Geographical heterogeneity of dengue transmission in two villages in southern Vietnam.

This study was performed to test the hypothesis that there are 'hotspots', i.e. geographical heterogeneity, of dengue transmission. Data from two repeat serosurveys in two villages in Vietnam were used to identify incident infections and to relate these to prevalence at baseline and thus assess geographical heterogeneity, i.e. clustering, in dengue transmission. A total of 400 households were surveyed; serological data from 521 children at baseline and from 119 children at follow-up were included in a spatial analysis. Geographical heterogeneity of dengue transmission was explored using a permutation null distribution test. This showed for the first time evidence of clustering of dengue virus transmission at the household level in asymptomatic children. Risk areas could be identified by seroprevalence surveys combined with mapping. Control of dengue virus transmission could be supported by identification and control of hotspots.

Nutritional status following malaria control in a Vietnamese ethnic minority commune.

OBJECTIVE: To study whether control of malaria leads to catch-up growth or an increase of obesity in a marginally nourished population. SETTING: A Vietnamese ethnic minority commune in southern Vietnam. DESIGN: Repeated annual anthropometric surveys were performed from 1995 to 2000. Z-scores for height, weight and BMI for age and weight-for-height were determined by using NCHS 1978 and CDC 2000 reference tables and by the LMS method. INTERVENTION: Active malaria control that reduced the parasite carrier rate from 50% in 1994 to practically nil in 1998. RESULTS: Inhabitants were generally of short stature and very thin. Using the US reference tables, the prevalence of moderate/severe stunting among children was 53/24% and of wasting 27/9% in the first survey in 1995. Physical condition and normal daily activities of most inhabitants were normal. The repeated LMS-Z-scores uncovered a significant recovery of stunting, extending into preadolescence, including the development of a pubertal growth spurt for girls and enhancement of pubertal growth in boys, after control of malaria. The mean (95% CI) annual increase of Z-height-for-age was 0.11 (0.09-0.12) for boys and 0.14 (0.13-0.15) for girls (P<0.001). As a consequence, weight-for-age and BMI Z-scores decreased without indication of developing obesity. CONCLUSION: Catch-up growth, extending into preadolescent age, was observed in a Vietnamese ethnic minority population with a chronic state of low food intake, without indication of developing obesity. The control of malaria was probably the most significant contribution to this catch-up growth.

Atovaquone-proguanil for recrudescent Plasmodium falciparum in Vietnam.

Malarone, a fixed combination of atovaquone with proguanil (AP), has recently been recognized as a promising treatment against multidrug-resistant Plasmodium falciparum. In Vietnam, the first-line treatment for P. falciparum malaria is currently a combination of mefloquine and an artemisinin derivative, and the use of AP has not been explored. The aim of the present study, based in Vietnam, was to assess the efficacy of AP when used to treat P. falciparum recrudescences that had occurred after primary treatment with mefloquine-artesunate. All but two of the 39 patients investigated completed follow-up. The mean parasite- and fever-clearance times [and 95% confidence intervals (CI)] after AP treatment were 36 (30-42) and 21 (18-24) h, respectively. Most (32) of the 37 infections that were followed adequately appeared to be eradicated by the AP, the other five recrudescing once more. The overall cure 'rate' and (CI) was 86% (76%-98%). All of the patients tolerated the AP well. Atovaquone-proguanil appears to be a safe and promising alternative treatment for P. falciparum infections in South-east Asia, although the combination is relatively expensive and may not clear some infections with multidrug-resistant parasites.

Pharmacokinetic interactions of antimalarial agents.

Combination of antimalarial agents has been introduced as a response to widespread drug resistance. The higher number of mutations required to express complete resistance against combinations may retard the further development of resistance. Combination of drugs, especially with the artemisinin drugs, may also offer complete and rapid eradication of the parasite load in symptomatic patients and thus reduce the chance of survival of resistant strains. The advantages of combination therapy should be balanced against the increased chance of drug interactions. During the last decade, much of the pharmacokinetics and metabolic pathways of antimalarial drugs have been elucidated, including the role of the cytochrome P450 (CYP) enzyme complex. Change in protein binding is not a significant cause of interactions between antimalarial agents. CYP3A4 and CYP2C19 are frequently involved in the metabolism of antimalarial agents. Quinidine is a potent inhibitor of CYP2D6, but it appears that this enzyme does not mediate the metabolism of any other antimalarial agent. The new combinations proguanil-atovaquone and chlorproguanil-dapsone do not show significant interactions. CYP2B6 and CYP3A4 are involved in the metabolism of artemisinin and derivatives, but further studies may reveal involvement of more enzymes. Artemisinin may induce CYP2C19. Several artemisinin drugs suffer from auto-induction of the first-pass effect, resulting in a decline of bioavailability after repeated doses. The mechanism of this effect is not yet clear, but induction by other agents cannot be excluded. The combination of artemisinin drugs with mefloquine and the fixed combination artemether-lumefantrine have been studied widely, and no significant drug interactions have been found. The artemisinin drugs will be used at an increasing rate, particularly in combination with other agents. Although clinical studies have so far not shown any significant interactions, drug interactions should be given appropriate attention when other combinations are used.

Artemisinin for treatment of uncomplicated falciparum malaria: is there a place for monotherapy?

The efficacy of artemisinin monotherapy was studied in 227 patients with uncomplicated falciparum malaria. They all received artemisinin at t = 0 hr, t = 8 hr, and thereafter once daily; treatment was extended at random until they had taken either 5 days of artemisinin followed by 2 days of placebo (A5), or 7 days (A7) of artemisinin. The adult artemisinin dose was 500 mg; children aged < 15 years received 10 mg/kg per dose. The median (range) parasite clearance time was 39 (8-112) hr for A5 and 43 (38-104) hr for A7 (P = 0.085). The recrudescence rates were similar between the groups. The lowest parasite count achieved during treatment (Pterm) was associated with the occurrence of recrudescence (P = 0.046, Cox regression model); it was lower for patients with a radical cure or late recrudescence than for early recrudescence (P = 0.034, t-test). Artemisinin monotherapy may offer rapid recovery and fast parasite clearance, but recrudescence is frequent. Extending the duration of monotherapy from 5 days to 7 days does not reduce recrudescence.