Naglaa M. Kamal

Burden of pediatric hepatitis C

Hepatitis C virus (HCV) is a major health burden infecting 170-210 million people worldwide. Additional 3-4 millions are newly-infected annually. Prevalence of pediatric infection varies from 0.05%-0.36% in the United States and Europe; up to 1.8%-5.8% in some developing countries. The highest prevalence occurs in Egypt, sub-Saharan Africa, Amazon basin and Mongolia. HCV has been present in some populations for several centuries, notably genotypes 1 and 2 in West Africa. Parenteral anti-schistosomal therapy practiced in the 1960s until the early 1980s had spread HCV infection throughout Egypt. Parenteral acquisition of HCV remains a major route for infection among Egyptian children. Insufficient screening of transfusions, unsterilized injection equipment and re-used needles and syringes continue to be major routes of HCV transmission in developing countries, whereas vertical transmission and adolescent high-risk behaviors (e.g., injection drug abuse) are the major routes in developed countries. The risk of vertical transmission from an infected mother to her unborn/newborn infant is approximately 5%. Early stages of HCV infection in children do not lead to marked impairment in the quality of life nor to cognitive, behavioral or emotional dysfunction; however, caregiver stress and family system strain may occur. HCV slowly progresses to serious complications as cirrhosis (1%-2%) and hepatocellular carcinoma (HCC) especially in the presence of risk factors as hemolytic anemias, obesity, treated malignancy, and concomitant human immune deficiency and/or hepatitis B virus co-infection. HCV vaccine remains elusive to date. Understanding the immune mechanisms in patients who successfully cleared the infection is essential for vaccine development. The pediatric standard of care treatment consists of pegylated interferon-α 2a or b plus ribavirin for 24-48 wk. The new oral direct acting antivirals, approved for adults, need further evaluation in children. Sustained virologic response varies depending on the viral load, genotype, duration of infection, degree of aminotransferase elevation, adiposity and single nucleotide polymorphisms of interleukin (IL)-28B locus. The goals of treatment in individual patients are virus eradication, prevention of cirrhosis and HCC, and removing stigmatization; meanwhile the overall goal is decreasing the global burden of HCV. IL-28B polymorphisms have been also associated with spontaneous clearance of vertically acquired HCV infection. The worldwide economic burden of HCV for children, families and countries is estimated to be hundreds of millions of US dollars per year. The United States, alone, is estimated to spend 199-336 million dollars in screening, monitoring and treatment during one decade. The emotional burden of having an HCV infected child in a family is more difficult to estimate.

Gastrointestinal basidiobolomycosis in children: an overlooked emerging infection?

Basidiobolus ranarum is a known cause of chronic subcutaneous zygomycosis. During the past decade, many cases have been reported with extracutaneous basidiobolomycosis. We aimed to review the medical literature on gastrointestinal basidiobolomycosis (GIB) as an emerging fungal infection causing a serious, and occasionally fatal, paediatric disease. We reviewed all reported cases of visceral basidiobolomycosis with special focus on the gastrointestinal involvement in children. Twenty-six cases of GIB have been reported worldwide, in 14 adults and 12 children. All cases presented with fever, abdominal pain with mass and high blood eosinophilia and were misdiagnosed as other chronic granulomatous diseases or malignancies. A few cases of retroperitoneal, pulmonary, nasal and disseminated basidiobolomycosis have also been reported. Basidiobolomycosis mostly affects young males as a subcutaneous infection. The visceral form of infection is rare. GIB has been scarcely reported in the medical literature, but recently it has been increasingly recognized. GIB poses diagnostic difficulties. Abdominal pain with mass and eosinophilia were present in all cases, highlighting the necessity of considering GIB in the differential diagnosis of this presentation. B. ranarum has been reported to cause disseminated fatal disease in both immune-competent and -compromised individuals. Culture is the gold standard for diagnosis, but the characteristic histopathological picture of chronic granulomas rich in eosinophils and the Splendore-Hoeppli phenomenon are the usual diagnostic tools. Surgery plus long courses of itraconazole treatment, up to 1 year, appear to be the best management options. GIB is an emerging infection that might lead to diagnostic confusion, morbidity and mortality. Diagnosis requires a high index of suspicion in the differential diagnosis of patients with fever, abdominal pain with mass and eosinophilia.

Gastrointestinal basidiobolomycosis: an emerging fungal infection causing bowel perforation in a child.

Basidiobolomycosis is an unusual fungal skin infection that rarely involves the gastrointestinal (GI) tract. We report a 10-year-old boy diagnosed as suffering GI basidiobolomycosis after being misdiagnosed first as suffering intestinal malignancy then schistosomiasis. The patient presented with fever, abdominal pain, vomiting, abdominal tenderness and rigidity with marked blood eosinophilia. Abdominal ultrasonographic and computed tomographic scans revealed a large caecal mass. Biopsy of the mass showed transmural granulomatous inflammation interpreted as schistosomal granuloma, ruling out lymphoma. The patients condition deteriorated despite anti-schistosomal therapy. Emergency surgery was then performed, and caecal perforation was found. The mass was excised; cultures were negative and histopathological examination was suggestive of schistosomal granuloma. The mass recurred 3 weeks post-operatively. Second-opinion histopathological examination diagnosed Basidiobolus ranarum infection. Treatment with itraconazole produced marked improvement, with diminution of the mass. B. ranarum was unequivocally identified in the archival formalin-fixed and paraffin-embedded (FFPE) tissue by PCR. This case emphasizes the need to consider GI basidiobolomycosis in children presenting with fever, abdominal mass and eosinophilia, especially those complicated by bowel perforation.

Biomarkers and early detection of late onset anthracycline-induced cardiotoxicity in children

Abstract Background The main strategy for minimizing anthracycline cardiotoxicity is early detection of high-risk patients. Aim of the study To investigate the role of cardiac biomarkers; cardiac troponin T (cTnT) and N-terminal probrain natriuretic peptide (NT-pro-BNP), and tissue Doppler imaging (TDI), as early predictors of chronic cardiotoxicity in survivors of acute leukemia. Patients and methods We carried a retrospective study on 50 asymptomatic survivors of acute leukemia who received anthracycline in their treatment protocols. All patients underwent blood sampling to determine the levels of NT-pro-BNP and cTnT along with conventional echocardiography and TDI. Results None had abnormal cTnT levels. About 20% had abnormal NT-pro-BNP levels. Diastolic dysfunction of the left ventricle was the most significant in conventional echocardiography. TDI was superior as it detected myocardial affection in 10% more than echo. TDI demonstrated global myocardial damage with significant aberrations in peak myocardial velocities and ratios. Conclusions NT-pro-BNP can be used as a sensitive cardiac biomarker in monitoring of anthracycline-induced cardiotoxicity. Follow up is essential to validate the role of NT-pro-BNP as an early marker for late onset anthracycline-induced cardiotoxicity. Tissue Doppler is marvelous as it could detect early cardiac dysfunction even in those with normal study by conventional echocardiography.

Nutritional Biomarkers in Children and Adolescents with Beta-Thalassemia-Major: An Egyptian Center Experience

Background and Aim. Trace elements and vitamins play a vital role in human body to perform its function properly. Thalassemic patients are at risk of micronutrient deficiency. This study estimated levels of vitamins A, C, E, B12, folic acid, total homocysteine (tHcy), and methylmalonic acid (MMA) along with trace elements, zinc, copper, and selenium in Beta-thalassemia-major patients. Methods. This study included 108 patients with Beta-thalassemia-major and 60 age and sex matched healthy children. Serum levels of vitamin A, E, C, tHcy, and MMA were estimated by high pressure liquid chromatography while serum levels of folic acid and B12 were estimated by thin layer chromatography. Serum zinc, copper, and selenium were determined by atomic absorption spectrometry. Results. There was a significant decrease of vitamins A, C, E, and B12 and trace elements zinc, copper, and selenium in thalassemic patients as compared to controls. tHcy and MMA were significantly elevated in patients. No significant correlations were found between the serum levels of the studied vitamins and trace elements as regards age, frequency of transfusion, duration of transfusion, and serum ferritin. Conclusion. The level of various nutritional biomarkers (vitamins A, C, E, and B12 and trace elements zinc, copper, selenium) was reduced in chronically transfused Egyptian thalassemic patient. These patients should have periodic nutritional evaluation and supplementation. Multicenter studies are highly recommended.

Outpatient blind percutaneous liver biopsy in infants and children: Is it safe?

Background/Aim: We aim to investigate the safety of outpatient blind percutaneous liver biopsy (BPLB) in infants and children with chronic liver disease (CLD). Patients and Methods: BPLB was performed as an outpatient procedure using the aspiration Menghini technique in 80 infants and children, aged 2 months to 14 yrs, for diagnosis of their CLD. Patients were divided into three groups: Group 1 (<1 year), group 2 (1–6 yrs), and group 3 (6–14 yrs). The vital signs were closely monitored 1 hr before biopsy, and then 1, 2, 6, and 24 hrs after biopsy. Twenty-four hours pre- and post-biopsy complete blood counts, liver enzymes, prothrombin time (PT), and abdominal ultrasonography, searching for a biopsy-induced hematoma, were done for all patients. Results: No mortality or major morbidities were encountered after BPLB. The rate of minor complications was 17.5% including irritability or “pain” requiring analgesia in 10%, mild fever in 5%, and drowsiness for >6 hrs due to oversedation in 2.5%. There was a statistically significant rise in the 1-hr post-biopsy mean heart and respiratory rates, but the rise was non-significant at 6 and 24 hrs except for group 2 where heart rate and respiratory rates significantly dropped at 24 hrs. No statistically significant difference was noted between the mean pre-biopsy and the 1, 6, and 24-hrs post-biopsy values of blood pressure in all groups. The 24-hrs post-biopsy mean hemoglobin and hematocrit showed a significant decrease, while the 24-hrs post-biopsy mean total leucocyte and platelet counts showed non-significant changes. The 24-hrs post-biopsy mean liver enzymes were non-significantly changed except the 24-hrs post-biopsy mean PT which was found to be significantly prolonged, for a yet unknown reason(s). Conclusions: Outpatient BPLB performed by the Menghini technique is safe and well tolerated even in infants and young children. Frequent, close monitoring of patients is strongly recommended to achieve optimal patient safety and avoid potential complications.

Benign intrascrotal lipoblastoma in a 4-month-old infant: a case report and review of literature

Lipoblastomas are rare benign soft tissue tumors that occur primarily in young children. Most lipoblastomas occur in the extremities, trunk, head, and neck. An intrascrotal location is unusual. We describe a case of a 4-month-old infant with an intrascrotal lipoblastoma and discuss the differential diagnosis and review the literature.

Predictive accuracy of serum hyaluronic acid as a non-invasive marker of fibrosis in a cohort of multi-transfused Egyptian children with β-thalassaemia major

BACKGROUND AND STUDY AIM Liver disease remains a major cause of morbidity and mortality in patients with β-thalassaemia major (β-TM); therefore, its identification at an early stage is of great significance. Serum hyaluronic acid (HA) is considered as a non-invasive marker that appears early before pathological changes occur. We aim to determine the predictive accuracy of HA in detecting and staging hepatic fibrosis in β-TM patients. PATIENTS AND METHODS 30 Egyptian children with β-TM, and 15 age and sex-matched controls were studied. All had abdominal ultrasonography (US), measurement of serum amino-transferases (ALT, AST); hepatitis C, B and human immunodeficiency viruses (HCV, HBV, HIV) sero-markers, serum ferritin and HA. Liver biopsy was done for patients and fibrosis was scaled using Metavir scoring system and liver iron concentration (LIC) was measured. RESULTS Twenty patients (67.7%) had sero-markers of HCV, none had HBV or HIV. Serum HA was significantly higher in patients (90.78±28.79 ng/ml) compared to controls (21.1±13.24 ng/ml) with p<0.05. No difference between HCV infected and non-infected patients was detected. Positive significant correlation was detected between serum HA and stages of fibrosis by histopathology and US. No correlation was found between serum HA and age, sex, weight, height, haemoglobin level, platelet count, AST, serum ferritin, necro-inflammatory grade, and LIC. CONCLUSIONS Serum HA is a valuable non-invasive marker that may contribute to the assessment of liver fibrosis in multi-transfused children and adolescents with β-TM, irrespective of concomitant HCV infection.

Diagnosis of gastrointestinal basidiobolomycosis: a mini‐review

Basidiobolus ranarum (Entomophthoromycotina) very rarely affects the gastrointestinal (GI) tract. To date, reported paediatric GI basidiobolomycosis cases are 27 worldwide; 19 from Saudi Arabia and 8 from other parts of the world. Often these cases present a diagnostic dilemma, are prone to misdiagnosis and lack of disease confirmation by proper molecular methodologies. The fungal mass removed by surgery is usually sent for conciliar histopathology, isolation by fungal cultures and final molecular testing for basidiobolomycosis. The incidence of basidiobolomycoses, their predisposing factors and the molecular diagnosis of the fungus causing the disease in combination with a phylogenetic framework are reviewed.

Diagnosis of spontaneous bacterial peritonitis in infants and children with chronic liver disease: A cohort study

BackgroundSpontaneous bacterial peritonitis (SBP) is a serious complication in infants and children with chronic liver disease (CLD); however its diagnosis might be difficult. We aimed to study the feasibility of diagnosing SBP by routine ascitic fluid tapping in infants and children with CLD.MethodsWe enrolled thirty infants and children with biopsy-proven CLD and ascites. Ascitic fluid was examined for biochemical indices, cytology and cell count. Aerobic and anaerobic bacteriological cultures of ascitic fluid were preformed. Direct smears were prepared from ascitic fluid deposit for Gram and Zheil-Nelson staining.ResultsPatients were divided into three groups: Group I included five patients with SBP in which the cell count was ≥ 250/mm3 and culture was positive (16.7%), Group II, eight patients with culture negative neutrocytic ascites (CNNA) with cells ≥ 250/mm3 and negative culture (26.7%) and Group III, seventeen negative patients (56.6%) in which cells were <250/mm3 and culture was negative. None of our patients had bacteriascites (i.e. culture positive with cells <250/mm3). Presence of fever was significantly higher in SBP and CNNA. The mean lactate dehydrogenase (LDH) level was significantly higher in ascitic fluid in the infected versus sterile cases (p < 0.002). A ratio of ascitic/serum LDH ≥ 0.5 gave a sensitivity of 80%, specificity of 88%, positive predictive value (PPV) of 66.7%, negative predictive value (NPV) of 93.7% and accuracy of 63.3%. The mean pH gradient (arterial - ascitic) was significantly higher in SBP and CNNA cases when compared to the negative cases (p < 0.001). Ascitic fluid protein level of ≤ 1 gm/dl was found in 13/30 (43.3%) of studied cases with a sensitivity of 100%, specificity of 64.7%, PPV of 45.5%, NPV of 100% and diagnostic accuracy of 53.3% (p = 0.0001).ConclusionsSBP is a rather common complication in children with CLD. Culture of the ascitic fluid is not always diagnostic of infection. Biochemical parameters of the ascitic fluid definitely add to the diagnostic accuracy. LDH ascitic/serum ratio ≥ 0.5, an arterial-ascitic pH gradient ≥ 0.1 and total ascitic fluid protein ≤ 1 gm/dl are the most significant parameters suggesting infection.