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

MOLECULAR ANALYSIS OF A COMPLETE HIV-1 Pol GENE ISOLATED IN CENTRAL JAVA, INDONESIA

Background: HIV-1 is an infectious agent causing global health problem. Molecular analysis of HIV-1 strains is crucial due to the association with viral fitness, drug resistance, serological failure, and more importantly, for vaccine development. However, HIV-1 molecular data in Indonesia is limited, including that of the HIV pol gene. Aims: The present study performed a molecular analysis of the pol gene of HIV isolated in Central Java, Indonesia, in order to enrich HIV-1 molecular data in Indonesia, particularly in Central Java.Methods: A complete coding sequence of pol gene was cloned from 09IDSKA-6 (HIV isolated in Central Java, Indonesia), inserted into an Escherichia coli expression plasmid, and sequenced. The sequencing results of the pol gene then subjected for virus subtyping, genotyping, and phylogenetic analysis. The drug resistance, identification of the HLA binding motifs and viral epitopes, proteomic motifs, and physicochemical analysis was performed.Results: The HIV-1 isolate analyzed in this study was CRF01_AE strain. The isolate remains in low evolutionary state due to the low level of nonsynonymous to synonymous substitutions ratio (dN/dS). None of mutations identified was related to ARV drug resistance. A total of 33 CTL/CD8+ epitopes, 6 T-helper/CD4+ epitopes and 2 antibody epitopes were identified in our isolate. Six distinct proteomic domains were found. Physicochemical analysis revealed the molecular weight (Mw), estimated half-life, instability index, aliphatic index, and hydrophilicity of each proteins encoded by the complete HIV-1 pol gene. Keywords: HIV-1, pol gene, Indonesia.

High glucose-induced apoptosis in human coronary artery endothelial cells involves up-regulation of death receptors

<p>Abstract</p> <p>Background</p> <p>High glucose can induce apoptosis in vascular endothelial cells, which may contribute to the development of vascular complications in diabetes. We evaluated the role of the death receptor pathway of apoptotic signaling in high glucose-induced apoptosis in human coronary artery endothelial cells (HCAECs).</p> <p>Methods</p> <p>HCAECs were treated with media containing 5.6, 11.1, and 16.7 mM of glucose for 24 h in the presence or absence of tumor necrosis factor (TNF)-α. For detection of apoptosis, DNA fragmentation assay was used. HCAEC expression of death receptors were analyzed by the PCR and flow cytometry methods. Also, using immunohistochemical techniques, coronary expression of death receptors was assessed in streptozotocin-nicotinamide-induced type 2 diabetic mice.</p> <p>Results</p> <p>Exposure of HCAECs to high glucose resulted in a significant increase in TNF-R1 and Fas expression, compared with normal glucose. High glucose increased TNF-α production by HCAECs and exogenous TNF-α up-regulated TNF-R1 and Fas expression in HCAECs. High glucose-induced up-regulation of TNF-R1 and Fas expression was undetectable in the presence of TNF-α. Treatment with TNF-R1 neutralizing peptides significantly inhibited high glucose-induced endothelial cell apoptosis. Type 2 diabetic mice displayed appreciable expression of TNF-R1 and Fas in coronary vessels.</p> <p>Conclusions</p> <p>In association with increased TNF-α levels, the death receptors, TNF-R1 and Fas, are up-regulated in HCAECs under high glucose conditions, which could in turn play a role in high glucose-induced endothelial cell apoptosis.</p

フィリピンのHIV流行阻止のためのハイリスク集団把握と流行経路予測の試み

日本のHIV流行阻止のために,隣国フィリピンの流行阻止は重要であるが,これらの低流行国で入手可能な少数のHIV解析に依存した流行様式の解析・流行阻止は困難である.そこで,HIVが性行為感染者よりも先に注射薬物使用者(IDU)に流行の端緒が作られることに着目し,血液を媒介にIDUに侵入するHCVを代用マーカーとして「流行の核」を早期に発見する試みを始めた.ルソン,ビサヤ,ミンダナオの主要な都市圏に監視地域を得た.総検査数は,IDU由来1494検体を含む,2645検体に達した.HIV抗体陽性事例は3検体であり,フィリピンのHIVの低流行を裏付けた.しかし,注射薬物使用や透析によるHCV感染の頻度は高く,セブ都市圏の市街地居住のIDUにみられるHIV感染比率がわずかに0.40%であるのに比べ,抗HCV抗体陽性比率は89%である.また,HCV株(ルソン,48株;ビサヤ,366株,ミンダナオ,30株)について検討したところ,株の多様性は,マニラ首都圏を含むルソン地域に高く,特に,Subtype-1b(n=11),4(n=1),6(n=1)はこの地域にしかみられない.また,マニラ首都圏の株には,当地由来・その他の地域由来の何れの株よりも外国株に類似の株が存在する.このように,マニラ首都圏は,最も外国の影響を受けやすいことが示唆された.一方,系統樹解析から,Subtype-1a群には,上記3地域の株が混在しており,HCV株は3地域の間を短期間に移動していることも示唆された.ミンダナオの株(n=30)は全てSubtype-1aであり,多様性は低く,海路による南方からの血液媒介感染経路の存在は確認されていない.HIVがHCVと同様の経路で侵入・伝播すると仮定する場合,血液を媒介に流行するHIVは,マニラ首都圏から侵入し,短期間の内にセブ都市圏やミンダナオ地域に広がることが推測された.The monitoring of an HIV infection is important for the prevention of an outbreak. However, it is difficult to identify the early phase of an epidemic only by HIV monitoring and we add the monitoring of Hepatitis C virus (HCV) to be used for a surrogate marker of blood-borne IIN infection. Blood-borne HIV infections have been considered to be the spread measures at initial phase of an outbreak before sexual contact-related infections.Surveillance areas have been organized in Luzon, Visaya, and Mindanao in the Philippines, and totally 2,645 samples have been tested including 1,494 ones from injecting drug users (IDUs). HIV has been rarely detected, which supports the low prevalence of HIV infection in the Philippines. However, the blood-borne HCV infections are prevalent among IDUs and dialysis patients. The percentage of HCV infections among IDUs at downtown in Metro Cebu (the center of Visaya) were 8936 although that of HIV was few, 0.40%. The profiles of HCV indicated that the variety of the strains prevalent in Metro Manila (capital of the Philippines and the center of Luzon) has been biggest Subtype-1b, genotype-4 and 6 were only observed in Metro Manila Moreover, some of them strains bad higher homology to foreign strains than those prevalent in Metro Manila. The strains variety may indicate that the foreign strains may preferentially enter into Metro Manila than other areas. Some strains collected in three areas (shown above) mixed together in the Phylogenetic trees, suggesting HCV stains may circulate quickly in the Philippines.The results of HCV study indicate that WV may enter into Metro Manila and circulate into other area in the Philippines.研究課題/領域番号:16406014, 研究期間(年度):2004-2007出典：「フィリピンのHIV流行阻止のためのハイリスク集団把握と流行経路予測の試み」研究成果報告書　課題番号16406014 (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)　　　本文データは著者版報告書より作

IMMUNOGLOBULIN-G ANTI-Toxoplasma gondii ANTIBODIES CONCENTRATION IN PERIPHERAL BLOOD SAMPLES AMONG MALE COMMERCIAL SEX WORKER IN SURAKARTA

Primary prevention of Toxoplasma gondii (T. gondii) infection among high risk-community of HIV transmission is very essential. The goal of the study was as preliminary study to quantify Immunoglobulin-G (IgG) anti-T. gondi protein concentration in peripheral blood samples among male CSW in Surakarta, Indonesia. In cross sectional study, peripheral blood samples of thirty male CSW in Surakarta were collected, and determined for IgG anti-T. gondii using commercial enzyme-linked immunosorbent assay (ELISA) kit. Then we conducted three statistical modeling approach using simple linear regression model, to predict the IgG protein concentration (Y) from each IgG index measurement (X). IgG index measurement was determined by dividing samples optical density (O.D) and cut-off calibrator O.D (O.D was measured in spectrophotometer). The models were Y1 = 21.3*X1 – 4.3 (for the range between 0.2 to 1.7 of IgG index), Y2 = 85.0*X2 – 112.5 (between 1.7 to 2.5 of IgG index), and Y3 = 666.7*X3 – 1566.7 (for more than 2.5 of IgG index). Pearson correlation analysis was used to measure relationship between IgG antibodies concentration and age (p &lt;0.05 was considered as significant). All data analysis was done using STATA® 12 statistical software and Python® 3.3 programming software. The result showed that by fitting linear regression model, we found high titer (more than 300 IU/ml) of IgG anti-T.gondii among 20% of male CSW. About 13.33% of them had moderate titer 100 – 300 IU/ml of IgG antibodies, and 66.67% of them had less than 100 IU/ml of IgG antibodies titer. There was mild negative correlation between IgG antibodies titers with age, but it was not significant. The present study was the first finding reported IgG anti-T. gondii concentration status among male commercial sex worker in Indonesia, indicating of a need more public health promotion for primary prevention of toxoplasmosis among this community.Keywords: Immunoglobulin-G concentration, Toxoplasma gondii, Male commercial sex worker, Indonesia, Linear regressio

Rapid detection of human immunodeficiency virus type 1 group M by a reverse transcription-loop-mediated isothermal amplification assay

金沢大学医薬保健研究域医学系A rapid one-step reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay targeting the pol-integrase gene was developed to detect human immunodeficiency virus type 1 (HIV-1) group M. This HIV-1 RT-LAMP assay is simple and rapid, and amplification can be completed within 35 min under isothermal conditions at 60 °C. The 100% detection limit of HIV-1 RT-LAMP was determined using a standard strain (WHO HIV-1 [97/656]) in octuplicate and found to be 120 copies/ml. The RT-LAMP assay was evaluated for use for clinical diagnosis using plasma samples collected from 57 HIV-1-infected and 40 uninfected individuals in Cameroon, where highly divergent HIV-1 strains are prevalent. Of the 57 samples from infected individuals, 56 harbored group-M HIV-1 strains, such as subtypes A, B, G, F2, and circulating recombinant forms (CRFs) _01, _02, _09, _11, _13; all were RT-LAMP positive. One sample harboring group-O HIV-1 and the 40 HIV-1-uninfected samples were RT-LAMP negative. These findings indicate that HIV-1 RT-LAMP can detect HIV-1 group-M RNA from plasma samples rapidly and with high sensitivity and specificity. These data also suggest that this RT-LAMP assay can be useful for confirming HIV diagnosis, particularly in resource-limited settings. © 2009 Elsevier B.V. All rights reserved

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

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