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Frontiers in Medicine 2020Malaria is a systemic febrile disease that may progress to prostration, respiratory distress, encephalopathy, anemia, and death. Malaria is also an established risk...
Malaria is a systemic febrile disease that may progress to prostration, respiratory distress, encephalopathy, anemia, and death. Malaria is also an established risk factor for invasive bacterial disease caused, in the majority of cases, by invasive enteropathogens and in particular by non-Typhoidal (NTS). Whilst various malaria-related pathologies have been implicated in the risk of NTS bacteraemia in animal models, including intestinal dysbiosis and loss of gut homeostasis, clinical evidence is lacking. As a first step in gathering such evidence, we conducted a systematic review of clinical and epidemiological studies reporting the prevalence of diarrhoea among malaria cases and . Database searches for "plasmodium" and "diarrhoea" identified 1,771 articles; a search for "plasmodium" and "gastroenteritis" identified a further 215 articles. After review, 66 articles specified an association between the search terms and referred primarily, but not exclusively, to infections. Overall, between 1.6 and 44% of patients with acute malaria infection reported symptoms of diarrhoea (812 of 7,267 individuals, 11%) whereas 5-42% of patients presenting to hospital with diarrhoea had an underlying malaria parasite infection (totaling 749 of 2,937 individuals, 26%). However, given the broad range of estimates, a paucity of purposeful case control or longitudinal studies, and varied or poorly specified definitions of diarrhoea, the literature provides limited evidence to draw any firm conclusions. The relationship between malaria and gastrointestinal disturbance thus remains unclear. Carefully designed case-control studies and prospective longitudinal studies are required to confidently assess the prevalence and significance of intestinal manifestations of malaria parasite infection.
PubMed: 33330549
DOI: 10.3389/fmed.2020.589379 -
Expert Review of Molecular Diagnostics 2023This review presents an overview of field findings on sequence variation of histidine-rich proteins 2/3 (HRP2/3) for which reference types (1-24) have been identified,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review presents an overview of field findings on sequence variation of histidine-rich proteins 2/3 (HRP2/3) for which reference types (1-24) have been identified, and its critical impact on HRP2-based rapid diagnostic test (RDT) detection.
RESEARCH DESIGN AND METHODS
This systematic review and meta-analysis was registered with PROSPERO, CRD42022316027, and conducted as per the PRISMA guidelines, and the methodological quality of studies was assessed.
RESULTS
Of the 2184 records identified, 34 studies were included mostly from Africa (47.1%) and Asia (35.3%). The reference HRP2 types 1, 2, 3, 6, and 7 are invariably found at proportions ≥ 80-100% in all areas with the exception of The Americas where their proportion is very low. The proteins exhibited high diversity of variants/unknown types, especially for types 1, 2, 4, and 7. Eleven major HRP2 epitopes were found at pooled proportion > 90%. The existing models to predict RDT detection are greatly limited by the impact of factors such as low (very low) parasitemia, RDT brand, and HRP3 cross-reactivity. HRP2 length and presence/number of a given reference repeat type/variant did not seem to impact RDT detection.
CONCLUSIONS
HRP2/3 are highly polymorphic and current findings are insufficient, conflicting and not convincing enough to conclude on the role of HRP2/3 sequence polymorphism in HRP2-based RDT detection.
Topics: Humans; Plasmodium falciparum; Histidine; Malaria, Falciparum; Rapid Diagnostic Tests; Protozoan Proteins; Antigens, Protozoan; Malaria; Diagnostic Tests, Routine
PubMed: 37698448
DOI: 10.1080/14737159.2023.2255136 -
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 -
The Lancet. Infectious Diseases Jan 2019A 14-day course of primaquine is used for radical cure of Plasmodium vivax and Plasmodium ovale malaria only. We quantified the risk of P vivax parasitaemia after... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A 14-day course of primaquine is used for radical cure of Plasmodium vivax and Plasmodium ovale malaria only. We quantified the risk of P vivax parasitaemia after treatment of Plasmodium falciparum with commonly used antimalarial drugs to assess the potential benefits of radical cure for all patients with uncomplicated malaria in co-endemic regions.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Science, and the Cochrane Database of Systematic Reviews for prospective clinical studies in any language, published between Jan 1, 1960, and Jan 5, 2018, assessing drug efficacy in patients with uncomplicated P falciparum malaria in countries co-endemic for P vivax. Studies were included if the presence or absence of P vivax parasitaemia was recorded after treatment. The primary outcome was the risk of P vivax parasitaemia between day 7 and day 42 after initiation of antimalarial treatment for P falciparum, with the pooled risk calculated by random-effects meta-analysis. We compared the risk of P vivax parasitaemia after treatment with different artemisinin-based combination therapies (ACTs). This study is registered with PROSPERO, number CRD42017064838.
FINDINGS
153 of 891 screened studies were included in the analysis, including 31 262 patients from 323 site-specific treatment groups: 130 (85%) studies were from the Asia-Pacific region, 16 (10%) from the Americas, and seven (5%) from Africa. The risk of P vivax parasitaemia by day 42 was 5·6% (95% CI 4·0-7·4; I=92·0%; 117 estimates). The risk of P vivax parasitaemia was 6·5% (95% CI 4·6-8·6) in regions of short relapse periodicity compared with 1·9% (0·4-4·0) in regions of long periodicity, and was greater after treatment with a more rapidly eliminated ACT: 15·3% (5·1-29·3) for artemether-lumefantrine compared with 4·5% (1·2-9·3) for dihydroartemisinin-piperaquine and 5·2% (2·9-7·9) for artesunate-mefloquine. Recurrent parasitaemia was delayed in patients treated with ACTs containing mefloquine or piperaquine compared with artemether-lumefantrine, but by day 63 the risk of vivax parasitaemia was more than 15% for all ACTs assessed.
INTERPRETATION
Our findings show a high risk of vivax parasitaemia after treatment of falciparum malaria, particularly in areas with short relapse periodicity and after rapidly eliminated treatment. In co-endemic regions, universal radical cure for all patients with uncomplicated malaria has the potential to substantially reduce recurrent malaria.
FUNDING
Australian National Health and Medical Research Council, Royal Australasian College of Physicians, Wellcome Trust, and Bill & Melinda Gates Foundation.
Topics: Adolescent; Adult; Antimalarials; Artemisinins; Child; Child, Preschool; Coinfection; Female; Humans; Malaria, Falciparum; Malaria, Vivax; Male; Parasitemia; Plasmodium falciparum; Plasmodium vivax; Quinolines; Risk; Treatment Outcome; Young Adult
PubMed: 30587297
DOI: 10.1016/S1473-3099(18)30596-6 -
Transactions of the Royal Society of... Nov 2016The present study is a systematic review of the literature on the efficacy and safety of the treatment of uncomplicated Plasmodium falciparum infections with... (Review)
Review
INTRODUCTION
The present study is a systematic review of the literature on the efficacy and safety of the treatment of uncomplicated Plasmodium falciparum infections with artesunate-mefloquine (ASMQ) compared to other artemisinin-based combination therapies (ACTs), designed to assist decision makers in Brazil.
METHODS
Twenty-four randomized controlled trials (RCTs) were selected in four electronic databases and in complementary sources. Meta-analyses were performed to evaluate the efficacy expressed by relative risks (RR) obtained from treatment failure confirmed by the PCR.
RESULTS
Due primarily to the presence of measurement bias in the selected studies, the quality of the evidence was considered predominantly moderate. Statistically significant associations were not observed when ASMQ was compared to artemether-lumefentrine and dihydroartemisinin-piperaquine. The results of studies performed in areas with a history of use of ASMQ, regardless of the intensity of transmission, were not statistically different from those presented in the meta-analyses. For comparisons with artesunate-amodiaquine and artesunate+sulfadoxine-pyrimethamine, the results were favourable to ASMQ. No deaths were attributed to ASMQ, severe adverse events were rare and some studies indicate a higher frequency of mild adverse events.
CONCLUSIONS
The use of ASMQ it is recommended to Brazil as first line treatment of uncomplicated P. falciparum infections.
PubMed: 28039388
DOI: 10.1093/trstmh/trw077 -
Tropical Medicine and Infectious Disease May 2023Disseminated intravascular coagulation (DIC) is a potentially life-threatening condition that causes systemic coagulation to be turned on and coagulation factors to be... (Review)
Review
Disseminated intravascular coagulation (DIC) is a potentially life-threatening condition that causes systemic coagulation to be turned on and coagulation factors to be used up. However, the evidence for DIC in malaria patients is still not clear, and small case series and retrospective studies have shown varying results. This meta-analysis was intended for the evaluation of the evidence of DIC among malaria patients using a meta-analysis approach. The protocol for the systematic review was registered at PROSPERO as CRD42023392194. Studies that investigated DIC in patients with malaria were searched in Ovid, Scopus, Embase, PubMed, and MEDLINE. The pooled proportion with 95% confidence intervals (CI) of DIC among malaria patients was estimated using a random-effects model. A total of 1837 articles were identified, and 38 articles were included in the meta-analysis. The overall proportion of DIC in malaria was 11.6% (95% CI: 8.9%-14.3%, I: 93.2%, 38 studies). DIC in severe malaria and fatal malaria was 14.6% (95% CI: 5.0-24.3%, I: 95.5%, 11 studies) and 82.2% (95% CI: 56.2-100%, I: 87.3, 4 studies). The estimates of DIC among severe malaria patients who had multi-organ dysfunction with bleeding, cerebral malaria, acute renal failure, and ≥2 complications were 79.6% (95% CI: 67.1-88.2%, one study), 11.9% (95% CI: 7.9-17.6%, one study), 16.7% (95% CI: 10.2-23.3%, ten studies), and 4.8% (95% CI: 1.9-7.7%, nine studies), respectively. The proportion estimates of DIC among the patients with malaria depended on the species, clinical severity, and types of severe complications. The information from this study provided useful information to guide the management of malaria patients. Future studies are needed to investigate the association between infection and DIC and to understand the mechanism of malaria-induced DIC.
PubMed: 37368707
DOI: 10.3390/tropicalmed8060289 -
Bulletin of the World Health... Aug 2020To calculate prevalence estimates and evaluate the quality of studies reporting lacking histidine-rich proteins 2 and 3, to inform an international response plan.
OBJECTIVE
To calculate prevalence estimates and evaluate the quality of studies reporting lacking histidine-rich proteins 2 and 3, to inform an international response plan.
METHODS
We searched five online databases, without language restriction, for articles reporting original data on -infected patients with deletions of the and/or genes (). We calculated prevalence estimates of deletions and mapped the data by country. The denominator was all -positive samples testing positive by microscopy and confirmed positive by species-specific polymerase chain reaction testing (PCR). If microscopy was not performed, we used the number of samples based on a different diagnostic method or PCR alone. We scored studies for risk of bias and the quality of laboratory methods using a standardized scoring system.
FINDINGS
A total of 38 articles reporting 55 studies from 32 countries and one territory worldwide were included in the review. We found considerable heterogeneity in the populations studied, methods used and estimated prevalence of parasites with deletions. The derived prevalence of deletions ranged from 0% to 100%, including focal areas in South America and Africa. Only three studies (5%) fulfilled all seven criteria for study quality.
CONCLUSION
The lack of representative surveys or consistency in study design impairs evaluations of the risk of false-negative results in malaria diagnosis due to deletions. Accurate mapping and strengthened monitoring of the prevalence of deletions is needed, along with harmonized methods that facilitate comparisons across studies.
Topics: Antigens, Protozoan; Humans; Malaria, Falciparum; Plasmodium falciparum; Polymerase Chain Reaction; Prevalence; Proteins; Protozoan Proteins
PubMed: 32773901
DOI: 10.2471/BLT.20.250621 -
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 -
Lancet (London, England) Jan 2023Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective,... (Meta-Analysis)
Meta-Analysis
Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis.
BACKGROUND
Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy.
METHODS
For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371.
FINDINGS
We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92).
INTERPRETATION
We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted.
FUNDING
Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.
Topics: Female; Pregnancy; Humans; Antimalarials; Pregnancy Outcome; Quinine; Pregnancy Trimester, First; Abortion, Spontaneous; Stillbirth; Prospective Studies; Artemether; Artemether, Lumefantrine Drug Combination; Malaria, Falciparum; Malaria; Drug Combinations; Ethanolamines
PubMed: 36442488
DOI: 10.1016/S0140-6736(22)01881-5 -
PLoS Neglected Tropical Diseases Jun 2022In areas with both Plasmodium vivax and Plasmodium falciparum malaria, interventions can reduce the burden of both species but the impact may vary due to their different...
BACKGROUND
In areas with both Plasmodium vivax and Plasmodium falciparum malaria, interventions can reduce the burden of both species but the impact may vary due to their different biology. Knowing the expected relative impact on the two species over time for vector- and drug-based interventions, and the factors affecting this, could help plan and evaluate intervention strategies.
METHODS
For three interventions (treated bed nets (ITN), mass drug administration (MDA) and indoor residual spraying (IRS)), we identified studies providing information on the proportion of clinical illness and patent infections attributed to P. vivax over time using a literature search. The change in the proportion of malaria attributed to P. vivax up to two years since implementation was estimated using logistic regression accounting for clustering with random effects. Potential factors (intervention type, coverage, relapse pattern, transmission intensity, seasonality, initial proportion of P. vivax and round of intervention) were assessed.
RESULTS
In total there were 55 studies found that led to 72 series of time-points for clinical case data and 69 series for patent infection data. The main reason of study exclusion was insufficient information on interventions. There was considerable variation in the proportion of malaria attributed to P. vivax over time by study and location for all of the interventions. Overall, there was an increase apart from MDA in the short-term. The potential factors could not be ruled in or out. Although not consistently significant, coverage, transmission intensity and relapse pattern are possible factors that explain some of the variation found.
CONCLUSION
While there are reports of an increase in the proportion of malaria due to P. vivax following interventions in the long-term, there was substantial variation for the shorter time-scales considered in this study (up to 24 months for IRS and ITN, and up to six months for MDA). The large variability points to the need for the monitoring of both species after an intervention. Studies should report intervention timing and characteristics to allow inclusion in systematic reviews.
Topics: Humans; Malaria; Malaria, Falciparum; Malaria, Vivax; Plasmodium falciparum; Plasmodium vivax; Recurrence
PubMed: 35767578
DOI: 10.1371/journal.pntd.0010541