Search

Abstract Background The area along the Thai-Cambodian border is considered an epicenter of anti-malarial drug resistance. Recently, parasite resistance to artemisinin-based therapies has been reported in the area. The artemisinin resistance containment project was initiated in November 2008, with the aim to limit resistant parasites and eliminate malaria in this region. This study describes the response to artemisinin-based therapy among falciparum malaria patients in the area, using data from the malaria surveillance programmed under the containment project. Methods The study was conducted in seven provinces of Thailand along the Thai-Cambodian border. Data of Plasmodium falciparum-positive patients during January 2009 to December 2011 were obtained from the electronic malaria information system (eMIS) Web-based reporting system. All P. falciparum cases were followed for 42 days, as the routine case follow-up protocol. The demographic characteristics of the patients were described. Statistical analysis was performed to determine the cure rate of the current standard anti-malarial drug regimen--mefloquine-artesunate combination therapy (MAS). The proportion of patients who remained parasite-positive at each follow-up day was calculated. In addition, factors related to the delayed parasite clearance on day-3 post-treatment, were explored. Results A total of 1,709 P. falciparum-positive cases were reported during the study period. Almost 70% of falciparum cases received MAS therapy (n = 1,174). The majority of cases were males, aged between 31 and 50 years. The overall MAS cure rate was >90% over the three-year period. Almost all patients were able to clear the parasite within 7 to 14 days post-treatment. Approximately 14% of patients undergoing MAS remained parasite-positive on day-3. Delayed parasite clearance was not significantly associated with patient gender, age, or citizenship. However, delayed parasite clearance varied across the study area. Conclusion Anti-malarial drug-resistant parasites should be closely monitored in the area along the Thai-Cambodian border. Although the MAS cure rate in this study area was above 90%, an increasing trend of treatment failure has been reported in neighboring parts. Effective malaria surveillance is an important component to monitor drug-resistance in the malaria containment project.

Abstract Background There is concern that artesunate resistance is developing in Southeast Asia. The purpose of this study is to investigate the prevalence of parasitaemia in the few days following treatment with artesunate-mefloquine (AM), which is an indirect measure of decreased artesunate susceptibility. Methods This is a retrospective analysis of 31 therapeutic efficacy studies involving 1,327 patients treated with AM conducted by the Thai National Malaria Control Programme from 1997–2007. Results The prevalence of patients with parasitaemia on day 2 was higher in the east compared to the west (east: 20%, west: 9%, OR 2.47, 95% CI: 1.77, 3.45). In addition, the prevalence of day-2 parasitaemia increased over time (OR for each year = 1.10, 95% CI: 1.03, 1.19). After controlling for initial parasitaemia and age, year and region remained important determinants of day-2 parasitaemia (OR for region = 3.98, 95%CI 2.63, 6.00; OR for year = 1.28, 95%CI: 1.17, 1.39). The presence of parasitaemia on day 2 and day 3 were specific, but not sensitive predictors of treatment failure. Discussion Delayed resolution of parasitaemia after AM treatment increased in eastern Thailand between 1997 and 2007, which may be an early manifestation of decreased artesunate susceptibility. However, clinical and parasitological treatment failure after 28 days (which is related to both mefloquine and artesunate decreased susceptibility) is not changing over time. The presence of parasitaemia on day 2 is a poor indicator of AM 28-day treatment failure.

This study examined the prevalence, availability, and use of antimalarial medicines (AMLs) along the Thai-Cambodian border. The study was divided into two parts: the first looked at the quality of AMLs available in six Thai provinces and the second obtained information about the availability and use of AMLs. A randomized sampling methodology was used to select locations and collect samples, which were screened using Global Pharma Health Fund (GPHF) Minilabs. A subset of samples was sent to quality control laboratories for verification testing. For the second part of the study, face-to-face interviews were conducted with members of randomly selected households and the staff of health facilities in villages with the highest malaria incidence to find out where they acquired their AMLs and which were used most frequently. The results of quality testing showed an overall failure rate of 1% (7 of 709 samples) for active pharmaceutical ingredients (API); however, the API failure rate varied from 0.0% to 2.2% by location and the overall failure rates of samples by province varied from 0.0% to 3.4%. A total of 97.9% (n = 272) of respondents had taken AMLS. The most commonly used medicines were primaquine (30% of respondents), chloroquine (15.8%), artesunate+mefloquine (12%), and quinine (10%). Most respondents (97.9%) had received medications from public hospitals or malaria clinics.

The informed consent process has become a universal requirement for research involving human subjects. Its goal is to inform volunteers regarding research in order to make decision to participate or not. This study aimed to measure volunteers' comprehension levels concerning the clinical trial and to find out factors associated with that comprehension levels. Eighty-one volunteers who enrolled in a malaria clinical trial were recruited into the study. A semi-structured questionnaire was used to collect the information. Non-participant observation was used to observe the process of informed consent. Volunteers were interviewed three days after being recruited into the trial. The results show the volunteers' comprehension was low. Only 44% of volunteers had an acceptable level of comprehension. It also revealed that 20 volunteers were not aware of being volunteers. Most volunteers knew about the benefits of participating in the trial and realized that they had the right to withdraw from the study, but not many knew about the risks of the trial. The results indicated the method of informing about the trial affected the volunteers' comprehension level. No relationship was found between comprehension level and volunteers' socio-demographic characteristics and their attitude toward the consent process. The findings from this study demonstrate volunteers who participated in the clinical trial were not truly informed. Further studies regarding enhancing volunteers' understanding of the trial are needed.

Substandard and counterfeit pharmaceutical products, including antimalarial drugs, appear to be widespread internationally and affect both the developing and developed countries. The aim of the study was to investigate the quality of antimalarial drugs, ie, artesunate (ART), chloroquine (CHL), mefloquine (MEF), quinine (QUI), sulfadoxine/pyrimethamine (S/P) and tetracycline (TT) obtained from the government sector and private pharmacies in 4 Thai provinces: Mae Hong Son, Kanchanaburi, Ranong, and Chanthaburi. Three hundred sixty-nine samples of 6 antimalarial drugs from 27 government hospitals, 27 malaria clinics, and 53 drugstores, were collected. Drug quality was assessed by simple disintegration test and semi-quantitative thin-layer chromatography in each province; 10% passed, 100% failed and doubtful samples were sent to be verified by high performance liquid chromatography (HPLC) at the Thai National Drug Analysis Laboratory, (NL). Fifteen point four percent of ART, 11.1% of CHL and 29.4% of QUI were substandard. Based on the finding, drug regulatory authorities in the country took appropriate action against violators to ensure that antimalarial drugs consumed by malaria patients are of good quality.

Mefloquine sensitivity of Plasmodium falciparum along the Thai-Myanmar border, both in vitro and in vivo, following different first-line treatments for uncomplicated falciparum malaria patients in these areas during the period 1997--2003 were studied. Standard in vitro micro tests and in vivo efficacy according to World Health Organization methodologies were performed. P. falciparum isolates along the Thai-Myanmar border with in vitro sensitivity to mefloquine have had up to a ten-fold decrease in sensitivity compared to a baseline done in 1986, conducted one year after the drug was first introduced to Thailand. The reduction in the mefloquine sensitivity of P. falciparum isolates in Tak Province developed rapidly, with the highest IC50 of 1,254 nM in 1997. The IC50 declined to 1,067 and 737 nM in 1999 and 2001, respectively, but there was no statistically significant difference in the sensitivity. The sensitivity of P. falciparum isolates from Mae Hong Son, Kanchanaburi, and Ranong, where the first line treatment was mefloquine 15 mg/kg single dose, continued to decline, where in 2001 the IC50 were 1,087, 941, and 1,116 nM, respectively, in these provinces. The difference in sensitivities of P. falciparum isolates in Mae Hong Son and Ranong in 2001, compared to 1997, was statistically significant (p<0.05). Good therapeutic efficacy of the artesunate-mefloquine combination in Tak Province was observed. Adequate clinical responses (ACR) were 89.5% and 92.3% in 1997 and 2002, respectively. The efficacy of mefloquine alone in Mae Hong Son, Kanchanaburi, and Ranong has significantly dropped. ACR in 1997 and 2001 in Mae Hong Son were 87.8% and 73.2%, respectively, in Kanchanaburi were 82% and 59.6%, respectively, and in Ranong were 96% and 31.6%, respectively.

In an expansion of the first Mekong Malaria monograph published in 1999, this second monograph updates the malaria database in the countries comprising the Mekong region of Southeast Asia. The update adds another 3 years' information to cover cumulative data from the 6 Mekong countries (Cambodia, China/Yunnan, Lao PDR, Myanmar, Thailand, Viet Nam) for the six-year period 1999-2001. The objective is to generate a more comprehensive regional perspective in what is a global epicenter of drug resistant falciparum malaria, in order to improve malaria control on a regional basis in the context of social and economic change. The further application of geographical information systems (GIS) to the analysis has underscored the overall asymmetry of disease patterns in the region, with increased emphasis on population mobility in disease spread. Of great importance is the continuing expansion of resistance of P. falciparum to antimalarial drugs in common use and the increasing employment of differing drug combinations as a result. The variation in drug policy among the 6 countries still represents a major obstacle to the institution of region-wide restrictions on drug misuse. An important step forward has been the establishment of 36 sentinel sites throughout the 6 countries, with the objective of standardizing the drug monitoring process; while not all sentinel sites are fully operational yet, the initial implementation has already given encouraging results in relation to disease monitoring. Some decreases in malaria mortality have been recorded. The disease patterns delineated by GIS are particularly instructive when focused on inter-country distribution, which is where more local collaborative effort can be made to rationalize resource utilization and policy development. Placing disease data in the context of socio-economic trends within and between countries serves to further identify the needs and the potential for placing emphasis on resource rationalization on a regional basis. Despite the difficulties, the 6-year time frame represented in this monograph gives confidence that the now well established collaboration is becoming a major factor in improving malaria control on a regional basis and hopefully redressing to a substantial degree the key problem of spread of drug resistance regionally and eventually globally.