Implementation and success factors from Thailand's 1-3-7 surveillance strategy for malaria elimination.

Thailand's National Malaria Elimination Strategy 2017-2026 introduced the 1-3-7 strategy as a robust surveillance and response approach for elimination that would prioritize timely, evidence-based action. Under this strategy, cases are reported within 1 day, cases are investigated within 3 days, and foci are investigated and responded to within 7 days, building on Thailand's long history of conducting case investigation since the 1980s. However, the hallmark of the 1-3-7 strategy is timeliness, with strict deadlines for reporting and response to accelerate elimination. This paper outlines Thailand's experience adapting and implementing the 1-3-7 strategy, including success factors such as a cross-sectoral Steering Committee, participation in a collaborative regional partnership, and flexible local budgets. The programme continues to evolve to ensure prompt and high-quality case management, capacity maintenance, and adequate supply of lifesaving commodities based on surveillance data. Results from implementation suggest the 1-3-7 strategy has contributed to Thailand's decline in malaria burden; this experience may be useful for other countries aiming to eliminate malaria.

The Evolution of the Malaria Clinic: The Cornerstone of Malaria Elimination in Thailand.

Background: Malaria Clinics (MCs) have served communities in Thailand since 1965 and are still playing a critical role in providing early diagnosis and effective treatment of malaria. Methods: We reviewed six decades of published manuscripts, articles, strategies, and plans regarding MC operations in Thailand;,and analyzed national program surveillance data in both malaria control and malaria elimination phases. Results: MCs accounted for 39.8% of malaria tests and 54.8% of positive cases by the end of the 1980s. The highest number of MCs established was 544 in 1997. MCs contributed to 6.7% of all tests and 30% of all positive cases over the 2015-2017 period. Between 2017 and June 2019, during the malaria elimination phase, MCs continued to test an average of 67% of all persons tested for malaria, and confirmed 38.3% of all positive cases detected in the country. Conclusions: Testing and positive rates of MCs are on a gradual decline as the overall burden of malaria declines annually, which may reflect decreasing transmission intensity. Although the number of MCs in the last three years has been stable (n = 240), the attrition of MC staff poses a real challenge to the longevity of MCs in the absence of a human resource plan to support the elimination phase. It is necessary to identify and support capacity gaps and needs as MCs are absorbed into an integrated and decentralized program, while ensuring that the Division of Vector Borne Diseases (DVBD) maintains its necessary technical and advisory role.

Implementation of G6PD testing and primaquine for P. vivax radical cure: Operational perspectives from Thailand and Cambodia.

Following progressive success in reducing the burden of malaria over the past two decades, countries of the Asia Pacific are now aiming for elimination of malaria by 2030. Plasmodium falciparum and Plasmodium vivax are the two main malaria species that are endemic in the region. P. vivax is generally perceived to be less severe but will be harder to eliminate, owing partly to its dormant liver stage (known as a hypnozoite) that can cause multiple relapses following an initial clinical episode caused by a mosquito-borne infection. Primaquine is the only anti-hypnozoite drug against P. vivax relapse currently available, with tafenoquine in the pipeline. However, both drugs may cause severe haemolysis in individuals with deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD), a hereditary defect. The overall incidence of malaria has significantly declined in both Thailand and Cambodia over the last 15 years. However, P. vivax has replaced P. falciparum as the dominant species in large parts of both countries. This paper presents the experience of the national malaria control programmes of the two countries, in their efforts to implement safe primaquine therapy for the radical cure, i.e. relapse prevention, of P. vivax malaria by introducing a rapid, point-of-care test to screen for G6PD deficiency.

Clinical and molecular surveillance of artemisinin resistant falciparum malaria in Myanmar (2009-2013).

BACKGROUND: Emergence of artemisinin-resistant malaria in Southeast Asian countries threatens the global control of malaria. Although K13 kelch propeller has been assessed for artemisinin resistance molecular marker, most of the mutations need to be validated. In this study, artemisinin resistance was assessed by clinical and molecular analysis, including k13 and recently reported markers, pfarps10, pffd and pfmdr2. METHODS: A prospective cohort study in 1160 uncomplicated falciparum patients was conducted after treatment with artemisinin-based combination therapy (ACT), in 6 sentinel sites in Myanmar from 2009 to 2013. Therapeutic efficacy of ACT was assessed by longitudinal follow ups. Molecular markers analysis was done on all available day 0 samples. RESULTS: True recrudescence treatment failures cases and day 3 parasite positivity were detected at only the southern Myanmar sites. Day 3 positive and k13 mutants with higher prevalence of underlying genetic foci predisposing to become k13 mutant were detected only in southern Myanmar since 2009 and comparatively fewer mutations of pfarps10, pffd, and pfmdr2 were observed in western Myanmar. K13 mutations, V127M of pfarps10, D193Y of pffd, and T448I of pfmdr2 were significantly associated with day 3 positivity (OR: 6.48, 3.88, 2.88, and 2.52, respectively). CONCLUSIONS: Apart from k13, pfarps10, pffd and pfmdr2 are also useful for molecular surveillance of artemisinin resistance especially where k13 mutation has not been reported. Appropriate action to eliminate the resistant parasites and surveillance on artemisinin resistance should be strengthened in Myanmar. Trial registration This study was registered with ClinicalTrials.gov, identifier NCT02792816.

LONGITUDINAL EVALUATION OF MALARIA EPIDEMIOLOGY IN AN ISOLATED VILLAGE IN WESTERN THAILAND: I. STUDY SITE AND ADULT ANOPHELINE BIONOMICS.

This is the first in a series of papers describing the epidemiology of malaria in an isolated village in western Thailand. The study site was the village of Kong Mong Tha, located in Sangkhla Buri District, Kanchanaburi Province, Thailand. In this paper we present an overview of the study site and results from our adult anopheline mosquito surveillance conducted over 56 consecutive months from June 1999 until January 2004. The collection site, indoor/outdoor location, parity, biting activity and Plasmodiumfalciparum (Pf) and P. vivax (Pv) infection rates were used to calculate seasonal entomological inoculation rates for the predominant four Anopheles species. A total of 21,566 anophelines representing 28 distinct species and 2 groups that were not identified to species were collected using human bait, with almost 95% of the collection consisting of Anopheles minimus, An. maculatus, An. sawadwongporni and An. barbirostris/campestris. Mosquitoes generally peaked during the wet season, were collected throughout the night, and were collected most often outside (ca. 75%) versus inside (ca. 25%) of houses. Approximately 50% of collected mosquitoes were parous. Overall Plasmodium infection rates were 0.27%, with a total of 16 and 42 pools of Pf- and Pv-positive mosquitoes, respectively. Annual EIRs were 2.3 times higher for Pv than for Pf, resulting in approximately 5.5 and 2.6 infective bites per person per year, respectively. The results suggest An. minimus and An. maculatus are the primary and secondary vectors of Pf and Pv transmission in Kong Mong Tha, while An. sawadwongporni and An. barbirostris/campestris also appear to play a role based on the presence of circumsporozoite protein (CSP) in the head/thorax of the specimens tested.

Comparison of microscopy, nested-PCR, and Real-Time-PCR assays using high-throughput screening of pooled samples for diagnosis of malaria in asymptomatic carriers from areas of endemicity in Myanmar.

Asymptomatic infection is an important obstacle for controlling disease in countries where malaria is endemic. Because asymptomatic carriers do not seek treatment for their infections, they can have high levels of gametocytes and constitute a reservoir available for new infection. We employed a sample pooling/PCR-based molecular detection strategy for screening malaria infection in residents from areas of Myanmar where malaria is endemic. Blood samples (n = 1,552) were collected from residents in three areas of malaria endemicity (Kayin State, Bago, and Tanintharyi regions) of Myanmar. Two nested PCR and real-time PCR assays showed that asymptomatic infection was detected in about 1.0% to 9.4% of residents from the surveyed areas. The sensitivities of the two nested PCR and real-time PCR techniques were higher than that of microscopy examination (sensitivity, 100% versus 26.4%; kappa values, 0.2 to 0.5). Among the three regions, parasite-positive samples were highly detected in subjects from the Bago and Tanintharyi regions. Active surveillance of residents from regions of intense malaria transmission would reduce the risk of morbidity and mitigate transmission to the population in these areas of endemicity. Our data demonstrate that PCR-based molecular techniques are more efficient than microscopy for nationwide surveillance of malaria in countries where malaria is endemic.

Containing artemisinin resistance of Plasmodium falciparum in Myanmar: achievements, challenges and the way forward.

Artemisinin resistance is a major threat to global malaria control and elimination efforts. Myanmar detected the first indication of the resistance in 2009 in the eastern part of the country, bordering Thailand. Since 2010, WHO has played a vital role in ensuring that a comprehensive programme on the containment of the resistance is in place. This paper documents achievement made in terms of output, outcomes and early impact on malaria from July 2011 to December 2013. It also identifies enabling factors to success and, most importantly, challenges awaiting the national programme and its partners.

Malaria control in Bhutan: case study of a country embarking on elimination.

BACKGROUND: Bhutan has achieved a major reduction in malaria incidence amid multiple challenges. This case study seeks to characterize the Bhutan malaria control programme over the last 10 years. METHODS: A review of the malaria epidemiology, control strategies, and elimination strategies employed in Bhutan was carried out through a literature review of peer-reviewed and grey national and international literature with the addition of reviewing the surveillance and vector control records of the Bhutan Vector-Borne Disease Control Programme (VDCP). Data triangulation was used to identify trends in epidemiology and key strategies and interventions through analysis of the VDCP surveillance and programme records and the literature review. Enabling and challenging factors were identified through analysis of socio-economic and health indicators, corroborated through a review of national and international reports and peer-review articles. FINDINGS: Confirmed malaria cases in Bhutan declined by 98.7% from 1994 to 2010. The majority of indigenous cases were due to Plasmodium vivax (59.9%) and adult males are most at-risk of malaria. Imported cases, or those in foreign nationals, varied over the years, reaching 21.8% of all confirmed cases in 2006. Strategies implemented by the VDCP are likely to be related to the decline in cases over the last 10 years. Access to malaria diagnosis in treatment was expanded throughout the country and evidence-based case management, including the introduction of artemisinin-based combination therapy (ACT) for P. falciparum, increasing coverage of high risk areas with Indoor Residual Spraying, insecticide-treated bed nets, and long-lasting insecticidal nets are likely to have contributed to the decline alongside enabling factors such as economic development and increasing access to health services. CONCLUSION: Bhutan has made significant strides towards elimination and has adopted a goal of national elimination. A major challenge in the future will be prevention and management of imported malaria infections from neighbouring Indian states. Bhutan plans to implement screening at border points to prevent importation of malaria and to targeted prevention and surveillance efforts towards at-risk Bhutanese and migrant workers in construction sites.

Malaria trends and challenges in the Greater Mekong Subregion.

This report provides an overview of the epidemiological patterns of malaria in the Greater Mekong Subregion (GMS) from 1998 to 2007, and highlights critical challenges facing national malaria control programs and partners in effort to build on their successes as they move towards malaria pre-elimination and elimination as a programmatic goal. Epidemiological data provided by malaria programs show a drastic decline in malaria deaths and confirmed malaria positive cases over the last 10 years in the GMS. More than half of confirmed malaria cases and deaths recorded in the GMS occur in Myanmar, however, reporting methods and data management are not comparable between countries despite effort made by WHO to harmonize data collection, analysis and reporting among WHO Member States. Malaria is concentrated in forested/forest-fringe areas of the region mainly along international borders providing strong rationale to develop harmonized cross-border pre-elimination programs in conjunction with national efforts. Across the Mekong Region, the declining efficacy of recommended first-line antimalarials, eg artemisinin-based combination therapies (ACTs) against falciparum malaria on the Cambodia-Thailand border, the prevalence of counterfeit and substandard antimalarial drugs, the lack of health services in general and malaria services in particular in remote settings, and the lack of information and services targeting migrants and mobile population present important barriers to reach or maintain malaria pre-elimination programmatic goals. Strengthening networking between research institutions and non-government organizations will increase knowledge-based decision and action.

Fighting malaria in Madhya Pradesh (Central India): are we losing the battle?

Malaria control in Madhya Pradesh is complex because of vast tracts of forest with tribal settlement. Fifty four million individuals of various ethnic origins, accounting for 8% of the total population of India, contributed 30% of total malaria cases, 60% of total falciparum cases and 50% of malaria deaths in the country. Ambitious goals to control tribal malaria by launching "Enhanced Malaria Control Project" (EMCP) by the National Vector Borne Disease Control Programme (NVBDCP), with the World Bank assistance, became effective in September 1997 in eight north Indian states. Under EMCP, the programme used a broader mix of new interventions, i.e. insecticide-treated bed nets, spraying houses with effective residual insecticides, use of larvivorous fishes, rapid diagnostic tests for prompt diagnosis, treatment of the sick with effective radical treatment and increased public awareness and IEC. However, the challenge is to scale up these services.A retrospective analysis of data on malaria morbidity and associated mortality reported under the existing surveillance system of the Madhya Pradesh (Central India) for the years 1996-2007 was carried out to determine the impact of EMCP on malaria morbidity and associated mortality. Analysis revealed that despite the availability of effective intervention tools for the prevention and control of malaria, falciparum malaria remains uncontrolled and deaths due to malaria have increased. Precisely, the aim of this epidemiological analysis is to draw lessons applicable to all international aid efforts, bureaucracy, policy makers and programme managers in assessing its project performance as a new Global Malaria Action Plan is launched with ambitious goal of reducing malaria and its elimination by scaling up the use of existing tools.

Estimating the burden of malaria in pregnancy: a case study from rural Madhya Pradesh, India.

BACKGROUND: Malaria in pregnancy (MiP) is inadequately researched in India, and the burden is probably much higher than current estimates suggest. This paper models the burden of MiP and associated foetal losses and maternal deaths, in rural Madhya Pradesh, India. METHODS: Number of pregnancies per year was estimated from the number of births and an estimate of pregnancies that end in foetal loss. The prevalence of MiP, risk of foetal loss attributable to MiP and case fatality rate of MiP were obtained from the literature. The estimated total number of pregnancies was multiplied by the appropriate parameter to estimate the number of MiP cases, and foetal loss and maternal deaths attributable to MiP per year. A Monte Carlo simulation sensitivity analysis was done to assess plausibility of various estimates obtained from the literature. The burden of MiP in tribal women was explored by incorporating the variable prevalence of malaria in tribal and non-tribal populations and in forested and non-forested regions within Madhya Pradesh. RESULTS: Estimates of MiP cases in rural Madhya Pradesh based on the model parameter values found in the literature ranged from 183,000-1.5 million per year, with 73,000-629,000 lost foetuses and 1,500-12,600 maternal deaths attributable to MiP. The Monte Carlo simulation gave a more plausible estimate of 220,000 MiP cases per year (inter-quartile range (IQR): 136,000-305,000), 95,800 lost foetuses (IQR: 56,800-147,600) and 1,000 maternal deaths (IQR: 650-1,600). Tribal women living in forested areas bore 30% of the burden of MiP in Madhya Pradesh, while constituting 18% of the population. CONCLUSION: Although the estimates are uncertain, they suggest MiP is a significant public health problem in rural Madhya Pradesh, affecting many thousands of women and that reducing the MiP burden should be a priority.

Early detection of malaria in an endemic area: model development.

A malaria epidemic warning system was established in Thailand in 1984 using graphs displaying the median or mean incidence of malaria over the previous five years compiled from malaria surveillance data throughout the country. This reporting mechanism is not timely enough to detect the occurrence of a malaria epidemic which usually occurs at the district level over a short period of time. An alternative method for early detection of a malaria epidemic employing the Poisson model has been proposed. The development of this early malaria epidemic detection model involved 3 steps: model specification, model validation and model testing. The model was based on data collected at the Vector Borne Disease Control Unit (VBDU) Level. The results of model testing reveal the model can detect increasing numbers of cases earlier, one to two weeks prior to reaching their highest peak of transmission. The system was tested using data from Kanchanaburi Province during 2000 to 2001. Results from model testing show the model may be used for monitoring the weekly malaria situation at the district level. The Poisson model was able to detect malaria early in a highly endemic province with a satisfactory level of prediction. As the application is essential for the malaria officers in monitoring of malaria epidemics, this early detection system was introduced into malaria epidemiological work. The model may be helpful in the decision making process, planning and budget allocation for the Malaria Control Program. The software for early malaria detection is currently implemented in several endemic areas throughout Thailand.

Strengthening of national capacity in implementation of antimalarial drug quality assurance in Thailand.

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.

Chronicle of malaria epidemics in Thailand, 1980-2000.

The occurrence of malaria epidemics in Thailand was reviewed from the malaria surveillance report of the National Malaria Control Program. The literature review revealed that the four epidemic periods recorded during 1980-2000 almost always occurred in the provinces and districts located along international borders. Malaria epidemics are caused by various factors such as: extensive population movement, multi-drug resistance development, low immune status of the population, lack of knowledge and appropriate personal protection against mosquito biting, and the re-emergence of malaria transmission in low malarious areas. Such factors can lead to changes in the parasite ratio and appearance of malaria epidemics throughout the country. Evidence related to the burden of malaria epidemics was also reviewed to identify causal factors that will be helpful in future research.

Mefloquine--its 20 years in the Thai Malaria Control Program.

Due to the deteriorating efficacy of sulfadoxine-pyrimethamine (SP or Fansidar), from the mid-1970s the Thai Malaria Control Program was actively involved in testing potential replacement drugs to be used as the primary therapy for falciparum malaria in Thailand. In 1983, a large-scale field trial of mefloquine, a long-acting antimalarial drug known for its efficacy against chloroquine- and SP-resistant Plasmodium falciparum, was initiated on the Thai-Cambodian border. The study enrolled over 60,000 patients and eventually led to the formal establishment of mefloquine as the first line drug for the treatment of uncomplicated falciparum malaria in the country. Mefloquine has played a significant role in the control of malaria in Thailand for the past two decades, initially in combination with SP, then by itself, and currently in selected areas as a partner drug in the combination therapy with artesunate. Thailand is the country with the most experience in the use of this drug in a malaria control program. We present here a review of mefloquine's pharmacology and usage in Thailand.

Trend of malaria incidence in highly endemic provinces along the Thai borders, 1991-2001.

The intercountry border areas of Thailand have high malaria receptivity and vulnerability that present numerous problems in the control of malaria transmission. This study focused on the 30 provinces of Thailand situated next to neighboring countries, which can be divided into 4 groups: the Thai-Myanmar border (10 provinces), the Thai-Cambodia border (6 provinces), the Thai-Lao border (10 provinces) and the Thai-Malaysia border (4 provinces). The purpose of the present study was to describe the pattern and trend of malaria incidence in the highly endemic provinces along the Thai borders for the 11 years from 1991 to 2001. Analysis of trends showed the distribution of malaria parasites to have shifted from a preponderance of Plasmodium falciparum to Plasmodium vivax along the western border with Myanmar, the northern border with Lao PDR and along the eastern border with Cambodia whereas the southern border with Malaysia the pattern changed from a preponderance of P. vivax to P. falciparum, since 1997. There was a significant difference in annual parasite incidence between borders and non-border districts, especially along the Thai-Myanmar and Thai-Cambodia borders. It is thus evident that all border districts should pay more attention to control of malaria transmission and the activities of the malaria surveillance system, and that monitoring and evaluation of the Thai Malaria Control Program needs to be performed consistently, including some areas where a few malaria cases were found as well as in malaria free areas.

Six-years monitoring the efficacy of the combination of artesunate and mefloquine for the treatment of uncomplicated falciparum malaria.

Plasmodium falciparum in Thailand is multi-drug resistant. In a previous study it was shown that artesunate and mefloquine were effective, as follow up, we monitored the efficacy of this regimen for six years. During 1997-2002, 516 adult male volunteer patients in Chanthaburi Province were enrolled (50 patients in the first year, 400 patients in 1998-2001 and 66 patients in 2002). The symptom complex and parasite count (thick blood film) were monitored on days 0, 1, 2, 7, 14, 21, 28, 35 and 42. The dosages used were artesunate (ATS) 150 mg and mefloquine (M) 750 mg at hour 0 and ATS 100 mg and M 500 mg at hour 24. Their ages ranged from 30-35 years and their mean body weights were 54-56 kg. The presenting symptoms were fever 100%, headache 97-100%, anorexia 78-90%, and nausea 28-40%. The geometric mean of parasitemia ranged from 7,357-12,750/mm3. Defervescence in one day was found in 42-76% of patients and 85-100% in 2 days. The sensitivity (S) ranged from 87-94% and RI resistance (recrudescence) ranged from 6-13%. Forty patients demonstrated RI type of response, 37 were cured after being retreated with the same dosage and another 3 patients were cured after the third course of treatment. The aggravated adverse effects included vomiting (8-20%), anorexia (1-41%) and diarrhea (0-16%). These side effects were mild and transient. The efficacy of the artesunate and mefloquine combination for the treatment of uncomplicated falciparum malaria was high. The RI type of response was possibly due to re-infection or multiple broods and not to drug resistance. The adverse effects of anorexia, nausea, vomiting and diarrhea were mild and transient for mefloquine. The combination can be used as stand by treatment in areas of multi-drug resistant falciparum malaria.

Mekong malaria. II. Update of malaria, multi-drug resistance and economic development in the Mekong region of Southeast Asia.

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.

Comparison of field and expert laboratory microscopy for active surveillance for asymptomatic Plasmodium falciparum and Plasmodium vivax in western Thailand.

Microscopy of Giemsa-stained thick and thin films by a skilled microscopist has remained the standard laboratory method for the diagnosis of malaria. However, diagnosis of malaria with this method is problematic since interpretation of results requires considerable expertise, particularly at low parasite levels. We compared the efficacy of "field" and "expert laboratory" microscopy for active surveillance of Plasmodium falciparum and P. vivax in western Thailand. Field microscopy consisted of an approximately five-minute read (50-100 fields) of a thick film at x700 using a natural light source, whereas expert laboratory microscopy consisted of a 20-minute read (number of parasites per 500 leukocytes) at x1,000 using a high-quality, well-maintained microscope with an artificial light source. All discordant and 20% of concordant results were cross-checked blindly. A total of 3,004 blood films collected between May and November 2000 were included in the study, of which 156 (5.2%) were positive for P. falciparum, 177 (5.9%) for P. vivax, and 4 (0.1%) for both P. falciparum and P. vivax by expert microscopy. A total of 84.4% (135 of 160) of the P. falciparum-positive slides and 93.9% of the P. vivax-positive slides had a parasitemia of less than 500/microL. Field microscopy was specific (99.3%) but not sensitive (10.0%) for the diagnosis of P. falciparum malaria, with a positive predictive value (PPV) of 43.2% and a negative predictive value (NPV) of 95.1%. The corresponding specificity and sensitivity for the diagnosis of P. vivax malaria were 99.2% and 7.1%, respectively, with a PPV of 38.7% and an NPV of 93.9%. Field microscopy, as defined in this study, is not an effective method for active malaria surveillance in western Thailand, where prevalence and parasitemia rates are low.

In vitro activity of tafenoquine alone and in combination with artemisinin against Plasmodium falciparum.

Emergence and spread of drug-resistant falciparum malaria has created an urgent demand for alternative therapeutic agents. This study was conducted to assess the in vitro blood schizontocidal activity of tafenoquine, the most advanced candidate drug of the 8-aminoquinolines, and of its 1:1 combination with artemisinin in fresh isolates of Plasmodium falciparum in an area with multi-drug resistance, measuring the inhibition of schizont maturation. In 43 successfully tested parasite isolates, the mean effective concentrations (ECs) of tafenoquine were 209 nmol/L for the EC50, and 1,414 nmol/L for the EC90. Tafenoquine showed no significant activity relationships with mefloquine, artemisinin, and chloroquine. With quinine, a highly significant activity relationship was observed at the EC50, but not at the EC90. The EC50, and EC90 of the tafenoquine-artemisinin combination were 15.9 nmol/L and 84.3 nmol/L. The combination was synergistic. Tafenoquine appears to be a promising candidate for treating multidrug-resistant falciparum malaria, especially in combination with artemisinin derivatives.