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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 -
The Cochrane Database of Systematic... Jun 2022The World Health Organization (WHO) recommends artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria. Concerns about... (Review)
Review
BACKGROUND
The World Health Organization (WHO) recommends artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria. Concerns about artemisinin resistance have led to global initiatives to develop new partner drugs to protect artemisinin derivatives in ACT. Pyronaridine-artesunate is a novel ACT.
OBJECTIVES
To evaluate the efficacy of pyronaridine-artesunate compared to alternative ACTs for treating people with uncomplicated P falciparum malaria, and to evaluate the safety of pyronaridine-artesunate and other pyronaridine treatments compared to alternative treatments.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; Embase; and LILACS. We also searched ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, and the ISRCTN registry for ongoing or recently completed trials. The date of the last search was 27 October 2021.
SELECTION CRITERIA
For the efficacy analysis, we included randomized controlled trials (RCTs) of pyronaridine-artesunate for treating uncomplicated P falciparum malaria. For the safety analysis, we included RCTs that used pyronaridine alone or in combination with any other antimalarials. In addition to these analyses, we conducted a separate systematic review summarizing data on safety from non-randomized studies (NRS) of any patient receiving pyronaridine (NRS safety review). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted all data and assessed the certainty of the evidence. We meta-analysed data to calculate risk ratios (RRs) for treatment failures between comparisons, and for safety outcomes between and across comparisons.
MAIN RESULTS
We included 10 relevant RCTs. Seven RCTs were co-funded by Shin Poong Pharmaceuticals, and three were funded by government agencies. Efficacy analysis (RCTs) For the efficacy analysis, we identified five RCTs comprising 5711 participants. This included 4465 participants from 13 sites in Africa, and 1246 participants from five sites in Asia. The analysis included 541 children aged less than five years. Overall, pyronaridine-artesunate had a polymerase chain reaction (PCR)-adjusted treatment failure rate of less than 5%. We evaluated pyronaridine-artesunate versus the following. • Artemether-lumefantrine. Pyronaridine artesunate may perform better for PCR-adjusted failures at day 28 (RR 0.59, 95% confidence interval (CI) 0.26 to 1.31; 4 RCTs, 3068 participants, low-certainty evidence); for unadjusted failures at day 28 (RR 0.27, 95% CI 0.13 to 0.58; 4 RCTs, 3149 participants, low-certainty evidence); and for unadjusted failures at day 42 (RR 0.61, 95% CI 0.46 to 0.82; 4 RCTs, 3080 participants, low-certainty evidence). For PCR-adjusted failures at day 42, there may be little or no difference between groups (RR 0.86, 95% CI 0.49 to 1.51; 4 RCTs, 2575 participants, low-certainty evidence). • Artesunate-amodiaquine. Pyronaridine artesunate may perform better for PCR-adjusted failures at day 28 (RR 0.55, 95% CI 0.11 to 2.77; 1 RCT, 1245 participants, low-certainty evidence); probably performs better for unadjusted failures at day 28 (RR 0.49, 95% CI 0.30 to 0.81; 1 RCT, 1257 participants, moderate-certainty evidence); may make little or no difference for PCR-adjusted failures at day 42 (RR 0.98, 95% CI 0.20 to 4.83; 1 RCT, 1091 participants, low-certainty evidence); and probably makes little or no difference for unadjusted failures at day 42 (RR 0.98, 95% CI 0.78 to 1.23; 1 RCT, 1235 participants, moderate-certainty evidence). • Mefloquine plus artesunate. Pyronaridine artesunate may perform better for PCR-adjusted failures at day 28 (RR 0.37, 95% CI 0.13 to 1.05; 1 RCT, 1117 participants, low-certainty evidence); probably performs better for unadjusted failures at day 28 (RR 0.36, 95% CI 0.17 to 0.78; 1 RCT, 1120 participants, moderate-certainty evidence); may make little or no difference for unadjusted failures at day 42 (RR 0.84, 95% CI 0.54 to 1.31; 1 RCT, 1059 participants, low-certainty evidence); but may lead to higher PCR-adjusted failures at day 42 (RR 1.80, 95% CI 0.90 to 3.57; 1 RCT, 1037 participants, low-certainty evidence). Safety analysis (RCTs) For the RCT safety analysis, we identified eight RCTs, one of which was delineated by study site, comparing pyronaridine-artesunate to other antimalarials. Pyronaridine-artesunate was associated with raised liver enzymes compared to other antimalarials: alanine aminotransferase (ALT) (RR 3.59, 95% CI 1.76 to 7.33; 8 RCTS, 6669 participants, high-certainty evidence) and aspartate transaminase (AST) (RR 2.22, 95% CI 1.12 to 4.41; 8 RCTs, 6669 participants, moderate-certainty evidence). No such effect was demonstrated with bilirubin (RR 1.03, 95% CI 0.49 to 2.18; 7 RCTs, 6384 participants, moderate-certainty evidence). There was one reported case in which raised ALT occurred with raised bilirubin. No study reported severe drug-induced liver injury. Electrocardiograph (ECG) abnormalities were less common with pyronaridine-artesunate compared to other antimalarials. We identified no other safety concerns. NRS safety review A review on safety in NRS allowed us to increase the population within which safety was assessed. We included seven studies with 9546 participants: five single-arm observational studies, one cohort event monitoring study, and one dose-escalation study. All studies provided data on adverse event frequency, with a small number of participants experiencing serious adverse events and adverse effects related to pyronaridine: serious adverse events average 0.37%; drug-related 9.0%. In two studies reporting elevations in liver enzymes, small percentages of participants (2.4% and 14.1% respectively) experienced increases in either ALT, AST, or bilirubin on day 7; however, these were small increases that returned to normal by day 42. AUTHORS' CONCLUSIONS: Pyronaridine-artesunate was efficacious against uncomplicated P falciparum malaria; achieved a PCR-adjusted treatment failure rate of less than 5% at days 28 and 42; and may be at least as good as, or better than, other marketed ACTs. Pyronaridine-artesunate increases the risk of episodes of abnormally raised ALT. The observational data did not signal an excess of clinically important adverse effects.
Topics: Antimalarials; Artemisinins; Artesunate; Bilirubin; Child; Drug Combinations; Humans; Malaria, Falciparum; Naphthyridines
PubMed: 35726133
DOI: 10.1002/14651858.CD006404.pub4 -
Infectious Diseases of Poverty Feb 2018Plasmodium vivax is the most geographically widespread species among human malaria parasites. Immunopathological studies have shown that platelets are an important... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Plasmodium vivax is the most geographically widespread species among human malaria parasites. Immunopathological studies have shown that platelets are an important component of the host innate immune response against malaria infections. The objectives of this study were to quantify thrombocytopaenia in P. vivax malaria patients and to determine the associated risks of severe thrombocytopaenia in patients with vivax malaria compared to patients with P. falciparum malaria.
MAIN BODY
A systematic review and meta-analysis of the available literature on thrombocytopaenia in P. vivax malaria patients was undertaken. Relevant studies in health-related electronic databases were identified and reviewed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Fifty-eight observational studies (n = 29 664) were included in the current review. Severe thrombocytopaenia (< 50 000/mm) to very severe thrombocytopaenia (< 20 000/mm) was observed in 10.1% of patients with P. vivax infection. A meta-analysis of 11 observational studies showed an equal risk of developing severe/very severe thrombocytopaenia between the patients with P. vivax malaria and those with P. falciparum malaria (OR: 1.98, 95% CI: 0.92-4.25). This indicates that thrombocytopaenia is as equally a common manifestation in P. vivax and P. falciparum malaria patients. One study showed a higher risk of developing very severe thrombocytopaenia in children with severe P. vivax malaria than with severe P. falciparum malaria (OR: 2.80, 95% CI: 1.48-5.29). However, a pooled analysis of two studies showed an equal risk among adult severe cases (OR: 1.19, 95% CI: 0.51-2.77). This indicates that the risk of developing thrombocytopaenia in P. vivax malaria can vary with immune status in both children and adults. One study reported higher levels of urea and serum bilirubin in patients with P. vivax malaria and severe thrombocytopaenia compared with patients mild thrombocytopaenia or no thrombocytopaenia, (P < 0.001 in all comparisons). A pooled analysis of two other studies showed a similar proportion of bleeding episodes with thrombocytopaenia in severe P. vivax patients and severe P. falciparum patients (P = 0.09). This implied that both P. vivax and P. falciparum infections could present with bleeding episodes, if there had been a change in platelet counts in the infected patients. A pooled analysis of another two studies showed an equal risk of mortality with severe thrombocytopaenia in both P. vivax and P. falciparum malaria patients (OR: 1.16, 95% CI: 0.30-4.60). However, due to the low number of studies with small sample sizes within the subset of studies that provided clinically relevant information, our confidence in the estimates is limited.
CONCLUSION
The current review has provided some evidence of the clinical relevance of severe thrombocytopaenia in P. vivax malaria. To substantiate these findings, there is a need for well designed, large-scale, prospective studies among patients infected with P. vivax. These should include patients from different countries and epidemiological settings with various age and gender groups represented.
Topics: Adult; Child; Female; Humans; Malaria, Falciparum; Malaria, Vivax; Male; Observational Studies as Topic; Plasmodium falciparum; Plasmodium vivax; Severity of Illness Index; Thrombocytopenia
PubMed: 29427995
DOI: 10.1186/s40249-018-0392-9 -
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 Jul 2020Severe complications among patients with Plasmodium malariae infection are rare. This is the first systematic review and meta-analysis demonstrating the global... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Severe complications among patients with Plasmodium malariae infection are rare. This is the first systematic review and meta-analysis demonstrating the global prevalence and mortality of severe P. malariae infection in humans.
METHODS
The systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All research articles published on the severity and mortality of P. malariae infection cases in humans were retrieved from three public databases: PubMed, Scopus, and ISI Web of Science. The pooled prevalence estimate and 95% confidence interval (CI) of complications in patients with P. malariae malaria was analysed using the random-effects model provided in Stata software. The pooled odds ratio (OR) and 95% CI of severe malaria for P. malariae infection and Plasmodium falciparum infection were analysed using Review Manager software.
RESULTS
Six studies were used to estimate the pooled prevalence of severe P. malariae malaria. Out of 10,520 patients infected with P. malariae, the pooled prevalence estimate of severe P. malariae infection was 3% (95% CI 2-5%), with high heterogeneity (I: 90.7%). Severe anaemia (3.32%), pulmonary complications (0.46%), and renal impairments (0.24%) were the most common severe complications found in patients with P. malariae infection. The pooled proportion of severe anaemia for P. malariae infection and P. falciparum infection was comparable among the four included studies (OR: 0.74, 95% CI 0.22-2.45, I = 98%). The pooled proportion of pulmonary complications was comparable between patients with P. malariae infection and those with P. falciparum infection among the four included studies (OR: 1.44; 95% CI 0.17-12.31, I: 92%). For renal complications, the funnel plot showed that the pooled proportion of renal complications for P. malariae infection and P. falciparum infection was comparable among the four included studies (OR: 0.94, 95% CI 0.18-4.93, I: 91%). The mortality rate of patients with P. malariae infection was 0.17% (18/10,502 cases).
CONCLUSIONS
This systematic review demonstrated that approximately two percent of patients with P. malariae infection developed severe complications, with a low mortality rate. Severe anaemia, pulmonary involvement, and renal impairment were the most common complications found in patients with P. malariae infection. Although a low prevalence and low mortality of P. malariae infection have been reported, patients with P. malariae infection need to be investigated for severe anaemia and, if present, treated aggressively to prevent anaemia-related death.
Topics: Humans; Malaria; Plasmodium malariae; Prevalence
PubMed: 32736635
DOI: 10.1186/s12936-020-03344-z -
Travel Medicine and Infectious Disease 2017With increased international travel over the world the need for safe and effective chemoprophylaxis for malaria is as great as ever. The choice of regimen is difficult,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With increased international travel over the world the need for safe and effective chemoprophylaxis for malaria is as great as ever. The choice of regimen is difficult, as effectiveness should be weighted against potential adverse effects. Although, some studies have reported high prophylactic efficacy of primaquine, there is no comprehensive evidence comparing its prophylactic effectiveness as well as toxicity. To fill the gap, this systematic review and meta-analysis study was carried out.
METHODS
Using MeSH terms, 756 records were detected through searching "Pubmed", "Embase","Web of Science"and "Cochrane" databases. From these,7 relevant full-text articles with 14 comparisons for final quantitative meta-analysis were included in our review. In order to make a comparison between the studies, Risk Ratios(RRs) and their 95% confidence intervals(CIs) were estimated.
RESULTS
Overall,74% reduction in the incidence of parasitaemia by primaquine versus other prophylactic regimens was estimated(RRoverall = 0.26, CI 95%:0.16-0.41--RRvivax = 0.16, CI 95%:0.07-0.36--RRfalciparum = 0.31, CI 95%:0.18-0.55). The incidence rate ratios for adverse effects showed no statistically significant difference between primaquine and control groups (p > 0.05).
CONCLUSIONS
For persons without G6PD deficiency, who are not pregnant, primaquine is the most effective presently available prophylactic for P. vivax malaria and comparable to such regimens as doxycycline, mefloquine and atovaquone-proguanil for the prevention of P. falciparum malaria.
Topics: Antibiotic Prophylaxis; Antimalarials; Humans; Malaria, Falciparum; Malaria, Vivax; Parasitemia; Plasmodium falciparum; Plasmodium vivax; Primaquine; Travel
PubMed: 28450185
DOI: 10.1016/j.tmaid.2017.04.005 -
Parasitology Nov 2023Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously... (Review)
Review
Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously considered a non-human primate (NHP) infecting species, is now a cause of human malaria in Malaysia. The other NHP species, , , , , and cause malaria in primates, which are mainly reported in southeast Asia and South America. The non- NHP species also emerged and were found to cross-transmit from their natural hosts (NHP) – to human hosts in natural settings. Here we have reviewed and collated data from the literature on the NHPs-to-human-transmitting species. It was observed that the natural transmission of these NHP parasites to humans had been reported from 2010 onwards. This study shows that: (1) the majority of the non- NHP mixed species infecting human cases were from Yala province of Thailand; (2) mono/mixed infections with other human-infecting species were prevalent in Malaysia and Thailand and (3) and were found in Central and South America.
Topics: Animals; Humans; Malaria; Plasmodium knowlesi; Primates; Asia, Southeastern; Plasmodium vivax
PubMed: 37929579
DOI: 10.1017/S003118202300077X -
BMC Medicine May 2016Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage,... (Meta-Analysis)
Meta-Analysis Review
Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy: a systematic review and meta-analysis of individual patient data.
BACKGROUND
Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are important for malaria elimination efforts. An individual patient clinical data meta-analysis was undertaken to identify the determinants of gametocyte carriage and the comparative effects of four ACTs: artemether-lumefantrine (AL), artesunate/amodiaquine (AS-AQ), artesunate/mefloquine (AS-MQ), and dihydroartemisinin-piperaquine (DP).
METHODS
Factors associated with gametocytaemia prior to, and following, ACT treatment were identified in multivariable logistic or Cox regression analysis with random effects. All relevant studies were identified through a systematic review of PubMed. Risk of bias was evaluated based on study design, methodology, and missing data.
RESULTS
The systematic review identified 169 published and 9 unpublished studies, 126 of which were shared with the WorldWide Antimalarial Resistance Network (WWARN) and 121 trials including 48,840 patients were included in the analysis. Prevalence of gametocytaemia by microscopy at enrolment was 12.1 % (5887/48,589), and increased with decreasing age, decreasing asexual parasite density and decreasing haemoglobin concentration, and was higher in patients without fever at presentation. After ACT treatment, gametocytaemia appeared in 1.9 % (95 % CI, 1.7-2.1) of patients. The appearance of gametocytaemia was lowest after AS-MQ and AL and significantly higher after DP (adjusted hazard ratio (AHR), 2.03; 95 % CI, 1.24-3.12; P = 0.005 compared to AL) and AS-AQ fixed dose combination (FDC) (AHR, 4.01; 95 % CI, 2.40-6.72; P < 0.001 compared to AL). Among individuals who had gametocytaemia before treatment, gametocytaemia clearance was significantly faster with AS-MQ (AHR, 1.26; 95 % CI, 1.00-1.60; P = 0.054) and slower with DP (AHR, 0.74; 95 % CI, 0.63-0.88; P = 0.001) compared to AL. Both recrudescent (adjusted odds ratio (AOR), 9.05; 95 % CI, 3.74-21.90; P < 0.001) and new (AOR, 3.03; 95 % CI, 1.66-5.54; P < 0.001) infections with asexual-stage parasites were strongly associated with development of gametocytaemia after day 7.
CONCLUSIONS
AS-MQ and AL are more effective than DP and AS-AQ FDC in preventing gametocytaemia shortly after treatment, suggesting that the non-artemisinin partner drug or the timing of artemisinin dosing are important determinants of post-treatment gametocyte dynamics.
Topics: Amodiaquine; Antimalarials; Artemisinins; Child, Preschool; Drug Combinations; Drug Therapy, Combination; Host-Parasite Interactions; Humans; Logistic Models; Malaria, Falciparum; Male; Microscopy; Middle Aged; Plasmodium falciparum; Proportional Hazards Models; Recurrence
PubMed: 27221542
DOI: 10.1186/s12916-016-0621-7 -
Parasitology Research Oct 2022A plethora of studies analyse the molecular markers of drug resistance and hence help in guiding the evidence-based malaria treatment policies in India. For reporting... (Review)
Review
A plethora of studies analyse the molecular markers of drug resistance and hence help in guiding the evidence-based malaria treatment policies in India. For reporting mutations, a number of techniques including DNA sequencing, restriction-fragment length polymorphism and mutation-specific polymerase chain reaction have been employed across numerous studies, including variations in the methodology used. However, there is no sufficient data from India comparing these methods as well as report the prevalence of polymorphisms in SP drug resistance molecular markers independently using such methods. Therefore, all data from Indian studies available for molecular marker studies of Plasmodium falciparum drug resistance to sulphadoxine-pyrimethamine was gathered, and a systematic review was performed. This systematic review identifies the molecular methods in use in India and compares each method for detecting sulphadoxine-pyrimethamine drug resistance marker. To delay the spread of drug-resistant parasite strains, a simplified and standardized molecular method is much needed which can be obtained by analysing the performance of each method in use and answering the necessity of newer methodological approaches.
Topics: Antimalarials; Drug Combinations; Drug Resistance; Humans; India; Malaria, Falciparum; Plasmodium falciparum; Pyrimethamine; Sulfadoxine
PubMed: 35980472
DOI: 10.1007/s00436-022-07623-3 -
The Cochrane Database of Systematic... Jan 2021Despite being preventable, malaria remains an important public health problem. The World Health Organization (WHO) reports that overall progress in malaria control has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite being preventable, malaria remains an important public health problem. The World Health Organization (WHO) reports that overall progress in malaria control has plateaued for the first time since the turn of the century. Researchers and policymakers are therefore exploring alternative and supplementary malaria vector control tools. Research in 1900 indicated that modification of houses may be effective in reducing malaria: this is now being revisited, with new research now examining blocking house mosquito entry points or modifying house construction materials to reduce exposure of inhabitants to infectious bites.
OBJECTIVES
To assess the effects of house modifications on malaria disease and transmission.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (OVID); Centre for Agriculture and Bioscience International (CAB) Abstracts (Web of Science); and the Latin American and Caribbean Health Science Information database (LILACS), up to 1 November 2019. We also searched the WHO International Clinical Trials Registry Platform (www.who.int/ictrp/search/en/), ClinicalTrials.gov (www.clinicaltrials.gov), and the ISRCTN registry (www.isrctn.com/) to identify ongoing trials up to the same date.
SELECTION CRITERIA
Randomized controlled trials, including cluster-randomized controlled trials (cRCTs), cross-over studies, and stepped-wedge designs were eligible, as were quasi-experimental trials, including controlled before-and-after studies, controlled interrupted time series, and non-randomized cross-over studies. We only considered studies reporting epidemiological outcomes (malaria case incidence, malaria infection incidence or parasite prevalence). We also summarised qualitative studies conducted alongside included studies.
DATA COLLECTION AND ANALYSIS
Two review authors selected eligible studies, extracted data, and assessed the risk of bias. We used risk ratios (RR) to compare the effect of the intervention with the control for dichotomous data. For continuous data, we presented the mean difference; and for count and rate data, we used rate ratios. We presented all results with 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach.
MAIN RESULTS
Six cRCTs met our inclusion criteria, all conducted in sub-Saharan Africa; three randomized by household, two by village, and one at the community level. All trials assessed screening of windows, doors, eaves, ceilings or any combination of these; this was either alone, or in combination with eave closure, roof modification or eave tube installation (a "lure and kill" device that reduces mosquito entry whilst maintaining some airflow). In two trials, the interventions were insecticide-based. In five trials, the researchers implemented the interventions. The community implemented the interventions in the sixth trial. At the time of writing the review, two of the six trials had published results, both of which compared screened houses (without insecticide) to unscreened houses. One trial in Ethiopia assessed screening of windows and doors. Another trial in the Gambia assessed full screening (screening of eaves, doors and windows), as well as screening of ceilings only. Screening may reduce clinical malaria incidence caused by Plasmodium falciparum (rate ratio 0.38, 95% CI 0.18 to 0.82; 1 trial, 184 participants, 219.3 person-years; low-certainty evidence; Ethiopian study). For malaria parasite prevalence, the point estimate, derived from The Gambia study, was smaller (RR 0.84, 95% CI 0.60 to 1.17; 713 participants, 1 trial; low-certainty evidence), and showed an effect on anaemia (RR 0.61, 95% CI 0.42, 0.89; 705 participants; 1 trial, moderate-certainty evidence). Screening may reduce the entomological inoculation rate (EIR): both trials showed lower estimates in the intervention arm. In the Gambian trial, there was a mean difference in EIR between the control houses and treatment houses ranging from 0.45 to 1.50 (CIs ranged from -0.46 to 2.41; low-certainty evidence), depending on the study year and treatment arm. The Ethiopian trial reported a mean difference in EIR of 4.57, favouring screening (95% CI 3.81 to 5.33; low-certainty evidence). Pooled analysis of the trials showed that individuals living in fully screened houses were slightly less likely to sleep under a bed net (RR 0.84, 95% CI 0.65 to 1.09; 2 trials, 203 participants). In one trial, bed net usage was also lower in individuals living in houses with screened ceilings (RR 0.69, 95% CI 0.50 to 0.95; 1 trial, 135 participants).
AUTHORS' CONCLUSIONS
Based on the two trials published to date, there is some evidence that screening may reduce malaria transmission and malaria infection in people living in the house. The four trials awaiting publication are likely to enrich the current evidence base, and we will add these to this review when they become available.
Topics: Adolescent; Adult; Africa South of the Sahara; Anemia; Animals; Architecture; Child; Child, Preschool; Construction Materials; Female; Housing; Humans; Incidence; Infant; Insecticides; Malaria, Falciparum; Male; Mosquito Nets; Mosquito Vectors; Plasmodium falciparum; Pregnancy; Prevalence; Randomized Controlled Trials as Topic
PubMed: 33471371
DOI: 10.1002/14651858.CD013398.pub3