Viral hepatitis and human immunodeficiency virus co-infections in Asia

Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) affect many people in Asian countries, although there are geographic differences. Both HBV and HIV (HBV/HIV) and HCV/HIV co-infections are highly prevalent in Asia. Hetero- and homosexual, injection drug use, and geographic area are strong predictors of HBV, HCV, and HIV serostatus. In HBV endemic regions, the prevalence and genotype distribution of HBV/HIV co-infection is almost comparable with that in the general population. In Japan, where HBV has low endemicity, the prevalence of HBV/HIV co-infection is approximately 10-fold higher than that in the general population, and HBV Ae is the most common subgenotype among HIV infected individuals. Highly active antiretroviral therapy (HAART) is an effective treatment for HIV/Acquired Immune Deficiency Syndrome. Lamivudine, a component of HAART, is an effective treatment for HBV, HIV, and HBV/HIV co-infection; however, cost, emerging drug resistance, antiretroviral-associated liver toxicity and liver-related morbidity due to HCV progression are particular concerns. HCV/HIV co-infection may accelerate the clinical progression of both HCV and HIV. The high prevalence of HBV/HIV and HCV/HIV co-infections in Asia underscores the need to improve prevention and control measures, as fewer evidence-based prevention strategies are available (compared with Western countries). In this review, the most recent publications on the prevalence of HBV/HIV and HCV/HIV co-infections and related issues, such as therapy and problems in Asia, are updated and summarized

Hepatitis B virus infection in Indonesia

Approximately 240 million people are chronically infected with hepatitis B virus (HBV), 75% of whom reside in Asia. Approximately 600000 of infected patients die each year due to HBV-related diseases or hepatocellular carcinoma (HCC). The endemicity of hepatitis surface antigen in Indonesia is intermediate to high with a geographical difference. The risk of HBV infection is high in hemodialysis (HD) patients, men having sex with men, and health care workers. Occult HBV infection has been detected in various groups such as blood donors, HD patients, and HIV-infected individuals and children. The most common HBV subgenotype in Indonesia is B3 followed by C1. Various novel subgenotypes of HBV have been identified throughout Indonesia, with the novel HBV subgenotypes C6-C16 and D6 being successfully isolated. Although a number of HBV subgenotypes have been discovered in Indonesia, genotype-related pathogenicity has not yet been elucidated in detail. Therefore, genotype-related differences in the prognosis of liver disease and their effects on treatments need to be determined. A previous study conducted in Indonesia revealed that hepatic steatosis was associated with disease progression. Pre-S2 mutations and mutations at C1638T and T1753V in HBV/B3 have been associated with advanced liver diseases including HCC. However, drug resistance to lamivudine, which is prominent in Indonesia, remains obscure. Although the number of studies on HBV in Indonesia has been increasing, adequate databases on HBV infection are limited. We herein provided an overview of the epidemiology and clinical characteristics of HBV infection in Indonesia

Improvement of Rotavirus Genotyping Method by Using the Semi-Nested Multiplex-PCR With New Primer Set

Rotavirus A (RVA) is a major cause of gastroenteritis in infants and young children. After vaccine introduction, RVA surveillance has become more important for monitoring changes in genotype distribution, and the semi-nested multiplex-PCR is a popular method for RVA genotyping. In particular, the VP7 primer set reported by Gouvea and colleagues in 1990 is still widely used worldwide as the recommended WHO primer set in regional and national reference RVA surveillance laboratories. However, this primer set yielded some mistakes with recent epidemic strains. The newly emerged equine-like G3 strains were mistyped as G1, G8 strains were mistyped as G3, the G9 lineage 3 strains showed very weak band, and the G9 lineage 6 strains showed a G9-specific band and a non-specific band. Gouvea’s standard protocol has become relatively unreliable for identifying genotypes correctly. To overcome this limitation, we redesigned the primer set to include recent epidemic strains. Our new primer set enabled us to correctly identify the VP7 genotypes of representative epidemic strains by agarose gel electrophoresis (G1, G2, human typical G3, equine-like G3, G4, G8, G9, and G12). We believe that the multiplex-PCR method with our new primer set is a useful and valuable tool for surveillance of RVA epidemics

Phylogenetic Molecular Analysis Human Immunodeficiency Virus (HIV) Patients in Surabaya, East Java

The Human Immunodeficiency Virus Type 1 (HIV-1) isolates are classified in three main groups: group M (main), group O (outlier) as well as group N (non-M/non-O). The HIV-1 M group, responsible for the majority of infections in the HIV-1 worldwide epidemic, can be further subdivided into 10 recognized phylogenetic subtypes or clades, A�D and F-K. HIV-1 phylogenetic classifications are currently based on nucleotide sequences derived from such as gag p17 region of the same isolates or on full-length genome sequence analysis. We do not know HIV subtype distribution in HIV suspected patients, in Surabaya, East Java. The aims of this study was to do molecular analysis HIV in patients with HIV infection, in Surabaya, East Java. Antibody to HIV were detected using 3 methods, paper and EIA (Acon) and ELISA (Axion) techniques from 51 plasma obtained from the patients suspected HIV infection, in Surabaya, Indonesia All of the samples were subjected to Polymerase Chain Reaction (PCR) using pairs of primers based on HIV gag p17 genes. The PCR positive samples were sequenced and analysed to identify the HIV subtype using Genetic Version 9 program. Fourty nine (96,08%) HIV antibody were detected from 51 patients suspected HIV infection and 57,14% (28/49) HIV RNA determination positives. All of 21 positives HIV DNA except one sample that have been analyzed was CRFs of HIV with mayority CRF01-AE subtype similar with HIV CRF01-AE subtype in Asia countries, e.g. Thailand, Japan, Malaysia, Cina and Hongkong. Those one sample has 18 nucleotides insertion look like a HIV new subtype but it is needed to confirm further. From gag p7 HIV gene in this study, one HIV has and CRF01-AE is majority HIV subtype in Surabaya, East Java which is located in the same branch with HIV common CRF01-AEHIV subtype in Asia

Another novel subgenotype of hepatitis B virus genotype C from papuans of Highland origin

Hepatitis B virus (HBV) genotypes and subtypes have been identified worldwide. As HBV genotypes/subtypes, the HBV subgenotypes seem to be associated with their geographical distribution and ethnic origin. A previous study showed the novel HBV subgenotype C6 based on the complete genome sequences of isolates in Papua, Indonesia. In the present study, further characterization of HBV in Jayapura (capital of Papua Province), particularly from native people of Papua originating from the highland (highland Papuans) and those from the lowland (lowland Papuans) were examined. Of 32 HBV isolates from both highland and lowland Papuan blood donors with HBsAg positive, part of the S gene and the core gene sequences were analyzed. Analyses of some isolates from highland Papuans were confirmed by the complete genome sequences. Most HBV isolates were classified into genotype C (78.1%), followed by genotype B (18.8%), and genotype D (3.1%). The subtype adr was predominant (71.9%), followed by adw2 (25.1%), and ayw2 (3.1%). As with previous findings, phylogenetic analyses revealed that most HBV isolates from Papuans, C/adr, belonged to subgenotype C6. Interestingly, some C/adr isolates from highland Papuans formed a distinct cluster from all reported subgenotypes of HBV/C, and they differed from HBV/C1‐C10 by 4.2–7.2% over the complete genome. SimPlot analysis showed no evidence of recombination with HBV/C1–C10. The isolated life and closed social systems of highland Papuans, even though some have been moving to Jayapura, likely contribute to the formation of this unique cluster of infection with a novel subgenotype of HBV, named C11

Hepatitis B Serology Profiles on Children Aged 1-13 Years Old in Sumenep, Madura

Background: Hepatitis B virus (HBV) which was acquired during perinatal or childhood would promote hepatocellular carcinoma with even higher percentage than that which was acquired during adult age. That is why HBV represents a serious public health threat for children. HBV vaccination has been integrated into national expanded programme on immunization (EPI) since 1997. The aim of they study is to investigate the prevalence of HBV among children who were born after 1997 in Sumenep. Material and Methods: a total of 102 children who were born after 1997 were enrolled in this study. All children were admitted in the Emergency Room and Pediatric Ward of dr. H. Moh Anwar General Hospital for some reasons. Written informed consents were obtained from parents/ guardians of all the children. Study protocol was reviewed and approved by the Ethics Committees. All of these cases were examined for hepatitis B surface antigen (HBsAg), antibody to HBsAg (Anti-HBs), and antibody to hepatitis B core antigen (Anti-HBc). Result and Discussion: Overall, 6 (5.88%) of 102 samples were positive for HBsAg, 51 (50.00%) of 102 samples were positive for anti-HBs, and 49 (48.04%) of 102 samples were positive for anti-HBc. All the children were born after 1997. Conclusion: HBsAg rate is still high even after universal vaccination program, acquired protective antibodies against hepatitis B surface antigen were sufficient, but there is a suspicion for occult hepatitis B infections (OBI). A further study to confirm OBI is needed

Oyygen uptake of adriamycin resistant cells of Ehrlich ascites tumor

エールリッヒ腹水癌細胞を用いアドリアマイシンに対する耐性細胞（ADR耐性細胞）を樹立した。電子顕微鏡を用い撮影写真から細胞質当たりのミトコンドリア（MT）の割合を面積比で求めた。親株に比較して1μg/ml ADR耐性細胞では1.32倍、10μg/ml ADR耐性細胞では1.47倍であった。これらの細胞の呼吸を測定した。耐性細胞の内発呼吸は親株に比較して増加していた。1μg/ml ADR耐性細胞では1.45倍、10μg/ml ADR耐性細胞では1.49倍であり、MTの増加量とほぼ同じ割合であった。これらのことから、細胞が耐性になるとエネルギー消費が高まるために細胞内MTが増加し、その結果呼吸（酸素消費）が増加することが推察された。Adriamycin-resistant cells of Ehrlich ascites tumor cells were established in our laboratory. Using electron microscope, the area of mitochondria (MT) per cytoplasm of ADR-resistant cells were measured with planimeter. The values of wild-type cells, 1μg/ml ADR-resistant cells and 10μg/ml ADR-resistant cells were 39.3, 51.8 and 57.7 μ(2) per 1,000 μ(2) of cytoplasm, respectively. Oxygen consumption of 1 μg/ml ADR-resistant cells and 10 μg/ml ADR-resistant cells were 1.45-fold and 1.49-fold compared to that of wild-type cells, respectively. These results indicate that ADR-resistant cells require more energy to work efflux pump than wild-type cells

High Rates of Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), and Human Immunodeficiency Virus Infections and Uncommon HBV Genotype/Subtype and HCV Subtype Distributions among Transgender Individuals in Surabaya, Indonesia

Transgender people are at a high risk for sexually transmitted viruses such as hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Moreover, Indonesia has a moderate-to-high rate of HBV infection and rapid epidemic growth of HIV infection; hepatitis C virus (HCV) infection can co-occur with HBV and HIV infections. In this study, 10 of 107 individuals (9.3%) were positive for HBV surface antigen (HBsAg) and/or HBV DNA, whereas 19 of 101 individuals (18.8%) with negative results for HBsAg were positive for HBV core antibody (anti-HBc). Seven of the 107 individuals (6.5%) were anti-HCV positive, and 16 of the 100 tested samples (16.0%) were HIV positive. Genotype and subtype analyses of all 10 HBV DNA (6 HBsAg positive and 4 anti-HBc positive) strains showed that 3 were of the HBV genotype/HBsAg subtype C/adrq+, one was of C/adw2, and 5 were of B/adw2. The HCV subtype distribution showed that 33.3% were of HCV-1b, and 66.7% were of HCV-3k (n = 6). These distributions differed from those found in the general population of Surabaya, Indonesia. Interestingly, HIV subtype analysis showed a high prevalence of HIV, with possible recombinants of CRF01_AE and subtype B

Molecular Epidemiology and Clinical Features of Rotavirus Infection Among Pediatric Patients in East Java, Indonesia During 2015–2018: Dynamic Changes in Rotavirus Genotypes From Equine-Like G3 to Typical Human G1/G3

Group A rotavirus (RVA) is the most important cause of severe gastroenteritis among children worldwide, and effective RVA vaccines have been introduced in many countries. Here we performed a molecular epidemiological analysis of RVA infection among pediatric patients in East Java, Indonesia, during 2015–2018. A total of 432 stool samples were collected from hospitalized pediatric patients with acute gastroenteritis. None of the patients in this cohort had been immunized with an RVA vaccine. The overall prevalence of RVA infection was 31.7% (137/432), and RVA infection was significantly more prevalent in the 6- to 11-month age group than in the other age groups (P < 0.05). Multiplex reverse transcription-PCR (RT-PCR) revealed that the most common G-P combination was equine-like G3P[8] (70.8%), followed by equine-like G3P[6] (12.4%), human G1P[8] (8.8%), G3P[6] (1.5%), and G1P[6] (0.7%). Interestingly, the equine-like strains were exclusively detected until May 2017, but in July 2017 they were completely replaced by a typical human genotype (G1 and G3), suggesting that the dynamic changes in RVA genotypes from equine-like G3 to typical human G1/G3 in Indonesia can occur even in the country with low RVA vaccine coverage rate. The mechanism of the dynamic changes in RVA genotypes needs to be explored. Infants and children with RVA-associated gastroenteritis presented more frequently with some dehydration, vomiting, and watery diarrhea, indicating a greater severity of RVA infection compared to those with non-RVA gastroenteritis. In conclusion, a dynamic change was found in the RVA genotype from equine-like G3 to a typical human genotype. Since severe cases of RVA infection were prevalent, especially in children aged 6 to 11 months or more generally in those less than 2 years old, RVA vaccination should be included in Indonesia’s national immunization program

Full genome characterization and phylogenetic analysis of hepatitis B virus in gibbons and a caretaker in Central Kalimantan, Indonesia

Hepatitis B virus (HBV) from gibbons was characterized, and the possibility of horizontal transmission between gibbons and humans was examined in a gibbon rehabilitation center in Central Kalimantan, Indonesia. Ten gibbons that were positive for the hepatitis B surface antigen (HBsAg) on arrival and 13 caretakers for those gibbons were included in this study. The duration of stay at the rehabilitation center ranged from 1 to 10 years. Serological and molecular analyses were performed. Six gibbons were positive for HBsAg, whereas HBV DNA was detected in all ten of the gibbons sampled. On the other hand, HBsAg was detected in only 1 of the 13 caretakers. HBV samples from seven gibbons and from the one infected human were chosen for complete genome sequencing. A phylogenetic analysis revealed that the cluster of gibbon strains in this study was distinct from strains previously reported from other countries. In the pre-S1 region, we found a unique amino acid residue substitution (P89K), three insertions between T87 and L88 in the genomes of three gibbons, and a 33-nucleotide deletion at the start of pre-S1 that is common in non-human primates. The caretaker sample was identified as HBV subgenotype B3, the most common type in Indonesia. For the complete HBV sequences, the similarity between gibbons in this study and other non-human primate and human HBV isolates was 90–91.9 % and 85.5–89.6 %, respectively. In conclusion, the gibbon HBV genotype was influenced by geographic location and species. To the best of our knowledge, this is the first report characterizing the HBV genes and genomes of indigenous gibbons in Indonesia