Burden of HIV, HBV and syphilis among children in urban Ethiopia: Community-based cross-sectional study.

BACKGROUND: Children have largely been ignored in the fight against sexually transmitted infection (STI). Among children, STI is reported to be a globally emerging public health challenge. We evaluated the burden of HIV, hepatitis B virus (HBV) and syphilis among children (< 15 years old) and its determinants in urban Ethiopia. METHODS: For this study, we used data from the Ethiopian Population-based HIV Impact Assessment (EPHIA), collected through a nationally representative, community-based study conducted in Ethiopia from October 2017 to April 2018. We used plasma samples from 4729 children. Moreover, we linked the data and analysed them alongside their respective mothers. Child and maternal HIV status was determined using the national testing algorithm. Plasma samples from children were also tested for syphilis and HBV surface antigen. A descriptive analysis was done followed by bivariable analysis with 95% confidence interval (CI) at a significance level of p < 0.05. We finally evaluated predictors of STIs using regression analysis. RESULTS: HIV, HBV and syphilis prevalence rates among urban children in Ethiopia were 0.36%, 1.48% and 0.28%, respectively. Children living in Gambella and Addis Ababa had a 6.41-fold (95% CI: 3.20-9.88) and 4.20-fold (95% CI: 3.24-5.46) higher risk of HIV infection compared with those in Dire Dawa. Children of HIV-positive mothers had a 10.31-fold (95% CI: 3.20-18.19) higher risk of HIV infection, and if those mothers were not taking highly active antiretroviral therapy (HAART), the risk was 7.27 times higher (95% CI: 2.57-12.64). Those who were from HIV-positive mothers with viral load ≥ 1000 copies/mL had a 18.64-fold (95% CI: 6.36-31.24) higher risk of HIV infection and those with a history of breastfeeding had a 3.27-fold (95% CI: 1.11-5.67) higher risk. Children from Addis Ababa had a 3.26-fold (95% CI: 1.64-6.66) higher risk of HBV infection compared with those from Dire Dawa. Moreover, for those from HIV-positive mothers and whose mother was not taking HAART, the risk of HBV transmission was 6.37 (95% CI: 2.20-19.96) and 3.62 (95% CI: 1.27-11.29), respectively. Children living in Gambella, Somali, Afar and Tigray had a 7.21-fold (95% CI: 2.30-18.68), 3.10-fold (95% CI: 1.28-3.74) and 1.32-fold (95% CI: 1.11-3.38) higher risk of acquiring active syphilis compared with those living in Dire Dawa, respectively. Those from HIV-positive mothers also had a 4.22-fold (95% CI: 1.16-8.39) higher risk of acquiring active syphilis. CONCLUSION: The burden of HIV, HBV and syphilis was high among children in urban Ethiopia. The key determinants for the high burden of HIV, syphilis and HBV were maternal factors including maternal HIV status and breastfeeding. This might be due to the challenges associated with mother-to-child transmission. Hence, the programme shall focus on the elimination of the triple infections of HIV, syphilis and HBV.

Bone marrow-derived mesenchymal stem cells attenuate pulmonary inflammation and lung damage caused by highly pathogenic avian influenza A/H5N1 virus in BALB/c mice.

BACKGROUND: The highly pathogenic avian influenza A/H5N1 virus is one of the causative agents of acute lung injury (ALI) with high mortality rate. Studies on therapeutic administration of bone marrow-derived mesenchymal stem cells (MSCs) in ALI caused by the viral infection have been limited in number and have shown conflicting results. The aim of the present investigation is to evaluate the therapeutic potential of MSC administration in A/H5N1-caused ALI, using a mouse model. METHODS: MSCs were prepared from the bone marrow of 9 to 12 week-old BALB/c mice. An H5N1 virus of A/turkey/East Java/Av154/2013 was intranasally inoculated into BALB/c mice. On days 2, 4, and 6 after virus inoculation, MSCs were intravenously administered into the mice. To evaluate effects of the treatment, we examined for lung alveolar protein as an indicator for lung injury, PaO2/FiO2 ratio for lung functioning, and lung histopathology. Expressions of NF-κB, RAGE (transmembrane receptor for damage associated molecular patterns), TNFα, IL-1ß, Sftpc (alveolar cell type II marker), and Aqp5+ (alveolar cell type I marker) were examined by immunohistochemistry. In addition, body weight, virus growth in lung and brain, and duration of survival were measured. RESULTS: The administration of MSCs lowered the level of lung damage in the virus-infected mice, as shown by measuring lung alveolar protein, PaO2/FiO2 ratio, and histopathological score. In the MSC-treated group, the expressions of NF-κB, RAGE, TNFα, and IL-1ß were significantly suppressed in comparison with a mock-treated group, while those of Sftpc and Aqp5+ were enhanced. Body weight, virus growth, and survival period were not significantly different between the groups. CONCLUSION: The administration of MSCs prevented further lung injury and inflammation, and enhanced alveolar cell type II and I regeneration, while it did not significantly affect viral proliferation and mouse morbidity and mortality. The results suggested that MSC administration was a promissing strategy for treatment of acute lung injuries caused by the highly pathogenic avian influenza A/H5N1 virus, although further optimization and combination use of anti-viral drugs will be obviously required to achieve the goal of reducing mortality.

Seroevidence for a High Prevalence of Subclinical Infection With Avian Influenza A(H5N1) Virus Among Workers in a Live-Poultry Market in Indonesia.

BACKGROUND: In Indonesia, highly pathogenic avian influenza A(H5N1) virus has become endemic in poultry and has caused sporadic deadly infections in human. Since 2012, we have conducted fixed-point surveillance of avian influenza viruses at a live-poultry market in East Java, Indonesia. In this study, we examined the seroprevalence of avian influenza A(H5N1) virus infection among market workers. METHODS: Sera were collected from 101 workers in early 2014 and examined for antibody activity against avian A(H5N1) Eurasian lineage virus by a hemagglutination-inhibition (HI) assay. RESULTS: By the HI assay, 84% of the sera tested positive for antibody activity against the avian virus. Further analysis revealed that the average HI titer in 2014 was 2.9-fold higher than in 2012 and that seroconversion occurred in 44% of paired sera (11 of 25) between 2012 and 2014. A medical history survey was performed in 2016; responses to questionnaires indicated that none of workers had had severe acute respiratory illness during 2013. CONCLUSIONS: This study provides evidence of a high prevalence of avian A(H5N1) virus infection in 2013 among workers at a live-poultry market. However, because no instances of hospitalizations were reported, we can conclude the virus did not manifest any clinical symptoms in workers.

PREVALENCE AND RISK FACTORS OF HEPATITIS B AND C VIRUS INFECTIONS AMONG HEMODIALYSIS PATIENTS FROM PRIVATE HEMODIALYSIS UNITS IN SURABAYA, INDONESIA.

The aims of the present study were to profile seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and possible risk factors among hemodialysis (HD) patients in private hemodialysis units (HDU) in Surabaya, Indonesia. Sera were obtained from 180 HD patients in 4 different private HDUs and tested for hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV). Patients without HBsAg and anti-HCV at first sampling were followed serologically every 3 months for 9 months, while those with HBsAg or anti-HCV positive sera were subjected continually to PCR to detect HBV DNA and HCV RNA. The prevalence of hepatitis infections varied widely between the HDUs, from 0% to 8.1% of patients positive for HBsAg and 0% to 60.6% of those positive for anti-HCV, respectively. These values were markedly higher than those among the general population, but not as high as in governmental HDUs in Indonesia. New incidence of HBV was not detected in any HDU, whereas that of HCV was found in two HDUs, HCV-1b in one HDU and HCV-1a in the other. Inappropriate practices were observed, such as shortage of medical staff and malfunctions in infection-control committees. Prevalence of HBV and HCV infection among HD patients in private HDUs were high and varied among the HDUs. Isolation of both HBV- and HCV-infected patients and staff education should help to reduce the prevalence of hepatitis infections in HDUs.

Interleukin-28B polymorphisms and response of chronic hepatitis C patients from Indonesia to pegylated interferon/ribavirin treatment.

This study demonstrated that Indonesian patients with chronic hepatitis C (mostly ethnic Java people) mostly were infected with hepatitis C virus (HCV) genotype 1; however, they carried mainly the major genotypes of interleukin 28B (IL-28B) single nucleotide polymorphisms (SNPs) (rs12979860 CC, rs11881222 TT, rs8103142 AA, and rs8099917 TT), and they mostly achieved sustained virological responses to pegylated interferon/ribavirin treatment.

Hepatitis E virus infection in two different regions of Indonesia with identification of swine HEV genotype 3.

Hepatitis E is an emerging disease with a high incidence globally. Few data are available on hepatitis E virus (HEV) infection in Indonesia. To obtain molecular information on HEV infection in two regions of Indonesia with different customs and swine breeding conditions, serum samples from 137 swine farm workers, 100 blood donors and 100 swine (27 fecal samples also obtained) in Yogyakarta (Central Java) and from 12 and 64 swine farm workers, 42 and 135 local residents and 89 and 119 swine in Tulungagung (East Java) and Mengwi (Bali), respectively, from our previous study, were compared.Serological tests for anti­HEV antibodies by ELISA, HEV­RNA detection by RT­PCR and phylogenetic analysis were performed. The total prevalence of anti­HEV antibodies in humans was higher in Bali(11.6%) than in Java (5.1%; P=0.015). No significant differences in anti­HEV prevalence among swine farm workers and local residents in Java were found. The finding of swine HEV genotype 3 in specimens from Yogyakarta and genotype 4 from Tulungagung and Bali is somewhat different from other reports.We suggest other factors in addition to close contact with swine might play an important role in HEV transmission of non­endemic/related custom groups. To the best of our knowledge, this is the first report on swine HEV genotype 3 in Indonesia.

Detection of highly prevalent hepatitis B virus co-infection with HIV in Indonesia.

AIM: The prevalence of hepatitis B virus (HBV) co-infection with HIV is increasing worldwide because of shared transmission routes. This study aimed to assess the prevalence of HBV and HIV co-infection in Indonesia, and its molecular and clinical characteristics. METHODS: A total of 118 serum samples from HIV-infected patients (age 33.3 ± 8.9 years, 99 male, 19 female) collected in 2009 were serologically examined. HBV DNA was assessed by polymerase chain reaction (PCR) analysis targeting the S region. RESULTS: Overall, 15.3% (18/118) of the patients were hepatitis B surface antigen (HBsAg) positive, whereas 27.1% (32/118) were HBsAg negative but HBV DNA positive, and were considered to have occult HBV infection. HBsAg antibodies and/or HBV core antibodies were detected in 45.6% (31/68) of HBV DNA negative patients. CONCLUSION: HBV co-infection, including occult HBV infection, was common in Indonesian HIV patients. Hepatic damage by the interaction of host immunity and HBV is still a remaining issue in these immunosuppressive patients, and further study will be needed.

Stem cell therapy and diabetic erectile dysfunction: A critical review.

Erectile dysfunction (ED) has been identified as one of the most frequent chronic complications of diabetes mellitus (DM). The prevalence of ED is estimated to be about 67.4% in all DM cases worldwide. The pathophysiological process leading to ED involves endothelial, neurological, hormonal, and psychological factors. In DM, endothelial and neurological factors play a crucial role. Damages in the blood vessels and erectile tissue due to insulin resistance are the hallmark of ED in DM. The current treatments for ED include phosphodiesterase-5 inhibitors and penile prosthesis surgery. However, these treatments are limited in terms of just relieving the symptoms, but not resolving the cause of the problem. The use of stem cells for treating ED is currently being studied mostly in experimental animals. The stem cells used are derived from adipose tissue, bone, or human urine. Most of the studies observed an improvement in erectile quality in the experimental animals as well as an improvement in erectile tissue. However, research on stem cell therapy for ED in humans remains to be limited. Nevertheless, significant findings from studies using animal models indicate a potential use of stem cells in the treatment of ED.

G2P[4] rotavirus outbreak in Belu, East Nusa Tenggara Province, Indonesia, 2018.

Rotavirus is a major cause of acute gastroenteritis (AGE) in children worldwide. However, rotavirus outbreak has rarely been reported in Indonesia. This study aims to identify the causative agent for AGE outbreak among children in Belu, East Nusa Tenggara, Indonesia in 2018. All the samples were negative for bacteria (Salmonella, V. cholera) and Norovirus. Ten out of 11 stool samples were rotavirus-positive by immunochromatography testing. Reverse-transcription polymerase chain reaction (RT-PCR) and phylogenetic analyses revealed that rotavirus G2P[4] was the possible causative agent for the AGE outbreak, although sample size was limited. These findings suggest that the AGE outbreak was caused by rotavirus G2P[4], highlighting the importance of rotavirus surveillance.

Comparison of Virulence and Lethality in Mice for Avian Influenza Viruses of Two A/H5N1 and One A/H3N6 Isolated from Poultry during Year 2013-2014 in Indonesia.

In Indonesia, the highly pathogenic avian influenza A/H5N1 virus has become endemic and has been linked with direct transmission to humans. From 2013 to 2014, we isolated avian influenza A/H5N1 and A/H3N6 viruses from poultry in Indonesia. This study aimed to reveal their pathogenicity in mammals using a mouse model. Three of the isolates, Av154 of A/H5N1 clade 2.3.2.1c, Av240 of A/H5N1 clade 2.1.3.2b, and Av39 of A/H3N6, were inoculated into BALB/c mice. To assess morbidity and mortality, we measured body weight daily and monitored survival for 20 d. Av154- and Av240-infected mice lost 25% of their starting body weight by day 7, while Av39-infected mice did not. Most of the Av154-infected mice died on day 8, while the majority of the Av240-infected mice survived until day 20. A 50% mouse lethal dose was calculated to be 2.0 × 101 50% egg infectious doses for Av154, 1.1 × 105 for Av240 and > 3.2 × 106 for Av39. The Av154 virus was highly virulent and lethal in mice without prior adaptation, suggesting its high pathogenic potential in mammals. The Av240 virus was highly virulent but modestly lethal, whereas the Av39 virus was neither virulent nor lethal. Several mammalian adaptive markers of amino acid residues were associated with the highly virulent and lethal phenotypes of the Av154 virus.

Post-vaccinated asymptomatic rotavirus infections: A community profile study of children in Surabaya, Indonesia.

BACKGROUND: Rotavirus gastroenteritis accounts for significant childhood morbidity and mortality worldwide. Vaccination using RotarixTM (GSK) and RotaTeq® (Merck) was introduced due to the tremendous disease burden. The possibility of asymptomatic infections following vaccinations was poorly understood. This study examined rotavirus cases in post-vaccinated children, their clinical manifestations and the genotypes of isolated strains. METHODS: Stool samples of healthy, vaccinated children under 5 years of age in Surabaya were collected monthly for 1 year between January 2016 and February 2017. Episodes of gastroenteritis were reported, and samples were collected. Rotavirus was identified using multiplex reverse transcription Polymerase Chain Reaction (QIAGEN, Inc., Valencia, CA). Clinical manifestations were measured using the Vesikari score. The genotype was analyzed by Applied Biosystems (Foster, CA). RESULTS: A total of 109 stool samples were collected from 30 subjects, of which 22 received Rotarix; 8 RotaTeq. Nine out of 109 samples were collected during diarrhea episodes of 8 subjects. Two asymptomatic rotavirus infections were identified by RT-PCR. The genotypes isolated were G1P[8] and G3P[8]. CONCLUSIONS: Asymptomatic rotavirus infections can occur in post-vaccinated children. Strains identified were homologous to serotypes eliciting gastroenteritis in unvaccinated children of the same community.

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.

Acute hepatitis due to hepatitis A virus subgenotype IA as an imported infectious disease from Indonesia.

A 25-year-old Japanese man was admitted with general malaise and fever, which had developed 12 days after coming back to Japan from Indonesia. Blood examination revealed elevated transaminase levels and positivity for the IgM anti-HAV antibody; therefore, he was diagnosed with acute hepatitis A. HAV-RNA was detected in his serum and phylogenetically classified as subgenotype IA. The partial genome in the VP1/P2A region was consistent with the strain recently isolated from Surabaya, which indicated that he had been infected during his stay in Indonesia. Thus, HAV vaccination is recommended before visiting HAV-endemic countries for a long period of time.

Genotype and subtype analyses of hepatitis B virus (HBV) and possible co-infection of HBV and hepatitis C virus (HCV) or hepatitis D virus (HDV) in blood donors, patients with chronic liver disease and patients on hemodialysis in Surabaya, Indonesia.

Four subtypes (adw, adr, ayw, and ayr ) and eight genotypes (A to H) of the hepatitis B virus (HBV) have been identified. They appear to be associated with particular geographic distribution, ethnicity, and possibly clinical outcomes. In this study, hepatitis B surface antigen (HBsAg) subtyping and HBV genotyping were carried out on sera obtained from HBsAg-positive HBV carriers, including healthy blood donors; patients with acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma; and patients on hemodialysis all located in Surabaya, Indonesia. We report here that all HBV isolates tested in Surabaya belonged to genotype B, with more than 90% of them being classified into subtype adw. Our results also revealed that prevalence of hepatitis C virus (HCV) co-infection among HBV carriers in Surabaya was approximately 10% for healthy blood donors and patients with chronic liver disease, and approximately 60% for patients on maintenance hemodialysis. Interestingly, HBsAg titers were lower in HBV carriers with HCV co-infection than in those without HCV co-infection. We also found that prevalence of hepatitis D virus (HDV) co-infection was < 0.5% among HBV carriers in Surabaya.