Sequence variants underlying severe combined immunodeficiency and leukocyte adhesion deficiency type 1 in six consanguineous families.

Inborn errors of immunity (IEI) are defined as genetic disorders affecting the immune system and resulting in diverse clinical signs and symptoms. Despite the lack of diagnosis and unavailability of IEI estimation in the Pakistani population, consanguinity is exacerbating its prevalence. The current study focuses on severe combined immunodeficiency (SCID) and leukocyte adhesion deficiency type 1 (LAD1). SCID is associated with the life-threatening symptoms developing at post-birth. LAD1 is clinically characterized by recurrent bacterial infections related to the skin, mouth, and respiratory tract owing to impaired leukocytes. Herein, in six consanguineous families, flow cytometry was used to evaluate the patient's immune status. Whole-exome sequencing (WES) was then conducted to search for the causative variations in immunodeficiency genes. Sanger sequencing was used to assess the segregation of the variants with the disorder within the families. Sequence analysis revealed five homozygous variants in four different causative genes. This included four novel nonsense variants in CD70 p.(Thr126Profs*33), CD3e p.(Trp151*), IL7R p.(Val138Ilefs*10), and ITGB2 p.(Ser627Valfs*61), and one previously reported in ITGB2 p.(Cys62*). In one of the families, two variants in two different genes, including DNAH6 p.(Tyr2653His) and NIPAL4 p.(Gly121Ser), were detected in an unclassified patient. All the identified variants were found in a homozygous state in the patient but in a heterozygous state in the available parents. The study will facilitate the diagnosis and management of IEI patients.

Identification of novel homozygous variants in FOXE3 and AP4M1 underlying congenital syndromic anophthalmia and microphthalmia.

BACKGROUND: Anophthalmia and microphthalmia are severe developmental ocular disorders that affect the size of the ocular globe and can be unilateral or bilateral. The disease is found in syndromic as well as non-syndromic forms. It is genetically caused by chromosomal aberrations, copy number variations and single gene mutations, along with non-genetic factors such as viral infections, deficiency of vitamin A and an exposure to alcohol or drugs during pregnancy. To date, more than 30 genes having different modes of inheritance patterns are identified as causing anophthalmia and microphthalmia. METHODS: In the present study, a clinical and genetic analysis was performed of six patients with anophthalmia and microphthalmia and/or additional phenotypes of intellectual disability, developmental delay and cerebral palsy from a large consanguineous Pakistani family. Whole exome sequencing followed by data analysis for variants prioritization and validation through Sanger sequencing was performed to identify the disease causing variant(s). American College of Medical Genetics and Genomics (ACMG) guidelines were applied to classify clinical interpretation of the prioritized variants. RESULTS: Clinical investigations revealed that the affected individuals are afflicted with anophthalmia. Three of the patients showed additional phenotype of intellectual disability, developmental delays and other neurological symptoms. Whole exome sequencing of the DNA samples of the affected members in the family identified a novel homozygous stop gain mutation (NM_012186: c.106G>T: p.Glu36*) in Forkhead Box E3 (FOXE3) gene shared by all affected individuals. Moreover, patients segregating additional phenotypes of spastic paraplegia, intellectual disability, hearing loss and microcephaly showed an additional homozygous sequence variant (NM_004722: c.953G>A: p.Arg318Gln) in AP4M1. Sanger sequencing validated the correct segregation of the identified variants in the affected family. ACMG guidelines predicted the variants to be pathogenic. CONCLUSIONS: We have investigated first case of syndromic anophthalmia caused by variants in the FOXE3 and AP4M1. The present findings are helpful for understanding pathological role of the mutations of the genes in syndromic forms of anophthalmia. Furthermore, the study signifies searching for the identification of second variant in families with patients exhibiting variable phenotypes. In addition, the findings will help clinical geneticists, genetic counselors and the affected family with respect to prenatal testing, family planning and genetic counseling.

Mutational analysis in different genes underlying severe combined immunodeficiency in seven consanguineous Pakistani families.

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.

Mutational spectrum of CFTR in cystic fibrosis patients with gastrointestinal and hepatobiliary manifestations.

BACKGROUND: Cystic fibrosis (CF) is a rare and debilitating autosomal recessive disorder. It hampers the normal function of various organs and causes severe damage to the lungs, and digestive system leading to recurring pneumonia. Cf also affects reproductive health eventually may cause infertility. The disease manifests due to genetic aberrations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This study aimed to screen for CFTR gene variants in Pakistani CF patients representing variable phenotypes. METHODS: Clinical exome and Sanger sequencing were performed after clinical characterization of 25 suspected cases of CF (CF1-CF25). ACMG guidelines were followed to interpret the clinical significance of the identified variants. RESULTS: Clinical investigations revealed common phenotypes such as pancreatic insufficiency, chest infections, chronic liver and lung diseases. Some patients also displayed symptoms like gastroesophageal reflux disease (GERD), neonatal cholestasis, acrodermatitis, diabetes mellitus, and abnormal malabsorptive stools. Genetic analysis of the 25 CF patients identified deleterious variants in the CFTR gene. Notably, 12% of patients showed compound heterozygous variants, while 88% had homozygous variants. The most prevalent variant was p. (Met1Thr or Met1?) at 24%, previously not reported in the Pakistani population. The second most common variant was p. (Phe508del) at 16%. Other variants, including p. (Leu218*), p. (Tyr569Asp), p. (Glu585Ter), and p. (Arg1162*) were also identified in the present study. Genetic analysis of one of the present patients showed a pathogenic variant in G6PD in addition to CFTR. CONCLUSION: The study reports novel and reported variants in the CFTR gene in CF patients in Pakistani population having distinct phenotypes. It also emphasizes screening suspected Pakistani CF patients for the p. (Met1Thr) variant because of its increased observance and prevalence in the study. Moreover, the findings also signify searching for additional pathogenic variants in the genome of CF patients, which may modify the phenotypes. The findings contribute valuable information for the diagnosis, genetic counseling, and potential therapeutic strategies for CF patients in Pakistan.

Frequency of vitamin D deficiency in children with iron deficiency anaemia and factors associated with vitamin D deficiency.

Objective: To evaluate vitamin D deficiency in children with iron-deficiency anaemia, and to identify the risk factors for such deficiency. METHODS: The cross-sectional study was conducted at the Children's Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from October 2021 to March 2022, and comprised children aged 1-5 years who had been diagnosed with iron-deficiency anaemia. Quantitative variables, like age, height, weight, gender, socioeconomic status and sibling status, were controlled by stratification. Data was compared to assess the risk factors of vitamin D deficiency among the subjects. Data was analysed using SPSS 22. RESULTS: Of the 236 children with iron-deficiency anaemia, 159(67.5%) also had vitamin D deficiency; 95(59%) girls and 65(41%) boys. Overall, 104(65.4%) subjects were aged 4-5 years and 55(34.6%) were aged 1-3 years. Vitamin D deficiency had significant association with female gender, older age, height and weight <5th centiles, educated parents, low to middle socioeconomic status, urban residence and higher number of siblings (p<0.05). CONCLUSIONS: The prevalence of vitamin D deficiency among children with iron-deficiency anaemia was found to be high.

Whole exome sequencing identified a novel splice donor site variant in interleukin 2 receptor alpha chain.

Interleukin 2 receptor alpha chain (IL-2Rα or CD25) deficiency (OMIM #606367) is an immune dysregulation disorder segregating in autosomal recessive form. The disease is caused by biallelic variants in the IL-2Rα gene encoding IL-2Rα also known as CD25 protein. IL-2Rα combines with γ and ß chains of interleukin 2 receptor to form a functional interleukin 2 receptor (IL-2R). In the present study, we identified a Pakistani family presenting a unique presentation of IL-2Rα deficiency. Clinical whole exome sequencing revealed a novel splice donor site variant (NM_001378789.1 (NP_001365718); c.64 + 1G > A) in the IL-2Rα gene. American College of Medical Genetics (ACMG) guidelines interpreted the identified variant as likely pathogenic. The IL-2Rα gene mutation usually presents with autoimmunity and immunodeficiency but in our patient, it presents with congenital diarrhea, metabolic crisis, and strong family history of death in infancy due to the similar complications. Her congenital diarrhea is attributed to autoimmunity in the form of autoimmune enteropathy and eczema. The laboratory findings revealed severe metabolic acidosis hypokalemia and elevated lactate and ammonia levels. This is a new presentation of IL-2Rα gene mutation. The present study highlights the importance of clinical whole exome sequencing in the correct diagnosis of congenital disorders. The study will also help clinical geneticists for genetic counseling and prevention of the disease in the affected family.

Epidemiology and clinical spectrum of pediatric patients with human immunodeficiency virus (HIV) infection: A 15 years' experience.

Objective: To view the different patterns of presentation of HIV in pediatric population along with mode of transmission and associated co infections and co morbidities. Methods: It was a retrospective study conducted at Pakistan Institute of Medical Sciences, Islamabad, in which we evaluated the records of pediatric patients diagnosed with HIV from 2005 to 2020. All the data like age, gender, area, presenting complaints, examination findings at the time of diagnosis, mode of transmission, co infection and co morbidities were recorded. Descriptive analysis was done to calculate frequencies and means of the variables. SPSS 20 was used for data analysis. Results: Ninety four participants were evaluated with male to female ratio as 1.8:1 and mean age of 5.2 years. Majority of patients (44%) were below 4 years. Fever (55%) was the most reported symptom followed by cough (39%), diarrhoea (29%), pallor (27%), shortness of breath (26%), weight loss (23%) and failure to thrive (22%). Co infection with TB was present in (16%). Eight (9%) patients were thalassaemic. Mother to child transmission (60%) was the commonest mode of transmission followed by blood transfusion (23%) and parenteral transmission (6%). Conclusion: In children HIV is more prevalent in males especially under 4 years with fever, cough, diarrhea and pallor being the common symptoms at presentation. Tuberculosis is the commonest co infection as we are endemic for TB and mother to child transmission is the commonest mode of transmission as there was no outbreak in our area.

A novel nonsense variant in EXOC8 underlies a neurodevelopmental disorder.

Human exocyst complex is an evolutionary conserved multimeric complex composed of proteins encoded by eight genes EXOC1-EXOC8. It is known that the exocyst complex plays a role in ciliogenesis, cytokinesis, cell migration, autophagy, and fusion of secretory vesicles. Recently, loss of function variants in EXOC7 and EXOC8 has been associated with abnormalities of cerebral cortical development leading to a neurodevelopmental phenotype. Neurodevelopmental disorders are a huge group of clinically and genetically heterogeneous disorders. In the present study, we recruited a large consanguineous family segregating a neurodevelopmental disorder in an autosomal recessive form. We performed clinical phenotyping by imaging the patient's brain followed by whole exome sequencing examining DNA from two affected individuals. The clinical phenotypes of the disease were suggestive of brain atrophy. Clinical examination revealed intellectual impairment with hypertonia and brisk reflexes. WES followed by Sanger sequencing revealed a novel homozygous nonsense mutation [EXOC8; NM_175876.5; c.1714G > T; p.(Glu572Ter)] in the DNA of affected individuals. Both parents of the patients were heterozygous for the identified mutation. All the pathogenicity prediction softwares predicted the identified variant as disease causing. This study reports a second protein-truncating variant in EXOC8. The findings confirm that loss of function variants in EXOC8 underlies a neurodevelopmental disorder. The identification of a protein-truncating variant in EXOC8 in the current study can be helpful in establishing genotype-phenotype correlations. Our results also provide new insights into genetic counseling and clinical management for the affected individuals.

Exome sequencing reveals the first intragenic deletion in ABCA5 underlying autosomal recessive hypertrichosis.

BACKGROUND: Hereditary hypertrichosis (HH) is characterized by excessive hair growth on various body areas, which is independent of the individual's age. This rare hair disorder has been classified by its origin (genetic or acquired), age of onset, breadth of hair distribution (universal or localized) and the affected body areas. HH is often linked to several additional congenital abnormalities involving teeth, heart and bones. Human HH is associated with heterozygous genomic duplications and deletions in the chromosomal region 17q24.2-q24.3, containing genes such as ABCA5, ABCA6, ABCA10 and MAP2K6. Recently, a homozygous splice-site variant in ABCA5 has been reported to cause autosomal recessive congenital generalized hypertrichosis terminalis (CGHT; OMIM 135400). AIM: To investigate the clinical and genetic basis of autosomal recessive hypertrichosis in a large consanguineous Pakistani family. METHODS: In the present study, we characterized a family of Pakistani origin segregating CGHT in an autosomal recessive pattern, using whole exome sequencing followed by Sanger sequencing. RESULTS: We identified a novel 2-bp intragenic deletion [NM_172232.4(ABCA5);c.977_978delAT] causing a frameshift variant (p.His326ArgfsTer5) in ABCA5. CONCLUSIONS: To our knowledge, this is the first intragenic deletion in ABCA5 underlying CGHT. The findings further validate the involvement of ABCA5 in hair development. The study will facilitate genetic counselling of families carrying CGHT-related features in Pakistani and other populations.

A case of multisystem inflammatory syndrome in children presenting as systemic onset juvenile idiopathic arthritis.

Multisystem inflammatory syndrome in children (MIS-C) is a rare and serious COVID-19 manifestation characterised by generalised inflammatory response including inflammation of the heart, blood vessels, lungs, kidneys, brain, skin, eyes and gastrointestinal system. Children usually present with fever lasting for 24 hours or more along with other symptoms such as abdominal pain, vomiting, diarrhoea, skin rash, red eyes, and swelling of the lips, tongue, hands and feet. Children with MIS-C usually have negative results for a current infection with COVID-19 but positive antibody results indicating that these children were infected with the COVID-19 virus in the past. We present the case of a 12-month-old girl with multisystem inflammatory syndrome presenting as systemic-onset juvenile idiopathic arthritis (SoJIA) and positive Covid-19 PCR. She was treated successfully with Dexamethasone and Naproxen.

Exome Sequencing Revealed a Novel Splice Site Variant in the CRB2 Gene Underlying Nephrotic Syndrome.

Background and Objectives: Nephrotic syndrome (NS) is a kidney disease where the patient has a classic triad of signs and symptoms including hypercholesterolemia, hypoalbuminemia, proteinuria (>3.5 g/24 h), and peripheral edema. In case of NS, the damaged nephrons (structural and functional unit of the kidney) filter unwanted blood contents to make urine. Thus, the urine contains unwanted proteins (proteinuria) and blood cells (hematuria), while the bloodstream lacks enough protein albumin (hypoalbuminemia). Nephrotic syndrome is divided into two types, primary NS, and secondary NS. Primary NS, also known as primary glomerulonephrosis, is the result of a glomerular disease that is limited to the kidney, while secondary NS is a condition that affects the kidney and other parts of the body. The main causes of primary NS are minimal change disease, membranous glomerulonephritis, and focal segmental glomerulosclerosis. In the present study we recruited a family segregating primary NS with the aim to identify the underlying genetic etiology. Such type of study is important in children because it allows counseling of other family members who may be at risk of developing NS, predicts risk of recurrent disease phenotypes after kidney transplant, and predicts response to immunosuppressive therapy. Materials and Methods: All affected individuals were clinically evaluated. Clinical examination, results of laboratory tests, and biopsy investigations led us to the diagnosis. The next-generation sequencing technique (whole-exome sequencing) followed by Sanger sequencing identified a novel homozygous splice site variant (NM_173689.7: c.941-3C>T) in the CRB2 gene. The variant was present in a homozygous state in the affected individuals, while in a heterozygous state in phenotypically normal parents. Results: The study expanded the spectrum of the mutations in the gene CRB2 responsible for causing NS. Conclusions: In addition, the study will also help in genetic counseling, carrier testing, and prenatal and/or postnatal early diagnosis of the disease in the affected family.

Risk factors for mortality among admitted children with complications of measles in Pakistan: An observational study.

OBJECTIVE: To identify the vaccination status and risk factors for mortality in children admitted with complications of measles. METHODS: The retrospective study was conducted at Children Hospital, Pakistan Institute of Medical Sciences, Islamabad, Pakistan, and comprised data of children admitted with complications of measles between 2013 and 2017. Information on vaccination history, complications of measles, anthropometry, hospital stay and outcome within 15 days of admission was retrieved from hospital records. Data was analysed using Stata 14. RESULTS: Of the 307 children admitted, 79(26%) were aged <9 months and were excluded. Of the remaining 228 subjects, 109(47.8) were unvaccinated. Risk factors significantly associated with mortality were an unvaccinated state of measles vaccine, being stunted, and encephalitis in comparison with pneumonia (p<0.05). A total of 39(17%) children died within 15 days of admission. CONCLUSIONS: Encephalitis, non-vaccination and under-nutrition were significantly associated with mortality in children with complications of measles.

Frequency of acute bacterial meningitis in children with first episode of febrile seizures.

OBJECTIVE: To determine the frequency of acute bacterial meningitis in children with first episode of febrile seizures. METHODS: This cross-sectional study was conducted at the Polyclinic, Postgraduate Medical Institute, Islamabad, Pakistan, from December 2012 to August 2013, and comprised patients with first episode of fever and seizure. SPSS 10 was used for data analysis. RESULTS: Of the157 patients, 12(7.6%) were diagnosed to have acute bacterial meningitis with 5(41.6%) in the age group of 6-12 months, 4(33.3%) in 13-18 months and 3(25%) in the age group of 19-60 months. CONCLUSIONS: Clinicians evaluating children after a febrile seizure should direct their attention toward identifying the cause of the child's fever.

Frequency of hyponatraemia and hypokalaemia in malnourished children with acute diarrhoea.

OBJECTIVE: To determine the frequency of hyponatraemia and hypokalaemia in malnourished children with acute diarrhoea. METHODS: This cross-sectional study was carried out at the Military Hospital, Rawalpindi, Pakistan, from September 2013 to March 2014, and comprised acute diarrhoea patients whose ages ranged from six months to five years. Blood samples for serum sodium and potassium were examined at the Armed Forces Institute of Pathology. Patients were labelled as having hyponatraemia, hypokalaemia, both or having normal serum sodium and potassium levels. RESULTS: Of the 80 patients, 49(61.3%) were boys and 31(38.7%) were girls with an overall mean age of 1.9±1.4 years. Besides, 41(51.3%) were aged below one year. The mean duration of diarrhoea was 3.2±1.7 days, with 53(66%) patients having the illness for 1-3 days. Hyponatraemia was observed in 26(32.5%) patients and hypokalaemia in 44(55%), whereas 10(12.5%) had no electrolyte imbalance. None of the participants had hypernatraemia or hyperkalaemia. CONCLUSIONS: Electrolyte disturbances among malnourished children may not be clinically evident, but diarrhoeal illness aggravated these imbalances.

Frequency, causes and outcome of neonates with respiratory distress admitted to Neonatal Intensive Care Unit, National Institute of Child Health, Karachi.

OBJECTIVE: To determine the frequency, aetiology and outcome of respiratory distress in neonates in intensive care unit. METHODS: The descriptive cross-sectional study was conducted at the Neonatal Intensive Care Unit, National Institute of Child Health, Karachi, from October 2009 to March 2010. It comprised neonates aged day 0 to 28 who were admitted to Neonatal Intensive Care Unit. The neonates were screened first for respiratory distress and presence of one or more signs and symptoms. History, examination and investigations were carried out to find out various aetiologies of respiratory distress. Outcome was measured in terms of discharge and death. Data was analysed using SPSS12. RESULTS: Of the 205 neonates in the study, 120(58.6%) were boys and 85(41.4%) were girls The overall mean age was 70.58±110.02 hours and the mean gestational age was 36.32±2.72 weeks while the mean weight was 2.41±2.4kg. Respiratory rate >60/min was found in all (100%) the neonates. In terms of signs and symptoms, 125(60.9%) had grunting, 205(100%) had subcostal retractions and nasal flaring, and 81(40%) had cyanosis. The aetiologies observed were birth asphyxia, sepsis, transient tachypnoea of the newborn, pneumonia, meconium aspiration syndrome and respiratory distress syndrome in 22(10.75%), 37(18.05%), 29(14.1%), 36(17.6%), 34(16.7%) and 47(23.0%) neonates respectively. The incidence of neonates with respiratory distress was 68(33.3%). CONCLUSIONS: The frequency of respiratory distress among the neonates was high, while mortality was high in neonates with respiratory distress, especially in pre-term and low birthweight neonates. Early diagnosis and management is important for better outcome.

Etiological Spectrum of Lymphadenopathy Among Children on Lymph Node Biopsy.

Background Pediatric peripheral lymphadenopathy is commonly a benign condition and most cases resolve spontaneously; however, it can be a manifestation of a serious underlying disease. This study aimed to determine the etiological spectrum of persistent pediatric lymphadenopathy on excisional biopsy in a tertiary care children's hospital in a low-middle-income country and to make recommendations regarding evaluation, diagnostic testing, and surgical interventions best suited to the population. Methodology A prospective cross-sectional study was conducted on 243 pediatric patients between the ages of one to 12 years undergoing excisional biopsy for persistent lymphadenopathy (more than four weeks duration) from April 1, 2021, to March 31, 2024. Patient demographic data along with signs, symptoms, and results of investigations including histopathological diagnosis were documented on a structured proforma. Results Patients' age range was two to 12 years (mean = 7.29 ± 2.30 years). The male-to-female ratio was 1:53. The Mean duration of lymphadenopathy was 35.89 ± 6.95 days (range = 25 to 57 days). The average size of lymph nodes ranged from 1 cm to a complex nodal mass of 7 cm. Histopathology showed reactive hyperplasia (40.32%, n = 98), tuberculosis (TB) (33.7%, n = 82), lymphoma (10.3%, n = 25), atypical mycobacterial adenitis (6.99%, n = 17), chronic granulomatous inflammation-histiocytosis (6.2%, n = 15), and Langerhans cell histiocytosis (2.5%, n = 6). The most common site was cervical. Sputum GeneXpert for TB had a true-positive rate of 78.84% while PPD was positive in only 13 TB patients. Atypical mycobacterial adenitis was successfully treated with excision and antibiotics. Supraclavicular nodes were strongly associated with lymphoma (p = 0.008). Conclusions Persistent pediatric lymphadenopathy is most commonly caused by TB followed by lymphoma. Positive sputum GeneXpert for TB with a suggestive clinical picture in endemic regions may be sufficient to start empiric therapy without the need for excisional biopsy in mycobacterial TB adenitis with negative PPD results and normal chest X-ray. In all other cases, excisional biopsy remains the gold standard for diagnosis. However, further studies should be conducted to formulate less invasive management algorithms.

Extensively Drug-Resistant Enteric Fever In Children: Surging Threats Of Antimicrobial Resistance And Possible Solutions.

BACKGROUND: Enteric fever is an infectious disease caused by Salmonella enterica including Salmonella Typhi and Paratyphi A and is associated with potentially serious outcomes, especially in developing countries. The study was conducted with the aim to present the clinical features, laboratory characteristics and antibiotic susceptibility in patients with culture-proven extensively drug-resistant (XDR) enteric fever and to explore drug combinations as a possible solution for the growing problem of antimicrobial resistance. METHODS: This descriptive cross-sectional study was conducted in the Paediatric unit of Ayub teaching hospital. Patients admitted with culture-proven XDR enteric fever were included. Patient characteristics were documented on a predesigned proforma. Response to antimicrobial agents including ceftriaxone and levofloxacin, azithromycin and meropenem and meropenem alone was assessed. Data was entered and analyzed using SPSS version 26. RESULTS: A total of 53 patients participated in this study. The majority of patients 36 (67.9%) were male and above 5 years of age(n=38,71.7%). The mean age of the participants was 7.08±3.02 years. The major presenting features included fever, anorexia and pain abdomen in 53 (100%), 51 (96.2%) and 41 (77.4%) respectively. The mean duration of symptoms prior to hospitalization was 8.92±3.361 days. Of the total patients, 32(60.4%) responded to the initial therapy with ceftriaxone and levofloxacin, 11(20.8%) patients responded to meropenem alone and 10 (18.9%) patients responded to meropenem and azithromycin in combination. There was no statistically significant difference in mean duration to show response in patients receiving either of the treatments (p=0.484). CONCLUSIONS: Paediatric patients with XDR enteric fever mainly presented with fever, anorexia and pain abdomen and showed good response to therapy with the combination of ceftriaxone and levofloxacin inspite of the apparent resistance on blood culture and sensitivity.

Primary Antibiotic Resistance And Effectiveness Of Clarithromycin Vs Metronidazole Based Therapy For Helicobacter Pylori Infection In Children.

BACKGROUND: NASPGHAN guidelines recommend regional antibiotic susceptibility profiling for H. pylori eradication treatment. Profiling local antibiotic resistance patterns is mandatory for successful H. pylori eradication in children. The aim of our study was to determine primary resistance to Clarithromycin and Metronidazole, most commonly used in the eradication regimens in children presenting with symptomatic H. pylori infection. This study was conducted at Children Hospital PIMS Islamabad from June 2020 to August 2021. METHODS: The children of either gender age 2-14 years having symptomatic H. pylori infection (hematemesis, chronic abdominal pain) underwent stool for H. pylori Antigen. Children requiring urgent diagnostic endoscopy underwent rapid urease tests. Biopsies were taken from children having positive stool H. pylori Ag and rapid urease test for histological examination. The biopsy specimens were cultured and subsequently tested for antibiotic sensitivity. RESULTS: Out of 54 children having H. pylori infection 40/54 (74.074%) children had strains susceptible to antimicrobials and 14/54 (25.92%) were having resistance to antimicrobials. According to the pattern of antimicrobial sensitivity, they were further grouped into three (a) Clarithromycin and Metronidazole sensitive group (18/40, 45%) (b) Clarithromycin sensitive and Metronidazole resistant group (12/40, 30%) (c) Metronidazole sensitive group (10/40 25%). CONCLUSIONS: Clarithromycin and Metronidazole cannot be used as1stline treatment for H. pylori eradication in children and can only be used with known antimicrobial susceptibility.

Comparison of quality of life among cardiac, hepatic, cancer, and dermatological patients.

OBJECTIVE: To assess the level of quality of life (QOL) in patients suffering from various cardiac, cancer, hepatic, and dermatological diseases. METHOD: A total of 339 patients of cardiac, cancer, hepatic, and dermatological diseases from DHQ/Allied hospitals of Faisalabad participated in this study through purposive convenient sampling technique. Quality of life was measured by WHO QOL-BREF (Validated Urdu Version) while demographic variables were recorded on a demographic sheet. The results were obtained by using analysis of variance (ANOVA) on SPSS 13. RESULTS: Out of 339, 156 (46%) patients were males while 183 (54%) patients were females. Of the total, 99 (29.2%) belonged to the lower socio economic status, 113 (33.3%) belonged to the lower middle, 62 (18.3%) belonged to the middle, and 65 (19.2%) belonged to the upper middle socio economic status. In terms of education, 49 (14.5%) were illiterate, 110 (32.3%) had primary level education, 118 (34.8%) had middle level education, 21 (6.2%) had done matriculation, 17 (5%) had intermediate, 14 (4.1%) were graduates, 8 (2.4%) had done masters. Of the whole lot, only 2 (0.6%) patients were professionals. Results showed that the quality of life was most deteriorated in the domain of physical health; while psychological health was the second most deteriorated domain. Social relationship was the least affected domain, while environment was the second least affected area. Quality of life of hepatic patients was significantly lower than dermatological patients with respect to physical health and environment, lower than cancer patients in relation to psychological health, and lower than cardiac patients in the social relationship domain. The quality of life of cardiac patients was noted to be significantly higher than the other three categories in the domains of psychological health and environment. CONCLUSION: In the face of the evidence of high deterioration in the quality of life of the patients in terms of physical and psychological health, medical units should be better equipped with facilities to enhance a sense of betterment in patients. The treating doctors should be better trained to give due consideration to this important aspect of management. Moreover, the role of liaison psychiatry should also be incorporated.

Comparison Of Efficacy Of Yogurt Versus Probiotics For The Management Of Acute Diarrhoea.

BACKGROUND: The advantages of probiotic administration for acute diarrhoea are mainly shorter duration of symptoms as well as reduced number of stools per day while use of traditional yogurt has similar results. So, this study was conducted to compare the efficacy of yogurt with probiotic in children with acute gastroenteritis. METHODS: This randomized controlled trial was conducted at department of Paediatrics, Children Hospital, Pakistan Institute of Medical Sciences, Islamabad over 1 year. A total of nine hundred and thirty (930) children between 1-5 years of age presenting with acute diarrhoea were enrolled and equally randomized to Group-A (yogurt) and Group-B (lactobacillus rhamnosus) with ORS. The primary outcome was mean frequency of diarrhoea in first 24 hours after initiation of treatment in both the groups. RESULTS: Gender distribution revealed that out of 930 patients, 643 (69.1%) were male and 287 (30.9%) were female while the mean age was 3.14±1.18 years. Mean duration of disease was 4.23±2.02 days. Mean no. of stools in first 24 hours after treatment in Group-A (yogurt) was 3.25±1.64 and 3.29±1.74 in Group-B (probiotics). Student t-test for independent samples was applied and no significant difference was found between the two groups (p=0.713). CONCLUSIONS: Mean frequency of diarrhoea in first 24 hours after treatment with traditional yogurt and commercially available probiotics was not statistically significant in this study.