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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since 1898, when it was established that malaria was transmitted by the Anopheles, the theory has had many sceptics and critics. One of the most serious objections was that Anopheles mosquitoes existed in regions which were not malarious, although they could have been, given the climatic and ecological conditions ('anophelism without malaria'). The history of this epidemiological problem passed through four different phases. In the first, it simply did not exist, because before Ross and Grassi's discoveries one can observe the presence of the Anopheles mosquitoes and the absence of malaria without considering it surprising. In the second phase it became a possible refutation of the mosquito theory of malaria transmission. In the third, after the definitive acceptance of this theory, anophelism without malaria was considered as a puzzle, a paradox, an enigma to be solved. Finally, in the fourth phase, after the discovery of the maculipennis subspecies complex, it became the aim of the antimalarial activities. The historical analysis of this epidemiological problem suggests many insights on the delicate and always changing malaria ecosystem.
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PMID:Anophelism without malaria: an ecological and epidemiological puzzle. 789 63

Though many details are known about the epidemiology of multiple sclerosis (MS), its aetiology has remained an enigma. To find a solution to this problem, the concept of so called 'anophelism without malaria' was put on trial. 'Anophelism without malaria' is a basic assumption of the epidemiology of malaria. It means that there is no transmission of malaria in the temperate zone, although the insect vector (the different species of anopheles) can be found nearly everywhere. Starting with the results from blood tests of five patients suffering from MS which indicate an infection with plasmodia, the old hypothesis of the malarial aetiology of MS (Mannaberg 1899) is reappraised and compared with today's pathological findings. A comparison of the old map of malaria with the later distribution of MS in the USA has been made, supporting the assumption that an infection with plasmodia in early childhood prevents a later disease, while a silent infection at the time of adolescence or later is its cause.
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PMID:Is multiple sclerosis caused by a silent infection with malarial parasites? A historico-epidemiological approach: part I. 1151 18

Women living in areas of intense P. falciparum transmission have acquired substantial protective immunity to malaria when they reach childbearing age. Nevertheless, pregnancies in such areas are associated with substantial malaria-related morbidity and mortality, particularly among women of low parity. The parity-dependency of susceptibility to malaria in pregnant women suggests that protective immunity to this type of malaria can be developed. However, until recently it has been poorly understood why the clinical protection against malaria, which young women in endemic areas acquire well before their first pregnancy, is suddenly rendered inadequate when they become pregnant, only to be regained during the course of a few pregnancies. In this article, I discuss some recent immuno-epidemiological studies of pregnancy-associated malaria, which, in combination with the generally improved understanding of how protective immunity to P. falciparum malaria operates and is acquired, have provided important insights into this enigma.
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PMID:The immuno-epidemiology of pregnancy-associated Plasmodium falciparum malaria: a variant surface antigen-specific perspective. 1577 83

The sera genes of the malaria-causing parasite Plasmodium encode a family of unique proteins that are maximally expressed at the time of egress of parasites from infected red blood cells. These multi-domain proteins are unique, containing a central papain-like cysteine-protease fragment enclosed between the disulfide-linked N- and C-terminal domains. However, the central fragment of several members of this family, including serine repeat antigen 5 (SERA5), contains a serine (S596) in place of the active-site cysteine. Here we report the crystal structure of the central protease-like domain of Plasmodium falciparum SERA5, revealing a number of anomalies in addition to the putative nucleophilic serine: (1) the structure of the putative active site is not conducive to binding substrate in the canonical cysteine-protease manner; (2) the side chain of D594 restricts access of substrate to the putative active site; and (3) the S(2) specificity pocket is occupied by the side chain of Y735, reducing this site to a small depression on the protein surface. Attempts to determine the structure in complex with known inhibitors were not successful. Thus, despite having revealed its structure, the function of the catalytic domain of SERA5 remains an enigma.
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PMID:Structural insights into the protease-like antigen Plasmodium falciparum SERA5 and its noncanonical active-site serine. 1959 43

Artemisinins have become essential antimalarial drugs for increasingly widespread drug-resistant malaria strains. Although tremendous efforts have been devoted to decipher how this class of molecules works, their exact antimalarial mechanism is still an enigma. Several hypotheses have been proposed to explain their actions, including alkylation of heme by carbon-centered free radicals, interference with proteins such as the sarcoplasmic/endoplasmic calcium ATPase (SERCA), as well as damaging of normal mitochondrial functions. Besides artemisinins, other endoperoxides with various backbones have also been synthesized, some of which showed comparable or even higher antimalarial effects. It is noteworthy that among these artemisinin derivatives, some enantiomers displayed similar in vitro malaria killing efficacy. In this article, the proposed mechanisms of action of artemisinins are reviewed in light of medicinal chemistry findings characterized by efficacy-structure studies, with the hope of gaining more insight into how these potent drugs work.
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PMID:Biological actions of artemisinin: insights from medicinal chemistry studies. 2033 87

The African malaria mosquito, Anopheles gambiae, inhabits diverse environments including dry savannas, where surface waters required for larval development are absent for 4-8 months per year. Under such conditions, An. gambiae virtually disappears. Whether populations survive the long dry season by aestivation (a dormant state promoting extended longevity during the summer) or are reestablished by migrants from distant locations where larval sites persist has remained an enigma for over 60 years. Resolving this question is important, because fragile dry season populations may be more susceptible to control. Here, we show unequivocally that An. gambiae aestivates based on a demographic study and a mark release-recapture experiment spanning the period from the end of one wet season to the beginning of the next. During the dry season, An. gambiae was barely detectable in Sahelian villages of Mali. Five days after the first rain, before a new generation of adults could be produced, mosquito abundance surged 10-fold, implying that most mosquitoes were concealed locally until the rain. Four days after the first rain, a marked female An. gambiae s.s. was recaptured. Initially captured, marked, and released at the end of the previous wet season, she has survived the 7-month-long dry season. These results provide evidence that An. gambiae persists throughout the dry season by aestivation and open new questions for mosquito and parasite research. Improved malaria control by targeting aestivating mosquitoes using existing or novel strategies may be possible.
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PMID:Aestivation of the African malaria mosquito, Anopheles gambiae in the Sahel. 2081 Aug 27

Artemisinin (ART) based combination therapy (ACT) is used as the first line treatment of uncomplicated falciparum malaria in over 100 countries and is the cornerstone of malaria control and elimination programs in these areas. However, despite the high potency and rapid parasite killing action of ART derivatives there is a high rate of recrudescence associated with ART monotherapy and recrudescence is not uncommon even when ACT is used. Compounding this problem are reports that some parasites in Cambodia, a known foci of drug resistance, have decreased in vivo sensitivity to ART. This raises serious concerns for the development of ART resistance in the field even though no major phenotypic and genotypic changes have yet been identified in these parasites. In this article we review available data on the characteristics of ART, its effects on Plasmodium falciparum parasites and present a hypothesis to explain the high rate of recrudescence associated with this potent class of drugs and the current enigma surrounding ART resistance.
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PMID:Artemisinin resistance in Plasmodium falciparum: A process linked to dormancy? 2342 May 6

Plasmodium falciparum, the causative agent of malaria, completely remodels the infected human erythrocyte to acquire nutrients and to evade the immune system. For this process, the parasite exports more than 10% of all its proteins into the host cell cytosol, including the major virulence factor PfEMP1 (P. falciparum erythrocyte surface protein 1). This unusual protein trafficking system involves long-known parasite-derived membranous structures in the host cell cytosol, called Maurer's clefts. However, the genesis, role, and function of Maurer's clefts remain elusive. Similarly unclear is how proteins are sorted and how they are transported to and from these structures. Recent years have seen a large increase of knowledge but, as yet, no functional model has been established. In this perspective we review the most important findings and conclude with potential possibilities to shed light into the enigma of Maurer's clefts. Understanding the mechanism and function of these structures, as well as their involvement in protein export in P. falciparum, might lead to innovative control strategies and might give us a handle with which to help to eliminate this deadly parasite.
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PMID:Maurer's clefts, the enigma of Plasmodium falciparum. 2428 72

Controversy surrounds the precise numbers of malaria deaths and clinical episodes in Africa. This would not have surprised malariologists working in Africa 60 years ago as they began to unravel the enigma that is 'malaria'. Malaria is a complex disease manifesting as a multitude of symptoms, degrees of severity and indirect morbid consequences. Clinical immunity develops quickly and the presence of infection cannot always be used to distinguish between malaria and other illnesses. During the 1950s and 1960s parasite prevalence was used in preference to statistics on malaria mortality and morbidity. An argument is made for a resurrection of this measure of the quantity of malaria across Africa as a more reliable means to understand the impact of control.
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PMID:Sixty years trying to define the malaria burden in Africa: have we made any progress? 2549 76