Deployment of Early Diagnosis and Mefloquine- Artesunate Treatment of Falciparum Malaria in Thailand: The Tak Malaria Initiative

BACKGROUND: Early diagnosis and treatment with artesunate-mefloquine combination therapy (MAS) have reduced the transmission of falciparum malaria dramatically and halted the progression of mefloquine resistance in camps for displaced persons along the Thai-Burmese border, an area of low and seasonal transmission of multidrug-resistant Plasmodium falciparum. We extended the same combination drug strategy to all other communities (estimated population 450,000) living in five border districts of Tak province in northwestern Thailand. METHODS AND FINDINGS: Existing health structures were reinforced. Village volunteers were trained to use rapid diagnostic tests and to treat positive cases with MAS. Cases of malaria, hospitalizations, and malaria-related deaths were recorded in the 6 y before, during, and after the Tak Malaria Initiative (TMI) intervention. Cross-sectional surveys were conducted before and during the TMI period. P. falciparum malaria cases fell by 34% (95% confidence interval [CI], 33.5–34.4) and hospitalisations for falciparum malaria fell by 39% (95% CI, 37.0–39.9) during the TMI period, while hospitalisations for P. vivax malaria remained constant. There were 32 deaths attributed to malaria during, and 22 after the TMI, a 51.5% (95% CI, 39.0–63.9) reduction compared to the average of the previous 3 y. Cross-sectional surveys indicated that P. vivax had become the predominant species in Thai villages, but not in populations living on the Myanmar side of the border. In the displaced persons population, where the original deployment took place 7 y before the TMI, the transmission of P. falciparum continued to be suppressed, the incidence of falciparum malaria remained low, and the in vivo efficacy of the 3-d MAS remained high. CONCLUSIONS: In the remote malarious north western border area of Thailand, the early detection of malaria by trained village volunteers, using rapid diagnostic tests and treatment with mefloquine-artesunate was feasible and reduced the morbidity and mortality of multidrug-resistant P. falciparum

Thiamine Diphosphate in Whole Blood, Thiamine and Thiamine Monophosphate in Breast-Milk in a Refugee Population

BACKGROUND: The provision of high doses of thiamine may prevent thiamine deficiency in the post-partum period of displaced persons. METHODOLOGY/PRINCIPAL FINDINGS: The study aimed to evaluate a supplementation regimen of thiamine mononitrate (100 mg daily) at the antenatal clinics in Maela refugee camp. Women were enrolled during antenatal care and followed after delivery. Samples were collected at 12 weeks post partum. Thiamine diphosphate (TDP) in whole blood and thiamine in breast-milk of 636 lactating women were measured. Thiamine in breast-milk consisted of thiamine monophosphate (TMP) in addition to thiamine, with a mean TMP to total thiamine ratio of 63%. Mean whole blood TDP (130 nmol/L) and total thiamine in breast-milk (755 nmol/L) were within the upper range reported for well-nourished women. The prevalence of women with low whole blood TDP (<65 nmol/L) was 5% and with deficient breast-milk total thiamine (<300 nmol/L) was 4%. Whole blood TDP predicted both breast-milk thiamine and TMP (R(2) = 0.36 and 0.10, p<0.001). A ratio of TMP to total thiamine ≥63% was associated with a 7.5 and 4-fold higher risk of low whole blood TDP and deficient total breast-milk thiamine, respectively. Routine provision of daily 100 mg of thiamine mononitrate post-partum compared to the previous weekly 10 mg of thiamine hydrochloride resulted in significantly higher total thiamine in breast-milk. CONCLUSIONS/SIGNIFICANCE: Thiamine supplementation for lactating women in Maela refugee camp is effective and should be continued. TMP and its ratio to total thiamine in breast-milk, reported for the first time in this study, provided useful information on thiamine status and should be included in future studies of breast-milk thiamine

Micronutrient status in lactating mothers before and after introduction of fortified flour: cross-sectional surveys in Maela refugee camp

Background Deficiency of micronutrients is common in refugee populations. Objectives Identify deficiencies and whether provided supplements and wheat flour fortified with 10 micronutrients impacts upon status among breast-feeding women from Maela refugee camp. Methods Two sequential cross-sectional studies were conducted in different groups of lactating mothers at 12 weeks postpartum. The first survey was before and the second 4-5 months after micronutrient fortified flour (MFF) had been provided to the camp (in addition to the regular food basket). Iron status and micronutrients were measured in serum, whole blood, and in breast milk samples. Results Iron and zinc deficiency and anemia were highly prevalent while low serum retinol and thiamine deficiency were rarely detected. Iron and zinc deficiency were associated with anemia, and their proportions were significantly lower after the introduction of MFF (21 vs. 35% with soluble transferrin receptor (sTfR)>8.5 mg/L, P = 0.042, and 50 vs. 73% with serum zinc<0.66 mg/L, P = 0.001). Serum sTfR, whole-blood thiamine diphosphate (TDP) and serum β-carotene were significant predictors (P<0.001) of milk iron, thiamine and β-carotene, respectively. Lower prevalence of iron deficiency in the MFF group was associated with significantly higher iron and thiamine in breast milk. Conclusions High whole-blood TDP and breast milk thiamine reflected good compliance to provided thiamine; high prevalence of iron deficiency suggested insufficient dietary iron and low acceptance to ferrous sulfate supplements. MFF as an additional food ration in Maela refugee camp seemed to have an effect in reducing both iron and zinc deficiency postpartum. © Springer-Verlag 2012

Changes in the Treatment Responses to Artesunate-Mefloquine on the Northwestern Border of Thailand during 13 Years of Continuous Deployment

Background: Artemisinin combination treatments (ACT) are recommended as first line treatment for falciparum malaria throughout the malaria affected world. We reviewed the efficacy of a 3-day regimen of mefloquine and artesunate regimen (MAS ), over a 13 year period of continuous deployment as first-line treatment in camps for displaced persons and in clinics for migrant population along the Thai-Myanmar border. Methods and Findings: 3,264 patients were enrolled in prospective treatment trials between 1995 and 2007 and treated with MAS. The proportion of patients with parasitaemia persisting on day-2 increased significantly from 4.5% before 2001 to 21.9% since 2002 (p<0.001). Delayed parasite clearance was associated with increased risk of developing gametocytaemia (AOR = 2.29; 95% CI, 2.00-2.69, p = 0.002). Gametocytaemia on admission and carriage also increased over the years (p = 0.001, test for trend, for both). MAS efficacy has declined slightly but significantly (Hazards ratio 1.13; 95% CI, 1.07-1.19, p<0.001), although efficacy in 2007 remained well within acceptable limits: 96.5% (95% CI, 91.0-98.7). The in vitro susceptibility of P. falciparum to artesunate increased significantly until 2002, but thereafter declined to levels close to those of 13 years ago (geometric mean in 2007: 4.2 nM/l; 95% CI, 3.2-5.5). The proportion of infections caused by parasites with increased pfmdr1 copy number rose from 30% (12/ 40) in 1996 to 53% (24/45) in 2006 (p = 0.012, test for trend). Conclusion: Artesunate-mefloquine remains a highly efficacious antimalarial treatment in this area despite 13 years of widespread intense deployment, but there is evidence of a modest increase in resistance. Of particular concern is the slowing of parasitological response to artesunate and the associated increase in gametocyte carriage. © 2009 Carrara et al

Whole blood TDP and thiamine, TMP and total thiamine in breast-milk of women with a low (<63%) compared to those with a high (≥63%) TMP to total thiamine ratio ^1–3.

1<p>WB TDP, whole blood thiamine diphosphate.</p>2<p>TMP, thiamine monophosphate.</p>3<p>Total thiamine, sum of thiamine and TMP.</p

Risk factors for deficient breast-milk total thiamine (<300 nmol/L; n = 26/636) and low whole blood TDP (<65 nmol/L; n = 31/636)^1–3.

1<p>Total thiamine, sum of TMP and thiamine.</p>2<p>WB TDP, whole blood thiamine diphosphate.</p>3<p>TMP, thiamine monophosphate.</p

Multivariate linear regression analysis on TDP in whole blood and thiamine, TMP, and total thiamine in breast-milk, <i>N</i> = 636^1–6.

1<p>Independent predictors are listed in the order they were entered in the forward models.</p>2<p>Indicates the increase in outcome per unit increase in risk factor.</p>3<p>WB TDP, whole blood thiamine diphosphate.</p>4<p>SR, Square root.</p>5<p>TMP, thiamine monophosphate.</p>6<p>Total thiamine, sum of thiamine and TMP.</p

Thiamine and thiamine monophosphate (TMP) in breast-milk by quartiles of whole blood thiamine diphosphate (TDP).

<p>Thiamine and thiamine monophosphate (TMP) in breast-milk by quartiles of whole blood thiamine diphosphate (TDP).</p

Characteristics of the study population, whole blood TDP and breast-milk thiamine at 12 weeks post partum ^1–6.

1<p>Median (interquartile range), all such values.</p>2<p>Days of provided thiamine mononitrate (daily 100 mg).</p>3<p>Mean and standard deviation, all such values.</p>4<p>TDP/Hb, thiamine diphosphate per hemoglobin.</p>5<p>Geometric mean (95% confidence interval), all such values.</p>6<p>Total thiamine, sum of thiamine and thiamine monophosphate (TMP).</p

Technical evaluation and usability of a quantitative G6PD POC test in cord blood: a mixed-methods study in a low-resource setting

Objectives New point-of-care (POC) quantitative G6PD testing devices developed to provide safe radical cure for Plasmodium vivax malaria may be used to diagnose G6PD deficiency in newborns at risk of severe neonatal hyperbilirubinaemia, improving clinical care, and preventing related morbidity and mortality. Methods We conducted a mixed-methods study analysing technical performance and usability of the ‘STANDARD G6PD’ Biosensor when used by trained midwives on cord blood samples at two rural clinics on the Thailand–Myanmar border. Results In 307 cord blood samples, the Biosensor had a sensitivity of 1.000 (95% CI: 0.859 to 1.000) and a specificity of 0.993 (95% CI: 0.971 to 0.999) as compared with gold-standard spectrophotometry to diagnose G6PD-deficient newborns using a receiver operating characteristic (ROC) analysis-derived threshold of ≤4.8 IU/gHb. The Biosensor had a sensitivity of 0.727 (95% CI: 0.498 to 0.893) and specificity of 0.933 (95% CI: 0.876 to 0.969) for 30%–70% activity range in girls using ROC analysis-derived range of 4.9–9.9 IU/gHb. These thresholds allowed identification of all G6PD-deficient neonates and 80% of female neonates with intermediate phenotypes. Need of phototherapy treatment for neonatal hyperbilirubinaemia was higher in neonates with deficient and intermediate phenotypes as diagnosed by either reference spectrophotometry or Biosensor. Focus group discussions found high levels of learnability, willingness, satisfaction and suitability for the Biosensor in this setting. The staff valued the capacity of the Biosensor to identify newborns with G6PD deficiency early (‘We can know that early, we can counsel the parents about the chances of their children getting jaundice’) and at the POC, including in more rural settings (‘Because we can know the right result of the G6PD deficiency in a short time, especially for the clinic which does not have a lab’). Conclusions The Biosensor is a suitable tool in this resource-constrained setting to identify newborns with abnormal G6PD phenotypes at increased risk of neonatal hyperbilirubinaemia