Is excessive acetaminophen intake associated with transaminitis in adult patients with dengue fever?

BACKGROUND: Dengue, an endemic infection causing severe flu-like symptoms and fever, is often treated with high-dose acetaminophen that can exceed recommended daily dosages. This leads to hepatotoxicity, although the underlying mechanism is poorly understood. We hypothesised that excessive acetaminophen causes hepatic toxicity in dengue patients. AIMS: To investigate a correlation between elevated serum transaminases and excessive acetaminophen intake, and other aggravating factors of liver injury in dengue cases. METHODS: This prospective observational study obtained blood samples from 150 participants with acute febrile illness for dengue serological tests, blood counts, and the detection of serum transaminases and acetaminophen levels. Other factors were determined by questionnaire. RESULTS: Of 150 participants enrolled, 77 had dengue fever. Abnormally high serum aspartate transaminase and alanine transaminase levels were present in 97.0% and 75.3% of dengue cases respectively. Multivariate analysis of cases with increased serum transaminases more than threefold normal upper limits indicated that male gender (odds ratio (OR) = 3.62, 95% confidence interval (CI) 1.38-9.42) and consuming >8 g acetaminophen orally (OR = 4.62, 95% CI 1.37-13.18) correlated with transaminitis. No correlation was found for other factors such as age, fever day at presentation, body mass index, alcohol intake or dengue severity classification (all P > 0.05). Chronic alcohol consumption was higher in non-dengue (2.6%) versus dengue cases (27.8%) (P < 0.01). CONCLUSIONS: Most dengue patients had mild-to-moderate transaminitis. Male gender and acetaminophen >8 g were associated with increased serum transaminases. Thus, 1000 mg acetaminophen every 8 h or <3000 mg/day is recommended for dengue cases. Chronic alcohol consumption might be protective against dengue infection.

Evaluation of an enzyme-linked immunosorbent assay in Thai scrub typhus patients.

We report the development of an improved enzyme-linked immunosorbent assay (ELISA) to detect Orientia (formerly Rickettsia) tsutsugamushi antibody in human sera. Results were compared with a standard test, the indirect immunoperoxidase assay (IIP). Control serum samples were collected from 96 American soldiers and 198 Royal Thai Army soldiers with no recent history of clinical illness. Sera were examined from 79 febrile, Thai scrub typhus patients presenting at Chiang Rai (76) and Bangkraui Nontaburi (3) Provincial hospitals (cases confirmed by elevated IIP IgG levels > or = 1:1,600, IgM levels > or = 1:400, or presence of an eschar). The mean + 2 SD, used for the upper limit of normal reactions in the IgG ELISA, was 0.10 for U.S. soldiers and 0.42 for Thai soldiers. Using the 0.10 cutoff value, 29% of the asymptomatic Thai soldiers would be designated as antibody positive. Variability of IgG ELISA values was greater in the Thai soldier group than in American soldiers, possibly reflecting previous exposure to O. tsutsugamushi. In the Thai patients, there was a significant correlation between IIP titers and single serum dilution (1:100) ELISA values (IgG, r = 0.75, n = 104; P < 0.0005; IgM, r = 0.70, n = 75; P < 0.0005) and between IIP titers and ELISA titers (IgG, r = 0.87, n = 103; P < 0.0005; IgM, r = 0.76, n = 75; P < 0.0005). The single serum dilution ELISA was as effective as the titration in determining presence of specific antibodies. The O. tsutsugamushi ELISA is a rapid and objective test amenable to accurately testing the large numbers of sera often obtained in seroepidemiologic investigations.

Scrub typhus infections poorly responsive to antibiotics in northern Thailand.

BACKGROUND: Rickettsia tsutsugamushi, the aetiological agent of scrub typhus, is common in Asia and readily infects visitors to areas where disease transmission occurs. Rapid defervescence after antibiotic treatment is so characteristic that it is used as a diagnostic test for R tsutsugamushi infection. Reports from local physicians that patients with scrub typhus in Chiangrai, northern Thailand responded badly to appropriate antibiotic therapy prompted us to do a prospective clinical evaluation and antibiotic susceptibility testing of human rickettsial isolates. METHODS: The clinical response to doxycycline treatment in patients with early, mild scrub typhus in northern Thailand was compared with the results of treatment in Mae Sod, western Thailand. Prototype and naturally occurring strains of R tsutsugamushi were tested for susceptibility to chloramphenicol and doxycycline in mice and in cell culture. FINDINGS: By the third day of treatment, fever had cleared in all seven patients from Mae Sod, but in only five of the 12 (40%) from Chiangrai (p < 0.01). Median fever clearance time in Chiangrai (80 h; range 15-190) was significantly longer than in Mae Sod (30 h; range 4-58; p < 0.005). Conjunctival suffusion resolved significantly more slowly in Chiangrai (p < 0.05). Antibiotics prevented death in mice infected by Chiangrai strains of R tsutsugamushi less often than after infection by the prototype strain (p < 0.05). Only one of three Chiangrai strains tested in cell culture was fully susceptible to doxycycline. INTERPRETATION: Chloramphenicol-resistant and doxycycline-resistant strains of R tsutsugamushi occur in Chiangrai, Thailand. This is the first evidence of naturally occurring antimicrobial resistance in the genus Rickettsia.