Showing papers on "Malaria published in 1987"

Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria.

Abstract: Tumor necrosis factor, or cachectin (TNF-alpha), a protein with a wide range of biological activities, is produced mainly by macrophages and may be important in inflammatory processes. The role of TNF-alpha in the pathogenesis of cerebral malaria was investigated in a murine model. Most CBA mice infected with Plasmodium berghei anka die between days 6 and 14 with acute neurological manifestations unrelated to the level of parasitemia, whereas mice of some other strains have malaria of the same severity that ends in death after 3 to 4 weeks without neurological manifestations. The activity of serum TNF-alpha was considerably increased in CBA/Ca mice with cerebral malaria but not in Plasmodium berghei-infected mice that did not develop this complication. One injection of rabbit antibody to TNF-alpha on day 4 or 7 fully protected infected mice from cerebral malaria without modifying the parasitemia, whereas immunoglobulins from normal rabbit had no effect. In mice with cerebral malaria, the cerebral vessels showed focal accumulations of packed macrophages often containing infected erythrocytes; this lesion was not seen in mice treated with antibody to TNF-alpha or in untreated mice without cerebral malaria. These findings indicate that TNF-alpha has an important role in the pathogenesis of cerebral malaria in this murine model and suggest that local accumulation and activation of macrophages may lead to the predominance of lesions in the central nervous system.

Mortality and morbidity from malaria among children in a rural area of The Gambia, West Africa

Abstract: Mortality and morbidity from malaria were measured among 3000 children under the age of 7 years in a rural area of The Gambia, West Africa. Using a post-mortem questionnaire technique, malaria was identified as the probable cause of 4% of infant deaths and of 25% of deaths in children aged 1 to 4 years. The malaria mortality rate was 6.3 per 1000 per year in infants and 10.7 per 1000 per year in children aged 1 to 4 years. Morbidity surveys suggested that children under the age of 7 years experienced about one clinical episode of malaria per year. Calculation of attributable fractions showed that malaria may be responsible for about 40% of episodes of fever in children. Although the overall level of parasitaemia showed little seasonal variation, the clinical impact of malaria was highly seasonal; all malaria deaths and a high proportion of febrile episodes were recorded during a limited period at the end of the rainy season.

Safety and immunogenicity in man of a synthetic peptide malaria vaccine against plasmodium falciparum sporozoites

Abstract: A 12 amino-acid synthetic peptide (NANP)3 comprising the immunodominant epitope of Plasmodium falciparum circumsporozoite protein was conjugated to tetanus toxoid (TT), adjuvanted with aluminium hydroxide, and administered intramuscularly in three doses at monthly intervals to 35 healthy males as a malaria vaccine. No significant adverse reactions were noted, with mild soreness at the injection site the only common symptom. Seroconversions against NANP occurred in 53% and 71% of recipients of 100 or 160 micrograms, respectively, measured by enzyme-linked immunosorbent assay (ELISA). Most ELISA-positive sera reacted with sporozoites by indirect immunofluorescence (IFA). Three vaccinees with the highest ELISA and IFA titres and four unimmunized controls were challenged with P. falciparum sporozoites introduced via the bites of infective Anopheles mosquitoes. Blood stage parasites were detected in all controls by 10 days (mean 8.5 days, range 7-10). In contrast, the two vaccinees who became infected did not manifest parasitaemia until day 11 and the third vacinee showed neither parasites nor symptoms during the 29 day observation period. This first synthetic peptide parenteral vaccine against a communicable disease tested in man is safe and stimulates biologically active antibodies. These observations encourage the development of improved vaccine formulations which, by enhancing immunogenicity, may lead to practical vaccines to assist in the control of falciparum malaria.

Naturally acquired antibodies to sporozoites do not prevent malaria: vaccine development implications

Abstract: The first human vaccines against the malaria parasite have been designed to elicit antibodies to the circumsporozoite protein of Plasmodium falciparum. However, it is not known whether any level of naturally acquired antibodies to the circumsporozoite protein can predict resistance to Plasmodium falciparum malaria. In this study, 83 adults in a malaria-endemic region of Kenya were tested for circumsporozoite antibodies and then treated for malaria. They were monitored for the development of new malaria infections for 98 days. Antibody levels, as determined by four assays in vitro, were indistinguishable between the 60 individuals who did and the 23 who did not develop parasitemia during follow-up, and there was no apparent relation between day of onset of parasitemia and level of antibodies to circumsporozoite protein. Unless immunization with sporozoite vaccines induces antibodies that are quantitatively or qualitatively superior to the circumsporozoite antibodies in these adults, it is unlikely that such antibodies will prevent infection in areas with as intense malaria transmission as western Kenya.

Plasmodium falciparum malaria and Salmonella infections in Gambian children.

Abstract: Le paludisme sevit a l'etat endemique en Gambie et les formes chimiques sont plus severes chez les enfants de moins de 5 ans. On constate que les septicemies a Salmonelles s'installent peu de temps apres le paludisme

Malaria transmission-blocking immunity induced by natural infections of Plasmodium vivax in humans.

Abstract: Immunity to malarial infections in human populations is known to affect the development of the asexual blood stages of the parasites in the human host and to be capable of conferring significant protection against morbidity and mortality due to the disease. In this study we show that during acute infection with Plasmodium vivax malaria, one of the two main malarial pathogens of humans, most individuals also develop immunity that suppresses the infectivity of the sexual stages of the parasite to mosquitoes. The immunity is antibody mediated and is directed against the parasites in the mosquito midgut shortly after ingestion of blood by a mosquito. This immunity could be expected to have significant effects on the natural transmission of P. vivax malaria.

A trial of permethrin-treated bed nets in the prevention of malaria in Gambian children

Abstract: A trial was undertaken in a rural area of The Gambia to investigate the impact of permethrin-treated bed nets on malaria. Two groups of children, matched for age, sex, and malaria exposure, were followed through the rainy season of 1985 for illness and febrile episodes. One group of 205 children slept under permethrin-treated bed nets (0.5 g/m2); 184 children who slept under placebo-treated nets formed the control group. At the end of the rains the children were examined for splenomegaly and blood samples were taken for determination of packed cell volume (PCV) and parasitaemia. Permethrin treatment of bed nets was well accepted and was without side-effects. Children who slept under treated nets had significantly fewer episodes of clinical malaria than control children. However, at the end of the rains there was no significant difference in the prevalence of splenomegaly or parasitaemia or in the mean PCV between the groups. It is suggested that permethrin treatment of nets may have a greater effect on the duration of probing by mosquitoes for a blood meal than on the number of bites received.

Malaria and urbanization in central Africa: the example of Brazzaville. Part III: Relationships between urbanization and the intensity of malaria transmission.

Abstract: The authors present a map of malaria transmission intensity in Brazzaville from which they analyse the impact of urbanization on anopheline density and transmission of malaria. Whereas at first each new human settlement promotes the introduction or the proliferation of A. gambiae, the major vector of malaria in Central Africa, urban growth later proves to be unfavourable to this vector. Apart from the canalization of surface water and improvement in sanitation, it is the increase in population density which seems, by its direct or indirect consequences in urban areas, to determine the decrease in malaria transmission intensity. By favouring the absorption of the last remaining open spaces and by the accompanying domestic pollution, urbanization tends to eliminate an increasing number of A. gambiae breeding places; by limiting the dispersion of anopheles from breeding sites, it tends to focus malaria transmission and by thinning out the subsisting anopheline population among a denser human population, it tends to reduce the degree of exposure of each person.

Pathophysiology of severe falciparum malaria in man.

Abstract: The term severe falciparum malaria implies an infection with manifestations and complications which are potentially fatal in man, the natural host for this parasite. Much that has been written on the pathophysiology of animal malarias is of doubtful relevance to the understanding of the mechanism of Plasmodium falciparum infection in man. The clinical picture of severe P. falciparum infection differs in several respects from severe animal malarias, even those of non-human primates. Cerebral dysfunction is the most common severe manifestation of falciparum malaria in man. Coma develops suddenly after a generalized convulsion or gradually towards the end of the first week of illness. There are signs of a symmetrical upper motor neurone lesion and brain-stem dysfunction, but only about 5% of survivors show persisting neurological deficit after 2 or 3 days of unconsciousness. The mortality of cerebral malaria depends on how it is defined and on the predominant age group and other factors. In patients with proved acute P. falciparum infection with unrousable coma, in whom other causes of encephalopathy have been excluded, the mortality is between 15 and 50% despite treatment with antimalarial drugs (Warrell, Looareesuwan, Warrell, Kasemsarn, Intaraprasert, Bunnag & Harinasuta, 1982).

A phase-III clinical trial of mefloquine in children with chloroquine-resistant falciparum malaria in Thailand.

Abstract: Mefloquine is a highly effective drug for the treatment of falciparum malaria among adults, but studies of its effects on children are lacking. An open, noncomparative trial of mefloquine was therefore carried out among 84 children aged 5-12 years who were patients at the Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand. The drug was administered as a single dose of 18-29 mg base per kg body weight. Eighty-two of the 84 children completed a 42-day period of post-treatment observation. The drug was well tolerated also by 11 children with glucose-6-phosphate dehydrogenase deficiency, and all the children in the study cleared their parasitaemia initially (average clearance time, 65 hours). Furthermore, the clinical-chemical parameters measured exhibited no drug-related changes during the study. The radical cure rate of nearly 98% and high tolerance indicate that mefloquine can be used effectively and safely for the treatment of children aged 5-12 years who are suffering from uncomplicated falciparum malaria.

Malaria and urbanization in Central Africa: the example of Brazzaville: Part V: Pernicious attacks and mortality

Abstract: The current incidence of pernicious attacks and of mortality due to malaria were studied in Brazzaville. The results of this study, which concerned all the medical units of the town, were analysed in terms of previous studies on the epidemiology of malaria transmission in the various districts of the town. It was estimated that the annual incidence of pernicious attacks in children in Brazzaville is 1.15 per thousand between 0 and 4 years, 0.25 per thousand between 5 and 9 years and 0.05 per thousand between 10 and 14 years. The annual mortality due to malaria was estimated at 0.43 per thousand between 0 and 4 years and 0.08 per thousand between 5 and 9 years. These values are about 30 times lower than those expected from the results of previous studies of the mortality due to malaria in intertropical Africa. Whereas considerable differences in intensity of malaria transmission exist in the different districts of Brazzaville, the incidence of pernicious attacks and the resulting mortality are remarkably unvarying whatever the level of transmission. In particular, similar results were observed for the sector Mfilou-Ngamaba-Ngangouoni, where malaria is holoendemic with over 100 infective bites per person per year and a parasite rate of 80.95% in schoolchildren, and the central sector of Poto-Poto-Ouenze-Moungali, where malaria is hypoendemic with less than one infective bite per person every three years and a parasite rate of less than 4% in schoolchildren. These results are discussed in terms of previous observations in urban and surrounding rural areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Absence of association between Plasmodium falciparum malaria and human immunodeficiency virus infection in children in Kinshasa, Zaire.

Abstract: The possible associations between Plasmodium falciparum malaria and HIV (human immunodeficiency virus) seropositivity were investigated in 1986 at the Mama Yemo Hospital in Kinshasa, Zaire. No significant difference was found in the HIV seropositivity rate of 164 children presenting with P. falciparum malaria (1.2%) and 169 healthy controls (0.6%). Secondly, no association was found between P. falciparum slide positivity (51.6%) and HIV seropositivity (3.8%) among 1046 children presenting to the hospital with medical complaints. Infants less than 6 months old had the lowest slide-positivity rate, but among infected children the younger ones more frequently had high parasitaemias. HIV seropositivity rates were highest for children less than 6 months old. In older children, seropositivity was strongly associated with a history of blood transfusion. Thus, in Kinshasa children, P. falciparum malaria is a major public health problem; perinatal transmission and blood transfusions constitute important mechanisms of HIV infection; and P. falciparum does not appear to act as an opportunistic agent in children infected with HIV.

Hereditary ovalocytosis and reduced susceptibility to malaria in Papua New Guinea

Abstract: Ovalocytosis, an hereditary condition in which most erythrocytes are oval in shape, is a polymorphism that occurs in up to 20% or more of the population in Papua New Guinea and Malaysia. Due to the geographical correlation of the trait with endemic malaria, the possibility of a selective advantage in resistance to malaria has been raised. In a study of 202 individuals with ⩾50% oval red cells matched by age, sex and village of residence with controls having ⩽30% oval cells, ovalocytic subjects had blood films negative for Plasmodium vivax (P = 0·009), for P. falciparum (P = 0·044), and for all species of malaria parasites (P = 0·013), more often than controls. Among individuals parasitaemic at any time there were no clear differences in density of parasitaemia. However, in children 2 to 4 years old, parasite densities of both species were lower in ovalocytic subjects than in controls (0·01 < P < 0·025). The differential susceptibility to malaria infection suggested by this study has implications for the evaluation of interventions, including possible future vaccine field trials, in populations where high-frequency ovalocytosis is present.

Malaria and its Control: Present Situation and Future Prospects

Abstract: The global program of malaria eradication coordinated and supported by the World Health Organization (WHO) since 1957 has been successful in most the countries in the temperate climate zones of the globe. However by the end of the 1960s it became evident that technical problems such as resistance of mosquito vectors to insecticides and resistance of malaria parasites to drugs presented serious obstacles to the pursuit of eradication programs in many tropical countries. Moreover the administrative and financial difficulties of the developing countries were such that a revised strategy of antimalaria campaigns became necessary. In 1969 the World Health Organization recommended that although eradication of malaria should remain an ultimate goal in countries where eradication does not appear to be feasible malaria control operations may form a transitional stage. All effective methods of attack on the parasite and on the Anopheles vector should be employed according to epidemiological conditions of the area involved and in relation to their technical and logistic feasibility. Nevertheless during the past decade the malaria situation has deteriorated in several countries especially in southern and southeast Asia and some parts of Latin America. There has been no improvement in the highly endemic countries of tropical Africa. (excerpt)

Kinetic constraints on the development of a malaria vaccine.

Abstract: In recent years, considerable effort has been made to identify malarial antigens which may be suitable vaccine candidates. A number of such antigens have been identified on gametocytes, sporozoites, merozoites and on the surface of infected erythrocytes (reviewed by Mitchell 1984b). Antibodies directed against these antigens have been shown to inhibit fertilization, invasion of the target cells or cytoadherence. Not all antigens recognized as the target for protective immunity in vitro will be useful for vaccines. One widely appreciated constraint is the degree of antigenic diversity of some of these molecules in natural populations. The purpose of this communication is to highlight another: the need to achieve relatively high antibody concentrations to overcome the physicochemical constraints imposed on antibody binding by the short exposure times of some stages of the parasite. Antibody binding can be considered a multistep process with an initial univalent reversible bond (i.e., AgAb) followed in some cases by further bivalent (or multivalent in the case of IgM) linkages (i.e., AgAb*). Each step is described by its associated forward and reverse rate constants, e.g.,

Assessment of the incidence and prevalence of clinical malaria in semi-immune children exposed to intense and perennial transmission

Abstract: In order to determine the incidence and prevalence of clinical malaria in children exposed since birth to intense and perennial transmission, two successive longitudinal surveys, a weekly survey over four months and a daily survey over 10 days, were carried out in 1983-1984 among 182 children aged 5-13 years in Linzolo, Republic of the Congo, a village where malaria is holoendemic. By age group, prevalence of clinical malaria was found to be between 3.2% and 2.4% at ages 5-6 years, between 2.5% and 1.8% at ages 7-8 years, between 1.6% and 1.1% at ages 9-10 years, and between 0.5% and 0.3% at ages 11-13 years. For these four age groups, respectively, the annual incidence of clinical malaria was estimated during the first survey as 3.0, 2.1, 1.8, and 1.2 attacks, and during the second survey as 5.2, 2.7, 2.0, and 0.8 attacks. No difference was observed in the incidence of malarial attacks between children who use bed-nets and those who do not use them. Also investigated were the customs of the inhabitants of the village in the presence of febrile syndromes in the children, and the importance of antimalarial drug consumption in these cases. It was observed that almost all of these syndromes were rapidly treated with antimalarials, and that in half of the cases these drugs were administered by the parents themselves.

Ethnic differences in the prevalence of splenomegaly and malaria in The Gambia

Abstract: Significant variations in the prevalence of splenomegaly were found among members of the three main ethnic groups resident in North Bank Division, The Gambia Among young children splenomegaly and malaria were less prevalent in Mandinkas than in Wollofs or Fulas, suggesting that some genetic or environmental factors protect Mandinka children from this infection Among older children and adults splenomegaly was found most frequently in Fulas Six of 22 adults with very large spleens had a high serum IgM level and probably had the hyperreactive malarial splenomegaly (tropical splenomegaly) syndrome Four of these six subjects were Fulas This finding, together with the results of a previous study in Nigeria, suggest that Fulas have a predisposition to this condition

Malaria on the Thai-Burmese border: treatment of 5192 patients with mefloquine-sulfadoxine-pyrimethamine.

Abstract: Multidrug-resistant falciparum malaria is a major health problem along the Thai-Burmese border. From July 1985 until December 1986 a total of 5192 patients with falciparum malaria (1734 males, 3458 females) from this area were given supervised treatment with the combination mefloquine-sulfadoxine-pyrimethamine (MSP). The radical cure rate, assessed 21 days after drug administration, was 98.4% for the first 1975 patients, and 98.8% when assessed at 28 days for the remaining 3217 patients. In 3.8% of cases, parasites were still detected in peripheral blood smears on day 7 after treatment but this had fallen to 0.27% by day 9. Adverse reactions among the first 1975 patients were: vertigo (7.5% of patients), vomiting (5.8%), epigastric pain (0.6%), and transient confusional state (one case). MSP is an effective and well-tolerated drug for the treatment of drug-resistant falciparum malaria; however, delayed parasite clearance may give a false impression of RII resistance.

The changed pattern of malaria endemicity and transmission at Amani in the eastern Usambara mountains, north-eastern Tanzania.

Abstract: Parasitological and entomological studies on malaria were conducted between 1980 and 1982 on the Amani hills in the eastern Usambara mountains of north-eastern Tanzania. Malaria vectors were scarce on the Amani hills until the late 1960s and it was generally presumed that any cases of malaria transmission must have been contracted by people while visiting lower altitudes where malaria is holoendemic. However, the malaria vectors Anopheles funestus and An. gambiae have both become more abundant during the 1970s and 1980s and sporozoite-positive specimens of both have been found. Malaria asexual parasite rates have been shown to have increased, for instance from 52.7% in 1980 to 53.8% and 63.7% in 1981 and 1982, respectively. The percentage of parasitized children aged below 1 year whose parents report that they have not visited lowland localities away from the Amani hills has increased, from 71.4% in 1980 to 80.0% and 91.0% in 1981 and 1982, respectively, suggesting possible local malaria acquisition. These parameters have been confirmed by increasing sporozoite rates from 0.0% in 1967-1971 to 0.09% in May-June 1973 and 11.1% in August and December 1980. Various factors including climatological changes and increased agricultural activities are attributable to this changed malaria endemicity and transmission.

The interaction of alpha thalassaemia with malaria.

Abstract: A controlled trial of iron dextran prophylaxis in infants 2 months old was carried out on the north coast of New Guinea, where malaria is holoendemic. These infants have a high carrier rate (80%) for α + thalassaemia. The neighbouring highland area has a low rate of both malaria and α + thalassaemia. The results of clinical and haematological examination of these infants at 6 and 12 months were analysed to determine the relationship between α thalassaemia and susceptibility to malaria. Infants were divided according to haemoglobin Bart's levels found at birth into 3 groups corresponding to probable genotypes. Homozygotes had higher slide malarial positivity and spleen rates at 6 and 12 month than the normal or heterozygote groups. Analysis of variance of haemoglobin levels showed that the anaemia associated with malaria was greatest in the normals and least in the homozygotes at 6 months. A possible protective mechanism of α thalassaemia is discussed.

Plasmodium falciparum malaria in an asplenic man

Abstract: An asplenic man with no prior exposure to malaria was infected with Plasmodium falciparum on a visit to Kenya. The peripheral blood showed a parasitaemia of 5% and displayed all developmental stages of the parasite, resembling the asplenic simian model of malaria.