Showing papers on "Malaria published in 1984"

Major surface antigen gene of a human malaria parasite cloned and expressed in bacteria

Abstract: The late blood stages of the human malaria parasite, Plasmodium falciparum, carry a major surface antigen, p190, of molecular weight (Mr) 190,000. This antigenically variable protein is actively processed, first as the parasite matures and again when it is released into the blood stream and invades a new erythrocyte to initiate a cycle of growth. It elicits a strong immune response in man; all tested adult sera from endemic areas have antibodies against this protein. Our evidence indicates that purified p190 can alter the course of parasitaemia in monkeys with falciparum malaria. We have also succeeded in cloning part of the gene for p190 and expressing it in Escherichia coli. To this end we have developed a new technique, antibody select, which greatly simplifies final identification of expressing clones.

Heterogeneities of the malaria vectorial system in tropical Africa and their significance in malaria epidemiology and control

Abstract: The most important units of the malaria vectorial system in tropical Africa are included in the Linnaean taxon Anopheles gambiae, which has been split into six sibling species recognized by the application of genetic techniques. More recent studies have shown further complexities involving chromosomal inversion polymorphism in some vector populations as well as incipient speciation processes. The significance for field research in malaria of the splitting of a morphological taxon into genetically defined units and subunits is discussed.

Cultivation of the liver forms of Plasmodium vivax in human hepatocytes

Abstract: The blood schizogonic cycle of human malaria parasites has thus far been the most exhaustively studied phase of parasite development. However, before entering red blood cells (RBCs), the parasite undergoes its first multiplication not in blood, but in hepatic cells. These hepatic stages were the last to be discovered1 and only a few studies have been performed in humans and other primates1–7. Despite recent advances8–11, in vivo studies have limitations and other approaches such as cultures of these liver forms may be necessary to investigate their chemosensitivity and their biochemical or immunological properties. Recently, sporozoites of species of rodent malaria have been made to infect cultured cell lines12–15 or primary hepatocyte cultures16–18. We report here that the complete cycle of the human malaria parasite Plasmodium vivax can be obtained in primary cultures of human hepatocytes up to release of merozoites able to penetrate RBCs.

Plasmodium falciparum strain-specific human antibody inhibits merozoite invasion of erythrocytes.

Abstract: The extent to which human antibodies involved in functional immunity react with antigenic determinants varying between different isolates or strains of the human malaria parasite Plasmodium falciparum will influence the design of vaccines against malaria. We identified nine immune sera from Cambodian refugees which blocked in vitro invasion of erythrocytes by merozoites of the Camp strain of P. falciparum and agglutinated Camp strain merozoites. However, none of these sera blocked invasion of erythrocytes by merozoites of the FCR-3 strain. We conclude that antibodies in these human sera recognized antigenic determinants present on the surface of viable merozoites of the Camp strain but not the FCR-3 strain. These parasite strains and in vitro assays can be used to analyze strain-specific functional immunity in humans.

Type-I HTLV antibody in urban and rural Ghana, West Africa.

Abstract: The prevalence of antibodies against the newly described human T-cell lymphoma virus, type I (HTLV-I) in two communities in Ghana, West Africa, is described. There was no difference by community (urban, 3.6% and rural, 4.0%). Prevalence increased with age, being 5.9% among persons greater than 10 years old, but did not differ by sex. There was no difference when data were analysed by housing status or crowding. Non-confirmed reactions in the assay system were frequent and correlated with both prevalence and titer of antibody against malaria. Possible explanations include vector-borne transmission like that of malaria, but the relationship is more probably due to a polyclonal stimulation of B cells, enhancing the potential for detecting reactivity in the assay. Because assay systems vary and because most laboratories do not routinely use a confirmation assay, results presented by different groups must be interpreted cautiously.

The biology of Plasmodium in the mosquito.

Abstract: Developpement du parasite, de la gametogenese du gamete, de la formation du zigote, du developpement de l'ookinete, de l'oocyste, du sporocyste. Inhibition de la gametogenese, inhibition de la fertilisation, inhibition du developpement de l'ookinete et de sa fonction, modification de la physiologie

Human ecology and behaviour in malaria control in tropical Africa

Abstract: Since about 250 BC, human modification of African environments has created increasingly favourable breeding conditions for Anopheles gambiae. Subsequent adaptations to the increased malaria risk are briefly described and reference is made to Macdonald's mathematical model for the disease. Since values for the variables in that model are high in tropical Africa, there is little possibility that simple, inexpensive, self-help primary health care initiatives can control malaria in the region. However, in combination with more substantial public health initiatives, simple primary health care activities might be done by communities to (1) prevent mosquitos from feeding on people, (2) prevent or reduce mosquito breeding, (3) destroy adult mosquitos, and (4) eliminate malaria parasites from human hosts. Lay methods of protection and self-care are examined and some topics for further research are indicated. Culturally appropriate health education methods are also suggested.

Target Antigens in Malaria Transmission Blocking Immunity

Abstract: Malaria transmission blocking immunity has been found to operate against two distinct phases of development of malaria parasites in the mosquito midgut: (i) against the extracellular gametes and newly fertilized zygotes shortly after ingestion by a mosquito of parasitized blood and (ii) against the zygotes during their subsequent development into ookinetes. Immunity is antibody-mediated and stage-specific. A set of three proteins, synthesized in the gametocytes, expressed on the surface of the gametes and newly fertilized zygotes and subsequently shed during later transformation of the zygotes, has been identified as the target antigens of anti-gamete fertilization blocking antibodies. A single protein, synthesized and expressed on the zygote surface during its development to ookinetes, has been identified as the target of antibodies which block the development of the fertilized parasites in the mosquito. Immunization of human populations against gamete or zygote antigens, while not directly protecting an immunized individual from inflection, would reduce the transfer of malaria within the population. Such immunity, in addition to reducing the overall rate of malaria transmission, would, if combined with a vaccine against the asexual (disease-causing) stages, reduce the chance of selection of parasites that are resistant to the asexual vaccine by preventing their entry into the mosquito population.

Comparison of immunity to malaria in Sudan and Indonesia : crisis-form versus merozoite-invasion inhibition

Abstract: Immunity to falciparum malaria was compared in two populations from malarious areas of southern Sudan and Flores, Indonesia. In Sudan, splenomegaly in adults was rare and anti-plasmodium indirect fluorescent antibody (IFA) titers were low to moderate, 1:1,280 being the modal titer. Sudanese serum was profoundly inhibitory to cultured Plasmodium falciparum, reducing incorporation of radiolabeled hypoxanthine by 63-93% and severely retarding intraerythrocytic parasite development, resulting in moribund crisis-form parasites and virtually no healthy schizonts. In Flores, 64% of the serum donors had splenomegaly greater than or equal to Hackett spleen grade 4 or 5, and the modal IFA titer was 1:10,240. Sera from Indonesia did not retard intraerythrocytic parasite development, but inhibited merozoite erythrocyte invasion 22-87%. Anti-merozoite activity did not correlate with IFA titers. The differences in principal modes of anti-parasitic activity suggest that immunity to malaria in Sudan is based on cell-mediated immune mechanisms associated with crisis forms, merozoite neutralization being of secondary importance. In contrast, malaria immunity in Flores appears to be principally based on anti-merozoite antibody, which does not cause crisis forms and allows for development of reduced numbers of healthy schizonts. This less efficient mechanism may lead to a continuous low-grade parasitemia, which could explain the high specific malaria antibody titers and adult splenomegaly in Flores as compared to Sudan. This latter approach to immunity, being less efficient than the former, apparently results in chronic malaria infections with associated high Ig titers and splenomegaly.

Cerebral malaria in Tanzania. Its epidemiology, clinical symptoms and neurological long term sequelae in the light of 66 cases

Abstract: A neurological study of 66 patients with the cerebral form of Plasmodium falciparum malaria is presented. The patients were diagnosed, treated and re-examined at the Mnero Hospital, south-east Tanzania. Epidemiological aspects, neurological symptoms and the results of re-examination within six months of discharge from hospital are described. Although the mortality rate was low, some degree of neurological disability could be detected in a number of children at the follow-up examination.

Serum C-reactive protein levels and falciparum malaria

Abstract: A microplate ELISA was developed to measure C-reactive protein (CRP) and it was used to establish the relationship between CRP levels and malaria. Highest serum CRP levels were found in African patients with high Plasmodium falciparum parastaemia. However, even African children with lower parasitaemia had higher CRP levels than others without parasitaemia. All African groups studied had CRP levels above those of a control UK group.

Malaria in urban and rural areas of southern Ghana: a survey of parasitaemia, antibodies, and antimalarial practices.

Abstract: A comparative cross-sectional survey was undertaken in two populations, urban and rural, in southern Ghana to assess the impact of urbanization on the prevalence of malaria parasitaemia and antibodies. At the same time, a survey of antimalarial practices was conducted on sample populations in the two communities. The results showed a low parasite rate (1.6%) and correspondingly low titres of malaria antibodies in a significant proportion of the urban community, particularly in children less than 10 years old. This was associated with widespread use in the urban community of antimalarial drugs, particularly chloroquine, as prophylaxis. The parasite rate in the rural community was 22%, and 97% of the sample population over 1 year of age had antibodies against Plasmodium falciparum. These results demonstrate that a substantial proportion of urban children are growing up with little exposure to malaria, even in a region considered endemic for malaria. The implications of these findings are discussed.

Absence of malaria mortality in villagers with chloroquine-resistant Plasmodium falciparum treated with chloroquine

Abstract: We carried out a series of malaria studies in Robek, Flores, Indonesia, a coastal village of 900 farmers and fishermen where malaria is hyperendemic by parasite rate and holoendemic by spleen rate. The studies showed that: (i) 28 of 31 isolates (90%) of Plasmodium falciparum were resistant to chloroquine in vitro, (ii) 3 of 12 isolates (25%) were resistant at the R-II level in vivo, (iii) 376 P. falciparum infections occurred in 301 individuals during one year, (iv) no villagers who were treated with chloroquine for P. falciparum infections during the year died, and (v) increasing the dosage of chloroquine base from 15 to 25 to 37.5 mg/kg led to improved clearing of parasitaemia. We conclude that chloroquine can still be used as the primary antimalarial in Robek, but the dosage may have to be increased to clear parasitaemia.

Automated Erythrocyte Exchange in Fulminant Falciparum Malaria

Abstract: Excerpt With increasing travel to endemic areas and negligent prophylaxis, the number of gravely ill patients with malaria in this country is increasing (1) Prompt, effective treatment is essentia

Anaemia in young primigravidae in the guinea savanna of Nigeria: sickle-cell trait gives partial protection against malaria.

Abstract: Haematological indices, malarial parasitaemia, serum and red cell folate (SFA, RCF), serum vitamin B12 and haemoglobin (Hb) electrophoretic patterns were studied in 228 non-elite young Hausa primigravidae at less than 24 weeks of gestation. The study was conducted in the guinea savanna of Nigeria, where malaria is hyperendemic. Ninety-nine (43%) were anaemic (Hb less than 11.0 g dl-1). The commonest cause of anaemia was malaria, in 28% of all and 40% of anaemic subjects. Plasmodium falciparum was predominant; P. malariae was seen in 1.3% and P. ovale was not recorded. Parasitaemia was more frequent and more dense in the wet than the dry season. Iron deficiency was diagnosed in 18% of all and 25% of anaemic women; 14% of all patients were folate-deficient; high MCV and MCH correlated with anaemia, and low SFA was associated weakly with anaemia and malaria. Serum vitamin B12 was normal or high in all 145 in whom it was measured; 3% had congenital elliptocytosis, but this did not contribute to the anaemia. Sickle-cell trait was present in 26% and Hb-AC in less than 1%. Hb-AS was associated with significantly lower frequency and density of P. falciparum; this has not been demonstrated in pregnancy in Africa previously. However, the parasitological advantage was not reflected in any haematological advantage. The roles of malaria, folate-deficiency and iron-deficiency in the causation of anaemia in Hausa primigravidae will be defined further by a double-blind trial of antimalarial prophylactics, iron supplements and folic acid supplements.

The impact of malaria chemoprophylaxis in Africa with special reference to Madagascar, Cameroon, and Senegal.

Abstract: Some past and present experiences in the use of antimalarial drugs, particularly for chemoprophylaxis, are reviewed. The failure in the long term of mass chemoprophylaxis with weekly chloroquine in children in Madagascar, Cameroon, and Senegal is discussed, the reasons for failure being an increasing lack of resources to ensure regular drug distribution and lack of supervision of dosage. The increasing number of reports confirming chloroquine resistance from East Africa over the last decade poses a serious threat to the future usefulness of chloroquine as an antimalarial agent in Africa. There is now an urgent need for extensive drug sensitivity tests, which should also include alternative antimalarial drugs. To rely on mass chemoprophylaxis as the main method of controlling malaria would appear to be no longer tenable.

Treatment of gonorrhoea in males in the Central African Republic with spectinomycin and procaine penicillin

Abstract: In order to define the scope of vector control as a component of malaria control in the WHO African Region, examples of recent experiences with different vector control methods in this region are reviewed. Residual house spraying applied alone or in combination with mass drug administration has failed to interrupt malaria transmission in savanna areas for several technical and administrative reasons. Nevertheless, there is evidence that residual house spraying has led to an improvement in general health. However, the existence of DDT and dieldrin/HCH and lately malathion resistance in the Sudan in Anopheles gambiae s.l. would militate against the use of residual house spraying as a main tool for long-term malaria control. It should therefore be used only to reduce malaria prevalence to an acceptable level until integrated control methods can be developed and become operational.Experience with larval control, space spraying, and biological control of vectors is also reviewed, and the value of self-help methods of reducing man-vector contact under African conditions is examined. All these methods need to be more thoroughly assessed. Several proposals are made for applied field research.

Population movement and malaria persistence in Rameswaram Island.

Abstract: During 1982-84 the Vector Control Research Center (VCRC) of the Indian Council for Medical Research (ICMR) at Pondicherry studied the role of population movement in the persistence of malaria transmission in Rameswaram Island Tamil Nadu between mainland India and Sri Lanka. While the island supports a population of 56000 mostly fishermen there is also a periodic back and forth migration of fishermen between mainland villages and Rameswaram. This population movement greatly contributes to the high prevalence of malaria in both areas since fishermen can be either donor or recipient of malaria in either place. The VCRC monitered and recorded the movement of fishermen in various seasonal camps by questioning them and by the VCRC staff accompanying them when possible. In 9 fishing camps 412 of 1098 families had migrated from mainland villages; 686 families had migrated from villages within Rameswaram Island. A mass blood survey found 138 of 4073 individuals examined positive for malaria; 107 of 680 fever cases examined were positive for malaria. Mosquito collections the lack of permanent treatment facilities for the transient population and ecological factors indicate a high receptivity for malaria on Rameswaram Island. With the island attracting between 1000-4000 tourists daily and over 200000 travelers annually between India and Sri Lanka evidence exists for considerable danger from the importation of chloroquinine resistant malaria strains into Rameswaram. Adequate attention to human ecology will be needed for malaria control in this area.

Malaria-induced immune thrombocytopenia.

Abstract: . On return from Liberia, a previously healthy 36-year-old man showed signs of malaria accompanied by severe haemolysis and slight thrombocytopenia. We found evidence of a platelet-associated IgG being responsible for the thrombocytopenia, inasmuch as the direct platelet suspension immunofluorescence test was strongly positive, the indirect immunofluorescence test and tests for drug-dependent antibodies at the same time being negative. We suggest that autoimmunity may be a contributing mechanism for platelet destruction in acute malaria.

Lessons learned from applied field research activities in Africa during the malaria eradication era

Abstract: The Malaria Conference in Equatorial Africa, convened by the World Health Organization in 1950 in Kampala, Uganda, was a milestone in the history of modern malaria control activities on the continent of Africa It presented and assessed the available international information on epidemiological aspects of this disease and attempted to coordinate the various methods of research and control of malaria Its two main recommendations were that malaria should be controlled by all available methods, irrespective of the degree of endemicity of the disease, and that the benefits that malaria control might bring to the indigenous population should be evaluated The first period of field research and pilot control projects in Africa was between 1950 and 1964 A large number of studies in several African countries showed that the use of residual insecticides such as DDT and HCH might decrease, at times considerably, the amount of malaria transmission, but interruption of transmission could not be achieved, except in two relatively small projects in the forest areas of Cameroon and Liberia During the second period, from 1965 to 1974, the difficulties of malaria eradication and control in Africa became more evident because of the development of resistance of Anopheles gambiae to DDT, HCH, and dieldrin; moreover administrative, logistic, and financial problems had emerged It became clear that the prospects for malaria control (let alone those for eradication) were related to the availability of a network of basic health services A number of “pre-eradication” programmes were set up in order to develop better methods of malaria control and to improve the rural health infrastructures Much field research on the chemotherapy of malaria was carried out and the value of collective or selective administration of antimalarial drugs was fully recognized, although it became obvious that this could not play an important part in the decrease of transmission of malaria in Africa The role of research as one of the ways of solving the technical problems of malaria control in tropical Africa was stressed from the early days of the global malaria eradication programme; the past ten years have seen an immense expansion of this activity

Aspects of the behaviour of five anopheline species in the endemic malaria area of Natal

Abstract: Investigations of a mosquito outbreak due to an irrigation overflow in the endemic malaria area of Natal, Republic of South Africa, showed the presence of five anopheline species, viz. Anopheles merus. A. quadriannulatus, A. pharoensis, A, squamosus and A. tenebrosus. Aspects of their behaviour and the implications of this research are discussed.

Altered expression of human monocyte Fc receptors in Plasmodium falciparum malaria.

Abstract: The state of activation of human peripheral blood monocytes was examined by using a rosette assay that detects changes in Fc receptor expression. Monocytes from patients with uncomplicated Plasmodium falciparum malaria showed a significant increase in the number of rosettes relative to healthy controls. In addition, the monocytes from these patients were tested for their ability to phagocytose Candida albicans, but this ability did not differ from that of normal individuals. Finally, the monocytes from patients with cerebral malaria were also tested for Fc receptor expression. In contrast to the results from uncomplicated cases, the activity of the monocytes from these patients was no different from that of controls. We concluded that uncomplicated P. falciparum malaria caused an increase in monocyte Fc receptor expression which did not occur in cerebral malaria and that this difference in activation may be important in the pathogenesis of cerebral malaria.

Factors contributing to the development of cerebral malaria. I. Humoral immune responses.

Abstract: Humoral immune responses to malaria were studied in 100 patients with cerebral malaria of whom 53 had added complications, 108 patients with acute malaria, and 100 blood donors. The methods employed were indirect hemagglutination (IHA), indirect fluorescent antibody (IFA), enzyme-linked immunosorbent assay (ELISA), and parasite growth inhibition (PGI) tests. Patients with cerebral malaria, especially those with complications, had histories of fewer attacks of malaria in the previous 5 years than did those with acute malaria, suggesting that the cerebral malaria patients were less immune. The combined cerebral malaria group (complicated and uncomplicated) did not show defective humoral immune responses, since the initial seronegative rate and the mean initial IHA and IFA antibody titers were not significantly different from those of acute malaria patients and the mean initial ELISA titer was even higher than that of the acute malaria group. Reduced humoral responses were found only in complicated cerebral malaria patients, as their mean initial IHA titer was lower and their IHA seronegative rate was higher than those in acute malaria patients and in the uncomplicated cerebral malaria group. The combined cerebral malaria group had greater PGI activity than that of acute malaria patients, but this increased activity was entirely due to the higher results obtained in the complicated cerebral malaria group. The increased PGI activity returned to normal after recovery. An IgG preparation from seven of eight of these sera failed to exert the growth inhibition effect. Factors other than IgG were therefore responsible for the inhibition of parasite growth.