Publications by authors named "Sonia Qureshi"

27 Publications

  • Page 1 of 1

Selected Thiadiazine-Thione Derivatives Attenuate Neuroinflammation in Chronic Constriction Injury Induced Neuropathy.

Front Mol Neurosci 2021 16;14:728128. Epub 2021 Dec 16.

Department of Pharmacy, University of Peshawar, Peshawar, Pakistan.

Neuropathic pain refers to a lesion or disease of peripheral and/or central somatosensory neurons and is an important body response to actual or potential nerve damage. We investigated the therapeutic potential of two thiadiazine-thione [TDT] derivatives, 2-(5-propyl-6-thioxo-1, 3, 5-thiadiazinan-3-yl) acetic acid [TDT1] and 2-(5-propyl-2-thioxo-1, 3, 5-thiadiazinan-3-yl) acetic acid [TDT2] against CCI (chronic constriction injury)-induced neuroinflammation and neuropathic pain. Mice were used for assessment of acute toxicity of TDT derivatives and no major toxic/bizarre responses were observed. Anti-inflammatory activity was assessed using the carrageenan test, and both TDT1 and TDT2 significantly reduced carrageenan-induced inflammation. We also used rats for the induction of CCI and performed allodynia and hyperalgesia-related behavioral tests followed by biochemical and morphological analysis using RT-qPCR, immunoblotting, immunohistochemistry and immunofluorescence. Our findings revealed that CCI induced clear-cut allodynia and hyperalgesia which was reversed by TDT1 and TDT2. To determine the function of TDT1 and TDT2 in glia-mediated neuroinflammation, Iba1 mRNA and protein levels were measured in spinal cord tissue sections from various experimental groups. Interestingly, TDT1 and TDT2 substantially reduced the mRNA expression and protein level of Iba1, implying that TDT1 and TDT2 may mitigate CCI-induced astrogliosis. molecular docking studies predicted that both compounds had an effective binding affinity for TNF-α and COX-2. The compounds interactions with the proteins were dominated by both hydrogen bonding and van der Waals interactions. Overall, these results suggest that TDT1 and TDT2 exert their neuroprotective and analgesic potentials by ameliorating CCI-induced allodynia, hyperalgesia, neuroinflammation and neuronal degeneration in a dose-dependent manner.
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http://dx.doi.org/10.3389/fnmol.2021.728128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716630PMC
December 2021

Long Term Impact on Lung Function of Patients With Moderate and Severe COVID-19. A Prospective Cohort Study.

Front Public Health 2021 7;9:663076. Epub 2021 Dec 7.

Departments of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan.

In Pakistan, the cases of COVID-19 have declined from 6000 per day in June to 600 in September 2020. A significant number of patients continue to recover from the disease, however, little is known about the lung function capacity among survivors. We aim to determine the long-term impact on lung function capacity in patients who have survived moderate or severe COVID-19 disease in a resource-poor setting. This prospective cohort study will be conducted at Aga Khan University Hospital (AKUH), Karachi Pakistan. Patients 15 years and above who have survived an episode of moderate or severe COVID-19, have reverse transcriptase-polymerase chain reaction (RT-PCR) positive for COVID 19 (nasopharyngeal or oropharyngeal) will be included. Patients with a pre-existing diagnosis of obstructive or interstitial lung disease, lung fibrosis, lung cancers, connective tissue disorders, autoimmune conditions affecting the lungs, underlying heart disease, history of syncope and those who refuse to participate will be excluded from the study. Pulmonary function will be assessed using spirometry and diffusion lung capacity for carbon monoxide (DLCO) at 3- and 6-months interval from the time of discharge from the hospital. Additionally, a chest X-ray and CT-chest will be performed if clinically indicated after consultation with the study pulmonologist or Infectious Disease (ID) physician. Echocardiogram (ECHO) will be performed to look for pulmonary hypertension at the 3 month visit and repeated at 6 months in case any abnormality is identified in the initial ECHO. Data analysis will be performed using standard statistical software. The study was approved by the Ethical Review Committee (ERC) of the institution (ERC reference number 2020-4735-11311). This cohort study will provide evidence on the long-term impact on lung function among COVID-19 survivors with moderate to severe disease. Such data will be key in understanding the impact of the disease on vital functions and will help devise rehabilitative strategies to best overcome the effects of disease. However, this will be a single-center, study recruiting only a limited number of COVID-19 survivors.
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http://dx.doi.org/10.3389/fpubh.2021.663076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688692PMC
January 2022

Salmonellosis Including Enteric Fever.

Pediatr Clin North Am 2022 02;69(1):65-77

Department of Paediatrics & Child Health, The Aga Khan University Hospital, Stadium Road, P.O Box 3500, Karachi 74800, Pakistan.

Salmonella is a gram-negative, motile, nonsporulating, facultative anaerobic bacillus, belongs to the family Enterobacteriaceae. The bacteria were first identified in 1884. It is transmitted through direct contact with an infected person or indirect contact by the consumption of contaminated food and water. More than 2500 serotypes of Salmonella enterica have been identified but less than 100 serotypes are known to cause infections in humans. S. enterica serovar typhi (S. typhi) and S. enterica serovar paratyphi (S. paratyphi A B C) cause enteric fever, whereas nontyphoidal Salmonella serotypes (NTS) cause diarrhea. NTS commonly presents with gastroenteritis and is a self-limiting disease. Enteric fever is a potentially life-threatening acute febrile systemic infection and is diagnosed by isolating a pathogen on culture. With the emergence of the extensive drug-resistant (XDR) S. typhi clone, limited treatment options are available. Vaccination of persons at risk, improvement of sanitation, promotion of food hygiene, and detection and control of chronic carriers are essential preventive control measures of enteric fever.
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http://dx.doi.org/10.1016/j.pcl.2021.09.007DOI Listing
February 2022

Tebipenem as an oral alternative for the treatment of typhoid caused by XDR Salmonella Typhi.

J Antimicrob Chemother 2021 11;76(12):3197-3200

University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.

Background: Antimicrobial therapy is essential for the treatment of enteric fever, the infection caused by Salmonella serovars Typhi and Paratyphi A. However, an increase in resistance to key antimicrobials and the emergence of MDR and XDR in Salmonella Typhi poses a major threat for efficacious outpatient treatments.

Objectives: We recently identified tebipenem, an oral carbapenem licensed for use for respiratory tract infections in Japan, as a potential alternative treatment for MDR/XDR Shigella spp. Here, we aimed to test the in vitro antibacterial efficacy of this drug against MDR and XDR typhoidal Salmonella.

Methods: We determined the in vitro activity of tebipenem in time-kill assays against a collection of non-XDR and XDR Salmonella Typhi and Salmonella Paratyphi A (non-XDR) isolated in Nepal and Bangladesh. We also tested the efficacy of tebipenem in combination with other antimicrobials.

Results: We found that both XDR and non-XDR Salmonella Typhi and Salmonella Paratyphi A are susceptible to tebipenem, exhibiting low MICs, and were killed within 8-24 h at 2-4×MIC. Additionally, tebipenem demonstrated synergy with two other antimicrobials and could efficiently induce bacterial killing.

Conclusions: Salmonella Paratyphi A and XDR Salmonella Typhi display in vitro susceptibility to the oral carbapenem tebipenem, while synergistic activity with other antimicrobials may limit the emergence of resistance. The broad-spectrum activity of this drug against MDR/XDR organisms renders tebipenem a good candidate for clinical trials.
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http://dx.doi.org/10.1093/jac/dkab326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8598285PMC
November 2021

Effectiveness of typhoid conjugate vaccine against culture-confirmed typhoid in a peri-urban setting in Karachi: A case-control study.

Vaccine 2021 09 28;39(40):5858-5865. Epub 2021 Aug 28.

Department of Pediatrics and Child Health, Aga Khan University Hospital, National Stadium Rd, Aga Khan University Hospital, Karachi City, Sindh 74800, Pakistan. Electronic address:

Background: Enteric fever, caused by Salmonella Typhi and S. Paratyphi, is a cause of high morbidity and mortality among children in South Asia. Rising antimicrobial resistance presents an additional challenge. Typhoid Conjugate Vaccines (TCV) are recommended by the World Health Organization for use among people 6 months to 45 years old living in endemic settings. This study aimed to assess the effectiveness of TCV against culture-confirmed S. Typhi in Lyari Town, Karachi, Pakistan. This peri-urban town was one of the worst affected by the outbreak of extensively drug resistant (XDR) typhoid that started in November 2016.

Methods: A matched case-control study was conducted following a mass immunization campaign with TCV at three key hospitals in Lyari Town Karachi, Pakistan. Children aged 6 months to 15 years presenting with culture-confirmed S. Typhi were enrolled as cases. For each case, at least 1 age-matched hospital control and two age-matched community controls were enrolled. Adjusted odds ratios with 95% confidence intervals (CIs) were calculated using conditional logistic regression.

Results: Of 82 typhoid fever patients enrolled from August 2019 through December 2019, 8 (9·8%) had received vaccine for typhoid. Of the 164 community controls and 82 hospital controls enrolled, 38 (23·2%) community controls and 27 (32·9%) hospital controls were vaccinated for typhoid. The age and sex-adjusted vaccine effectiveness was found to be 72% (95% CI: 34% - 88%). The consumption of meals prepared outside home more than once per month (adjusted odds ratio: 3·72, 95% CI: 1·55- 8·94; p-value: 0·003) was associated with the development of culture-confirmed typhoid.

Conclusion: A single dose of TCV is effective against culture confirmed typhoid among children aged 6 months to 15 years old in an XDR typhoid outbreak setting of a peri-urban community in Karachi, Pakistan.
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http://dx.doi.org/10.1016/j.vaccine.2021.08.051DOI Listing
September 2021

Detection of typhoid carriers by duodenal fluid culture in a tertiary care hospital, Karachi: A cross-sectional study.

J Pak Med Assoc 2021 Aug;71(8):2069-2072

Department of Paediatrics and Child Health, Aga Khan University Hospital, Karachi, Pakistan.

We aimed to detect typhoid carriers by performing duodenal fluid culture in patients in a tertiary care hospital in Pakistan. A cross-sectional study was conducted during 2017 at the Aga Khan University Hospital, Karachi. Patients who underwent upper gastrointestinal endoscopy were included. Participants were interviewed, and duodenal fluid samples were taken for culture to detect Salmonella typhi (S. typhi) and paratyphi. A polymerase chain reaction on 100 randomly selected sub-samples was also conducted. A total of 477 participants were enrolled. The mean age was 42.4±15.5 years. History of typhoid fever was present in 73 (15.3%) participants. Out of the 477 duodenal fluid cultures tested for various micro-organisms, 250 (52.4%) were positive. Neither S. typhi nor paratyphi were isolated. S. typhi was also not detected by PCR. To better detect S. typhi carriage in general population, future studies should target people with gall bladder diseases and screen them using culture and PCR based methods.
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http://dx.doi.org/10.47391/JPMA.580DOI Listing
August 2021

Effectiveness of typhoid conjugate vaccine against culture-confirmed Salmonella enterica serotype Typhi in an extensively drug-resistant outbreak setting of Hyderabad, Pakistan: a cohort study.

Lancet Glob Health 2021 08;9(8):e1154-e1162

Department of Paediatrics and Child Health, Aga Khan University Hospital, Karachi, Pakistan. Electronic address:

Background: Salmonella enterica serotype Typhi (S Typhi) is a major public health problem in low-income and middle-income countries. We aimed to investigate the effectiveness and impact of the typhoid conjugate vaccine Typbar-TCV against S Typhi among children in an outbreak setting of extensively drug-resistant (XDR) S Typhi in Pakistan.

Methods: This cohort study was done from Feb 21, 2018, to Dec 31, 2019. A census survey of all households located in the Qasimabad and Latifabad subdistricts of Hyderabad, Pakistan, was done at baseline, and 174 005 households were registered in the census. The Typbar-TCV immunisation campaign was initiated at temporary vaccination centres and 207 000 children aged 6 months to 10 years were vaccinated from Feb 21, 2018, to Dec 31, 2018. Social mobilisers informed parents about the vaccination process. Vaccination records were maintained electronically and linked with the household census surveys. Active surveillance for suspected and blood-culture-confirmed S Typhi was established in hospitals, clinics, and laboratories to assess the following outcomes: cases of suspected typhoid fever, culture-confirmed S Typhi, and antimicrobial resistance. An age-stratified cohort of 1100 vaccinated children was randomly selected from the vaccination registry, tested for Vi-IgG antibodies (data not reported), and followed up fortnightly (via telephone calls or household visits) until Dec 31, 2019, for ascertainment of outcomes during the study period. 20 847 vaccinated and unvaccinated children were randomly selected from the census registry as a quality control cohort and followed up from Oct 1 to Dec 31, 2019, for ascertainment of outcomes. Vaccine effectiveness against suspected, culture-confirmed, and XDR S Typhi was calculated.

Findings: 23 407 children from the census registry and surveillance system were included in the vaccine effectiveness analysis. 13 436 (57·4%) children were vaccinated, 12 214 (52·2%) were male, and 10 168 (43·4%) were aged 6-59 months. 5378 (23·0%) of 23 407 children had suspected S Typhi, among whom 775 (14·4%) had culture-confirmed S Typhi and 361 (68·6%) of 526 had XDR S Typhi. Vaccine effectiveness was 55% (95% CI 52-57) against suspected S Typhi (regardless of culture confirmation), 95% (93-96) against culture-confirmed S Typhi, and 97% (95-98) against XDR S Typhi.

Interpretation: Typbar-TCV is effective in protecting children against S Typhi infection in an outbreak setting, and was able, with moderate deployment, to curtail a major XDR S Typhi outbreak in a densely populated setting. The vaccine shows efficacy against S Typhi irrespective of antimicrobial resistance.

Funding: Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S2214-109X(21)00255-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315145PMC
August 2021

A retrospective review on antibiotic use in acute watery diarrhea in children in a tertiary care hospital of Karachi, Pakistan.

PLoS One 2021 15;16(7):e0253712. Epub 2021 Jul 15.

Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan.

Introduction: Responsible for at least one in nine pediatric deaths, diarrheal diseases are the leading, global cause of death. Further abetted by improper antibiotic use in a hospital setting, children with acute watery diarrhea can see prolonged hospital stays, and unwanted adverse effects such as antibiotic resistance. Hence, this study is aimed to identify the association between antibiotic usage for the treatment of acute watery diarrhea in children, and the impact this line of management has on the duration of their hospital stay.

Methods: A retrospective review was conducted at the department of Pediatric of Aga Khan University Hospital (AKUH) in Karachi. A total of 305 records of children aged 6 months to 5 years who were admitted with a diagnosis of acute watery diarrhea from June 2017 -December 2018 was screened, of which 175 fulfilled the eligibility criteria. A predesigned questionnaire was used to collect demographic information, comorbidities, and clinical features, severity of dehydration, clinical examination, treatment received, and laboratory investigations. The primary outcome of this study was the length of hospital stay measured against the number of hours a child stayed in hospital for treatment of acute watery diarrhea. The statistical analysis was carried out using STATA version 14 to reach conclusive results.

Results: 175 patients presented with acute watery diarrhea, out of which 106 (60.6%) did not receive antibiotics. The median (IQR) age of the group that did not receive antibiotics was 12.0 (12.0) months compared to 15.0 (12.0) months for the group that did receive antibiotics. In both groups, there were more males than females, less than 15% of the patients were severely malnourished (WHZ score -3SD) and less than 10% of the patients were severely dehydrated. The median (IQR) length of hospital stay (hours) was 32.0 (19.0) respectively for the group that did not receive antibiotic and 41.0 (32.0) for the group that did receive antibiotic therapy. The expected length of hospital stay for the group that received antibiotic therapy was 0.22 hours higher than the group that did not. Finally, as compared to females, hospital stay for males was longer by 0.25 hours.

Conclusion: In conclusion, antibiotic use was associated with a prolonged hospital stay in children with acute watery diarrhea as compared to children who did not receive antibiotics. Large scale robust prospective studies are needed to establish this association using this observational data.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253712PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282082PMC
November 2021

A review of toolkits and case definitions for detecting enteric fever outbreaks in Asian and African countries from 1965-2019.

J Glob Health 2021 May 29;11:04031. Epub 2021 May 29.

Department of Pediatrics and Child Health, The Aga Khan University Hospital, Aga Khan University Karachi, Pakistan.

Background: This review assessed the case definitions, diagnostic criteria, antimicrobial resistance, and methods used for enteric fever outbreaks and utilization of any unified outbreak score or checklist for early identification and response in Asia and Africa from 1965-2019.

Methods: We searched enteric fever outbreaks using PubMed, Google Scholar, and the Cochrane library. Studies describing a single outbreak event of enteric fever in Asia and Africa from 1965-2019 were reviewed. We excluded case reports, letter to editors, studies reporting typhoid in conjunction with other diseases, the Centers for Disease Control and Prevention (CDC) trip reports, the World Health Organization (WHO) bulletins report, data from mathematical modeling and simulation studies, reviews and ProMed alert. Also, non-typhoidal salmonella outbreaks were excluded.

Results: A total of 5063 articles were identified using the key terms and 68 studies were selected for data extraction. Most (48, 71%) outbreaks were from Asian countries, 20 (29%) were reported from Africa. Only 15 studies reported the case definition used for case identification during an outbreak and 8 of those were from Asia. A third (20, 29%) of the studies described antibiotic resistance pattern. 43 (63%) studies contained information regarding the source of the outbreak. Outcomes (hospitalization and deaths) were reported in a quarter of studies. Only 23 (29%) of the studies reported outbreak control strategies while none reported any unified outbreak score or a checklist to identify the outbreak.

Conclusion: This review highlights the variability in detection and reporting methods for enteric fever outbreaks in Asia and Africa. No standardized case definitions or laboratory methods were reported. Only a few studies reported strategies for outbreak control. There is a need for the development of a unified outbreak score or a checklist to identify and report enteric fever outbreaks globally.
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http://dx.doi.org/10.7189/jogh.11.04031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183158PMC
May 2021

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.

BMC Infect Dis 2021 Jun 9;21(1):547. Epub 2021 Jun 9.

Department of Pediatrics and Child Health, Aga Khan University Hospital, Karachi, Pakistan.

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 > 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 > 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.
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http://dx.doi.org/10.1186/s12879-021-06275-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191205PMC
June 2021

Strategies to Improve Coverage of Typhoid Conjugate Vaccine (TCV) Immunization Campaign in Karachi, Pakistan.

Vaccines (Basel) 2020 Nov 19;8(4). Epub 2020 Nov 19.

Department of Pediatrics and Child Health, Aga Khan University Hospital, National Stadium Rd, Aga Khan University Hospital, Karachi City, Sindh 74800, Pakistan.

The emergence and spread of extensively drug-resistant (XDR) typhoid in Karachi, Pakistan led to an outbreak response in Lyari Town, Karachi utilizing a mass immunization campaign with typhoid conjugate vaccine (TCV), Typbar TCV®. The mass immunization campaign, targeted Lyari Town, Karachi, one of the worst affected towns during the XDR typhoid outbreak. Here we describe the strategies used to improve acceptance and coverage of Typbar TCV in Lyari Town, Karachi. The mass immunization campaign with Typbar TCV was started as a school- and hospital-based vaccination campaign targeting children between the age of 6 months to 15 years old. A dose of 0.5 mL Typbar TCV was administered intramuscularly. A mobile vaccination campaign was added to cope with high absenteeism and non-response from parents in schools and to cover children out of school. Different strategies were found to be effective in increasing the vaccination coverage and in tackling vaccine hesitancy. Community engagement was the most successful strategy to overcome refusals and helped to gain trust in the newly introduced vaccine. Community announcements and playing typhoid jingles helped to increase awareness regarding the ongoing typhoid outbreak. Mop-up activity in schools was helpful in increasing coverage. Networking with locally active groups, clubs and community workers were found to be the key factors in decreasing refusals.
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http://dx.doi.org/10.3390/vaccines8040697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711991PMC
November 2020

Response of extensively drug resistant Salmonella Typhi to treatment with meropenem and azithromycin, in Pakistan.

PLoS Negl Trop Dis 2020 10 15;14(10):e0008682. Epub 2020 Oct 15.

Department of Pediatrics and Child Health, Aga Khan University Hospital, Karachi, Pakistan.

Introduction: Salmonella Typhi is one of the leading health problems in Pakistan. With the emergence of extensively drug resistant (XDR) Salmonella Typhi, treatment options are limited. Here we report the clinical manifestations and the response to treatment of patients with XDR Typhoid fever. The patients were treated with either Meropenem or Azithromycin or a combination of both.

Methods: We reviewed the records of culture confirmed XDR typhoid who visited Aga Khan University Hospital (AKUH), Karachi and Aga Khan Secondary Care Hospital, Hyderabad from April 2017 to June 2018. Symptoms developed during disease, unplanned treatment extension and complications developed while on antimicrobials was recorded. Means with standard deviation were calculated for duration of treatment, time to defervescence, and cost of treatment.

Results: Records of 81 culture confirmed XDR typhoid patients admitted at the AKU hospitals were reviewed. Most, (n = 45; 56%) were male. Mean age of the cases was 8.03 years with range (1-40). About three quarter (n = 66) of the patients were treated as inpatient. Fever and vomiting were the most common symptoms at the time of presentation. Oral azithromycin alone (n = 22; 27%), intravenous meropenem alone (n = 20; 25%), or a combination of azithromycin and meropenem (n = 39; 48%) were the options used for treatment. Average (95% confidence interval) time to defervescence was 7.1(5.5-8.6), 6.7(4.7-8.7), and 6.7(5.5-7.9) days for each treatment option respectively whereas there were 1,0 and 3 treatment failures in each treatment option respectively. Average cost of treatment per day for azithromycin was US$5.87 whereas it was US$88.46 for meropenem.

Conclusion: Patients treated with either Azithromycin, Meropenem alone or in combination showed similar time to defervescence. Because of the lower cost of azithromycin, it is preferable in lower socio-economic areas. Background estimates for power calculation can be made for more robust clinical trials using this observational data.
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http://dx.doi.org/10.1371/journal.pntd.0008682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561124PMC
October 2020

The spectrum of primary immunodeficiencies at a tertiary care hospital in Pakistan.

World Allergy Organ J 2020 Jul 5;13(7):100133. Epub 2020 Aug 5.

Department of Pediatrics and Child Health, Aga Khan University, Stadium Road, Karachi, 74800, Pakistan.

Background: Primary Immunodeficiency Disorders (PIDs) are well-known disorders in the West. but the recognition and diagnosis of these disorders is challenging in developing countries. We present the spectrum of PIDs seen at a tertiary care center in Pakistan, identified using clinical case definitions and molecular methods.

Methods: A retrospective chart review of children suspected to have PID was conducted at the Aga Khan University Hospital (AKUH) Karachi, Pakistan from 2010 to 2016. Data on demographics, clinical features, family history of consanguinity, sibling death, details of laboratory workup done for PID and molecular tests targeted panel next generation sequencing (NGS) or whole exome sequencing (WES) performed at the Geha laboratory at Boston Children's Hospital, USA was collected. The study was exempted from the Ethical Review Committee of AKUH.

Results: A total of 43 children visited the hospital with suspected PID during the study period. Genetic testing was performed in 31/43 (72.1%) children. A confirmed diagnosis of PID was established in 20/43 (46.5%) children. A pathogenic gene variant was identified in 17(85%) of the 20 confirmed cases (Table 1). Twelve (60%) of the confirmed cases of PID were male. The most common presenting symptom was recurrent diarrhea 11/20 (55%). The mean (±S.D) age of the cases at the time of diagnosis was 4.2 (±4.1) years. Chronic granulomatous disease (CGD) was the most common 6/20 (30%) disorder, followed by severe combined immunodeficiency (SCID) 3/20 (15%), leukocyte adhesion deficiency (LAD) 3/20 (15%), agammaglobulinemia/hypogammaglobulinemia 3/20 (15%), and Hermansky-Pudlak Syndrome (HPS) 2/20 (10%). Wiskott-Aldrich Syndrome, Immunodeficiency Centromeric Instability and Facial Anomalies Syndrome (ICF 2), Trichohepatoenteric syndrome (TRES), and C3 deficiency were each diagnosed once {1/20 (4.3%) each} (Table 1). Of these 20 confirmed cases, almost all 19/20 (95%) had a family history of consanguinity. Sibling death was reported in 5/20 (25%) of these cases. Five out of the 20 (25%) children died over the 7-year period for various reasons.

Conclusion: PIDs are not uncommon in Pakistan; their diagnosis may be missed or delayed due to the overlapping of clinical features of PID with other diseases and a lack of diagnostic facilities. There is a need to build capacity for early recognition and diagnosis of PIDs to decrease morbidity and mortality.
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http://dx.doi.org/10.1016/j.waojou.2020.100133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414008PMC
July 2020

Acute Kidney Injury after Congenital Heart Disease Surgery: A Single-Center Experience in a Low- to Middle-Income Country.

Cureus 2020 Apr 18;12(4):e7727. Epub 2020 Apr 18.

Pediatrics and Child Health, Aga Khan University Hospital, Karachi, PAK.

Background Acute kidney injury (AKI) is a commonly recognized clinical problem after congenital heart disease (CHD) surgery. Increased perioperative morbidity, development of chronic kidney disease, and increased mortality are the major concerns. We investigated frequency, risk factors, and outcomes of AKI after CHD surgery at our hospital. Methods This study was a retrospective analytic review conducted from January 2013 to October 2016 on patients aged between 1 month and 45 years who underwent cardiopulmonary bypass (CPB) for CHD surgery. The modified Kidney Disease Improving Global Outcomes criteria based on serum creatinine value was adopted to diagnose AKI. We assessed AKI frequency and its staging, and outcomes as AKI resolution, length of stay, and mortality. Stages II and III (plasma creatinine level two or more times the baseline) were labeled as severe AKI. Univariate and multivariate logistic regression analyses were conducted, and results were reported as mean with standard deviation and as frequencies with percentage. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported for factors associated with the development of AKI. Results Of the 840 patients who underwent CHD surgery, 237 (28%) developed AKI. AKI stages II1 and III were seen in 101 (42%) and 103 (43%) patients, respectively. Prolonged CPB time > 120 minutes (adjusted OR [AOR]: 1.87; 95% CI: 1.22-2.88; p = 0.004) and hemoglobin > 16 gm/dL (AOR: 1.80; 95% CI: 1.16-2.78; p = 0.008) were associated with the development of AKI on multivariate analysis. AKI resolved spontaneously in 222 (94%) patients, and 10 (4%) patients who developed AKI died. Conclusions Most patients with AKI showed spontaneous resolution. Prolonged CPB time and increased hemoglobin were found to be significant risk factors. Our study found spontaneous resolution of AKI in most cases. However, preplanning and careful monitoring in patients with expected prolonged CPB time and increased baseline hemoglobin can prevent and identify AKI at an early stage.
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http://dx.doi.org/10.7759/cureus.7727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234068PMC
April 2020

Comparison of Xpert MTB/RIF with AFB smear and AFB culture in suspected cases of paediatric tuberculosis in a tertiary care hospital, Karachi.

J Pak Med Assoc 2019 Sep;69(9):1273-1278

Aga Khan University Hospital, Karachi, Pakistan.

Objective: To evaluate the sensitivity, specificity, positive predictive and negative predictive values of Xpert mycobacterium tuberculosis and resistance to rifampicin by comparing it with acid-fast bacilli smear and culture in suspected tuberculosis patients.

Methods: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised patient data from January 2013 to December 2016. Data related to children with clinical suspicion of pulmonary and extra-pulmonary tuberculosis based on Modified Kenneth Jones criteria, aged 1 month to 18 years whose samples (respiratory or non-respiratory) were sent for Xpert mycobacterium tuberculosis and resistance to rifampicin and acid-fast bacilli smear and culture con currently. Analysis was carried out by STATA 12 and Med Calc softwares .

Results: Of the 91 cases, 50(54.9%) related to females. The overall median age of the patients was 12.5 years (interquartile range: 8 years). Overall, 42(46.2%) cases had extra-pulmonary tuberculosis. The Xpert test had 66.7% sensitivity compared to smear microscopy 47.6%. Overall sensitivity, specificity, positive predictive value and negative predictive value were 95.7%, 72%, 51.2% and 98.3% respectively when the two tests were compared.

Conclusions: Xpert mycobacterium tuberculosis was found to be more sensitive than acid-fast bacilli smear and culture in both pulmonary and extra-pulmonar y tuberculosis in children.
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September 2019

Clinical profile and outcome of antibiotic lock therapy for bloodstream infections in pediatric hematology/oncology patients in a tertiary care hospital, Karachi, Pakistan.

Int J Pediatr Adolesc Med 2019 Mar 29;6(1):25-28. Epub 2019 Jan 29.

Department of Pediatrics and Child Health, Aga Khan University, Stadium Road, Karachi, 74800, Pakistan.

Background: Intravascular catheters are susceptible to infections, thus requiring catheter removal and leading to increased morbidity and costs. Antibiotic lock therapy (ALT) is a therapeutic technique that is used to salvage the catheter. The aim of this study was to evaluate the outcome of antibiotic lock therapy in bloodstream infections in pediatric hematology/oncology patients in a tertiary care hospital, Karachi.

Methods: A retrospective review was performed from January 2013 to December 2017 of pediatric hematology/oncology patients with bloodstream infections and who received ALT at Aga Khan University Hospital. All cases of polymicrobial infections, catheter removal, or malfunction before the completion of ALT were excluded. Descriptive analysis was carried out using SPSS version 20.

Results: A total of nine hematology/oncology patients were eligible. The catheter was salvaged in 7/9 (77.8%) children, and in 2/9 (22.2%) cases, catheter was removed because of persistent bacteremia. The most common organism isolated was species (33.3%). Relapse with a similar pathogen occurred in 2 (22.2%) patients and 2 (22.2%) of them developed an exit-site infection.

Conclusion: In our experience, in almost two thirds of the cases, the catheter was salvaged, but disappointingly, relapses were high when the infection was due to spp. Although this is a small study, our results show that ALT can be a potential safe adjunctive strategy to treat catheter-related bloodstream infections (CRBSI). However, we need larger prospective studies to test the safety and efficacy of ALT to develop specific ALT recommendations and guidelines particularly in children.
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http://dx.doi.org/10.1016/j.ijpam.2019.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602921PMC
March 2019

Outcome of inadvertent high dose BCG administration in newborns at a tertiary care hospital, Karachi- Case series.

PLoS One 2019 10;14(7):e0219324. Epub 2019 Jul 10.

Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan.

Bacillus Calmette-Guérin (BCG) vaccine is given to newborns soon after birth. BCG vaccine overdose has been rarely reported. Here we report the outcome of newborns who accidently received high dose BCG at a tertiary care hospital, Karachi. We reviewed records of 26 newborns, who accidentally received intradermal high dose BCG, used for the treatment of urinary bladder cancers and 80 times higher dose than the BCG used for routine vaccination. The incident happened from 14-16th April, 2016 at Aga Khan University Hospital, Karachi. Analysis was carried out using SPSS. A total of 23/26(88.5%) newborns were followed for atleast 3 months and 11/26 (42.3%) were followed for atleast one year. 13/26 (50%) were male. All 26 patients were prescribed isoniazid and rifampicin for 3 months. 3/26 (11.5%) were lost to follow-up before completion of anti-tuberculous drugs (ATT). Lesions at the BCG site were observed in 16/26 (61.5%) infants, of which 15 (93.8%) had a papule, 3 (18.8%) developed a pustule, 3 (18.8%) had skin induration and 2 (12.5%) had skin erythema. Axillary lymphadenopathy was observed in 1/26 (3.8%) patient. Coagulation was deranged in 3/26 (11.5%) of babies. Intracranial bleeding was observed in 1/26 (3.8%) case. Localized skin lesions were the most common adverse events. None of them developed clinical tuberculosis. Chemoprophylaxis for inadvertent high dose BCG administration should be given for atleast 3 months. Furthermore, vigilant follow-up, transparency and disclosure are the vital steps in the management of any medical error.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0219324PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619743PMC
February 2020

X-linked agammaglobulinemia (XLA):Phenotype, diagnosis, and therapeutic challenges around the world.

World Allergy Organ J 2019 22;12(3):100018. Epub 2019 Mar 22.

Department of Medicine and Sciences of Aging, University "G. d'Annunzio" of Chieti-Pescara, Italy.

Background: X-linked agammaglobulinemia is an inherited immunodeficiency recognized since 1952. In spite of seven decades of experience, there is still a limited understanding of regional differences in presentation and complications. This study was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to better understand regional needs, challenges and unique patient features.

Methods: A survey instrument was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to collect both structured and semi-structured data on X-linked agammaglobulinemia. The survey was sent to 54 centers around the world chosen on the basis of World Allergy Organization participation and/or registration in the European Society for Immunodeficiencies. There were 40 centers that responded, comprising 32 countries.

Results: This study reports on 783 patients from 40 centers around the world. Problems with diagnosis are highlighted by the reported delays in diagnosis>24 months in 34% of patients and the lack of genetic studies in 39% of centers Two infections exhibited regional variation. Vaccine-associated paralytic poliomyelitis was seen only in countries with live polio vaccination and two centers reported mycobacteria. High rates of morbidity were reported. Acute and chronic lung diseases accounted for 41% of the deaths. Unusual complications such as inflammatory bowel disease and large granular lymphocyte disease, among others were specifically enumerated, and while individually uncommon, they were collectively seen in 20.3% of patients. These data suggest that a broad range of both inflammatory, infectious, and autoimmune conditions can occur in patients. The breadth of complications and lack of data on management subsequently appeared as a significant challenge reported by centers. Survival above 20 years of age was lowest in Africa (22%) and reached above 70% in Australia, Europe and the Americas. Centers were asked to report their challenges and responses (n = 116) emphasized the difficulties in access to immunoglobulin products (16%) and reflected the ongoing need for education of both patients and referring physicians.

Conclusions: This is the largest study of patients with X-linked agammaglobulinemia and emphasizes the continued morbidity and mortality of XLA despite progress in diagnosis and treatment. It presents a world view of the successes and challenges for patients and physicians alike. A pivotal finding is the need for education of physicians regarding typical symptoms suggesting a possible diagnosis of X-linked agammaglobulinemia and sharing of best practices for the less common complications.
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http://dx.doi.org/10.1016/j.waojou.2019.100018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439403PMC
March 2019

Accuracy of echocardiography in diagnosing total anomalous pulmonary venous return.

Pak J Med Sci 2018 Sep-Oct;34(5):1094-1098

Dr. Mehnaz Atiq, FCPS (Pediatrics), FCPS (Pediatric Cardiology). Department of Pediatrics and Child Health, The Aga Khan University Hospital, Karachi, Pakistan.

Objective: Total anomalous pulmonary venous return is an uncommon cyanotic congenital heart defect. Echocardiography is the initial diagnostic tool. Complimentary non-invasive modalities like cardiac computerized tomographic angiography and cardiac magnetic resonance imaging have replaced the need for cardiac catheterization in difficult cases. This study aimed to determine the accuracy of echocardiography in diagnosing total anomalous pulmonary venous return, and to determine the factors that may decrease its sensitivity.

Methods: This was a cross-sectional study conducted at the Aga Khan University Hospital Karachi, Pakistan from January 2010 to August 2016. All patients who were diagnosed with Total anomalous pulmonary venous return on echocardiography and had subsequent confirmation either on cardiac CT angiography or surgery were included. The diagnostic accuracy of echocardiography was expressed as sensitivity. Previously described taxonomy was used to define diagnostic error. Univariate and multivariate analysis were done by logistic regression OR (95% CI) were reported to identify factors causing the diagnostic error.

Results: High diagnostic sensitivity (81%) was found in isolated total anomalous pulmonary venous return and low (27%) in heterotaxy and mixed (20%) varieties. Poor acoustic windows and right isomerism were found to be significant factors responsible for the diagnostic error on multivariate analysis.

Conclusion: Echocardiography can diagnose isolated total anomalous pulmonary venous return with high accuracy. Use of additional modalities may be required for a complete diagnosis in cases with mixed variety, heterotaxy and poor acoustic windows.
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http://dx.doi.org/10.12669/pjms.345.15766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191797PMC
October 2018

Human primary immunodeficiency caused by expression of a kinase-dead p110δ mutant.

J Allergy Clin Immunol 2019 02 16;143(2):797-799.e2. Epub 2018 Oct 16.

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2018.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387453PMC
February 2019

Autosomal Recessive Agammaglobulinemia - first case with a novel TCF3 mutation from Pakistan.

Clin Immunol 2019 01 29;198:100-101. Epub 2018 Jul 29.

Department of Pediatric and Child Health, Aga Khan University Hospital, Pakistan. Electronic address:

Autosomal Recessive Agammaglobulinemia (ARA) is an uncommon type of primary immunodeficiency characterized by mutations in genes responsible for early B cell differentiation and function. One such gene is the TCF3 gene, which encodes a transcription factor important for immunoglobulin gene expression. We present the case of a 9 year old girl with history of diarrhea and recurrent pneumonias. Laboratory investigation showed significantly reduced levels of immunoglobulins along with a significant fall in the number of CD19+ cells. Genetic analysis identified a TCF3 gene base deletion covering exons 5-11.
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http://dx.doi.org/10.1016/j.clim.2018.07.016DOI Listing
January 2019

Using Polarized Spectroscopy to Investigate Order in Thin-Films of Ionic Self-Assembled Materials Based on Azo-Dyes.

Nanomaterials (Basel) 2018 Feb 15;8(2). Epub 2018 Feb 15.

Nano-Science Center & Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 København Ø, Denmark.

Three series of ionic self-assembled materials based on anionic azo-dyes and cationic benzalkonium surfactants were synthesized and thin films were prepared by spin-casting. These thin films appear isotropic when investigated with polarized optical microscopy, although they are highly anisotropic. Here, three series of homologous materials were studied to rationalize this observation. Investigating thin films of ordered molecular materials relies to a large extent on advanced experimental methods and large research infrastructure. A statement that in particular is true for thin films with nanoscopic order, where X-ray reflectometry, X-ray and neutron scattering, electron microscopy and atom force microscopy (AFM) has to be used to elucidate film morphology and the underlying molecular structure. Here, the thin films were investigated using AFM, optical microscopy and polarized absorption spectroscopy. It was shown that by using numerical method for treating the polarized absorption spectroscopy data, the molecular structure can be elucidated. Further, it was shown that polarized optical spectroscopy is a general tool that allows determination of the molecular order in thin films. Finally, it was found that full control of thermal history and rigorous control of the ionic self-assembly conditions are required to reproducibly make these materials of high nanoscopic order. Similarly, the conditions for spin-casting are shown to be determining for the overall thin film morphology, while molecular order is maintained.
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http://dx.doi.org/10.3390/nano8020109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853740PMC
February 2018

A novel mutation in the JH4 domain of JAK3 causing severe combined immunodeficiency complicated by vertebral osteomyelitis.

Clin Immunol 2017 10 14;183:198-200. Epub 2017 Sep 14.

Department of Allergy and immunology, Boston Children's Hospital, United States.

JAK3 is a tyrosine kinase essential for signaling downstream of the common gamma chain subunit shared by multiple cytokine receptors. JAK3 deficiency results in TBNK severe combined immune deficiency (SCID). We report a patient with SCID due to a novel mutation in the JAK3 JH4 domain. The function of the JH4 domain remains unknown. This is the first report of a missense mutation in the JAK3 JH4 domain, thereby demonstrating the importance of the JH4 domain of JAK3 in host immunity.
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http://dx.doi.org/10.1016/j.clim.2017.09.007DOI Listing
October 2017

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

J Pak Med Assoc 2017 Mar;67(3):471-473

Department of Paediatrics and Child Health, The Aga Khan University Hospital, Karachi, 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.
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March 2017

Abdominal Lymphonodular Cryptococcosis in an Immunocompetent Child.

Case Rep Pediatr 2015 16;2015:347403. Epub 2015 Nov 16.

Department of Pediatrics and Child Health, Aga Khan University, Stadium Road, Karachi 74800, Pakistan.

We describe our experience with an apparently immunocompetent child presenting with pyrexia of unknown origin without focal signs. Investigations revealed lymphadenopathy at lung hila, mesentery, and porta hepatis. The child had received at least two months of empiric antituberculous therapy (ATT) before she came to us. A CT-guided biopsy revealed granulomatous inflammation. PAS stain showed yeasts which stained blue with Alcian blue, suggesting C. neoformans.
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http://dx.doi.org/10.1155/2015/347403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663295PMC
December 2015

Urinary tract infection presenting as jaundice in neonates.

J Pak Med Assoc 2012 Jul;62(7):735-7

Department of Pediatrics and Child Health, The Aga Khan University Hospital, Karachi.

Neonatal Hyperbilirubinaemia is a common finding during the first postnatal week. Physiological jaundice occurs in first week of life in 60% of term and 80% of premature neonates. Non physiologic or pathologic jaundice occurs in 5-10% of newborns which require intervention. According to AAP guidelines laboratory investigation for jaundice include total serum bilirubin, blood Type and coombs test and if the baby has an elevation of direct reacting or conjugated bilirubin, there should be a urine analysis and urine culture. Here we are presenting 5 cases that developed indirect hyperbilirubinaemia and routine workup done according to AAP guidelines were normal. On extensive investigation all cases found to have urinary tract infection despite of having indirect bilirubin and they needed course of antibiotics according to sensitivities and follow up ultrasound. From our experience we suggest that UTI should be considered as a cause of neonatal jaundice especially when indirect bilirubin peaks after one week of life at mean age of 10.8 +/- 2.38 days.
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July 2012

Idiopathic pulmonary haemosiderosis presenting as severe iron deficiency anaemia--a case from Pakistan.

J Pak Med Assoc 2012 Aug;62(8):845-7

Department of Paediatrics, Aga Khan Secondary Hospital, Karimabad.

Idiopathic pulmonary haemosiderosis is an uncommon disorder, which is characterized by iron deficiency, recurrent haemoptysis and diffuse parenchymal infiltration on chest radiograph. We report an 8 year old child who had past history of multiple blood transfusions with diagnosis of iron deficiency anaemia and recurrent chest infection since the age of 21/2 year. At the age of 8 years, the child presented with fever and severe respiratory distress requiring intubation and ventilation. On Chest X-ray, bilateral white out was found and CT scan lung showed diffuse alveolar involvement. Lung biopsy confirmed haemosiderin-laden macrophages. Child was put on steroids and despite severe anaemia (Hb 3.2 g/dl), he showed improvement and survived. To our knowledge, this is the first case of idiopathic pulmonary haemosiderosis reported from Pakistan.
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August 2012
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