Showing papers on "Malaria published in 1969"

Glucose-6-Phosphate Dehydrogenase Deficient Red Cells: Resistance to Infection by Malarial Parasites

Abstract: Erythrocyte mosaicism occurs in females heterozygous for glucose-6-phosphate dehydrogenase deficiency. In blood from female children with acute Plasmodium falciparum malaria the parasite rate was 2 to 80 times higher in normal than in deficient erythrocytes. This may be the mechanism whereby the gene for glucose-6-phosphate dehydrogenase deficiency confers selective advantage against malaria to heterozygous females, and thus may have attained the polymorphic frequency occurring in populations living in areas with endemic malaria.

Malaria, anaemia and pregnancy.

Abstract: Physicians at University College Hospital in Ibadan Nigeria selected 250 initially unmarried 17-25 year old women employed at the hospital as subjects of a prospective study of the relationship between malaria anemia and 1st pregnancy. 60 women later became pregnant. Physicians gave full physical examination to each of the 250 women which included urine analysis determination of liver and spleen size and a variety of hematologic tests such as packed cell volume (PCV) and blood film for malaria parasites. The frequency of malaria parasitemia and the density of infection were higher in pregnant women (4-12 times more frequent and 1775 parasites/cubic mm respectively) than the same women prior to pregnancy or in the nonpregnant women. Plasmodium falciparum caused infection in almost all cases with P. malariae being responsible for only 4 cases. The incidence of splenomegaly was much higher in the group of pregnant women (42%) than found in the same women before pregnancy. 38 women did not take antimalaria chemoprophylaxis until that point in pregnancy when treatment was necessary and 24 (63%) of them developed hemolytic anemia (PCV <28%). On the other hand none of the 19 women who received antimalarial drugs developed hemolytic anemia but 1 did develop megaloblastic anemia in the 18th week. The hemolytic anemia occurred between weeks 16-24. In some cases PCV fell before the appearance of detectable parasite densities and hemolysis continued for 2 weeks after chloroquine therapy effectively eliminated parasites. In a country where malaria is endemic administering antimalarial drugs prophylactically throughout pregnancy is the most important antenatal treatment.

Immunological aspects of malaria infection.

Abstract: Publisher Summary This chapter discusses the immunological aspects of malaria infection. The chapter is particularly concerned with specific acquired immunity to malaria and includes a discussion only of innate and nonspecific resistance. The chapter discusses immunity in malaria, an old subject that contains considerable current interest. New methods for the study of the relevant antibodies and a new appreciation for a role for cell-mediated immunity are responsible for this development. The very diverse contributions to this subject present unusual difficulties for a reviewer. However, a clear and interesting summary of the subject has emerged and is of considerable value as a reference for all immunologists. In adults, malaria sometimes occurs as epidemics but more often it is insidious in its effect; it reduces the vigor of communities and by its continued presence causes a retardation of social and economic growth. The effect of malaria on a community is accentuated by the occurrence of other endemic diseases such as schistosomiasis and hookworm. Suggestions are made in recent years to revise the nomenclature of malaria parasites and to institute several new genera.

Drug resistance in malaria-a perspective.

Abstract: One of the major technical problems facing malaria eradication in certain areas is the development of drug resistance. Resistance presents difficulties mainly in relation to P. falciparum infection. Proguanil and pyrimethamine resistance have seldom been reported in other species in the field and chloroquine resistance so far is restricted to P. falciparum malaria. The distribution of chloroquine resistance and multiple resistance in P. falciparum in South America and South-east Asia is reviewed and figured in two maps. The history of the development of resistance is discussed. The main predisposing conditions to resistance appear to be the influx of people with low levels of immunity into an area of continuing transmission, the presence there of resistant mutant parasites and free availability of the respective antimalarials. It is suggested that the underlying mechanisms by which resistant strains emerge are essentially the same for chloroquine as for folic reductase inhibitors. It is suggested moreover that chloroquine resistance may emerge in time in Africa where, until now, no proved foci of such strains have been recorded. The main weapon against drug resistance is the interruption of malaria transmission by residual spraying but in certain problem areas this is not possible. In these areas little can be done when multiple-resistant parasites are present until better drugs are available. A brief reference is made to the treatment of chloroquine-resistant P. falciparum malaria.

Infectivity of Chloroquine Resistant Plasmodium berghei to Anopheles stephensi enhanced by Chloroquine

Abstract: DRUG resistance is an increasing problem in parts of South America and South-East Asia where numerous strains of the malignant tertian malaria parasite, Plasmodium falciparum, are refractory to chloroquine and other widely used antimalarials1. The rapidity with which new chloroquine-resistant strains are being recognized suggests that they may have, as well as drug resistance, some biological advantage over the accompanying sensitive falciparum parasites either in the vertebrate host (man) or the invertebrate host (certain species of Anopheles mosquitoes).

Ferrokinetic studies and erythropoiesis in malaria.

Abstract: The anemia associated with human malaria cannot be completely explained by increased hemolysis. Depression of erythropoiesis associated with parasitemia has been suggested as an additional aggravating factor. This suggestion is supported by the following clinical evidence: (1) absence of reticulocytosis during malarial infection in which hemolysis was observed1-3and (2) a decreased number of erythroid precursors in the bone marrow during acute primary infection, followed by a normal or increased number of these cells after the removal of the parasites from the blood.3Although the latter study3has clearly demonstrated a depression of erythropoiesis during acute primary malarial infection, the situation is less clear in chronic or secondary malaria where normal or increased numbers of erythroid precursors are found in the bone marrow during parasitemia. Furthermore, the mechanism of erythropoietic depression remains unsolved. Further investigation into the effect of human malaria on bonemarrow function was carried out

Social factors and resistance to malaria in the mouse: effects of group Vs individual housing on resistance to Plasmodium berghei infection.

Abstract: &NA; Mortality rate of malaria‐infected mice was related to number of animals per cage, population sizes ranging from 1 to 20. This was independent of age, sex, and number of animals per cage infected. Individually housed mice died as fast as grouped mice with room temperature at 82°F rather than 70°F. If housing conditions were reversed after infection, mortality was dependent primarily on postreversal conditions. This, combined with failure to discriminate between differentially housed animals by weight, parasitemia, reticulocytosis or hematocrit on the sixth day after infection suggested that differences in mortality rate arise from responses to situations occurring after that day. Since cage size did not affect mortality rate, it was concluded that the housing effect is dependent upon population size, rather than density. Finally, grouped mice separated by screening died as slowly as individuals, suggesting a role of physical contact in the high mortality rate of grouped mice.

Malaria in American Soldiers

Abstract: A study of malaria occurring in 176 soldiers returning from Vietnam was undertaken to determine the type, clinical course, complications, prognosis, and most effective treatment. In contrast to other studies, malaria in 93% of our patients was due toPlasmodium vivaxand only 3% toP falciparum. Anemia was found in 15% of our patients, and hemolysis was the most frequent cause. Leukopenia and thrombocytopenia were relatively frequent. A significant number had intestinal parasites. Outstanding complications in these patients were spontaneous rupture of spleen and malarial hepatitis. Patients withP vivaxmalaria frequently were not cured with the modes of therapy presently used and had up to four recurrences. Recurrent malaria will be seen frequently by physicians in civilian practice.

Immunological studies on simian malaria. III. Immunity to challenge and antigenic variation in P. knowlesi.

Abstract: Immunity to reinfection in the simian malaria system studied was evidenced by (a) a delay in development of infections, (b) a milder course of parasitaemia, or (c) complete resistance to challenge. The immunity produced by repeated exposure to one antigenic variant was effective against subsequent challenge with heterologous variants. Populations of parasites isolated from different recrudescences of chronic P. knowlesi infections were shown to be antigenically distinct.

Global eradication of malaria: changes of strategy and future outlook.

Abstract: The concept of nation-wide or even global eradication of malaria originated from the findings that 1) interruption of transmission of the four species of plasmodia infecting man throughout large areas was possible with indoor residual spraying with DDT, and 2) malaria parasites usually disappear spontaneously from infected persons in less than 3 years, permanently interrupting transmission. From this standpoint three types of malaria may be considered: 1) responsive, when the vectors die after alighting on a sprayed surface for sufficient time, carrying with them malaria parasites that may be within their bodies, thereby interrupting transmission; 2) refractory, when due to a natural or acquired behavior of the mosquitoes, or to resistance to the insecticide, some of the vectors may survive the application of the insecticide; and 3) inaccessible, when due to cultural patterns or to the state of mind of the affected populations it is not possible to spray dwellings. Only responsive malaria is now eradicable; fortunately it is extensive, and current successes prefigure further benefits. Eradication of refractory malaria must be deferred, with few exceptions, but the disease can be reduced by adequate application of residual insecticides. Inaccessible malaria must await profound changes in cultural patterns or states of mind, but fortunately the affected populations are small and frequently isolated, and the required changes may not be far away. Therefore, eradication of malaria must at present be considered unstable, regional, and temporary. Until malaria disappears from the world there are risks of losing what has been accomplished in a given country. That more than one-third of the population of former malarious areas lives in zones where the disease has been eradicated, and that another third inhabits regions under eradication programs, constitute a great achievement. Slow progress, however, in the rest of the world indicates that further efforts should be made, particularly in financing the relevant programs in the developing countries. It is also of great importance to delimit the areas where malaria, because of being refractory or inaccessible, will not be soon eradicated. Changes in strategy are necessary—general public-health activities in hyperendemic areas are not effective in the presence of malaria; the funds they use might be better designated for efficient indoor residual spraying. On the other hand, simple control programs should be regarded with more enthusiasm in countries that are at present unable to undertake eradication, as the insecticide represents the best method to improve health in the highly endemic areas. As the maintenance phase will be long-lasting, it is essential that the work performed be simple and of low cost. I advise that the malaria-eradication service be transformed, after the objective is achieved, into a vector-borne-diseases control service, which would maintain eradication while producing benefits in other fields.

Quinine, pyrimethamine, and sulphorthodimethoxine: clinical response, plasma levels, and urinary excretion during the initial attack of naturally acquired falciparum malaria.

Abstract: Plasma concentrations and urinary excretion rates of antimalarial drugs were studied during acute illness in 15 patients with naturally acquired falciparum malaria despite chloroquine‐primaquine prophylaxis. The therapeutic regimen included single oral doses of sulphorthodimethoxine and pyrimethamine in combination with a 14 day course of quinine. The plasma half‐life of a 1 Gm. dose of sulphorthodimethoxine was 200 hours with levels exceeding 8 mg. per 100 ml. for 4 days. Plasma‐pyrimethamine concentrations remained relatively stable during the 14 day study. For both drugs a slow rate of urinary elimination accounts for sustained plasma levels following single doses. Doses of 650 mg. of quinine every 8 hours produced mean plasma levels in excess of 11 mg. per liter during the first 5 days. Thereafter the concentration gradually declined to levels observed in patients receiving quinine during relapse and experimental infections. Transient hepatic dysfunction during the acute phase of the illness may account for the initial elevation and subsequent decline during continued administration. In all patients the clinical illness was promptly controlled and no toxicity developed. There were no relapses. The advantages of single‐dose oral therapy, the promising clinical results, and low incidence of toxicity suggest that sulphorthodimethoxine may be an important antimalarial drug and that further clinical and pharmacological investigation is warranted.

Imported malaria in the United Kingdom

Abstract: Over 2,000 cases of imported malaria have been confirmed by blood examination. Ninety percent. of cases from tropical Africa were infected with P. falciparum. Most of the patients were Caucasians and had primary infections. All developed fever within a month after arrival and most of them within two weeks of arrival. In some patients malaria parasites were seen in routine blood films.Developing forms of P. falciparum were always present in the peripheral blood of patients suffering from a primary attack which was not diagnosed or treated until a week or more after the onset of fever.All deaths investigated were caused by P. falciparum and were primary infections.In not one of the P. falciparum infections did the victim continue taking prophylactic drugs for more than a few days after leaving the endemic area. Had drugs been continued for one month probably not a single overt case of P. falciparum would have occurred.A primary attack of P. falciparum malaria is seldom, if ever, classical in that the fever is never tertian and may resemble clinically many other diseases.Children in boarding-schools returning from the tropics should be supplied with prophylactic tablets and instructions to the matron. If there is an epidemic of a fever any students who have recently returned from the tropics should have a blood film examined for malaria.The risk of contracting malaria among drug addicts is considerable, especially with P. falciparum.

Renal and hematologic complications of acute falciparum malaria in Vietnam.

Abstract: : Hematologic complications of malaria or malaria therapy include decreased circulating platelets, erythrocytes, and leukocytes. Thrombocytopenia is seen in association with consumptive coagulopathy or rarely in association with drug therapy. Severe hemolysis, although generally related to intense parasitemia, may be associated with specific red cell enzyme defects or with the administration of quinine. The usual patient with hemolysis secondary to malaria infections has a delayed erythropoietic response until parasitemia has been eradicated. Pyrimethamine probably does not contribute to the delayed response unless anemia is severe. Leukopenia is common during the first few days of an acute attack of malaria, but the count of white blood cells approaches normal with therapy. A decrease in circulating leukocytes to levels less than 3000/cu mm during therapy may represent an idiosyncratic reaction.

Malaria imported to the United States from Vietnam. Chemoprophylaxis evaluated in returning soldiers.

Abstract: In addition to the high incidence of malaria among the American millitary in Vietnam, there has been a progressive increase in the number of imported cases occurring in such persons following their return to the United States. Most of these cases are due to Plasmodium vivax infection. The combined chloroquine-primaquine tablet, taken once a week for 8 consecutive weeks, is effective for radical cure for vivax infection, and all returnees supposedly complete this course of therapy. This study was made to assess the effectiveness of this prophylactic program. A questionnaire survey was made of 671 Army officers and enlisted men regarding malaria prophylaxis. Of the total group, 70% failed to complete the full course of therapy. The rate of failure among officers and enlisted men was nearly equal. There was no predominant cause for failure, but common reasons given included 1) forgetting to take medication, 2) loss of pills, 3) not receiving sufficient number of pills, and 4) untoward side-effects of therapy. Persons stationed in “high-risk” malaria areas were more likely to complete therapy successfully, although previous clinical malaria did not improve the success rate in such affected persons. This extremely high failure rate of the current malaria chemoprophylaxis program would appear to be a significant factor contributing to the high incidence of imported malaria occurring in the United States.

Enlarged livers and spleens in an area endemic for malaria and schistosomiasis

Abstract: The prevalence of hepatic and splenic enlargement, S. mansoni and S. haematobium infection, malaria and malnutrition have been surveyed in an area endemic for malaria and schistosomiasis. Malaria was commonest at age 0–4, and both liver and splenic enlargement were significantly associated with it. At 5–9 years hepatomegaly was found to be significantly associated with S. mansoni infection and with combined malaria and S. mansoni infection. Hepatosplenomegaly was also associated with the combined infection. Splenomegaly was associated with malaria but not with S. mansoni. Neither hepatomegaly or splenomegaly was associated with S. haematobium infection. Malnutrition as determined by weight for age was not associated with liver enlargement. In the 10–14 and the 15+ age groups the only significant association found was that between liver and splenic enlargement.

The impact of insecticide-resistance on control of vectors and vector-borne diseases

Abstract: A questionnaire inquiring into the nature of schemes for the insecticidal control of disease vectors, the development of resistance in these vectors, and the effect of any such resistance on their control and on the extent of disease was sent to more than 100 health authorities throughout the world. The replies to the questionnaire are summarized in this paper.Until recently, the use of insecticides in public health has been largely based on three organochlorine compounds-DDT, HCH and dieldrin. However, in some countries resistance to these has now severely affected control both of many insect species and of the diseases they transmit (e.g., malaria, yellow fever, filariasis, typhus, plague). Certain other public health problems (onchocerciasis, Chagas' disease, trypanosomiasis, leishmaniasis) have not so far been greatly affected by resistance, but it is difficult to be sure of the continued reliability of the organochlorines.Research in the past 5 years, much of it sponsored by WHO, has shown the value of various organophosphorus and carbamate insecticides as replacements for the organochlorines, although resistance to them, too, can occur. Attention must therefore be focused on all facets of the use of these newer compounds and particular scrutiny made of possible instances of resistance to them.

Experimental malaria control and demography in a rural East African community : a retrospect.

Abstract: The aftermath of the Pare-Taveta Malaria Scheme, an experiment to control malaria in rural East Africa, provided opportunities to study the recovery of malaria vectors after the suspension of the dieldrin spraying programme. The vector status of A. gambiae did not return until some 6 years after the final round of spraying; similarly, there was a delay of almost 8 years before A. funestus was able to re-establish itself in the Mkomazi valley of South Pare. These findings are tentatively attributed to recurrent potentiation of dieldrin remaining in the mud walls of huts treated during the Scheme, which seemed to take place each year at the onset of the wet season. The opportunity was taken to examine the effects of the resurgence of malaria on local vital rates. Through the generosity of the Nuffield Foundation, a 5-year programme for the collection of vital statistics was initiated in 1961 in two communities where these rates had recently improved, coincidentally with protection from malaria transmission. A parallel series of observations were made in a neighbouring upland community, that was malaria-free. The improvements in vital rates that occurred during the Malaria Scheme in the lowland communities have been well maintained among most age-groups, at least until the end of 1966, despite the progressive return of malaria. However, there was evidence of a rising death rate during this period among young children and infants, that could be confidently connected with malaria infections. No evidence has been found to indicate that the resumption of malaria transmission was interfering with fertility in these communities.

Humoral Immunity in Rodent Malaria I. Estimation of Parasitemia by Electronic Particle Counting

Abstract: Parasitemia in young rats infected with Plasmodium berghei can be monitored by electronic counting of particles in blood lysates. The number of particles so obtained provides an estimate of the number of parasitized cells in the blood sample. The method is highly reproducible as compared to conventional techniques, especially as applied to low levels of parasitemia. The further advantage of rapidity is also inherent in the procedure.