Showing papers on "Malaria published in 1988"

A vaccine candidate from the sexual stage of human malaria that contains EGF-like domains.

Abstract: Malaria vaccines are being developed against different stages in the parasite's life cycle, each increasing the opportunity to control malaria in its diverse settings. Sporozoite vaccines are designed to prevent mosquito-induced infection; first generation recombinant or synthetic peptide vaccines have been tested in humans. Asexual erythrocytic stage vaccines, developed to prevent or reduce the severity of disease, have been tested in animals and in humans. A third strategy is to produce sexual stage vaccines that would induce antibodies which would prevent infection of mosquitoes when ingested in a bloodmeal containing sexual stage parasites. Although not directly protective, the sexual stage vaccine combined with a sporozoite or asexual stage vaccine (protective component) could prolong the useful life of the protective component by reducing transmission of resistant vaccine-induced mutants. In areas of low endemnicity, the sexual stage vaccine could reduce transmission below the critical threshold required to maintain the infected population, thereby assisting in the control or eradication of malaria. Transmission of Plasmodium falciparum, the major human malaria, can be blocked by monoclonal antibodies against three sexual stage-specific antigens. We have cloned the gene encoding the surface protein of relative molecular mass Mr 25,000 (25K; Pfs25), expressed on zygotes and ookinetes of P. falciparum. The deduced amino-acid sequence consists of a signal sequence, a hydrophobic C-terminus, and four tandem epidermal growth factor EGF-like domains.

Human cerebral malaria.

Abstract: Possible factors contributing to the development of cerebral malaria were discussed based on pathological changes in Burmese patients who died of cerebral malaria Blockage of cerebral capillaries by Plasmodiumfakiparum infected erythrocytes appeared to be the principal cause of cerebral malaria From electron microscopic results, it was concluded that knobs on infected erythrocytes acted as focal junctions which mediated adhesion to endothelial cells The knobs are, therefore, important contributors to the blockage of the capillary lumen and ensuing pathological changes in cerebral tissues Host cell molecules such as OKM5 and thrombospondin may function as endothelial cell surface receptors for the attachment of knobs of Pfakiparum infected erythrocytes Immunological events might also play a role in the pathogenesis of cerebral malaria This was suggested by the presence of IgG, 1gM, P falciparum antigens, and knob proteins in the cerebral capillaries of the people with cerebral malaria It will be important to assess the candidate malaria vaccines now in development not only for their efficacy in reducing parasitemia but for effects they may have on the sequestration of infected erythrocytes in the brain

Use and limitations of light microscopy for diagnosing malaria at the primary health care level

Abstract: Recent developments in diagnostic techniques for malaria, particularly DNA probes and sero-immunology, have raised questions as to how these techniques might be used to facilitate malaria diagnosis at the most peripheral levels of the primary health care system. At present, malaria diagnosis is based on the light microscope and is likely to remain so in the immediate future. This article describes how the diagnosis of malaria by light microscopy has been improved over the years, and expresses the need for further improvement while concomitant research into other standardized and simplified techniques for the diagnosis of malaria is vigorously pursued.

Permethrin-treated bed nets (mosquito nets) prevent malaria in Gambian children

Abstract: The incidence of clinical attacks of malaria was significantly less in Gambian children aged 1-9 years who slept in villages where all the bed nets (mosquito nets) were treated with permethrin than in children who slept in control villages with placebo-treated nets. Significant differences in changes in spleen size and in packed cell volume were also observed between the 2 groups during the course of a rainy season. No side effect was noted. Treatment of bed nets with insecticide is a form of malaria control that is well suited to community participation and can readily be incorporated into primary health care programmes. Insecticide-treated nets may be more effective in areas of seasonal or low intensity transmission than in areas with heavy perennial challenge.

The association between malaria, blood transfusions, and HIV seropositivity in a pediatric population in Kinshasa, Zaire.

Abstract: SincePlasmodium falciparummalaria is a frequent cause of anemia among African children, and blood transfusions, unscreened for human immunodeficiency virus (HIV) antibody, are used frequently in the treatment of children with severe malaria, the relationships between malaria, transfusions, and HIV seropositivity were investigated in a pediatric population in Kinshasa, Zaire. In a cross-sectional survey of 167 hospitalized children, 112 (67%) had malaria, 78 (47%) had received transfusions during the current hospitalization, and 21 (13%) were HIV seropositive. Ten of the 11 seropositive malaria patients had received transfusions during the current hospitalization; pretransfusion specimens were available for four of these children and were seronegative. Of all blood transfusions, 87% were administered to malaria patients, and there was a strong dose-response association between transfusions and HIV seropositivity. A review of 1000 emergency ward records demonstrated that 69% of transfusions were administered to malaria patients, and 97% of children who received transfusions had pretransfusion hematocrits of 0.25 or less (≤25%). The treatment of malaria with blood transfusions is an important factor in the exposure of Kinshasa children to HIV infection. (JAMA1988;259:545-549)

A trial of bed nets (mosquito nets) as a malaria control strategy in a rural area of The Gambia, West Africa

Abstract: An intervention trial was undertaken in a rural area of The Gambia to assess the impact on malaria morbidity of the use of bed nets. Bed nets were allocated at random among a group of 16 Fula hamlets, where they were previously rarely used. The incidence of febrile episodes with associated malaria parasitaemias throughout the rainy season and the prevalence of splenomegaly and parasitaemia at the end of the rainy season were determined in 233 children aged 1-9 years who slept under bed nets and in 163 children who did not. Bed nets were used correctly by the children in the study cohort, but direct observations showed that a significant number of children left their nets for a period during the night. There was no significant difference in the incidence of clinical attacks of malaria or in any other malariometric measurement between the 2 groups. Thus, bed nets were not effective in reducing malaria morbidity in this group of children. The apparent protection from bed nets demonstrated in previous retrospective surveys may have been due to an increased number of infective bites being received by exposed individuals sleeping close to users of bed nets.

Malaria studies and control in Brazil

Abstract: In the greater part of Brazil's extensive territory climatic conditions are propitious for the establishment of endemic malaria, which has been causing pain and death among the country's inhabitants for generations. In Brazil the epidemiology of malaria has presented some peculiar aspects: besides being transmitted in most areas by anophelines breeding in groundwater collections, its dissemination in a restricted but economically important zone was entirely due to mosquitoes breeding in water accumulated in plants of the family Bromeliaceae. It is the so called “bromeliad malaria.” To the native vector species, the alien Anopheles gambiae, introduced to the country, added a new problem. Considerable efforts have been made by Brazilians and foreigners to understand malaria epidemiology and control its transmission. Among the foreigners one immediately thinks of Fred Lowe Soper. Following his contribution to the elimination of Aedes aegypti and urban yellow fever in Brazil, Soper was one of those most directly responsible for the eradication of An. gambiae from this part of the world.

Chloroquine treatment of severe malaria in children. Pharmacokinetics, toxicity, and new dosage recommendations.

Abstract: Although empirical regimens of parenteral chloroquine have been used extensively to treat severe malaria for 40 years, recent recommendations state that parenteral chloroquine should no longer be used because of potential toxicity. We studied prospectively the pharmacokinetics and toxicity of seven chloroquine regimens in 58 Gambian children with severe chloroquine-sensitive falciparum malaria. In all regimens the total cumulative dose was 25 mg of chloroquine base per kilogram of body weight. Chloroquine was rapidly absorbed after either intramuscular or subcutaneous administration (5 mg of base per kilogram every 12 hours), producing high peak blood concentrations but transient hypotension in 5 of 18 patients (28 percent). Intermittent intravenous infusion (5 mg of base per kilogram over 4 hours, repeated every 12 hours) also produced wide fluctuations in chloroquine levels, suggesting incomplete distribution from a small central compartment. Continuous infusion (0.83 mg of base per kilogram per hour for 30 hours) and smaller, more frequent intramuscular or subcutaneous injections of chloroquine (3.5 mg of base per kilogram every 6 hours) produced smoother blood-concentration profiles with lower early peak levels and no adverse cardiovascular or neurologic effects. Chloroquine given by nasogastric tube (initial dose, 10 mg of base per kilogram) was absorbed well, even in comatose children. We conclude that simple alterations in dosage and frequency of administration can give parenteral chloroquine an acceptable therapeutic ratio and reinstate it as the treatment of choice for severe malaria in areas where chloroquine resistance is not a major problem.

Cellular immune responses to Plasmodium falciparum antigens in Gambian children during and after an acute attack of falciparum malaria.

Abstract: Peripheral blood mononuclear cells from 63 Gambian children with acute Plasmodium falciparum malaria were examined for lymphoproliferation and interferon-gamma (IFN) production in response to stimulation by mitogens, malaria antigens and other soluble antigens. Mitogen or Candida-induced proliferation was not depressed during acute infection but was enhanced 2 to 4 weeks after treatment. Responses to partially purified soluble P. falciparum antigens were minimal or absent in all children in the acute phase but approximately 50% of the children responded by proliferation or IFN-gamma production during the 2 to 8 week convalescent period. These proliferative responses were severely depressed in the presence of the patient's own serum. Nine children with significant convalescent phase proliferative responses were re-examined several months after acute infection. Of these, four remained responsive for at least 8 months in the probable absence of reinfection.

Malaria in Korea.

Abstract: Malaria was steadily decreasing in Korea except in certain counties of the mountainous and hilly areas, in the 1960s. Judging from the present epidemiological, social and economic conditions, it can be said with confidence that malaria with "unstable" characteristic in the Republic of Korea has already been disappeared. No doubt, the causes of the disappearance of malaria are complex. Certainly improved living conditions and life style; better medical and educational facilities in the wake of a rapid economic development could all have some role. On the other hand, the disappearance of malaria without large scale control operations could be ascribed to the two main factors: one is malaria case detection and simultaneous drug therapy available through the nation-wide passive case detection network during the 1960s and the other is rapidly improved farming practices begun in 1970s, which resulted in the use of a huge quantity of pesticides and other chemicals for agriculture, which, in turn, might affect local anopheline vectors which were originally not effective ones any way.

Monoclonal and polyclonal antibodies both block and enhance transmission of human Plasmodium vivax malaria.

Abstract: Antibodies against gametes of the malarial parasite inhibit the development of the parasite in the mosquito and curtail the transmission of malaria. We now report that a monoclonal antibody against gametes of the human malaria pathogen Plasmodium vivax and antibodies induced during natural infections of P. vivax in humans which suppress infectivity of the parasites to the vector at high concentrations can, at lower concentrations, have the opposite effect and enhance the level of malaria infection in the mosquitoes. Infectivity enhancing effects of up to 12-fold were demonstrated when a transmission blocking monoclonal antibody and immune human sera were diluted, in some undiluted immune human sera, and in the sera of vivax malaria patients during convalescence after drug cure.

Prevalence and levels of antibodies to the circumsporozoite protein of Plasmodium falciparum in an endemic area and their relationship to resistance against malaria infection.

Abstract: A study on malaria transmission, prevalence of infection and anti-sporozoite antibodies was carried out in Burkina Faso (West Africa). The prevalence and the levels of antibodies to (NANP)3 were found to be related to the entomological sporozoite inoculation rates measured at the same time in a defined area. The major inducer of anti-(NANP)3 antibody production under field conditions is sporozoite inoculation by infected mosquitoes. Levels of antibodies to (NANP)3 vary considerably with age and transmission season. High levels of anti-(NANP)3 antibodies raised under field conditions might offer protection against small inocula of sporozoites.

Defective production of and response to IL-2 in acute human falciparum malaria.

Abstract: Patients with acute Plasmodium falciparum malaria have defective cell-mediated immune responses to malaria-specific Ag (MA). This immunologic defect may partially explain the difficulty with which natural immunity to falciparum malaria develops and may have important implications for the efficacy of potential malaria vaccines in endemic areas. To investigate the basis of this immune defect, we have examined the capacity of PBMC from patients with acute falciparum malaria to produce IL-2 and to express I1-2R in response to Ag stimulation. The effect of exogenous IL-1 and IL-2 on lymphocyte proliferation was studied. Soluble IL-2R levels were measured in acute and convalescent sera. Our results showed that no detectable IL-2 was produced and no IL-2R were expressed by PBMC in response to MA during the acute infection. IL-2 production and IL-2R expression were also depressed when PBMC were exposed to streptococcal Ag. The specific immune defect was not reconstituted by the addition of graded doses of purified human IL-1 or IL-2 and could not be attributed to suppressor adherent cells. In contrast to the absence of IL-2 and cell-bound IL-2R, circulating soluble IL-2R was elevated in acute sera. These findings suggest that the lack of IL-2, through either a defect in its production or inhibition of its activity, may be the basis of the Ag-specific immune unresponsiveness in acute P. falciparum malaria.

Drug treatment and prevention of malaria.

Abstract: Recommendations for the treatment and prevention of malaria vary considerably. There are two reasons for this: first, many recommendations are empirical, or based on studies performed before the development of modem techniques of drug measurement and modem concepts of pharmacokinetics; second, falciparum malaria has rapidly developed alarming resistance to the antimalarial drugs. Recent studies of the pharmacokinetic properties of the antimalarial drugs (reviewed by White 1985) have led to changes in recommendations for treatment, partictdarly in severe infections. The revised recommendations attempt to improve efficacy and reduce toxicity by providing blood concentration profiles that rapidly reach concentrations considered to be efficacious, do not \"overshoot\" into the toxic range, and maintain these concentrations during the acute phase of the disease. However, more information is needed on the relationship between plasma (or whole blood) concentrations and the response to antimalarial treatment, so that the ratio of toxicity risk to therapeutic benefit can be optimized. Advice on antimalarial prophylaxis remains confused. The demise of chloroquine in ever larger areas of the tropics has produced a void in the prophylactic armamentarium. There is no simple alternative, and there is consequently considerable variation in the advice given to travellers visiting areas endemic for drug-resistant falciparum malaria. The Cinchona Alkaloids

Peripheral blood and bone marrow leucocytes in Gambian children with malaria: numerical changes and evaluation of phagocytosis.

Abstract: Neutrophilia, monocytosis, eosinopenia and reactive lymphocytes were found in the peripheral blood of infants and children with acute malaria at presentation. These changes were mostly reversed by days 3 and 7 after starting treatment. Mild rebound eosinophilia was seen in three cases after starting treatment. In patients with low grade malaria and anaemia, peripheral blood counts did not alter significantly after treatment. Two patients with mild eosinophilia at presentation were subsequently found to have strongyloidiasis and the eosinophil count rose markedly in one after treatment of malaria. Bone marrows were hypercellular in all cases. There was a low mean percentage of myeloid precursors in the marrow of all children as compared with the normal. This was due to increased lymphocyte percentage in those with acute malaria and to marked erythroid hyperplasia in those with low grade malaria. Phagocytosis of parasitized and non-parasitized red cells by bone marrow macrophages was seen most frequently in children with high parasitaemias, but erythroblast phagocytosis was more commonly seen in those with low grade malaria. There was no absolute correlation between the presence or absence of erythrophagocytosis in marrow macrophages and the presence or absence of a positive direct antiglobulin test (DAT) in children with malaria. This indicates that immunological mechanisms cannot be implicated as the sole cause of erythrophagocytosis in these bone marrows.

Relation between falciparum malaria and HIV seropositivity in Ndola, Zambia.

Abstract: A study was conducted at the Ndola Central Hospital Zambia in 1987 to determine whether human immunodeficiency virus (HIV) infection increases the risk or severity of infection with falciparum malaria in patients aged 12 years and over. The 170 patients examined all presented with symptoms suggestive of malaria including fever chills rigors headaches joint pains myalgia acute diarrhea and vomiting. 67 (39%) were diagnosed as having falciparum malaria and 28 (17%) were positive for the HIV antibody. The prevalence of malarial parasitemia in patients with HIV antibodies was lower than that in patients without such antibodies (29% versus 42% respectively) and differences in densities of parasites also failed to provide evidence of increased susceptibility to malaria in patients infected in HIV. There were no significant differences in antibody titers to P falciparum in patients who were positive for HIV antibody and in those who were negative whether or not they had parasitemia. The earlier finding of a significant association between malaria and HIV infection is now believed attributable to false positive results with the 1st enzyme linked immunosorbent assays and to interpretation difficulties with the Western blot test. Of interest is the fact that 20 patients in this study had symptoms suggestive of malaria but had negative results for parasites and positive results for HIV antibody. This indicates that many patients with HIV infection may be presenting with an illness clinically similar to malaria before acquired immunodeficiency syndrome (AIDS)-related complex or AIDS is recognizable.

Combating severe malaria in African children.

Abstract: An initiative to reduce childhood mortality due to malaria, diarrhoea and vaccine-preventable diseases, called the Africa Child Survival Initiative-Combatting Childhood Communicable Diseases (CCCD) project, was started in 1982 and is now operating in 13 African countries, 12 of which are endemic for malaria. The project's malaria control strategy relies on the use of drugs, mainly chloroquine, to prevent severe illness and death in children less than 5 years of age; chemoprophylaxis for pregnant women is also advised to prevent low birth weight in newborns. The strategy is based on WHO recommendations which focus on improved diagnosis and treatment of cases and chemoprophylaxis for pregnant women.In 9 out of the 13 CCCD countries the sensitivity of Plasmodium falciparum to chloroquine in children was investigated and a drug sensitivity surveillance network was established. In areas with chloroquine-resistant P. falciparum, treatment with chloroquine was found to decrease the temperature in febrile children and to greatly reduce the parasite density, thus preventing severe illness and possible death. Baseline surveys in 6 countries have shown a wide range of treatment practices, e.g., use of chloroquine in various doses without standard guidelines and the excessive use of quinine and chloroquine injections in some health units. As pregnant women are often not taking chemoprophylaxis, research has been started on alternative approaches to drug treatment to prevent the adverse effects of malaria on the fetus.Only 4 of the 12 malarious countries had malaria control units when their CCCD programme began and these were concerned mainly with vector control issues; 11 of 12 countries now have such units and a written CCCD malaria plan. These countries have now integrated malaria control activities into primary health care and have begun to implement standardized treatment and prevention practices that are described in their national CCCD malaria plans.

Control of malaria using mosquito nets impregnated with pyrethroids in Burkina Faso

Abstract: An experimental trial of malaria control was carried out in the village of Karangasso in the south-west Burkina Faso. It was based on the use by the whole population of deltamethrin impregnated bed nets at 25 mg/m2. During the first year pretreatment data on entomology, parasitology and pathological incidence of malaria were collected in the whole village. During the second year a quarter of the village with a population of 1,200 was chosen for the experiment and impregnated bed nets were given to everybody while the other quarter of the same population size was kept as a control area. Malaria transmission was reduced by 82% due to the decrease of both vector populations and sporozoitic indexes. It should be pointed out that this reduction in transmission was evaluated on non-protected catchers and consequently was underestimated for the villagers sleeping under nets. Parasitic index remained about the same but the mean parasitic load decreased significantly. Pathological incidence, based on the number of clinical malaria cases confirmed by blood examination, decreased by 59%. This trial shows that mass use of deltamethrin impregnated bed nets should be considered as a valuable tool for malaria control. The purchase of bed net is expensive but could be reduced sharply. The cost of the impregnation is very low regarding the residual effect which remains one year. The acceptance by the population was good.