タイの紹介病院において見つかったHIV血清学的に一致しない夫婦にHIVに相当暴露されたにもかかわらず抗HIV抗体陰性の配偶者が蓄積している

長崎大学学位論文 [学位記番号]博（医）乙第1,796号 [学位授与年月日]平成22年3月31

Impact of HIV vaccination on laboratory diagnosis: case reports

BACKGROUND: It has not been clearly demonstrated whether HIV vaccination can complicate routine HIV testing. In this report, we describe the laboratory data of two prisoners who received rgp120 vaccine in a phase III trial underway in Thailand. These data indicate that previous vaccination may complicate the interpretation of screening HIV diagnostic tests. CASE PRESENTATION: The participants were identified from a cohort study on "Health factors related to HIV-1 and other viral infections among incarcerated people" that was approved by The Ethical Committee for Research in Human Subjects, Ministry of Public Health, Thailand. HIV diagnosis was definitively established with serial specimens using multi-screening tests, Western blot and diagnostic PCR. Anti-HIV screening tests consistently exhibited either weakly reactive or inconclusive results. The band patterns of the Western blot analysis corresponded to those found in individuals who received the rgp120 vaccination. Definite results were established using diagnostic PCR, which exhibited consistently negative results with follow-up specimens. Such problems in HIV testing are not easily resolved in the routine clinical setting in Thailand. CONCLUSIONS: These data demonstrate that HIV-1 vaccination interferes with routine diagnostic tests. Similar cases will not be uncommon in Thailand, where 2,545 people have already participated in a phase III trial

Regional Differences in the Prevalence of Major Opportunistic Infections among Antiretroviral-Naive Human Immunodeficiency Virus Patients in Japan, Northern Thailand, Northern Vietnam, and the Philippines

To identify regional differences in the distribution of opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in Asia, the medical records of antiretroviral therapy (ART)-naive patients who attended the following tertiary hospitals from 2003 to 2011 were reviewed: Nagoya Medical Center (NMC, Nagoya, Japan), Lampang Hospital (LPH, Lampang, northern Thailand), Bach Mai Hospital (BMH, Hanoi, northern Vietnam), and Philippine General Hospital (PGH, Manila, Philippines). Logistic regression analyses were performed to identify associations between country of origin and risk of major OIs. In total, 1,505 patients were included: NMC, N = 365; LPH, N = 442; BMH, N = 384; and PGH, N = 314. The median age was 32 years, and 73.3% of all patients were male. The median CD4 count was 200 cells/μL. Most patients at NMC and PGH were men who have sex with men. Injection drug users were most common at BMH (35.7%). Mycobacterium tuberculosis (TB) was most common at PGH (N = 75) but was rare at NMC (N = 4). Pneumocystis pneumonia (PCP) prevalence was highest at NMC (N = 74) and lowest at BMH (N = 13). Multivariable logistic regression showed increased odds of TB at PGH (adjusted odds ratio [aOR] = 42.2, 95% confidence interval [CI] = 14.6?122.1), BMH (aOR = 12.6, CI = 3.9?40.3), and LPH (aOR = 6.6, CI = 2.1?21.1) but decreased odds of PCP at BMH (aOR = 0.1, CI = 0.04?0.2) and LPH (aOR = 0.2, CI = 0.1?0.4) compared with those at NMC. The cryptococcosis risk was increased at LPH (aOR = 6.2, CI = 0.9?41.0) compared with that at NMC. Cytomegalovirus (CMV) retinitis prevalences were similar in all countries. OI prevalence remained high among ART-naive patients in our cohort. The risks of TB, PCP, and cryptococcosis, but not CMV retinitis, differed between countries. Improved early HIV detection is warranted

Frequency and mortality rate following antimicrobial-resistant bloodstream infections in tertiary-care hospitals compared with secondary-care hospitals

There are few studies comparing proportion, frequency, mortality and mortality rate following antimicrobial-resistant (AMR) infections between tertiary-care hospitals (TCHs) and secondary-care hospitals (SCHs) in low and middle-income countries (LMICs) to inform intervention strategies. The aim of this study is to demonstrate the utility of an offline tool to generate AMR reports and data for a secondary data analysis. We conducted a secondary-data analysis on a retrospective, multicentre data of hospitalised patients in Thailand. Routinely collected microbiology and hospital admission data of 2012 to 2015, from 15 TCHs and 34 SCHs were analysed using the AMASS v2.0 (www.amass.website). We then compared the burden of AMR bloodstream infections (BSI) between those TCHs and SCHs. Of 19,665 patients with AMR BSI caused by pathogens under evaluation, 10,858 (55.2%) and 8,807 (44.8%) were classified as community-origin and hospital-origin BSI, respectively. The burden of AMR BSI was considerably different between TCHs and SCHs, particularly of hospital-origin AMR BSI. The frequencies of hospital-origin AMR BSI per 100,000 patient-days at risk in TCHs were about twice that in SCHs for most pathogens under evaluation (for carbapenem-resistant Acinetobacter baumannii [CRAB]: 18.6 vs. 7.0, incidence rate ratio 2.77; 95%CI 1.72–4.43, p0.20). Due to the higher frequencies, all-cause in-hospital mortality rates following hospital-origin AMR BSI per 100,000 patient-days at risk were considerably higher in TCHs for most pathogens (for CRAB: 10.2 vs. 3.6,mortality rate ratio 2.77; 95%CI 1.71 to 4.48, p<0.001; CRPA: 1.6 vs. 0.8; p = 0.020; 3GCREC: 4.0 vs. 2.4, p = 0.009; 3GCRKP, 4.0 vs. 1.8, p<0.001; CRKP: 0.8 vs. 0.3, p = 0.042; and MRSA: 2.3 vs. 1.1, p = 0.023). In conclusion, the burden of AMR infections in some LMICs might differ by hospital type and size. In those countries, activities and resources for antimicrobial stewardship and infection control programs might need to be tailored based on hospital setting. The frequency and in-hospital mortality rate of hospital-origin AMR BSI are important indicators and should be routinely measured to monitor the burden of AMR in every hospital with microbiology laboratories in LMICs

Efficacy and safety of topical trikatu preparation in, relieving mosquito bite reactions: a randomized controlled trial

Introduction: Trikatu is composed of dried fruits of Piper nigrum L and Piper retrofractum Vahl, and dried rhizomes of Zingiber officinale R. Although this preparation has been used to relieve pruritis, pain, and inflammation for a long time, there is no clinical evidence to confirm its efficacy and safety. Therefore, we performed a double-blind, within person-randomized controlled study of 30 healthy volunteers to determine efficacy and safety of topical Trikatu on mosquito bite reactions. Methods: All subjects were bitten by Aedes aegypti laboratory mosquitoes on their forearms and they were randomly assigned arms to apply either Trikatu or reference product on the mosquito bite papule. The main outcome was the difference of papule size reduction at 30. min, measured by a caliper, between the Trikatu and reference arms. Pruritis, redness, pain, and patient satisfaction were assessed at 15, 30, 60, 180, and 360. min as secondary outcomes. Results: There were no significant differences between treatment and reference arms on any outcome at any time of measurement. Conclusion: Trikatu did not show additional effects for relieving mosquito bite reaction as compared with the reference product containing camphor, menthol, and eucalyptus. For further study, it is very important to consider a proper selection of subjects, comparator product, and concentration of extract when Trikatu preparation is investigated

Changing Burden of HIV/AIDS to Clinical Settings in Northern Thailand over 15 Years

We conducted a hospital-based descriptive study to describe the changing pattern of patient numbers, characteristics, and mortality rates among human immunodeficiency virus (HIV)-infected patients in northern Thailand over 15 years. The survival status on October 31, 2010 of all HIV-infected adults who attended an HIV center in a government hospital between 1995 and 2010 was ascertained. In total, 3,706 patients were registered, 2,118 (57.2%) of which were male. The survival status of 3,439 patients (92.9%) was available. In addition, 1,543 deaths were identified out of 12,858 person-year-observations (PYO) resulting in a mortality rate of 12.4 deaths/100 PYO (95% confidence interval [CI], 11.3-13.0). An initial decline in mortality rates was observed prior to 1999, probably because of an increase in the proportion of less symptomatic patients. After the introduction of the national highly active antiretroviral therapy (HAART) program, a profound decline in mortality rates was observed, reaching 2.0 deaths/100 PYO (95% CI, 1.4-2.9) in 2010. Simultaneously, the number of patients on follow-up increased by nearly fourfold. Although HAART has drastically improved the survival of HIV-infected patients, the number of patients receiving therapy at this HIV clinic has substantially increased. While referral of HIV patients to general physicians\u27 care should be urged, we cannot overemphasize the importance of preventing new HIV infections

Safety of the aqueous extract of Portulaca grandiflora Hook in healthy volunteers

A phase 1 clinical trial was performed in 16 healthy volunteers to primarily investigate safety of Portulaca grandiflora (P. grandiflora) as well as to preliminarily assess its efficacy on the immune system. The volunteers received 500 mg/day of P. grandiflora aqueous extract (250 mg capsule twice daily) for 2 months. No major side effects were reported from any of the subjects throughout the study. It was found that some significant changes in biochemical parameters were within normal limits. Hematological and immunological parameters were not altered after oral administration of P. grandiflora. Our results indicated that the P. grandiflora aqueous extract at the dose of 500 mg/day given to normal volunteers for 2 months was safe

Frequent Detection of Epstein-Barr Virus and Cytomegalovirus but Not JC Virus DNA in Cerebrospinal Fluid Samples from Human Immunodeficiency Virus-Infected Patients in Northern Thailand

Applying nested-PCRs, we frequently detected DNA of Epstein-Barr virus and cytomegalovirus but not JC virus in cerebrospinal fluid samples from 140 human immunodeficiency virus-infected patients with central nervous system symptoms in northern Thailand. Despite the low incidence of primary central nervous system lymphoma or cytomegalovirus encephalitis among Thai AIDS patients, Epstein-Barr virus and cytomegalovirus infections in the central nervous system are common

Deficiency of mannose-binding lectin is a risk of Pneumocystis jirovecii pneumonia in a natural history cohort of people living with HIV/AIDS in Northern Thailand.

BackgroundMannose-binding lectin (MBL) plays a pivotal role in innate immunity; however, its impact on susceptibility to opportunistic infections (OIs) has not yet been examined in a natural history cohort of people living with HIV/AIDS.MethodsWe used archived samples to analyze the association between MBL expression types and risk of major OIs including Pneumocystis jirovecii pneumonia (PCP), cryptococcosis, talaromycosis, toxoplasmosis, and tuberculosis in a prospective cohort in Northern Thailand conducted from 1 July 2000 to 15 October 2002 before the national antiretroviral treatment programme was launched.ResultsOf 632 patients, PCP was diagnosed in 96 (15.2%) patients, including 45 patients with new episodes during the follow-up period (1006.5 person-years). The total history of PCP was significantly associated with low MBL expression type: high/intermediate (81/587, 13.8%), low (10/33, 30.3%) and deficient (5/12, 41.7%) (p = 0.001), whereas the history of other OIs showed no relation with any MBL expression type. Kaplan-Meier analysis (n = 569; log-rank p = 0.011) and Cox's proportional hazards model revealed that deficient genotype dramatically increased the risk of PCP, which is independent upon sex, age, CD4 count, HIV-1 viral load and hepatitis B and C status (adjusted hazard ratio 7.93, 95% confidence interval 2.19-28.67, p = 0.002).ConclusionsDeficiency of MBL expression is a strong risk factor determining the incidence of PCP but not other major OIs