Hepatitis B vaccination coverage among Iranian children aged 15-26 months in 2006

This study in 2006 estimated the hepatitis B virus (HBV) vaccination coverage in the Islamic Republic of Iran at the national and district levels in urban, rural and remote populations of 41 university health service areas. Of 21 905 children recruited to the study, vaccination coverage based on vaccination card records was 100% in 14, 15 and 10 of the 41 university areas for the 1st, 2nd and 3rd doses of HBV respectively. National levels of HBV1, HBV2 and HBV3 coverage were 98.9%, 98.8% and 98.4% respectively. The lowest HBV vaccination coverage rate was 90.7% (in a remote district). HBV vaccination coverage was at an acceptable level in Iranian children

Sentinel hospital-based surveillance of Rotavirus diarrhea in Iran

Background. Rotavirus is the most common causes of severe, acute diarrhea during childhood and is an important cause of morbidity and mortality in developing countries. We established active hospital-based surveillance of childhood diarrhea to assess the scope of severe rotavirus disease in Iran. Methods. From May 2006 through April 2007, prospective surveillance of rotavirus diarrhea among children aged <5 years was conducted in 5 sentinel hospitals in Iran. Stool samples were tested for rotavirus using a commercially available enzyme immunoassay, and rotavirus-positive samples were genotyped using reverse-transcriptase polymerase chain reaction. Results. Of 2198 children admitted to the hospital for acute gastroenteritis, 1298 (59.1%) had stool samples test positive for rotavirus by enzyme immunoassay. Of the rotavirus episodes, 85% occurred during the first 2 years of life, with the peak prevalence of severe rotavirus disease occurring from September through January. Among the 110 rotavirus-positive samples that were genotyped, G4P[8] was the most commonly detected rotavirus genotype (30.9% of strains). Other commonly detected genotypes included P[8] with G nontypeable (21.8%), G4 with P nontypeable (13.6%), G1[P8] (10.9%), and G2[P4] (5.5%). Conclusions. Rotavirus is the most common cause of severe diarrhea in Iran, which indicates that safe and effective rotavirus vaccination in Iran is a public health priority. © 2009 by the Infectious Diseases Society of America. All rights reserved

Erythropoietic protoporphyria without skin symptoms-you do not always see what they feel

Erythropoietic protoporphyria (EPP) is an inherited disorder of the porphyrin metabolism that often remains undiagnosed in children. We report on a 4-year-old girl who had been suffering for 1 year from recurrent painful crises affecting her hands, feet, and nose following sun exposure. Objective skin lesions were absent until the age of 6. Porphyrin analysis revealed elevated free erythrocyte protoporphyrin (FEP) levels confirming the diagnosis of EPP. This illustrates that skin lesions might be completely absent in children affected with EPP, a fact that has only been reported once previously. Because EPP can manifest with few and unspecific cutaneous symptoms or no skin lesions at all, like in this patient, the diagnosis of EPP might be delayed or missed. EPP should be excluded in all photosensitive children, especially when discomfort is disproportionate to the extent of the cutaneous lesions. The clinic, pathophysiology, diagnosis, complications, and therapy of EPP are discussed

Efficacy and safety of givosiran for acute hepatic porphyria: 24-month interim analysis of the randomized phase 3 ENVISION study

Background &amp; Aims Upregulation of hepatic delta-aminolevulinic acid synthase 1 with accumulation of potentially toxic heme precursors delta-aminolevulinic acid and porphobilinogen is fundamental to the pathogenesis of acute hepatic porphyria. Aims: evaluate long-term efficacy and safety of givosiran in acute hepatic porphyria. Methods Interim analysis of ongoing ENVISION study (NCT03338816), after all active patients completed their Month 24 visit. Patients with acute hepatic porphyria (≥12 years) with recurrent attacks received givosiran (2.5 mg/kg monthly) (n=48) or placebo (n=46) for 6 months (double-blind period); 93 received givosiran (2.5 mg or 1.25 mg/kg monthly) in the open-label extension (continuous givosiran, n=47/48; placebo crossover, n=46/46). Endpoints included annualized attack rate, urinary delta-aminolevulinic acid and porphobilinogen levels, hemin use, daily worst pain, quality of life, and adverse events. Results Patients receiving continuous givosiran had sustained annualized attack rate reduction (median 1.0 in double-blind period, 0.0 in open-label extension); in placebo crossover patients, median annualized attack rate decreased from 10.7 to 1.4. Median annualized days of hemin use were 0.0 (double-blind period) and 0.0 (open-label extension) for continuous givosiran patients and reduced from 14.98 to 0.71 for placebo crossover patients. Long-term givosiran led to sustained lowering of delta-aminolevulinic acid and porphobilinogen and improvements in daily worst pain and quality of life. Safety findings were consistent with the double-blind period. Conclusions Long-term givosiran has an acceptable safety profile and significantly benefits acute hepatic porphyria patients with recurrent attacks by reducing attack frequency, hemin use, and severity of daily worst pain while improving quality of life

Erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. EPP has been reported worldwide, with prevalence between 1:75,000 and 1:200,000. It usually manifests in early infancy upon the first sun exposures. EPP is characterised by cutaneous manifestations of acute painful photosensitivity with erythema and oedema, sometimes with petechiae, together with stinging and burning sensations upon exposure to sunlight, without blisters. These episodes have a variable severity depending on the exposure duration and may result in chronic permanent lesions on exposed skin. As protoporphyrin is a lipophilic molecule that is excreted by the liver, EPP patients are at risk of cholelithiasis with obstructive episodes, and chronic liver disease that might evolve to rapid acute liver failure. In most patients, EPP results from a partial deficiency of the last enzyme of the haem biosynthetic pathway, ferrochelatase, EC 4.99.1.1/FECH (encoded by the FECH gene). EPP appears to be inherited as an autosomal dominant disease, the clinical expression of which is modulated by the presence of the hypomorphic FECH IVS3-48C allele trans, but recessive inheritance with two mutated FECH alleles has also been described. In about 2% of patients, overt disease was recently shown to be caused by gain-of-function mutations in the erythroid-specific aminolevulinic acid synthase 2 (ALAS2/ALAS, EC 2.3.1.27) gene and named X-linked dominant protoporphyria. Diagnosis is established by finding increased levels of protoporphyrin in plasma and red blood cells, and detection of a plasma fluorescence peak at 634 nm. Investigations for hepatic involvement, ferrochelatase activity level, genetic analysis (FECH mutations, presence of the hypomorphic FECH IVS3-48C allele trans and ALAS2 mutations) and family studies are advisable. Differential diagnosis includes phototoxic drug reactions, hydroa vacciniforme, solar urticaria, contact dermatitis, angio-oedema and, in some cases, other types of porphyria. Management includes avoidance of exposure to light, reduction of protoporphyrin levels and prevention of progression of possible liver disease to liver failure. As the major risk in EPP patients is liver disease, a regular follow-up of hepatic involvement is essential. Sequential hepatic and bone marrow transplantation should be considered as a suitable treatment for most severe cases of EPP with hepatic involvement. EPP is a lifelong disorder whose prognosis depends on the evolution of the hepatic disease. However, photosensitivity may have a significant impact on quality of life of EPP patients

Mitochondrial energetic defects in muscle and brain of a Hmbs-/- mouse model of acute intermittent porphyria

Acute intermittent porphyria (AIP), an autosomal dominant metabolic disease (MIM #176000), is due to a deficiency of hydroxymethylbilane synthase (HMBS), which catalyzes the third step of the heme biosynthetic pathway. The clinical expression of the disease is mainly neurological, involving the autonomous, central and peripheral nervous systems. We explored mitochondrial oxidative phosphorylation (OXPHOS) in the brain and skeletal muscle of the Hmbs(-/-) mouse model first in the basal state (BS), and then after induction of the disease with phenobarbital and treatment with heme arginate (HA). The modification of the respiratory parameters, determined in mice in the BS, reflected a spontaneous metabolic energetic adaptation to HMBS deficiency. Phenobarbital induced a sharp alteration of the oxidative metabolism with a significant decrease of ATP production in skeletal muscle that was restored by treatment with HA. This OXPHOS defect was due to deficiencies in complexes I and II in the skeletal muscle whereas all four respiratory chain complexes were affected in the brain. To date, the pathogenesis of AIP has been mainly attributed to the neurotoxicity of aminolevulinic acid and heme deficiency. Our results show that mitochondrial energetic failure also plays an important role in the expression of the disease

Prevalence and risk factors for HBV and HCV in prisoners in Iran: a national bio-behavioural surveillance survey in 2015

Objectives: To provide more accurate estimates of the prevalence of Hepatitis B (HBV) and Hepatitis C (HCV) and their contributing factors among prisoners in Iran. Methods: Cross-sectional study of 6200 Iranian prisoners in 2015. Data were collected through questionnaires and interviews. HBV infection and HCV exposure status of the participants was determined by HBsAg and HCV antibodies blood tests using enzyme-linked immunosorbent assay (ELISA). Data were analysed in STATA-12. Result: Prevalence of HCV exposure was 9.48 (95 CI: 8.73�10.27), and prevalence of HBV was 2.48 (95 CI: 2.07�2.89) in the general prison population. In multivariate analysis, the most important risk factor for HBV was a history of drug use in lifetime (adjusted odds ratio, AOR: 1.8, 95 CI: 1.17�3.02). The main risk factors for HCV exposure were a history of drug use in lifetime (AOR: 4.08, CI: 2.56�6.27), age over 30 (AOR: 2.68, CI: 2.01�3.56), and having tattoos (AOR = 1.67, CI: 1.35�2.07). Conclusion: Although vaccination is used to control HBV among prisoners, prevalence of HCV exposure is alarming in the prison population of Iran, especially among people who inject drugs. Eliminating viral hepatitis in Iran by 2030 requires a national commitment and rapid measures for targeting this high-risk group. Given the increased efficiency of HCV treatment in recent years, prisons provide an opportunity to access patients for treatment. © 2018 John Wiley & Sons Lt

Prevalence and risk factors for HBV and HCV in prisoners in Iran: a national bio-behavioural surveillance survey in 2015

Objectives: To provide more accurate estimates of the prevalence of Hepatitis B (HBV) and Hepatitis C (HCV) and their contributing factors among prisoners in Iran. Methods: Cross-sectional study of 6200 Iranian prisoners in 2015. Data were collected through questionnaires and interviews. HBV infection and HCV exposure status of the participants was determined by HBsAg and HCV antibodies blood tests using enzyme-linked immunosorbent assay (ELISA). Data were analysed in STATA-12. Result: Prevalence of HCV exposure was 9.48 (95 CI: 8.73�10.27), and prevalence of HBV was 2.48 (95 CI: 2.07�2.89) in the general prison population. In multivariate analysis, the most important risk factor for HBV was a history of drug use in lifetime (adjusted odds ratio, AOR: 1.8, 95 CI: 1.17�3.02). The main risk factors for HCV exposure were a history of drug use in lifetime (AOR: 4.08, CI: 2.56�6.27), age over 30 (AOR: 2.68, CI: 2.01�3.56), and having tattoos (AOR = 1.67, CI: 1.35�2.07). Conclusion: Although vaccination is used to control HBV among prisoners, prevalence of HCV exposure is alarming in the prison population of Iran, especially among people who inject drugs. Eliminating viral hepatitis in Iran by 2030 requires a national commitment and rapid measures for targeting this high-risk group. Given the increased efficiency of HCV treatment in recent years, prisons provide an opportunity to access patients for treatment. © 2018 John Wiley & Sons Lt

Acute intermittent porphyria causes hepatic mitochondrial energetic failure in a mouse model

Acute intermittent porphyria (AIP), an inherited hepatic disorder, is due to a defect of hydroxymethylbilane synthase (HMBS), an enzyme involved in heme biosynthesis. AIP is characterized by recurrent, life-threatening attacks at least partly due to the increased hepatic production of 5-aminolaevulinic acid (ALA). Both the mitochondrial enzyme, ALA synthase (ALAS) 1, involved in the first step of heme biosynthesis, which is closely linked to mitochondrial bioenergetic pathways, and the promise of an ALAS1 siRNA hepatic therapy in humans, led us to investigate hepatic energetic metabolism in Hmbs KO mice treated with phenobarbital. The mitochondrial respiratory chain (RC) and the tricarboxylic acid (TCA) cycle were explored in the Hmbs−/− mouse model. RC and TCA cycle were significantly affected in comparison to controls in mice treated with phenobarbital with decreased activities of RC complexes I (−52%, **p &lt; 0.01), II (−50%, **p &lt; 0.01) and III (−55%, *p &lt; 0.05), and decreased activity of α-ketoglutarate dehydrogenase (−64%, *p &lt; 0.05), citrate synthase (−48%, **p &lt; 0.01) and succinate dehydrogenase (−53%, *p &lt; 0.05). Complex II-driven succinate respiration was also significantly affected. Most of these metabolic alterations were at least partially restored after the phenobarbital arrest and heme arginate administration. These results suggest a cataplerosis of the TCA cycle induced by phenobarbital, caused by the massive withdrawal of succinyl-CoA by ALAS induction, such that the TCA cycle is unable to supply the reduced cofactors to the RC. This profound and reversible impact of AIP on mitochondrial energetic metabolism offers new insights into the beneficial effect of heme, glucose and ALAS1 siRNA treatments by limiting the cataplerosis of TCA cycle