A trial of suppression of malaria by administration of combined sulphadoxine-pyrimethamine tablets every 28 days was undertaken in West Malaysia during 1972. One thousand subjects were followed over a 10-month period, including control groups on placebo and on weekly chloroquine. Subjects were examined monthly for parasitaemia, drug reactions, leucopenia, teratogenicity and haemolysis among the subjects deficient in glucose-6-phosphate dehydrogenase. Rates of new infections in the placebo group were 8.0% with Plasmodium falciparum and 6.2% with P. vivax; in the group receiving weekly chloroquine, 5.1% P. falciparum and 0.3% P. vivax; and in the group receiving monthly sulphadoxine-pyrimethamine, 0.3% P. Falciparum and 1.0% P. vivax. The effective rate of cure of new infections with P. falciparum by a single suppressive dose of combined sulphadoxine-pyrimethamine given the following month was 88.7%. No serious side effects were observed.
Thirty isolations of Tembusu virus and four of Sindbis virus were obtained from approximately 280 000 mosquitoes collected between October 1968 and February 1970 in Sarawak, particularly from K. Tijirak, a Land Dyak village 19 miles South of Kuching. Twenty-two isolations of Tembusu virus and two of Sindbis virus were from Culex tritaeniorhynchus; two of Tembusu virus and two of Sindbis virus came from Culex gelidus. Tembusu virus was active throughout the year at K. Tijirak, the highest infection rates in C. tritaeniorhynchus being in January-March and May-August, when the C. tritaeniorhynchus population was declining and ageing. These results confirm that C. tritaeniorhynchus is the principal arthopod host of Tembusu virus in Sarawak. Antibody studies suggest that birds, particularly domestic fowl, are probably vertebrate maintenance hosts of Tembusu and Sindbis viruses in Sarawak.
Serum was collected from six adults participating in a field trial of sulfadoxine and pyrimethamine in combination which was being administered once monthly for malaria suppression. Samples were drawn during each of two consecutive months three hours, and 7, 14 and 28 days following a dose of 1 500 mg sulfadoxine. Serum sulfadoxine concentration was measured using the method of Bratton and Marshall (1939). Initial serum concentrations averaged 19-9 plus or minus 2-4 (SD) mg/100 ml and decayed to 6-2 plus or minus 2-8 mg/100 ml at 14 days. Serum sulfadoxine concentrations were still detectable at 28 days following a dose (2-1 plus or minus 1-5 mg/100 ml). Elimination half-time averaged 195 plus or minus 44 hours. The presistent serum concentrations of sulfadoxine following monthly doses documented here during field-use of this drug are in agreement with the successful clinical results reported for such a regimen (Lewis and Ponnampalam, 1974; O'Holohan and Hugoe-Mathews, 1971; Wolfensberger, 1971).
Histochemical demonstration of acid phosphatase activity in microfilariae gives sufficiently characteristic and consistent results for the differentiation of even closely related species. No difference could be detected among nocturnally periodic, nocturnally subperiodic and diurnally subperiodic Brugia malayi, but they could readily be distinguished from B. pahangi. Similarly, Dirofilaria repens could be readily distinguished from D. immitis and B. booliati from B. sergenti. The enzyme distribution pattern of a Malaysian rural strain of Wuchereria bancrofti was different from those of other regions.
One hundred and nine (9·8%) out of 1103 malaria patients examined in Sabah were deficient in glucose-6-phosphate dehydrogenase (G6PD). Sixty-nine of these G6PD-deficient patients were randomly allocated to one of three treatment regimes with (a) chloroquine, (b) chloroquine and primaquine or (c) sulfadoxine-pyrimethamine (Fansidar). No haemolysis was observed in group (a); except for a single mild case, no haemolysis was seen in group (c). However, in the primaquine group (23 patients), haemolysis occurred in seven of the 16 patients who had complete G6PD deficiency. Of these seven, five required blood transfusion and the other two developed acute renal failure, one requiring peritoneal dialysis. In the Fansidar group (c), four of the 22 patients took more than 15 days to clear the parasitaemia. Chloroquine resistance to falciparum infection was common in the patients given this anti-malarial.
Study site: Queen Elizabeth Hospital, Kola Kinabalu, Sabah, Malaysia
Field observations were made on Coquillettidia crassipes during a study of Mansonia in a swamp forest ecotype in Tanjong Karang. There was an increase in abundance in July consistent with the increase in abundance of Mansonia and an increase in rainfall. The biting cycle showed a dramatic early peak during the period 1900-2000 hours. The probability of daily survival through one day for the first three gonotrophic cycles was 0.770, 0.722 and 0.759. Two of the 54 Cq. crassipes dissected were infective, with two and 25 L3 larvae of Brugia. Both subperiodic B. malayi and B. pahangi developed into L3 larvae in laboratory bred Cq. crassipes. The index of experimental infection was higher for B. pahangi. Mansonia bonneae and Ma. uniformis showed higher indices of experimental infection than Cq. crassipes for subperiodic B. malayi. It is concluded that in an endemic area with a high density of Cq. crassipes it could act as a secondary vector of Brugian filariasis.
Surveillance methods for Coquillettidia crassipes were studied in an open housing estate near Kuala Lumpur using three types of traps Trinidad 10 trap, modified Lard can trap and IMR trap, each baited with chicken or pigeon. All traps attracted Cq. crassipes. There was no significant difference in the catches in the three traps. There was also no significant difference between chicken and pigeon as bait. Catches at heights of 1.5, 3, 4.5 and 6 m did not show any significant difference in density. Cq. crassipes was active at night with an early peak during the first hour of the night and a minor peak between 0100 and 0200 hours. The activity of the parous and nulliparous sections of the population was similar, except that a higher proportion of the parous females was active during the second peak compared with the nulliparous females. The parous rate was 22.3%, and the probability of survival through one day for two gonotrophic cycles was 0.711 and 0.650. The infection rate for Cardiofilaria was 29 out of 1052 (2.76%) and the infective rate (L3 larvae) was 13 out of 1052 (1.24%). 48.3% of the infected Cq. crassipes had a worm burden of more than ten larvae. One of the chickens in the traps was positive for microfilariae of Cardiofilaria four weeks after exposure as bait. Laboratory bred Cq. crassipes fed on this chicken produced infective larvae in ten days, and these were inoculated into clean chickens and pigeons. Microfilariae appeared in the chickens but not in pigeons. The adult worms recovered await identification.
Holoendemic malaria transmission in two small isolated forest communities and a coastal village was studied by (1) all night human bait collections of Anopheles species from inside and outside houses and (2) buffalo-biting and CDC light-trapping catches during March and November 1984. During the same period thick and thin blood films were collected from the human population, and spleen rates were determined in children from two to nine years of age. Using both the immunoradiometric assay (IRMA) and the dissection technique, more sporozoite-positive infections were detected in An. balabacensis and An. flavirostris in November than in March. IRMA confirmed the presence of Plasmodium falciparum sporozoites. An average of 76.2% of the An. balabacensis population lived long enough to have reached a point where infectivity with P. falciparum was possible in November. Although fewer than five adult females bit humans per night at any time, a resident could theoretically have received more than 160 infective bites in one year. A high frequency of feeding on humans, coupled with increased anopheline life expectancy, contributed to high estimates of falciparum malaria vectorial capacity (number of infections distributed per case per day); for An. balabacensis (1.44-7.44 in March and 9.97-19.7 in November) and for An. flavirostris (0.19-5.14 in March and 6.27-15.8 in November). These high values may explain the increased malaria parasite rates obtained from at least two forest communities. Correlation between actual and calculated rates of gametocytaemia was poorest in Kapitangan due to inadequate sampling of the human population. In Banggi island, malaria is stable and holoendemic, and the population enjoys a high degree of immunity.
An intense global collaborative effort under the leadership of the Steering Committee of the Filariasis Scientific Working Group of the Tropical Diseases Research Programme, World Health Organization, has brought together researchers, pharmaceutical chemists and clinicians in the development and search for antifilarial compounds which are more effective and more convenient to administer than diethylcarbamazine citrate, the current drug of choice for lymphatic filariasis. The Brugia spp.-rodent model has been used extensively for the primary screening and B. pahangi infections in the dog or cat for the secondary screening, of potential filaricides. Recently, the leaf-monkey (Presbytis spp.) infected with subperiodic B. malayi or Wuchereria kalimantani has been used for the tertiary evaluation and pharmacokinetic studies of compounds which have shown effectiveness in the primary and secondary screens. Both P. cristata and P. melalophos are extremely susceptible to subperiodic B. malayi infection, but the former is a better host as a higher peak microfilaremia and adult worm recovery rate were obtained. Although more than 30 potential filaricides have been evaluated in the tertiary screen, only a few compounds have shown some promise against lymphatic filariasis. CGP 20376, a 5-methoxyl-6-dithiocarbamic-S-(2-carboxy-ethyl) ester derivative of benzothiazole, had complete adulticidal and microfilaricidal activities against the parasite at a single oral dose of 20 mg kg-1. However, as the compound or its metabolites caused hepatotoxicity, its clinical use in the present formulation is not recommended.(ABSTRACT TRUNCATED AT 250 WORDS)