Causes of Fever in Rural Southern Laos.

The etiology of fever in rural Lao People's Democratic Republic (Laos) has remained obscure until recently owing to the lack of laboratory facilities. We conducted a study to determine the causes of fever among 229 patients without malaria in Savannakhet Province, southern Laos; 52% had evidence of at least one diagnosis (45% with single and 7% with apparent multiple infections). Among patients with only one diagnosis, dengue (30.1%) was the most common, followed by leptospirosis (7.0%), Japanese encephalitis virus infection (3.5%), scrub typhus (2.6%), spotted fever group infection (0.9%), unspecified flavivirus infection (0.9%), and murine typhus (0.4%). We discuss the empirical treatment of fever in relation to these findings.

Randomized comparison of chloroquine plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether-lumefantrine in the treatment of uncomplicated falciparum malaria in the Lao People's Democratic Republic.

BACKGROUND: Recent clinical trials in the Lao People's Democratic Republic have demonstrated that chloroquine and sulfadoxine-pyrimethamine, which are national malaria treatment policy, are no longer effective in the treatment of uncomplicated Plasmodium falciparum malaria. METHODS: A randomized comparison of 3 oral antimalarial combinations--chloroquine plus sulfadoxine-pyrimethamine versus artesunate plus mefloquine versus artemether-lumefantrine--with 42-day follow-up period, was conducted among 330 patients with acute uncomplicated falciparum malaria in southern Laos. RESULTS: The 42-day cure rates, as determined by intention-to-treat analysis and adjusted for reinfection, were 100%, 97%, and 93% for the groups receiving artesunate plus mefloquine, artemether-lumefantrine, and chloroquine plus sulfadoxine-pyrimethamine, respectively. Of 8 patients receiving chloroquine plus sulfadoxine-pyrimethamine who experienced treatment failure, 6 had early treatment failure. The mean parasite clearance time was significantly longer in patients treated with chloroquine plus sulfadoxine-pyrimethamine (2.9 days; 95% confidence interval [CI], 2.8-3.0 days) than in those treated with artesunate plus mefloquine (2.07 days; 95% CI, 2.0-2.1 days; P<.001) and artemether-lumefantrine (2.08 days; 95% CI, 2.0-2.1 days; P<.001). Cure rates with artemether-lumefantrine were high despite low mean daily dietary fat intake (13.8 g; 95% CI, 12.5-15.1 g) and day 7 plasma lumefantrine concentrations (0.47 mu g/mL; 95% CI, 0.38-0.56 mu g/mL). CONCLUSION: Oral artesunate plus mefloquine and artemether-lumefantrine are highly effective for the treatment of uncomplicated falciparum malaria in Laos.

A phase III, randomized, non-inferiority trial to assess the efficacy and safety of dihydroartemisinin-piperaquine in comparison with artesunate-mefloquine in patients with uncomplicated Plasmodium falciparum malaria in southern Laos.

We conducted an open, randomized clinical trial of oral dihydroartemisinin-piperaquine (DP) versus artesunate-mefloquine (AM) in 300 patients in Laos with uncomplicated Plasmodium falciparum malaria as part of a multicentre study in Asia. Survival analysis and adjustment for re-infection showed that the 63-day cure rates (95% confidence interval [CI]) were 100% for AM and 99.5% (96.4-99.8%) for DP. The 63-day cure rates per protocol were 99% (97 of 98) for AM and 99.5% (196 of 197) for DP (P = 0.55). The difference (AM minus DP) in cure rates (95% CI) was -0.5% (-5.1 to 2.0%), which is within the 5% non-inferiority margin. The median fever and parasite clearance times were also similar for AM and DP. The proportion of patients with at least one recorded potential adverse event was significantly higher in the AM group (38 of 87, 44%) than in the DP group (57 of 182, 31%) (relative risk = 0.6, 95% CI = 0.4-0.9; P = 0.04). Dihydroartemisinin-piperaquine is not inferior to AM in the treatment of uncomplicated P. falciparum malaria in Laos and is associated with fewer adverse effects. The results of this study were similar to those of the larger multicentre study.

Thiamin deficiency and uncomplicated falciparum malaria in Laos.

OBJECTIVE: Thiamin deficiency complicates severe Plasmodium falciparum malaria in Thailand and may contribute to acidosis. We therefore estimated the frequency of biochemical thiamin deficiency in patients presenting with uncomplicated falciparum malaria in southern Laos. METHODS: Red cell transketolase activation coefficients (alpha) were measured in 310 patients presenting with uncomplicated falciparum malaria and 42 days after starting treatment. RESULTS: Twelve per cent of patients had biochemical evidence of severe deficiency (alpha values >1.31) at presentation, declining to 3% 42 days later. CONCLUSION: Thiamin deficiency was common in Lao patients admitted with uncomplicated P. falciparum infection and was reduced following treatment of malaria and multivitamin supplementation. The role of this preventable and treatable disorder in malaria and other acute infections, and the incidence of beriberi in rural Laos, needs further investigation.

Improving tuberculosis case detection rate with a lay informant questionnaire: an experience from the Lao People's Democratic Republic.

PROBLEM: In many countries, the tuberculosis (TB) annual case detection rate is below the target of 70%. In the Lao People's Democratic Republic in 2005, it did not exceed 55% APPROACH: The DOTS strategy promotes passive case detection of TB. In order to increase the detection rate, we validated a questionnaire targeting lay informants at village level to notify patients with chronic cough and assessed the relevance for TB case-finding. A three-item questionnaire was sent through the district health departments to all villages in six districts in six provinces. The village headmen were asked to notify chronic cough patients. Answers were validated in a door-to-door survey (20 villages/district). In a sub-sample (four villages/district) all confirmed patients were screened for TB and paragonimiasis. LOCAL SETTING: Attapeu, Luang Namtha, Luang Prabang, Saravane, Savanakhet and Vientiane provinces in the Lao People's Democratic Republic. RELEVANT CHANGES: Lay informant questionnaires sent from district health offices to villages are cost-effective and foster interaction between the health services and remote and underserved communities. Although the correct detection of patients is highly dependent on direct respondents, a substantial number of new TB and paragonimiasis cases were consistently diagnosed in chronic cough patients. LESSONS LEARNED: Out of 456 questionnaires, 295 were returned (65%). Return rates were highly variable between districts (48-87%), questionnaires' sensitivity (56-98%), positive predictive value (34-88%) and correlation between number of notified and confirmed patients (r: 0.26-0.78). In sub-sampled villages (13,541 population) 19 (5.1%) TB and 26 (7.0%) paragonimiasis cases were detected in 374 chronic cough patients. This quick questionnaire approach proved motivating for district authorities and village key informants, although no incentives were provided. The highly operator-dependent approach yielded a consistent detection rate of TB and paragonimiasis cases. This approach brings health services and populations in need in close contact, which is particularly crucial in remote and underserved areas.