Immunologic study of human encephalitic and paralytic rabies. Preliminary report of 16 patients

Lymphocyte proliferation tests to rabies antigen and myelin basic protein were performed on peripheral blood lymphocytes from nine patients with the encephalitic form and on seven with the paralytic form of human rabies. Six of the nine patients with encephalitis had proliferative responses to rabies antigen, whereas all of the patients with paralysis had no response. Two patients in each group also had a proliferative response to myelin basic protein. The myelin basic protein-reactive patients had a more rapidly fatal disease than the non-reactive patients. This preliminary study suggests that host immune responses may influence the clinical manifestations and course in human rabies.     

Comparison of Ashdown's medium, Burkholderia cepacia medium, and Burkholderia pseudomallei selective agar for clinical isolation of Burkholderia pseudomallei

Ashdown's medium, Burkholderia pseudomallei selective agar (BPSA), and a commercial Burkholderia cepacia medium were compared for their abilities to grow B. pseudomallei from 155 clinical specimens that proved positive for this organism. The sensitivity of each was equivalent; the selectivity of BPSA was lower than that of Ashdown's or B. cepacia medium.     

An effective economical intradermal regimen of human diploid cell rabies vaccination for post-exposure treatment.

A closely-spaced multisite intradermal regimen of human diploid cell rabies vaccine (HDCV) was evaluated in 39 patients after low-risk exposure to rabies, in comparison to full-dose intramuscular HDCV and sheep brain-derived rabies (Semple) vaccine. The regimen consisted of four intradermal injections, 0.1 ml each of HDCV on days 0, 3 and 7, followed by two booster doses of only 0.1 ml each on days 28 and 91 administered intradermally. Although the total amount of HDCV used in this intradermal regimen was 1.4 ml or one-quarter of the conventional intramuscular regimen, a higher proportion of the recipients of this economical intradermal regimen, as compared to the full-dose intramuscular regimen, developed neutralizing antibodies above the hypothetical protective level of 0.5 iu/ml 7 days after starting immunization. Besides the earlier antibody response, the peak antibody level of the intradermal regimen was also satisfactorily high and not significantly different from that after the intramuscular regimen. Simultaneous administration of inosiplex, an antiviral and immunopotentiating agent, during the first 10 days of intradermal immunization resulted in an even higher antibody response for as long as 91 days. In contrast, but not unexpectedly, Semple vaccine evoked lower, more sluggish and inconsistent antibody responses. The side-effects of intradermal HDCV were mild, mainly local and self-remitting. We therefore recommend our intensive intradermal regimen of HDCV vaccination for safe, effective and economical use in post-exposure rabies immunization.     

Three-year durability of dual-nucleoside versus triple-nucleoside therapy in a Thai population with HIV infection

We compared the long-term immunologic and virologic efficacy of the dual- and triple-nucleoside therapy for HIV infection. This was a retrospective analysis of 2 randomized clinical trials in antiretroviral-naive patients. In the dual-nucleoside group, 15 started with didanosine (ddI) monotherapy and then added stavudine (d4T) after 24 weeks, 63 started with various doses of d4T and ddI, and 53 started with zidovudine (ZDV) and lamivudine (3TC). In the triple-nucleoside group, 53 started with ZDV, 3TC, and ddI. After 48 weeks, patients who were not failing were randomized to immediate (before treatment failure) versus delayed (at the time of virologic failure) switching from ddI and d4T to ZDV and 3TC or vice versa and from ZDV, 3TC, and ddI to d4T, 3TC, and abacavir (ABC). Failure was defined as a plasma HIV-1 RNA level>or=1 log10 above nadir or >or=10,000 copies/mL when nadir was <500 copies/mL. Patients failing therapy before week 48 received the new treatment as in the immediate switching group. Hydroxyurea was added to the last treatment regimen if patients failed after week 96. CD4 count and plasma HIV-1 RNA level (branched DNA assay with a cutoff point of 50 copies/mL) at week 144 were analyzed by intention to treat. Compared with the dual-nucleoside group, the triple-nucleoside group had a higher proportion of patients with <50 copies/mL at 144 weeks (60% vs. 18%; P<0.001), higher median CD4 count (388 cells/microL vs. 346 cells/microL; P=0.018), and longer duration of response, defined as the time from onset of viral suppression (<500 copies/mL) to the time of treatment failure (the first of 2 consecutive HIV-1 RNA measurements >500 copies/mL never followed by 2 consecutive visits showing suppressible viremia to <500 copies/mL) or discontinuation from the study (144 weeks vs. 104 weeks; P=0.002). Multivariate regression analyses showed that significant predictors for treatment success, defined as a plasma viral load <50 copies/mL at week 144, were asymptomatic clinical status at enrollment, a baseline plasma viral load 相似文献   

Significant differences between plasma HIV-1 RNA assays in HIV-1 subtype E infected patients treated with antiretroviral therapy

A total of 72 HIV-1 infected Thai patients treated with didanosine (ddI) or stavudine (d4T) plus ddI at the time of interim analysis were analyzed. Sixty patients (83%) carried subtype E documented by HIV-1 V3 serotyping. HIV-1 RNA levels were measured using three commercial viral load assays. At baseline (n = 57), Quantiplex 2.0 and NucliSens 2.0 showed mean log10 HIV-1 RNA of 0.7 log10 or 5 fold lower than Amplicor 1.5 (mean 4.29 versus 5.0 log10, respectively, p < 0.001). At week 20 of treatment (n = 29), HIV-1 RNA levels were detected in 55.2%, 31%, and 33.5% of subjects tested by Amplicor 1.5, Quantiplex 2.0, and NucliSens 2.0, respectively. In conclusion: plasma HIV-1 RNA analyses showed comparable values with Quantiplex 2.0 and NucliSens 2.0 assays. In contrast, Amplicor 1.5 resulted in approximately 5 folds higher HIV-1 RNA levels and a 25% higher rate of detection of plasma HIV-1 RNA as compared to the other two assays. As the current goal of therapy is to suppress plasma viral load below the detection limit of the assays, the significant differences between the assays may influence antiretroviral efficacy evaluation and management.     

The risk of occupational HIV exposure among Thai healthcare workers

To analyze the incidence of occupational exposure to HIV in a large group of healthcare workers at the 2 Thai Red Cross hospitals, prospectively collected during a seven-year period in order to find out the causes and circumstances that prone to exposure, the interventions that may minimize the exposure and the consequences of the accidents. The first 200 incident reports from 198 hospital workers of the Thai Red Cross Society who had occupational exposure to HIV-infected blood and body fluids during 1991-1997 were analyzed. We analyzed the demographic data, the timing and place of exposure, the nature and cause of exposure, HIV status at baseline and at follow-up at 3, 6 and 12 months as well as the received antiretroviral prophylaxis. All of the 198 HCW had negative anti-HIV at baseline and remained negative throughout the one-year follow-up although only 55% submitted the results of their anti-HIV testing at 6 months. However, none claimed for work-related life insurance against HIV during those 7 years indicating that nosocomial rate of transmission is less than 1 in 200 or less than 0.5%. Analysis of the incidents indicated that the risk group was the 20-40 years old nursing personnel who worked in the medical wards during the regular working hours. The procedures that were responsible for most of the injuries were venepuncture, intravenous access, injection and waste collection. Most of the injuries could be prevented if the work place safety guidelines were strictly followed and if personnel were more careful at work. The results can be used to implement more effective preventive measures for hospitals in Thailand. Postexposure management at the Thai Red Cross hospitals conformed with the international guidelines. However, only 78% of those who should receive postexposure prophylaxis were recommended for treatment and only 69% of those recommended actually took the treatment. This emphasizes the need to educate clinicians involved in postexposure care as well as to ensure them and the injured subjects about the safety of the antiretroviral prophylaxis.     

Anogenital HIV RNA in Thai men who have sex with men in Bangkok during acute HIV infection and after randomization to standard vs. intensified antiretroviral regimens

Introduction

HIV transmission risk is highest during acute HIV infection (AHI). We evaluated HIV RNA in the anogenital compartment in men who have sex with men (MSM) during AHI and compared time to undetectable HIV RNA after three-drug versus five-drug antiretroviral therapy (ART) to understand risk for onward HIV transmission.

Methods

MSM with AHI (n=54) had blood, seminal plasma and anal lavage collected for HIV RNA at baseline, days 3 and 7, and weeks 2, 4, 12 and 24. Data were compared between AHI stages: 1 (fourth-generation antigen-antibody combo immunoassay [IA]–, third-generation IA–, n=15), 2 (fourth-generation IA+, third-generation IA–, n=9) and 3 (fourth-generation IA+, third-generation IA+, western blot–/indeterminate, n=30) by randomization to five-drug (tenofovir+emtricitabine+efavirenz+raltegravir+maraviroc, n=18) versus three-drug (tenofovir+emtricitabine+efavirenz, n=18) regimens.

Results

Mean age was 29 years and mean duration since HIV exposure was 15.4 days. Mean baseline HIV RNA was 5.5 in blood, 3.9 in seminal plasma and 2.6 log₁₀ copies/ml in anal lavage (p<0.001). Blood and seminal plasma HIV RNA were higher in AHI Stage 3 compared to Stage 1 (p<0.01). Median time from ART initiation to HIV RNA <50 copies/ml was 60 days in blood, 15 days in seminal plasma and three days in anal lavage. Compared with the three-drug ART, the five-drug ART had a shorter time to HIV RNA <1500 copies/ml in blood (15 vs. 29 days, p=0.005) and <50 copies/ml in seminal plasma (13 vs. 24 days, p=0.048).

Conclusions

Among MSM with AHI, HIV RNA was highest in blood, followed by seminal plasma and anal lavage. ART rapidly reduced HIV RNA in all compartments, with regimen intensified by raltegravir and maraviroc showing faster HIV RNA reductions in blood and seminal plasma.