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Full-Text Articles in Pathology

Potassium Channel Subfamily T Member 1(Kcnt1) Pathological Variant Causing Epilepsy Of Infancy With Migrating Focal Seizures: A Case Report, Prem Chand, Meher Angez, Ayesha Nasir Hameed, Salman Kirmani Aug 2023

Potassium Channel Subfamily T Member 1(Kcnt1) Pathological Variant Causing Epilepsy Of Infancy With Migrating Focal Seizures: A Case Report, Prem Chand, Meher Angez, Ayesha Nasir Hameed, Salman Kirmani

Department of Paediatrics and Child Health

Pathological mutation of potassium channel subfamily T member 1 (KCNT1) gene causes an autosomal dominant disorder characterised by secondarily generalised seizures/migratory focal seizure, cyanosis, and dysmorphic features. We report the case of a five-month old male with pathological KCNT1 variant who presented with focal clonic seizures, Mongol spots, and grade two systolic murmur at the left lower sternal border and loud P2. The seizures were refractory to most anti-epileptic drugs but showed some response to Valproic acid. This case demonstrated that EIMFS is a grave infantile epileptic encephalopathy which is refractory to anti epileptic drugs and can present with a …


Effect Of 3 Days Of Oral Azithromycin On Young Children With Acute Diarrhea In Low-Resource Settings: A Randomized Clinical Trial, Antibiotics For Children With Diarrhea (Abcd) Study Group, Tahmeed Ahmed, Farah Naz Qamar, Mohammad Tahir Yousafzai, Shahida Qureshi, Sadia Shakoor, Rozina Thobani, Aneeta Hotwani, Furqan Kabir, Jan Mohammed Dec 2021

Effect Of 3 Days Of Oral Azithromycin On Young Children With Acute Diarrhea In Low-Resource Settings: A Randomized Clinical Trial, Antibiotics For Children With Diarrhea (Abcd) Study Group, Tahmeed Ahmed, Farah Naz Qamar, Mohammad Tahir Yousafzai, Shahida Qureshi, Sadia Shakoor, Rozina Thobani, Aneeta Hotwani, Furqan Kabir, Jan Mohammed

Department of Paediatrics and Child Health

Importance: World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth.
Objective: To determine whether the addition of azithromycin to standard case management of acute nonbloody watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished could reduce mortality and improve linear …


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, Sonia Qureshi, Noshi Maria, Mohammad Zeeshan, Seema Irfan, Farah Naz Qamar Jun 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, Sonia Qureshi, Noshi Maria, Mohammad Zeeshan, Seema Irfan, Farah Naz Qamar

Department of Paediatrics and Child Health

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 …


Impact Of 10-Valent Pneumococcal Conjugate Vaccine (Pcv10) On Nasopharyngeal Carriage In Children 2 Years Of Age: Data From A Four-Year Time Series Cross-Sectional Study From Pakistan, Muhammad Imran Nisar, Shahira Shahid, Sajid Muhammad, Farah Khalid, Amjad Hussain, Sheraz Ahmed, Sadia Shakoor, Furqan Kabir, Aneeta Hotwani, Syed Asad Ali, Anita K. M. Zaidi, Fyezah Jehan, Najeeha Talat Iqbal Feb 2021

Impact Of 10-Valent Pneumococcal Conjugate Vaccine (Pcv10) On Nasopharyngeal Carriage In Children 2 Years Of Age: Data From A Four-Year Time Series Cross-Sectional Study From Pakistan, Muhammad Imran Nisar, Shahira Shahid, Sajid Muhammad, Farah Khalid, Amjad Hussain, Sheraz Ahmed, Sadia Shakoor, Furqan Kabir, Aneeta Hotwani, Syed Asad Ali, Anita K. M. Zaidi, Fyezah Jehan, Najeeha Talat Iqbal

Department of Paediatrics and Child Health

The dataset described in this paper was collected for a time-series cross-sectional study exploring the impact of 10-valent Pneumococcal Conjugate Vaccine (PCV10) on nasopharyngeal (NP) carriage in children under 2 years of age from a rural population in Sindh, Pakistan. The study was carried out in two union councils of Matiari - Khyber and Shah Alam Shah Jee Wasi (Latitude 25.680298 / Longitude 68.502711). Data was collected on socio-demographics, clinical characteristics and vaccination status using android phone-based application. NP samples were collected using standard World Health Organisation (WHO) techniques, culture and serotyping was done using sequential Multiplex PCR described by …


Characteristics Of Salmonella Recovered From Stools Of Children Enrolled In The Global Enteric Multicenter Study, Irene N. Kasumba, Caisey V. Pulford, Blanca M. Perez-Sepulveda, Sunil Sen, Nurulla Sayed, Jasnehta Permala-Booth, Sofie Livio Sofie Livio, Darren Heavens Darren Heavens, Ross Low Ross Low, Shahida Qureshi, Anita K. M. Zaidi Jan 2021

Characteristics Of Salmonella Recovered From Stools Of Children Enrolled In The Global Enteric Multicenter Study, Irene N. Kasumba, Caisey V. Pulford, Blanca M. Perez-Sepulveda, Sunil Sen, Nurulla Sayed, Jasnehta Permala-Booth, Sofie Livio Sofie Livio, Darren Heavens Darren Heavens, Ross Low Ross Low, Shahida Qureshi, Anita K. M. Zaidi

Department of Paediatrics and Child Health

Background: The Global Enteric Multicenter Study (GEMS) determined the etiologic agents of moderate-to-severe diarrhea (MSD) in children under 5 years old in Africa and Asia. Here, we describe the prevalence and antimicrobial susceptibility of non-typhoidal Salmonella (NTS) serovars in GEMS and examine the phylogenetics of Salmonella Typhimurium ST313 isolates.
Methods: Salmonella isolated from children with MSD or diarrhea-free controls were identified by classical clinical microbiology and serotyped using antisera and/or whole genome sequence data. We evaluated antimicrobial susceptibility using the Kirby-Bauer disk diffusion method. Salmonella Typhimurium sequence types were determined using multi-locus sequence typing and whole genome sequencing was performed …


Direct And Indirect Effect Of 10 Valent Pneumococcal Vaccine On Nasopharyngeal Carriage In Children Under 2 Years Of Age In Matiari, Pakistan, Muhammad Imran Nisar, Sheraz Ahmed, Fyezah Jehan, Shahira Shahid, Sadia Shakoor, Furqan Kabir, Aneeta Hotwani, Sahrish Munir, Sajid Muhammad, Farah Khalid, Syed Asad Ali, Anita K. M. Zaidi, Najeeha Talat Iqbal Jan 2021

Direct And Indirect Effect Of 10 Valent Pneumococcal Vaccine On Nasopharyngeal Carriage In Children Under 2 Years Of Age In Matiari, Pakistan, Muhammad Imran Nisar, Sheraz Ahmed, Fyezah Jehan, Shahira Shahid, Sadia Shakoor, Furqan Kabir, Aneeta Hotwani, Sahrish Munir, Sajid Muhammad, Farah Khalid, Syed Asad Ali, Anita K. M. Zaidi, Najeeha Talat Iqbal

Department of Paediatrics and Child Health

Background: Pakistan introduced Ten-valent pneumococcal-conjugate-vaccine PCV10 in 2012 as a 3 + 0 schedule without catch-up.
Methods: Children <2 years old in Matiari, Sindh provided nasopharyngeal swabs between 2014 and 2018, which were cultured for pneumococcus and serotyped through multiplex PCR at the Aga Khan University Hospital. Carriage rates over time for Vaccine-Type (VT) and Non-VT (NVT) serotypes were used to estimate direct, indirect, total and overall effects of vaccination. Regression analysis was used to determine factors associated with VT carriage.
Results: Pneumococcus was detected in 2370/3140 (75%). VT carriage decreased overall, 16.1-9.6% (p-trend <0.001); vaccinated (all 3 doses of PCV10 received) 11.3-8.1% (p-trend 0.031) and unvaccinated (no PCV10 dose received) 17.4-10.3% (p-trend 0.003) with a decline in serotypes 6B, 9V/9A and 19F. Immunization increased from 41.0% to 68.4% (p-trend 0.001). Direct effect of vaccine was 32.8% (95% CI 14.7-47.0%) and indirect effect 44.6%(95% CI 40.6-48.6%). Factors associated with decreased VT colonization were education 1-5 years (aOR 0.7, 95%CI 0.6-1.0), history of difficulty breathing (aOR 0.7, 95%CI 0.5-1.0), exposure to smoke (aOR 0.8, 95% CI 0.6-1.0), child fully immunized (aOR 0.7, 95%CI 0.5-1.0) and enrolled in 3rd (aOR 0.6, 95%CI 0.4-0.8) and 4th (aOR 0.6, 95%CI 0.5-0.9) year of the study whereas history of runny nose (aOR 1.5, 95% CI 1.2-1.9) was positively associated.
Conclusions: Decrease in VT pneumococcal carriage in vaccinated and unvaccinated children indicates herd immunity. Sustained increase in vaccine coverage and close long-term surveillance is warranted.


Burden Of Culture Confirmed Enteric Fever Cases In Karachi, Pakistan: Surveillance For Enteric Fever In Asia Project (Seap), 2016-2019, Mohammad Tahir Yousafzai, Seema Irfan, Rozina Thobani, Abdul Momin Kazi, Aneeta Hotwani, Ashraf M. Memon, Khalid Iqbal, Saqib Hamid Qazi, Nasir S. Saddal, Najeeb Rehman, Irum Fatima Dehraj, Mohammed J. Hunzai, Junaid Mehmood, Farah Naz Qamar Dec 2020

Burden Of Culture Confirmed Enteric Fever Cases In Karachi, Pakistan: Surveillance For Enteric Fever In Asia Project (Seap), 2016-2019, Mohammad Tahir Yousafzai, Seema Irfan, Rozina Thobani, Abdul Momin Kazi, Aneeta Hotwani, Ashraf M. Memon, Khalid Iqbal, Saqib Hamid Qazi, Nasir S. Saddal, Najeeb Rehman, Irum Fatima Dehraj, Mohammed J. Hunzai, Junaid Mehmood, Farah Naz Qamar

Department of Paediatrics and Child Health

Background: The Surveillance for Enteric Fever in Asia Project (SEAP) is a multicenter, multicountry study conducted in Pakistan, Nepal, and Bangladesh. The objectives of the study were to characterize disease incidence among patients with enteric fever. We report the burden of enteric fever at selected sites of Karachi, Pakistan.
Methods: During September 2016 to September 2019, prospective surveillance was conducted at inpatient, outpatient, surgical departments, and laboratory networks of Aga Khan University Hospital, Kharadar General Hospital, and surgery units of National Institute of Child Health and Jinnah Postgraduate Medical Centre. Socio-demographic, clinical, and laboratory data were obtained from all suspected …


Antimicrobial Resistance In Typhoidal Salmonella: Surveillance For Enteric Fever In Asia Project, 2016-2019, Farah Naz Qamar, Mohammad Tahir Yousafzai, Irum Fatima Dehraj, Sadia Shakoor, Seema Irfan, Aneeta Hotwani, Muhammad J. Hunzai, Rozina Thobani, Najeeb Rahman, Junaid Mehmood, Ashraf M. Memon Dec 2020

Antimicrobial Resistance In Typhoidal Salmonella: Surveillance For Enteric Fever In Asia Project, 2016-2019, Farah Naz Qamar, Mohammad Tahir Yousafzai, Irum Fatima Dehraj, Sadia Shakoor, Seema Irfan, Aneeta Hotwani, Muhammad J. Hunzai, Rozina Thobani, Najeeb Rahman, Junaid Mehmood, Ashraf M. Memon

Department of Paediatrics and Child Health

Background: Clinicians have limited therapeutic options for enteric as a result of increasing antimicrobial resistance, and therefore typhoid vaccination is recommended as a preventive measure. As a part of the Surveillance for Enteric Fever in Asia Project (SEAP), we investigated the extent measured the burden of antimicrobial resistance (AMR) among confirmed enteric fever cases in Bangladesh, Nepal, and Pakistan.
Methods: From September 2016-September 2019, SEAP recruited study participants of all age groups from its outpatient, inpatient, hospital laboratory, laboratory network, and surgical sites who had a diagnosis of febrile illness that was either suspected or blood culture confirmed for enteric …


Beyond Sequencing: Re-Visiting Annotations For Pjl As A Test Case, Waqasuddin Khan, Aisha Ghani, Muhammad Bilal Azmi, Safina Abdul Razzak Jul 2019

Beyond Sequencing: Re-Visiting Annotations For Pjl As A Test Case, Waqasuddin Khan, Aisha Ghani, Muhammad Bilal Azmi, Safina Abdul Razzak

Department of Paediatrics and Child Health

Objectives: Current developments in sequencing techniques have enabled rapid and high-throughput generation of sequence data. however, there is a growing gap between the generation of raw sequencing data and the extraction of meaningful biological information. variant annotation is a crucial step in the analysis of genome sequencing data. incorrect or incomplete annotations can cause researchers to dilute interesting variants in a pool of false positives. we require consistent, accurate and reliable annotation of variants for making diagnostic and treatment decisions. current annotation depends on the set of transcripts, and software used can be managed, with sufficient care, in the research …


A Retrospective Study Of Laboratory-Based Enteric Fever Surveillance, Pakistan, 2012-2014, Farah Naz Qamar, Mohammad Tahir Yousafzai, Shazia Sultana, Attaullah Baig, Sadia Shakoor, Farzeen Hirani, Abdul Wassay, Sehrish Khushboo, Junaid Mehmood, Alexander Freeman Nov 2018

A Retrospective Study Of Laboratory-Based Enteric Fever Surveillance, Pakistan, 2012-2014, Farah Naz Qamar, Mohammad Tahir Yousafzai, Shazia Sultana, Attaullah Baig, Sadia Shakoor, Farzeen Hirani, Abdul Wassay, Sehrish Khushboo, Junaid Mehmood, Alexander Freeman

Department of Paediatrics and Child Health

Introduction: The Surveillance for Enteric Fever in Asia Project (SEAP) is a multisite surveillance study designed to capture morbidity and mortality burden of enteric fever (typhoid and paratyphoid) in Bangladesh, Nepal, and Pakistan. We aim to describe enteric fever disease burden, severity of illness, and antimicrobial resistance trends in Pakistan.
Methods: In this retrospective, cross-sectional study, laboratory records of hospitalized patients who received a blood culture in any of 3 Aga Khan University hospitals in Karachi and Hyderabad, Pakistan, from 2012 to 2014 were reviewed. A case was defined as having a positive blood culture for Salmonella Typhi (S. Typhi) …


Direct Detection Of Shigella In Stool Specimens By Use Of A Metagenomic Approach, Jie Liu, Mathieu Almeida, Furqan Kabir, Sadia Shakoor, Shahida Qureshi, Anita K. M. Zaidi, Shan Li, Boubou Tamboura, Samba O. Sow, Inacio Mandomando Jan 2018

Direct Detection Of Shigella In Stool Specimens By Use Of A Metagenomic Approach, Jie Liu, Mathieu Almeida, Furqan Kabir, Sadia Shakoor, Shahida Qureshi, Anita K. M. Zaidi, Shan Li, Boubou Tamboura, Samba O. Sow, Inacio Mandomando

Department of Paediatrics and Child Health

The underestimation of Shigella species as a cause of childhood diarrhea disease has become increasingly apparent with quantitative PCR (qPCR)-based diagnostic methods versus culture. We sought to confirm qPCR-based detection of Shigella via a metagenomics approach. Three groups of samples were selected from diarrheal cases from the Global Enteric Multicenter Study: nine Shigella culture-positive and qPCR-positive (culture+ qPCR+) samples, nine culture-negative but qPCR-positive (culture- qPCR+) samples, and nine culture-negative and qPCR-negative (culture- qPCR-) samples. Fecal DNA was sequenced using paired-end Illumina HiSeq, whereby 3.26 × 108 ± 5.6 × 10 …


Experience With The Quantitative Lyta Gene Real-Time Polymerase Chain Reaction For The Detection Of Streptococcus Pneumoniae From Pediatric Whole Blood In Pakistan, Furqan Kabir, Sahrish Muneer, Adil Kalam, Ana Sami, Shahida Qureshi, Aneeta Hotwani, Atif Riaz, Syed Mohiuddin, Mohammad Tahir Yousafzai, Sara Hussain, Syed Asad Ali, Sadia Shakoor Jul 2017

Experience With The Quantitative Lyta Gene Real-Time Polymerase Chain Reaction For The Detection Of Streptococcus Pneumoniae From Pediatric Whole Blood In Pakistan, Furqan Kabir, Sahrish Muneer, Adil Kalam, Ana Sami, Shahida Qureshi, Aneeta Hotwani, Atif Riaz, Syed Mohiuddin, Mohammad Tahir Yousafzai, Sara Hussain, Syed Asad Ali, Sadia Shakoor

Department of Paediatrics and Child Health

Background: We present our experience with optimization and diagnostic use of quantitative real-time polymerase chain reaction (PCR) targeting the lytA gene of Streptococcus pneumoniae for the detection of S. pneumoniae in whole blood of children ≥5 CFU/10 μl or 1 copy of DNA/2 μl of blood.
Methods: This assay was applied on 1912 whole blood specimens collected from children pneumonia, of which 35 specimens were lytA positive. The bacterial loads were determined through categorization of load into five different categories, i.e., very high load, high load, moderate load, low load, and very low load.
Results: Of the 35 lytA-positive …


Simplified Antibiotic Regimens For Treatment Of Clinical Severe Infection In The Outpatient Setting When Referral Is Not Possible For Young Infants In Pakistan (Simplified Antibiotic Therapy Trial [Satt]): A Randomised, Open-Label, Equivalence Trial, Fatima Mir, Imran Nisar, Shiyam S. Tikmani, Benazir Baloch, Sadia Shakoor, Fyezah Jehan, Imran Ahmed, Simon Cousens, Anita K M Zaidi Dec 2016

Simplified Antibiotic Regimens For Treatment Of Clinical Severe Infection In The Outpatient Setting When Referral Is Not Possible For Young Infants In Pakistan (Simplified Antibiotic Therapy Trial [Satt]): A Randomised, Open-Label, Equivalence Trial, Fatima Mir, Imran Nisar, Shiyam S. Tikmani, Benazir Baloch, Sadia Shakoor, Fyezah Jehan, Imran Ahmed, Simon Cousens, Anita K M Zaidi

Department of Paediatrics and Child Health

Background: Parenteral antibiotic therapy for young infants (aged 0–59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection.
Methods: We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0–59 days) who either presented at a primary health-care …


Interplay Of Chemo Attractant Peptides (Cathelicidin And Chemerin) With Vitamin-D In Patients With Pulmonary Tuberculosis, Najeeha Talat Iqbal, Syeda Sadia Fatima, Rabia Hussain, Nisar Ahmed Rao, Narius Virji, Bushra Jamil, Muhammad Irfan Jan 2015

Interplay Of Chemo Attractant Peptides (Cathelicidin And Chemerin) With Vitamin-D In Patients With Pulmonary Tuberculosis, Najeeha Talat Iqbal, Syeda Sadia Fatima, Rabia Hussain, Nisar Ahmed Rao, Narius Virji, Bushra Jamil, Muhammad Irfan

Department of Paediatrics and Child Health

Aim: Both Cathelicidin and Chemerin are chemoattractant proteins and possess antimicrobial activity.Sufficient level of Vitamin D is important for optimum response of Cathelicidin for its antimycobacterial activity. Studies on the role of these antimicrobial peptides and their relationship withVitamin D level are limited in tuberculosis. The aim of this study was to investigate an associationof Vitamin D with antimicrobial peptide (Cathelicidin) and an adipokine (Chemerin) in patients with pulmonary tuberculosis (TB). Methods: In a case control study we estimated level of Vitamin D, Chemerin, Cathelicidin and TNFα in pulmonary TB patients (n=22) and healthy endemic controls (n=17) using sandwich ELISA …