Involvement of TLR4 in Acute Hepatitis Associated with Airway Infection of Murine γ-Herpesvirus 68.

Extrahepatic viral infections are often accompanied by acute hepatitis, as evidenced by elevated serum liver enzymes and intrasinusoidal infiltration of CD8+ T cells, without direct infection of the liver. An example is infectious mononucleosis caused by primary infection with EBV. Previously, we demonstrated that airway infection of mice with murine γ-herpesvirus 68 (MHV68), a murine model of EBV, caused liver inflammation with elevated serum liver enzymes and intrahepatic infiltration of IFN-γ-producing CD8+ T cells and NK cells. Mechanistically, the expression of the CXCR3-ligand chemokines, which are commonly induced by IFN-γ and attract IFN-γ-producing Th1-type cells via CXCR3, was upregulated in the liver. Importantly, the liver inflammation was suppressed by oral neomycin, an intestine-impermeable aminoglycoside, suggesting an involvement of some products from the intestinal microbiota. In this study, we showed that the liver inflammation and the expression of the CXCR3-ligand chemokines in the liver were effectively ameliorated by i.p. administration of anti-TLR4 mAb or C34, a TLR4 blocker, as well as in TLR4-deficient mice. Conversely, intrarectal inoculation of Escherichia coli as an extraintestinal source of LPS aggravated liver inflammation in MHV68-infected mice with increased expression of the CXCR3-ligand chemokines in the liver. In contrast, the lung inflammation in MHV68-infected mice was not affected by oral neomycin, i.p. administration of C34, or TLR4 deficiency. Collectively, the LPS-TLR4 pathway plays a pivotal role in the liver inflammation of MHV68-infected mice at least in part by upregulating the CXCR3-ligand chemokines in the liver.

Increased knowledge levels of patients with diabetes in resource-limited communities after receiving peer-led education.

Diabetes self-management education through peer support has been beneficial, especially in regions with limited medical resources. Studying the effects of education offered by trained peers of patients will facilitate tailoring the peer-led education programs to the regions' specific needs. Here, we evaluated changes in diabetes-related indicators in Filipino patients who received a peer-led education. We used data on 23 patients (age, 67.83 ± 6.69 years; 82.6% female) who participated in all five surveys performed every 6 months from March 2017 to March 2019. After the second survey until the end of this study, the participants were educated in diabetes self-management by their 13 peers who previously had received the training in diabetes self-management. Participants' knowledge of diabetes and the related 'cause, risk factors, nature of diabetes and complications' subindicator were greater on all surveys after starting the peer-led education compared with those on the second survey (i.e. before starting the education); these values did not differ between the first two surveys. Because increasing patients' knowledge can enhance their ability to self-manage their disease and thus improve their quality of life, strategies to expand patients' knowledge about diabetes should be included when organizing peer-led education in regions with limited medical resources.

Rapid Multiplex RT-PCR for Influenza A and B by Genesoc®, a Microfluidic PCR System.

Background: Rapid antigen tests are widely used to diagnose influenza. However, despite their simplicity and short turnover time, the sensitivity of these tests is relatively low, and molecular tests with greater sensitivity are being sought. In this study, we developed and clinically evaluated a protocol for the rapid multiplex testing of influenza A and B, using a rapid real-time PCR system, GeneSoC®, that is based on microfluidic thermal cycling technology. Methods: The specificity of the developed assay was validated using cultured viral strains of influenza A/B, human metapneumovirus, and respiratory syncytial virus. Analytical sensitivity was evaluated using serially diluted RNA synthesized via in vitro transcription and nasopharyngeal swab samples collected from consecutive patients seeking medical attention for a combination of upper respiratory and general symptoms. Cross-validation of GeneSoC® based on comparisons with conventional real-time RT-PCR and rapid antigen tests was performed by parallel testing of influenza-positive clinical specimens. Results: The GeneSoC® assay detected the target sequences of influenza A and B at minimum concentrations of 38 and 65 copies/µL in reaction, respectively. For the analysis of clinical specimens, the positive, negative, and overall agreement between GeneSoC® RT-PCR and a conventional real-time RT-PCR was in all cases 100%, whereas for the comparison between GeneSoC® RT-PCR and the rapid antigen test, the agreements for positive, negative, and overall findings were 100%, 90.9%, and 95.7%, respectively. The mean time for completing GeneSoC® RT-PCR was 16 min 29 s (95% confidence interval, 16 min 18 s to 16 min 39 s). Conclusion: The microfluidic real-time PCR system, GeneSoC®, has an analytical performance comparable to that of conventional real-time RT-PCR with rapid turnover time, and represents a promising alternative to rapid antigen tests for diagnosing influenza A and B.

Cognitive and Emotional Changes in Peer Educators of Type 2 Diabetes Patients After Starting Peer-Support Activities.

Background: Diabetes self-management education through peer support has beneficial effects, especially in regions with limited medical resources. To ensure peer educators continue to provide peer-led education programs, it is important that they remain motivated to instruct patients. Here, to explore measures to enhance peer-educators' motivation toward such programs, we examined the cognitive and emotional changes in Filipino type 2 diabetics after 7-month activities as peer educators. Methods: We individually performed semi-structured interviews with 13 peer educators with 20 years of age or above in August 2017 (immediately before starting their peer-education activities) and in March 2018 (7 months after the start). The first interview was performed after the peer educators had received 2-day training of diabetes self-management. In both interviews, we asked the peer educators about their feelings toward peer-led educational activities (e.g., satisfaction, difficulty, reward, confidence, and challenges). Their replies about their own cognition and emotions were interpreted and integrated, and then analyzed qualitatively. Results: Four and seven categories were extracted from the first and second interviews, respectively. The category "Cognition of patients' active learning attitudes and of positive changes in patients' physical conditions and behavior" observed in the second interview led to "Cognition of growth as a peer educator" and "Satisfaction with supporting patients as a peer educator." These two feelings gave the peer educators' "Increased motivation to continue the activities as a peer educator." This motivation was also associated with "Active collaboration among peer educators," which was affected by "Difficulties and concerns in working as a peer educator." Conclusion: To sustain diabetic peer-led education programs, we suggest that interventions be implemented that increase peer educators' motivation toward their activities and stimulate their awareness of the importance of collaborating with one another. Such collaboration should help to overcome the difficulties they may face in providing peer-led education.

In Vitro Susceptibility of HIV Isolates with High Growth Capability to Antiretroviral Drugs.

It has been considered that reduced susceptibility to antiretroviral drugs is influenced by drug adherence, drug tolerance and drug-resistance-related mutations in the HIV genome. In the present study, we assessed the intrinsic high viral growth capability as a potential viral factor that may influence their susceptibility to antiretroviral drugs using an in vitro model. Phytohemagglutinin-activated peripheral blood mononuclear cells (1.5 × 106 cells) were infected with HIV isolates (106 copies/mL). The culture was carried out at different concentrations (0.001-20 µM) of 13 synthetic antiretroviral compounds (six nucleoside/nucleotide reverse transcriptase inhibitors, one non-nucleoside reverse transcriptase inhibitor, four integrase inhibitors, and two protease inhibitors), and HIV production was assessed using HIV-RNA copies in culture. The 90% inhibitory concentration (IC90) and pharmacokinetics of an antiretroviral agent were used as parameters to determine the reduced antiretroviral drug susceptibility of HIV isolates with high growth capability to synthetic antiretroviral compounds. The high growth capability of HIV isolates without any known drug resistance-related mutation affected their susceptibility to tenofovir (IC90 = 2.05 ± 0.40 µM), lamivudine (IC90 = 6.83 ± 3.96 µM), emtricitabine (IC90 = 0.68 ± 0.37 µM), and efavirenz (IC90 = 3.65 ± 0.77 µM). These antiretroviral drugs showed IC90 values close to or above the maximum plasma concentration against HIV isolates with high growth capability without any known drug resistance-related mutation. Our results may contribute to the development of effective strategies to tailor and individualize antiretroviral therapy in patients harboring HIV isolates with high growth capability.

Pro-Inflammatory Cytokines and Interferon-Stimulated Gene Responses Induced by Seasonal Influenza A Virus with Varying Growth Capabilities in Human Lung Epithelial Cell Lines.

In a previous study, we described the diverse growth capabilities of circulating seasonal influenza A viruses (IAVs) with low to high viral copy numbers in vitro. In this study, we analyzed the cause of differences in growth capability by evaluating pro-inflammatory cytokines (TNF-α, IL-6, IFN-ß) and antiviral interferon-stimulated genes (ISG-15, IFIM1, and TRIM22). A549 cells (3.0 × 105 cells) were inoculated with circulating seasonal IAV strains and incubated for 6 and 24 h. In cells inoculated for 6 h, IAV production was assessed using IAV-RNA copies in the culture supernatant and cell pellets to evaluate gene expression. At 24 h post-infection, cells were collected for IFN-ß and ISG-15 protein expression. A549 cells inoculated with seasonal IAV strains with a high growth capability expressed lower levels of IFN-ß and ISGs than strains with low growth capabilities. Moreover, suppression of the JAK/STAT pathway enhanced the viral copies of seasonal IAV strains with a low growth capability. Our results suggest that the expression of ISG-15, IFIM1, and TRIM22 in seasonal IAV-inoculated A549 cells could influence the regulation of viral replication, indicating the existence of strains with high and low growth capability. Our results may contribute to the development of new and effective therapeutic strategies to reduce the risk of severe influenza infections.

Local spread of influenza A (H1N1) viruses without a mutation for the maximum duration of an epidemic season in Japan.

Close observation of the local transmission of influenza A(H1N1) viruses enabled an estimate of the length of time the virus was transmitted without a mutation. Of 4,448 isolates from 11 consecutive years, 237 isolates could be categorized into 57 strain groups with identical hemagglutinin genes, which were monitored for the entire duration of an epidemic season. In addition, 35 isolates with identical sequences were identified at the study site and in other countries within 147 days. Consequently, it can be postulated that once an influenza virus enters a temperate region, the strain rarely mutates before the end of the season.

Growth capability of epidemic influenza viruses in Japan since the 2009 H1N1 pandemic.

The correlation of viral growth capability (n = 156) with the viral load in nasopharyngeal swabs (n = 76) was assessed. Epidemic influenza A/H1N1, A/H3N2, and B viruses showed a wide range of growth capability (104-1011 copies/mL) in Madin-Darby canine kidney cells. The growth was correlated with the nasopharyngeal viral load (r = 0.53). Six selected strains showed growth-dependent cell death (r = 0.96) in a growth kinetics assay. Epidemic influenza viruses exhibit a wide range of growth capability. Growth capability should be considered one of the key factors in disease prognosis.

Effects of a Self-efficacy Theory-Based Training Program for Peers of Patients with Type 2 Diabetes.

BACKGROUND: Training peer leaders to deliver patient education is expected to be a low-cost approach to providing healthcare in urban-poor areas affected by a shortage of healthcare professionals. The purpose of this study was to examine the effects of a training program on the self-efficacy and knowledge of peer leaders with type 2 diabetes. METHODS: A single-group longitudinal survey with baseline, intervention, and follow-up periods was conducted at a diabetes clinic in a small municipality in Metro Manila, Philippines. The intervention, a self-efficacy theory-based training program for peer-leaders of diabetic patients conducted in August 2017, comprised hands-on learning, demonstrations, quizzes, role-playing, group sharing, physical exercise, and a buffet lunch. The primary outcome was participants' self-efficacy for management of their diabetes. Secondary outcomes were participants' knowledge of diabetes and levels of emotional distress, motivation, and confidence for guiding their peers, satisfaction with the training program, hemoglobin A1c, and quality of life. RESULTS: At 12 and 18 months after the intervention, participants' knowledge of diabetes was significantly increased compared with baseline (both P < 0.05). At earlier time points, an increasing, but not significant, trend was observed. The change in knowledge of diabetes from baseline to 18 months after intervention tended to be positively correlated with the change in self-efficacy (r = 0.594, P = 0.054). No significant differences were observed for any of the other outcomes, although the descriptive statistics showed an increasing trend for all of the outcomes except motivation. CONCLUSION: The training program significantly improved participants' knowledge of diabetes at 12 and 18 months after the training programs compared with baseline. A positive correlation between the changes in the levels of knowledge and self-efficacy suggested that the observed improvement of self-efficacy was facilitated by the improvement of knowledge of diabetes.

Intrinsic Replication Competences of HIV Strains After Zidovudine/Lamivudine/Nevirapine Treatment in the Philippines.

Although drug-resistant HIV variants are considered to be less fit than drug-susceptible viruses, replication competence of these variants harbored by patients has not yet been elucidated in detail. We herein assessed the replication competence of strains obtained from individuals receiving antiretroviral therapy. Among 11 306 participants in a drug resistance surveillance in the Philippines, 2629 plasma samples were obtained from individuals after a 12-month treatment with zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP). The replication competence of HIV isolates was then assessed by reinoculation into seronegative peripheral blood mononuclear cells in the absence of drugs in vitro. The drug resistance rate was estimated to be 9.2%. Drug-resistant strains were still a minority of closely related strains in a phylogenetic cluster. Among the available 295 samples, 37 HIV strains were successfully isolated. Progeny viruses were produced at a wide range (5.1 × 106 to 3.4 × 109 copies/mL) in primary culture of peripheral blood mononuclear cells. The viral yields were higher than the corresponding plasma viral load (1300 to 3.4 × 106 copies/mL) but correlated with those (r = 0.4). These results suggest that strains with higher intrinsic replication competence are one of the primary targets of newly selected drugs at the increasing phase of the plasma viral load during antiretroviral therapy.

In Vitro Inhibition of Cytopathic Effect of Influenza Virus and Human Immunodeficiency Virus by Bamboo Leaf Extract Solution and Sodium Copper Chlorophyllin.

BACKGROUND: Although the link between oral and oropharyngeal health status and susceptibility to infection has long been recognized, there is a limit to the selection of antiseptics for oral care. METHODS: Madin-Darby canine kidney (MDCK) cells were exposed to influenza virus and cultured in the presence or absence of test reagents: bamboo leaf extract solution and sodium copper chrolophyllin. MDCK cells were pre-incubated with the reagents to assess the inhibitory activity at adsorption (viral attachment). Similarly, anti-HIV activity and the inhibitory mechanism at adsorption were assessed by MT-2 cell culture system. Mixture of HIV and bamboo leaf extract solution was fixed and examined by transmission electron microscopy. RESULTS: The 50% inhibitory concentration (IC50) of bamboo leaf extract solution against influenza virus and the 50% cytotoxic concentration (CC50) in MDCK cells of the solution lay between 0.0313-0.0625% and 0.5-1.0%. The solution inhibited the influenza virus adsorption at the concentration of 0.5% (P < 0.05). The values of IC50 and CC50 of sodium copper chlorophyllin lay between 50-100 µM and 200-400 µM, respectively. This inhibited the virus adsorption at 200 µM (P < 0.05). The bamboo leaf extract solution showed values of IC50 against HIV and CC50 in MT-2 cells at around 0.0313% and between 0.25-0.5%, respectively. This solution inhibited HIV adsorption at 1.25% (P < 0.05). The IC50 and CC50 of sodium copper chlorophyllin lay between 50-100 µM and 200-400 µM, respectively. Sodium copper chlorophyllin inhibited HIV adsorption at 2.5 mM (P < 0.05). HIV particles survived after the exposure to 0.5% bamboo leaf extract solution. CONCLUSION: Sodium copper chlorophyllin exerted antiviral activities against influenza virus and HIV as the major ingredient of bamboo leaf extract solution by blocking adsorption. This mechanism of action is different completely from the one of povidone-iodine.

The APOBEC3B deletion polymorphism is associated with prevalence of hepatitis B virus, hepatitis C virus, Torque Teno virus, and Toxoplasma gondii co-infection among HIV-infected individuals.

BACKGROUND: Data regarding the influence of the APOBEC3B deletion on infectious diseases remain limited and shown discrepancies. OBJECTIVES: To characterize the APOBEC3B deletion polymorphism status and its association with prevalence of co-infection with blood-borne pathogens in Indonesian HIV-infected individuals. MATERIALS AND METHODS: A total of 597 HIV-positive blood samples were tested for the hepatitis B virus (HBV), hepatitis C virus (HCV), Torque Teno virus (TTV), GB virus-C (GBV-C), and Toxoplasma gondii. Nucleic acid was extracted from plasma samples and used for the molecular detection of HIV RNA, HBV DNA, HCV RNA, TTV DNA, and GBV-C RNA, whereas HBsAg, anti-HCV, IgM and IgG anti-T. gondii were detected through serological testing. The APOBEC3B deletion polymorphism was genotyped by polymerase chain reaction (PCR). RESULTS: The deletion genotype was associated with HCV viremia (p<0.001) as well as elevated IgG anti-T. gondii (adjusted OR [aOR]=3.4). The deletion genotype was also associated with decreased levels of HBsAg (aOR=0.03), and anti-HCV (aOR=0.1). D/D was frequently found in HIV-infected individuals with CD4+T cells<14% (aOR=5.8). The intact genotype was associated with a reduced likelihood of a CD4+T cell count<200 cells/µL (aOR=0.2) but a higher prevalence of TTV co-infection (aOR=8.6). CONCLUSIONS: The APOBEC3B deletion polymorphism was found to be associated with HBV, HCV, TTV, and T. gondii co-infection in Indonesian HIV-infected individuals.

Respiratory viruses and torque teno virus in adults with acute respiratory infections.

OBJECTIVE: To define the molecular epidemiology of respiratory viral infections in adult patients. METHODS: Nasal and throat swabs were collected from all adult patients with influenza-like illness (ILI), acute respiratory infection (ARI), or severe ARI (SARI) admitted to a tertiary hospital in Surakarta, Indonesia, between March 2010 and April 2011 and analyzed for 19 respiratory viruses and for torque teno virus (TTV) and human gyrovirus (HGyV). RESULTS: Respiratory viruses were detected in 61.3% of the subjects, most of whom had ARI (90.8%, OR = 11.39), were hospitalized (96.9%, OR = 22.31), had asthma exacerbation (90.9%, OR = 8.67), and/or had pneumonia (80%, OR = 4.0). Human rhinovirus (HRV) A43 predominated. Influenza A H3N2, human metapneumovirus (HMPV) subtypes A1 and A2, the influenza B virus, human adenovirus B, and human coronavirus OC43 were also detected. All respiratory viruses were detected in the transition month between the rainy and dry seasons. No mixed respiratory virus infection was found. Coinfections of the influenza A H3N2 virus with TTV, HMPV with TTV, HRV with TTV, and human parainfluenza virus-3 with TTV were found in 4.7, 2.8, 19.8, and 0.9% of the samples, respectively. CONCLUSIONS: This study highlights the need to perform routine detection of respiratory viruses in adults hospitalized with ARI, asthma exacerbation, and/or pneumonia.

Frequent Isolations of Influenza A Viruses (H1N1)pdm09 with Identical Hemagglutinin Sequences for More Than Three Months in Japan.

BACKGROUND: Although it has been suggested that antigenic drift does not occur in a single epidemic season in temperate countries, there is not enough evidence on the circulation period of influenza virus with identical nucleotide sequences. Therefore, strains of influenza virus were isolated sequentially during five consecutive epidemic seasons in Japan and their nucleotide sequences were determined. METHODS: Nasal swabs or aspirated nasal discharges were collected from influenza A virus antigen-positive individuals living in Tottori Prefecture, Japan for five consecutive winters starting in 2009-2010, and subjected to viral isolation, determination of hemagglutinin nucleotide sequence and phylogenic analyses. The nucleotide sequences were compared with each other and also with those of foreign strains in the International Nucleotide Sequence Database. RESULTS: Totally 288 A(H1N1)pdm09 strains were tested and those composed 38 clusters with identical ones displaying 100% nucleotide homology. One strain showed sequential infections more than three months without any detectable mutation, and a maximum interval of two detection timings of strains was 94 days. This implies that influenza viruses mutate rarely in an epidemic season in Japan if they can be hypothesized, mutation frequency of influenza viruses being mostly the same among strains. Among these identical strains, two strains were not only identical to other Japanese isolates, but also to those isolated in Mongolia and Thailand in the same epidemic season. CONCLUSION: These results suggest that genetic drift has occurred infrequently in Japan as shown in some other countries. The drifted strains may have generated somewhere else and entered into Japan. These results support the proposed 'sink-source' model of viral ecology in which new lineages are seeded from a persistent influenza reservoir in tropical countries to 'sink' populations in temperate regions including Japan.

Men having sex with men in Surakarta, Indonesia: demographics, behavioral characteristics and prevalence of blood borne pathogens.

The objectives of this study were to investigate the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), human T-lymphotropic virus types 1 and 2 (HTLV-1/2), Torque teno virus (TTV) and Toxoplasma gondii (T. gondii) infection among men who have sex with men (MSM) in Surakarta, Indonesia, and the risk factors and sexual behavior associated with these infections. A cross sectional study was performed from October 2009 to October 2011 among 143 MSM by face-to-face interviews to complete an interviewer-administered questionnaire. Subjects were tested for ,HIV, HBV, HCV, HDV, HTLV-1/2 and toxoplasma infection using serology and for TTV using molecular detection. The seropositive rates for anti-HIV, HBsAg, anti-HCV, anti-HDV, anti-HTLV-1/2, IgM anti-T. gondii, IgG anti-T, gondii and TTV DNA were 9.1%, 9.8%, 28.0%, 0.7%, 0.7%, 1.4%, 30.8%, and 26.6%, respectively. Risk factors associated with HIV infection were a history of injecting drug use (IDU) [adjusted OR (aOR) 6.0; 95% CI: 1.10-33.01] and a receptive role in sexual activity (aOR 8.1; 95% CI: 1.30-50.04) [corrected]. Having a tattoo (aOR 3.2; 95% CI: 1.28-7.98) and practicing both anal and vaginal sex without a condom (aOR 2.3; 95% CI: 1.06-4.92) were associated with toxoplasma infection. A history of IDU (aOR 32; 95% CI: 5.93-177.93) was associated with TTV infection. The subjects examined in this study were found to be infected with HIV, HBV, HCV, HDV, HTLV-1/2, TTV, and T. gondii. These infections were associated with high-risk behavior.

Possible HIV transmission modes among at-risk groups at an early epidemic stage in the Philippines.

A concentrated human immunodeficiency virus (HIV) epidemic might have started in the Philippines. A subsequent characterization of viruses was carried out to estimate HIV transmission modes. Most HIV strains from injecting drug users belonged to subtype-B. CRF-01 was a major subtype harbored by three other at-risk populations: male visa applicants who had sex with men, "men who have sex with men," and visa applicants. An HIV phylogeny suggested that two strain groups of injecting drug users and others circulated separately. In contrast, there was substantial genetic overlap between two strain groups from "men who have sex with men" and visa applicants. Mean nucleotide distance within strains was shorter among subtype-B strains harbored by the injecting drug users (0.010) than among CRF-01 strains of the other three populations: male visa applicants who had sex with men (0.034), "men who have sex with men" (0.023), and visa applicants (0.032). Closely related strains of hepatitis C virus were derived from not only HIV-positive but also -negative individuals. These results suggest that there is potential for transmission from visa applicants to "men who have sex with men," and that once HIV occurs in injecting drug users, it spreads rapidly among them. Close contacts of hepatitis C virus carriers composed of HIV-negative and -positive individuals indicated ongoing HIV spread via blood and possible intervention points. Large-scale analysis is needed to provide more precise information on the transmission directions and to help curb the growth of this HIV epidemic in the Philippines.

Reduced replication capacity of influenza A(H1N1)pdm09 virus during the 2010-2011 winter season in Tottori, Japan.

A novel swine-origin influenza A(H1N1)pdm09 virus has been circulating in humans since March-April, 2009. The 2009-2010 epidemic involved predominantly a single subtype of A(H1N1)pdm09 (at 96%, 46/48) in the sentinel sites of this study. However, A(H1N1)pdm09 started to circulate together with other type/subtype (49%, 33/68) at the first peak in the next epidemic season in 2010-2011: A(H1N1)pdm09/A(H3N2) (9%, 6/68), A(H1N1)pdm09/B (35%, 24/68), and A(H1N1)pdm09/A(H3N2)/B (4%, 3/68). Single infection of A(H1N1)pdm09 became a rare event (8%, 5/65) at the second peak of the same season in 2010-2011 compared with that at the first peak (50%, 34/68). Concurrently with this decline, single infections of others, A(H3N2) or B, became evident (6%, 4/65; 14%, 9/65, respectively). Triple infections were more common (29%, 19/65) at the second peak than at the first peak (4%). The A(H1N1)pdm09 detected in 2010-2011 produced less virus upon 72 hr of incubation in vitro after the inoculations at 10(4) and 3,300 copies/ml (2.3 × 10(9) and 2.3 × 10(9) copies/ml on average) than that in 2009-2010 (3.7 × 10(9) and 1.3 × 10(10) copies/ml on average; P<0.05 by ANOVA test), respectively. As described above, the replication capacity of A(H1N1)pdm09 seems to have deteriorated in the 2010-2011 season presumably due to substantial herd immunity and allowed the existence of other type/subtype. These results suggest that assessment of replication capacity is indispensable for analysis of influenza epidemics.

Molecular epidemiology of HIV, HBV, HCV, and HTLV-1/2 in drug abuser inmates in central Javan prisons, Indonesia.

INTRODUCTION: This study was conducted to determine the current molecular prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and human T lymphotropic virus-1/2 (HTLV-1/2) circulating among drug abuser inmates incarcerated in prisons located in Central Java, Indonesia. METHODOLOGY: Socio-epidemiological data and blood specimens were collected from 375 drug abuser inmates in four prisons. The blood samples were analyzed with serological and molecular testing for HIV, HBV, HCV, HDV, and HTLV-1/2. RESULTS: The seroprevalence of HIV, HBsAg, HCV, HDV, and HTLV-1/2 in drug abuser inmates was 4.8% (18/375), 3.2% (12/375), 34.1% (128/375), 0% (0/375), and 3.7% (14/375), respectively. No co-infections of HIV and HBV were found. Co-infections of HIV/HCV, HIV/HTLV-1/2, HBV/HCV, HBV/HTLV-1/2, and HCV/HTLV-1/2 were prevalent at rates of 4% (15/375), 1.3% (5/375), 1.1% (4/375), 0.3% (1/375), and 2.1% (8/375), respectively. The HIV/HCV co-infection rate was significantly higher in injection drug users (IDUs) compared to non-IDUs. Triple co-infection of HIV/HCV/HTLV-1/2 was found only in three IDUs (0.8%). HIV CRF01_AE was found to be circulating in the inmates. HBV genotype B3 predominated, followed by C1. Subtypes adw and adr were found. HCV genotype 1a predominated among HCV-infected inmates, followed by 1c, 3k, 3a, 4a, and 1b. All HTLV-1 isolates shared 100% homology with HTLV-1 isolated in Japan, while all of the HTLV-2 isolates were subtype 2a. CONCLUSION: Drug abuser inmates in prisons may offer a unique community to bridge prevention and control of human blood-borne virus infection to the general community.

The early phase of an HIV epidemic in a population exposed previously to HCV in the Philippines.

Human immunodeficiency virus (HIV) sentinel surveillance program for injecting drug users has been conducted in Metro Cebu, the Philippines. A low prevalence (0-0.52%) of anti-HIV-positivity had been detected in this population from 2002 to 2007. However, a 10-fold increase in HIV prevalence was detected in the 2009 national HIV sentinel surveillance program. It prompted an additional outreach program to be conducted in Metro Cebu in January 2010, which recorded the highest HIV prevalence rate ever documented in the Philippines (75%, 44/59). HIV genes from fourteen 2009 to 2010 Metro Cebu strains were clustered closely in the phylogenetic tree, but no other strain collected outside Metro Cebu and none stored in the International Nucleotide Sequence Database was allocated to the same phylogenetic cluster. All these HIV infections have emerged in the anti-hepatitis C virus (HCV)-positive population (100%, 62/62) in Metro Cebu from 2009 to 2010. The five HCV strains from the individuals harboring the closely related HIV strains were categorized into different subtypes. These results strongly suggest that HIV infections occurred recently and spread rapidly among injecting drug users, while HCV had been circulating previously among them. Considering the fact that injecting drug use was the first mode of HIV transmission in Asia, extensive monitoring of injecting drug users and associated bridging populations is necessary. Therefore, HCV-guided characterization of the spread of HIV to populations that are vulnerable to blood-borne infections could play an important role in alerting health authorities to the early phase of an HIV epidemic.

Pandemic influenza: a never-ending story.

A novel pandemic influenza emerged in 2009, something that hasn't been seen since 1977. The following issues will be introduced and discussed in this review: the history of influenza pandemics, the emergence of the novel pandemic influenza of 2009, epidemics in the southern and northern hemispheres after the recognition of index cases in the United States, mortality, viral characteristics, prevention in the household setting, clinical aspects, diagnosis, treatment and immunization. Some questions have been answered. However, a number of other questions remain. Scientific research must follow up on these unanswered questions.