Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

8-Aminoquinolines are an important class of antiparasitic agents, with broad utility and excellent efficacy, but also limitations due to hematological toxicities, primarily methemoglobinemia and hemolysis. One representative from this class, (+/-)-8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3,4-dichlorophenoxy]quinoline succinate (NPC1161C), proved extremely efficacious in animal models of malaria and pneumocystis pneumonia. This racemic mixture was separated into its component enantiomers by chemical and chromatographic means. The enantiomers were evaluated for antiparasitic activity in murine models of Plasmodium berghei, Pneumocystis carinii, and Leishmania donovani infection, as well as the propensity to elicit hematotoxicity in dogs. The (-)-enantiomer NPC1161B was found to be more active (by severalfold, depending on the dosing regimen) than the (+)-enantiomer NPC1161A in all of these murine models. In addition, the (-) enantiomer showed markedly reduced general toxicity in mice and reduced hematotoxicity in the dog model of methemoglobinemia. It is concluded that the configuration at the asymmetric center in the 8-amino side chain differentially affects efficacy and toxicity profiles and thus may be an important determinant of the "therapeutic window" for compounds in this class.
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PMID:Antiparasitic activities and toxicities of individual enantiomers of the 8-aminoquinoline 8-[(4-amino-1-methylbutyl)amino]-6-methoxy-4-methyl-5-[3,4-dichlorophenoxy]quinoline succinate. 1837 16

Kala-azar was a lethal disease in colonial India. Charles Donovan of the Indian Medical Service (IMS) in Madras discovered the parasite independently in 1903 while William Boog Leishman was carrying out his research in Great Britain. Donovan's discovery ended the confusion prevalent over the anomalous and puzzling cases of malarial fevers in India and proved they were not related to malaria. This added to the promotion of medical knowledge, initiated further research and created enthusiasm among medical scientists throughout the world. Donovan was the first person to see the kala-azar parasite in the peripheral blood and thus provided a clue to the carriage and transmission of the kala-azar parasite by the insect through peripheral blood. Donovan's research on kala-azar also convinced the government of its utility and the need for further investigation; he fell victim to professional rivalry.
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PMID:Pursuit of medical knowledge: Charles Donovan (1863-1951) on kala-azar in India. 1846 75

Visceral leishmaniasis is present in 61 countries but 90% of the 500,000 new cases that arise annually occur in five countries, i.e., India, Bangladesh, Nepal, Sudan, and Brazil. Annual mortality is approximately 59000 cases. Agents based on pentavalent antimony have been the mainstay of treatment for the last 60 years. In recent years, however, clinical resistance to these agents has been reported especially in the state of Bihar in India. Pentamidine and amphotericin B were introduced in the 1950s and 1960s. More recent additions to the therapeutic arsenal include liposomal amphotericin B, miltefosine, and paromomycin. Among these recent molecules, miltefosine, i.e., the only oral agent, appears most vulnerable because it involves long-term treatment and has a long half-life. The main therapeutic problems now being encountered are the emergence of acquired resistance to antimonials, the high cost of treatment, and failure of therapy in immunocompromised patients mainly due to concurrent human immunodeficiency virus (HIV) infection. For eradication initiatives such as the one aimed at eliminating leishmaniasis on the Indian subcontinent, the appearance of drug resistance increases the risk associated to parasite infection and, as for malaria, tuberculosis and HIV infection, raises fears that the problems in the implementation of public health policies will lead to highly refractory forms.
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PMID:[Visceral leishmaniasis: clinical sensitivity and resistance to various therapeutic agents]. 1847 81

Visceral leishmaniasis continues to be an important public health problem worldwide. This vector-borne infection affects approximately 500,000 people annually with more than 50,000 associated deaths, a number that among parasite diseases is surpassed by malaria only. Leishmaniasis was recently selected by the World Health Organization for elimination by 2015. Major obstacles for achieving this goal include lack of an antileishmanial vaccine, wide-spread resistance to pentavalent antimonials in the State of Bihar, India where half of cases globally occur, and drawbacks of alternative antileishmanial drugs, including prolonged administration, serious adverse effects, and high costs in poor endemic areas. During the past decade, significant progress has been made towards the development of new and less toxic antileishmanial agents, including the oral agent miltefosine. Currently, there are several agents with antileishmanial activity under investigation as well as patents that may deserve further testing within combination regimens. In order to preserve the activity of available antileishmanial agents, monitoring of their delivery, response, and resistance should be implemented globally. Combination regimens should be further investigated in large trials. The costs of antileishmanial agents should be minimized in poor endemic areas where there are needed most.
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PMID:Visceral leishmaniasis: advances in treatment. 1899 1

In the current academic circle, there are different opinions about the types of the statutory infectious diseases in the Republican period, including the nine-, ten-, eleven- and thirteen-type hypotheses being the most popular. They are different not only on the diseases types, but also about the time of its announcement. This article argues that there were eight kinds of statutory infectious diseases in 1916, i.e. cholera, dysentery, typhoid, smallpox, diphtheria, scarlatina,plague, and typhus; nine in 1928, with cerebrospinal meningitis being added; ten in 1944, with relapsing fever being added; after that, there were no changes. The appointed infectious diseases were initially relapsing fever and malaria; when the relapsing fever became the statutory one, then the appointed ones were the malaria and kala-azar. The establishment of the statutory and the appointed infectious diseases signified that the government of the Republican period had intervened in the administration of infectious diseases.
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PMID:[A type analysis of the statutory infectious diseases in the Republican period]. 1912 45

In vitro screening of the dichloromethane extracts of 16 Asteraceae species native to Sudan for activity against major protozoan pathogens revealed that a Xanthium brasilicum Vell. [syn. X. strumarium var. brasilicum (Vell.) Baker in Mart.] extract was the most active against Trypanosoma brucei rhodesiense, the etiological agent of East African human trypanosomiasis (IC(50) = 0.1 microg/mL). This plant extract also exhibited noticeable activities against T. cruzi (Chagas disease), Leishmania donovani (Kala-Azar) as well as Plasmodium falciparum (Malaria tropica). Bioactivity-guided fractionation resulted in the isolation of four bioactive sesquiterpene lactones (STL) of the xanthanolide series (4,5-seco-guaianolide-type). They were identified by spectroscopic means as 8-epixanthatin (1), 8-epixanthatin 1beta,5beta-epoxide (2), and as the dimers pungiolide A (4) as well as pungiolide B (5). Two further modified xanthanolide sesquiterpene lactones, xanthipungolide (3) and 4,15-dinor-1,11(13)-xanthadiene-3,5beta:12,8beta-diolide (6) were isolated. While xanthipungolide turned out to be inactive against the tested parasites, the dinor-xanthanlide showed significant activity against T. brucei rhodesiense and L. donovani. All isolated compounds were previously known from other Xanthium species but this is the first report on their occurrence in X. brasilicum, and, most notably, on their antiprotozoal activity. As the most active single compound from this extract, 8-epixanthatin 1beta,5beta-epoxide showed IC(50) values of 0.09, 2.95, 0.16 and 1.71 microg/mL (0.33, 11.3, 0.6 and 6.5 microM) against T. brucei rhodesiense, T. cruzi, L. donovani and P. falciparum, respectively, while its cytotoxicity against rat myoblast cells used as control was determined at 5.8 microg/mL (22.1 microM). Besides assessment of their antiprotozoal activity, the structural assignments for the dimeric xanthanolides pungiolide A and B were reinvestigated and fully established.
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PMID:The antiprotozoal activity of sixteen asteraceae species native to Sudan and bioactivity-guided isolation of xanthanolides from Xanthium brasilicum. 1943 Oct 98

Travel medicine deals with travellers' diseases. The target group is therefore distinct from tropical medicine. It has gained in significance due to the increase in tourism and professional work abroad in the last 50 years. Dangerous and widespread diseases in tropical countries, in particular tropical malaria, have come into focus in industrialized countries because of their appearance in travellers. Travel medicine deals not only with infectious or transmittable diseases, but also with the ability of patients with chronic diseases to travel, the medical aspects of flying, as well as the health hazards of professional work or high-risk sports abroad. The risk of disease as a result of travelling can be minimized by advice and prophylactic measures, such as vaccinations and drug prophylaxis against malaria, if indicated. On return, medical symptoms should be investigated promptly to ensure early detection of life-threatening disease courses, particularly tropical malaria, as well as to prevent the occurrence of small-scale epidemics. A small number of diseases can also emerge after several years, such as benign types of malaria, amoebic liver abscess and visceral leishmaniasis (kala-azar). Aids also belongs to these diseases. Therefore, in this era of HIV pandemic travellers concerned should be made aware of the risks.
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PMID:[Travel medicine]. 1948 93

Global warming, globalisation, and constantly increasing number of people involved in long-distance tourism and travel to exotic destinations are likely to increase the number of cases of exotic diseases "imported" to nonendemic countries. One of the often forgotten and neglected diseases has been visceral leishmaniasis (VL or kala-azar). The disease is endemic to 62 countries, with India and Sudan accounting for the majority of the cases. It is typically fatal if left untreated. Each year about 500 000 new cases are reported worldwide, and 50 000 die as a result of the disease. Kala-azar is present in the Mediterranean Europe and 70% of cases are imported to non-endemic countries of European Union from that area. Immunocompromised status of patients, like HIV carriers are the principal prospective target for kala-azar. HIV/VL-coinfected patients have significantly higher relapse rates and decreased life expectancy. There is no formal system of reporting imported cases in Europe, except from Germany. In non-endemic countries, including Poland, there is usually the substantial delay between the onset of symptoms and the final diagnosis, with an average exceeding 3 months. This fact suggests that physicians are not familiar with leishmania infections. Despite progress in vaccine development, the only way to prevent the infection is avoiding sandfly bites. Mosquito nets, wearing appropriate clothes and repellents containing DEET (diethyl toluamide) can reduce number of bites and protect also from the other vector-borne diseases like malaria or dengue. Education concerning kala-azar risk and ways of the disease prevention is a needed for tourists and the other travelers.
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PMID:[Visceral leishmaniasis as a threat for non-endemic countries]. 1985 34

It is unequivocal that climate change is happening and is likely to expand the geographical distribution of several vector-borne diseases, including malaria and dengue etc. to higher altitudes and latitudes. India is endemic for six major vector-borne diseases (VBD) namely malaria, dengue, chikungunya, filariasis, Japanese encephalitis and visceral leishmaniasis. Over the years, there has been reduction in the incidence of almost all the diseases except chikungunya which has re-emerged since 2005. The upcoming issue of climate change has surfaced as a new threat and challenge for ongoing efforts to contain vector-borne diseases. There is greater awareness about the potential impacts of climate change on VBDs in India and research institutions and national authorities have initiated actions to assess the impacts. Studies undertaken in India on malaria in the context of climate change impact reveal that transmission windows in Punjab, Haryana, Jammu and Kashmir and north-eastern states are likely to extend temporally by 2-3 months and in Orissa, Andhra Pradesh and Tamil Nadu there may be reduction in transmission windows. Using PRECIS model (driven by HadRM2) at the resolution of 50 x 50 Km for daily temperature and relative humidity for year 2050, it was found that Orissa, West Bengal and southern parts of Assam will still remain malarious and transmission windows will open up in Himachal Pradesh and north-eastern states etc. Impact of climate change on dengue also reveals increase in transmission with 2 C rise in temperature in northern India. Re-emergence of kala-azar in northern parts of India and reappearance of chikungunya mainly in southern states of India has also been discussed. The possible need to address the threat and efforts made in India have also been highlighted. The paper concludes with a positive lead that with better preparedness threat of climate change on vector-borne diseases may be negated.
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PMID:Climate change and threat of vector-borne diseases in India: are we prepared? 2015 69

Acute schistosomiasis is a systemic hypersensitivity reaction against the migrating schistosomula and eggs. A variety of clinical manifestations appear during the migration of schistosomes in humans: cercarial dermatitis, fever, pneumonia, diarrhoea, hepatomegaly, splenomegaly, skin lesions, liver abscesses, brain tumours and myeloradiculopathy. Hypereosinophilia is common and aids diagnosis. The disease has been overlooked, misdiagnosed, underestimated and underreported in endemic areas, but risk groups are well known, including military recruits, some religious congregations, rural tourists and people practicing recreational water sports. Serology may help in diagnosis, but the finding of necrotic-exudative granulomata in a liver biopsy specimen is pathognomonic. Differentials include malaria, tuberculosis, typhoid fever, kala-azar, prolonged Salmonella bacteraemia, lymphoma, toxocariasis, liver abscesses and fever of undetermined origin. For symptomatic hospitalised patients, treatment with steroids and schistosomicides is recommended. Treatment is curative in those timely diagnosed.
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PMID:Acute schistosomiasis mansoni: revisited and reconsidered. 2072 85


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