C.C. Draper

Field studies of some of the basic factors concerned in the transmission of malaria

Summary (1) Observations made on the human population and the vector mosquitoes in a coastal area of tropical Africa where malaria is holo-endemic are described. (2) The actual malaria inoculation rate in infants as derived by analysis of parasite indices—about once in every 100 days—was much less than the theoretical rate derived from entomological data (vector densities, feeding habits and sporozoite rates)—from once every 10 days to once a day. Possible reasons for this discrepancy are discussed; the chief factor is considered to be suppression by the infants of the majority of sporozoite inoculations before parasitaemia occurs. It is not thought that selective biting of different age-groups occurs to any great extent. (3) Studies of the vector species, A. gambiae and A. funestus , confirmed that in this area they are strongly anthropophilic, will feed within 24 hours of emergence, probably require two blood feeds to mature the first batch of eggs, have a 48-hour gonotrophic cycle, and that a significant proportion of half-gravid A. gambiae leave human habitations to mature their eggs elsewhere. (4) The survival rate of the vector species has been measured by a new technique involving the comparison of the immediate sporozoite rate on capture with that found after keeping wild-caught mosquitoes alive for the duration of the extrinsic cycle. We estimate that in this area A. gambiae showed a natural daily mortality of the order of 7 per cent. and A. funestus of the order of 8 per cent. Mortalities among wild-caught mosquitoes kept in cages, while generally lower than these, confirm that A. funestus shows a higher mortality than A. gambiae . Such values of naturally occurring mortalities are perfectly consistent with the sporozoite rates found. (5) The implications of these findings in relation to control by residual insecticides are discussed.

Chagas's disease in the Amazon Basin: I. Trypanosoma cruzi infections in silvatic mammals, triatomine bugs and man in the State of Pará, north Brazil

A total of 1,197 wild animals from Pará State north Brazil, were examined for haematozoa. Trypanosoma cruzi-like parasites were found in 13 different species, and were particularly common in a variety of marsupials (Didelphidae), porcupines (Coendou spp.), armadillos (Dasypus novemcinctus) and coatimundis(Nasua nasua). Three human infections are reported, making a total of seven autochthonous cases of Chagass disease from Pará since the first were described in 1969. A serological survey of 5,319 inhabitants from the Belém suburbs revealed 14 positive reactions with immunofluorescent antibody titres greater than 1:64, and 15 equivocal reactions at 1:16. No evidence was found of silvatic species of triatomine bugs (Hemiptera: Reduviidae) colonizing houses, but occasional infected specimens of Panstrongylus geniculatus and Rhodnius pictipes were found in suburban houses, near the forest. Human infection is considered to be silvatic in origin. Chagass disease could become endemic in the Amazon Basin if silvatic triatomine bugs were able to adapt to a domestic habitat: the real danger, however, is in the possible importation of already domiciliated vector-species along the newly opened highways, from other endemic regions of Brazil. Other Trypanosoma species were recorded in a variety of wild animals. Haemogregarines were found in some marsupials and rodents, and piroplasms in marsupials and a single armadillo.

Malaria in an urban and a rural area of Zambia

Children in Lusaka and in a rural area in central Zambia were examined during November 1984 and April 1985 to assess the effect of urbanization on malaria transmission. Of 423 urban children examined in November, 2.4% had scanty parasitaemia, and low titres of malarial antibodies were found in 46%. These proportions increased in April to a parasite rate of 10.3% and malaria antibodies were detected by indirect fluorescent antibody tests (IFAT) in 62%. The presence of malaria antibodies was positively associated with journeys outside the main towns. Examination of paired sera from the 2 periods showed an association between a history of malaria and an increased antibody titre, but failed to show an association between travel outside the main towns and conversion from a negative to a positive IFAT. The spleen rate in children under 15 years old in Lusaka was 3%, indicating hypoendemic malaria. In rural children the parasite rate was 10% and 27% in the 2 seasons, respectively, and over 97% of the children had malaria antibodies. The spleen rate was 20%, indicating mesoendemic malaria. It is concluded that there is only low transmission of malaria in Lusaka so that many people do not develop resistance and are therefore at risk of severe attacks if they do become infected. Possible measures to protect the urban population are discussed.

Malaria in the Pare area of Tanzania. IV. Malaria in the human population 11 years after the suspension of residual insecticide spraying, with special reference to the serological findings

Abstract A parasitological and serological survey was made in the South Pare area in 1970, where a residual insecticide spraying campaign had previously caused a great reduction in the transmission of malaria. Although the densities of the vectors and the theoretical inoculation rates had almost returned to pre-spraying levels the prevalence of malaria parasites in the human population was still significantly less than formerly. Serological findings, however, suggested that more transmission was occurring than was shown by the parasite rates. As well as pre-existing immunity, an important factor in the delayed resurgence of malaria, and in the dissociation between parasite rates on the one hand and inoculation and antibody prevalence rates on the other, was the widespread use of antimalaria drugs. There was an indication of a fall in mean haemoglobin levels towards those of the period before malaria control.

Observations on the infectiousness of gametocytes in hyperendemic malaria

Abstract 1. (1) There is a correlation between the probability of a mosquitos becoming infected and the gametocyte density of the carrier, when densities are broadly grouped. 2. (2) A small series of experiments in the hyperendemic zone of S. W. Nigeria are reported in which A. gambiae gambiae were allowed to feed on children carrying different densities of P. falciparum gametocytes. 3. (3) In the community from which these subjects came the average density of gametocytes was low, approximately 5 6 of all gametocyte carriers showing less than 100 per c.mm., and 1 6 more than 100 per c.mm. 4. (4) Of mosquitoes feeding once on the first group (less than 100 gametocytes per c.mm.) 5 per cent. could become infected if they survived long enough for completion of the extrinsic cycle, while of mosquitoes feeding on the second group (more than 100 per c.mm.) 50 per cent. could become infected. Other workers have found a higher proportion infected in the first group. 5. (5) These figures are used in a hypothetical example to calculate the proportion of all A. gambiae feeding on the population at one moment which could become infected.

Observations on early and late post-sporozoite tissue stages in primate malaria. III. Further attempts to find early forms and to correlate hypnozoites with growing exo-erythrocytic schizonts and parasitaemic relapses in Plasmodium cynomolgi bastianellii infections

Rhesus monkeys were heavily infected with sporozoites of Plasmodium cynomolgi bastianellii in an attempt to demonstrate the site of invasion of sporozoites into tissue cells and their growth there. Further attempts were made to correlate the appearance and loss of hypnozoites with parasitaemic relapses. Hypnozoites were demonstrated and once again shown to decrease in numbers over 229 days during which time the infection showed parasitaemic relapses. Liver biopsies taken at two-day intervals for 12 days showed that hypnozoites decreased in numbers over-all and growing schizonts were demonstrated in the liver. At this time a parasite the size of a hypnozoite was seen with two nuclei and another was seen with an elongate, possibly dividing nucleus in one monkey. an attempt to find the location of the early intracellular exoerythrocytic forms in the liver at various times less than 40 hours after infection using smears and immunological staining with newly prepared anti-sera failed. Large numbers of sporozoites of P. knowlesi were also injected into a rhesus monkey the liver of which on the fifth day after infection showed no hypnozoites among 157 sections of growing schizonts and no parasites at all on the 42nd day after infection. In P. cynomolgi bastianellii infections parasites, mostly hypnozoites, were found in the liver up to 229 days after infection.

Experimental Trypanosoma cruzi infections in rhesus monkeys. II. The early chronic phase

Information on the acute and early chronic phases of infection with Trypanosoma cruzi in eight rhesus monkeys is reported with particular reference to the pattern of subpatent parasitaemia and serology. Xenodiagnosis was superior to animal inoculation and blood culture in its capacity to detect subpatent parasitaemia. Each monkey showed an individual, relatively constant pattern of this not related to the nature of the inoculum. Levels of indirect fluorescent and indirect haemagglutinating antibodies remained elevated during a year of observations. One monkey died with a megaoesophagus. Another monkey after challenge with a heterologous strain by orbital inoculation failed to develop Romanas sign and showed no change in serum antibody levels or degree of xenopositivity.

Ahaptoglobinaemia in Melanesia: DNA and malarial antibody studies

To assess the relative contributions of genetic and acquired factors, particularly malaria, to the high frequencies of ahaptoglobinaemia found in Melanesia we have performed DNA and malarial antibody studies in a population from Vanuatu. No gene deletion or rearrangement was found on gene mapping in any ahaptoglobinaemic individual and the frequencies of the Hp1 and Hp2 alleles in the ahaptoglobinaemic group were similar to controls. However, antibodies to Plasmodium falciparum were significantly elevated in the ahaptoglobinaemics. These data suggest that malaria rather than genetic factors is the major cause of ahaptoglobinaemia in Melanesia.