A changing picture of shigellosis in southern Vietnam: shifting species dominance, antimicrobial susceptibility and clinical presentation.

BACKGROUND: Shigellosis remains considerable public health problem in some developing countries. The nature of Shigellae suggests that they are highly adaptable when placed under selective pressure in a human population. This is demonstrated by variation and fluctuations in serotypes and antimicrobial resistance profile of organisms circulating in differing setting in endemic locations. Antimicrobial resistance in the genus Shigella is a constant threat, with reports of organisms in Asia being resistant to multiple antimicrobials and new generation therapies. METHODS: Here we compare microbiological, clinical and epidemiological data from patients with shigellosis over three different periods in southern Vietnam spanning 14 years. RESULTS: Our data demonstrates a shift in dominant infecting species (S. flexneri to S. sonnei) and resistance profile of the organisms circulating in southern Vietnam. We find that there was no significant variation in the syndromes associated with either S. sonnei or S. flexneri, yet the clinical features of the disease are more severe in later observations. CONCLUSIONS: Our findings show a change in clinical presentation of shigellosis in this setting, as the disease may be now more pronounced, this is concurrent with a change in antimicrobial resistance profile. These data highlight the socio-economic development of southern Vietnam and should guide future vaccine development and deployment strategies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN55945881.

Double blind comparison of ibuprofen and paracetamol for adjunctive treatment of uncomplicated typhoid fever.

BACKGROUND: Antipyretics reduce the prolonged, high fever characteristic of typhoid fever. The benefits of nonsteroidal drugs in this role have not been quantified. There have been concerns about the safety of antipyretics in typhoid. METHODS: In a double blind randomized study, 80 Vietnamese children with uncomplicated typhoid fever were randomized to receive identical syrup preparations of ibuprofen (10 mg/kg) or paracetamol (12 mg/kg) every 6 h until 36 h after defervescence. Children with a nalidixic acid-susceptible (Na) isolate of Salmonella typhi were treated with ofloxacin (15 mg/kg/day) for 3 days and those with a nalidixic acid-resistant (Na) isolate were treated for 7 days. RESULTS: S. typhi was isolated from 36 of 40 children randomized to ibuprofen (11 isolates Na) and 37 of 40 randomized to paracetamol (13 isolates Na). The median (range) fever clearance time (hours) was shorter in the ibuprofen group than the paracetamol group (68, 4 to 260 vs. 104, 12 to 404; P = 0.055) as was the area under the temperature time curve above 37 degree C (74, 0 to 237 vs. 127, 0 to 573; P = 0.013). The differences occurred predominantly in the children infected with a NaS. typhi whose infections responded more slowly to antibiotic treatment. There were no major side effects associated with the use of either drug. There were no differences between the two treatment arms in the concentrations of circulating interleukin-6 and tumor necrosis factor alpha during the course of treatment. CONCLUSION: The antipyretic effect of ibuprofen is superior to that of paracetamol in children with typhoid fever, particularly those with prolonged fever. Both antipyretics appeared to be safe.

A multi-center randomized trial to assess the efficacy of gatifloxacin versus ciprofloxacin for the treatment of shigellosis in Vietnamese children.

BACKGROUND: The bacterial genus Shigella is the leading cause of dysentery. There have been significant increases in the proportion of Shigella isolated that demonstrate resistance to nalidixic acid. While nalidixic acid is no longer considered as a therapeutic agent for shigellosis, the fluoroquinolone ciprofloxacin is the current recommendation of the World Health Organization. Resistance to nalidixic acid is a marker of reduced susceptibility to older generation fluoroquinolones, such as ciprofloxacin. We aimed to assess the efficacy of gatifloxacin versus ciprofloxacin in the treatment of uncomplicated shigellosis in children. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a randomized, open-label, controlled trial with two parallel arms at two hospitals in southern Vietnam. The study was designed as a superiority trial and children with dysentery meeting the inclusion criteria were invited to participate. Participants received either gatifloxacin (10 mg/kg/day) in a single daily dose for 3 days or ciprofloxacin (30 mg/kg/day) in two divided doses for 3 days. The primary outcome measure was treatment failure; secondary outcome measures were time to the cessation of individual symptoms. Four hundred and ninety four patients were randomized to receive either gatifloxacin (n=249) or ciprofloxacin (n=245), of which 107 had a positive Shigella stool culture. We could not demonstrate superiority of gatifloxacin and observed similar clinical failure rate in both groups (gatifloxacin; 12.0% and ciprofloxacin; 11.0%, p=0.72). The median (inter-quartile range) time from illness onset to cessation of all symptoms was 95 (66-126) hours for gatifloxacin recipients and 93 (68-120) hours for the ciprofloxacin recipients (Hazard Ratio [95%CI]=0.98 [0.82-1.17], p=0.83). CONCLUSIONS: We conclude that in Vietnam, where nalidixic acid resistant Shigellae are highly prevalent, ciprofloxacin and gatifloxacin are similarly effective for the treatment of acute shigellosis.