Showing papers on "Malaria published in 1991"

Common West African HLA antigens are associated with protection from severe malaria

Abstract: A large case-control study of malaria in West African children shows that a human leucocyte class I antigen (HLA-Bw53) and an HLA class II haplotype (DRB1*1302-DQB1*0501), common in West Africans but rare in other racial groups, are independently associated with protection from severe malaria. In this population they account for as great a reduction in disease incidence as the sickle-cell haemoglobin variant. These data support the hypothesis that the extraordinary polymorphism of major histocompatibility complex genes has evolved primarily through natural selection by infectious pathogens.

Malaria during pregnancy in an area of unstable endemicity

Abstract: A prospective study of malaria during pregnancy was conducted between September 1986 and December 1989 in an area of unstable (mesoendemic) malaria transmission on the Thai-Burmese border. Antenatal clinics were set up in camps for displaced persons of the Karen ethnic minority and 1358 pregnant women were enrolled at a mean estimated gestational age of 23 weeks (standard deviation 5.7 weeks) and were followed weekly until delivery. Malaria developed in 505 women (37.2%); 80.2% of infections were Plasmodium falciparum, 17.1% were P. vivax, and 2.7% were mixed. Primigravidae were infected more commonly than multigravidae: 153/322 (47.5%) compared with 318/953 (33.3%) (P less than 0.001). The incidence of malaria declined from the 20th week of gestation (12%) towards term (4.4%). Most infections were detected before symptoms developed, and there were no deaths associated with malaria. Despite this, malaria was associated with an overall 123 g reduction in birthweight (95% confidence interval [CI] 34-212 g). This reduction was largely accounted for by lower birthweights of babies born to infected primigravidae (mean reduction 151 g, 95% CI 21-282 g) and women in their 2nd and 3rd pregnancies (mean reduction 185 g, 95% CI 84-286 g). The incidence of anaemia requiring treatment was higher in women who developed malaria, 149/420 (35.4%) compared with 191/670 (28.5%), and was proportional to the number of parasitaemic episodes. Thus, despite regular antenatal clinic attendance with prompt detection and treatment of malaria (the currently employed antimalarial strategy in areas with multidrug-resistant P. falciparum), malaria still had a significant adverse effect on pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Malaria: Obstacles and Opportunities

Abstract: Malaria is making a dramatic comeback in the world. The disease is the foremost health challenge in Africa south of the Sahara, and people traveling to malarious areas are at increased risk of malaria-related sickness and death.This book examines the prospects for bringing malaria under control, with specific recommendations for U.S. policy, directions for research and program funding, and appropriate roles for federal and international agencies and the medical and public health communities.The volume reports on the current status of malaria research, prevention, and control efforts worldwide. The authors present study results and commentary on the

Age-dependent acquired protection against Plasmodium falciparum in people having two years exposure to hyperendemic malaria.

Abstract: An epidemiologic study of susceptibility to frequent and high-grade parasitemia by Plasmodium falciparum revealed that age-dependent acquired protection developed within a two-year period of exposure to hyperendemic infection pressure The study was conducted in a single village in northeastern Irian Jaya, Indonesia, where half the residents were native to the province and the other half were transmigrants from areas of Java, where there is little or no malaria transmission Five separate measures of susceptibility to the asexual parasitemia of falciparum malaria were derived from results of four months of biweekly surveillance of 240 volunteers Increasing protection as a function of age among the Javanese was a consistent pattern among the five estimates of susceptibility These age-dependent functions of protection were quantitatively parallel to those among life-long residents of Irian Jaya When humoral immune responsiveness to ring-infected erythrocyte surface antigen (RESA) was measured by ELISA, a similar pattern emerged; the relative level of antibody to RESA increased as parallel functions of age among the two subpopulations Acquired protective immunity against P falciparum was not the cumulative product of many years of heavy exposure to antigen Instead, the full benefit of protection appeared to develop quickly The degree of protection was governed by recent exposure and age, independent of history of chronic heavy exposure

Clustering of Malaria Infections within an Endemic Population: Risk of Malaria Associated with the Type of Housing Construction

Abstract: The occurrence of malaria infections due to Plasmodium vivax and P. falciparum was monitored in a population of 3,023 people living in six contiguous villages in Kataragama, an area of endemic malaria in southern Sri Lanka, over a period of 17 months. The annual incidence of malaria in this population during the study period was 25.8%. Malaria attacks were clustered, occurring more frequently than expected in certain individuals and housing groups and less frequently than expected in others. In one of these villages, the distribution of cases was examined in relation to locality and to the type of house construction. There was a strong association between the malaria incidence and house construction, independent of location. The risk of getting malaria was greater for inhabitants of the poorest type of house construction (incomplete, mud, or cadjan (palm) walls, and cadjan thatched roofs) compared to houses with complete brick and plaster walls and tiled roofs. Houses that were better constructed had a significantly lower malaria incidence rate (10.5%) than those that were poorly constructed (21.2%; P less than 0.01, by Student's t-test). There was also a significantly higher number of indoor resting mosquitoes collected from the poorly constructed houses than from those better constructed; the average (geometric mean) of mosquito densities found in houses of better versus poor construction were 0.97 and 1.89 per collection in the dry season, and 1.95 and 3.42 per collection in the wet season, respectively (P less than 0.05 in both seasons). This indicated that the higher malaria risk associated with poorly constructed houses was at least partly due to higher human-mosquito contact among their inhabitants.

Malaria Infection Rate of Amazonian Primates Increases with Body Weight and Group Size

Abstract: The quantitative relationship between the emission rate of host attractants (whether olfactory or visual) and the host-seeking rate of insect vectors of disease will determine the relationship between host group size and the prevalence of vector-borne diseases within each group. A comparative study was carried out to test whether interspecific differences in social behaviour significantly influence the malaria infection rates of different Amazonian primate species. The aetiological agent of monkey malaria in Amazonia is Plasmodium brasilianum Gonder & BerenbergGossler, 1908, and blood smear examinations of 3599 Amazonian primates over three decades have demonstrated an average infection rate with P. brasilianum of 10 4%. P. brasilianum has been detected in only 17/33 species examined, and the infection rate of those 17 species ranged from 2 1 to 5000%. Logistic and standard linear regressions, at three different taxonomic levels, demonstrate that a significant proportion of the interspecific variation in infection rate can be explained by variation in average body weight (W) and average sleeping group size (G). Infection rate could increase with W and G due to enhanced odour production attracting a greater number of anopheline mosquito vectors of monkey malaria per host. Given that parasites reduce host fitness, the results suggest that, contrary to conventional wisdom, mosquito-borne diseases are a significant cost associated with larger group size. Key-words: Body weight, host-seeking behaviour, monkey malaria, mosquito, Plasmodium brasilianum, sleeping group size

Identification of Plasmodium falciparum histidine-rich protein 2 in the plasma of humans with malaria.

Abstract: Plasmodium falciparum histidine-rich protein 2 (PfHRP-2) is a water-soluble protein released from parasitized erythrocytes into in vitro culture supernatants. This study sought to determine whether PfHRP-2 could be detected in the plasma of humans with P. falciparum malaria. A monoclonal antibody (1E1) is described that binds to PfHRP-2. By using monoclonal antibody 1E1, PfHRP-2 was identified by Western blot (immunoblot) analysis in the plasma of 37 of 39 (95%) patients experiencing either a first or repeat episodes of P. falciparum malaria and by dot blot analysis in the plasma of 40 of 41 patients tested. PfHRP-2 was not detected in 30 control, uninfected subjects. The current demonstration of PfHRP-2 in plasma, plus the fact that it is a structurally well-characterized molecule present in all natural isolates of P. falciparum tested, makes PfHRP-2 of interest for its potential effects on the host immune system and as an antigen for specific diagnosis of malaria.

Cytokines kill malaria parasites during infection crisis: extracellular complementary factors are essential.

Abstract: Malaria infection crisis, at which the parasitemia drops precipitously and the parasite loses infectivity to the mosquito vector, occurs in many natural malaria systems, and has not been explained. We demonstrate that in a simian malaria parasite (Plasmodium cynomolgi in its natural host, the toque monkey), the loss of infectivity during crisis is due to the death of circulating intraerythrocytic gametocytes mediated by crisis serum. These parasite-killing effects in crisis serum are due to the presence in the serum of cytokines tumor necrosis factor and interferon gamma, which are produced by the host as a result of the malaria infection. The killing activity of each cytokine is absolutely dependent upon the presence of additional, as yet unidentified factor(s) in the crisis serum.

Tumor necrosis factor and severe malaria.

Abstract: To investigate the relation of tumor necrosis factor-alpha (TNF alpha) to Plasmodium falciparum infection, plasma TNF alpha concentrations were measured in Zairian children with severe malaria, mild malaria, or other illnesses. The initial geometric mean plasma concentration of TNF alpha among 61 children with P. falciparum infection, (71 pg/ml) was higher than the level in 26 severely ill, aparasitemic children (10 pg/ml; P less than .001). Among 29 parasitemic children, initial geometric mean TNF alpha levels decreased from 77 to 5 pg/ml (P less than .001) at day 7. TNF alpha levels increased with parasite density and were associated with hyperparasitemia, severe anemia, hypoglycemia, and young age but not with cerebral malaria or fatal outcome. However, TNF alpha levels were elevated equally in children with cerebral malaria and with other signs of severe malaria. With multiple linear regression, TNF alpha levels were elevated independently in children with hyperparasitemia (P = .001) and severe anemia (P = .04). In this study, high TNF alpha levels were associated with several manifestations of severe malaria and were not specific to cerebral malaria.

Human malaria infectiousness measured by age-specific sporozoite rates in Anopheles gambiae in Tanzania.

Abstract: In an area of holoendemic malaria in Northern Tanzania, Anopheles gambiae s.l. females were age-graded by Polovodova's method and dissected for sporozoites. Age-specific sporozoite rates implied that mosquitoes acquired new infections at all ages. The extrinsic period lasted just over 3 gonotrophic cycles (9-11 days). Very high sporozoite rates in the oldest females implied the absence or rarity of genetic refractoriness to infection. A method is described for estimating the proportion of bloodmeals which result in mosquito infection. This method makes relatively few assumptions about mosquito behaviour, and could be useful for evaluating transmission-blocking interventions. Overall, it is estimated that about 21% of meals are infectious. This is much higher than previous estimates derived either from experimental mosquito feeding studies or from similar age-grading data collected from the same area in 1962. Various alternative explanations are considered, and it is concluded that there has been a 2.5-fold increase in human infectiousness in the last 25 years. This is partly attributable to suppression of human infectiousness by widespread chloroquine usage during the 1960s, followed by removal of this effect by drug resistance. It is argued that chloroquine would be expected to select for increased infectivity in the parasite, and this may also have contributed to the observed increase.

Periodic and chaotic host-parasite interactions in human malaria.

Abstract: It has been recognized since ancient times that malaria fever is highly periodic but the mechanism has been poorly understood. Malaria fever is related to the parasite growth cycle in erythrocytes. After a fixed period of replication, a mature parasite (schizont) causes the infected erythrocyte to rupture, releasing progeny that quickly invade other erythrocytes. Simultaneous rupture of a large number of schizonts stimulates a host fever response. Febrile temperatures are damaging to Plasmodium falciparum, particularly in the second half of its 48-hr replicative cycle. Using a mathematical model, we show that these interactions naturally tend to generate periodic fever. The model predicts chaotic parasite population dynamics at high multiplication rates, consistent with the classical observation that P. falciparum causes less regular fever than other species of parasite.

Plasmodium falciparum malaria and perinatally acquired human immunodeficiency virus type 1 infection in Kinshasa Zaire. A prospective longitudinal cohort study of 587 children.

Abstract: Background. It is uncertain whether Plasmodium falciparum malaria is more frequent or more severe in children with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection and whether P. falciparum infection accelerates the progression of HIV-related disease. Methods. We conducted a prospective, longitudinal cohort study in Kinshasa, Zaire. Two hundred sixty children 5 to 9 months of age who had been born to HIV-1—seropositive mothers and 327 children of the same age who had been born to seronegative mothers were monitored intensively for malaria over a 13-month period. All episodes of fever were evaluated with blood smears for malaria, and children found to be infected with P. falciparum were treated with a standard regimen of oral quinine. Results. A total of 2899 fevers were evaluated, with 271 cases of malaria identified. No statistically significant differences were found in the incidence, severity, or response to therapy of malaria among four well-defined groups of children: those ...

An Assessment of Low Birthweight Risk in Primiparae as an Indicator of Malaria Control in Pregnancy

Abstract: Malaria is an important environmental factor which reduces fetal growth in primiparae more than multiparae living under holoendemic conditions for malaria. This relates to greater susceptibility to malaria infection in first pregnancies. The relative risk for low birthweight (less than 2500 g) associated with primiparity is increased in malaria-endemic areas and significantly correlates with the malaria parasite rate at delivery in primiparae. Because of this association, the relative risk is proposed as an indicator to assess malaria control in pregnant women as well as in the community. The sensitivity and specificity of the relative risk for low birthweight in primiparae are calculated for 13 malarious and 15 non-malarious populations. The highest sensitivity and specificity is achieved at a relative risk of 1.7. Social and environmental variables which could alter the sensitivity of the estimate are discussed. Estimates of the population-attributable risk per cent of low birthweight due to malaria in primiparae are calculated and vary between 10% and 40% in endemic areas. The method is applied to observations from malaria-intervention studies in pregnancy in the Solomon Islands and Papua New Guinea and appears sensitive in these prospective studies to changes in malaria prevalence. Calculation of these estimates is straightforward and their use to assess malaria control measures in areas of high transmission has not been suggested previously, it could have wide epidemiological application and requires further field evaluation.

Protection against malaria morbidity: near-fixation of the alpha-thalassemia gene in a Nepalese population.

Abstract: We have previously reported that the Tharu people of the Terai region in southern Nepal have an incidence of malaria about sevenfold lower than that of synpatric non-Tharu people. In order to find out whether this marked resistance against malaria has a genetic basis, we have now determined in these populations the prevalence of candidate protective genes and have performed in-vitro cultures of Plasmodium falciparum in both Tharu and non-Tharu red cells. We have found significant but relatively low and variable frequencies of beta-thal, beta S, G6PD (-), and Duffy (a-b-) in different parts of the Terai region. The average in-vitro rate of invasion and of parasite multiplication did not differ significantly in red cells from Tharus versus those from non-Tharu controls. By contrast, the frequency of alpha-thalassemia is uniformly high in Tharus, with the majority of them having the homozygous alpha-/alpha-genotype and an overall alpha-thal gene (alpha-) frequency of .8. We suggest that holoendemic malaria has caused preferential survival of subjects with alpha-thal and that this genetic factor has enabled the Tharus as a population to survive for centuries in a malaria-holoendemic area. From our data we estimate that the alpha-thal homozygous state decreases morbidity from malaria by about 10-fold. This is an example of selection evolution toward fixation of an otherwise abnormal gene.

The relationship between anthropometric measurements and measurements of iron status and susceptibility to malaria in Gambian children.

Abstract: Anthropometric measurements were made and serum iron and ferritin levels determined in a group of Gambian children at the beginning of the rainy season and these findings were related to the malaria experience of the children during the following malaria transmission season. Susceptibility to malaria was not correlated with prior weight-for-age, height-for-age, weight-for-height or serum albumin, or with serum iron, serum iron binding capacity nor serum ferritin. Thus, our findings do not provide any support for the view that poor nutritional status, as assessed by anthropometric measurements, or iron deficiency protect against malaria infection. Children who developed a clinical attack of malaria accompanied by a high level of parasitaemia tended to have a higher mean weight-for-age at the beginning of the rainy season than did children who had a clinical attack accompanied by a low level of parasitaemia, but the difference between groups was not statistically significant. However, they had a significantly higher mean serum ferritin level (P less than 0.01).

Human antibody response to the major merozoite surface antigen of Plasmodium falciparum is strain specific and short-lived.

Abstract: The precursor of the major merozoite antigen of Plasmodium falciparum, gp190, is considered a candidate for inclusion in a malaria vaccine. This protein, which consists of conserved, dimorphic, and polymorphic sequences, is very immunogenic in humans. In a longitudinal study carried out with 94 inhabitants of a rural community in Mali, West Africa, we show that in this endemic area naturally acquired gp190-specific antibodies are predominantly directed against the dimorphic parts of one of the main alleles of gp190. The presence of antibodies against these dimorphic regions correlates with the prevalence of the corresponding antigen in the infecting parasite population. Moreover, qualitative as well as quantitative differences were found in the time course of the humoral immune response to the dimorphic regions in adults and children, who differ in their susceptibility to malaria infection.

Cytokines in the pathogenesis of malaria: levels of IL-I beta, IL-4, IL-6, TNF-alpha and IFN-gamma in plasma of healthy individuals and malaria patients in a holoendemic area.

Abstract: A longitudinal study was conducted between October 1989 and February 1990 in a malaria holoendemic area of Gabon to determine the plasma concentration of various cytokines in individuals continuously exposed to infection with malaria parasites. No cases of severe malaria were seen and fever was the main presenting symptom of clinical malaria. Parasite rates were highest in children 6-9 years old but clinical malaria was seen essentially in children below 6 years of age. The incidence of clinical malaria was highest in November and February corresponding to the beginning and end of heavy rains respectively. Parasite rates did not show any seasonal variations. Overall, there was no seasonal variation in plasma cytokine levels but both IL-6 and IL-4 levels were highest in February. Plasma concentration of TNF-alpha and IFN-gamma were higher in parasitaemic than aparasitaemic individuals and donors who had clinical malaria had higher levels of TNF-alpha, IFN-gamma and IL-6 than asymptomatic parasitaemic donors. There was a negative correlation between age of the individual and the concentration of plasma TNF-alpha and IFN-gamma suggesting that the production of these cytokines could be modulated by repeated malarial infections. Asymptomatic parasitaemic children 5-7 years of age had higher levels of plasma TNF-alpha than clinically similar children below or above this age group suggesting that refractoriness to the clinical effects of TNF-alpha may be an important factor in the ability of these children to resist clinical malaria.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA Associations with Malaria in Africa: Some Implications for MHC Evolution

Abstract: A recent large case-control study of malaria in West African children has demonstrated the first clear HLA associations with a fatal infectious disease of humans, supporting the theory that MHC polymorphism is pathogen driven. The time for the protective HLA alleles to rise in frequency as a result of natural selection by malaria, and the possible mechanisms of this selection, overdominant, frequency-dependent or fluctuating, are discussed.

Human immunodeficiency virus and malaria in a representative sample of childbearing women in Kigali, Rwanda.

Abstract: In 1986-1987 researchers tested sera from 3702 year old women attending either the prenatal care or pediatric clinics at Centre Hospitalier de Kigali in Rwanda (the only hospital) for HIV infection and malaria parasites. 90% lived with a sexual partner. Overall HIV seroprevalence was 29%. Malaria parasites were present in 9% of all women. Malaria parasitemia significantly decreased with age (13% for 18-20 year olds to 7% for 31-35 year olds; [ 30 years old and married to farmers or military men. 40% of the women who had had a blood transfusion were HIV seropositive compared to 28% of those who had never had a blood transfusion (p<.001). Almost everyone had the transfusion in Rwanda particularly at the hospital in Kigali. <5% of the HIV positive women had acquired HIV from a blood transfusion after blood screening began in Rwanda in 1985 in 1985. Yet 94% of the women had never had a blood transfusion. Thus blood transfusions only accounted for a small percentage of infection in Kigali. Sexual transmission stood as the leading mode of transmission. In conclusion health personnel need to develop an effective prevention program aimed at sexual transmission.

Malaria and health in Africa: the present situation and epidemiological trends.

Abstract: The World Health Organization does not give any data on the malaria situation in Africa in its regular reports because of the "insufficiency and irregularity of reporting". Estimates on the total number of cases and the number of deaths vary considerably. They range from 35 million to 189 million per year depending on whose figures one uses. An intensive search of the literature using computer-based systems identified more than 1000 titles on the epidemiology of malaria. Out of them and from other sources finally 426 articles were used to describe the current malaria situation and observable trends in Africa. Major findings were that malaria is responsible for about 40% of fever cases, mortality is about 5 per 1000 per year, case fatality ranges from 2% to 24%. Admissions for malaria account for 20% to 50% of all admissions in African health services although only 8% to 25% of persons with malaria visit health services. Self-treatment is more common in urban areas (more than 60%) but an increasing number of people use some form of self protection in rural areas (2% to 25%). The resistance of malaria parasites to chloroquine and other drugs is widespread. Chloroquine resistance has reached a prevalence of about 30% at the RII level in most countries. Malaria incidence shows annual growth rates of 7.3% for Zambia, 10.4% for Togo, and 21.0% for Rwanda. The data for Burkina Faso show a downward trend of--14.7% during the years from 1973 to 1981. Since then malaria incidence is increasing at 11.0% per year. Hospital data reported from Zambia indicate that mortality is rising 5.2% per annum in children and 9.7% per annum in adults. Reasons for the increase of malaria and its role for development are discussed.