Comparison of Thiamin Diphosphate High-Performance Liquid Chromatography and Erythrocyte Transketolase Assays for Evaluating Thiamin Status in Malaria Patients without Beriberi.

Thiamin deficiency, or beriberi, is an increasingly re-recognized cause of morbidity and mortality in the developing world. Thiamin status has traditionally been measured through the erythrocyte activation assay (ETKA) or basal transketolase activity (ETK), which indirectly measure thiamin diphosphate (TDP). Thiamin diphosphate can also be measured directly by high-performance liquid chromatography (HPLC), which may allow a more precise estimation of thiamin status. We compared the direct measurement of TDP by HPLC with basal ETK activity and ETKA in 230 patients with Plasmodium falciparum malaria in rural southern Laos without overt clinical beriberi, as part of a trial of thiamin supplementation. Admission thiamin status measured by basal ETK activity and ETKA (α) were compared with thiamin status assessed by the measurement of TDP by HPLC. 55% of 230 included patients were male, and the median age was 10 (range 0.5-73) years. Using α ≥ 25% as the gold standard of thiamin deficiency, the sensitivity of TDP < 275 ng/gHb as a measure of thiamin deficiency was 68.5% (95% CI: 54.4-80.5%), with specificity of 60.8 (95% CI: 53.2-68.1%). There was a significant inverse correlation between the results of the two tests (Kendall's tau = -0.212, P < 0.001). Basal ETK activity was also significantly positively correlated with TDP levels (Kendall's tau = 0.576, P < 0.001). Thiamin diphosphate measurement may have a role in measuring thiamin levels in clinical settings. Further studies evaluating TDP concentration in erythrocytes with basal ETK activity and ETKA (α) in beriberi patients would help establish comparative values of these assays.

Do health care providers give sufficient information and good counseling during ante-natal care in Lao PDR?: an observational study.

BACKGROUND: It is increasingly recognized that improving the quality of maternal health care delivery is of utmost importance in many countries. In Laos, the quality of antenatal care (ANC) service remains inadequate, but it has never been assessed thoroughly. This study aims to determine the ANC quality at the urban and rural public health facilities in Laos and provides suggestions to improve health education and counseling in addition to other routine care in public ANC services. METHODS: This health-facility based, cross-sectional observation study included both health providers (n = 77) and pregnant women (n = 421) from purposively selected health facilities (n = 16). Information on the mothers' current pregnancies, previous visits and their last children was collected. The time spent for each ANC session as well as ANC services provided were recorded. Descriptive and inferential statistics were applied to analyze the data. RESULTS: Overall performance of ANC services by health care providers was poor in both urban and rural areas. Insufficient provision of information on danger signs during pregnancy, nutrition, breast feeding and iron supplements was revealed. Generally the communication skills, behavior and attitude of health providers were very poor. Less than a quarter of pregnant women were treated with kindness and respect. Only 4% of the observed ANC session took privacy into consideration. Less than 10% of available information materials were used during each ANC session. None of the health providers in both rural and urban areas performed specific counseling. Overall mean (SD) time-spent for each ANC session was 16.21 (4.28) minutes. A positive correlation was identified between the length of working experience of health providers and their physical performance scores (adjusted R square = 0.017). CONCLUSIONS: The overall performance of ANC services by health care providers was inadequate in both urban and rural areas. Insufficient provision of health education and poor communication skills of health care providers were revealed. Existing IEC materials were scarcely used. Taking action to improve the quality of ANC services by training and providing specific guidelines, creating dedicated rooms, and providing sufficient and effective materials for counseling are all greatly needed in public health facilities in Laos.

Treatment-seeking behaviour for febrile illnesses and its implications for malaria control and elimination in Savannakhet Province, Lao PDR (Laos): a mixed method study.

BACKGROUND: How people respond to febrile illness is critical to malaria prevention, control, and ultimately elimination. This article explores factors affecting treatment-seeking behaviour for febrile illnesses in a remote area of Lao PDR. METHODS: Household heads or their representatives (n = 281) were interviewed using a structured questionnaire. A total of twelve focus group discussions (FGDs) each with eight to ten participants were conducted in four villages. In addition, observations were recorded as field notes (n = 130) and were used to collect information on the local context, including the treatment seeking behaviour and the health services. RESULTS: Almost three-quarters (201/281) of respondents reported fever in past two months. Most (92%, 185/201) sought treatment of which 80% (149/185) sought treatment at a health centre. Geographic proximity to a health centre (AOR = 6.5; CI = 1.74-24.25; for those < 3.5 km versus those > 3.6 km) and previous experience of attending a health centre (AOR = 4.7; CI = 1.2-19.1) were strong predictors of visiting a health centre for febrile symptoms. During FGDs, respondents described seeking treatment from traditional healers and at health centre for mild to moderate illnesses. Respondents also explained how if symptoms, including fever, were severe or persisted after receiving treatment elsewhere, they sought assistance at health centres. Access to local health centres/hospitals was often constrained by a lack of transportation and an ability to meet the direct and indirect costs of a visit. CONCLUSION: In Nong District, a rural area bordering Vietnam, people seek care from health centres offering allopathic medicine and from spiritual healers. Decisions about where and when to attend health care depended on their economic status, mobility (distance to the health centre, road conditions, availability of transport), symptoms severity and illness recognition. Current and future malaria control/elimination programmes could benefit from greater collaboration with the locally accessible sources of treatments, such as health volunteers and traditional healers.

Prevalence of malaria in pregnancy in southern Laos: a cross-sectional survey.

BACKGROUND: There are no data on the burden of malaria in pregnancy (MiP) in Laos, where malaria still remains prevalent in the south. METHODS: Two cross-sectional surveys were conducted in 2014 to assess the prevalence of MiP in Vapi District, Salavan Province, southern Laos: the first consisted of screening 204 pregnant women during pregnancies [mean (95 % CI) gestational age: 23 (22-25) weeks] living in 30 randomly selected villages in Vapi District; the second was conducted among 331 pregnant women, who delivered during the study period in Vapi and Toumlane District Hospitals and in Salavan Provincial Hospital. Peripheral and placental malaria was detected using rapid diagnostic tests (RDT), thick blood smears (TBS) and real-time quantitative polymerase chain reactions (RT-qPCR). Factors associated with low birth weight (LBW) and maternal anaemia were assessed. RESULTS: In the villages, 12/204 women (5.9 %; 95 % CI 3.1-10.0) were infected with malaria as determined by RT-qPCR: 11 were Plasmodium vivax infections and 1 was mixed Plasmodium vivax/Plasmodium falciparum infection, among which 9 were sub-microscopic (as not detected by TBS). History of malaria during current pregnancy tended to be associated with a higher risk of MiP (aIRR 3.05; 95 % CI 0.94-9.88). At delivery, two Plasmodium falciparum sub-microscopic infections (one peripheral and one placental) were detected (4.5 %; 0.6-15.5) in Vapi District. In both surveys, all infected women stated they had slept under a bed net the night before the survey, and 86 % went to the forest for food-finding 1 week before the survey in median. The majority of infections (94 %) were asymptomatic and half of them were associated with anaemia. Overall, 24 % of women had LBW newborns. Factors associated with a higher risk of LBW were tobacco use (aIRR 2.43; 95 % CI 1.64-3.60) and pre-term delivery (aIRR 3.17; 95 % CI 2.19-4.57). Factors associated with a higher risk of maternal anaemia were no iron supplementation during pregnancy, Lao Theung ethnicity and place of living. CONCLUSIONS: The prevalence of MiP in this population was noticeable. Most infections were asymptomatic and sub-microscopic vivax malaria, which raises the question of reliability of recommended national strategies for the screening and prevention of MiP in Laos.

Thiamin supplementation does not reduce the frequency of adverse events after anti-malarial therapy among patients with falciparum malaria in southern Laos.

BACKGROUND: In a recent study one third of Lao patients presenting with uncomplicated Plasmodium falciparum malaria had biochemical evidence of thiamin deficiency, which was associated with a higher incidence of adverse events. Thiamin supplementation might, therefore, reduce adverse events in this population. METHODS: An exploratory, double-blind, parallel group, placebo-controlled, superiority trial of thiamin supplementation in patients of all ages with uncomplicated and severe falciparum malaria was conducted in Xepon District, Savannakhet Province, southern Laos. Patients were randomly assigned to either oral thiamin 10 mg/day for 7 days immediately after standard anti-malarial treatment then 5 mg daily until day 42, or identical oral placebo. RESULTS: After interim analyses when 630 patients (314 in thiamin and 316 in placebo groups) had been recruited, the trial was discontinued on the grounds of futility. On admission biochemical thiamin deficiency (alpha ≥ 25%) was present in 27% of patients and 9% had severe deficiency (alpha > 31%). After 42 days of treatment, the frequency of thiamin deficiency was lower in the thiamin (2%, 1% severe) compared to the placebo (11%, 3% severe) groups (p < 0.001 and p = 0.05), respectively. Except for diarrhoea, 7% in the placebo compared to 3% in the thiamin group (p = 0.04), and dizziness on day 1 (33% vs 25%, p = 0.045), all adverse events were not significantly different between the groups (p > 0.05). Clinical, haematological, and parasitological responses to treatment did not differ significantly between the two groups. CONCLUSION: Thiamin supplementation reduced biochemical thiamin deficiency among Lao malaria patients following anti-malarial drug treatment, but it did not reduce the frequency of adverse events after anti-malarial therapy or have any detected clinical or parasitological impact. TRIAL REGISTRATION: ISRCTN 85411059.

Efficacy of artemether-lumefantrine, the nationally-recommended artemisinin combination for the treatment of uncomplicated falciparum malaria, in southern Laos.

BACKGROUND: The Lao Government changed the national policy for uncomplicated Plasmodium falciparum malaria from chloroquine to artemether-lumefantrine (AL) in 2005. Since then, no information on AL efficacy has been reported. With evidence of resistance to artemisinin derivatives in adjacent Cambodia, there has been a concern as to AL efficacy. Monitoring of AL efficacy would help the Lao Government to make decisions on appropriate malaria treatment. METHODS: The efficacy of a three-day, twice daily oral artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Xepon District, Savannakhet Province, southern Laos was studied over 42 days follow-up. This was part of a trial of thiamin supplementation in falciparum malaria. RESULTS: Of 630 patients with P. falciparum enrolled in the trial of thiamin treatment, 549 (87%, 357 children ≤15 years and 192 adults) were included in this study. The per protocol 42-day cure rates were 97% (524/541) [96% (337/352) for children and 99% (187/189) for adults, p = 0.042]. By conventional intention-to-treat analysis, the 42-day cure rates adjusted for re-infection, were 97% (532/549) [96% (342/357) in children and 99% (190/192) in adults, p = 0.042]. The proportion of patients who remained parasitaemic at day 1 after treatment was significantly higher in children [33% (116/356)] compared to adults [15% (28/192)] (p < 0.001) and only one adult patient had detectable parasitaemia on day 2. There were no serious adverse events. Potential side effects after treatment were reported more commonly in adults (32%) compared to children (15%) (p < 0.001). Patients with recrudescent infections were significantly younger, had longer mean time to fever clearance, and had longer median time to parasite clearance compared to those who were cured. CONCLUSIONS: The current nationally-recommended anti-malarial treatment (artemether-lumefantrine) remains highly efficacious for the treatment of uncomplicated falciparum malaria five years after introduction in Laos. Regular monitoring is required in case artemisinin-resistant P. falciparum parasites should appear. TRIAL REGISTRATION: ISRCTN85411059.

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.

A randomized comparison of oral chloramphenicol versus ofloxacin in the treatment of uncomplicated typhoid fever in Laos.

We conducted a randomized open trial of oral chloramphenicol (50mg/kg/day in four divided doses for 14 days) versus ofloxacin (15 mg/kg/day in two divided doses for 3 days) in 50 adults with culture-confirmed uncomplicated typhoid fever in Vientiane, Laos. Patients had been ill for a median (range) of 8 (2-30) days. All Salmonella enterica serotype typhi isolates were nalidixic acid-sensitive, four (8%) were chloramphenicol-resistant and three (6%) were multidrug-resistant. Median (range) fever clearance times were 90 (24-224) hours in the chloramphenicol group and 54 (6-93) hours in the ofloxacin group (P<0.001). One patient in the chloramphenicol group developed an ileal perforation. Three days ofloxacin was more effective than 14 days chloramphenicol for the in-patient treatment of typhoid fever, irrespective of antibiotic susceptibility, and was of similar cost.

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.