hours of admission. Correlates of guideline non-adherence were identified using generalised estimating equations., Results: Fully adherent care was delivered to 32% of children admitted with diarrhoea, 34% of children with pneumonia and 28% of children with SM when a strict definition of adherence was applied. Non-adherence to recommendations was most common for oxygen and antibiotics for pneumonia; fluid, zinc and antibiotics for diarrhoea; and vitamin A and zinc for SM. Non-adherence varied by site. Pneumonia guideline non-adherence was more likely among patients with severe disease (OR 1.82; 95% CI 1.38, 2.34) compared with non-severe disease. Diarrhoea guideline non-adherence was more likely among lower asset quintile groups (OR 1.16; 95% CI 1.01, 1.35), older children (OR 1.10; 95% CI 1.06, 1.13) and children presenting with wasting (OR 6.44; 95% CI 4.33, 9.57) compared with those with higher assets, younger age and not wasted., Conclusions: Non-adherence to paediatric guidelines was common and associated with older age, disease severity, and comorbidities, and lower household economic status. These findings highlight opportunities to improve guidelines by adding clarity to specific recommendations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Severe Combined Immunodeficiency (SCID) is an autosomal recessive inborn error of immunity (IEI) characterized by recurrent chest and gastrointestinal (GI) infections and in some cases associated with life-threatening disorders., Methodology and Results: This current study aims to unwind the molecular etiology of SCID and also extended the patients' phenotype associated with identified particular variants. Herein, we present 06 disease-causing variants identified in 07 SCID-patients in three different SCID related genes. Whole Exome Sequencing (WES) followed by Sanger Sequencing was employed to explore genetic variations. The results included identification of two previously reported heterozygous variants in homozygous form for the first time in RAG1gene [(p.Arg410Gln);(p.Arg737His)], followed by a recurrent variant (p.Trp959*) in RAG1, a novel variant in IL2RG (p.Asp48Lfs*24), a recurrent variant in IL2RG (p.Gly271Glu) and a recurrent variant in DCLRE1C (p.Arg191*) gene., Conclusion: To conclude, the immune-profiling and WES revealed two novel, two as homozygous state for the first time, and two recurrent disease causing variants contributing valuably to our existing knowledge of SCID., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

This was a follow-up study conducted in 2020 assessing changes in levels of type 2 poliovirus-neutralizing antibodies 2 years postimmunization in children who received inactivated poliovirus vaccine (IPV) in Karachi, Pakistan. Unexpectedly, the findings revealed an increase in seroprevalence of type 2 antibodies from 73.1% to 81.6% 1 year and 2 years after IPV, respectively. The increase in type 2 immunity could result from the intensive transmission of circulating vaccine-derived poliovirus type 2 (cVDPV2) in Karachi during the second year of IPV administration. This study suggests that the cVDPV2 outbreak detected in Pakistan infected large proportions of children in Karachi. Clinical Trials Registration . NCT03286803., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To assess the current status of implementation of the Antimicrobial Stewardship Program (ASP) across Tertiary Care Hospitals in Karachi, Pakistan., Design: Exploratory qualitative case study., Setting: Public and private tertiary care hospitals in Karachi, Pakistan., Participants and Methods: The study data were collected from 3 public and 4 private tertiary care hospitals. Twenty-eight in-depth interviews were conducted from the Chief Executive Officer, Chief Medical Officer, Medical Superintendent, and departmental heads of internal medicine, general surgery, and pediatric, respectively. Purposive sampling was done to include higher and middle managers, whereas the infectious diseases consultant, infectious diseases/clinical pharmacist, and clinical microbiologist were interviewed through snowball sampling methodology. Analysis was done using NVivo. Data were source-triangulated within and among the study setting and study participants., Results: We found that more than two-thirds (n = 5, 71%) of tertiary care hospitals in Karachi do not have a structured ASP which includes major public sector hospitals (n = 3, 43%) and half of the private sector hospitals (n = 4, 29%). The study results led to four broad themes, (1) ASP structure, (2) ASP interventions, (3) hospital medical record-keeping system, and (4) structured way for analyzing and reporting mechanism of data related to the ASP. At H1 and H2, there was a consistency in ASP structure and interventions, whereas paucity seen among remaining tertiary care hospitals., Conclusion: There is an alarming need for ASP in the public and private sector hospitals in Karachi. This study can inform future stakeholders regarding ASP and strategies for structural change at hospitals., Competing Interests: There are no competing interests for any author., (© The Author(s) 2023.)

Scientific literature suggests that pregnant women are at greater risk of acquiring a more severe form of COVID-19 exposing both mother and child to a higher risk of obstetric and neonatal complications. These include increased hospitalization rates, ICU admissions, or ventilatory support among pregnant women when compared to COVID-19 negative pregnant womenA case-control study was conducted at the Aga Khan University Hospital, Karachi, Pakistan with the objective of evaluating the clinical presentation of COVID-19 in pregnancy and its effect on maternal and neonatal outcomes. Data was retrospectively collected from April 2020 till January 2022 of obstetric patients with COVID-19 positive cases and were compared with COVID-19 negative cases from the same time. A total of 491 women were included in the study, 244 cases and 247 controls. The most common complication amongst cases was gestational diabetes mellitus (n = 59, 24%), followed by gestational hypertension (n = 16, 31.7%), pre-eclampsia (n = 13, 5%) Pre-rupture of membrane (85.7%). Amongst the COVID positive mothers the most common presenting complaints were fever followed by dry cough, headache, and shortness of breath. It was observed that COVID-19 did not result in increased adverse maternal or neonatal outcomes compared to COVID-19 negative mothers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zehra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Most biomarker studies of sepsis originate from high-income countries, whereas mortality risk is higher in low- and middle-income countries. The second version of the Pediatric Sepsis Biomarker Risk Model (PERSEVERE-II) has been validated in multiple North American PICUs for prognosis. Given differences in epidemiology, we assessed the performance of PERSEVERE-II in septic children from Pakistan, a low-middle income country. Due to uncertainty regarding how well PERSEVERE-II would perform, we also assessed the utility of other select biomarkers reflecting endotheliopathy, coagulopathy, and lung injury., Design: Prospective cohort study., Setting: PICU in Aga Khan University Hospital in Karachi, Pakistan., Patients: Children (< 18 yr old) meeting pediatric modifications of adult Sepsis-3 criteria between November 2020 and February 2022 were eligible., Interventions: None., Measurements and Main Results: Plasma was collected within 24 hours of admission and biomarkers quantified. The area under the receiver operating characteristic curve for PERSEVERE-II to discriminate 28-day mortality was determined. Additional biomarkers were compared between survivors and nonsurvivors and between subjects with and without acute respiratory distress syndrome. In 86 subjects (20 nonsurvivors, 23%), PERSEVERE-II discriminated mortality (area under the receiver operating characteristic curve, 0.83; 95% CI, 0.72-0.94) and stratified the cohort into low-, medium-, and high-risk of mortality. Biomarkers reflecting endotheliopathy (angiopoietin 2, intracellular adhesion molecule 1) increased across worsening risk strata. Angiopoietin 2, soluble thrombomodulin, and plasminogen activator inhibitor 1 were higher in nonsurvivors, and soluble receptor for advanced glycation end-products and surfactant protein D were higher in children meeting acute respiratory distress syndrome criteria., Conclusions: PERSEVERE-II performs well in septic children from Aga Khan University Hospital, representing the first validation of PERSEVERE-II in a low-middle income country. Patients possessed a biomarker profile comparable to that of sepsis from high-income countries, suggesting that biomarker-based enrichment strategies may be effective in this setting., Competing Interests: Drs. Famularo’s, Kazi’s, Parkar’s, Thompson’s, and Yehya’s institutions received funding from the National Heart, Lung, and Blood Institute. Drs. Kazi, Parkar, Thompson, and Yehya received support for article research from the National Institutes of Health. Drs. Parkar’s and Yehya’s institutions received funding from Pfizer outside of the scope of this work. Dr. Thomas received funding from Bayer AG. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objective: To determine the complementary feeding patterns and their association with malnutrition., Study Design: Prospective observational study. Place and Duration of the Study: Outpatient clinics of Aga Khan University Hospital, Pakistan, from June to November 2019., Methodology: A total of 207 children from age six to twenty-four months, who presented in the outdoor clinics of the study place, were enrolled. Data were recorded in a predesigned data sheet adopted from the infant and young child feeding module. Chi-square test was applied post-stratification and a p-value of <0.05 was taken as significant., Results: Among a total of 207 children, 115 (55.6%) were males and 92 (44.4%) were females, with a mean age of 14.15 ± 5.6 months. Complementary feeding was started at an appropriate age in 124 (60%) children. Normal weight was seen in 133 (64.3%) children, while 73 (35.3%) were underweight. Stunting was presented in 44 (21.3%) children, whereas 163 (78.7%) children were of normal length. The most common reason for early initiation of complementary feeding was difficulty in continuing to breastfeed (n=50, 24.2%); the most common reason behind late complementary feeding was bottle feeding (n=45, 21.7%)., Conclusion: Only sixty percent of mothers living in an urban setting started complementary feeding at an appropriate age. Various myths are counteracting complementary feeding practices., Key Words: Complementary feeding, Infant's nutrition, Stunting, Wasting, Z-score.

Background and Objectives: Acute illness with malnutrition is a common indication for hospitalization among children in low- and middle-income countries. We investigated the association between wasting recovery trajectories and neurodevelopmental outcomes in young children 6 months after hospitalization for an acute illness., Methods: Children aged 2 to 23 months were enrolled in a prospective observational cohort of the Childhood Acute Illness & Nutrition Network, in Uganda, Malawi, and Pakistan between January 2017 and January 2019. We grouped children on the basis of their wasting recovery trajectories using change in mid-upper arm circumference for age z-score. Neurodevelopment was assessed with the Malawi Developmental Assessment Tool (MDAT development-for-age z-score [DAZ]) at hospital discharge and after 6 months., Results: We included 645 children at hospital discharge (mean age 12.3 months ± 5.5; 55% male); 262 (41%) with severe wasting, 134 (21%) with moderate wasting, and 249 (39%) without wasting. Four recovery trajectories were identified: high-stable, n = 112; wasted-improved, n = 404; severely wasted-greatly improved, n = 48; and severely wasted-not improved, n = 28. The children in the severely wasted-greatly improved group demonstrated a steep positive MDAT-DAZ recovery slope. This effect was most evident in children with both wasting and stunting (interaction wasted-improved × time × stunting: P &lt; .001). After 6 months, the MDAT DAZ in children with wasting recovery did not differ from community children. In children who never recovered from wasting, there remained a significant delay in MDAT DAZ scores., Conclusions: Neurodevelopment recovery occurred in parallel with wasting recovery in children convalescing from acute illness and was influenced by stunting.

The objective of this study was to determine the frequency and outcome of preterm infants diagnosed with Necrotising Enterocolitis (NEC). In a case series, 320 preterm infants were enrolled during a period of 12 months at Aga Khan University Hospital, Karachi, a tertiary care hospital. Diagnosis and staging was done as per Bell's staging criteria. Possible confounders were filtered. Analysis was based on the form of treatment and symptom progression. During the study, NEC was observed in 29(9.06%) babies of which stages I, II and III were 69%, 24% and 7%, respectively. Outcome analysis showed that among the 29 neonates diagnosed with NEC, 23 were discharged and 6 expired. A 9% prevalence observed during the study suggests this to be to be a major challenge in neonatology. Mortality outcome of 21% diagnosed with NEC recommends an early diagnosis coupled with prompt and appropriate treatment and preventive measures to reduce the burden of NEC in future.

Background: Current guidelines for the management of childhood wasting primarily focus on the provision of therapeutic foods and the treatment of medical complications. However, many children with wasting live in food-secure households, and multiple studies have demonstrated that the etiology of wasting is complex, including social, nutritional, and biological causes. We evaluated the contribution of household food insecurity, dietary diversity, and the consumption of specific food groups to the time to recovery from wasting after hospital discharge. Methods: We conducted a secondary analysis of the Childhood Acute Illness Network (CHAIN) cohort, a multicenter prospective study conducted in six low- or lower-middle-income countries. We included children aged 6−23 months with wasting (mid-upper arm circumference [MUAC] ≤ 12.5 cm) or kwashiorkor (bipedal edema) at the time of hospital discharge. The primary outcome was time to nutritional recovery, defined as a MUAC > 12.5 cm without edema. Using Cox proportional hazards models adjusted for age, sex, study site, HIV status, duration of hospitalization, enrollment MUAC, referral to a nutritional program, caregiver education, caregiver depression, the season of enrollment, residence, and household wealth status, we evaluated the role of reported food insecurity, dietary diversity, and specific food groups prior to hospitalization on time to recovery from wasting during the 6 months of posthospital discharge. Findings: Of 1286 included children, most participants (806, 63%) came from food-insecure households, including 170 (13%) with severe food insecurity, and 664 (52%) participants had insufficient dietary diversity. The median time to recovery was 96 days (18/100 child-months (95% CI: 17.0, 19.0)). Moderate (aHR 1.17 [0.96, 1.43]) and severe food insecurity (aHR 1.14 [0.88, 1.48]), and insufficient dietary diversity (aHR 1.07 [0.91, 1.25]) were not significantly associated with time to recovery. Children who had consumed legumes and nuts prior to diagnosis had a quicker recovery than those who did not (adjusted hazard ratio (aHR): 1.21 [1.01,1.44]). Consumption of dairy products (aHR 1.13 [0.96, 1.34], p = 0.14) and meat (aHR 1.11 [0.93, 1.33]), p = 0.23) were not statistically significantly associated with time to recovery. Consumption of fruits and vegetables (aHR 0.78 [0.65,0.94]) and breastfeeding (aHR 0.84 [0.71, 0.99]) before diagnosis were associated with longer time to recovery. Conclusion: Among wasted children discharged from hospital and managed in compliance with wasting guidelines, food insecurity and dietary diversity were not major determinants of recovery.

Objective: To assess epidemiological, clinical, and radiological characteristics of the coronavirus disease in children and adults., Methods: The scoping review comprised search on PubMed and Scopus Cochrane databases from January 2020 to April 2021 for English-language articles dealing with clinical and radiological manifestations amongst children and adults affected by coronavirus disease. Two reviewers independently screened the titles and abstracts., Results: Of the 389 studies initially identified, 39(10%) were reviewed in detail. Data suggested that children were less frequently affected by the coronavirus disease. The affected children showed milder disease with low case fatalities compared to the adults., Conclusions: There exists significant gaps in knowledge of clinical and radiological aspects of coronavirus disease, but the available scientific data showed that the disease seems to be unusual in children.

Introduction: Children with primary immunodeficiency disorders (PID) are more susceptible to developing viral infections and are at a substantially increased risk of developing paralytic poliomyelitis. Such children, if given oral polio vaccines tend to excrete poliovirus chronically that may lead to the propagation of highly divergent vaccine-derived poliovirus (VDPV). Consequently, they may act as a reservoir for the community by introducing an altered virus potentially imposing a risk to global polio eradication. However, the risks of chronic and prolonged excretion are not well characterised in the study context. This study seeks to establish a pilot surveillance system for successful identification and monitoring of VDPV excretion among children with PID. It will assess whether the Jeffrey Modell warning signs of PID can be used as an appropriate screening tool for PID in Pakistan., Methods and Analysis: In this pilot surveillance, recruitment of PID cases is currently done at participating hospitals in Pakistan. Potential children are screened and tested against the Jeffrey Modell Foundation (JMF) warning signs for immunodeficiency and their stool is collected to test for poliovirus excretion. Cases excreting poliovirus are followed until the two consecutive negative stool samples are obtained over a period of 6 months. The data will be analysed to calculate hospital-based proportions of total Immunodeficiency-related vaccine-derived poliovirus (iVDPV) cases over a 2-year period and to determine the sensitivity and specificity of the JMF signs., Ethics and Dissemination: This protocol was reviewed and approved by the WHO (WHO Reference-2018/811124-0), Aga Khan University (AKU ERC-2018-0380-1029) and National Bioethics Committee (Ref No. 4-87 NBC-308-Y2). The results will be published in an open access peer-reviewed scientific journal and presented to the iVDPV Working Group members, policy-makers, paediatric consultants and fellow researchers with the same domain interest. It may be presented in scientific conferences and seminars in the form of oral or poster presentations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To determine clinical, laboratory features and outcomes of Multisystem Inflammatory Syndrome in children (MIS-C) and its comparison with historic Kawasaki Disease (KD) and Viral Myocarditis (VM) cohorts., Methods: All children (1 month- 18 years) who fulfilled the World Health Organization criteria of MIS-C presenting to two tertiary care centers in Karachi from May 2020 till August 31st were included. KD and VM admitted to one of the study centers in the last five years prior to this pandemic, was compared to MIS-C., Results: Thirty children with median age of 24 (interquartile range (IQR)1-192) months met the criteria for MIS-C. Three phenotypes were identified, 12 patients (40%) with KD, ten (33%) VM and eight (26%) had features of TSS. Echocardiography showed coronary involvement in 10 (33%), and moderate to severe Left Ventricular dysfunction in 10 (33%) patients. Steroids and intravenous immunoglobulins (IVIG) were administered to 24 (80%) and 12 (41%) patients respectively while 7 (23%) received both. Overall, 20% children expired. During the last five years, 30 and 47 children were diagnosed with KD and VM, respectively. Their comparison with MIS-C group showed lymphopenia, thrombocytosis, and higher CRP as well as more frequent atypical presentation in MIS-C KD group with less coronary involvement. The MIS-C VM was more likely to present with fulminant myocarditis., Conclusions: Our MIS-C cohort is younger with higher mortality compared to previous reports. MIS-C is distinct from historic cohorts of KD and VM in both in clinical features and outcomes., Competing Interests: The authors have declared that no competing interests exist.

Objective: To determine population-based estimates of coronavirus disease 2019 (COVID-19) in a densely populated urban community of Karachi, Pakistan., Methods: Three cross-sectional surveys were conducted in April, June and August 2020 in low- and high-transmission neighbourhoods. Participants were selected at random to provide blood for Elecsys immunoassay for detection of anti-severe acute respiratory syndrome coronavirus-2 antibodies. A Bayesian regression model was used to estimate seroprevalence after adjusting for the demographic characteristics of each district., Results: In total, 3005 participants from 623 households were enrolled in this study. In Phase 2, adjusted seroprevalence was estimated as 8.7% [95% confidence interval (CI) 5.1-13.1] and 15.1% (95% CI 9.4-21.7) in low- and high-transmission areas, respectively, compared with 0.2% (95% CI 0-0.7) and 0.4% (95% CI 0-1.3) in Phase 1. In Phase 3, it was 12.8% (95% CI 8.3-17.7) and 21.5% (95% CI 15.6-28) in low- and high-transmission areas, respectively. The conditional risk of infection was 0.31 (95% CI 0.16-0.47) and 0.41 (95% CI 0.28-0.52) in low- and high-transmission neighbourhoods, respectively, in Phase 2. Similar trends were observed in Phase 3. Only 5.4% of participants who tested positive for COVID-19 were symptomatic. The infection fatality rate was 1.66%, 0.37% and 0.26% in Phases 1, 2 and 3, respectively., Conclusion: Continuing rounds of seroprevalence studies will help to improve understanding of secular trends and the extent of infection during the course of the pandemic., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Fractional dose (one-fifth of full intramuscular dose) of inactivated poliovirus vaccine (fIPV) administered intradermally is used as IPV dose-sparing strategy. We compared the rate of decline of poliovirus antibodies (PVA) in recipients of 2 doses of fIPV or IPV., Methods: A community-based randomized controlled trial was conducted in Karachi, Pakistan. Children aged 14 weeks were randomized into fIPV or full IPV (study arms A, B) and received 1 vaccine dose at age 14 weeks and 1 at age 9 months. PVAs were measured at age 14, 18 weeks and 10, 21 months., Results: Seroprevalence of poliovirus type 2 antibodies in 170/250 (68%) children after 2 IPV or fIPV doses at age 10 months in A and B reached 100% vs 99% (P = .339), and at 21 months, 86% vs 67% (P = .004). Between age 10 and 21 months antibody log2 titers dropped from ≥ 10.5 to 6.8 in A and from 9.2 to 3.7 in B., Conclusions: There was a significant decline in antibody titers 12 months following the second IPV dose. The slope of decline was similar for full IPV and fIPV recipients. The results provide further evidence that fIPV is a viable option for IPV dose-sparing., Clinical Trials Registration: NCT03286803., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

In order to identify the literature and research available on development and implementation of Antimicrobial Stewardship Programme (ASP) in Pakistan, a systematic search of various electronic databases such as PubMed, Cochrane, CINAHL and PakMedinet from January 1, 2008 till November 2018 was conducted. Studies were included if they were focused around the development and implementation of the ASP within Pakistan. The search revealed that a significant knowledge gap exists regarding antimicrobial/antibiotic stewardship within Pakistan and not much is known about the current status of the development and implementation of antimicrobial stewardship programme. Only two research studies were found to be significant. Antimicrobial Stewardship Programme's development and implementation is highly essential and important. Currently, there exists a huge knowledge and systematic gap regarding ASP implementation at healthcare institutions.

A retrospective chart review was carried out in children (neonates to 18 years) who underwent acute surgical abdominal exploration during 2012-2016 at the Aga Khan University Hospital, Karachi, to evaluate the postoperative surgical site infection rates in emergency paediatric abdominal surgery. Incidence of surgical site infection (SSI) was estimated. P-value was calculated, chisquare and non-parametric tests were performed by comparing pre-surgical and post-surgical procedure pathogen occurrence and pre-procedure wound status. Pathogen occurrence related to time-trend of 98 paediatric patients who underwent emergency abdominal surgery was plotted. Of the 94 who were discharged in stable condition, it was found that there was no significant difference between pre- and postsurgical pathogens. Escherichia coli (n=10) was found to be the most common pathogen. Contaminated wounds were associated with higher SSI (p=0.036, OR 1.95 95% CI 0.7-5.4). The study found that pre-surgery wound status could be an indicator for risk of SSI in a post-operative scenario.

The recent rapid rise of multi-drug resistant Enterobacteriaceae (MDR-E) is threatening the treatment of common infectious diseases. Infections with such strains lead to increased mortality and morbidity. Using a cross-sectional study, we aimed to estimate the prevalence of gut colonization with extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae among healthy infants born in Pakistan, a setting with high incidence of MDR-E infections. Stool samples were collected from 104 healthy infants between the ages of 5 and 7 months. Enterobacteriaceae isolates were screened for resistance against several antimicrobial classes. Presence of ESBL and carbapenemase genes was determined using multiplex PCR. Sequence types were assigned to individual strains by multi-locus sequence typing. Phylogenetic analysis of Escherichia coli was done using the triplex PCR method. Forty-three percent of the infants were positive for ESBL-producing Enterobacteriaceae, the majority of which were E. coli. We identified several different ESBL E. coli sequence types most of which belonged to the phylogenetic group B2 (23%) or D (73%). The widespread colonization of infants in a developing country with ESBL-producing Enterobacteriaceae is concerning. The multiple sequence types and reported non-human sources support that multiple non-epidemic MDR lineages are circulating in Pakistan with healthy infants as a common reservoir., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Objective: The aim of this project was to broaden the secondary care hospital's scope of services and provide safe, effective and quality care for the patient presenting with measles., Methods: Six Sigma DMAIC [define measure, analyze, improve, and control (DMAIC)] methodology was used in this quality improvement project. The quality project was started in October 2015 using a Gantt chart quality tool., Results: The paediatric team with the support of administration of the hospital has established isolation rooms and devised a policy for the care and management of patient with airborne infection to avoid cross transmission. During six months period after establishment of isolation room there were sixty two suspected or confirmed measles cases who were admitted in our hospital, out of them only 4(6.4%) of patients were referred because of their sick condition and need of ventilator support. Further, the percentage of patient's satisfaction level also improved from 60 to 80%., Conclusions: After this clinical service innovation, there was significant reduction in referrals of measles patients to another hospital and consequently there was an increase in the patient's satisfaction.

Background: Outbreaks of circulating vaccine derived polioviruses type 2 (cVDPV2) remain a risk to poliovirus eradication in an era without live poliovirus vaccine containing type 2 in routine immunization. We evaluated existing outbreak response strategies recommended by the World Health Organization (WHO) for control of cVDPV2 outbreaks., Methods: Seronegative children for poliovirus type 2 (PV2) at 22 weeks of life were assigned to one of four study groups and received respectively (1) one dose of trivalent oral poliovirus vaccine (tOPV); (2) monovalent OPV 2 (mOPV2); (3) tOPV together with a dose of inactivated poliovirus vaccine (IPV); or (4) mOPV2 with monovalent high-potency IPV type 2. Stool and blood samples were collected and assessed for presence of PV2 (stool) and anti-polio antibodies (sera)., Results: We analyzed data from 265 children seronegative for PV2. Seroconversion to PV2 was achieved in 48, 76, 98 and 100% in Groups 1-4 respectively. mOPV2 was more immunogenic than tOPV alone (p < 0.001); and OPV in combination with IPV was more immunogenic than OPV alone (p < 0.001). There were 33%, 67%, 20% and 43% PV2 excretors in Groups 1-4 respectively. mOPV2 resulted in more prevalent shedding of PV2 than when tOPV was used (p < 0.001); and tOPV together with IPV resulted in lower excretion of PV2 than tOPV alone (p = 0.046)., Conclusion: mOPV2 was a more potent vaccine than tOPV. Adding IPV to OPV improved immunological response; adding IPV also seemed to have shortened the duration of PV2 shedding. mIPV2 did not provide measurable improvement of immune response when compared to conventional IPV. WHO recommendation to use mOPV2 as a vaccine of first choice in cVDPV2 outbreak response was supported by our findings. Clinical Trial registry number: NCT02189811., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: We assessed immunity against polioviruses induced with a new Pakistani poliovirus immunization schedule and compared it to alternative poliovirus immunization schedules., Methods: Newborns were randomized to undergo vaccination based on 1 of 5 vaccination schedules, with doses administered at birth and at 6, 10, and 14 weeks of age. Arm A received inactivated poliovirus vaccine (IPV) at all time points. Arm B received bivalent oral poliovirus vaccine (bOPV) at all time points. Arms C and D received bOPV at the first 3 time points and bOPV plus IPV at the final time point (the current schedule). Arm E received trivalent OPV (tOPV) at all time points. At 22 weeks of age, all children received 1 challenge dose of tOPV, and children in arm D received 1 additional IPV dose. Sera were analyzed for the presence of poliovirus neutralizing antibodies at birth and 14 and 22 weeks of age., Results: Seroconversion for poliovirus type 1 (PV1) at 22 weeks of age was observed in 80% of individuals in arm A, 97% in arm B, 94% in arm C, 96% in arm D, and 94% in arm E; for PV2, seroconversion frequencies were 84%, 19%, 53%, 49%, and 93%, respectively; and for PV3, seroconversion frequencies were 93%, 94%, 98%, 94%, and 85%, respectively., Conclusions: The current immunization schedule in Pakistan induced high seroconversion rates for PV1 and PV3; however, it induced PV2 seroconversion in only half of study subjects. There is a growing cohort of young children in Pakistan who are unprotected against PV2; and this creates an increasing risk of a large-scale outbreak of poliomyelitis caused by circulating vaccine-derived PV2., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Administration of intradermal fractional dose of inactivated poliovirus vaccine (fIPV) has proven to be safe and immunogenic; however, its intradermal application using needle and syringe is technically difficult and requires trained personnel., Methods: We assessed feasibility of conducting an intradermal fIPV campaign in polio high risk neighborhood of Karachi using Tropis needle-free injector. During the one-day fIPV campaign, we measured average "application time" to administer fIPV with Tropis, collected ergonomic information and measured vaccine wastage., Results: Eleven vaccinator teams, after two-day training, immunized 582 children between 4 months and 5 years of age. Average "application time" ranged from 35-75 seconds; the "application time" decreased with the number of children vaccinated from 68 to 38 seconds between 1st and 30th child. 10/11 (91%) vaccinator teams found no ergonomic issues; 1/11 (9%) assessed that it was not easy to remove air bubbles when filling the device. There was 0% vaccine loss reported. No adverse events following immunizations were reported., Interpretation: We demonstrated that it is feasible, safe and efficient to use Tropis for the administration of fIPV in a campaign setting.

Backgound: A higher incidence of neonatal tetanus implies failure of the vaccination program in Pakistan., Objectives: The objective of this study was to assess knowledge, attitudes and practices related to tetanus toxoid (TT) vaccine in women of childbearing age., Methods: We performed a cross-sectional survey in peri-urban Karachi, Pakistan, among women of childbearing age, stratified into three mutually exclusive groups as: married pregnant; married non-pregnant; and unmarried. Descriptive and inferential analyses were performed to estimate vaccine coverage and knowledge attributes., Results: A total of 450 women participated, of which the largest proportion were married and non-pregnant (n = 185/450, 41%). Over 50% of women (n = 258/450) had not received TT vaccine. Most unmarried women (n = 139, 97%) were unvaccinated. Non-vaccination predictors included: women aged <25 years without any formal education (adjusted odds ratio [OR], 2.1; 95% confidence interval [CI], 1.0-4.4), lack of knowledge about free vaccination (adjusted OR, 4.0; 95% CI, 1.64-10.20), poor knowledge of tetanus disease/vaccination (adjusted OR, 4.6; 95%, 2.2-9.6), living with extended family (adjusted OR, 2.0; 95% CI, 1.04-3.96); family non-supporting vaccination (adjusted OR, 5.7; 95% CI, 2.3-13.9); and husband/other family member deciding upon issues related to women's health (adjusted OR, 2.9; 95% CI, 1.3-6.6)., Conclusion: Low coverage of TT vaccine is largely influenced by poor knowledge, family structure and family decision-making in the local communities of Pakistan., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Administration of 1/5th dose of Inactivated poliovirus vaccine intradermally (fIPV) provides similar immune response as full-dose intramuscular IPV, however, fIPV administration with BCG needle and syringe (BCG NS) is technically difficult. We compared immune response after one fIPV dose administered with BCG NS to administration with intradermal devices, referred to as Device A and B; and assessed feasibility of conducting a door-to-door vaccination campaign with fIPV. In Phase I, 452 children 6-12months old from Karachi were randomized to receive one fIPV dose either with BCG NS, Device A or Device B in a health facility. Immune response was defined as seroconversion or fourfold rise in polio neutralizing antibody titer 28days after fIPV among children whose baseline titer ≤362. In Phase II, fIPV was administered during one-day door-to-door campaign to assess programmatic feasibility by evaluating vaccinators' experience. For all three poliovirus (PV) serotypes, the immune response after BCG NS and Device A was similar, however it was lower with Device B (34/44 (77%), 31/45 (69%), 16/30 (53%) respectively for PV1; 53/78 (68%), 61/83 (74%), 42/80 (53%) for PV2; and; 58/76 (76%), 56/80 (70%), 43/77 (56%) for PV3; p<0.05 for all three serotypes). Vaccinators reported problems filling Device B in both Phases; no other operational challenges were reported during Phase II. Use of fIPV offers a dose-saving alternative to full-dose IPV., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Reaching high population immunity against polioviruses (PV) is essential to achieving global polio eradication. Efficacy of oral poliovirus vaccine (OPV) varies and is lower among children living in tropical areas with impoverished environments. Malnutrition found as a risk factor for lower serological protection against PV. We compared whether inactivated polio vaccine (IPV) can be used to rapidly close the immunity gap among chronically malnourished (stunted) infants in Pakistan who will not be eligible for the 14 week IPV dose in routine EPI schedule. A phase 3, multicenter 4-arm randomized controlled trial conducted at five Primary Health Care (PHC) centers in Karachi, Pakistan. Infants, 9-12 months were stratified by length for age Z score into chronically malnourished and normally nourished. Infants were randomized to receive one dose of either bivalent OPV (bOPV) alone or bOPV+IPV. Baseline seroprevalence of PV antibodies and serum immune response to study vaccine dose were assessed by neutralization assay. Vaccine PV shedding in stool was evaluated 7 days after a bOPV challenge dose. Sera and stool were analyzed from 852/928 (92%) enrolled children. At baseline, the seroprevalence was 85.6% (n=386), 73.6% (n=332), and 70.7% (n=319) in malnourished children against PV types 1, 2 and 3 respectively; and 94.1% (n=448), 87.0% (n=441) and 83.6% (n=397) in the normally nourished group (p<0.05). Children had previously received 9-10 doses of bOPV (80%) or tOPV (20%). One dose of IPV+bOPV given to malnourished children increased their serological protection (PV1, n=201, 97.6%; PV2, n=198, 96.1% and PV3, n=189, 91.7%) to parity with normally nourished children who had not received IPV (p=<0.001). Seroconversion and boosting for all three serotypes was significantly more frequent in children who received IPV+bOPV than in those with bOPV only (p<0.001) in both strata. Shedding of polioviruses in stool did not differ between study groups and ranged from 2.4% (n=5) to 7.1% (n=15). In malnourished children the shedding was reduced after bOPV+IPV compared to bOPV only. Chronically malnourished infants were more likely to be unprotected against polioviruses than normal infants. bOPV+IPV helped close the immunity gap better than bOPV alone., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine the efficacy of N-acetylcysteine (NAC) in children aged > 1 month to 16 years admitted with Fulminant Hepatic Failure (FHF) secondary to Acute Viral Hepatitis (AVH) in a tertiary care center of a developing country., Study Design: Analytical study., Place and Duration of Study: Department of Paediatrics, The Aga Khan University Hospital, Karachi, Pakistan, from January 2007 to December 2011., Methodology: Medical records of children (> 1 month - 16 years) with FHF admitted with AVH of known etiology who received NAC were reviewed retrospectively. Liver function tests (mean ± SD) at baseline, 24 hours after NAC and before or at the time of discharge/death were recorded and compared via using repeated measures ANOVA(r-ANOVA). Efficacy of NAC is defined in improvement in biochemical markers, liver function test and discharge disposition (survived or died). Mortality associated risk factors were identified by using logistic regression analysis. P-value and 95% confidence interval were recorded., Results: Forty children (mean age was 80 ± 40 months) with FHF secondary to AVH received NAC. Majority were males (n=25; 63%). Vomiting (75%) and jaundice (65%) were the main presenting symptoms, one-third had hypoglycemic, while 40% had altered sensorium at the time of admission. There was significant statistical difference in liver enzymes and prothrombin time on admission comparing at discharge in children received NAC (p < 0.001). Fifteen (38%) children died. Severe vomiting {Odds Ratio (OR) 0.22, 95% Confidence Interval (CI) 0.05 - 0.8}, jaundice (OR 9.3, CI 1.1 - 82.6), inotropic support (OR 20.6, CI 3.5 - 118.3) and mechanical ventilation (OR 4.3, CI 1.1 - 16.6) at the time of admission are associated with risk factors for mortality in children with FHF secondary to AVH., Conclusion: NAC used in children with FHF secondary to AVH is associated with markedly improved liver function tests and recovery. FHF with complications is high risk for mortality.

Isoniazid (INH) is the mainstay of management against Mycobacterium tuberculosis. INH-induced acute pancreatitis is an uncommon association and with dearth of literature on it. We are reporting a case of an 11 years old girl who developed acute pancreatitis after 2 weeks of antituberculous therapy. An INH free regimen was started. She was discharged and followed without complications.

High measles incidence and frequent epidemics are reported in Pakistan, given the low coverage for measles vaccine. This study evaluated coverage of mass measles campaign 2011 and estimated parental awareness and determinants for low/no coverage. Household survey was conducted 4 months after the measles campaign in Karachi, Pakistan. Parents of children younger than 5 years were administered structured questionnaire about their knowledge and participation in measles campaign. Of 1020 eligible households, only 282 (28%) parents knew about measles supplementary immunization activity, mainly from public announcements (49%). Of these, 174 (62%) children received measles vaccine, whereas, 108 (38%) parents refused measles vaccine. Overall, only 17% children received measles vaccine during this campaign. Low maternal education, not having received DPT/Pentavalent-3 vaccine, and routine vaccination from public Expanded Program on Immunization facility were significant determinants for low coverage. Measles vaccine coverage in Karachi remains low, and sporadic outbreaks of measles every 2 to 3 years are expected unless population coverage can be rapidly increased., (© 2012 APJPH.)

Subacute sclerosing panencephalitis (SSPE) is a rare disorder in the developed world. However, an upsurge has been seen lately in our part of the world owing to inadequate measles immunization coverage. At the midst of our struggle against polio, we are struggling with the war against other vaccine-preventable childhood illnesses like measles. The increasing numbers of SSPE that we reported over the past half decade suggest an underlying periodic measles epidemic in Pakistan. In addition, children are now presenting with SSPE in early childhood, warranting a relook, reinforcement and strengthening of primary immunization and mandatory two-dose measles vaccination for all children nationwide. Previously undertaken Measles Supplementary Immunization Activity were a failure in terms of providing the expected cover against measles in young children. Intensive surveillance and establishment of SSPE registers at the district level is essential for eradication of this easily preventable disorder. Unless timely efforts are made to achieve global immunization, SSPE is bound to add to the national disability burden., (© The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This cluster-randomized interventional trial at periurban settings of Karachi was conducted to evaluate the impact of maternal educational messages regarding appropriate complementary feeding (CF) on the nutritional status of their infants after 30 weeks of educational interventions delivered by trained community health workers. Mothers in the intervention group received three education modules about breastfeeding (BF) and appropriate CF at a baseline visit and two subsequent visits 10 weeks apart. The control group received advice about BF according to national guidelines. Infants' growth [weight, length, and mid-upper arm-circumference (MUAC), stunting, wasting, and underweight] were measured at four time points. At the end of the study, infants in the intervention group had a higher mean weight of 350 g (p=0.001); length of 0.66 cm (p=0.001), and MUAC of 0.46 cm (p=0.002) compared to the controls; proportionate reduction of stunting and underweight were 10% (84% vs. 74%; OR(adj) 8.36 (5.6-12.42) and 5% (25% vs. 20%; OR(adj) 0.75 (0.4-1.79) in the intervention compared to the control group. For relatively food-secure populations, educational interventions about appropriate CF to mothers had a direct positive impact on linear growth of their infants.

Objective: To determine the etiology, clinical manifestation, management (medical and surgical) and complications of children with empyema thoracis in a tertiary care hospital from Karachi, Pakistan., Study Design: Descriptive, analytical study., Place and Duration of Study: Department of Surgery, The Aga Khan University Hospital, Karachi, from January 1996 to December 2010., Methodology: Medical records of admitted children aged > a month to 15 years with discharge diagnosis of empyema thoracis and data was collected on demographic features, clinical manifestation, management and complications. Children managed medically were compared with those managed surgically by using interquartile range and median comparison. Mann-Whitney U test was used to compare age in months, weight (kg) and length of stay in days and presenting complaint, duration of illness; chi-square test was used to compare thrombocytosis in between groups and p-value was calculated., Results: Among the 112 patients, 59 (53%) were younger than 5 years of age. Males (n=83, 74%) were predominant. Fifty (45%) children were admitted in winter. Thirty (27%) children found unvaccinated and one fourth (n=27; 24%) were severely malnourished. Fever, cough, and dyspnea were the major presenting symptoms. Sixty-six (59%) were on some antibiotics prior to admission. Staphylococcus aureus (n=13) and Streptococcus pneumoniae (n=5) were the commonest organism isolated from blood and pleural fluid cultures. Majority of the children required some surgical intervention (n=86). Surgically managed children were younger (p=0.01); had less weight (p=0.01) and prolonged fever (p=0.02); and stayed longer in hospital (p < 0.001) as compared to medically managed children. Requiring readmission (n=8), subcutaneous emphysema (n=5) and recollection of pus (n=5) were the major complications., Conclusion: Staphylococcus aureus was the major organism associated with paediatric empyema thoracis. Early identification and empiric antibiotic as per local data is essential to prevent short and long-term complications. Younger, lower weight children with prolonged fever required surgical management.

A two and a half year old Kenyan girl presented with recurrent chest infections and difficulty in swallowing. Her clinical and laboratory workup was suggestive of lower respiratory tract infection for which she received a course of antibiotics; however, she remains symptomatic after the management of her suspected diagnosis. Therefore, further radiological workup including a chest CT scan and barium study were performed. This showed a homogeneous mass surrounded by ascending and descending aorta in the posterior mediastinum that was compressing the middle esophagus. She had a posterolateral thoracotomy which revealed a cystic mass with smooth surfaces (5x5 cm) in the posterior mediastinum. Histopathology showed branchial cleft cyst predominately lined by stratified squamous epithelium, with lymphocytes predominance. A final diagnosis of posterior mediastinal branchial cleft cyst was made. She was discharged home and remained well at follow-up.

Introduction: Prolonged rupture of membrane (PROM) is an important risk factor for early onset neonatal sepsis (EONS), which is associated with increased neonatal morbidity and mortality. We reported the incidence and associated risk factors of PROM for culture-proven EONS., Methodology: The medical records of all neonates born at Aga Khan University, Karachi over a period of five years (2007-2011) with PROM (> 18 hours) were reviewed. Data about maternal and neonatal risk factors for EONS was collected and adjusted logistic regression (AOR) analysis was applied., Results: Incidence of PROM in this neonatal birth cohort was 27/1,000 live births. A total of 17 (4%) cases with blood-culture proven bacterial sepsis were identified within 72 hours of birth. Klebsiella pneumonia (n = 5; 29%) and Pseudomonas aeruginosa (n = 4; 24%) were the commonest isolates followed by group B Streptococcus (n = 3; 18%) and Escherichia coli (n = 2; 12%). Maternal fever (p = <0.001; AOR, 36.6), chorioamnionitis (p < 0.001; AOR, 4.1), PROM > 48 hr. (p < 0.001; AOR, 8.2), neonatal prematurity < 34 weeks (p < 0.001; AOR, 4.1) and low birth weight < 1,500 grams (p 0.001; AOR, 9.8) along with neonatal thrombocytopenia and raised CRP were found to be independent risk factors associated with culture-proven EONS in PROM., Conclusions: Preventive measures should focus on recognition of these high-risk infants with prompt laboratory screening for sepsis and early institution of empirical antibiotic based on local data. Such approaches would be a safe and cost-effective strategy, especially in developing countries.

Objectives: To identify anthracycline-induced acute (within 1 month) and early-onset chronic progressive (within 1 year) cardiotoxicity in children younger than 16 years of age with childhood malignancies at a tertiary care centre of Pakistan., Design: Prospective cohort study., Setting: Aga Khan University, Karachi, Pakistan., Participants: 110 children (aged 1 month-16 years)., Intervention: Anthracycline (doxorubicin and/or daunorubicin)., Outcome Measurements: All children who received anthracycline as chemotherapy and three echocardiographic evaluations (baseline, 1 month and 1 year) between July 2010 and June 2012 were prospectively analysed for cardiac dysfunction. Statistical analysis including systolic and diastolic functions at baseline, 1 month and 1 year was carried out by repeated measures analysis of variance., Results: Mean age was 74±44 months and 75 (68.2%) were males. Acute lymphoblastic leukaemia was seen in 70 (64%) patients. Doxorubicin alone was used in 59 (54%) and combination therapy was used in 35 (32%). A cumulative dose of anthracycline <300 mg/m(2) was used in 95 (86%). Fifteen (14%) children developed cardiac dysfunction within a month and 28 (25%) children within a year. Of these 10/15 (66.6%) and 12/28 (43%) had isolated diastolic dysfunction, respectively, while 5/15 (33.3%) and 16/28 (57%) had combined systolic and diastolic dysfunction. Seven (6.4%) patients expired due to severe cardiac dysfunction. Eight of 59 (13.5%) children showed dose-related cardiotoxicity (p=<0.001). Cardiotoxicity was also high when the combination of doxorubicin and daunorubicin was used (p=0.004)., Conclusions: Incidence of anthracycline-induced cardiotoxicity is high. Long-term follow-up is essential to diagnose its late manifestations.

Introduction: The incidence, change in antibiotic susceptibility, and risk factors associated with mortality of late-onset Klebsiella pneumoniae sepsis during 2006-2011, in a neonatal intensive care unit (NICU) of a developing country, were analyzed., Methods: The medical records of neonates with a discharge diagnosis of sepsis due to late-onset K. pneumoniae were retrieved. Demographic features, gestational age, date and year of admission, antibiotic susceptibility of isolates, and discharge status were recorded. The late-onset K. pneumoniae incidence per 1000 NICU admissions and risk factors for mortality due to late-onset K. pneumoniae sepsis are reported., Results: During the period 2006-2011, 104 of 2768 neonates developed late-onset K. pneumoniae sepsis. The overall incidence of late-onset K. pneumoniae sepsis was 3.7% (37/1000 NICU admissions), with the highest annual incidence being 53/1000 in 2010. Most cases were males (n = 64; 62%) and most were premature and very low birth weight (n = 68; 65%). More than 80% of isolates were resistant to ampicillin + clavulanic acid, gentamicin, aztreonam, and cephalosporins. An increasing trend of resistance to amikacin, fluoroquinolones, piperacillin/tazobactam, and imipenem was observed. In 2011, three-quarters (72%; n=13) of late-onset K. pneumoniae were CR K. pneumoniae. Seventeen (16%) neonates died. Being male (p = 0.06, adjusted odds ratio (AOR) 9.2, 95% confidence interval (CI) 1.3-66.9), having an extremely low birth weight (p = 0.01, AOR 6.1, 95% CI 0.8-44.4), having severe thrombocytopenia (p = 0.07, AOR 3.9, 95% CI 1.2-13.0), and failure to achieve microbiological clearance (p < 0.001, AOR 19.6, 95% CI 4.0-98.0) were significantly associated with mortality due to late-onset K. pneumoniae sepsis., Conclusion: There has been a rise in carbapenem-resistant strains of late-onset K. pneumoniae, associated with an increased mortality and limited antibacterial choices. Antimicrobial stewardship and rigorous infection control measures seem to be the only way to limit the spread of these strains., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the clinico-demographic features and laboratory parameters of children with severe combined immunodeficiency (SCID)., Study Design: Case series., Place and Duration of Study: Department of Paediatrics and Child Health, the Aga Khan University, Karachi, from July 2006 to July 2011., Methodology: Thirteen infants who were discharged with a diagnosis of SCID were inducted in the study. Their clinicodemographic features and laboratory parameters were determined. Descriptive statistics has been used for computing frequency and percentage., Results: The median age at diagnosis was five months; 5 infants presented within 3 months of life. Three-fourth (77%) were males. Most of the infants were severely malnourished (85%) at the time of presentation. More than two-thirds (69%) were products of consanguineous marriages. All subjects had severe lymphopenia {absolute lymphocyte count (ALC) ranging between 170 - 2280} and low T and B lymphocyte counts., Conclusion: SCID should be considered in infants presenting with severe and recurrent infections. Low ALC (< 2500/mm³), is a reliable diagnostic feature of SCID. These infants should be promptly referred to a facility where stem cell transplant can be done.

The low gestational ages and morbidities of premature neonates in neonatal intensive care units exert a significant impact on neurodevelopmental outcomes. This longitudinal cohort study assessed the neurodevelopmental status of premature neonates after discharge from neonatal intensive care units in resource-limited countries such as Pakistan. Developmental assessment involved the Denver Development Screening Test II. One hundred and ten infants discharged from our neonatal intensive care unit completed follow-up at age 6 months. Overall developmental delay was evident in 32% of infants. Birth weight and gestational age exerted significant impacts on development. The mean gestational age of developmentally normal infants was 34 weeks, whereas that of delayed infants was 30.7 weeks (P < 0.01). The mean birth weight of developmentally normal infants was 2.17 kg vs 1.27 kg in delayed infants (P < 0.01). Neonates who developed complications such as respiratory distress syndrome, intraventricular hemorrhage, thrombocytopenia, hypoglycemia, hyponatremia, or hypothermia in neonatal intensive care units proved to be delayed at age 6 months (P < 0.05). Prematurity and its associated complications are linked to adverse neurodevelopmental outcomes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Fanconi anaemia (FA) is an autosomal recessive inherited disorder with progressive bone marrow failure, associated congenital malformation and solid and haematological malignancies. Acute myeloid leukemia is the commonest haematological malignancy followed by myelodysplastic syndrome in children with FA. FA transformed into acute lymphoblastic leukemia (ALL) is a rare phenomenon and one of the rarest haematological malignancies associated with this disorder. We are reporting a 13 years old girl with FA and positive chromosomal breakage. She required regular blood product transfusion. She was planned for haematopoietic stem cell transplantation (HSCT) but the sibling-matched donor was found to have chromosomal breaks as well. Later on, her peripheral smear showed blast cell. Bone marrow showed pre-B ALL. She was started on chemotherapy but died shortly due to complications of the treatment. For this rare condition conservative management is indeed essential, however, safe and appropriate chemotherapy regimen is needed.

Introduction: Multidrug-resistant strains of Acinetobacter pose a serious therapeutic dilemma in hospital practice, particularly when they cause meningitis, as the few antimicrobial agents to which these isolates are susceptible have poor central nervous system (CNS) penetration., Methodology: We retrospectively reviewed the clinical course and outcome of eight consecutive cases of meningitis due to Acinetobacter spp. in children ages 15 years or less, seen in a tertiary care medical center in Karachi, Pakistan., Results: Of the eight cases of Acinetobacter meningitis, isolates from five patients were pan-resistant, and two were multidrug-resistant. A neurosurgical procedure was performed in five of eight patients followed by external ventricular drain insertion prior to the development of infection. Seven received intravenous (IV) polymyxin (mean; 12.8 days), while 5/8 also received intrathecal (IT) polymyxin (mean; 12.0 days). The mean length of hospitalization was 38.7 ± 19 days. All patients achieved cerebrospinal fluid (CSF) culture negativity by the end of treatment (mean; 5.4 days). Two patients died: one with pan-resistant Acinetobacter, and the second with a multi-drug resistant isolate., Conclusion: Post-neurosurgical multidrug-resistant and pan-resistant Acinetobacter meningitis can be successfully treated if appropriate antimicrobial therapy is instituted early. The role of IT polymyxin B administration alone versus combination therapy (IV and IT) needs further study.

The objective of this study was to determine the incidence, causes, and factors associated with unplanned return visits to emergency department of a tertiary care centre in a low-income country. We conducted a retrospective chart review of all patients who had unplanned returned visit to our emergency department within 48 h of their initial visit during a 1-year study period. The incidence of unplanned revisits is 2%. Two-thirds (69%) of these patients were adults. The most common presenting complaint was fever (29%). During return visits 55% of patients required admission. On multivariable logistic regression model; fever, triage categories 1 and 2, and patients leaving against medical advice were the independent risk factors for revisits requiring admission. Infectious diseases are the leading cause of return visits in our setting., (© 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.)