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Abstract Dengue or breakbone fever is one of the most important causes of febrile illness in children residing in tropical and subtropical regions. This mosquito-borne viral disease is mediated by the bite of the infected Aedes mosquito. Dengue infection has been expanding rapidly throughout the globe in the past few decades. The virus has hepatotoxic effects. However, the pathophysiology of liver involvement in dengue is still not entirely clear. The reported clinical spectrum of dengue hepatitis ranges from mild asymptomatic elevation in transaminaselevels to acute liver failure in children. This review focuses on hepatic manifestation, the pathogenesis of liver injury, and treatment option of the effects of dengue on the liver in the pediatric population.

Abstract Hepatitis C virus infection is an emerging problem for children and adolescents. Chronic HCV infection affects approximately 3.5–5 million children worldwide. Unaddressed HCV infection in children progresses to decompensated liver disease and hepatocellular carcinoma during adulthood. Early detection of HCV and the administration of appropriate antiviral therapy are required for the prevention of long-term morbidity associated with chronic HCV infection. The perinatal route is the most common source of childhood HCV infection. Anti-HCV positivity at or after 18 months of age necessitates an HCV-RNA assay after age 3 to recognize chronic HCV infection. Both anti-HCV and HCV-RNA positivity are the indications for antiviral therapy. At present, various combinations of oral, direct-acting antivirals (DAAs) have been approved for children above 3 years of age. Their efficacy is high. Apart from the effectiveness of DAA therapy, steps should be taken to screen pregnant women to prevent the transmission of viral infection from mother to child. To increase awareness about the mode of HCV spread, NAT-based tests in blood banks for better screening and making the DAAs available at a subsidized rate in the public sector are necessary to eradicate HCV infection.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most unabating cause of chronic liver disease in children and adolescents. This study aimed to examine the association of single nucleotide polymorphism in patatin-like phospholipase domain containing 3 (PNPLA3) gene with paediatric non-alcoholic fatty liver disease. Methods: This case-control study was conducted from June 2021 to December 2022. Fifty-one overweight children aged 6–17 years were recruited in this study and divided into NAFLD (cases) and non-NAFLD (controls) groups based on hepatic steatosis detected by liver ultrasonography. We analysed the rs738409 polymorphism by TaqMan assay and examined its association with NAFLD. Results: Thirty-one (60.8%) children were in the case group and 20 (39.2%) children were in the control group. Alanine aminotransferase (P

Background: We aimed to examine the persistence of anti-HBs in Bangladeshi children aged 5 and 10 years after primary vaccination, and this response to a booster dose. Methods: A total of 100 children were enrolled who were divided into two groups (A and B). Group A comprised of 50 children vaccinated 5 years ago, and group B had 50 children vaccinated 10 years ago. Hepatitis B surface antibody titer was measured, and a booster dose of the vaccine was administered to those who had anti-HBs less than 10 mlU/ml. Seventeen such children from group A and 27 from group B were vaccinated with a booster dose. After one month, 12 children from group A and 18 children from group B were retested for hepatitis B surface antibody levels. Results: After 5 and 10 years of primary vaccination, 66.0% and 46.0% children had protective antibody levels. After one month of booster dose, 91.6% children responded to the increased level of anti-HBs in group A. Among them, 66.6% showed an adequate response. In group B, 88.8% had an increased level of anti-HBs antibody where 83.3% had an adequate response. Geometric mean titre of anti-HBs antibody boosted by 35 and 75 times from pre-booster time to post-booster vaccination in group A and B, respectively. Conclusion: Children had protective levels of anti-HBs antibodies at 5 and 10 years after completion of the primary vaccinations. Anamnestic response to booster vaccination confirmed the persistence of an effective immunological memory in vaccines. Bangabandhu Sheikh Mujib Medical University Journal 2023;16(2): 101-105

Chronic liver disease is a uncommon manifestation in the children and many of them presents with oesophageal varices. The aim of this study was to observe the association between severity of chronic liver diseases determined by Child- Pugh score with grading of oesophageal varices. 62 cases (male, 34) were included in the present study. Mean age of the study population was 9.5±3.3 years. Male to female ratio was 1.2:1. Wilson’s disease was the most common etiology of chronic liver disease (64.5%). Of the 62 children, 30.7% had Child class A, 16.1% had Child class B and the remaining 53.2% had Child class C cirrhosis. Oesophageal varices were found in 43 (69.3%) children. On univariate ananlysis low platelet count and splenomegaly were found to be associated with the presence of esophageal varices. Splenomegaly was found as independent predictor for presence of varices on multivariate analysis (OR; 15.51, 95% CI, 3.7-63.5). Furthermore, splenomegaly was also independent risk factor for large esophageal varices. No association was found between Child-Pugh classification (child A, B, C) with grading of oesophageal varices (Grade - I, II, III, IV). Our study showed no positive association between Child-Pugh classifications with grading of esophageal varices. Splenomegaly predicts the presence of oesophageal varices as well as the presence of large esophageal varices. BSMMU J 2022; 15(1): 29-34

Simple Summary: This study focused on the trends of Head and Neck Cancers (HNC) in the First Nations people of Australia. There is an underwhelming amount of literature holistically analysing the trend of HNC among the First Nations people. This study comprehensively analysed incidence, mortality, and survival rates in the First Nations people, and compared these trends with the non-Indigenous Australian population. This emphasized the need to investigate the underlying causes and barriers for differences in the HNC burden between First Nations people and non-Indigenous Australians. Collaborative efforts, spanning from local to national levels, are required to address the HNC burden in Australia, particularly, in First Nations communities. Background: We aim to assess and compare the HNC trends between the First Nations and non-Indigenous population. Methods: HNC incidence (1998–2013) and mortality (1998–2015) data in First Nations people and non-Indigenous Australians were utilised from the Australian Cancer Database. The age-standardised incidence and mortality trends along with annual percentage changes were analysed using Joinpoint models. Age-standardised incidence and mortality rates according to remoteness, states, and five-year survival rates among First Nations people and non-Indigenous Australians were presented as graphs. Results: First Nations people had over twice the age-standardised incidence (2013; 29.8/100,000 vs. 14.7/100,000) and over 3.5 times the age-standardised mortality rates (2015; 14.2/100,000 vs. 4.1/100,000) than their non-Indigenous counterparts. Both populations saw a decline in mortality, but the decline was only statistically significant in non-Indigenous Australians (17.1% decline, 1998: 4.8/100,000, 2015: 4.1/100,000; p < 0.05). Across all remoteness levels and states, First Nations people consistently had higher age-standardised incidence and mortality rates. Furthermore, the five-year survival rate was lower by 25% in First Nations people. Conclusion: First Nations people continue to shoulder a disproportionate HNC burden compared to non-Indigenous Australians. [ABSTRACT FROM AUTHOR]

Abstract Background Histoplasmosis is a rare infectious condition with mainly pulmonary involvement. Disseminated histoplasmosis may occur in immunocompromised condition. It can present in different ways but jaundice and ascites is very uncommon. Case presentation A 8- year old girl visited to department of pediatric gastroenterology & nutrition, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Child presented with fever, jaundice and abdominal distension for 2 ½ months. There was no history of contact with tuberculosis patient and travelling to kala-azar, malaria endemic zone and no history of previous jaundice, blood or blood product transfusion, history of sib death, family history of jaundice or neuropsychiatric disorder, significant weight loss. On general examination she was fretful, febrile, moderately icteric, mildly pale, vitally stable, severely wasted and moderately stunted, skin survey revealed infected scabies, BCG vaccine mark was absent, generalized lymphadenopathy, hepato-splenomegaly and ascites present. After evaluating the physical findings, several investigations was done including lymphnode biopsy, then the case was finally diagnosed as Disseminated histoplasmosis with portal hypertension. Child was treated with injectable Deoxycholate Amphotericin B for 28 days and improved on follow up. Conclusion We suggest that children presenting with fever, jaundice, lymphadenopathy and hepatosplenomegaly and portal hypertension, disseminated histoplasmosis can be one differential.

Abstract not available BSMMU J 2021; 14(3): 92-98

Aim: The study was aimed to find out the efficacy of a stool color card (SCC) in differentiating biliary atresia (BA) from non-BA in resource-limited countries. Background: stool color screening system was introduced in 2004 which lead to marked improvement in sensitivity of detecting BA. Methods: This cross-sectional observational study was conducted from January, 2019 through July, 2022 on purposively sampled infants who developed jaundice before three months of age, had direct bilirubin of > 20 % of total with pale stool and dark urine. Results: 144 cases (male, 96) were included in the study and their mean age at admission was 87.3±37.2 days and mean age at onset of jaundice was 6.1±7.7 days. BA was confirmed in 106 (73.6%) cases and 38 (26.4%) children were in non-BA group. Frequency of persistent pale stool between BA and non- BA were 88 vs 8 (83.0 % Vs 21.0 %) which was highly significant (p=0.000). Mean difference of total and direct serum bilirubin, median alanine transferase and alkaline phosphatase were not statistically significant between two groups. Median of serum gamma glutamyl transpeptidase (GGT) in BA was 570 U/L and in non-BA it was 138.0 U/L which was statistically significant (p=0.000). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SCC were 83%, 78.9%, 91.7%, 62.5% and 81.9% respectively. Conclusion: SCC has good sensitivity to diagnose BA but failed to prove better specificity to rely simply on it. SCC may be used as early screening tool for prompt referral to appropriate medical care centers for final evaluation of BA. [ABSTRACT FROM AUTHOR]

A 12-year-old immunized girl with only issue of non-consanguineous parents presented with the complaints of severe, agonizing, and continued upper abdominal pain which radiated to the back, aggravated after taking food and partially relieved on leaning forward for the last 4 days. The pain was associated with several episodes of vomiting. She had a history of similar types of 3 attacks within the last 1 year and in between attacks, she was comparatively well. On query, the mother gave a history of gradual weight loss.

A 10-year-old immunized girl, 6th issue of consanguineous parents, presented with the complaints of jaundice for the last 2 years and deterioration of school performance for the same duration. She also had generalized itching for the last 6 months. She had no history of altered sleep pattern, any gastrointestinal bleeding, surgical or dental procedures, history of blood and blood products transfusion, taking any offending drugs, sib death or family history of such type of illness.

Purpose: Although the 24-hours urinary copper excretion is useful for the diagnosis of Wilson disease (WD), there are practical difficulties in the accurate and timed collection of urine samples. The purpose of this study was to verify if the spot morning urinary Copper/Zinc (Cu/Zn) ratio could be used as a replacement parameter of 24-hours urinary copper excretion in the diagnosis of WD. Methods: A cross-sectional study was conducted at the Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from June 2019 to May 2021 on 67 children over three years of age who presented with liver disease. Twenty-seven children who fulfilled the inclusion criteria for WD were categorized into the test group, and the remaining forty children were considered to have non-Wilsonian liver disease and were categorized into the control group. Along with other laboratory investigations, spot morning urinary samples were estimated for the urinary Cu/Zn ratio in all patients and were compared to the 24-hour urinary copper excretion. The diagnostic value of the Cu/Zn ratio was then analyzed. Results: Correlation of spot morning urinary Cu/Zn ratio with 24-hours urinary copper excretion was found to be significant (r=0.60). The area under ROC curve with 95% confidence interval of morning urinary Cu/Zn ratio measured using 24-hours urine sample was 0.84 (standard error, 0.05; p<0.001). Conclusion: Spot morning urinary Cu/Zn ratio seems to be a promising parameter for the replacement of 24-hours urinary copper excretion in the diagnosis of WD. [ABSTRACT FROM AUTHOR]

In brief: DGCR8 microprocessor complex, which is important for miRNA biogenesis, is regulated by peptidylarginine deiminase 2 and expression fluctuates in gonadotrope cells across the mouse estrous cycle. Canonical miRNA biogenesis requires DGCR8 microprocessor complex subunit, which helps cleave pri-miRNAs into pre-miRNAs. Previous studies found that inhibiting peptidylarginine deiminase (PAD) enzyme activity results in increased DGCR8 expression. PADs are expressed in mouse gonadotrope cells, which play a central role in reproduction by synthesizing and secreting the luteinizing and follicle stimulating hormones. Given this, we tested whether inhibiting PADs alters expression of DGCR8, DROSHA, and DICER in the gonadotrope-derived LßT2 cell line. To test this, LßT2 cells were treated with vehicle or 1 µM pan-PAD inhibitor for 12 h. Our results show that PAD inhibition leads to an increase in DGCR8 mRNA and protein. To corroborate our results, dispersed mouse pituitaries were also treated with 1 µM pan-PAD inhibitor for 12 h which increases DGCR8 expression in gonadotropes. Since PADs epigenetically regulate gene expression, we hypothesized that histone citrullination alters Dgcr8 expression thereby affecting miRNA biogenesis. LßT2 samples were subjected to ChIP using an antibody to citrullinated histone H3, which shows that citrullinated histones are directly associated with Dgcr8. Next, we found that when DGCR8 expression is elevated in LßT2 cells, pri-miR-132 and -212 are reduced, while mature miR-132 and -212 are increased suggesting heightened miRNA biogenesis. In mouse gonadotropes, DGCR8 expression is higher in diestrus as compared to estrus, which is the inverse of PAD2 expression. Supporting this idea, treatment of ovariectomized mice with 17ß-estradiol results in an increase in PAD2 expression in gonadotropes with a corresponding decrease in DGCR8. Collectively, our work suggests that PADs regulate DGCR8 expression leading to changes in miRNA biogenesis in gonadotropes. [ABSTRACT FROM AUTHOR]

Purpose: Perinatal cytomegalovirus (CMV) infection can lead to biliary atresia (BA) in different entities. This study aimed to compare the clinical, hematological, biochemical, and histological features of infants with BA based on their CMV immunoglobulin M (IgM) status at presentation. Methods: This cross-sectional descriptive study was carried out between January 2019 and June 2020 at the Department of Pediatric Gastroenterology and Nutrition at the Bangabandhu Sheikh Mujib Medical University (BSMMU) in Dhaka. Forty-three patients with BA were selected purposively and categorized into either the CMV IgM-positive or CMV IgM-negative BA group. Categorical variables were compared using Fisher's exact test and chi-square tests, while the Student's t-test and Mann-Whitney U-test were used to compare continuous variables. For all statistical tests, a p-value <0.05 was considered statistically significant. Results: Thirty-three (76.7%) of the cases were between 2 and 3 months of age on admission. The clinical, hematological, and biochemical parameters did not differ significantly between the CMV IgM-positive and CMV IgM-negative BA groups. Most (50.0%) of the CMV IgMpositive cases had fibrosis stage F2, while 43.5% of the CMV IgM-negative cases had fibrosis stage F3, with no significant difference between the groups (p=0.391). Conclusion: Our data shows no significant distinction between CMV IgM-positive and CMV IgM-negative BA, suggesting that CMV does not contribute to BA pathogenesis. [ABSTRACT FROM AUTHOR]

Early-life exposure to arsenic (As) increases risks of respiratory diseases/infections in children. However, data on the ability of the innate immune system to combat bacterial infections in the respiratory tracts of As-exposed children are scarce. To evaluate whether persistent low-dose As exposure alters innate immune function among children younger than 5 years-of-age, mothers and participating children (N = 51) that were members of the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in rural Bangladesh were recruited. Household water As, past and concurrent maternal urinary As (U-As) as well as child U-As were all measured at enrollment. In addition, U-As metabolites were evaluated. Innate immune function was examined via measures of cathelicidin LL-37 in plasma, ex vivo monocyte-derived-macrophage (MDM)-mediated killing of Streptococcus pneumoniae (Spn), and serum bactericidal antibody (SBA) responses against Haemophilus influenzae type b (Hib). Cyto-/chemokines produced by isolated peripheral blood mononuclear cells (PBMC) were assayed using a Multiplex system. Multivariable linear regression analyses revealed that maternal (p < 0.01) and child (p = 0.02) U-As were positively associated with plasma LL-37 levels. Decreased MDM-mediated Spn killing (p = 0.05) and SBA responses (p = 0.02) were seen to be each associated with fractions of mono-methylarsonic acid (MMA; a U-As metabolite) in the children. In addition, U-As levels were seen to be negatively associated with PBMC formation of fractalkine and IL-7, and positively associated with that for IL-13, IL-17 and MIP-1α. These findings suggested that early-life As exposure may disrupt the innate host defense pathway in these children. It is possible that such disruptions may have health consequences later in life. [ABSTRACT FROM AUTHOR]

Background: Development of new tuberculosis (TB) drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3) and 4-phenyl butyrate (PBA) are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects. Objective: To examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to standard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients. Methods: Adult TB patients (n = 288) were enrolled in a randomized, double-blind, placebo-controlled trial conducted in Bangladesh. Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8. Clinical assessments and sputum smear microscopy were performed weekly up to week 4, fortnightly up to week 12 and at week 24; TB culture was performed at week 0, 4 and 8; concentrations of LL-37 in cells, 25-hydroxyvitamin D3 (25(OH)D3) in plasma and ex vivo bactericidal function of monocyte-derived macrophages (MDM) were determined at week 0, 4, 8, 12 and additionally at week 24 for plasma 25(OH)D3. Results: At week 4, 71% (46/65) of the patients in the PBA+vitD3-group (p = 0.001) and 61.3% (38/62) in the vitD3-group (p = 0.032) were culture negative compared to 42.2% (27/64) in the placebo-group. The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group (p = 0.001) and 2.2 times higher in vitD3-group (p = 0.032) compared to placebo. The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 (p = 0.034). Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo (log rank 11.38, p = 0.01). Conclusion: Adjunct therapy with PBA+vitD3 or vitD3 or PBA to standard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy in the treatment of TB. Trial Registration: clinicaltrials.gov [ABSTRACT FROM AUTHOR]

When facing an acute viral infection, our immune systems need to function with finite precision to enable the elimination of the pathogen, whilst protecting our bodies from immune-related damage. In many instances however this "perfect balance" is not achieved, factors such as ageing, cancer, autoimmunity and cardiovascular disease all skew the immune response which is then further distorted by viral infection. In SARS-CoV-2, although the vast majority of COVID-19 cases are mild, as of 24 August 2020, over 800,000 people have died, many from the severe inflammatory cytokine release resulting in extreme clinical manifestations such as acute respiratory distress syndrome (ARDS) and hemophagocytic lymphohistiocytosis (HLH). Severe complications are more common in elderly patients and patients with cardiovascular diseases. Natural killer (NK) cells play a critical role in modulating the immune response and in both of these patient groups, NK cell effector functions are blunted. Preliminary studies in COVID-19 patients with severe disease suggests a reduction in NK cell number and function, resulting in decreased clearance of infected and activated cells, and unchecked elevation of tissue-damaging inflammation markers. SARS-CoV-2 infection skews the immune response towards an overwhelmingly inflammatory phenotype. Restoration of NK cell effector functions has the potential to correct the delicate immune balance required to effectively overcome SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is associated with secondary malignancies. Previous studies have suggested that mutated cancer proteins, such as RNA polymerase III, are autoantigens promoting an inflammatory response in SSc. However, it has never been previously investigated whether non-neoplastic tissue in SSc harbors mutations which may play a role in SSc pathogenesis. Skin biopsies were obtained from 8 sequential patients with a progressive form of early stage SSc (with severe skin and/or lung involvement). Areas of dermal fibrosis were microdissected and analyzed with deep, whole exome sequencing. Gene mutation patterns were compared to autologous buccal mucosal cells as a control. SSc skin biopsies were hypermutated with an average of 58 mutations/106 base pairs. The mutational pattern in all samples exhibited a clock-like signature, which is ubiquitous in cancers and in senescent cells. Of the 1997 genes we identified which were mutated in at least two SSc patients, 39 genes represented cancer drivers (i.e. tumor suppressor genes or oncogenes) which are commonly found in gynecological, squamous and gastrointestinal cancer signatures. Of all the mutations, the most common mutated genes were important in regulating pathways related to epigenetic histone modifications, DNA repair and genome integrity. Somatic hypermutation occurs in fibrotic skin in patients with early progressive SSc. Cancer driver gene mutations may potentially play a fundamental role in the pathogenesis of SSc. • Non-synonymous genomic mutations are common in the dermis of patients with early systemic sclerosis. • Genomic mutations have a clock-like signature, which is commonly present in cancer. • Many mutated genes are important in the maintenance of genomic integrity. [ABSTRACT FROM AUTHOR]

Very early onset inflammatory bowel disease (VEO-IBD) is called when age of onset of IBD occurs below 6 years. Though it is rare, it has been increasing over last decade with decreasing age of onset. VEO-IBD is different compared with pediatric and adult-onset IBD in many aspects, including the disease type, location of the lesion, disease behavior and genetic susceptibility. These children with VEO-IBD are usually present with more severe disease than older children and adults. VEO-IBD is associated with monogenic defect. The thought of a monogenic cause of VEO-IBD was first confirmed by the detection of mutations of interleukin 10 (IL-10) receptor genes that cause impaired IL-10 signaling. Monogenic IBD possesses significant concern because it usually presents with refractory to conventional IBD treatment or fistulous Crohn's disease, so early treatment with biologics or an alternative approach such as hematopoietic stem cell transplantation (HSCT) might be looked-for. Before establishing IBD, we must think of more common diseases of this age group. Infection and Cow's milk protein allergy (CMPA) are two common conditions and it can cause severe colitis. Confirmation of chronic intestinal inflammation by endoscopies is of greatest significance for the diagnosis of IBD. There should be no age limit for performing endoscopies. Severe disease should be treated with biologic agents and surgery. Identification of genes associated with IBD leads to better understanding of its pathogenesis, which could help to provide more targeted interventions. We discuss the topic here to create awareness among Pediatricians so that the patients can be benefited.

Solitary rectal ulcer syndrome (SRUS) is an uncommon benign rectal disorder. Typically, young adults are affected and it is rare in children. Straining during defecation, self-induced trauma and paradoxical contraction of puborectalis muscle are the major contributing factors of this condition. Clinical features of SRUS are rectal bleeding, mucorrhoea, excessive straining during defecation, tenesmus, feeling of incomplete defecation and constipation. A complete and thorough history is most important for diagnosis of SRUS. Rectal bleeding may be misinterpreted as originating from an anal fissure caused by constipation or as other causes of rectal bleeding such as a juvenile polyp. The best and most accurate diagnostic method of SRUS is rectal biopsy. The major histological feature of SRUS is fibromuscular obliteration of the lamina propria. Avoiding straining, regular toilet habit, use of bulk laxatives, steroid and sucralfate enemas are the mainstay of treatment. Biofeedback mechanism is another treatment option. Because the clinical presentation varies, the diagnosis requires a high index of suspicion for both the clinician and the pathologist.

Alport syndrome is an inherited disorder of type IV collagen most commonly leading to glomerulonephritis and kidney failure. Various extrarenal manifestations have been reported, including a spectrum of aortic and aortic valve diseases. We report a case of a 34-year-old man with Alport syndrome presenting with chest pain. Work-up showed a dilated aortic root, bicuspid aortic valve, aortic insufficiency, and small ascending aortic dissection necessitating surgical repair. We provide a review of the literature describing aortic pathology in Alport syndrome and suggest that clinicians caring for patients with Alport syndrome have a high index of suspicion for such entities in patients presenting with symptoms of chest pain., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)