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The Lancet. Microbe Aug 2021Adoption of molecular techniques to detect infection has revealed many previously undetected (by microscopy) yet transmissible low-density infections. The proportion of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adoption of molecular techniques to detect infection has revealed many previously undetected (by microscopy) yet transmissible low-density infections. The proportion of these infections is typically highest in low transmission settings, but drivers of submicroscopic infection remain unclear. Here, we updated a previous systematic review of asexual prevalence by microscopy PCR in the same population. We aimed to explore potential drivers of submicroscopic infection and to identify the locations where submicroscopic infections are most common.
METHODS
In this systematic review and meta-analysis we searched PubMed and Web of Science from Jan 1, 2010, until Oct 11, 2020, for cross-sectional studies reporting data on asexual prevalence by both microscopy and PCR. Surveys of pregnant women, surveys in which participants had been chosen based on symptoms or treatment, or surveys that did not involve a population from a defined location were excluded. Both the number of individuals tested and the number of individuals who tested positive by microscopy or PCR, or both, for infection were extracted. Bayesian regression modelling was used to explore determinants of the size of the submicroscopic reservoir including geographical location, seasonality, age, methodology, and current or historical patterns of transmission.
FINDINGS
Of 4893 identified studies, we retained 121 after screening and removal of duplicates. 45 studies from a previous systematic review were included giving 166 studies containing 551 cross-sectional survey microscopy and PCR prevalence pairs. Our results show that submicroscopic infections predominate in low-transmission settings across all regions, but also reveal marked geographical variation, with the proportion of infections that are submicroscopic being highest in South American surveys and lowest in west African surveys. Although current transmission levels partly explain these results, we find that historical transmission intensity also represents a crucial determinant of the size of the submicroscopic reservoir, as does the demographic structure of the infected population (with submicroscopic infection more likely to occur in adults than in children) and the PCR or microscopy methodology used. We also observed a small yet significant influence of seasonality, with fewer submicroscopic infections observed in the wet season than the dry season. Integrating these results with estimates of infectivity in relation to parasite density suggests the contribution of submicroscopic infections to transmission across different settings is likely to be highly variable.
INTERPRETATION
Significant variation in the prevalence of submicroscopic infection exists even across settings characterised by similar current levels of transmission. These differences in submicroscopic epidemiology potentially warrant different approaches to targeting this infected subgroup across different settings to eliminate malaria.
FUNDING
Bill & Melinda Gates Foundation, The Royal Society, and the UK Medical Research Council.
Topics: Adult; Bayes Theorem; Child; Cross-Sectional Studies; Female; Humans; Malaria; Malaria, Falciparum; Plasmodium falciparum; Pregnancy
PubMed: 34382027
DOI: 10.1016/S2666-5247(21)00055-0 -
BMC Medicine Sep 2022In 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns.
METHODS
A systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models.
RESULTS
Data comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17-0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19-0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms.
CONCLUSIONS
Our results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients.
TRIAL REGISTRATION
PROSPERO, CRD42019128185.
Topics: Antimalarials; Artemisinins; Child; Child, Preschool; Glucosephosphate Dehydrogenase; Hemoglobins; Humans; Malaria, Falciparum; Plasmodium falciparum; Primaquine
PubMed: 36109733
DOI: 10.1186/s12916-022-02504-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 -
International Journal of Infectious... Dec 2021Plasmodium falciparum gametocytaemia has been associated with anaemia. The aim of this review was to synthesize available evidence on the comparative effect of... (Meta-Analysis)
Meta-Analysis Review
Comparative effect of dihydroartemisinin-piperaquine and artemether-lumefantrine on gametocyte clearance and haemoglobin recovery in children with uncomplicated Plasmodium falciparum malaria in Africa: a systematic review and meta-analysis of randomized control trials.
BACKGROUND
Plasmodium falciparum gametocytaemia has been associated with anaemia. The aim of this review was to synthesize available evidence on the comparative effect of dihydroartemisinin-piperaquine (DHA-PQ) and artemether-lumefantrine (AL) on gametocyte clearance and haemoglobin recovery in children with uncomplicated P. falciparum malaria in Africa.
METHODS
A systematic literature search was undertaken to identify relevant articles from online databases. The search was performed from August 2020 to 30 April 2021. Extracted data from eligible studies were pooled as risk ratios with 95% confidence intervals (CI).
RESULTS
Gametocyte carriage was reduced in both treatment groups, with no significant difference found between the groups. However, on days 28 and 42, a significant increase in serum haemoglobin level from baseline was observed in the DHA-PQ group (standardized mean difference 0.15, 95% CI 0.05-0.26; participants=2715; studies=4; I32%, high quality of evidence) compared with the AL group (mean difference 0.35, 95% CI 0.12-0.59; participants=1434; studies=3; I=35%, high quality of evidence).
CONCLUSION
DHA-PQ had a greater impact on haemoglobin recovery than AL on days 28 and 42; this difference was significant.
Topics: Africa; Antimalarials; Artemether; Artemether, Lumefantrine Drug Combination; Artemisinins; Child; Drug Combinations; Fluorenes; Hemoglobins; Humans; Malaria, Falciparum; Plasmodium falciparum; Quinolines; Randomized Controlled Trials as Topic
PubMed: 34653658
DOI: 10.1016/j.ijid.2021.10.013 -
The Lancet Regional Health. Southeast... Jul 2022The long-term maintenance of parasite biomass below the detection threshold of microscopy may stymie malaria elimination. Variation in microscopists' competencies to...
BACKGROUND
The long-term maintenance of parasite biomass below the detection threshold of microscopy may stymie malaria elimination. Variation in microscopists' competencies to detect and correctly identify parasite species reflect in microscopy sensitivity, resulting in incorrect species-specific burden.
METHODS
The study estimated SMI pooled burden from published reports using a random effect model & identifies their hotspots in India. The study applied a prediction model for the first time on Indian data, emphasizing the importance of such models that can predict PCR-prevalence from slide- prevalence.
FINDINGS
A total of 17,449 samples from 39 districts were examined for by microscopy and PCR. The overall heterogeneity in clinic-based and community-based studies was 91% and 96%, respectively, with the pooled prevalence of 3.63%. The SMI prevalence in individual studies ranged from 38.4% to 0.4%. Sensitivity of microscopy for mono- (91%) was found to be better than mono- (82 %). But surprisingly, it was much lower for mixed PfPv (45%).
INTERPRETATION
Primary regional data in the form of SMIs hot spots should be generated from countries on the verge of malaria elimination, and genetic monitoring should be integrated into national programs, particularly in key areas for successful malaria elimination.
FUNDING
Not applicable.
PubMed: 37383294
DOI: 10.1016/j.lansea.2022.05.001 -
Journal of Infection and Public Health May 2022A wide spread of chloroquine resistance prompted its discontinued use for treatment of uncomplicated malaria in several African countries. However, disappearances of... (Review)
Review
Molecular surveillance of chloroquine-resistant Plasmodium falciparum in sub-Saharan African countries after withdrawal of chloroquine for treatment of uncomplicated malaria: A systematic review.
BACKGROUND
A wide spread of chloroquine resistance prompted its discontinued use for treatment of uncomplicated malaria in several African countries. However, disappearances of chloroquine-resistant parasites have been reported in areas with restricted use of chloroquine. This review reports the current prevalence of chloroquine-resistant Plasmodium falciparum using Pfcrt K76T and Pfmdr1 N86Y genotypes.
METHODS
A PROSPERO registered systematic review searched evidence from PubMed/MEDLINE, Science Direct and Google Scholar. The search included studies on chloroquine-resistant/ susceptible P. falciparum in humans between January 1st, 2000 and May 15th, 2020. The search was conducted on 15th of May, 2020.
RESULTS
Out of 519 searched records, 15 studies qualified for final analysis with 8040 samples genotyped for Pfcrt K76T. Of 8040, 43.6% (837/1572; 95%CI: -0.9 to 88.1%) carried resistant genotypes versus 23.0% (1477/6468; 95%CI: 15.7-30.2%) while for 4698 samples analyzed for Pfmdr1 N86Y, 52.4% (592/1090; 95%CI: 42.3-62.5%) had resistant genotypes versus 25.9% (1314/3608; 95%CI: 5.8-46.0%), before and after chloroquine withdrawal, respectively. The median time since chloroquine withdrawal to data collection was 7.0 (interquartile range: 4.5-13.5) years. Low prevalence of resistant genotypes (Pfcrt K76T) was reported in Zambia (0%) in 2013, Malawi (0.1%) in 2009, Tanzania (0.2%) in 2018 and Madagascar (0.3%) in 2007 with significant variations in the included studies.
CONCLUSIONS
Chloroquine-resistant P. falciparum continues to disappear in countries with withdrawal of chloroquine. Areas with significant susceptible parasites, reintroduction of chloroquine can be considered, preferably in combination with other safe and affordable antimalarials.
Topics: Africa South of the Sahara; Antimalarials; Chloroquine; Drug Resistance; Humans; Malaria; Malaria, Falciparum; Membrane Transport Proteins; Plasmodium falciparum; Protozoan Proteins
PubMed: 35447389
DOI: 10.1016/j.jiph.2022.03.015 -
Clinical Infectious Diseases : An... Jan 2022The emergence and spread of Plasmodium falciparum parasites that lack HRP2/3 proteins and the resulting decreased utility of HRP2-based malaria rapid diagnostic tests...
BACKGROUND
The emergence and spread of Plasmodium falciparum parasites that lack HRP2/3 proteins and the resulting decreased utility of HRP2-based malaria rapid diagnostic tests (RDTs) prompted the World Health Organization and other global health stakeholders to prioritize the discovery of novel diagnostic biomarkers for malaria.
METHODS
To address this pressing need, we adopted a dual, systematic approach by conducting a systematic review of the literature for publications on diagnostic biomarkers for uncomplicated malaria and a systematic in silico analysis of P. falciparum proteomics data for Plasmodium proteins with favorable diagnostic features.
RESULTS
Our complementary analyses led us to 2 novel malaria diagnostic biomarkers compatible for use in an RDT format: glyceraldehyde 3-phosphate dehydrogenase and dihydrofolate reductase-thymidylate synthase.
CONCLUSIONS
Overall, our results pave the way for the development of next-generation malaria RDTs based on new antigens by identifying 2 lead candidates with favorable diagnostic features and partially de-risked product development prospects.
Topics: Antigens, Protozoan; Biomarkers; Diagnostic Tests, Routine; Humans; Malaria; Malaria, Falciparum; Plasmodium falciparum; Protozoan Proteins; Sensitivity and Specificity
PubMed: 34718455
DOI: 10.1093/cid/ciab251 -
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 -
Malaria Journal Aug 2021Artemisinin-based combination therapy (ACT) was deployed in 2005 as an alternative to chloroquine and is considered the most efficacious treatment currently available... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Artemisinin-based combination therapy (ACT) was deployed in 2005 as an alternative to chloroquine and is considered the most efficacious treatment currently available for uncomplicated falciparum malaria. While widespread artemisinin resistance has not been reported to date in Africa, recent studies have reported partial resistance in Rwanda. The purpose of this study is to provide a current systematic review and meta-analysis on ACT at Mali study sites, where falciparum malaria is highly endemic.
METHODS
A systematic review of the literature maintained in the bibliographic databases accessible through the PubMed, ScienceDirect and Web of Science search engines was performed to identify research studies on ACT occurring at Mali study sites. Selected studies included trials occurring at Mali study sites with reported polymerase chain reaction (PCR)-corrected adequate clinical and parasite response rates (ACPRcs) at 28 days. Data were stratified by treatment arm (artemether-lumefantrine (AL), the first-line treatment for falciparum malaria in Mali and non-AL arms) and analysed using random-effects, meta-analysis approaches.
RESULTS
A total of 11 studies met the inclusion criteria, and a risk of bias assessment carried out by two independent reviewers determined low risk of bias among all assessed criteria. The ACPRc for the first-line AL at Mali sites was 99.0% (95% CI (98.3%, 99.8%)), while the ACPRc among non-AL treatment arms was 98.9% (95% CI (98.3%, 99.5%)). The difference in ACPRcs between non-AL treatment arms and AL treatment arms was not statistically significant (p = .752), suggesting that there are potential treatment alternatives beyond the first-line of AL in Mali.
CONCLUSIONS
ACT remains highly efficacious in treating uncomplicated falciparum malaria in Mali. Country-specific meta-analyses on ACT are needed on an ongoing basis for monitoring and evaluating drug efficacy patterns to guide local malaria treatment policies, particularly in the wake of observed artemisinin resistance in Southeast Asia and partial resistance in Rwanda.
Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Humans; Malaria, Falciparum; Mali; Plasmodium falciparum
PubMed: 34461901
DOI: 10.1186/s12936-021-03890-0 -
The Lancet. Planetary Health Mar 2022Rice fields in Africa are major breeding sites for malaria vectors. However, when reviewed in the 1990s, in settings where transmission was relatively intense, there was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rice fields in Africa are major breeding sites for malaria vectors. However, when reviewed in the 1990s, in settings where transmission was relatively intense, there was no tendency for malaria indices to be higher in villages with irrigated rice fields than in those without. Subsequently, intervention coverage in sub-Saharan Africa has been massively scaled up and malaria infection prevalence has halved. We re-examined this rice-malaria relationship to assess whether, with lower malaria transmission, malaria risk is greater in rice-growing than in non-rice-growing areas.
METHODS
For this systematic review and meta-analysis, we searched EMBASE, Global Health, PubMed, Scopus, and Web of Science to identify observational studies published between Jan 1, 1900, and Sept 18, 2020. Studies were considered eligible if they were observational studies (cross-sectional, case-control, or cohort) comparing epidemiological or entomological outcomes of interest between people living in rice-growing and non-rice-growing rural communities in sub-Saharan Africa. Studies with pregnant women, displaced people, and military personnel as participants were excluded because they were considered not representative of a typical community. Data were extracted with use of a standardised data extraction form. The primary outcomes were parasite prevalence (P falciparum parasite rate age-standardised to 2-10-year-olds, calculated from total numbers of participants and number of infections [confirmed by microscopy or rapid diagnostic test] in each group) and clinical malaria incidence (number of diagnoses [fever with Plasmodium parasitaemia confirmed by microscopy or rapid diagnostic test] per 1000 person-days in each group). We did random-effects meta-analyses to estimate the pooled risk ratio (RR) for malaria parasite prevalence and incidence rate ratio (IRR) for clinical malaria in rice-growing versus non-rice-growing villages. RRs were compared in studies conducted before and after 2003 (chosen to mark the start of the mass scale-up of antimalaria interventions). This study is registered with PROSPERO (CRD42020204936).
FINDINGS
Of the 2913 unique studies identified and screened, 53 studies (including 113 160 participants across 14 African countries) were eligible for inclusion. In studies done before 2003, malaria parasite prevalence was not significantly different in rice-growing versus non-rice-growing villages (pooled RR 0·82 [95% CI 0·63-1·06]; 16 studies, 99 574 participants); however, in post-2003 studies, prevalence was significantly higher in rice-growing versus non-rice growing villages (1·73 [1·01-2·96]; seven studies, 14 002 participants). Clinical malaria incidence was not associated with residence in rice-growing versus non-rice-growing areas (IRR 0·75 [95% CI 0·47-1·18], four studies, 77 890). Potential limitations of this study include its basis on observational studies (with evidence quality rated as very low according to the GRADE approach), as well as its omission for the effects of seasonality and type of rice being cultivated. Risk of bias and inconsistencies was relatively serious, with I greater than 90% indicating considerable heterogeneity.
INTERPRETATION
Irrigated rice-growing communities in sub-Saharan Africa are exposed to greater malaria risk, as well as more mosquitoes. As increasing rice production and eliminating malaria are two major development goals in Africa, there is an urgent need to improve methods for growing rice without producing mosquitoes.
FUNDING
Wellcome Trust Our Planet Our Health programme, CGIAR Agriculture for Nutrition and Health.
Topics: Africa South of the Sahara; Animals; Cross-Sectional Studies; Female; Humans; Malaria; Observational Studies as Topic; Oryza; Pregnancy; Prevalence
PubMed: 35278391
DOI: 10.1016/S2542-5196(21)00349-1