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Malaria Journal Apr 2017Parasite resistance to anti-malarials represents a great obstacle for malaria elimination. The majority of studies have investigated the association between... (Review)
Review
Assessment of copy number variation in genes related to drug resistance in Plasmodium vivax and Plasmodium falciparum isolates from the Brazilian Amazon and a systematic review of the literature.
BACKGROUND
Parasite resistance to anti-malarials represents a great obstacle for malaria elimination. The majority of studies have investigated the association between single-nucleotide polymorphisms (SNPs) and drug resistance; however, it is becoming clear that the copy number variation (CNV) is also associated with this parasite phenotype. To provide a baseline for molecular surveillance of anti-malarial drug resistance in the Brazilian Amazon, the present study characterized the genetic profile of both markers in the most common genes associated with drug resistance in Plasmodium falciparum and Plasmodium vivax isolates. Additionally, these data were compared to data published elsewhere applying a systematic review of the literature published over a 20-year time period.
METHODS
The genomic DNA of 67 patients infected by P. falciparum and P. vivax from three Brazilian States was obtained between 2002 and 2012. CNV in P. falciparum multidrug resistance gene-1 (pfmdr1), GTP cyclohydrolase 1 (pfgch1) and P. vivax multidrug resistance gene-1 (pvmdr1) were assessed by real-time PCR assays. SNPs in the pfmdr1 and pfcrt genes were assessed by PCR-RFLP. A literature search for studies that analysed CNP in the same genes of P. falciparum and P. vivax was conducted between May 2014 and March 2017 across four databases.
RESULTS
All analysed samples of P. falciparum carried only one copy of pfmdr1 or pfgch1. Although the pfcrt K76T polymorphism, a determinant of CQ resistance, was present in all samples genotyped, the pfmdr1 N86Y was absent. For P. vivax isolates, an amplification rate of 20% was found for the pvmdr1 gene. The results of the study are in agreement with the low amplification rates for pfmdr1 gene evidenced in the Americas and Africa, while higher rates have been described in Southeast Asia. For P. vivax, very low rates of amplification for pvmdr1 have been described worldwide, with exceptions in French Guiana, Cambodia, Thailand and Brazil.
CONCLUSIONS
The present study was the first to evaluate gch1 CNV in P. falciparum isolates from Brazil, showing an absence of amplification of this gene more than 20 years after the withdrawal of the Brazilian antifolates therapeutic scheme. Furthermore, the rate of pvmdr1 amplification was significantly higher than that previously reported for isolates circulating in Northern Brazil.
Topics: Adult; Brazil; Drug Resistance; Female; Gene Dosage; Gene Frequency; Humans; Male; Middle Aged; Plasmodium falciparum; Plasmodium vivax; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Protozoan Proteins; Real-Time Polymerase Chain Reaction
PubMed: 28420389
DOI: 10.1186/s12936-017-1806-z -
PloS One 2020Plasmodium ovale can infect humans, causing malaria disease. We aimed to investigate the severity and mortality of severe P. ovale infection to increase the awareness of... (Meta-Analysis)
Meta-Analysis
Plasmodium ovale can infect humans, causing malaria disease. We aimed to investigate the severity and mortality of severe P. ovale infection to increase the awareness of physicians regarding the prognosis of this severe disease and outcome-related deaths in countries in which this disease is endemic. Articles that were published in the PubMed, Scopus, and ISI Web of Science databases prior to January 5, 2020 and reported the prevalence of severe P. ovale infection were systematically searched and reviewed. Studies that mainly reported severe P. ovale infection according to the 2014 WHO criteria for the treatment of malaria were included. Two reviewers selected, identified, assessed, and extracted data from studies independently. The pooled prevalence of severe P. ovale mono-infections was estimated using the command "metaprop case population, random/fixed", which yielded the pooled estimate, 95% confidence interval (CI) and the I2 value, indicating the level of heterogeneity. Meta-analyses of the proportions were performed using a random-effects model to explore the different proportions of severity between patients with P. ovale and those with other Plasmodium species infections. Among the eight studies that were included and had a total of 1,365 ovale malaria cases, the pooled prevalence of severe P. ovale was 0.03 (95% CI = 0.03-0.05%, I2 = 54.4%). Jaundice (1.1%), severe anemia (0.88%), and pulmonary impairments (0.59%) were the most common severe complications found in patients infected with P. ovale. The meta-analysis demonstrated that a smaller proportion of patients with P. ovale than of patients with P. falciparum had severe infections (P-value = 0.01, OR = 0.36, 95% CI = 0.16-0.81, I2 = 72%). The mortality rate of severe P. ovale infections was 0.15% (2/1,365 cases). Although severe complications of P. ovale infections in patients are rare, it is very important to increase the awareness of physicians regarding the prognosis of severe P. ovale infections in patients, especially in a high-risk population.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Malaria; Male; Middle Aged; Plasmodium falciparum; Plasmodium ovale; Prevalence
PubMed: 32559238
DOI: 10.1371/journal.pone.0235014 -
Molecular Diversity Dec 2022Malaria accounts for over two million deaths globally. To flatten this curve, there is a need to develop new and high potent drugs against Plasmodium falciparum. Some... (Review)
Review
Malaria accounts for over two million deaths globally. To flatten this curve, there is a need to develop new and high potent drugs against Plasmodium falciparum. Some major challenges include the dearth of suitable animal models for anti-P. falciparum assays, resistance to first-line drugs, lack of vaccines and the complex life cycle of Plasmodium. Gladly, newer approaches to antimalarial drug discovery have emerged due to the release of large datasets by pharmaceutical companies. This review provides insights into these new approaches to drug discovery covering different machine learning tools, which enhance the development of new compounds. It provides a systematic review on the use and prospects of machine learning in predicting, classifying and clustering IC values of bioactive compounds against P. falciparum. The authors identified many machine learning tools yet to be applied for this purpose. However, Random Forest and Support Vector Machines have been extensively applied though on a limited dataset of compounds.
Topics: Animals; Plasmodium falciparum; Quantitative Structure-Activity Relationship; Antimalarials; Machine Learning; Drug Discovery
PubMed: 35064444
DOI: 10.1007/s11030-022-10380-1 -
Malaria Journal Sep 2015Multiple studies in various parts of the world have analysed the association of nutritional status on malaria using anthropometric measures, but results differ due to... (Review)
Review
BACKGROUND
Multiple studies in various parts of the world have analysed the association of nutritional status on malaria using anthropometric measures, but results differ due to the heterogeneity of the study population, species of the parasite, and other factors involved in the host and parasite relationship. The aim of this study was to perform a systematic review on the inter-relationship of nutritional status based on anthropometry and malarial infection.
METHODS
Two independent reviewers accessed the MEDLINE and LILACS databases using the same search terms related to malaria and anthropometry. Prospective studies associating anthropometry and malaria (incidence or severity) were selected. References from the included studies and reviews were used to increase the review sensitivity. Data were extracted using a standardized form and the quality of the prospective studies was assessed. Selected articles were grouped based on exposures and outcomes.
RESULTS
The search identified a total of 1688 studies: 1629 from MEDLINE and 59 from LILACS. A total of 23 met the inclusion criteria. Five additional studies were detected by reading the references of the 23 included studies and reviews, totaling 28 studies included. The mean sample size was 662.1 people, ranging from 57 to 5620. The mean follow-up was 365.8 days, ranging from 14 days to 1 year and 9 months, and nine studies did not report the follow-up period. Prospective studies assessing the relationship between malaria and malnutrition were mostly carried out in Africa. Of the 20 studies with malarial outcomes, fifteen had high and five had average quality, with an average score of 80.5 %. Most anthropometric parameters had no association with malaria incidence (47/52; 90.4 %) or parasite density (20/25; 80 %). However, the impact of malnutrition was noted in malaria mortality and severity (7/17; 41.2 %). Regarding the effects of malaria on malnutrition, malaria was associated with very few anthropometric parameters (8/39; 20.6 %).
CONCLUSIONS
This systematic review found that most of the evidence associating malaria and malnutrition comes from P. falciparum endemic areas, with a significant heterogeneity in studies' design. Apparently malnutrition has not a great impact on malaria morbidity, but could have a negative impact on malaria mortality and severity. Most studies show no association between malaria and subsequent malnutrition in P. falciparum areas. In Plasmodium vivax endemic areas, malaria was associated with malnutrition in children. A discussion among experts in the field is needed to standardize future studies to increase external validity and accuracy.
Topics: Adolescent; Adult; Anthropometry; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Malaria, Falciparum; Malaria, Vivax; Nutritional Status; Observational Studies as Topic; Plasmodium falciparum; Plasmodium vivax; Young Adult
PubMed: 26377094
DOI: 10.1186/s12936-015-0870-5 -
Malaria Journal Apr 2017Naturally acquired immunity can reduce parasitaemia and potentially influence anti-malarial treatment outcomes; however, evidence for this in the current literature... (Review)
Review
BACKGROUND
Naturally acquired immunity can reduce parasitaemia and potentially influence anti-malarial treatment outcomes; however, evidence for this in the current literature provides conflicted results. The available evidence was synthesized to determine and quantify the association between host immunity and anti-malarial treatment failure.
METHODS
Four databases were searched to identify studies investigating malaria antibody levels in patients receiving anti-malarial treatment for symptomatic malaria with treatment failure recorded according to the World Health Organization classification. Odds ratios or hazard ratios were extracted or calculated to quantify the association between malarial antibody levels and treatment failure, and findings from different studies were visualized using forest plots.
RESULTS
Eight studies, including patients with falciparum malaria treated with mono- and combination therapy of artemisinin derivatives, sulfadoxine, pyrimethamine and chloroquine, were identified. Reported and calculated effect estimates varied greatly between studies, even those assessing the same antigens and treatments. An association between blood-stage IgG responses and treatment efficacy was observed. The greatest magnitudes of effect were observed for artemisinin [OR/HR (95% CI) range 0.02 (0.00, 0.45)-1.08 (0.57, 2.06)] and chloroquine [0.24 (0.04, 1.37)-0.32 (0.05, 1.96)] treatments, and larger magnitudes of effect were observed for variant surface antigen responses [0.02 (0.00, 0.45)-1.92 (0.94, 3.91)] when compared with merozoite specific responses [0.24 (0.04, 1.37)-2.83 (1.13, 7.09)].
CONCLUSIONS
Naturally acquired malarial immunity is associated with reduced anti-malarial treatment failure in malaria endemic populations. Anti-malarial IgG effects treatment outcome differently for different anti-malarial drugs and antigen targets, and had the greatest impact during treatment with the current first-line treatments, the artemisinins. This has implications for the assessment of the therapeutic efficacy of anti-malarials, particularly in the context of emerging artemisinin resistance.
Topics: Antibodies, Protozoan; Antimalarials; Humans; Immunoglobulin G; Malaria, Falciparum; Plasmodium falciparum; Treatment Failure
PubMed: 28427418
DOI: 10.1186/s12936-017-1815-y -
PloS One 2019Toxoplasma gondii (T. gondii) is an obligate intracellular opportunistic parasite that is the causative agent of toxoplasmosis. This parasite accounts for mental... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Toxoplasma gondii (T. gondii) is an obligate intracellular opportunistic parasite that is the causative agent of toxoplasmosis. This parasite accounts for mental disorders; however, the relationship between T. gondii infection and depressive disorder is unclear. Regarding this, the present systematic review and meta-analysis was conducted to investigate the scientific evidence regarding the potential association between major depression disorder (MDD) and Toxoplasma infection.
METHODS
For the purpose of the study, the articles related to the subject of interest were systematically searched in seven electronic databases. Special attention was given to the studies examining T. gondii seropositivity level in depressed patients and controls.
RESULTS
The search process resulted in the identification of a total of 30 publications meeting the inclusion criteria and published up to April 2018 for the systematic review. Furthermore, 29 studies met the inclusion criteria to be entered into meta-analysis. Our meta-analysis involved the review of cross-sectional studies including 1657 depressed patients and 19565 individuals as controls and case-control studies entailing 1311 depressed cases and 6015 controls without depression. 1582 depressed people participated in cross-sectional studies whose results were reported as odds ratio (OR). In addition, the total number of participants was 15068 in this type of studies. Statistical analysis indicated that the pooled OR of the risk of anti-T. gondii IgG antibody in depressed individuals in case-control and cross-sectional studies was 1.15 (95% confidence interval (CI): 0.95-1.39).
CONCLUSIONS
As the findings of the reviewed articles indicated, toxoplasmosis is not a risk factor for MDD. However, it is necessary to perform further research to clarify the detailed association between T. gondii and dysthymia or mild and moderate depression. Furthermore, it is recommended to better investigate the effect of antibody titers on the relationship between depression and T. gondii infection.
Topics: Antibodies, Protozoan; Case-Control Studies; Cross-Sectional Studies; Depressive Disorder; Female; Humans; Male; Odds Ratio; Toxoplasma; Toxoplasmosis
PubMed: 31194852
DOI: 10.1371/journal.pone.0218524 -
Malaria Journal Jul 2014While significant advances have been made in the prevention and treatment of malaria in recent years, these successes continue to fall short of the World Health... (Review)
Review
While significant advances have been made in the prevention and treatment of malaria in recent years, these successes continue to fall short of the World Health Organization (WHO) goals for malaria control and elimination. For elimination strategies to be effective, limited disease transmission, achieved through rapid reduction in the infectious parasite reservoir and decreased gametocyte carriage, will be critical. Artemisinin-based combination therapy (ACT) forms the cornerstone of WHO-recommended treatment for uncomplicated Plasmodium falciparum malaria, and in combination with other effective interventions will undoubtedly play a vital role in elimination programmes. The gametocytocidal properties of artemisinins are a bonus attribute; there is epidemiological evidence of reductions in malaria incidence and transmission in African regions since the introduction of these agents. Many studies and analyses have specifically investigated the effects of the ACT, artemether-lumefantrine (AL) on gametocyte carriage. In this systematic review of 62 articles published between 1998 and January 2014, the effects of AL on gametocyte carriage and malaria transmission are compared with other artemisinin-based anti-malarials and non-ACT. The impact of AL treatment of asymptomatic carriers on population gametocyte carriage, and the potential future role of AL in malaria elimination initiatives are also considered. Despite the inherent difficulties in comparing data from a range of different studies that also utilized different diagnostic approaches to assess baseline gametocyte counts, the gametocytocidal effect of AL was proportionately consistent across the studies reviewed, suggesting that AL will continue to play a vital role in the treatment of malaria and contribute to clearing the path towards malaria elimination. However, the specific place of AL is the subject of much ongoing research and will undoubtedly be dependent on different demographic and geographical scenarios. Utilizing ACT, such as AL, within malaria elimination strategies is also associated with a number of other challenges, such as balancing potential increased use of ACT (e g, treatment of asymptomatic carriers and home-based treatment) with rational use and avoidance of drug resistance development.
Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Drug Combinations; Ethanolamines; Fluorenes; Humans; Malaria, Falciparum; Plasmodium falciparum; Trophozoites
PubMed: 25069530
DOI: 10.1186/1475-2875-13-291 -
Pathogens and Global Health May 2020, as an opportunistic neurotropic parasite of the Apicomplexa family, was firstly described in 1908. As attention-deficit hyperactivity disorder (ADHD) is one of the... (Meta-Analysis)
Meta-Analysis
, as an opportunistic neurotropic parasite of the Apicomplexa family, was firstly described in 1908. As attention-deficit hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders in children and adolescents and often persists into adulthood, the purpose of this systematic review and meta-analysis was to investigate the relationship between infection and ADHD.The data were systematically collected from seven electronic databases up to May 1 2019 with no language restriction. This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO; code: CRD42020149353). Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using a random effects model. Seven studies involving five cross-sectional and two case-control studies were included in this meta-analysis.Results indicated that there was a statistically non-significant association between exposure to infection and increased risk of ADHD based on the detection of immunoglobulin G (IgG) antibody (2.02 [95% CI: 0.97-4.20]; I=58.7%). However, obtained results of Egger's tests for anti- IgG antibody showed publication bias (P=0.014).Sensitivity analysis revealed stable results for the association between anti- IgG antibody with ADHD.Given the small number of studies in this field and the obtained results, it cannot be conclusively stated that is a risk factor for ADHD.It is important to have reliable information about the relationship between and ADHD around the world; as it may lead to better insight to elucidate the possible association of toxoplasmosis and the pathogenesis of ADHD.
Topics: Antibodies, Protozoan; Attention Deficit Disorder with Hyperactivity; Cross-Sectional Studies; Humans; Risk Factors; Seroepidemiologic Studies; Toxoplasma; Toxoplasmosis
PubMed: 32186992
DOI: 10.1080/20477724.2020.1738153 -
Scientific Reports Apr 2022The dual effects of co-infection of Plasmodium spp. and hookworm on malaria remain under debate. This study investigated prevalence, prevalence odds ratio (POR) of... (Meta-Analysis)
Meta-Analysis
The dual effects of co-infection of Plasmodium spp. and hookworm on malaria remain under debate. This study investigated prevalence, prevalence odds ratio (POR) of co-infection and impact of co-infection on malaria parasite density and haemoglobin levels in comparison to Plasmodium mono-infection. The protocol for this systematic review and meta-analysis is registered at PROPERO under ID: CRD42020202156. Relevant literatures were obtained from PubMed, ISI Web of Science, and Scopus on 25 December 2020. Mean difference (MD) and confidence interval (CI) of malaria parasite density and haemoglobin were compared using a random effect model. Heterogeneity was assessed using Cochrane Q and I statistics. Publication bias was determined by visualising funnel plot asymmetry. Of 1756 articles examined, 22,191 malaria cases across 37 studies included 6096 cases of co-infection of Plasmodium spp. and hookworm. The pooled prevalence was 20% (95% CI 15-26%, I 99.6%, 37 studies) and was varied in terms of geographical region. Co-infection occurred by chance (OR 0.97, p 0.97, 95% CI 0.73-1.27, I 95%, 30 studies). The mean malaria parasite density for co-infection (478 cases) was similar to Plasmodium mono-infection (920 cases) (p 0.24, MD 0.86, 95% CI - 0.58-2.29, I 100%, 7 studies). The mean haemoglobin level for co-infection (90 cases) was similar to Plasmodium mono-infection (415 cases) (p 0.15, MD - 0.63, 95% CI - 1.49-0.23, I 98%, 4 studies). Co-infection was common and occurred by chance but varied by geographic region. Further studies are required to investigate the mechanism of hookworm infection on malaria severity. Additionally, detection of hookworm infections among patients with malaria in endemic areas of both diseases is recommended to prevent severe malaria.
Topics: Ancylostomatoidea; Animals; Coinfection; Hookworm Infections; Humans; Malaria; Parasites; Plasmodium; Prevalence
PubMed: 35477943
DOI: 10.1038/s41598-022-10569-2 -
Malaria Journal Apr 2024In sub-Saharan Africa (SSA), Plasmodium falciparum causes most of the malaria cases. Despite its crucial roles in disease severity and drug resistance, comprehensive... (Meta-Analysis)
Meta-Analysis Review
Plasmodium falciparum genetic diversity and multiplicity of infection based on msp-1, msp-2, glurp and microsatellite genetic markers in sub-Saharan Africa: a systematic review and meta-analysis.
BACKGROUND
In sub-Saharan Africa (SSA), Plasmodium falciparum causes most of the malaria cases. Despite its crucial roles in disease severity and drug resistance, comprehensive data on Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) are sparse in SSA. This study summarizes available information on genetic diversity and MOI, focusing on key markers (msp-1, msp-2, glurp, and microsatellites). The systematic review aimed to evaluate their influence on malaria transmission dynamics and offer insights for enhancing malaria control measures in SSA.
METHODS
The review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Two reviewers conducted article screening, assessed the risk of bias (RoB), and performed data abstraction. Meta-analysis was performed using the random-effects model in STATA version 17.
RESULTS
The review included 52 articles: 39 cross-sectional studies and 13 Randomized Controlled Trial (RCT)/cohort studies, involving 11,640 genotyped parasite isolates from 23 SSA countries. The overall pooled mean expected heterozygosity was 0.65 (95% CI: 0.51-0.78). Regionally, values varied: East (0.58), Central (0.84), Southern (0.74), and West Africa (0.69). Overall pooled allele frequencies of msp-1 alleles K1, MAD20, and RO33 were 61%, 44%, and 40%, respectively, while msp-2 I/C 3D7 and FC27 alleles were 61% and 55%. Central Africa reported higher frequencies (K1: 74%, MAD20: 51%, RO33: 48%) than East Africa (K1: 46%, MAD20: 42%, RO33: 31%). For msp-2, East Africa had 60% and 55% for I/C 3D7 and FC27 alleles, while West Africa had 62% and 50%, respectively. The pooled allele frequency for glurp was 66%. The overall pooled mean MOI was 2.09 (95% CI: 1.88-2.30), with regional variations: East (2.05), Central (2.37), Southern (2.16), and West Africa (1.96). The overall prevalence of polyclonal Plasmodium falciparum infections was 63% (95% CI: 56-70), with regional prevalences as follows: East (62%), West (61%), Central (65%), and South Africa (71%).
CONCLUSION
The study shows substantial regional variation in Plasmodium falciparum parasite genetic diversity and MOI in SSA. These findings suggest a need for malaria control strategies and surveillance efforts considering regional-specific factors underlying Plasmodium falciparum infection.
Topics: Humans; Merozoite Surface Protein 1; Plasmodium falciparum; Antigens, Protozoan; Protozoan Proteins; Genetic Markers; Genetic Variation; Malaria, Falciparum; Genotype; Alleles; Microsatellite Repeats; South Africa
PubMed: 38589874
DOI: 10.1186/s12936-024-04925-y