Showing papers on "Malaria published in 1989"

Malaria: Principles and Practice of Malariology

Abstract: Conceived as a comprehensive review of natural science and the methods of malaria control, this book brings together the results of laboratory research and epidemiological field studies. For the novice, it provides a an introduction to malariology as a biological system, a disease and a serious public health problem. For the initiated reader, it gives wide-ranging information intended to aid the further orientation of work. After a historical introduction, this account covers the biology of malaria parasites and their arthopod vectors, host/parasite relationships, the clinical features, diagnosis and treatment of the disease, and its epidemiology. This is followed by a review of animal models in malaria studies, and the trends of chemotherapeutic and immunological research.

Antibodies to blood stage antigens of Plasmodium falciparum in rural Gambians and their relation to protection against infection.

Abstract: Cross-sectional and longitudinal studies were performed in a rural population living in The Gambia to examine the relationship between several in vitro assays of the host immune response to asexual stages of Plasmodium falciparum and protection from malaria in vivo. Assays included an enzyme-linked immunosorbent assay for antibodies to schizont antigens; an indirect immunofluorescence assay for total antiblood-stage antibodies; an immunofluorescence assay on glutaraldehyde-fixed parasites to detect antibodies to antigen Pf 155; an assay for serum inhibition of red blood cell invasion; a micro-agglutination assay to detect antibodies to neo-antigens on the surface of infected red blood cells; and an assay using polymorphonuclear leucocytes to detect antibodies capable of opsonizing schizont infected red blood cells. There were marked differences in the age-related pattern of response for different assays performed on sera obtained at a cross-sectional survey of 280 individuals. Examination of the correlation between the various immune responses and malariometric indices at the population level and at the individual level provided no evidence that any of the in vitro assays were related to protective immunity. The relationship between in vitro measurements of the anti-malarial immune response and protection from clinical episodes of malaria was examined in a group of 134 children aged 11 years and under who were monitored weekly throughout an entire malaria transmission season. The only immune factor to show a consistent protective effect against clinical malaria was the titre of antibodies to neo-antigens on the infected erythrocyte surface (P = 0.01). The same longitudinal techniques were used to examine the effect of two non-immunological factors, sickle cell trait and mosquito net usage, both of which showed significant protection against clinical episodes and malaria.

Rationale for the development of an engineered sporozoite malaria vaccine.

Abstract: Publisher Summary This chapter discusses the rationale for developing sporozoite vaccines Sporozoites are the infective stages of the parasite found in the salivary glands of female Anopheles mosquitoes Infection by Plasmodium vivax is also widespread and causes an acute or subacute disease, chronic anemia and splenomegaly but is not usually lethal or drug resistant At the other end of the spectrum, Plasmodium malariue is well adapted to the human host and produces chronic illness that can persist for many years The symptoms are similar to those of P vivax infection, but relapses are less frequent Attempts to control the spread of the infection by combating the Anopheles mosquito vectors have failed Vaccine development has become an important research priority Unfortunately, however, this task is complicated by several problems; some are associated with unique features of this parasite and others, of a more fundamental nature, are associated with the obstacles facing the design of rational, efficient, engineered subunit vaccines that contain multiple B and T cell epitopes One of the problems in developing a malaria vaccine is that this parasite has a very complex life cycle and each stage bears different protective antigens In spite of the formidable obstacles, considerable progress has been made in the past few years and a few candidate malaria vaccines have been tried in humans with partial success

Tumour necrosis factor production in Falciparum malaria and its association with schizont rupture.

Abstract: To investigate the involvement of tumour necrosis factor (TNF) in human malaria, we studied TNF production in patients infected with Plasmodium falciparum, and in co-cultures of human mononuclear cells and malaria parasites in vitro In the examined sample, plasma TNF levels of over 39 pg/ml were detected in the plasma of 59% of Gambian children with acute malaria, 17% of convalescents, 9% of children with mild infections other than malaria, and 7% of healthy Gambian adults Mononuclear cells of acute malaria patients, when stimulated with endotoxin in vitro, secreted twice as much TNF as did those of convalescent individuals, and three times that of healthy adult controls Erythrocytic cultures of P falciparum stimulated increased TNF secretion by mononuclear cells from uninfected individuals, and a sharp rise in the rate of secretion occurred shortly after schizont rupture We suggest that malaria fever is mediated, at least in part, through paroxysmal TNF release associated with schizont rupture

3. Impact of culture and environmental changes on epidemiology and control of malaria and babesiosis. The microepidemiology of malaria and its importance to malaria control

Abstract: Recent studies in West Africa and in Papua New Guinea have shown that the prevalence of malaria can vary widely between neighbouring villages and within different parts of the same village. Both genetic and environmental factors are likely to contribute to these variations. Clustering in households of genetically determined red cell abnormalities, and possibly of immune response genes, may contribute to differences in the prevalence of malaria within a village. Environmental factors probably play the major part in explaining differences between villages. The position of a village in relation to mosquito breeding sites, die design of houses and the level at which anti-mosquito measures are used will all influence the degree to which its inhabitants are exposed to infection. Attitudes to the treatment of a case of malaria may also contribute to local variations in the prevalence of malaria. Malaria parasitaemia and splenomegaly will be less frequent in a community where effective treatment is given immediately at home, or sought promptly from a primary health care worker, than in a neighbouring community where there is a much greater reliance on traditional medicines. Recognition of local variations in the prevalence of malaria is important because identification of the factors responsible for a low prevalence in one village but a high one in a neighbouring community may indicate a possible control measure. Local variations in the epidemiology of malaria must also be taken into account when any kind of malaria intervention trial is planned.

Febrile temperatures can synchronize the growth of Plasmodium falciparum in vitro.

Abstract: To investigate the possibility that the host fever response in malaria may affect parasite development, we studied the effect of temperature on Plasmodium falciparum in erythrocytic culture in vitro. Growth was markedly suppressed at 40 degrees C compared with 37 degrees C, due to disruption of the second half of the 48-h erythrocytic cycle. However, young intraerythrocytic parasites, which are highly exposed to fever during natural infection, appeared to develop normally at 40 degrees C. Because of the differential temperature sensitivity within the erythrocytic cycle, asynchronous cultures could be synchronized by transient elevations of temperature. Pronounced synchronization was observed when cultures were exposed to periodic elevations of temperature that simulated the 48-h fever cycle of tertian malaria. These findings indicate that malaria fever might act to promote parasite synchronization in vivo.

Tropical obstetrics and gynaecology. 1. Anaemia in pregnancy in tropical Africa

Abstract: Major causes of anaemia in pregnancy in tropical Africa are malaria, iron deficiency, folate deficiency and haemoglobinopathies: now there is added also the acquired immune deficiency syndrome (AIDS). Anaemia is often multifactorial, with the different causes interacting in a vicious cycle of depressed immunity, infection and malnutrition. Anaemia progresses through 3 stages: compensation, with breathlessness on exertion only; decompensation, with breathlessness at rest and haemoglobin (Hb) below about 70 g/litre; cardiac failure, with Hb below about 40 g/litre. Without treatment, over half of the women with haematocrit less than 0.13 and heart failure die. Maternal anaemia, malaria and deficiencies of iron and folate cause intrauterine growth retardation, premature delivery and, when severe, perinatal mortality. Surviving infants have low birthweights, immune deficiency and poor reserves of iron and folate. They have entered already the vicious cycle of infection, malnutrition and impaired immunity. Treatment with blood transfusions is even more hazardous since the advent of AIDS, and should be limited to saving the life of the mother. Treatment of malaria is complex as chloroquine-resistant strains are now common. Prevention remains relatively easy with proguanil and supplements of iron and folic acid and is highly cost-effective in the improvement of maternal and infant health; it is more important than ever as it avoids the unnecessary exposure of women and infants to HIV transmitted through blood transfusion.

Treatment of malaria: some considerations and limitations of the current methods of assessment

Abstract: The currently used methods for assessing the therapeutic response to antimalarial drugs are relatively imprecise and insensitive. These methods are inadequate in severe malaria when the objectives of treatment are to save life and prevent complications. Very large studies are needed to demonstrate significant differences in mortality, but measurement of the rates of clinical, biochemical, and parasitological response may provide useful comparative information. Definitions, assessment criteria, procedures, and data collection forms should be standardized and evaluated prospectively. Antimalarial drug treatment in different clinical situations should be assessed in terms of the balance between the risks of drug toxicity and the benefits of the antimalarial drug action. This balance is considerably different in severe falciparum malaria compared with uncomplicated malaria infections.

Hospital-based surveillance of malaria-related paediatric morbidity and mortality in Kinshasa, Zaire.

Abstract: Although Plasmodium falciparum malaria is a leading cause of paediatric morbidity and mortality in Africa, few quantitative estimates are available about the impact of malaria on childhood health. To quantify the impact of the disease in an urban African setting, we reviewed the paediatric ward and mortuary records at Mama Yemo Hospital in Kinshasa, Zaire. From June 1985 to May 1986, 6208 children were admitted to the hospital, 2374 (38.2%) of whom had malaria; 500 of those with malaria died (case fatality rate, 21.1%). During this same period, there were 10,036 paediatric deaths, 1323 (13.2%) of which were attributed to malaria; 823 (62.2%) of these occurred in the emergency ward prior to hospitalization. Minimum population-based malaria mortality rates were highest for children aged less than 1 year (4.0 per 1000 per year). Over 70% of children admitted with malaria and greater than 80% of children who died from the disease were less than 5 years old. The total number of paediatric admissions and deaths remained relatively constant between 1982 and 1986; however, the proportional malaria admission rate increased from 29.5% in 1983 to 56.4% in 1986, and the proportional malaria mortality rate, from 4.8% in 1982 to 15.3% in 1986. These increases were temporally related to the emergence of chloroquine-resistant Plasmodium falciparum malaria in Kinshasa. Malaria is therefore a major cause of paediatric morbidity and mortality in the city, and this study indicates that hospital-based surveillance may be useful in monitoring disease-specific morbidity and mortality elsewhere in Africa.

Reduced Hepatic Blood Flow and Intestinal Malabsorption in Severe Falciparum Malaria

Abstract: We have studied intestinal function and liver blood flow in Thai adults with complicated and uncomplicated falciparum malaria. The absorption of 3 orally administered test sugars, D-xylose, 3-O-methyl-D-glucose, and L-rhamnose, was greatly reduced in complicated malaria, while the lactulose/rhamnose absorption ratio was significantly increased. Hepatic blood flow was concomitantly reduced in severe malaria. These deviations reverted to normal in convalescence. Neither sugar absorption nor liver blood flow was reduced in uncomplicated falciparum malaria.

Suppression of cell-mediated immune responses to malaria antigens in pregnant Gambian women.

Abstract: In malaria endemic areas, pregnancy predisposes previously immune women to clinical and subclinical malaria infection. While parameters of humoral immunity do not seem to be affected to pregnancy, suppression of cellular immunity has been demonstrated for a number of antigens. In this study of women from a rural area of the Gambia where falciparum malaria is holoendemic, we show that lymphoproliferative responses to Plasmodium falciparum antigens are depressed in pregnant women compared to parity matched non-pregnant women, and that this effect is particularly marked in primigravidae. The data also indicate that malaria antigen induced γ-interferon production may be depressed in pregnant women. There was no significant difference in antimalarial antibody titers between the 2 groups.

Diversity of antigens expressed on the surface of erythrocytes infected with mature Plasmodium falciparum parasites in Papua New Guinea.

Abstract: Antigens were detected on the surface of erythrocytes from children with acute falciparum malaria in Madang, Papua New Guinea. These parasite-induced erythrocyte surface antigens (PIESA) were serotyped with convalescent sera from children and hyperimmune sera from adults in parasite infected cell agglutination assays (PICAs) and by inhibition of binding of infected cells to melanoma cells. Extensive serological diversity of PIESA was demonstrated. A significant correlation between serotypes defined by reactivity of immune sera in PICA and inhibition of melanoma cell binding (MCB) was observed. This suggests that both assays measure antibody responses to the same antigen(s). Increased recognition of different PIESA specificities with age is consistent with the hypothesis that repeated exposure to malaria confers immunity against a range of PIESA serotypes and parallels the development of clinical immunity to malaria in this area of Papua New Guinea.

Airport malaria: a review.

Abstract: Cases of malaria occasionally arise among individuals who have never visited a malarious area. Such patients, who also lack a history of blood transfusions or intravenous drug abuse, are usually shown to have "airport malaria". Most reports of airport malaria consist of case histories, although some epidemiological reviews have also appeared. The clinical and epidemiological features of 29 cases of airport malaria that were reported in Europe from 1969 to 1988 are reviewed here. Although airport malaria is rare, the apparent absence of risk factors for the disease in a patient's history can result in delays in diagnosis and appropriate treatment. Tests to exclude malaria should therefore be carried out on patients who work at or live near an international airport and who present with acute febrile illnesses.

Dissection of the human antibody response to the malaria antigen Pf155/RESA into epitope specific components.

Abstract: The development of vaccines is presently receiving major attention in malaria research. As it is not possible to base malaria vaccines on the use of killed or attenuated organisms, the vaccines which are being developed are subunit vaccines in which the immunogens consist of defined parasite antigens or antigenic fragments. Since protective immunity to malaria involves both antibody-dependent and antibody-independent mechanisms, the immunogens in a subunit vaccine must have the capacity to induce relevant B- and T-cell responses in the majority of vaccinees. In turn, this requires good knowledge of these responses in humans who have acquired immunity through natural infection. In this paper we have summarized our recent work on the dissection into epitope-specific components of the human antibody response to the Plasmodium falciparum antigen Pf155/RESA, a recognized candidate for a vaccine against the asexual blood stages of this parasite. Epitope mapping of the antigen by means of short synthetic peptides led to the identification in several molecular regions of short amino acid sequences constituting linear and probably immunodominant B-cell epitopes. The antigenically most active region was located in the C-terminus of the molecule. This region, which consists of approximately 40 related, 4- or 8-amino acid long repeats, induced higher antibody concentrations in a larger number of malaria-immune donors than any of the other regions. A large fraction of these antibodies bound to short synthetic peptides representing the major repeat motifs of Pf155/RESA. Although these repeats are made up of closely related amino acid sequences, the antibody response to them was highly polyclonal, indicating the presence of several linear and probably also conformational epitopes which gave rise to a variety of cross-reacting as well as monospecific antibodies. Further analysis revealed that the levels of antibodies differing in specificity and/or avidity for different peptides varied independently of each other in individual donors. In an area (Liberia) where malaria transmission is holoendemic and perennial, these antibody profiles remained constant when individual donors were followed over several years. Since the C-terminal repeat region of Pf155/RESA is conserved in different P. falciparum strains, the results reflect differences in the genetic regulation of epitope-specific host responses rather than antigenic differences between infecting parasites. In donors living in an area with high but seasonal malaria transmission, antibody levels usually drop to lower levels when there is no transmission.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of a malaria suppression program on the incidence of african burkitt's lymphoma

Abstract: From 1977 to 1982, the authors attempted a malaria suppression trial in North Mara District, Tanzania, to see whether the incidence of Burkitt's lymphoma (BL) could be lowered by reducing the level of malarial infection in a child population below 10 years of age. Immediately after initiation of the suppression trial, the prevalence of malaria fell drastically in the Mara children; however, soon after, the rate of malarial infection rose again in the trial area in spite of continued chloroquine distribution, and by 1981 the prevalence of malarial infection again reached the high levels that had prevailed in the North Mara lowlands before 1977. However, during the period of chloroquine distribution in North Mara, the level of malarial infection there was constantly lower than that observed in a comparison area in South Mara, although the two areas had been similar with respect to malaria endemicity prior to the intervention. During the years of chloroquine distribution in North Mara, the incidence rate of BL there fell considerably, from about 4 per 100,000 population to about 1 per 100,000 population, and it rose again to pretrial levels in 1984, that is, about two years after the chloroquine distribution had been terminated. This apparent association between malaria suppression and decline in BL incidence at first seemed to indicate that malaria is a causal factor in BL production. A close scrutiny of the survey data revealed, however, that the decline in BL incidence might have started several years before the chloroquine distribution began; thus it appears that the malaria suppression could not have been the sole cause of the BL decline.

The effects on malaria of treatment of iron-deficiency anaemia with oral iron in Gambian children

Abstract: In order to determine whether giving iron to iron-deficient children increases their susceptibility to malaria, 213 Gambian children aged between 6 months and 5 years with iron-deficiency anaemia were randomized to receive either oral iron or placebo during the rainy season when malaria transmission is maximal. Haematological and iron measurements improved significantly in the group given iron. Regular morbidity surveys showed that fever associated with parasitaemia occurred more frequently in the iron-treated group than in the placebo group. This difference was not significant for all parasitaemias grouped together, but became significant and progressively larger for parasitaemias of ten or more positive fields per 100 high power fields (P less than 0.025), and for parasitaemias of 50 or more positive fields per 100 high power fields (P less than 0.01). Three children in the iron-treated group but none in the placebo group had more than one episode of fever and parasitaemia. Splenomegaly rates rose appreciably during the study in both groups, but in children at age 2 years the splenomegaly rate at the end of the study was significantly greater in the iron-treated group. We concluded that there is a significantly increased risk of fever associated with severe malarial parasitaemia for children with iron-deficiency anaemia given iron during the season of maximal malaria transmission in this part of The Gambia.

Effectiveness of zooprophylaxis in malaria control: a theoretical inquiry, with a model for mosquito populations with two bloodmeal hosts

Abstract: A model for a vector mosquito population with two bloodmeal hosts (man and a domestic animal) was developed to study the influences of domestic animals on the frequency of mosquito bites on man and the endemicity of human malaria. The vector population model, including blood-feeding success in the adult stage (depending on host density and biting efficiency) and density-dependent regulation in the larval stage, was combined with the Ross-Macdonald malaria transmission model. Model analyses suggested that introduction of domestic animals easily fed upon by mosquitoes increases mosquito density and, in some situations, frequency of mosquito bites on man and the infection rate of malaria through increased success of blood-feeding. Extinction of malaria was predicted only when an extremely large number of easily accessible (as compared to man) domestic animals are introduced. Limitations in the concept of zooprophylaxis and problems of livestock management in malaria control are discussed.

The effect of iron therapy on malarial infection in Papua New Guinean schoolchildren.

Abstract: The effect of iron therapy on malarial infection was investigated in Papua New Guinea, where malaria is endemic. Prepubescent schoolchildren with hemoglobin levels of 8-12 g/dl were randomly assigned to receive either 200 mg ferrous sulfate or a placebo twice daily for 16 weeks. Iron status and malarial infection were assessed at baseline, after 6 and 16 weeks of therapy, and 8 weeks after therapy was discontinued. Iron status was significantly improved by the treatment. The treatment did not significantly affect parasite rate, parasite density, or levels of anti-malarial IgG. No changes in spleen size were observed in either group. Furthermore, there was no significant difference between the groups in reported episodes of suspected malaria during the therapy. These results suggest that, in malaria endemic areas, oral treatment for iron deficiency can be carried out in semi-immune or immune schoolchildren without adverse consequences.

Malaria, Epstein-Barr Virus, and the Genesis of Lymphomas

Abstract: Publisher Summary This chapter discusses the pathogenesis of endemic Burkitt's lymphoma (eBL) emphasizing on the role of malaria and Epstein–Barr virus (EBV) and their respective interactions with the immune system in the genesis of the lymphoma. The immunosuppressive features of malaria are also discussed. There are three major immunological roles for malaria as a cofactor—as a stimulator of the polyclonal B-cell proliferation, as a mediator of the defective cytotoxic T-cell (CTL) response to EBV, and as an enhancer of the EBV-induced lymphocyte transformation and the EBV genome amplification. The risk of all genetic accidents is directly related to the number of cell divisions, and malaria therefore enhances the chance of a chromosomal translocation. Malaria is postulated as a risk factor for the genesis of BL as it causes hyperactivity of the germinal centers. The lymphoproliferative (antigenic and mitogenic) effect of malaria and the subsequent drive towards Ig production can enhance the chance of chromosomal aberrations.

The aetiology of severe anaemia in pregnancy in Ndola, Zambia

Abstract: The aetiology of severe anaemia (haemoglobin less than 7.0 g dl-1) has been studied in 37 pregnant Zambians. Aetiology was usually multiple; 31 (84%) had Plasmodium falciparum malaria, 23 (62%) were folate deficient, 13 (35%) were iron deficient, one had sickle-cell anaemia and one had the acquired immunodeficiency syndrome (AIDS). Folate deficiency was most often secondary to malarial haemolysis: iron deficiency was nutritional, but hookworm was contributory in about one-third of patients. The anaemia of malaria and folate deficiency was both more common and more severe than anaemia due to iron deficiency; it was seen in younger women although primigravidae were not over-represented, it occurred earlier in pregnancy, and was associated with low birthweight. AIDS must now be included in the differential diagnosis of anaemia in pregnancy. Vigorous antimalarial treatment and prophylaxis are essential in the management and prevention of anaemia in pregnancy. Total dose iron infusion is indicated only when severe iron deficiency anaemia has been proven, and must be accompanied by antimalarial therapy and folic acid supplements. Because of the risk of transmission of human immunodeficiency virus, it is more important than ever to prevent anaemia and malaria in pregnancy, and to give blood transfusion only as a life-saving treatment.

Mechanisms of splenic control of murine malaria: cellular reactions of the spleen in lethal (strain 17XL) Plasmodium yoelii malaria in BALB/c mice, and the consequences of pre-infective splenectomy.

Abstract: The splenic response in lethal 17XL Plasmodium yoelii murine malaria is vigorous, displaying marked phagocytosis, erythropoiesis, lymphopoiesis, plasmacytopoiesis, and, from day 3 of infection, increasing levels of parasitized erythrocytes. There is also a pronounced response of newly characterized fibroblastic stromal cells which branch and fuse with one another, forming extensive, complex, irregular, syncytial membranous sheets which provide a variety of barriers. Hence, I term these barrier cells (BC), and their fusion results in barrier-forming complexes (BFC). BC form adherent surfaces, trapping parasitized erythrocytes and monocytes-macrophages, facilitating phagocytosis. They envelop single plasma cells, erythrocytes, erythroblasts, lymphocytes, reticulocytes, monocytes-macrophages, or clusters of them. They surround blood vessels, forming blood-spleen barriers. They are insinuated into the circumferential reticulum at the periphery of white pulp, isolating white pulp. They form channels in red pulp, directing blood flow. They are associated with collagen. There appear to be several sources of BC. They may originate by activation of established reticular cells which form the filtration beds, by activation of reticular cells covering the pulp surface of capsule and trabeculae, and as a major source in this malaria, from circulating progenitors entering the splenic pulp from the vasculature. In non-lethal malaria, these barrier systems protect splenic reticulocytes from parasitization. In the lethal 17XL malaria they do not, and there follows a considerable increase in parasitization in the spleen with a corresponding increase in active macrophages. Large-scale parasitization and parasite recycling through the great stores of splenic reticulocytes in the lethal malaria, and the failure of parasitization of these splenic reticulocytes reserves on the non-lethal malaria, suggests that the actions of the spleen aggravate the lethal malaria and ameliorate the non-lethal. This is supported by the finding that non-lethal malaria is aggravated and lethal malaria ameliorated by splenectomy.