Recent Advances in Malaria Drug Discovery
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Malaria is responsible for over 300 million clinical cases annually and claims the lives of approximately 1-2 million. With a disease that has plagued humanity throughout history, one would think that better control measures would be in place to decrease the mortality and morbidity associated with malaria. Due to malaria drug resistance, an increase in the number of clinical infections and deaths is soon likely to be observed. Therefore, there is a push to identify and introduce new drug entities for malaria treatment and prophylaxis. In an effort to develop new malaria drugs, several different approaches have been implemented. These include the use of drug combinations of either new or existing antimalarials, exploitation of natural products, identification of resistance reversal or sensitizing agents and the targeting of specific malarial enzymes. Past experience has shown that introduction of the same chemical entities, such as quinolines and antifolates, results in only limited efficacy with resistance developing rapidly within one year of introduction. New approaches to drug discovery should identify novel chemotypes which circumvent the parasites disposition to drug resistance. This review summarizes current efforts in malaria drug discovery as uncovered in recent patent literature. Keywords: Malaria, Plasmodium, inhibitors, chemotherapy, antimalarials, antimalarial drug resistance reversal agents, natural products as antimalarials, malaria drug optimization, drug discoveryTopics:
Intraleucocytic malaria pigment has been suggested as a measure of disease severity in malaria. We have tested this hypothesis by studying 146 children aged 6 months to 14 years in 4 categories--cerebral malaria, mild malaria, asymptomatic malaria and 'no malaria'--in Ibadan, Nigeria, an area of intense malaria transmission in Africa. Children with cerebral malaria were studied at the university hospital, those with mild malaria at 2 primary health centres and the other 2 groups were studied in a primary school. The proportion of pigment-containing neutrophils showed a clear rise across the spectrum no malaria--asymptomatic malaria--mild malaria--cerebral malaria (median values 2.0%, 6.5%, 9.0% and 27.0%, respectively; P < 0.0001). The proportion of pigment-containing monocytes did not differ significantly between the mild malaria, asymptomatic malaria and no malaria groups but the cerebral malaria group had a higher median value than the other 3 groups. The ratio of pigment-containing neutrophils to pigment-containing monocytes showed the same trend across the groups of subjects as was observed with the number of pigment-containing neutrophils. It is concluded that the pigment-containing neutrophil count is a simple marker of disease severity in childhood malaria in addition to the parasite count.
Cerebral Malaria
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Objective To study the malaria epidemic characteristics and control measures, so as to control malaria and eradicate falciparum malaria in Guangxi Autonomous Region of China. Methods During attack phase integrated measures were taken to control falciparum malaria in natural villages which were classified according to the prevalence of malaria; post control of malaria, the major control measure was seeking and getting rid of the malaria infection source through examining the fever patients and the annul blood examination rate was up to 10%. Results The malaria morbidity in Guangxi was reduced from 296.7 to 0.07; during 1997-2001 a total of 6 241 011 fever patients and foci residents were examined and only 485 cases of vivax malaria were found out, but falciparum malaria was not discovered. Conclusion The measures were very effective for basically eliminating malaria and falciparum malaria in Guangxi.
Vivax malaria
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[Objective]To understand the malaria prevalence before and after basic elimination of malaria in the county.[Methods]Collected and collated the internal and external sources of malaria in the county from 1980-2008.Excel statistical software was used for statistical analysis.[Results]During the last 28 years,there 1 128 malaria cases were reported.Before eradication of malaria,48.32% were the local malaria patients,51.68% were the floating population.After the malaria eradication,it found all 116 malaria cases were floating population.The places where the population infected were respectively 65.25% for Hainan,10.80% for Guangdong,2.66% Myanma,2.19% Yunnan.And Plasmodium falciparum malaria and mixed infection were found.[Conclusion]After the eradication of malaria,internal malaria patients are not found in the county.Malaria cases are mainly from the floating population.It dose not find secondary malaria patients.The effect of anti-malaria has been consolidated.
Floating population
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Malaria parasites occur in endemic areas such as the detection of parasites in a blood film from a febrile individual does not necessarily indicate clinical malaria, the fraction that has malaria symptoms and is attributable to malaria has been a major concern especially when symptomatic patients presume that they have malaria before confirming from laboratory test. The aim of the study is to determine the proportion of the patients that actually has malaria among the symptomatic patients. The objectives are to determine the predisposing factors that will tell us if a patient has malaria before laboratory test and a model that is clinically interpretable to describe the relationship between an outcome (malaria or no malaria) and a set of independent variables. As a result of high rate of malaria cases, there is a need to conduct research on factors influencing malaria. Logistic regression was used to analyse the secondary data collected from University of Ilorin Clinic from 1st January, 2015 to 30thJune, 2015. The attributable fraction for malaria was 49.2% and 50.8% was attributable to other diseases though they have identical symptoms. Males are 2.899 times likely to have malaria than females even after controlling for genotype. Patients of AA are 4.212 times likely to have malaria than the SS patients, patients of AS are 3.991 times likely to have malaria than the SS patients.
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Diagnosis of malaria
Tropical Medicine
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A small molecule can cure malaria infections in mice with a single dose, researchers report. They also show that the malaria parasite Plasmodium falciparum has a tough time developing resistance to the compound, known as MMV688533. If shown to be safe and effective in people, MMV688533 could be a powerful weapon in the fight against malaria. Malaria infections and deaths declined between 2000 and 2015 thanks to preventative measures, diagnostics, and therapeutics, but the number of people who get malaria has plateaued since 2016. Malaria parasites in Southeast Asia have developed resistance to the current arsenal of antimalarial drugs, making them ineffective in many cases. This same resistance threatens to become a problem in Africa, where malaria takes the biggest toll. Malaria killed about 409,000 people in 2019, according to the World Health Organization. "It could easily get a lot worse if we lose our first-line drugs," says malaria researcher
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Malarial parasites
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More than 200 million people worldwide contract malaria from mosquito bites. In sub-Saharan Africa, 100 million clinical cases of malaria are reported every year, resulting in almost one million deaths. Malaria has been implicated in the causation of deafness in several studies in the West Africa subregion. This paper examines the association between malaria and deafness, and considers which factors may be involved in the causation of deafness. Although age, immunity, the type of malaria parasite, fever, complications of malaria, and complications resulting from the drug treatment of malaria may contribute to the development of deafness in malaria, the actual mechanism of causation is not clearly understood. Deafness in malaria is associated with P. falciparum parasitic infection. The author is certain that the high fever in malaria, leading to febrile convulsions and cerebral involvement, can result in deafness. Further investigation is needed to determine whether the presence of untreated malaria parasites in the blood causes deafness.
Cerebral Malaria
Causation
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After mentioning the main differences between malaria control and malaria eradication, it is suggested that all anti–malaria activities in Iran should be renamed as malaria control. Applied research in malaria is identified into four categories covering the following subjects. 1- Malaria parasites and anti-malaria drugs. 2- Malaria vectors. 3- Malaria in the community. 4- Use of epidemiological techniques in malaria field research. Various research programs that at present could or should be carried out in each category have been discussed in the text.
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Any drug selects for drug resistance. But super-antagonistic drug combinations can select for drug sensitivity. This has important application not only for antibacterial therapy but also for cancer therapy: to control cancer with lesser side effects and to eliminate drug-resistant cancer cells, while sparing sensitive normal cells.
Cancer drugs
Cancer Therapy
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Objective To undersand the results of malaria control in Hainan a year after simplementation of Global Fund Malaria Projexct and provide evidence for elimination of malaria in Hainan province.Methods Data of malaria project activities in Hainan from July,2010 to July,2011 were collected and analyzed.Results No Plasmodium falciparum malaria cases were reported from 2010 to 2011,annual blood microscopy rate was 1.39%;the standard treatment rate of malaria cases was 90%.Conclusion The microscopy examiantion rate and standard treatment rate of of malaria infections attained the requirements of Glopbal Fund Malaria Project.
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Malaria may be encountered in parts of South Africa not known to have malaria, in ways not typical of how it is usually transmitted or acquired. In this issue of SAMJ two articles discuss two clinical forms of malaria in non-endemic areas, imported malaria and odyssean malaria. Imported malaria is defined as malaria presenting in a country other than that in which it was acquired, while odyssean malaria is acquired in non-malarious area from the bite of an imported mosquito. Imported and odyssean malaria are important because of the high incidence of complications and mortality often associated with them, and should be remembered as a cause of unexplained fever and thrombocytopenia. Key to reducing the complications and mortality related to malaria is early recognition and treatment.
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