Showing papers on "Malaria published in 1986"

The epizootiology and ecological significance of malaria in hawaiian land birds

Abstract: Laboratory and field experiments were conducted on the island of Hawaii from 1977- 1980 in an effort to determine the impact of avian malaria on the forest birds. At 16 study sites from sea level to tree line in mesic and xeric habitat, birds were captured and bled to determine the host and altitudinal distribution of blood parasites. In the laboratory, six bird species were challenged with malarial parasites to measure host susceptibility. Distributions, activity cycles, and transmission po- tentials of malarial parasite vectors were also analyzed. One species of Plasmodium was present from sea level to tree line, concentrated in the mid- elevational ranges in the ecotonal area where vectors and native birds had the greatest overlap. Native forest birds were: (a) more susceptible to malaria than were introduced species; (b) most likely to have malaria during the nonbreeding, wet season; (c) found ranging lower in xeric than in mesic forests; and (d) found to have a lower prevalence of malaria in xeric forests. Temporal as well as elevational differences in prevalence and parasitemia levels of wild birds were apparent throughout the annual cycle, a result of differing host and parasite responses to biotic and abiotic factors. Avian malaria probably did not reach epizootic proportions on Hawaii until after z 1920. However, since that time it has had a negative impact on the population dynamics of the native forest birds and is today a major limiting factor, restricting both abundance and distribution of these species on the island. In response, a number of native bird species have developed immunogenetic and behavioral responses that reduce the impact of the parasite on host populations.

Genetic Selection of a Plasmodium-Refractory Strain of the Malaria Vector Anopheles gambiae

Abstract: The anopheline mosquito is the target in most malaria control programs, primarily through the use of residual insecticides. A mosquito was studied that is refractory to most species of malaria through a genetically controlled mechanism. A strain of Anopheles gambiae, which was selected for complete refractoriness to the simian malaria parasite Plasmodium cynomolgi, also has varying degrees of refractoriness to most other malaria species examined, including the human parasites P. falciparum, P. ovale, and P. vivax for which this mosquito is the principal African vector. Furthermore, the refractoriness extends to other subhuman primate malarias, to rodent malaria, and to avian malaria. Refractoriness is manifested by encapsulation of the malaria ookinete after it completes its passage through the mosquito midgut, approximately 16 to 24 hours after ingestion of an infective blood meal. Fully encapsulated ookinetes show no abnormalities in parasite organelles, suggesting that refractoriness is due to an enhanced ability of the host to recognize the living parasite rather than to a passive encapsulation of a dead or dying parasite. Production of fully refractory and fully susceptible mosquito strains was achieved through a short series of selective breeding steps. This result indicates a relatively simple genetic basis for refractoriness. In addition to the value these strains may serve in general studies of insect immune mechanisms, this finding encourages consideration of genetic manipulation of natural vector populations as a malaria control strategy.

The Epidemiology of Malaria in a Population Surrounding Madang, Papua New Guinea

Abstract: Malaria is prevalent throughout coastal and lowland Papua New Guinea. Recent changes, including a shift from predominance of Plasmodium vivax to Plasmodium falciparum, appearance of chloroquine-resistant P. falciparum and decreased effectiveness of vector control programs have been observed. Epidemiological features of malaria were studied through four six-month surveys of a population of 16,500 in Madang Province from 1981-1983. Baseline data on parasitology, splenic enlargement, serology, hemoglobin levels, prevalence of 4-aminoquinolines, utilization of mosquito nets and incidence of fever were collected for use in future evaluation of malaria control measures including possible field trials of an antimalarial vaccine. Prevalence of parasitemia (all species, all ages) varied from 35.0% to 42.7% over the four surveys each of which covered a random sample of 25% of the population. The ratio of parasite species was: P. falciparum 70:P. vivax 25:P. malariae 5 in the dry seasons, shifting slightly in favor of P. falciparum during the wet seasons. Intense year-round transmission was indicated by decreasing parasite prevalence and splenic enlargement with age, low density asymptomatic parasitemias and high prevalence of antimalarial antibodies (i.e., greater than 80% of the population over five years of age was ELISA-positive). Levels of endemicity varied geographically, presence of 4-aminoquinolines in urine samples was relatively common (12.7% positive) and chloroquine resistance was widespread (81.6% in vitro, 46.6% in vivo).

Iron supplementation increases prevalence and effects of malaria: report on clinical studies in Papua New Guinea

Abstract: A placebo-controlled trial of intramuscular iron dextran prophylaxis for two-month-old infants was carried out on the north coast of Papua New Guinea where there is high transmission of malaria. The results indicate that the placebo group became relatively iron deficient whereas the iron dextran group had adequate iron stores and, in the absence of malaria, a higher mean haemoglobin. However in the iron dextran group there was a higher prevalence of malaria, as judged by parasite and spleen rates at 6- and 12-month follow-up; a lower haemoglobin associated with malaria when compared with the placebo group and a greater reticulocytosis in response to malaria infection. Within the placebo group it was noticed that the malaria rates were lower at follow-up in those infants who had had a low birth haemoglobin. In neither group was there apparent suppression of marrow activity in the presence of malaria. Malaria infection in both groups was associated with a significantly raised serum ferritin level and transferrin saturation. Over-all these data give evidence for a protective role of iron deficiency against malaria and would argue against the injudicious use of iron replacement in areas where malaria is endemic.

Research toward malaria vaccines

Abstract: Malaria exacts a toll of disease to people in the Tropics that seems incomprehensible to those only familiar with medicine and human health in the developed world. The methods of molecular biology, immunology, and cell biology are now being used to develop an antimalarial vaccine. The Plasmodium parasites that cause malaria have many stages in their life cycle. Each stage is antigenically distinct and potentially could be interrupted by different vaccines. However, achieving complete protection by vaccination may require a better understanding of the complexities of B- and T-cell priming in natural infections and the development of an appropriate adjuvant for use in humans.

Severe Cutaneous Reactions among American Travelers Using Pyrimethamine-Sulfadoxine (Fansidar®) for Malaria Prophylaxis

Abstract: In 1982, the fixed combination of pyrimethamine and sulfadoxine (Fansidar®) became available in the United States, and was recommended for use in travelers at risk of acquiring chloroquine-resistant Plasmodium falciparum. Prior to that time, no reports of severe cutaneous reactions had appeared in the medical literature despite widespread use for more than 8 years in both Europe and malarious areas of the developing world. In the fall of 1984, the Centers for Disease Control received reports of 4 cases of toxic epidermal necrolysis (including 3 fatalities) among Americans who had used pyrimethamine-sulfadoxine (PYR/SDX) for the prevention of malaria. Subsequent investigation into severe cutaneous reactions associated with the use of this drug by American travelers detected 24 cases of erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. Twenty-three of the 24 patients concurrently used chloroquine. Seven patients died. No risk factors in the development of these reactions other than the use of PYR/SDX could be identified. Among American travelers, we estimate that these reactions occur in 1 per 5,000–8,000 users, and that fatal reactions occur in 1 per 11,000–25,000 users. This higher than expected incidence necessitates that the use of PYR/SDX for the prevention of malaria be reconsidered. In the United States it is now recommended that the routine weekly use of the drug be reserved for those travelers at highest risk of acquiring chloroquine-resistant P. falciparum, when alternate prophylactic regimens are not deemed appropriate.

Potential vectors of malaria and their different susceptibility to Plasmodium falciparum and Plasmodium vivax in northern Brazil identified by immunoassay.

Abstract: During the period from May 1983 to July 1985 we conducted an epidemiological study to determine potential vectors of malaria in 6 districts in the state of Para in northern Brazil. The examination of random human blood smears, prepared at the time of mosquito capture, indicated overall human infection rates of 16.7% and 10.9% for Plasmodium falciparum and P. vivax, respectively. Two immunoassays, the immunoradiometric assay (IRMA) and the enzyme-linked immunosorbent assay (ELISA), based on the use of species-specific antisporozoite monoclonal antibodies, were used to analyze a total of 9,040 field-collected Anopheles mosquitoes for plasmodial infection. P. falciparum sporozoite antigen was detected in A. darlingi at rates varying from 2.7% to 4.2%, and in small numbers of A. oswaldoi collected in 1 of the districts. In contrast, sporozoite antigen of P. vivax was found in A. darlingi, A. triannulatus, A. nuneztovari, and A. albitarsis at rates ranging from 0.9% to 12.0%. By dissection, sporozoites were found in the salivary glands of these same 4 species at rates ranging from 0.8% to 2.2%. The latter 3 species had not previously been implicated as malaria vectors of any significance in northern Brazil.

Antigen-specific immunosuppression in human malaria due to Plasmodium falciparum.

Abstract: Proliferative responses of T lymphocytes to antigens specific and not specific for malaria were investigated in 32 adult patients in eastern Thailand during acute infection with Plasmodium falciparum malaria and during their convalescence. Immune unresponsiveness to malarial antigen, which persisted for more than four weeks in 37.5% of the individuals, was present in all patients, irrespective of parasitemia or severity of clinical illness. Suppression of responses to nonspecific antigens was less profound and observed only in patients with moderately severe or cerebral malaria. The depressed functional responses were associated with a loss of T lymphocytes--both helper and suppressor subsets--from the peripheral blood; these responses were recovered once parasites were cleared. These results indicate that blood-stage plasmodial infections may suppress responses important for immunity to malaria and so allow the parasite to survive. They further suggest that patients acutely or even recently infected with P. falciparum may not respond as well to a malaria vaccine as would uninfected individuals.

Malaria transmitted to humans by mosquitoes infected from cultured Plasmodium falciparum.

Abstract: Malaria was transmitted to six normal human volunteers by mosquitoes infected from cultured gametocytes of Plasmodium falciparum. This method, which offers advantages over other methods of infecting volunteers, will be useful for evaluating the efficacy of human malaria vaccines.

A review of the malaria situation in Zimbabwe with special reference to the period 1972–1981

Abstract: Information on the prevalence, incidence, and geographical distribution of malaria in Zimbabwe is reviewed. Malaria control operations carried out during the last 30 years are briefly described together with available information of their impact on malaria. From 1972 to 1981, 51,962 positive blood slides were submitted to Blair Research Laboratory from health institutions, of which 97·8% were Plasmodium falciparum, 1·8% P. malariae and 0·3% P. ovale. Blood slide surveys undertaken from 1969 to 1981 during which time 156,194 slides were examined showed P. falciparum to constitute 92·5% of malaria infections, P. malariae 8·3% and P. ovale 0·7%. The data from active and passive case finding are used to describe the seasonal and geographical pattern of malaria in Zimbabwe. The seasonal peak of transmission occurs from February to May each year with very low transmission from July to October. Endemicity of malaria is shown to be markedly influenced by altitude varying from hyperendemic in the low altitude areas to hypoendemic or absent on the central watershed.

Epidemiology of the emergence and spread of drug-resistant falciparum malaria in South-East Asia and Australasia.

Abstract: A review is presented of the development of drug-resistant malaria in Pailin on the Thai-Kampuchean border and its spread to other parts of the region and beyond. Resistance of P. falciparum to chloroquine appears to have emerged in this area in the early 1960s and evidence of resistance to the combination of sulfadoxine and pyrimethamine and to the combination of diaphenylsulfone and pyrimethamine came from the same area towards the end of the same decade. The factors leading to the emergence and increase of drug resistance appear to have been: the continuous introduction of non-immune migrants to a hyperendemic malaria area, an increase in already intense transmission resulting from the living and working conditions of the migrants and prolonged drug pressure resulting from individual drug consumption and mass drug administration, particularly from the medicated salt project which covered the area in which resistance emerged. These conditions lead to the selection of resistant mutants. Moreover, resistant parasites were exposed to multiple and increasing doses of chloroquine, pyrimethamine and sulfathiazole during repeated passages through non-immune hosts who were being treated for primary attacks, early recrudescences and reinfections. This probably resulted in increasing the degree of resistance and in the selection of parasites resistant to sulfathiazole with cross-resistance to other sulfonamides. In Irian Jaya, Indonesian New Guinea, where there had been a chloroquinized salt project, the level of chloroquine resistance was much lower than in Pailin; this is associated with the absence of a non-immune population and the lower dose of chloroquine base used in the salt. The spread of chloroquine resistance is then discussed. At first resistance was found only in three foci in South-East Asia where A. balabacensis is the vector of malaria. It then spread to all A. balabacensis areas, and finally to areas outside the area of distribution of A. balabacensis. The spread of resistance is found to be favoured by the presence of the vector A. balabacensis and by the introduction of a non-immune population.

In vivo efficacy of chloroquine treatment for Plasmodium falciparum in Malawian children under five years of age.

Abstract: In 1984 the government of Malawi instituted a program to reduce malaria mortality and morbidity in children less than 5 years of age as a part of the Combatting Childhood Communicable Diseases (CCCD) program. To define the appropriate malaria therapy regimen, investigators used a quality assurance design in a simplified 7-day in vivo drug response study with follow-up observations on day 2 (D2), D3, and D7 after the initial day of the study (D0). The efficacy of oral chloroquine was assessed in 224 children who were enrolled at 6 sites, 2 in each of the 3 administrative regions of Malawi. Parasitological failure, defined as failure of parasitemia to decrease by 75% of the value by D3 or presence of any detectable parasitemia on D7, ranged from 41%-65% following administration of chloroquine 25 mg (base)/kg. However, only 8% of children who were parasitemic on D7 were febrile or judged to be ill. Considering these therapeutic results and the higher cost and limited availability of alternative therapies, chloroquine 25 mg/kg therapy was adopted as the primary therapy for malaria.

Leishmaniasis and malaria: new tools for epidemiologic analysis

Abstract: Parasitic diseases are still prevalent in many parts of the world, causing both human suffering and economic loss. Recent developments in biotechnology, such as the use of monoclonal antibodies and recombinant DNA, have the potential for providing both more extensive and detailed information on the parasite in the infected human and in insect vectors. New methods of detection, both in man and insect vectors, have been developed for two parasitic diseases, leishmaniasis and malaria. These new methodologies will be important in epidemiologic studies on the prevalence and transmission of these parasitic diseases.

Small-area variations in the epidemiology of malaria in Madang Province.

Abstract: SUMMARY Small-area variations in the epidemiology of malaria can have important consequences in the evaluation of malaria control or intervention programs. Epidemiological features of malaria were studied in six villages in Madang Province through six-monthly surveys over a two-year period and three-monthly surveys for a single year. Data on parasite prevalence, infection density, splenic enlargement and morbidity were analyzed to determine the existence of variation within a previously defined study area. While average parasite rates did not differ greatly among villages, rates in the 1-4 years age group in the dry season were significantly higher (60.2%) in the villages north of Madang town compared with those located to the south (37.7%) ( = 0.05). There were also differences in the parasite species ratio (i.e., 21.7% of infections in one village were Plasmodium vivax compared with 12.6% in another), in spleen rates and in degree of splenic enlargement. Utilization data from village aides were used to estimate fever attacks over a 12-month period, but interpretation of these rates was complicated by the alternative sources of treatment available to the village populations.

Total dose iron infusion, malaria and pregnancy in Papua New Guinea.

Abstract: A study was made of 544 mothers and their 556 newborns in an area of endemic malaria, to analyse effects of total dose intravenous iron infusion (TDI) to mothers during pregnancy. 34% of these mothers received TDI before delivery. A range of haematological tests was carried out on newborns and mothers in addition to anthropometry. 84% of mothers had had ante-natal care and data were also collected retrospectively from ante-natal records. TDI was associated with more slide positive peri-natal malaria in primipara (odds ratio: 5·46) but not in multipara. When all relevant factors were considered TDI was not associated with an overall improvement in haemoglobin status from the first ante-natal level recorded to the post-natal check. Post-natal malaria was associated with lower ante-natal and post-natal haemoglobin levels. There was no evidence of any effect of TDI in pregnancy or of maternal malaria on foetal maturity or birth weight. Gestational age, maternal weight, parity and maternal post-natal haemoglobin were all significantly correlated with birth weight. TDI to the mother was associated with higher neo-natal serum ferritins and lower neo-natal haemoglobins. Maternal post-natal malaria was associated with significantly lower iron in serum in newborns. It is suggested that routine total dose iron infusion to anaemic pregnant mothers in malaria endemic areas may be contraindicated.

Evidence against immune haemolysis in falciparum malaria in Thailand.

Abstract: Evidence of immune mediated haemolysis was sought in 83 patients with P. falciparum malaria in eastern Thailand. Amongst 73 patients with uncomplicated infection 12 (16.4%) had a weakly positive direct antiglobulin test (DAT). The incidence in 32 children aged 8-16 years was similar to that in adults. Of 10 patients with cerebral malaria, six adults, all of whom were in unrousable coma, had a positive DAT. Erythrocyte-bound IgG1 accounted for the positive DAT in all cases; sensitization with complement or other IgG subclasses was not found. Patients with uncomplicated malaria had a median value of 70 IgG molecules per erythrocyte compared with 65 molecules per cell in 67 healthy controls. This difference was not statistically significant but could account for the lower incidence of a positive DAT in control subjects (4.5%). There was no correlation between the number of IgG molecules per cell and the degree of anaemia during the acute or convalescent phases of the infection. There is no evidence from this study that an immunohaemolytic process contributes to the anaemia of falciparum malaria in eastern Thailand.

Resistance to falciparum malaria among adults in central Sudan

Abstract: Adults claiming resistance to malaria were identified in the Sennar region of central Sudan, where P. falciparum is hyperendemic but seasonal in transmission. Indirect fluorescent antibody (IFA) titers of sera from these individuals were comparable to those of malaria patients with positive blood films, indicating equal exposure, while in vitro antiparasitic activity of their sera tended to be higher, indicating an effective immunological response to falciparum malaria. Hemoglobin S (Hb S) was significantly more prevalent in adults resistant to malaria. This trait offers protection at the erythrocyte level and it is also possible that it could enhance the ability of carrier adults to acquire protective immunity. Erythrocyte 6-phosphogluconate dehydrogenase A (PGDA) and phosphoglucomutase 1 (PGM1), phenotypes of unknown relevance to protection against falciparum malaria, were also significantly more prevalent in those claiming resistance to malaria. A trend of higher prevalence for erythrocyte glucose-6-phosphate dehydrogenase deficiency (G6PD-), Kell (+) and transferrin D (TfD) was detected among resistant individuals and higher KP(a+) and P2 among malaria patients, but the numbers evaluated in this study did not allow determination of statistical significance. No association was found with erythrocyte glyoxalases, ABO and Duffy blood groups and serum haptoglobins.

Epidemiology of emergence and spread of drug-resistant falciparum malaria in Southeast Asia.

Abstract: In Southeast Asia the medicated salt project of Pailin, on the Kampuchea-Thai border, demonstrated that drug resistance, especially chloroquine resistance, can develop when a large population of P. falciparum parasites is exposed to intense transmission under intense drug pressure. The selection of resistant parasites being activated by the introduction of non-immune groups. Emergence of drug resistance was the result of continuous and prolonged mass exposure of P. falciparum to pyrimethamine and chloroquine resulting in the selection of resistant mutants. This selection was associated with multiple exposures of the parasites to much higher drug doses, during repeated passages through the non-immune hosts, increasing the degree of resistance. Resistances spread to the receptive areas of Kampuchea and other neighbouring countries through the movements of the temporary migrants who, by then, had become carriers infected with drug resistant falciparum parasites. The rapid and early spread of chloroquine resistance in A. balabacensis areas was not a coincidence but the result of the biological advantages of this species complex in relation to malaria transmission. In Australasia the medicated salt project carried out in Irian Jaya, on the border with Papua New Guinea, also resulted in the development of drug resistance in P. falciparum.