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BMC Medicine Apr 2018Methylene blue (MB) was the first synthetic antimalarial to be discovered and was used during the late 19th and early 20th centuries against all types of malaria. MB has... (Review)
Review
BACKGROUND
Methylene blue (MB) was the first synthetic antimalarial to be discovered and was used during the late 19th and early 20th centuries against all types of malaria. MB has been shown to be effective in inhibiting Plasmodium falciparum in culture, in the mouse model and in rhesus monkeys. MB was also shown to have a potent ex vivo activity against drug-resistant isolates of P. falciparum and P. vivax. In preclinical studies, MB acted synergistically with artemisinin derivates and demonstrated a strong effect on gametocyte reduction in P. falciparum. MB has, thus, been considered a potentially useful partner drug for artemisinin-based combination therapy (ACT), particularly when elimination is the final goal. The aim of this study was to review the scientific literature published until early 2017 to summarise existing knowledge on the efficacy and safety of MB in the treatment of malaria.
METHODS
This systematic review followed PRISMA guidelines. Studies reporting on the efficacy and safety of MB were systematically searched for in relevant electronic databases according to a pre-designed search strategy. The search (without language restrictions) was limited to studies of humans published until February 2017.
RESULTS
Out of 474 studies retrieved, a total of 22 articles reporting on 21 studies were eligible for analysis. The 21 included studies that reported data on 1504 malaria patients (2/3 were children). Older studies were case series and reports on MB monotherapy while recent studies were mainly controlled trials of combination regimens. MB was consistently shown to be highly effective in all endemic areas and demonstrated a strong effect on P. falciparum gametocyte reduction and synergy with ACT. MB treatment was associated with mild urogenital and gastrointestinal symptoms as well as blue coloration of urine. In G6PD-deficient African individuals, MB caused a slight but clinically non-significant haemoglobin reduction.
CONCLUSIONS
More studies are needed to define the effects of MB in P. falciparum malaria in areas outside Africa and against P. vivax malaria. Adding MB to ACT could be a valuable approach for the prevention of resistance development and for transmission reduction in control and elimination programs.
SYSTEMATIC REVIEW REGISTRATION
This study is registered at PROSPERO (registration number CRD42017062349 ).
Topics: Enzyme Inhibitors; Female; Humans; Malaria, Falciparum; Male; Methylene Blue
PubMed: 29690878
DOI: 10.1186/s12916-018-1045-3 -
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 -
Malaria Journal Jan 2021Malaria and HIV are two important public health issues. However, evidence on HIV-Plasmodium vivax co-infection (HIV/PvCo) is scarce, with most of the available...
BACKGROUND
Malaria and HIV are two important public health issues. However, evidence on HIV-Plasmodium vivax co-infection (HIV/PvCo) is scarce, with most of the available information related to Plasmodium falciparum on the African continent. It is unclear whether HIV can change the clinical course of vivax malaria and increase the risk of complications. In this study, a systematic review of HIV/PvCo studies was performed, and recent cases from the Brazilian Amazon were included.
METHODS
Medical records from a tertiary care centre in the Western Brazilian Amazon (2009-2018) were reviewed to identify HIV/PvCo hospitalized patients. Demographic, clinical and laboratory characteristics and outcomes are reported. Also, a systematic review of published studies on HIV/PvCo was conducted. Metadata, number of HIV/PvCo cases, demographic, clinical, and outcome data were extracted.
RESULTS
A total of 1,048 vivax malaria patients were hospitalized in the 10-year period; 21 (2.0%) were HIV/PvCo cases, of which 9 (42.9%) had AIDS-defining illnesses. This was the first malaria episode in 11 (52.4%) patients. Seven (33.3%) patients were unaware of their HIV status and were diagnosed on hospitalization. Severe malaria was diagnosed in 5 (23.8%) patients. One patient died. The systematic review search provided 17 articles (12 cross-sectional or longitudinal studies and 5 case report studies). A higher prevalence of studies involved cases in African and Asian countries (35.3 and 29.4%, respectively), and the prevalence of reported co-infections ranged from 0.1 to 60%.
CONCLUSION
Reports of HIV/PvCo are scarce in the literature, with only a few studies describing clinical and laboratory outcomes. Systematic screening for both co-infections is not routinely performed, and therefore the real prevalence of HIV/PvCo is unknown. This study showed a low prevalence of HIV/PvCo despite the high prevalence of malaria and HIV locally. Even though relatively small, this is the largest case series to describe HIV/PvCo.
Topics: Adolescent; Adult; Aged; Brazil; Child; Coinfection; Female; HIV Infections; HIV-1; Humans; Incidence; Malaria, Vivax; Male; Middle Aged; Plasmodium vivax; Prevalence; Young Adult
PubMed: 33407474
DOI: 10.1186/s12936-020-03518-9 -
Malaria Journal May 2023Understanding malaria epidemiology is a critical step toward efficient malaria control and elimination. The objective of this meta-analysis was to derive robust... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Understanding malaria epidemiology is a critical step toward efficient malaria control and elimination. The objective of this meta-analysis was to derive robust estimates of malaria prevalence and Plasmodium species from studies conducted in Mauritania and published since 2000.
METHODS
The present review followed the PRISMA guidelines. Searches were conducted in various electronic databases such as PubMed, Web of Science, and Scopus. To obtain pooled prevalence of malaria, meta-analysis was performed using the DerSimonian-Laird random-effects model. Methodological quality of eligible prevalence studies was assessed using Joanna Briggs Institute tool. Inconsistency and heterogeneity between studies were quantified by the I index and Cochran's Q test. Publication bias was assessed with funnel plots and Egger's regression tests.
RESULTS
A total of 16 studies with a good individual methodological quality were included and analysed in this study. The overall random effects pooled prevalence of malaria infection (symptomatic and asymptomatic) across all included studies was 14.9% (95% confidence interval [95% CI]: 6.64, 25.80, I = 99.8%, P < 0.0001) by microscopy, 25.6% (95% CI: 8.74, 47.62, I = 99.6%, P < 0.0001) by PCR and 24.3% (95% CI: 12.05 to 39.14, I = 99.7%, P < 0.0001) by rapid diagnostic test. Using microscopy, the prevalence of asymptomatic malaria was 1.0% (95% CI: 0.00, 3.48) against 21.46% (95% CI: 11.03, 34.21) in symptomatic malaria. The overall prevalence of Plasmodium falciparum and Plasmodium vivax was 51.14% and 37.55%, respectively. Subgroup analysis showed significant variation (P = 0.039) in the prevalence of malaria between asymptomatic and symptomatic cases.
CONCLUSION
Plasmodium falciparum and P. vivax are widespread in Mauritania. Results of this meta-analysis implies that distinct intervention measures including accurate parasite-based diagnosis and appropriate treatment of confirmed malaria cases are critical for a successful malaria control and elimination programme in Mauritania.
Topics: Humans; Prevalence; Mauritania; Malaria; Malaria, Vivax; Plasmodium; Plasmodium vivax; Plasmodium falciparum; Malaria, Falciparum
PubMed: 37131226
DOI: 10.1186/s12936-023-04569-4 -
Heliyon Apr 2023Malaria is one of the major public health issues globally. Malaria infection spreads through mosquito bites from infected female Anopheles mosquitoes. This study aims to...
Malaria is one of the major public health issues globally. Malaria infection spreads through mosquito bites from infected female Anopheles mosquitoes. This study aims to conduct a systematic review and meta-analysis on malaria prevalence in Pakistan from 2006 to 2021. We searched PubMed, Science Direct, EMBASE, EMCare, and Google Scholar to acquire data on the prevalence of malaria infections. We performed a meta-analysis with a random-effects model to obtain the pooled prevalence of malaria, Plasmodium vivax, and Plasmodium falciparum. Meta-analysis was computed using R 4.1.2 Version statistical software. I and time series analysis were performed to identify a possible source of heterogeneity across studies. A funnel plot and the Freeman-Tukey Double Arcsine Transformed Proportion were used to evaluate the presence of publication bias. Out of the 315 studies collected, only 45 full-text articles were screened and included in the final measurable meta-analysis. Pooled malaria prevalence in Pakistan was 23.3%, with , , and mixed infection rates of 79.13%, 16.29%, and 3.98%, respectively. Similarly, the analysis revealed that the maximum malaria prevalence was 99.79% in Karachi and the minimum was 1.68% in the Larkana district. Amazingly, this systematic review and meta-analysis detected a wide variation in malaria prevalence in Pakistan. Pakistan's public health department and other competent authorities should pay close attention to the large decrease in mosquito populations to curb the infection rate.
PubMed: 37123939
DOI: 10.1016/j.heliyon.2023.e15373 -
Annals of the Academy of Medicine,... Jul 2016Chloroquine, in combination with primaquine, is used as the firstline treatment for uncomplicated P. vivax malaria in Thailand. In view of the declining efficacy of... (Review)
Review
INTRODUCTION
Chloroquine, in combination with primaquine, is used as the firstline treatment for uncomplicated P. vivax malaria in Thailand. In view of the declining efficacy of chloroquine in many P. vivax endemic areas, the possibility of emergence of chloroquine- resistant P. vivax in Thailand is a concern. The aim of this study was to assess the trends in therapeutic efficacy of chloroquine and primaquine for the treatment of uncomplicated P. vivax malaria and to assess the utility of parasite clearance times as a measure of efficacy.
MATERIALS AND METHODS
This study consisted of: 1) review of medical records of patients who were hospitalised for a period during their treatment for uncomplicated P. vivax malaria at the Hospital for Tropical Diseases, Bangkok, Thailand between 2004 and 2013. Treatment consisted of chloroquine (1500 mg base administered over 3 days) or chloroquine (as before) plus primaquine (15 to 30 mg base/daily for 14 days from day 2); and 2) systematic review of the literature in English to assess current standards in the reporting of parasite clearance times.
RESULTS
The 28-day cure rate was 99.1%. The range of median parasite clearance time over the 10-year period was 46 to 59 hours, and there was statistical evidence for an increasing trend in parasite clearance times between 2009 and 2013. Heterogeneity was noted among previous chloroquine efficacy studies in the measurement and reporting of parasite clearance.
CONCLUSION
The treatment of P. vivax infection with a combination of chloroquine and primaquine has remained efficacious in Thailand. Increasing rates of parasite clearance in a population over time may be a useful early warning mechanism for the emergence of chloroquine resistance. The utility of monitoring time-trends in parasite clearance to detect resistance may be enhanced if parasite clearance measurements are standardised.
Topics: Antimalarials; Chloroquine; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Malaria, Vivax; Plasmodium vivax; Primaquine; Thailand; Time Factors; Treatment Outcome
PubMed: 27523511
DOI: No ID Found -
The American Journal of Tropical... Sep 2020and form dormant liver hypnozoites that can reactivate weeks to months following initial infection. Malaria recurrences caused by relapses are an important cause of... (Meta-Analysis)
Meta-Analysis
and form dormant liver hypnozoites that can reactivate weeks to months following initial infection. Malaria recurrences caused by relapses are an important cause of morbidity and source of transmission. To estimate the proportions of malaria recurrences caused by relapses in different geographical locations, we systematically reviewed clinical efficacy studies of uncomplicated malaria, in which patients were randomized to treatment with or without radical cure primaquine regimens and were followed up for 1 year. The minimum proportion of recurrences caused by relapses was estimated for each study site by assuming primaquine prevented all relapses and did not augment blood-stage efficacy. Of the 261 studies identified, six were eligible enrolling 4,092 patients from 14 treatment arm comparisons across seven countries. Of the 2,735 patients treated with primaquine, 24.3% received low dose (2.5 to < 5.0 mg/kg total) and 75.7% received high-dose primaquine (≥ 5.0 mg/kg total). The overall pooled incidence rate ratio of relapses for patients treated with primaquine versus no primaquine was 0.15 (95% CI: 0.10-0.21; = 83.3%), equating to a minimum of 79% of recurrences attributable to relapse. Country-specific incidence rate ratios ranged from 0.05 (95% CI: 0.01-0.34; one estimate) in Pakistan to 0.34 in Nepal (95% CI: 0.12-0.83; one estimate) and Afghanistan (95% CI: 0.22-0.51; three estimates). Relapses account for a very high proportion of recurrent infections following schizontocidal treatment of acute malaria across diverse geographic locations. This emphasizes the importance of implementing hypnozoitocidal treatment.
Topics: Antimalarials; Geography; Humans; Malaria; Malaria, Vivax; Plasmodium vivax; Primaquine; Recurrence
PubMed: 32524950
DOI: 10.4269/ajtmh.20-0186 -
Biomedica : Revista Del Instituto... Jun 2022Introduction: Tafenoquine was approved in 2018 by the Food and Drug Administration in the United States and in 2019 by the Therapeutic Goods Administration in Australia.... (Meta-Analysis)
Meta-Analysis
Introduction: Tafenoquine was approved in 2018 by the Food and Drug Administration in the United States and in 2019 by the Therapeutic Goods Administration in Australia. Its administration in a single dose and its mechanism of action in the acute and latent phases of the disease have been studied to change the treatment regimen for Plasmodium vivax malaria. Objective: To evaluate the available scientific evidence of the efficacy of tafenoquine in prophylaxis and treatment between 2009 and 2019. Materials and methods: We established the MeSH and DeCS descriptors and we used the syntax ((Malaria Vivax) AND (tafenoquine) AND (prophylaxis)) OR [(Malaria Vivax) AND (tafenoquine) AND (relapse)] in the following databases: Pubmed, The Cochrane Central Register of Controlled Clinical Trials (CENTRAL), ISIS Web of Science, Lilacs, and Scopus. The results obtained were subjected to critical analysis (CASPE matrix). The quantitative analysis was performed with risk differences in survival analysis (Kaplan Meier) in the final three articles. Results: Three studies underwent meta-analysis (Llanos-Cuentas, 2014; Llanos-Cuentas, 2019, and Lacerda, 2019) to evaluate the efficacy of the treatment with tafenoquine compared to primaquine. A global risk difference of 0.04 was obtained (95% CI: 0.00-0.08; p=0.07). Tafenoquine did not show inferiority in the efficacy of treatment compared to the primaquine scheme. Conclusion: Tafenoquine is a therapeutic alternative to primaquine that improves adherence, which could bring Colombia closer to the goals of the World Technical Strategy against Malaria 2016-2030.
Topics: Colombia; Plasmodium vivax; Retrospective Studies
PubMed: 35867928
DOI: 10.7705/biomedica.5988 -
Malaria Journal Jul 2017Ethiopia is among countries with a high malaria burden. There are several studies that assessed the efficacy of anti-malarial agents in the country and this systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ethiopia is among countries with a high malaria burden. There are several studies that assessed the efficacy of anti-malarial agents in the country and this systematic review and meta-analysis was performed to obtain stronger evidence on treatment outcomes of malaria from the existing literature in Ethiopia.
METHODS
A systematic literature search using the preferred reporting items for systematic review and meta-analysis (PRISMA) statement was conducted on studies from Pubmed, Google Scholar, and ScienceDirect databases to identify published and unpublished literature. Comprehensive meta-analysis software was used to perform all meta-analyses. The Cochrane Q and the I were used to evaluate heterogeneity of studies. Random effects model was used to combine studies showing heterogeneity of Cochrane Q p < 0.10 and I > 50.
RESULTS
Twenty-one studies were included in the final analysis with a total number of 3123 study participants. Treatment outcomes were assessed clinically and parasitologically using World Health Organization guidelines. Adequate clinical and parasitological response was used to assess treatment success at the 28th day. Overall, a significant high treatment success of 92.9% (95% CI 89.1-96.6), p < 0.001, I = 98.39% was noticed. However, treatment success was higher in falciparum malaria patients treated with artemether-lumefantrine than chloroquine for Plasmodium vivax patients [98.1% (97.0-99.2), p < 0.001, I = 72.55 vs 94.7% (92.6-96.2), p < 0.001, I = 53.62%]. Seven studies reported the adverse drug reactions to anti-malarial treatment; of 822 participants, 344 of them were exposed to adverse drug reactions with a pooled event rate of 39.8% (14.1-65.5), p = 0.002.
CONCLUSIONS
On the basis of this review, anti-malarial treatment success was high (92.9%) and standard regimens showed good efficacy against Plasmodium falciparum (98.1%) and P. vivax (94.7%) infections in Ethiopia, but associated with high rates of adverse drug reactions (ADRs). However, these ADRs were not serious enough to discontinue anti-malarial treatment. The results of this study suggest that the current anti-malarial medications are effective and safe; however, greater priority should be placed on the discovery of new anti-malarial drugs to achieve successful outcomes as resistance seems inevitable since cases of anti-malarial drug resistance have been reported from other areas of the world.
Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Chloroquine; Drug Combinations; Ethanolamines; Ethiopia; Fluorenes; Humans; Malaria, Falciparum; Malaria, Vivax; Primaquine; Pyrimethamine; Sulfadoxine; Treatment Failure
PubMed: 28673348
DOI: 10.1186/s12936-017-1922-9 -
Biology Dec 2021The understanding of platelet biology under physiological and pathological conditions like malaria infection is critical importance in the context of the disease outcome... (Review)
Review
The understanding of platelet biology under physiological and pathological conditions like malaria infection is critical importance in the context of the disease outcome or model systems used. The importance of severe thrombocytopenia (platelet count < 50,000 cells (µL) and profound thrombocytopenia (platelet count < 20,000 cells/µL) in malaria patients remains unclear. This study aimed to synthesize evidence regarding the risks of severe and profound thrombocytopenia in patients with severe non- malaria. Our overall aim was to identify potential indicators of severe non- malaria and the species that cause severe outcomes. This systematic review was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under registration ID CRD42020196541. Studies were identified from previous systematic reviews ( = 5) and the MEDLINE, Scopus, and Web of Science databases from 9 June 2019 to 9 June 2020. Studies were included if they reported the outcome of severe non-Plasmodium species infection, as defined by the World Health Organization (WHO) criteria, in patients with known platelet counts and/or severe and profound thrombocytopenia. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). Data were pooled, and pooled prevalence (PP) and pooled odds ratios (ORs) were calculated using random effects models. Of the 118 studies identified from previous meta-nalyses, 21 met the inclusion criteria. Of the 4807 studies identified from the databases, three met the inclusion criteria. Nine studies identified from reference lists and other sources also met the inclusion criteria. The results of 33 studies reporting the outcomes of patients with severe and infection were pooled for meta-analysis. The PP of severe thrombocytopenia (reported in 21 studies) was estimated at 47% (95% confidence interval (CI): 33-61%, I: 96.5%), while that of profound thrombocytopenia (reported in 13 studies) was estimated at 20% (95% CI: 14-27%, 85.2%). The pooled weighted mean difference (WMD) in platelet counts between severe uncomplicated infections (reported in 11 studies) was estimated at -28.51% (95% CI: -40.35-61%, I: 97.7%), while the pooled WMD in platelet counts between severe non- and severe infections (reported in eight studies) was estimated at -3.83% (95% CI: -13.90-6.25%, I: 85.2%). The pooled OR for severe/profound thrombocytopenia comparing severe to uncomplicated infection was 2.92 (95% CI: 2.24-3.81, I: 39.9%). The PP of death from severe and profound thrombocytopenia was estimated at 11% (95% CI: 0-22%). These results suggest that individuals with severe non- infection (particularly and ) who exhibit severe or profound thrombocytopenia should be regarded as high risk, and should be treated for severe malaria according to current WHO guidelines. In addition, severe or profound thrombocytopenia coupled with other clinical and microscopic parameters can significantly improve malaria diagnosis, enhance the timely treatment of malaria infections, and reduce the morbidity and mortality of severe non- malaria.
PubMed: 34943190
DOI: 10.3390/biology10121275