X-linked agammaglobulinemia - first case with bruton tyrosine kinase mutation from Pakistan

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency with more than 600 mutations in Bruton tyrosine kinase (Bkt) gene which are responsible for early-onset agammaglobulinemia and repeated infections. Herein we present a case of a 3-year-old boy with history of repeated diarrhoea and an episode of meningoencephalitis with hemiplegia. The workup showed extremely low levels of immunoglobulin with low CD+19 cells. Genetic analysis showed Btk mutation 18 c.1883delCp.T628fs. To the best of our knowledge this is the first report of a case of XLA confirmed by molecular technique from Pakistan

Isoniazid induced acute pancreatitis in a young girl

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

Comparison of clinical and CSF profiles in children with tuberculous and pyogenic meningitis; role of CSF protein: Glucose ratio as diagnostic marker of tuberculous meningitis

Objectives: To compare the clinical and laboratory features of tuberculous meningitis with bacterial meningitis and to determine if protein glucose ratio in the cerebrospinal fluid can be predictive of the condition.Methods: It was a retrospective descriptive study at the Paediatric Ward of Aga Khan University Hospital, Karachi, for which records of 46 patients with tuberculous meningitis and 33 with bacterial meningitis were reviewed. All records related to the study period that was from January 2005 to October 2010. The records were retrieved in December 2010. Tuberculous meningitis was defined as illness \u3e or = 14 days, basal enhancement or tuberculoma on computerised tomography scan and response to anti-tuberculous therapy. Pyogenic meningitis was defined by the presence of a pathogenic isolate inthe cerebrospinal fluid (bacterial culture) or by positive latex particle agglutination or a pathogen on cerebrospinal fluid gram stain and clinical improvement with antibiotics. Logistic regression was used to model the probability of having tuberculous meningitis. To define the optimal protein-glucose ratio, cutoff point for the diagnosis of tuberculous meningitis, a receiver operating characteristic curve was applied. All analysis were done using SPSS 16.Results: Features predictive of a diagnosis of tuberculous meningitis were protein:glucose ratio of \u3e or = 2 (OR 21 95% CI 4.7-93); cerebrospinal fluid total leukocyte count \u3c 800 (OR 58, 95% CI 5-649); and the presence of hydrocephalus (OR 19, 95% CI 3.3-109).Conclusion: A set of simple clinical, laboratory and radiological criteria can help in predicting tuberculous meningitis. The value of cerebrospinal fluid protein:glucose ratio needs to be validated in larger studies with bacteriologically-confirmed cases of tuberculous meningitis

Prevalence and risk factors associated with multi-drug resistant organisms (MDRO) carriage among pediatric patients at the time of admission in a tertiary care hospital of a developing country. A cross-sectional study

Background: The rise of Multidrug-resistant organisms (MDROs) poses a considerable burden on the healthcare systems, particularly in low-middle income countries like Pakistan. There is a scarcity of data on the carriage of MDRO particularly in the pediatrics population therefore, we aimed to determine MDRO carriage in pediatric patients at the time of admission to a tertiary care hospital in Karachi, Pakistan, and to identify the risk factors associated with it.Methods: A cross-sectional study conducted at the pediatric department of Aga Khan University Hospital (AKUH) from May to September 2019 on 347 children aged 1-18 years. For identification of MDRO (i.e., Extended Spectrum Beta-Lactamase (ESBL) producers, Carbapenem Resistant Enterobacteriaceae (CRE), Vancomycin Resistant Enterococci (VRE), Methicillin Resistant Staphylococcus aureus (MRSA), Multidrug-resistant (MDR) Acinetobacter species and MDR Pseudomonas aeruginosa), nasal swabs and rectal swabs or stool samples were cultured on specific media within 72 h of hospitalization. Data was collected on a predesigned structured questionnaire on demographics, prior use of antibiotics for \u3e 48 h in the last 6 months, history of vaccination in last 6 months, exposure to health care facility regardless of the time of exposure, ICU stay for \u3e 72 h, and about the prior use of medical devices (urinary catheter, central venous lines etc.) in last 1 year. Statistical analysis was performed by Standard statistical software.Results: Out of 347 participants, 237 (68.3%) were found to be MDRO carriers. Forty nine nasal swabs from 346 children (14.2%) showed growth of MRSA. The majority of the stool/rectal swabs (n = 222 of 322; 69%) collected were positive for MDRO. The most isolated species were ESBL Escherichia coli 174/222 (78.3%) followed by ESBL Enterobacter species 37/222 (16.7%) and ESBL Klebsiella pneumoniae 35/222 (15.8%). On univariate analysis, none of the risk factors showed statistically significant association with MDRO carriage.Conclusion: Overall, a high prevalence of MDRO carriage was identified among admitted pediatric patients. Implementation of systematic screening may help to identify true burden of MDROs carriage in the health care settings

Multi-drug resistant gram negative infections and use of intravenous polymyxin B in critically ill children of developing country: Retrospective cohort study

Background: Patients in pediatric intensive care Units (PICU) are susceptible to infections with antibiotic resistant organisms which increase the morbidity, mortality and cost of care. To describe the clinical characteristics and mortality in patients with Multi-Drug Resistant (MDR) gram negative organisms. We also report safety of Polymyxin B use in these patients.Methods: Files of patients admitted in PICU of Aga Khan University Hospital, from January 2010 to December 2011, one month to 15 years of age were reviewed. Demographic and clinical features of patients with MDR gram negative infections, antibiotic susceptibility pattern of isolates, discharge disposition and adverse effects of Polymyxin B were recorded.Results: A total of 44.8/1000(36/803) admitted patients developed MDR gram negative infections, of which 47.2%(17/36) were male, with mean age of 3.4 yrs(+/-4.16). Acinetobacter Species (25.5%) was the most frequently isolated MDR organisms followed by Klebsiella Pneumoniae (17%). Sensitivity of isolates was 100% to Polymyxin B, followed by Imipenem (50%), and piperacillin/tazobactem (45%). The crude mortality rate of patients with MDR gram negative infections was 44.4% (16/36). Fourteen of 36 patients received Polymyxin B and 57.1%; (8/14) of them were cured. Nephrotoxicity was observed in 21.4% (3/14) cases, none of the patients showed signs of neuropathy.Conclusion: Our study highlights high rates of Carbapenem resistant gram negative isolates, leading to increasing use of Polymyxin B as the only drug to combat against these critically ill children. Therefore, we emphasizeon Stewardship of Antibiotics and continuous surveillance system as strategies in overall management of these critically ill children

Community-based management and outcome of omphalitis in newborns in Karachi, Pakistan

Objectives: To describe the clinical profile and outcome in newborns with omphalitis managed with home or clinic-based therapy.Methods: The descriptive study was conducted from September 2004 to August 2007 in three low-income communities in Karachi, Pakistan. Newborns with omphalitis detected by community health workers through active surveillance were referred to local clinics. Those with physician-confirmed omphalitis were treated for 7 days with topical gentian violet or oral cephalexin (as monotherapy) or topical gentian violet and oral cephalexin (combination therapy) at physician discretion, or injectable therapy (procaine penicillin and gentamicin) if clinical signs of sepsis were also present and family refused hospital referral. Follow-up was at 48-72 hours and 7 days. SPSS 16 was used for statistical analysis.Results: Among 1083 newborns with omphalitis, 578 (53.4%) had peri-umbilical cellulitis without purulent discharge; 365 (33.7%) had purulent discharge (with or without cellulitis); and 140 (13%) had omphalitis with sepsis Review of outcome data at one week showed that among 943 newborns without signs of sepsis, 938 (99.5%) had improved; 2 (0.2%) died, and 2 (0.2%) were lost to follow-up. There were 5 (3.6%) therapy failures, among 140 newborns with omphalitis and sepsis managed with parenteral antibiotics at 48 hours, but 139 (99.2%) had improved by one week, while 1 (0.8%) died.Conclusion: In resource-constrained environments, omphalitis can be managed in the community with minimal need for hospital referral. Further research to define optimal therapeutic regimens is needed

Systematic review of the global epidemiology, clinical and laboratory profile of enteric fever

Background: Children suffer the highest burden of enteric fever among populations in South Asian countries. The clinical features are non-specific, vary in populations, and are often difficult to distinguish clinically from other febrile illnesses, leading to delayed or inappropriate diagnosis and treatment. We undertook a systematic review to assess the clinical profile and laboratory features of enteric fever across age groups, economic regions, level of care and antibiotic susceptibility patterns.Methods: We searched PubMed (January 1964-December 2013) for studies describing clinical features in defined cohorts of patients over varying time periods. Studies with all culture-confirmed cases or those with at least 50% culture-confirmed cases were included. 242 reports were screened out of 4398 relevant articles and 180 reports were included for final review.Results: 96% of studies were from an urban location, 96% were hospital-based studies, with 41% of studies were from South Asia. Common clinical features in hospitalized children include high-grade fever, coated tongue, anaemia, nausea/vomiting, diarrhea, constipation, hepatomegaly, splenomegaly neutrophilia, abdominal distension and GI bleeding. In adults\u27 nausea/vomiting, thrombocytopenia and GI perforation predominate. The case-fatality rate in children under 5 years is higher than school aged children and adolescents, and is highest in Sub Saharan Africa and North Africa/Middle East regions. Multi-drug resistant enteric fever has higher rates of complications than drug sensitive enteric fever, but case fatality rates were comparable in both.CONCLUSIONS: Our findings indicate variability in disease presentation in adults compared to children, in different regions and in resistant vs sensitive cases. Majority of studies are from hospitalized cases, and are not disaggregated by age. Despite higher complications in MDR enteric fever, case fatality rate is comparable to sensitive cases, with an overall hospital based CFR of 2%, which is similar to recent global estimates. This review underscores the importance of further epidemiological studies in community settings among children and adults, and the need for further preventable measures to curtail the burden of disease

Serum lipid profile as a marker of liver impairment in hepatitis B Cirrhosis patients

Representative GC chromatogram of serum total and free fatty acids of HBV patients and controls along with standards of fatty acid methyl esters.(DOCX 761 kb

Prevalence of hypertension in healthy school children in Pakistan and its relationship with body mass index, proteinuria and hematuria

To determine the prevalence of high blood pressure (BP) in healthy school Pakistani children and its association with high body mass index (BMI), asymptomatic hematuria and proteinuria, we studied 661 public school children and measured their body weight, height and BP and urine dipstick for hematuria performed on a single occasion. Hypertension (BP \u3e95 th centile) and pre-hypertension (BP \u3e90 th centile) were defined based on the US normative BP tables. Over-weight and obesity were defined according to the World Health Organization (WHO) classification of BMI. The mean age of the children was 14 ± 1.3 years. The mean BMI was 18.5 ± 4.3 kg/m 2 . The majority (81.8%) of the children were found to be normotensive (BP centile). Pre-hypertension was observed in 15% and hypertension in 3% of the children. Overweight was observed in 7.7% and obesity in 1% of the children. The independent risk factors for hypertension and pre-hypertension were age of the child (RR 1.2 95% CI 1-1.4), gender (RR 2.0 for being female 95% CI 1-4.4), BMI \u3e25 (RR for BMI b/w 25-30 = 2.6, RR for BMI \u3e30 = 4.3), positive urine dipstick for proteinuria (RR = 2.3 95% CI 0.7-7.7) and positive urine dipstick for hematuria (RR 1.0 95% CI 0.2-8.3). Hypertension in children is strongly correlated with obesity, asymptomatic proteinuria and hematuria. Community based screening programs for children should include BP recording, BMI assessment and urine dipsticks analysis and approach high-risk groups for early detection and lifestyle modifications