Showing papers on "Malaria published in 1976"

Culture of human malaria parasites Plasmodium falciparum

Abstract: MALARIA is a major cause of morbidity and mortality, claiming an estimated one million lives a year in Africa alone1. Plasmodium falciparum, the most important agent of human malaria, has not been maintained for more than 2–6 d in vitro2–10. The development of a vaccine for malaria depends on suitable culture methods for the production of relevant antigens1. We describe here a new culture method for P. falciparum, which involves an inoculum of cryopre-served parasites and make possible an analysis of merozoite–erythrocyte interactions, growth for more than 3 weeks in vitro and the collection of merozoites. Merozoites are of particular interest because vaccination with the merozoites of P. knowlesi protects rhesus monkeys from infection with this species of malaria parasite11.

Malaria transmission blocked by immunisation with gametes of the malaria parasite

Abstract: IN view of the limited success of malaria eradication schemes based on concepts of vector control and chemotherapy, serious efforts are being made to investigate the possibility of developing an antimalarial vaccine. So far two classes of vaccine have been under investigation: (1) an anti-sporozoite vaccine designed to prevent malarial infection by blocking the infectivity of sporozoites introduced by mosquito bite1,2, and (2) vaccines directed against the asexual stages in the blood3–5. Although the potential value of such vaccines is unquestionable, their realisation faces technical problems6. The latest proposition is to induce immunity against the parasite stages which infect the mosquito and by so doing prevent transmission of the disease by the vector. Gwadz has shown that the infectivity of malarious chickens to mosquitoes can be reduced greatly by prior vaccination with formalin-treated or X-irradiated blood infected with the malaria parasite P. gallinaceum7. The number of oocysts (the stage of the parasite developing on the wall of the mosquito gut) in mosquitoes fed on vaccinated chickens was reduced by 95–98% below that recorded in mosquitoes fed unvaccinated birds. To achieve this reduction, chickens were given three weekly intravenous inoculations of a total of 4.5 ml of formalin-treated or irradiated blood. Using the same schedule, but with partially purified gametes of the malaria parasite, we have now reduced the infectivity of malarious chickens to mosquitoes at least 99.9% below control levels. To achieve this reduction we had to use a minimum of 0.1 µl of packed cellular material.

Suppression of malaria infection by oxidant-sensitive host erythrocytes

Abstract: DEFICIENCY of the red cell enzyme, glucose-6-phosphate dehydrogenase (G-6-PD), predisposes erythrocytes to oxidant-induced haemolysis and is thought to protect humans against severe malaria infection. We have already shown that the malaria parasite exerts an oxidant stress on infected red cells and suggested that premature lysis of malaria infected erythrocytes might occur in G-6-PD deficient humans1, thus limiting the severity of infection by enforcing the release of immature parasites incapable of propagating the infection2.

The treatment of malaria.

Abstract: At least four doses of quinine followed by a single dose of mefloquine or by a single dose of sulfadoxine-pyrimethamine are two highly effective regimens for chloroquine-resistant falciparum malaria. Mefloquine alone is valuable in ambulant patients. Chloroquine-sensitive falciparum malaria can be treated with a course of chloroquine. Vivax and all other types of malaria should be treated with sequential chloroquine and primaquine. Quinine, by intravenous infusion, is the most effective drug for severe falciparum malaria. The optimum intravenous dose varies between 5 mg/kg and 10 mg/kg administered over four hours. Intravenous or oral quinine should be administered about every 12 hours and the total daily dose of quinine should rarely exceed 20 mg/kg. Intravenous fluid input should be controlled in falciparum malaria to prevent pulmonary oedema. Established renal failure is best treated by dialysis. The value of adrenocortical steroids for falciparum coma has not been established. Fresh blood transfusion may be helpful in small doses for severe anaemia and to replace clotting factors. Anticoagulants, such as heparin, should not be used in falciparum malaria.

Genetics of chloroquine resistance in malaria parasites

Abstract: THE resistance of the malaria parasite of man, Plasmodium falciparum, to treatment with chloroquine is a growing problem, especially in South-east Asia and South America1. It is not known whether the emergence of resistance is attributable to the selection of resistant mutants under drug pressure, to the spread of naturally resistant forms in the parasite population or to adaptation to the drug by previously sensitive parasites. In malaria parasites of rodents, it has been shown that resistance to the antifolate drug pyrimethamine arises by mutation2 and that the genetic factors involved can undergo recombination with other markers in crosses between resistant and sensitive parasite lines3. Resistance to chloroquine in rodent plasmodia seems to take several forms. P. yoelii isolates are innately resistant to the drug4, whereas P. berghei and P. vinckei are sensitive. Stable chloroquine resistance has been produced in P. vinckei by drug selection in the laboratory5 but resistance developed in this way in P. berghei is usually unstable in the absence of the drug6.

Impact of control measures on malaria transmission and general mortality.

Abstract: This paper is an attempt to relate modifications observed in general and infant mortality rates with the dynamic changes in transmission induced by malaria control measures. The observations indicated relationships between the efficacy of control and a decrease in mortality. The daily parasitological inoculation rate was reduced from 0.00958 infective bites per individual before treatment to 0.00037 after treatment (a decrease of 96%). In two years, general mortality decreased from 23.9 to 13.5 deaths per 1000 population and infant mortality decreased from 157 to 93 per 1000 live births. This indirect benefit of malaria control deserves attention in a wider assessment of measures directed against vector-borne diseases.

Malaria eradication and control from a global standpoint.

Abstract: The effectiveness of DDT applied to the walls of houses in interrupting the transmission of malaria by shortening the life of the Anopheles vector was the basis of national malaria programs until 1956, of the world malaria eradication campaign until 1968, and of the revised strategy of control or eradication until the present. Areas supporting nearly 800 million people, comprising most of the temperate-zone countries, have been thus liberated from malaria. The global incidence of malaria is now about 120 million cases annually, of which nearly 100 million are in tropical Africa; this may be compared with the estimate of 300 million annual cases before 1946, when the population was roughly 1/2 what it is in 1976. The principal problems in southern Asia, which is experiencing setbacks, are increasing insecticide-resistance in the vectors and a decrease in available funds in face of increasing operational costs.

Infectivity of falciparum malaria patients for anopheline mosquitoes before and after chloroquine treatment.

Abstract: The infectivity of 25 falciparum malaria patients for Anopheles balabacensis and Anopheles minimus, before and after chloroquine therapy, was studied in central Thailand. The proportion of patients infective for these mosquitoes was not affected by the administration of chloroquine, however, an elevation was observed in the median values for the numbers of oocysts on the guts of the A. balabacensis, but not the A. minimus, fed on infective patients after initiation of treatment.

Malaria of the orang-utan (Pongo Pygmaeus) in Borneo

Abstract: The primary objective of this project was to study the life cycle and ecology of Plasmodium pitheci, a malaria parasite of the orang-utan. The field work was based on the orang-utan rehabilitation centre in the Sepilok Forest Reserve of eastern Sabah. Two visits were made to Sepilok, the first in February and March, 1972, and the second (by W.P.) in January 1974. On the first visit two species of "surrogate host" were taken to Sabah, i.e. chimpanzees and Aotus monkeys for experimental work. The arboreal habitat of the orang-utan in the dipterocarp forests of eastern Sabah is described. In the Sepilok Forest Reserve dwell gibbons and leaf-monkeys, in addition to a small population of semi-domesticated and wild, free-ranging orang-utans of various ages. Although numerous species of anopheline mosquitoes have been collected in eastern Sabah, longitudinal studies are not available. Anopheles balabacensis was caught both attracted to orang-utans and to man at Sepilok. This species which is the main vector of human malaria in the north of Borneo, is suspected also of transmitting orang-utan malaria in this part of Sabah. Repeated blood examinations have been made on a number of orang-utans in the centre since 1966 and a high prevalence of infection was recorded with Plasmodium pitheci. In 1966 10 out of 19 animals had demonstrable parasitaemia. Detailed case histories are presented to show the course of parasitaemia in several orang-utans. Infections of P. pitheci were found to run a very chronic course. During the 1972 expedition a second, previously undescribed malaria parasite of the orang-utan was discovered, and was named P. silvaticum. The new parasite was successfully transmitted both by blood inoculation and, later, by sporozoite inoculation, into splenectomized chimpanzees. Although both species of malaria parasite may cause transitory signs of illness, orang-utans in general appear to be little discomforted by the infection. The animals do however suffer from other infectious diseases such as amoebic and balantidial dysentery, and melioidosis is a serious natural hazard which may have accounted for several deaths of wild orang-utans. An unidentified, intraerythrocytic structure that appeared in the blood of one chimpanzee, which had been inoculated with blood from an orang-utan, may have contributed to its death. Detailed descriptions and illustrations of P. pitheci and P. silvaticum are given. All stages of the life cycle of P. silvaticum are known (the tissue stages having been described in the liver of a "surrogate host", the chimpanzee) but only the blood and sporogonic stages of P. pitheci have been seen. This species was not infective to a chimpanzee, although there is an earlier report of a transient infection in this host by other workers. In the blood both parasites showed a tertian periodicity. From the appearance of the tissue schizonts on the seventh day it was estimated that the complete pre-erythrocytic cycle of P. silvaticum in the chimpanzee would occupy 8 days. P...

Suppressive activity of mefloquine in sporozoite-induced human malaria.

Abstract: Mefloquine hydrochloride [WR 142,490; α-(2-piperidyl)-2,8-bis(trifluoromethyl)-4-quinolinemethanol hydrochloride] was tested for suppressive effect on sporozoite-induced malaria in nonimmune volunteers living in an area where malaria is not naturally transmitted. Single doses of 250 mg were given at weekly intervals, 500 mg at intervals of 2 weeks and 1,000 mg at intervals of 4 weeks, to men bitten by 10 to 15 mosquitoes heavily infected with a chloroquine- and pyrimethamine-resistant strain of Plasmodium falciparum. None of the individuals so treated developed infections during the period of drug delivery or during the follow-up period of 60 days. Doses of 250 or 500 mg produced no adverse reactions; mild epigastric discomfort occurred in all three men given 1,000 mg. Sporozoite-induced P. vivax infections were suppressed by single doses of 250 mg of mefloquine given at weekly intervals, but malaria developed after completion of the course. At treatment intervals longer than 1 week, vivax malaria was not suppressed.

Biological features of Anopheles fluviatilis and its role in the transmission of malaria in Iran.

Abstract: Anopheles fluviatilis is a vector of malaria in the southern regions of Iran. Its biological features and its significance are described.

Malaria complicating neoplastic disease.

Abstract: Two patients with neoplastic disease had transfusion-induced malaria. In a patient with acute myelogenous leukemia infected with Plasmodium vivax , neither his underlying disease nor intensive cytotoxic chemotherapy appeared to ameliorate or worsen the clinical course of his infection. In a splenectomized patient with metastatic carcinoma of the colon, P malariae infection was associated with a fulminant course simulating cerebral malaria. Despite delay in diagnosis, both patients responded dramatically to antimalarial chemotherapy and both developed appreciable antibody responses. ( Arch Intern Med 136:807-810, 1976)

Epstein-Barr virus-malaria interaction models for Burkitt's lymphoma: implications for preventive trials.

Abstract: Summary Infections with both Epstein-Barr virus (EBV) and malaria have been implicated as causal factors in the pathogenesis of Burkitt9s lymphoma (BL). Proposed trials of preventive measures for both infections are receiving serious consideration as possible means of establishing a causal relationship with BL. In this paper we examine certain models for the interaction of EBV and malaria in the induction of BL, and also review the aims of the longitudinal, population-based study being conducted in the West Nile District of Uganda. Given existing knowledge, the outcome of preventive trials, even for the most simple interaction models, is unpredictable and, under certain circumstances, trials of an EBV vaccine could actually increase the incidence of BL. It is suggested that trials of an EBV vaccine at this time would be premature and should be delayed at least until the results from the West Nile prospective study are clear.

Malaria in Ceylon.

Abstract: Malaria has been prevalent in Ceylon for many centuries. As long ago as 1638 a map of the island, published by the Dutch, showed great areas, particularly the North-Central Province, depopulated by ‘fever sickness’. These depopulated regions were the site of the ancient civilization of Ceylon; and there can be little doubt that malaria played a part in the ruin of that civilization. But today we can only speculate whether, as some believe, the importation of malaria from India was the primary factor in that decay, or whether the repeated Tamil invasions so disorganized the elaborate system of irrigation and agriculture developed by the Sinhalese as to create everywhere breeding places for Anopheles mosquitoes, and cause such general poverty and distress, that malaria which existed previously in manageable proportions became an insupportable disease.

Chloroquine-resistant falciparum malaria in East Kalimantan, Indonesia.

Abstract: Following the discovery of four imported chloroquine-resistant P. falciparum infections in the Province of Yogyakarta (Island of Java) sensitivity tests were carried out in the Province of East Kalimantan Island of Borneo). Twenty subjects were given 25 mg. of chloroquine base per kilogram of body weight over three days. Two infections were found resistant at the RII level and a third at the RI level with early recrudescence on day 7. In the other 17 cases followed up to day 21, six were found again with asexual parasites between day 9 and day 14 and a seventh on day 21. These results confirm the presence of chloroquine resistance in P. falciparum in East Kalimantan and, together with previous findings, suggest a widespread distribution of chloroquine-resistant falciparum malaria in this Province of Indonesia. It is particularly interesting to note that chloroquine-resistant falciparum malaria has now been detected in almost all the area of dispersion of A. balabacensis.

The Conquest of the Major Infectious Diseases in the United States: A Bicentennial Retrospect

Abstract: TYPHOID FEVER . MALARIA . YELLOW FEVER .. . . . . . .. DIPHTHERIA •.... POLIOMYELITIS , .

Chloroquine-resistant falciparum malaria acquired in Papua New Guinea.

Abstract: widely known as the fastest man over a short distance in his company, if not in the unit as a whole. Outside Tobruk, there was a large gun, known to all as \"Bardia Bill\". It must have projected a large shell to a considerable height, with the result that after the characteristic double boom, there was a delay of some 12 seconds before the shell duly arrived in the Tobruk township, during which time all soldiers with good hearing were prone to take shelter. Conservancy arrangements at the Beach Hospital in Tobruk were sited at the end of a jetty, and while communing with nature there one day, Frank heard an ominous double boom. He waited not on the order of his going, but left at once with the speed of a gazelle, dressing as he went; he never lived down the fact that the double boom he heard was caused by two of the brutal and licentious infantry \"fishing\" in Tobruk harbour with Italian grenades. Frank left a widow and two children; one of these succeeds his father as Secretary to the South Australian Branch of the AMA which is fortunate indeed to have a third-generation Dobbie on its executive.