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Fundamental & Clinical Pharmacology Jun 2024Benzothiazole derivatives have been reported to possess a wide range of biological activities, including antimalarial activity. This systematic review aims to summarize... (Review)
Review
BACKGROUND
Benzothiazole derivatives have been reported to possess a wide range of biological activities, including antimalarial activity. This systematic review aims to summarize and evaluate the antimalarial activities of benzothiazole analogs.
METHODS
We conducted an electronic search using nine databases in October 2017 and subsequently updated in September 2022. We included all original in vitro and in vivo studies that documented the antimalarial activities of compounds containing benzothiazole analogs with no restriction. The risk of bias of each included study was assessed by ToxRTool.
RESULTS
Twenty-eight articles were included in our study, which are in vitro, in vivo, or both. Of these, 232 substances were identified to have potent antiplasmodial activity against various strains of the malaria parasite. Benzothiazole analogs show different antimalarial mechanisms, including inhibition of Plasmodium falciparum enzymes in in vitro studies and inhibition of blood parasites in in vivo studies.
CONCLUSIONS
Benzothiazole derivatives are promising substances for treating malaria. The structure-activity relationship studies suggest that the substitution pattern of the benzothiazole scaffold plays a crucial role in determining the antimalarial activity of the analog.
Topics: Antimalarials; Benzothiazoles; Plasmodium falciparum; Humans; Structure-Activity Relationship; Animals; Malaria
PubMed: 38146774
DOI: 10.1111/fcp.12974 -
Bioorganic Chemistry Feb 2024The increasing resistance of various malarial parasite strains to drugs has made the production of a new, rapid-acting, and efficient antimalarial drug more necessary,... (Review)
Review
The increasing resistance of various malarial parasite strains to drugs has made the production of a new, rapid-acting, and efficient antimalarial drug more necessary, as the demand for such drugs is growing rapidly. As a major global health concern, various methods have been implemented to address the problem of drug resistance, including the hybrid drug concept, combination therapy, the development of analogues of existing medicines, and the use of drug resistance reversal agents. Artemisinin and its derivatives are currently used against multidrug- resistant P. falciparum species. However, due to its natural origin, its use has been limited by its scarcity in natural resources. As a result, finding a substitute becomes more crucial, and the peroxide group in artemisinin, responsible for the drugs biological action in the form of 1,2,4-trioxane, may hold the key to resolving this issue. The literature suggests that 1,2,4-trioxanes have the potential to become an alternative to current malaria drugs, as highlighted in this review. This is why 1,2,4-trioxanes and their derivatives have been synthesized on a large scale worldwide, as they have shown promising antimalarial activity in vivo and in vitro against Plasmodium species. Consequently, the search for a more convenient, environment friendly, sustainable, efficient, and effective synthetic pathway for the synthesis of 1,2,4-trioxanes continues. The aim of this work is to provide a comprehensive analysis of the synthesis and mechanism of action of 1,2,4-trioxanes. This systematic review highlights the most recent summaries of derivatives of 1,2,4-trioxane compounds and dimers with potential antimalarial activity from January 1988 to 2023.
Topics: Antimalarials; Artemisinins; Heterocyclic Compounds; Plasmodium falciparum
PubMed: 38134523
DOI: 10.1016/j.bioorg.2023.107043 -
The American Journal of Tropical... Apr 2024Malaria remains a significant cause of morbidity and mortality, even in low-transmission settings. With the advent of longer acting, more effective, and well-tolerated... (Meta-Analysis)
Meta-Analysis
Malaria remains a significant cause of morbidity and mortality, even in low-transmission settings. With the advent of longer acting, more effective, and well-tolerated antimalarials, there is renewed interest in the efficacy of mass drug administration (MDA) to accelerate to elimination. We conducted a systematic review and meta-analysis to assess the efficacy of MDA to reduce the incidence and prevalence of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) infection. From 1,044 articles screened, 14 articles, including 10 randomized controlled trials (RCTs), were identified. Five included data on Pf only; five included Pf and Pv. Two of the Pf studies were conducted in areas of high-moderate transmission, the remainder were in areas of low-very low transmission. In higher transmission areas, MDA reduced incidence of Pf parasitemia (rate ratio = 0.61, 95% CI: 0.40-0.92; moderate certainty) 1 to 3 months after drug administration; no significant effect of MDA on Pf parasitemia prevalence was detected 1 to 3 months post-MDA (risk ratio [RR] = 1.76, 95% CI: 0.58-5.36; low certainty). In lower transmission settings, both incidence and prevalence of Pf parasitemia were reduced 1 to 3 months post-MDA (rate ratio = 0.37, 95% CI: 0.21-0.66; RR = 0.25, 95% CI: 0.15-0.41, respectively). Pv prevalence was reduced 1 to 3 months post-MDA (RR = 0.15, 95% CI: 0.10-0.24); there were no RCTs providing data on incidence of Pv. There was no significant effect of MDA at later time points. MDA may have short-term benefits; however, there was no evidence for longer term impact, although none of the trials assessed prolonged interventions.
Topics: Humans; Mass Drug Administration; Parasitemia; Antimalarials; Malaria; Malaria, Vivax; Plasmodium falciparum
PubMed: 38118174
DOI: 10.4269/ajtmh.22-0766 -
Imported malaria in pregnancy in Europe: A systematic review of the literature of the last 25 years.Travel Medicine and Infectious Disease 2023Malaria during pregnancy is associated with a greater risk of complications for the mother and fetus. The aim of the study is to analyze the features of imported cases... (Review)
Review
BACKGROUND
Malaria during pregnancy is associated with a greater risk of complications for the mother and fetus. The aim of the study is to analyze the features of imported cases of malaria in pregnant women in Europe and evaluate which factors are associated with a non-favourable outcome.
METHODS
A computerized search of the literature was performed combining the terms plasmod*, malaria, pregnan*, maternal, gravid, parturient, expectant, and congenital, from January 1997 to July 2023.
RESULTS
28 articles reporting 57 cases of malaria in pregnant women immigrant in non-endemic areas were included. The patients mainly came from Sub-Saharan Africa. There were 10 asymptomatic cases, while the predominant clinical syndrome among the symptomatic women was fever associated with anaemia. The median latency period from permanence in endemic areas and diagnosis in European countries was 180 days (IQR 15-730). Pregnancy outcomes were favourable in 35 cases (61 %): all term pregnancies, no low-birth-weight newborns. There were 4 abortions; 1 child was delivered pre-term; 7 babies were reported to have a low birth weight; 10 cases of congenital malaria were documented. P. falciparum was found with a higher frequency in women with a favourable outcome, while P. vivax was, in all cases, associated with a worse prognosis.
CONCLUSIONS
Diagnosis of malaria in pregnant woman in non-endemic countries may be challenging and a delay in diagnosis may lead to an adverse outcome. Screening for malaria should be performed in pregnant women from endemic areas, especially if they present anaemia or fever.
Topics: Child; Female; Pregnancy; Infant, Newborn; Humans; Malaria; Malaria, Falciparum; Pregnancy Outcome; Malaria, Vivax; Anemia; Europe
PubMed: 38008239
DOI: 10.1016/j.tmaid.2023.102673 -
Tropical Medicine and Health Nov 2023The Democratic Republic of Congo (DRC), one of the most malaria-affected countries worldwide, is a potential hub for global drug-resistant malaria. This study aimed at... (Review)
Review
CONTEXT
The Democratic Republic of Congo (DRC), one of the most malaria-affected countries worldwide, is a potential hub for global drug-resistant malaria. This study aimed at summarizing and mapping surveys of malaria parasites carrying molecular markers of drug-resistance across the country.
METHODS
A systematic mapping review was carried out before July 2023 by searching for relevant articles through seven databases (PubMed, Embase, Scopus, African Journal Online, African Index Medicus, Bioline and Web of Science).
RESULTS
We identified 1541 primary studies of which 29 fulfilled inclusion criteria and provided information related to 6385 Plasmodium falciparum clinical isolates (collected from 2000 to 2020). We noted the PfCRT K76T mutation encoding for chloroquine-resistance in median 32.1% [interquartile interval, IQR: 45.2] of analyzed malaria parasites. The proportion of parasites carrying this mutation decreased overtime, but wide geographic variations persisted. A single isolate had encoded the PfK13 R561H substitution that is invoked in artemisinin-resistance emergence in the Great Lakes region of Africa. Parasites carrying various mutations linked to resistance to the sulfadoxine-pyrimethamine combination were widespread and reflected a moderate resistance profile (PfDHPS A437G: 99.5% [IQR: 3.9]; PfDHPS K540E: 38.9% [IQR: 47.7]) with median 13.1% [IQR: 10.3] of them being quintuple IRN-GE mutants (i.e., parasites carrying the PfDHFR N51I-C59R-S108N and PfDHPS A437G-K540E mutations). These quintuple mutants tended to prevail in eastern regions of the country. Among circulating parasites, we did not record any parasites harboring mutations related to mefloquine-resistance, but we could suspect those with decreased susceptibility to quinine, amodiaquine, and lumefantrine based on corresponding molecular surrogates.
CONCLUSIONS
Drug resistance poses a serious threat to existing malaria therapies and chemoprevention options in the DRC. This review provides a baseline for monitoring public health efforts as well as evidence for decision-making in support of national malaria policies and for implementing regionally tailored control measures across the country.
PubMed: 37968745
DOI: 10.1186/s41182-023-00551-7 -
Nutrients Oct 2023Despite several studies examining the relationship between calcium levels and malaria, inconsistencies and varied results remain in the literature. This study aimed to... (Meta-Analysis)
Meta-Analysis
Despite several studies examining the relationship between calcium levels and malaria, inconsistencies and varied results remain in the literature. This study aimed to synthesize the evidence on the association between blood calcium levels and malaria severity. A systematic literature search was conducted in the Embase, Scopus, PubMed, Ovid, and Google Scholar databases. The studies that investigated calcium levels in participants with malaria were reviewed and included for synthesis. The quality of included studies was assessed based on a standardized checklist by the Joanna Briggs Institute (JBI) critical appraisal checklists. The thematic synthesis had been used for qualitative synthesis. For the quantitative synthesis, the meta-analysis was performed to estimate the pooled effect sizes for differences in calcium levels between groups of participants using a random effect model using Hedge's g as a measure of effect size. Out of the 4574 identified records, 14 studies were reviewed. The thematic synthesis across these studies noted a consistent theme: reduced calcium levels in malaria patients compared to uninfected controls. However, the meta-analysis encompassing three specific analyses-comparing calcium levels between malaria patients and controls, severe and non-severe malaria cases, and fatal cases versus survivors-showed no significant difference in calcium levels. The statistics were as follows: (1) = 0.15, Hedge's g: -1.00, 95% CI: -2.37-0.38, : 98.97, 9 studies; (2) = 0.35, Hedge's g: -0.33, 95% CI: -1.02-0.36, : 81.61, 3 studies; and (3) = 0.71, Hedge's g: -0.14, 95% CI: -0.91-0.62, : 87.05, 3 studies. Subgroup analyses indicated that regional disparities, especially between Africa and Asia, and participant age groups may influence these outcomes. While a trend of decreased calcium levels in malaria patients was observed, the meta-analytical results suggest regional and age-related variations. Further investigations should emphasize these differences to better guide clinical management, prognostic applications, and the crafting of policies concerning malaria's metabolic effects.
Topics: Humans; Malaria, Vivax; Plasmodium falciparum; Calcium; Malaria; Africa
PubMed: 37960176
DOI: 10.3390/nu15214522 -
Parasitology Nov 2023Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously... (Review)
Review
Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously considered a non-human primate (NHP) infecting species, is now a cause of human malaria in Malaysia. The other NHP species, , , , , and cause malaria in primates, which are mainly reported in southeast Asia and South America. The non- NHP species also emerged and were found to cross-transmit from their natural hosts (NHP) – to human hosts in natural settings. Here we have reviewed and collated data from the literature on the NHPs-to-human-transmitting species. It was observed that the natural transmission of these NHP parasites to humans had been reported from 2010 onwards. This study shows that: (1) the majority of the non- NHP mixed species infecting human cases were from Yala province of Thailand; (2) mono/mixed infections with other human-infecting species were prevalent in Malaysia and Thailand and (3) and were found in Central and South America.
Topics: Animals; Humans; Malaria; Plasmodium knowlesi; Primates; Asia, Southeastern; Plasmodium vivax
PubMed: 37929579
DOI: 10.1017/S003118202300077X -
Frontiers in Public Health 2023In 2021, India contributed for ~79% of malaria cases and ~ 83% of deaths in the South East Asia region. Here, we systematically and critically analyzed data... (Review)
Review
INTRODUCTION
In 2021, India contributed for ~79% of malaria cases and ~ 83% of deaths in the South East Asia region. Here, we systematically and critically analyzed data published on malaria in pregnancy (MiP) in India.
METHODS
Epidemiological, clinical, parasitological, preventive and therapeutic aspects of MiP and its consequences on both mother and child were reviewed and critically analyzed. Knowledge gaps and solution ways are also presented and discussed. Several electronic databases including Google scholar, Google, PubMed, Scopus, Wiley Online library, the Malaria in Pregnancy Consortium library, the World Malaria Report, The WHO regional websites, and ClinicalTrials.gov were used to identify articles dealing with MiP in India. The archives of local scientific associations/journals and website of national programs were also consulted.
RESULTS
Malaria in pregnancy is mainly due to () and (), and on rare occasions to spp. and too. The overall prevalence of MiP is ~0.1-57.7% for peripheral malaria and ~ 0-29.3% for placental malaria. Peripheral infection at antenatal care (ANC) visits decreased from ~13% in 1991 to ~7% in 1995-1996 in Madhya Pradesh, while placental infection at delivery unit slightly decreased from ~1.5% in 2006-2007 to ~1% in 2012-2015 in Jharkhand. In contrast, the prevalence of peripheral infection at ANC increased from ~1% in 2006-2007 to ~5% in 2015 in Jharkhand, and from ~0.5% in 1984-1985 to ~1.5% in 2007-2008 in Chhattisgarh. Clinical presentation of MiP is diverse ranging from asymptomatic carriage of parasites to severe malaria, and associated with comorbidities and concurrent infections such as malnutrition, COVID-19, dengue, and cardiovascular disorders. Severe anemia, cerebral malaria, severe thrombocytopenia, and hypoglycemia are commonly seen in severe MiP, and are strongly associated with tragic consequences such as abortion and stillbirth. Congenital malaria is seen at prevalence of ~0-12.9%. Infected babies are generally small-for-gestational age, premature with low birthweight, and suffer mainly from anemia, thrombocytopenia, leucopenia and clinical jaundice. Main challenges and knowledge gaps to MiP control included diagnosis, relapsing malaria, mixed infection treatment, self-medication, low density infections and utility of artemisinin-based combination therapies.
CONCLUSION
All taken together, the findings could be immensely helpful to control MiP in malaria endemic areas.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Abortion, Spontaneous; Anemia; India; Malaria; Malaria, Vivax; Placenta; Thrombocytopenia
PubMed: 37927870
DOI: 10.3389/fpubh.2023.1150466 -
Malaria Journal Oct 2023Malaria and dengue fever are the leading causes of acute, undifferentiated febrile illness. In Africa, misdiagnosis of dengue fever as malaria is a common scenario.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malaria and dengue fever are the leading causes of acute, undifferentiated febrile illness. In Africa, misdiagnosis of dengue fever as malaria is a common scenario. Through a systematic review of the published literature, this study seeks to estimate the prevalence of dengue and malaria coinfection among acute undifferentiated febrile diseases in Africa.
METHODS
Relevant publications were systematically searched in the PubMed, Cochrane Library, and Google Scholar until May 19, 2023. A random-effects meta-analysis and meta-regression were used to summarize and examine the prevalence estimates.
RESULTS
Twenty-two studies with 22,803 acute undifferentiated febrile patients from 10 countries in Africa were included. The meta-analysis findings revealed a pooled prevalence of malaria and dengue coinfection of 4.2%, with Central Africa having the highest rate (4.7%), followed by East Africa (2.7%) and West Africa (1.6%). Continent-wide, Plasmodium falciparum and acute dengue virus coinfection prevalence increased significantly from 0.9% during 2008-2013 to 3.8% during 2014-2017 and to 5.5% during 2018-2021 (p = 0.0414).
CONCLUSION
There was a high and increasing prevalence of malaria and acute dengue virus coinfection in Africa. Healthcare workers should bear in mind the possibility of dengue infection as a differential diagnosis for acute febrile illness, as well as the possibility of coexisting malaria and dengue in endemic areas. In addition, high-quality multicentre studies are required to verify the above conclusions. Protocol registration number: CRD42022311301.
Topics: Humans; Dengue Virus; Coinfection; Dengue; Cross-Sectional Studies; Prevalence; Malaria; Africa; Fever
PubMed: 37803381
DOI: 10.1186/s12936-023-04723-y -
Scientific Reports Sep 2023Reduced glutathione (GSH) is a crucial antioxidant with recognized roles in malaria pathogenesis and host response. Despite its importance, reports on the association of... (Meta-Analysis)
Meta-Analysis
Reduced glutathione (GSH) is a crucial antioxidant with recognized roles in malaria pathogenesis and host response. Despite its importance, reports on the association of GSH with malaria are inconsistent. Therefore, this systematic review and meta-analysis investigated the differences in GSH levels in relation to Plasmodium infection. A comprehensive literature search of six electronic databases (Embase, MEDLINE, Ovid, PubMed, Scopus, and ProQuest) was conducted. Of the 2158 initially identified records, 18 met the eligibility criteria. The majority of studies reported a significant decrease in GSH levels in malaria patients compared with uninfected controls, and this was confirmed by meta-analysis (P < 0.01, Hedges g: - 1.47, 95% confidence interval [CI] - 2.48 to - 0.46, I: 99.12%, 17 studies). Additionally, there was no significant difference in GSH levels between Plasmodium falciparum malaria and P. vivax malaria (P = 0.80, Hedges g: 0.11, 95% CI - 0.76 to 0.98, I: 93.23%, three studies). Similarly, no significant variation was observed between symptomatic and asymptomatic malaria cases (P = 0.78, Hedges g: 0.06, 95% CI - 0.34 to 0.46, I: 48.07%, two studies). In conclusion, although GSH levels appear to be generally lower in malaria patients, further detailed studies are necessary to fully elucidate this complex relationship.
Topics: Humans; Malaria, Vivax; Plasmodium falciparum; Glutathione; Plasmodium vivax; Malaria, Falciparum; Malaria
PubMed: 37777547
DOI: 10.1038/s41598-023-43583-z