Wirach Maek-a-nantawat

A Randomized, Double-Blind, Placebo-Controlled Trial of Acetazolamide for the Treatment of Elevated Intracranial Pressure in Cryptococcal Meningitis

We conducted a trial of oral acetazolamide for the treatment of cryptococcal meningitis in 22 Thai adults with headache and an opening cerebrospinal fluid pressure of >/=200 mm H(2)0. The trial was terminated prematurely because patients who received acetazolamide developed significantly lower venous bicarbonate levels and higher chloride levels and had more-frequent serious adverse events than did subjects who received placebo.

Safety and Reactogenicity of Canarypox ALVAC-HIV (vCP1521) and HIV-1 gp120 AIDSVAX B/E Vaccination in an Efficacy Trial in Thailand

Background A prime-boost vaccination regimen with ALVAC-HIV (vCP1521) administered intramuscularly at 0, 4, 12, and 24 weeks and gp120 AIDSVAX B/E at 12 and 24 weeks demonstrated modest efficacy of 31.2% for prevention of HIV acquisition in HIV-uninfected adults participating in a community-based efficacy trial in Thailand. Methodology/Principal Findings Reactogenicity was recorded for 3 days following vaccination. Adverse events were monitored every 6 months for 3.5 years, during which pregnancy outcomes were recorded. Of the 16,402 volunteers, 69% of the participants reported an adverse event any time after the first dose. Only 32.9% experienced an AE within 30 days following any vaccination. Overall adverse event rates and attribution of relatedness did not differ between groups. The frequency of serious adverse events was similar in vaccine (14.3%) and placebo (14.9%) recipients (p = 0.33). None of the 160 deaths (85 in vaccine and 75 in placebo recipients, p = 0.43) was assessed as related to vaccine. The most common cause of death was trauma or traffic accident. Approximately 30% of female participants reported a pregnancy during the study. Abnormal pregnancy outcomes were experienced in 17.1% of vaccine and 14.6% (p = 0.13) of placebo recipients. When the conception occurred within 3 months (estimated) of a vaccination, the majority of these abnormal outcomes were spontaneous or elective abortions among 22.2% and 15.3% of vaccine and placebo pregnant recipients, respectively (p = 0.08). Local reactions occurred in 88.0% of vaccine and 61.0% of placebo recipients (p<0.001) and were more frequent after ALVAC-HIV than AIDSVAX B/E vaccination. Systemic reactions were more frequent in vaccine than placebo recipients (77.2% vs. 59.8%, p<0.001). Local and systemic reactions were mostly mild to moderate, resolving within 3 days. Conclusions/Significance The ALVAC-HIV and AIDSVAX B/E vaccine regimen was found to be safe, well tolerated and suitable for potential large-scale use in Thailand. Trial Registration ClinicalTrials.gov NCT00223080

Anaphylaxis and Biphasic Phase in Thailand: 4-year Observation

BACKGROUND Anaphylaxis, a severe systemic allergic reaction, can be fatal. However, its prevalence has been underestimated especially in biphasic phase, due to a lack of case awareness. This study aimed to determine the rate of anaphylaxis, describe clinical manifestations and management, and identify the causative agents and risk factors of biphasic anaphylactic reaction. METHODS An observational study was conducted at the Emergency Department of Thammasat University Hospital, Thailand, during the period 2004-2008. RESULTS Of total 208 cases of anaphylaxis identified, the median age was 20.67 years; 52.9% were male. The anaphylaxis rate was 49 per 100,000 patient-years. No fatal case was found; 58.7% had a history of atopy, and 38.5% had experienced a previous allergic reaction, of whom 8.8% had had a previous anaphylactic reaction. The causative allergens were identified in 82.2% of cases; food allergy was most common. Urticaria was the most common presentation (87%). Among 6.3% of the patients who developed biphasic reaction, a significantly longer time from onset of symptoms to administration of epinephrine was detected, with a median of 240 minutes for those with biphasic anaphylaxis, versus 70 minutes for those without (p = 0.002). The median times from onset to hospital arrival and the arrival to administration of epinephrine were also significantly longer in the biphasic group than the non-biphasic patients (p = 0.002 and p = 0.001, respectively). In multivariable regression models, the time intervals from onset and hospital arrival to administration of epinephrine continued to predict biphasic phase occurrence (p < 0.01). CONCLUSIONS Anaphylaxis predominantly occurs among children and young adults. Delayed administration of epinephrine was associated with the occurrence of biphasic anaphylaxis.

Virologic and Immunologic Outcomes of the Second-Line Regimens of Antiretroviral Therapy Among HIV-Infected Patients in Thailand

Goal of the second-line therapy among HIV-1-infected patients is to re-establish virological suppression, although treatment options in resource-limited settings are limited. An observational cohort of patients with first-line antiretroviral therapy (ART) failure was conducted in a university hospital in Thailand. Of 95 patients, mean age 39 years, 65% were male. Median CD4 and HIV-1 RNA at second-line ART initiation were 158 cells/mm3 and 4.1 copies/mL, respectively. Boosted protease inhibitor plus 2 nucleoside reverse transcriptase inhibitors (NRTIs), indicated by genotype results, was commonly used as second-line regimen. At 6, 12, 24, and 36 months of second-line ART, 67%, 62%, 84%, and 90% of patients achieved HIV-1 RNA <50 copies/mL; median CD4 were 258, 366, 444, and 522 cells/mm 3, respectively. Good adherence, high baseline CD4, and early Centers for Centers for Disease Control and Prevention (CDC) staging were associated with virologic success (P < .05). Second-line ART based on the results of genotype testing yields the good virologic and immunologic outcomes in a resource-limited setting, and scaling-up of second-line ART is indicated.

Pregnancy Outcomes Among HIV-Infected Women Undergoing Antiretroviral Therapy

Background: The use of antiretroviral drugs (ARV) to prevent mother-to-child HIV transmission (PMTCT) promises to be effective. However, limited data on the adverse effects of ARV among pregnant women and pregnancy outcomes have been reported in clinical practice. Objectives: This study aimed to assess adverse effects and outcomes among pregnant HIV-infected women receiving antiretroviral drugs for either antiretroviral therapy (ART) or PMTCT. Study Design: This cohort study was at Chonburi Hospital, Thailand, in 2002-2006. Results: A total of 246 pregnant HIV-infected women with the median age (range) of 27 (16-41) years were included in this study. ART was initiated in 16.3% for treatment during ANC, 66.7% for PMTCT during ANC, and 17.1% for PMTCT in labor. Adverse effects, especially anemia, were significantly associated with continuing combined ART in pregnancy (p<0.001). 88.9% delivered normal-term neonates. The prevalence of pre-term delivery was 10.2%. Overall, 24 adverse events from 21 pregnant women (8.5%) were noted. A significantly higher prevalence of pre-term delivery was noted in the groups continuing combined ART, or initiating of PMTCT during labor rather than ANC (p=0.02). The incidence of low Apgar scores was 3.6%, and these were associated with initiation of PMTCT during labor (p=0.004). Conclusion: Adverse ARV events were more numerous among the pregnant women who needed ART than PMTCT. ANC is beneficial and strongly recommended for all pregnant HIV-infected women for better pregnancy outcomes.

Presence of autoimmune antibody in chikungunya infection.

Chikungunya infection has recently re-emerged as an important arthropod-borne disease in Thailand. Recently, Southern Thailand was identified as a potentially endemic area for the chikungunya virus. Here, we report a case of severe musculoskeletal complication, presenting with muscle weakness and swelling of the limbs. During the investigation to exclude autoimmune muscular inflammation, high titers of antinuclear antibody were detected. This is the report of autoimmunity detection associated with an arbovirus infection. The symptoms can mimic autoimmune polymyositis disease, and the condition requires close monitoring before deciding to embark upon prolonged specific treatment with immunomodulators.

HIV-1 drug resistance at virological failure versus immunological failure among patients failing first-line antiretroviral therapy in a resource-limited setting.

Antiretroviral treatment failure has been defined by immunological failure (IF) in some resource-limited settings whereas defining by virological failure (VF) has been widely used in developed countries. There is limited comparison of the levels of HIV-1 drug resistance between using VF and IF for the diagnosis of treatment failure. A retrospective cohort study was conducted among HIV-1-infected patients failing first-line antiretroviral therapy (ART). Of 95 patients, median CD4 and HIV-1 RNA were 158 cells/mm3 and 10,200 copies/mL, respectively. Patients in the IF group had higher HIV-1 RNA than those in VF group (23,820 versus 9510 copies/mL, P = 0.008). Nucleoside reverse transcriptase inhibitor (NRTI)-, non-NRTI- and protease inhibitor-resistance-associated mutations (RAMs) were observed in 57.9%, 94.7% and 5.3%, respectively. Q151M, a multidrug RAM, was more commonly observed in the IF group (14.8% versus 2.9%, P = 0.032). Using IF to diagnose treatment failure is associated with higher HIV-1 RNA levels and a higher rate of Q151M, which can limit the options for second-line ART.

Diagnosis of gnathostomiasis by skin testing using partially purified specific antigen and total IgE levels.

BACKGROUND A finding of antibodies to Gnathostoma spinigerum 24-kDa antigen by immunoblot analysis is currently used to confirm a diagnosis of gnathostomiasis. A simple skin test for the diagnosis of gnathostomiasis was developed, and the results were evaluated and compared with the standard Western blot (WB) test. METHODS This cross-sectional study was conducted at the Hospital for Tropical Diseases, Bangkok, Thailand, in 2008-2011. All eligible patients were tested with partially purified proteins of mAb-detected fractions pooled and sterilized by 0.2 μm diameter syringe filter, with a phenol saline solution of 1:10 w/v. RESULTS A total of 69 cases, 39 gnathostomiasis cases and 30 controls, were enrolled into the study; the median age (IQR) was 40 (30.5-52.5) years. The most common presenting symptom was edema (56/69, 81%). Gnathostomiasis cases having strong cutaneous reactions to the intradermal test (81%) were also positive by immunoblot. A significant correlation between skin and immunoblot tests was detected (p<0.001). The difference in total IgE levels between cases and controls was not statistically significant (p=0.51). Logistic regression models showed that positive WB and skin-test results were significantly associated with gnathostomiasis (p=0.001 and p=0.007, respectively). CONCLUSION Gnathostoma skin testing, using prepared fractionated antigen solution of Gnathostoma spinigerum, yields good reactivity and significantly correlates with the results of immunoblot testing.