A comparison of three malaria diagnostic tests, under field conditions in North-west Thailand.

A hospital-based trial to compare the clinical diagnosis of malaria; microscopy, and a rapid diagnostic antigen capture detection dipstick (ParaSight-F) was conducted in North-west Thailand. 301 people who presented themselves at the hospital were selected. 204 (68%) were presumptively diagnosed as having malaria by the triage nurses; 64 (21.3%) were P. falciparum parasite positive, and 94 (32%) tested positive for P. falciparum with the ParaSight-F test strips. There was no association between hemoglobin levels (<10g/dl and > or = 10g/dl) and malaria, and although there was a good statistical association between temperature and malaria the specificity, sensitivity and positive predictive values were all low, indicating that temperature alone is a poor indicator of the disease. Based on the microscopy results, we found that a presumptive clinical diagnosis dramatically over-diagnosed malaria, and similarly there were a large number of false positives using the ParaSight-F test. We believe that many of the patients had received some form of malaria treatment prior to presentation at the hospital, and that the high number of false positives are explained by persistent antigenemia and the possibility of there being sequestered parasites following incomplete chemotherapy.

A comparative study of artesunate and artemether in combination with mefloquine on multidrug resistant falciparum malaria in eastern Thailand.

Plasmodium falciparum in Thailand is highly resistant to chloroquine, sulfadoxine-pyrimethamine and there is increasing resistance to quinine and mefloquine. The use of qinghaosu derivatives alone or in combination with mefloquine has been shown successfully effective against multidrug resistant P. falciparum in many clinical trials. However their applications with ambulatory treatment should be assessed. 394 uncomplicated falciparum malaria cases studied at Trat and Chanthaburi malaria clinics, eastern Thailand, were allocated at random to receive either one of the seven following regimens: A) artesunate 600 mg over 2 days and mefloquine 1,250 mg in divided doses. B) artemether 640 mg over 2 days and mefloquine 1,250 mg in divided doses. C) artesunate alone 700 mg over 5 days period. D) artemether alone 800 mg over 5 days period. E) quinine plus tetracycline for 7 days. F) mefloquine 1,250 mg in divided doses and G) artesunate 600 mg over 2 days period and mefloquine 750 mg. The follow-up was on Days 1, 2, 7, 14, 21 and 28. Patients tolerated all regimens very well and there was no serious side effects. The adverse effects did not differ among the seven regimens. The cure rates were 98.7, 97.1, 97.9, 96.7, 92.3, 100 and 95.2%, respectively. There was no significant difference of cure rates among various regimens. A total of 16 P. vivax and 1 P. malariae reinfections were reported among the study groups during the second half of the follow-up period, 14 of which were from the groups administered short action drugs (artesunate, artemether or quinine). The results suggested that either artesunate 600 mg or artemether 640 mg in combination with mefloquine 1,250 mg over a period of two days should be considered as alternative regimens for treating uncomplicated multi-drug resistant falciparum malaria.

Operational trial of ParaSight-F (dipstick) in the diagnosis of falciparum malaria at the primary health care level.

The rapid manual ParaSight-F test of Plasmodium falciparum malaria, an antigen capture test for detecting trophozoite-derived histidine rich protein-2 (PF HRP-2), is simple to perform and provides a definite diagnosis within 10 minutes. During an operational trial at health centers and mobile malaria units where microscopical diagnosis is not available and using defined symptom screening criteria, 3,361 subjects were tested yielding 618 positives (18.4%) for PF-HRP-2 by ParaSight-F. Microscopic examination of the same subjects by thick blood film examined 7 days later at a malaria clinic showed 578 falciparum, and 349 vivax and mixed infection (F+V) 41. The technology proved highly effective in detecting falciparum malaria at the peripheral levels where access to malaria laboratory services are difficult, thus allowing immediate administration of a complete course of treatment in the absence of a microscopic examination.

In vivo study of the response of Plasmodium falciparum to standard mefloquine/sulfadoxine/pyrimethamine (MSP) treatment among gem miners returning from Cambodia.

An in vivo study of the response of P. falciparum to the combination drug, MSP, was conducted among gem miners who contracted malaria from Cambodia in 1991-1992. High level resistance (RII, RIII responses) was observed in 22.5% of the 40 cases attending Mae Sot malaria clinic, west Thailand border, and in 28.1% of the 96 cases attending Bo Rai malaria clinic, east Thailand border. The observations on in vitro studies conducted prior to the MSP treatment and after recrudescence, together with the findings on adequate mefloquine blood levels strongly indicated the serious deterioration of mefloquine efficacy. The first line treatment for the malaria control program needs to be revised and the use of qinghaosu derivatives considered. Intensive measures to combat spreading of the highly resistant strains to other parts of the country should be taken into account.

Mefloquine level monitoring in patients with multidrug resistant Plasmodium falciparum on the Thai Myanmar border.

A total of 42 patients with uncomplicated falciparum malaria who attended the malaria clinic in Mae Sot, Tak Province were treated with single oral dose of MSP 3 tablets (Fansimef, equivalent to 750 mg of mefloquine) concurrently with primaquine (30 mg). They all contracted the infection from Cambodia. The aim of the study was to monitor the efficacy of MSP 3 tablets for the treatment of this highly multiple drug resistant strains of Plasmodium falciparum in this area. Of the 39 patients included for efficacy assessment, 13 (33.3%) patients had sensitive responses, whereas 15 (38.5%) and 8 (20.5%) had RI and RII types of response, respectively. Melfoquine concentrations on Day-3 after treatment in patients with sensitive and treatment failure groups were comparable; the respective mean (SD) values were 665 (279) and 772 (264) ng/ml.

Mefloquine levels in patients with mefloquine resistant Plasmodium falciparum in the eastern part of Thailand.

A total of 99 patients with uncomplicated falciparum malaria who attended the malaria clinic in Bo Rai, Trat Province were treated with a single oral dose of MSP 3 tablets (Fansimef; equivalent to 750 mg of mefloquine) concurrently with primaquine (30 mg). The aim of the study was to detect RII and RIII types of response with 3 tablets of MSP. Seven (8.1%) and 22 patients (25.3%) had RII and RIII types of response, respectively, and 58 (66.8%) had no parasitemia on Day-7 (S or RI response). Mefloquine concentrations on Day-3 after treatment in patients in the S/RI group were significantly higher than those with early treatment failure (RII, RIII), with the respective mean (SD) values of 1,959 (696) and 1,622 (863) ng/ml. The mean concentrations of mefloquine in these patients with RII and RIII types of response were higher than those with a sensitive response in a previous study. The result suggests that Plasmodium falciparum strains in this part of the country are highly resistant to mefloquine and that blood levels of mefloquine on Day-3 may also be a good indicator of treatment outcome in this particular area.

Dynamics of multi-drug resistance in Plasmodium falciparum in Thailand.

Since the initial report of resistance of Plasmodium falciparum to chloroquine in 1960 in the Thai-Cambodian border resistance to alternative drugs occurred early after their introduction. This development is considered to be the result of population migration and excessive drug pressure along with the presence of a multi-resistance gene within the parasite population. Multi-resistant strains as such have been disseminated throughout the country by returning migrant populations.

Overview: epidemiology of malaria and its control in countries of the WHO South-East Asia region.

The malaria situation in the WHO South-East Asia Region is reviewed in terms of its epidemiological diversity, problems encountered and implications for control. Varying host-parasite-vector interrelationships are shown to be influenced significantly by prevailing environmental conditions (eg topographic, climatic) as well as behavioral and socio-economic determinants. Drug-resistant falciparum malaria and vector resistance to insecticides are the main biological deterrents to the success of control programs. Thus, the potential for malaria transmission remains high in many places. The malaria control strategy includes Primary Health Care and integration with basic health services. However, operational research is needed in many of the countries in the Region.

Comparative trial on the response of Plasmodium falciparum to halofantrine and mefloquine in Trat Province, eastern Thailand.

With the appearance of strains of Plasmodium falciparum in the Trat Province, eastern Thailand, reported to have developed resistance to mefloquine there is a need for an alternative drug. This comparative trial with mefloquine and halofantrine has demonstrated extremely low cure rates with both drugs (33.3% and 28.13% respectively), cross-resistance is suggested.

Phase III double-blind comparative study of Fansimef and Lariam for the curative treatment of Plasmodium falciparum infections in Thailand.

A double-blind comparative study of Fanismef-mefloquine/sulfadoxine/pyrimethamine (MSP) and Lariam-mefloquine (MEF) for the treatment of falciparum malaria, was carried out at malaria clinics in Kanchanaburi, in western Thailand, in the years 1987 and 1988. The cure rates obtained were 96% for the MSP group and 93% for the MEF and there was no significant difference. Vomiting and diarrhea were common side effects in both the MSP and MEF groups. Less common side effects were epigastric pain, minor skin rashes and dizziness. Significant differences in vomiting and epigastric pain only occurred in the patients who did not have these symptoms before treatment: vomiting MSP 23%, MEF 8%, epigastric pain MSP 22% and MEF 11%.

In vitro sensitivity of multiresistant Plasmodium falciparum to new candidate antimalarial drugs in western Thailand.

The present study, carried out in 1987 in Thailand, has been designed to validate the in vitro microtest system, standardized by the World Health Organization (WHO), for the new antimalarials pyronaridine and halofantrine. The sensitivity of naturally acquired, multiresistant populations of Plasmodium falciparum has been assessed in order to develop a data base for further longitudinal investigations. For both drugs the in vitro microtest system seems to be suitable. The concentration range of plates can be considered as almost ideal for pyronaridine (0.1-6.40 mumol/l) while for halofantrine (0.002-0.128 mumol/l) an upward extension of the concentration range would be appropriate. Validation studies with artemisinin demonstrated the need for revising the protocol for the production of the dosing solutions. In the light of current knowledge about therapeutic concentration levels it would probably be appropriate to adopt a range of 0.2-12.8 mumol/l. All tested isolates, except possibly three, showed sensitive responses to pyronaridine. The high EC99 value of halofantrine could be indicative of some resistance to this drug. Rank correlation analysis suggested cross-resistance of pyronaridine and chloroquine which could be of consequence for the future introduction of pyronaridine.