SummaryDengue is highly endemic in southern Vietnam and all four serotypes of dengue virus have already been identified. To determine the age-specific prevalence of dengue and associated risk factors, we conducted a serological study at two primary schools and assessed risk factors by analysing children's questionnaires and household surveys. Sera were collected from 961 primary schoolchildren in Binh Thuan Province and tested for the presence of dengue virus serum antibodies using an indirect immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA). The antibody prevalence of the total population was 65.7% (n ¼ 631) which increased from 53.0 to 88.2% with age. The annual incidence of a first dengue infection, estimated by binary regression of the seroprevalence by age, was 11.7%. Interestingly, the prevalence of dengue IgG antibodies was significantly higher in children who confirmed using a pit latrine (RR 1.467, 95% CI: 1.245-1.730) and whose domestic environment contained discarded cans (RR 1.238, 95% CI: 1.042-1.470) and pigs (RR 1.228, 95% CI: 1.002-1.504). The epidemiology of dengue in southern Vietnam is stable with a constantly high annual incidence of first infections. Transmission occurs mainly peri-domestically, which has important public health implications.

To provide novel data relating to the dispositions, effects, and toxicities of the artemisinin derivatives in severe malaria, we studied 30 Vietnamese adults with slide-positive falciparum malaria treated with intravenous artesunate. Twelve patients with complications (severe; group 1) and 8 patients without complications but requiring parenteral therapy (moderately severe; group 2) received 120 mg of artesunate by injection, and 10 patients with moderately severe complications (group 3) were given 240 mg by infusion. Serial concentrations of artesunate and its active metabolite dihydroartemisinin in plasma were measured by high-performance liquid chromatography. The time to 50% parasite clearance (PCT 50 ) was determined from serial parasite densities. Full clinical (including neurological) assessments were performed at least daily. In noncompartmental pharmacokinetic analyses, group mean artesunate half-lives (t 1/2 ) were short (range, 2.3 to 4.3 min). The dihydroartemisinin t 1/2 (range, 40 to 64 min), clearance (range, 0.73 to 1.01 liters/h/kg), and volume of distribution (range, 0.77 to 1.01 liters/kg) were also similar both across the three patient groups (P > 0.1) and to previously reported values for patients with uncomplicated malaria. Parasite clearance was prompt (group median PCT 50 range 6 to 9 h) and clinical recovery was complete under all three regimens. These data indicate that the pharmacokinetics of artesunate and dihydroartemisinin are not influenced by the severity of malaria. Since the pharmacokinetic parameters for both artesunate and dihydroartemisinin were similar regardless of whether injection or infusion was used, artesunate can be considered a prodrug that is converted stoichiometrically to dhydroartemisinin. Conventional doses of artesunate are safe and effective when given to patients with complications of falciparum malaria.

Background: Dengue is a common cause of fever in the tropics but its contribution to the total burden of febrile illnesses that is presented to primary health facilities in endemic regions such as Vietnam, is largely unknown. We aimed to report the frequency of dengue as a cause of fever in Binh Thuan Province, to describe the characteristics of dengue patients, and analyze the diagnostic accuracy of the health care workers and the determinants of the diagnostic process.

Aims To obtain comprehensive bioavailability data for artesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) following their separate oral administration to Vietnamese volunteers and to patients with acute, uncomplicated falciparum malaria. Methods Volunteers were randomized to receive either i.v. ARTS (120 mg) followed by oral ARTS (150 mg) 8 h later (Group 1, n=10), or i.v. ARTS (120 mg) followed by oral DHA (120 mg) 8 h later. Patients, also received oral ARTS (150 mg; Group 3, n=8) or DHA (120 mg; Group 2, n=7), in a randomized cross-over study design. Multiple blood samples were collected after each administration and plasma ARTS and/or DHA concentrations were determined by h.p.l.c. Pharmacokinetic descriptors were obtained from noncompartmental analysis and bioavailability was calculated from AUC data. In the patients, the time to 50% parasite clearance (PCT 50 ) and fever clearance time (FCT) also were measured. Results In Group 1 (volunteers), the mean (95% CI) absolute bioavailability of oral ARTS was 80% (62,98%), while in Group 2 (volunteers), the bioavailability of oral DHA was 45% (34,56%). In the patients (Group 3), the bioavailability of oral DHA relative to oral ARTS was 88% (49,127%). The median PCT 50 and FCT were 2.3 and 28 h, respectively. Conclusions The study shows that the absolute bioavailability of DHA was signi®-cantly lower than that for ARTS in healthy volunteers. The bioavailability of ARTS in volunteers was consistent with previous studies in patients with uncomplicated falciparum malaria. The dose-normalized C max and AUC(0,?) for DHA were signi®cantly greater in patients with falciparum malaria than in healthy volunteers. The high relative bioavailability of DHA in the patients may have been due to lower ®rst-pass clearance. We conclude that, for the treatment of malaria, DHA is likely to be a suitable oral substitute for ARTS. Based on our mean AUC measurements, it appears that equal doses of DHA and ARTS (mg basis) should give equivalent systemic exposure to bioactive DHA in uncomplicated falciparum malaria.

SummaryObjectivesTo explore clinical and virological characteristics and describe the epidemiology of dengue in patients who presented with acute undifferentiated fever (AUF) at primary health centers (PHC) in Binh Thuan Province, Vietnam.MethodsA prospective observational study was conducted from 2001 to 2006 to study the aetiology in AUF patients. Demographic and clinical information was obtained, and dengue polymerase chain reaction (RT-PCR) and serology were performed on a random selection of patients.ResultsThree hundred fifty-one serologically confirmed dengue patients including 68 primary and 283 secondary infections were included in this study. In 25% (86/351) dengue virus (DENV) was detected by RT-PCR among which 32 DENV-1, 16 DENV-2, 1 DENV-3 and 37 DENV-4 were identified. The predominant dengue serotype varied by year with seasonal fluctuation: DENV-4 in 2001–2002, DENV-1 and DENV-2 from 2003 to 2006. Primary dengue was more common in children. Higher viraemia levels (P = 0.010) were found in primary infections compared to secondary infections. DENV-1 infected patients had higher viraemia levels than DENV-2 (P = 0.003) and DENV-4 (P < 0.001) infected patients. Clinical symptoms were often seen in adults. Few differences in clinical symptoms were found between primary and secondary infection and no significant differences in clinical symptoms between the serotypes were observed.ConclusionsOur data provide insight in the epidemiology, clinical profile and virological features of mild symptomatic dengue patients who presented to PHC with AUF in Vietnam.

Summary Objectives  To describe the characteristics of patients consulting commune primary healthcare posts for acute undifferentiated fever not being malaria (AUF), and to explore the diagnostic and therapeutic responses of the healthcare workers. Methods  All patients presenting with AUF at 12 commune health posts and one clinic at the provincial malaria station, Binh Thuan, a dengue endemic province in southern Vietnam, were included. Record forms were used to fill in patient and diseases characteristics, pre‐referral treatment, signs and symptoms, provisional diagnosis and installed treatment, referral and final outcome. Results  Two thousand ninety‐six patients were included from April 2001 to March 2002. The median delay to attend the health posts was, 0.87 day for >5, 1.15 days for children aged 5–15 years and 1.41 days for adults (P < 0.001). Sixty‐five per cent of patients took some measures before consulting the health post, of whom 82% applied self‐medication and 69% took antibiotics. Pre‐referral medication with antibiotics increased with age (RR 1.012 per year of age; 95% CI: 1.004–1.019). The diagnostic and therapeutic response of healthcare workers was very unspecific. The tourniquet test was inappropriately used as general discriminating test, not only for detecting dengue haemorrhagic fever. Empiric antibiotic therapy was installed in 77.2% of cases. Conclusions  Management of uncomplicated fever, not being malaria, at the primary healthcare level in Vietnam is non‐specific, dominated by searching signs of hemorrhagic dengue and empiric antibiotic treatment. This can probably be improved by better education.

Aims  To obtain pharmacokinetic data for artesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) following i.m. ARTS and rectal DHA administration. Methods  Twelve Vietnamese patients with uncomplicated falciparum malaria were randomized to receive either i.v. or i.m. ARTS (120 mg), with the alternative preparation given 8 h later in an open crossover design. A further 12 patients were given i.v. ARTS (120 mg) at 0 h and rectal DHA (160 mg) 8 h later. Results  Following i.v. bolus, ARTS had a peak concentration of 42 µm (16 mg l−1), elimination t1/2 = 3.2 min, CL = 2.8 l h−1 kg−1 and V = 0.22 l kg−1. The Cmax for DHA was 9.7 µm (2.7 mg l−1), t1/2 = 59 min, CL = 0.64 l h−1 kg−1 and V =  0.8 l kg−1. Following i.m. ARTS, Cmax was 2.3 µm (3.7 mg l−1), the apparent t1/2 = 41 min, CL = 2.9 l h−1 kg−1 and V = 2.6 l kg−1. The relative bioavailability of DHA was 88%, Cmax was 4.1 µm (1.16 mg l−1) and t1/2 = 64 min. In the rectal DHA study, relative bioavailability of DHA was 16%. Conclusions  For patients with uncomplicated falciparum malaria i.m. ARTS is a suitable alternative to i.v. ARTS, at equal doses. To achieve plasma DHA concentrations equivalent to parenteral administration of ARTS, rectal DHA should be given at approximately four‐fold higher milligram doses. Further studies are needed to determine whether these recommendations can be applied to patients with severe malaria.

Our data emphasize the importance of leptospirosis among children in Vietnam, despite the absence of severe disease, and stress the need for adequate and cheap diagnostics.