Chemoprophylaxis against malaria in Papua New Guinea: a trial of amodiaquine and a combination of dapsone and pyrimethamine.

A placebo-controlled chemoprophylaxis trial was carried out in 1980 in 318 semi-immune school children in the Madang area of Papua New Guinea, where there was a high prevalence of strains of Plasmodium falciparum resistant to 4-aminoquinolines. Since prophylaxis with amodiaquine at 5 mg/kg weekly had failed, amodiaquine at a dose of 10mg/kg weekly and Maloprim (half a tablet or one tablet depending on body weight, which gave ranges of dapsone of 1.7-3.3mg/kg and pyrimethamine 0.2-0.4 mg/kg) weekly were tried. Neither regimen was completely successful in preventing parasitaemia, though after 13 weeks of prophylaxis the slide positivity rate was 16% for the amodiaquine group and 2% for the Maloprim group, which was in each case significantly lower than the normal baseline rate in the controls of 42%. Amodiaquine was completely successful in suppressing Plasmodium vivax infections. Breakthrough parasitaemia occurred, with either P. falciparum or P. vivax, in 5% of subjects on Maloprim at some time during the 13-week period of prophylaxis. Significantly more children in both the amodiaquine and Maloprim groups than in the placebo group showed a reduction in spleen size. All groups showed an unexplained fall in haemoglobin level over the study period but the fall was significantly less in both the prophylaxis groups. There was no adverse effect on white cell counts by either drug regimen. Chemoprophylaxis as a component of an integrated malaria control program should not be overlooked, provided that compliance can be maintained. However, in this particular case the principal purpose of the study had been to evaluate the proposed chemoprophylactic regimens in school children before embarking on an intervention study in young children. As a result of this study it was decided not to go ahead with the chemoprophylactic intervention in young children but to adopt an approach based on early presumptive treatment.

Measurement of malarial infectivity of human populations to mosquitoes in the Madang area, Papua, New Guinea.

The proportion of blood meals taken on humans which are infectious to mosquitoes in the Madang area, Papua New Guinea was estimated by two methods. In the first, laboratory reared Anopheles farauti were fed on individuals of all ages at village surveys. The results showed that 3.8% of people were infectious and that the mean percentage of mosquitoes which became infected by feeding on these people was 37.9%. From the average proportion of mosquitoes infected, the probability that a mosquito feeding on a human would pick up infection was 0.013 +/- 0.005. In the second approach mosquitoes were fed on identified Plasmodium falciparum, P. vivax and P. malariae gametocyte carriers. The results indicated that 46% of gametocyte carriers were infectious and that the mean probability of a mosquito becoming infected after feeding on a gametocyte carrier was 0.151 +/- 0.029. Gametocyte prevalence rates in all ages measured over 18 months in three villages averaged 3.3% P. falciparum, 4.0% P. vivax and 0.7% P. malariae, totalling 8.0 +/- 0.7%. Combining gametocyte prevalence rates with the probability of a mosquito becoming infected from a gametocyte carrier, the probability of a mosquito becoming infected following a blood meal on a member of the human population was estimated to be 0.012 +/- 0.003.

The interaction of alpha thalassaemia with malaria.

A controlled trial of iron dextran prophylaxis in infants 2 months old was carried out on the north coast of New Guinea, where malaria is holoendemic. These infants have a high carrier rate (80%) for alpha + thalassaemia. The neighbouring highland area has a low rate of both malaria and alpha + thalassaemia. The results of clinical and haematological examination of these infants at 6 and 12 months were analysed to determine the relationship between alpha thalassaemia and susceptibility to malaria. Infants were divided according to haemoglobin Bart's levels found at birth into 3 groups corresponding to probable genotypes. Homozygotes had higher slide malarial positivity and spleen rates at 6 and 12 month than the normal or heterozygote groups. Analysis of variance of haemoglobin levels showed that the anaemia associated with malaria was greatest in the normals and least in the homozygotes at 6 months. A possible protective mechanism of alpha thalassaemia is discussed.

Reduction in incidence and prevalence of Plasmodium falciparum in under-5-year-old children by permethrin impregnation of mosquito nets.

The malaria incidence and prevalence rates among children who slept under permethrin-impregnated mosquito nets in four villages near Madang, Papua New Guinea, were compared with the rates among children who slept under unimpregnated nets in four paired control villages. Immediately following a parasitological survey in the eight villages, malaria parasites were cleared from the children with chemotherapy, and the mosquito nets in the four experimental villages were impregnated with permethrin. Follow-up parasitological surveys were performed 4 and 10 weeks later. Sporozoite rates in female mosquitos of the Anopheles punctulatus complex decreased significantly in two of the experimental villages after impregnation. Also, the incidence of Plasmodium falciparum between the 4-week and 10-week surveys was significantly lower among the 0-4-year olds in villages with impregnated nets than in those with unimpregnated nets, leading to reduced prevalence of P. falciparum in this age group. Use of permethrin-impregnated nets had no effect on the incidence or prevalence of P. falciparum among 5-9-year olds or on that of P. vivax among the 0-4- or 5-9-year olds.

Hereditary ovalocytosis and reduced susceptibility to malaria in Papua New Guinea.

Ovalocytosis, an hereditary condition in which most erythrocytes are oval in shape, is a polymorphism that occurs in up to 20% or more of the population in Papua New Guinea and Malaysia. Due to the geographical correlation of the trait with endemic malaria, the possibility of a selective advantage in resistance to malaria has been raised. In a study of 202 individuals with greater than or equal to 50% oval red cells matched by age, sex and village of residence with controls having less than or equal to 30% oval cells, ovalocytic subjects had blood films negative for Plasmodium vivax (P = 0.009), for P. falciparum (P = 0.044), and for all species of malaria parasites (P = 0.013), more often than controls. Among individuals parasitaemic at any time there were no clear differences in density of parasitaemia. However, in children 2 to 4 years old, parasite densities of both species were lower in ovalocytic subjects than in controls (0.01 less than P less than 0.025). The differential susceptibility to malaria infection suggested by this study has implications for the evaluation of interventions, including possible future vaccine field trials, in populations where high-frequency ovalocytosis is present.

The efficiency of sporozoite transmission in the human malarias, Plasmodium falciparum and P. vivax.

Reported are malaria sporozoite and inoculation rates over a 1-year period in eight epidemiologically defined villages of different endemicity in Madang Province, Papua New Guinea. In the study, more than 41 000 wild-caught mosquitos were analysed for Plasmodium falciparum and P. vivax sporozoites by ELISA. In a given village the entomological inoculation rates correlated strongly with the prevalences of both these malarial parasites in children. However, the prevalence of P. falciparum infections in children was much higher than that of P. vivax, despite similar inoculation rates for the two species. These data suggest that in Papua New Guinea P. falciparum is more efficiently transmitted than P. vivax from mosquito to man. The increased efficiency of transmission of P. falciparum may be due to the heavier sporozoite densities in wild-caught mosquitos naturally infected with P. falciparum sporozoites that were tenfold greater than the sporozoite densities in mosquitos infected with P. vivax.

The epidemiology of malaria in a population surrounding Madang, Papua New Guinea.

Malaria is prevalent throughout coastal and lowland Papua New Guinea. Recent changes, including a shift from predominance of Plasmodium vivax to Plasmodium falciparum, appearance of chloroquine-resistant P. falciparum and decreased effectiveness of vector control programs have been observed. Epidemiological features of malaria were studied through four six-month surveys of a population of 16,500 in Madang Province from 1981-1983. Baseline data on parasitology, splenic enlargement, serology, hemoglobin levels, prevalence of 4-aminoquinolines, utilization of mosquito nets and incidence of fever were collected for use in future evaluation of malaria control measures including possible field trials of an antimalarial vaccine. Prevalence of parasitemia (all species, all ages) varied from 35.0% to 42.7% over the four surveys each of which covered a random sample of 25% of the population. The ratio of parasite species was: P. falciparum 70:P. vivax 25:P. malariae 5 in the dry seasons, shifting slightly in favor of P. falciparum during the wet seasons. Intense year-round transmission was indicated by decreasing parasite prevalence and splenic enlargement with age, low density asymptomatic parasitemias and high prevalence of antimalarial antibodies (i.e., greater than 80% of the population over five years of age was ELISA-positive). Levels of endemicity varied geographically, presence of 4-aminoquinolines in urine samples was relatively common (12.7% positive) and chloroquine resistance was widespread (81.6% in vitro, 46.6% in vivo).

Iron supplementation increases prevalence and effects of malaria: report on clinical studies in Papua New Guinea.

A placebo-controlled trial of intramuscular iron dextran prophylaxis for two-month-old infants was carried out on the north coast of Papua New Guinea where there is high transmission of malaria. The results indicate that the placebo group became relatively iron deficient whereas the iron dextran group had adequate iron stores and, in the absence of malaria, a higher mean haemoglobin. However in the iron dextran group there was a higher prevalence of malaria, as judged by parasite and spleen rates at 6- and 12-month follow-up; a lower haemoglobin associated with malaria when compared with the placebo group and a greater reticulocytosis in response to malaria infection. Within the placebo group it was noticed that the malaria rates were lower at follow-up in those infants who had had a low birth haemoglobin. In neither group was there apparent suppression of marrow activity in the presence of malaria. Malaria infection in both groups was associated with a significantly raised serum ferritin level and transferrin saturation. Over-all these data give evidence for a protective role of iron deficiency against malaria and would argue against the injudicious use of iron replacement in areas where malaria is endemic.

A large-scale field trial of malathion as an insecticide for antimalarial work in Southern Uganda.

Malathion shows promise as a substitute for chlorinated-hydrocarbon insecticides in the control of malaria whenever the latter are unsuitable because of Anopheles resistance or other reasons. A field trial of malathion was carried out in 1963-64, covering an area of about 500 km(2) with a population of about 26 000, in Masaka District, southern Uganda. All houses and animal shelters were sprayed with malathion at 2 g/m(2) at roughly 4-month intervals. The average combined densities of the females of the two main malaria vectors, Anopheles funestus and An. gambiae, fell from an average of 66 per shelter per day in a pre-trial survey in 1960-61 to 0.0011 at the end of 1964 in the sprayed area; no significant changes were noted in unsprayed comparison areas. The transmission of the infection in humans was apparently interrupted when allowance was made for imported cases.The presence of unsprayed surfaces in houses which had recently been built or altered interfered somewhat with complete coverage. Case detection was reliable and achieved excellent coverage.No toxic effects of malathion in humans were noted, while the effect on mosquitos was considerable even in the absence of direct contact. This effect of malathion lasted for a considerably shorter period of time in houses roofed with corrugated iron than with thatch; this should be borne in mind in the design of spraying programmes.

Studies on chloroquine-resistance of Plasmodium falciparum in Upper Volta and Liberia, West Africa.

The emergence of strains of Plasmodium falciparum resistant to normal dosages of chloroquine or other 4-aminoquinolines has caused concern in a number of malarious areas. Well-documented reports have confirmed this resistance in wide areas of South-East Asia and in some areas of South America. Occasional reports have been received from parts of West Africa, and the present investigation sought to clarify the situation in two areas, Ouagadougou, Upper Volta, and Kpain, Liberia, from which such reports had emanated. Studies were carried out to determine the sensitivity of local strains of P. falciparum to chloroquine. The results, based on the rapidity of parasite clearance, indicated a normal sensitivity in the cases treated. Although it is concluded that strains of P. falciparum with significant resistance to chloroquine are not at present a problem in the areas concerned, a watch should be kept for the possible future emergence of this problem.