M. Willcox

A case-control study in northern Liberia of Plasmodium falciparum malaria in haemoglobin S and beta-thalassaemia traits.

A case-control study was carried out on 558 patients with malaria attending a hospital in Yekepa, northern Liberia; 94 patients (16.8%) were aged at least ten years, probably because of a low level of protective immunity in town dwellers due to malaria control. The proportion of sickle cell traits (1.8%) among the patient group was lower than in the population (7.2%) served by the hospital (chi 2, 21.455, 1 df, P less than 0.001). A stratified analysis showed the relative risk for Plasmodium falciparum malaria in sickle cell trait over normal homozygotes, as 0.29 (upper 95%) confidence interval, 0.56). For beta-thalassaemia trait, the proportion among patients was 5.5% as against 9.0% in the general population (chi 2, 6.158, 1 df, 0.025 greater than P greater than 0.010). Stratified analysis gave a weighted relative risk for beta-thalassaemia heterozygotes of 0.49 (upper 95% confidence interval, 0.74). Although there were four beta-thalassaemia traits in the 10-14 year stratum with moderate to high parasitaemias, we consider that the overall results are consistent with relative resistance against P. falciparum malaria of both sickle cell and beta-thalassaemia heterozygotes in this population. No conclusions were possible from this investigation with regard to HbC and the malaria hypothesis. We found no evidence that P. falciparum malaria elevates HbA2 concentrations into the beta-thalassaemia range.

Falciparum malaria and β-thalassaemia trait in northern Liberia

In a study in northern Liberia of the malaria and beta-thalassaemia hypothesis, the frequencies of beta-thalassaemia and HbS traits were 9.1 and 3.4% in the Mano and 9.5 and 1.7% in the Gio tribal samples. HbC and HbN were present at low frequency. G6PD deficiency was found in 16% of males. An observed increase with age of beta-thalassaemia trait frequencies was consistent with the selection hypothesis. However, we could not entirely exclude that associated iron deficiency influenced the results in the six to 11 month age group. Malaria was holoendemic; Plasmodium falciparum predominated, P. malariae and P. ovale were also identified. Plasmodium falciparum prevalence rates were similar in normal and beta-thalassaemia trait children but parasite densities were consistently lower in the latter. Using the criterion of a falciparum parasite density of 1 x 10(9) 1(-1) or greater to indicate a potentially important infection, the relative risk in beta-thalassaemia traits one to four years old from the cross-sectional study was 0.45 (upper 95% confidence interval 0.79) and 0.41 (0.61) in two to nine year trait carriers from a longitudinal study. Plasmodium falciparum gametocyte rates were lower in beta-thalassaemia trait children (P less than 0.005). The geometric mean titre of P. falciparum antibodies was lower in beta-thalassaemia trait children from the one to four year group (P less than 0.05). Otherwise immunological studies showed little difference between the different Hb types. Parasitological findings were consistent with relative resistance of HbS trait carriers towards P. falciparum infection. We found no evidence for relative resistance of beta-thalassaemia traits towards P. malariae infection nor that G6PD deficient males were more resistant to P. falciparum than those with normal activity. We conclude that the results are consistent with relative resistance of beta-thalassaemia trait carriers to P. falciparum malaria.

Different malaria control activities in an area of Liberia--effects on malariometric parameters.

The epidemiology of malaria was studied in a West African mining town (Yekepa) and three surrounding zones defined as Close, Middle and Far areas. Malariometric parameters were investigated in children two to nine years of age at the end of the rainy season. In Yekepa, vector control measures and intense suppression of malaria with drugs had created an almost hypoendemic situation with a spleen rate of 11%. In Close area, vector control was applied to some extent and malaria drugs were frequently used for treatment; the spleen rate was 40%. In Middle area, a mobile clinic provided sporadic malaria treatment to small children, but the clinic did not reach out to Far area. The spleen rates were 95 and 99%, respectively. Three species of Plasmodium were found in all areas. The prevalences in Far area were P. falciparum 82%, P. malariae 39% and P. ovale 9%. The crude parasite rates increased from 13% in Yekepa to 92% in Far area, whereas haematocrit levels decreased from 37.6 to 35.2, respectively. Plasmodium falciparum seropositivity, as measured by indirect immunofluorescence, was 74% in Yekepa and 99% in Middle and Far areas. Total IgG concentrations ranged from 18 g1(-1) in Yekepa to 33 g1(-1) in Far area. Three main anopheline species were found in the zones outside Yekepa. Their relative frequencies in Far area were Anopheles funestus 45%, A. hancocki 37%, and A. gambiae 18%. The local inoculation rates gradually increased outwards from Yekepa from less than 0.01 to 0.17 inoculations per man and night at the beginning of the dry season.(ABSTRACT TRUNCATED AT 250 WORDS)

Monthly antimalarial chemotherapy to children in a holoendemic area of Liberia

Two hundred and eighty-two children, two to nine years old, were included in a prospective three-year study in four villages with holoendemic malaria. In three villages the children received monthly doses of either chloroquine, pyrimethamine or chlorproguanil respectively for two years. In the fourth, vitamin tablets were used as placebo. Presumptive treatment with chloroquine (10 mg base kg-1) was given to all children with fever of suspected malarial origin. The two-year drug distribution was satisfactorily fulfilled to 168 children. Surveys, including physical and laboratory examinations were performed every six months, four weeks after medication. A fifth village was only visited at the start of the study and after two years. The mean crude parasite rate was initially 92%. Plasmodium falciparum was the main species. Splenomegaly was recorded in all children. In the chloroquine-treated children, the parasite rates varied between 30% and 50% during the study. By the end of the second year the spleen rate was reduced from 100% to 50%. Reported episodes of fever were reduced to half and mean haematocrit levels increased by 6% in comparison with children receiving the placebo. Total IgG concentrations were reduced from 36.7 g l-1 to 25.9 g l-1, whereas no significant decrease was observed in malarial seropositivity as measured by indirect immunofluorescence. Chlorproguanil had a weaker impact on parasitaemia with parasite rates between 50% and 90%. However, the spleen rate was reduced to 67% and there was a significant reduction of reported fever episodes. Mean haematocrits increased by 4%. Total IgG decreased from 31.8 g l-1 to 23.8 g l-1. In contrast, in the pyrimethamine group, the placebo group and the untreated group from the fifth village, the malariometric indices after two years were comparable to each other and to the initial values. During the third year only presumptive chloroquine treatment was given, and by the end of the study all malariometric indices were again comparable. From clinical observations there was no apparent impairment of protective immunity to malaria from the two years of regular distribution of the drugs. We conclude that a certain degree of malaria control could be achieved in Liberian children by the administration of monthly doses of chloroquine 10 mg base kg-1. The administration of chlorproguanil (1.5 mg kg-1) represents an alternative regimen.

Malaria control by chlorproguanil. I. Clinical effects and susceptibility of Plasmodium falciparum in vivo after seven years of monthly chlorproguanil administration to children in a Liberian village.

For seven years, chlorproguanil (1.0 to 2.0 mg kg-1) was administered monthly to the children below 15 years of age in a village with holoendemic malaria. Malariometric indices were recorded every six months. Susceptibility in vivo was monitored by the clearance of Plasmodium falciparum parasitaemia after drug intake. Three parasite species were found initially: P. falciparum (52%), P. malariae (8%) and P. ovale (4%). The parasites found during the study were mainly P. falciparum, and parasite rates ranged from 37 to 87% at the different surveys one month after respective drug intake. A fifty-fold decrease of mean parasite density was generally observed seven days after drug intake. Splenomegaly was initially recorded in all two to nine year old children, with a mean size of 2.64 according to Hacketts index. From 18 months onwards as the mean spleen index was 1.15 in the same age group. Chlorproguanil may represent an important alternative drug to groups at risk in malaria control schemes.

In vitro susceptibility of Plasmodium falciparum to amodiaquine, mefloquine, quinine and chloroquine in Liberia, West Africa

The in vitro susceptibility of seven Plasmodium falciparum isolates to four schizonticidal drugs was studied in Yekepa area, northern Liberia, by the Rieckmann 24-hour micro method. The seven patients were successfully treated with the standard chloroquine regimen. The results of the individual in vitro tests all indicated full susceptibility to the four drugs. By probit analysis, the drug concentrations achieving 50% (EC 50) and 99% (EC 99) inhibition, respectively, were 0.2 and 0.7 microM chloroquine, 0.04 and 0.2 microM amodiaquine, 0.01 and 0.07 microM mefloquine and 1.4 and 3.0 microM quinine.

In vivo and in vitro susceptibility of Plasmodium falciparum to sulphadoxine/pyrimethamine in Liberia, West Africa

The in vivo response of Plasmodium falciparum to standard treatment with sulphadoxine/pyrimethamine was studied in 19 hospital patients from Yekepa town with hypoendemic malaria and in 28 children, two to nine years old, living in a village with holoendemic malaria. In vitro tests were performed on eight isolates. In the hospital patients all parasites cleared with mean clearance time of 2.2 (range one to three) days and no recrudescence occurred during a 28-day follow-up period. In the village children, despite a high sporozoite inoculation rate, recurrent parasitaemias were only recorded after 28 days, suggesting a rather long-lasting prophylactic effect against reinfection by the drug combination. In vitro, inhibition of parasite multiplication was achieved by 3 X 10(-7) M sulphadoxine and 3.8 X 10(-9) M pyrimethamine.

Susceptibility of Plasmodium falciparum to chloroquine in northern Liberia after 20 years of chemosuppression and therapy.

The in vivo and in vitro susceptibility of Plasmodium falciparum to chloroquine was investigated in northern Liberia after 20 years of continuous chemosuppression and therapy with 4-aminoquinolines. In all patients studied (n = 53) parasitaemias were cleared within four days. There were no recrudescences in 16 patients followed-up for 28 days. All isolates of P. falciparum tested in vitro (n = 26) showed sensitive patterns. Schizont maturation was inhibited by a chloroquine concentration of between 0.25 and 0.75 mumol-1. In this area of Liberia no resistance to chloroquine was found in spite of extensive use of 4-aminoquinolines. This may support the view that importation of at least partially resistant strains, rather than local mutation of P. falciparum, precedes selection of resistant strains. Hence, we conclude that regular intake of chloroquine by groups at risk is justified if it is combined with regular monitoring of drug susceptibility.

Is the working capacity of Liberian industrial workers increased by regular malaria prophylaxis

In a study of the impact of malaria prophylaxis upon the physical working capacity of Liberian industrial workers, two groups of men, one with and the other without malaria prophylaxis, were compared over a period of one year. At the beginning and at the end of the study, the haemoglobin concentration, haematocrit, blood volume and physical performance--measured by bicycle ergometry and expressed as work load at heart rate 170--were compared. No significant differences were found, either within or between the two groups. Routinely distributed malaria prophylaxis thus seems to be of little importance with respect to working capacity in this type of community, where malaria is meso-endemic.

Malaria and haemoglobin A2 levels in northern Liberia.

The influence of malaria on HbA2 levels was investigated in two groups of children aged two to nine years from the Mano tribe of northern Liberia. One group, 174 children living in a town where there is malaria control, had a parasite rate of 6.5%, only a few having palpable spleens, but 282 children living in an area of intense malaria transmission had a parasite rate of 92%. All but one child in this group had enlarged spleens. However, the difference in proportions of elevated HbA2 values within the limits for beta-thalassaemia, 8% and 10.3% respectively, was not statistically significant (0.5 greater than P greater than 0.1). It was concluded that the influence of malaria on HbA2 levels is not significant and that this parameter is valid for detecting beta-thalassaemia trait in this population. Further, iron deficiency may be a more important factor than malaria to consider when assessing the results of HbA2 estimations.