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The Cochrane Database of Systematic... Sep 2021Studies evaluating mass drug administration (MDA) in malarious areas have shown reductions in malaria immediately following the intervention. However, these effects vary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies evaluating mass drug administration (MDA) in malarious areas have shown reductions in malaria immediately following the intervention. However, these effects vary by endemicity and are not sustained. Since the 2013 version of this Cochrane Review on this topic, additional studies have been published.
OBJECTIVES
Primary objectives To assess the sustained effect of MDA with antimalarial drugs on: - the reduction in malaria transmission in moderate- to high-transmission settings; - the interruption of transmission in very low- to low-transmission settings. Secondary objective To summarize the risk of drug-associated adverse effects following MDA.
SEARCH METHODS
We searched several trial registries, citation databases, conference proceedings, and reference lists for relevant articles up to 11 February 2021. We also communicated with researchers to identify additional published and unpublished studies.
SELECTION CRITERIA
Randomized controlled trials (RCTs) and non-randomized studies comparing MDA to no MDA with balanced co-interventions across study arms and at least two geographically distinct sites per study arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for eligibility and extracted data. We calculated relative risk (RR) and rate ratios with corresponding 95% confidence intervals (CIs) to compare prevalence and incidence, respectively, in MDA compared to no-MDA groups. We stratified analyses by malaria transmission and by malaria species. For cluster-randomized controlled trials (cRCTs), we adjusted standard errors using the intracluster correlation coefficient. We assessed the certainty of the evidence using the GRADE approach. For non-randomized controlled before-and-after (CBA) studies, we summarized the data using difference-in-differences (DiD) analyses.
MAIN RESULTS
Thirteen studies met our criteria for inclusion. Ten were cRCTs and three were CBAs. Cluster-randomized controlled trials Moderate- to high-endemicity areas (prevalence ≥ 10%) We included data from two studies conducted in The Gambia and Zambia. At one to three months after MDA, the Plasmodium falciparum (hereafter, P falciparum) parasitaemia prevalence estimates may be higher compared to control but the CIs included no effect (RR 1.76, 95% CI 0.58 to 5.36; Zambia study; low-certainty evidence); parasitaemia incidence was probably lower (RR 0.61, 95% CI 0.40 to 0.92; The Gambia study; moderate-certainty evidence); and confirmed malaria illness incidence may be substantially lower, but the CIs included no effect (rate ratio 0.41, 95% CI 0.04 to 4.42; Zambia study; low-certainty evidence). At four to six months after MDA, MDA showed little or no effect on P falciparum parasitaemia prevalence (RR 1.18, 95% CI 0.89 to 1.56; The Gambia study; moderate-certainty evidence) and, no persisting effect was demonstrated with parasitaemia incidence (rate ratio 0.91, 95% CI 0.55 to 1.50; The Gambia study). Very low- to low-endemicity areas (prevalence < 10%) Seven studies from Cambodia, Laos, Myanmar (two studies), Vietnam, Zambia, and Zanzibar evaluated the effects of multiple rounds of MDA on P falciparum. Immediately following MDA (less than one month after MDA), parasitaemia prevalence was reduced (RR 0.12, 95% CI 0.03 to 0.52; one study; low-certainty evidence). At one to three months after MDA, there was a reduction in both parasitaemia incidence (rate ratio 0.37, 95% CI 0.21 to 0.55; 1 study; moderate-certainty evidence) and prevalence (RR 0.25, 95% CI 0.15 to 0.41; 7 studies; low-certainty evidence). For confirmed malaria incidence, absolute rates were low, and it is uncertain whether MDA had an effect on this outcome (rate ratio 0.58, 95% CI 0.12 to 2.73; 2 studies; very low-certainty evidence). For P falciparum prevalence, the relative differences declined over time, from RR 0.63 (95% CI 0.36 to 1.12; 4 studies) at four to six months after MDA, to RR 0.86 (95% CI 0.55 to 1.36; 5 studies) at 7 to 12 months after MDA. Longer-term prevalence estimates showed overall low absolute risks, and relative effect estimates of the effect of MDA on prevalence varied from RR 0.82 (95% CI 0.20 to 3.34) at 13 to 18 months after MDA, to RR 1.25 (95% CI 0.25 to 6.31) at 31 to 36 months after MDA in one study. Five studies from Cambodia, Laos, Myanmar (2 studies), and Vietnam evaluated the effect of MDA on Plasmodium vivax (hereafter, P vivax). One month following MDA, P vivax prevalence was lower (RR 0.18, 95% CI 0.08 to 0.40; 1 study; low-certainty evidence). At one to three months after MDA, there was a reduction in P vivax prevalence (RR 0.15, 95% CI 0.10 to 0.24; 5 studies; low-certainty evidence). The immediate reduction on P vivax prevalence was not sustained over time, from RR 0.78 (95% CI 0.63 to 0.95; 4 studies) at four to six months after MDA, to RR 1.12 (95% CI 0.94 to 1.32; 5 studies) at 7 to 12 months after MDA. One of the studies in Myanmar provided estimates of longer-term effects, where overall absolute risks were low, ranging from RR 0.81 (95% CI 0.44 to 1.48) at 13 to 18 months after MDA, to RR 1.20 (95% CI 0.44 to 3.29) at 31 to 36 months after MDA. Non-randomized studies Three CBA studies were conducted in moderate- to high-transmission areas in Burkina Faso, Kenya, and Nigeria. There was a reduction in P falciparum parasitaemia prevalence in MDA groups compared to control groups during MDA (DiD range: -15.8 to -61.4 percentage points), but the effect varied at one to three months after MDA (DiD range: 14.9 to -41.1 percentage points). AUTHORS' CONCLUSIONS: In moderate- to high-transmission settings, no studies reported important effects on P falciparum parasitaemia prevalence within six months after MDA. In very low- to low-transmission settings, parasitaemia prevalence and incidence were reduced initially for up to three months for both P falciparum and P vivax; longer-term data did not demonstrate an effect after four months, but absolute risks in both intervention and control groups were low. No studies provided evidence of interruption of malaria transmission.
Topics: Antimalarials; Humans; Malaria; Malaria, Falciparum; Mass Drug Administration; Parasitemia
PubMed: 34585740
DOI: 10.1002/14651858.CD008846.pub3 -
The Cochrane Database of Systematic... Feb 2018Malaria is an important cause of illness and death across endemic regions. Considerable success against malaria has been achieved within the past decade mainly through... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Malaria is an important cause of illness and death across endemic regions. Considerable success against malaria has been achieved within the past decade mainly through long-lasting insecticide-treated nets (LLINs). However, elimination of the disease is proving difficult as current control methods do not protect against mosquitoes biting outdoors and when people are active. Repellents may provide a personal protection solution during these times.
OBJECTIVES
To assess the impact of topical repellents, insecticide-treated clothing, and spatial repellents on malaria transmission.
SEARCH METHODS
We searched the following databases up to 26 June 2017: the Cochrane Infectious Diseases Group Specialized Register; the Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; Embase; US AFPMB; CAB Abstracts; and LILACS. We also searched trial registration platforms and conference proceedings; and contacted organizations and companies for ongoing and unpublished trials.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and cluster-randomized controlled trials of topical repellents proven to repel mosquitoes; permethrin-treated clothing; and spatial repellents such as mosquito coils. We included trials that investigated the use of repellents with or without LLINs, referred to as insecticide-treated nets.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed trials for inclusion, extracted the data, and assessed the risk of bias. A third review author resolved any discrepancies. We analysed data by conducting meta-analysis and stratified by whether the trials had included LLINs. We combined results from cRCTs with individually RCTs by adjusting for clustering and presented results using forest plots. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
Eight cRCTs and two RCTs met the inclusion criteria. Six trials investigated topical repellents, two trials investigated insecticide-treated clothing, and two trials investigated spatial repellents.Topical repellentsSix RCTS, five of them cluster-randomized, investigated topical repellents involving residents of malaria-endemic regions. Four trials used topical repellents in combination with nets, but two trials undertaken in displaced populations used topical repellents alone. It is unclear if topical repellents can prevent clinical malaria (RR 0.65, 95% CI 0.4 to 1.07, very low certainty evidence) or malaria infection (RR 0.84, 95% CI 0.64 to 1.12, low-certainty evidence) caused by P. falciparum. It is also unclear if there is any protection against clinical cases of P. vivax (RR 1.32, 95% CI 0.99 to 1.76, low-certainty evidence) or incidence of infections (RR 1.07, 95% CI 0.80 to 1.41, low-certainty evidence). Subgroup analysis of trials including insecticide-treated nets did not show a protective effect of topical repellents against malaria. Only two studies did not include insecticide-treated nets, and they measured different outcomes; one reported a protective effect against clinical cases of P. falciparum (RR 0.40, 95% CI 0.23 to 0.71); but the other study measured no protective effect against malaria infection incidence caused by either P. falciparum or P. vivax.Insecticide-treated clothingInsecticide-treated clothing were investigated in trials conducted in refugee camps in Pakistan and amongst military based in the Colombian Amazon. Neither study provided participants with insecticide-treated nets. In the absence of nets, treated clothing may reduce the incidence of clinical malaria caused by P. falciparum by approximately 50% (RR 0.49, 95% CI 0.29 to 0.83, low-certainty evidence) and P. vivax (RR 0.64, 95% CI 0.40 to 1.01, low-certainty evidence).Spatial repellentsTwo cluster-randomized RCTs investigated mosquito coils for malaria prevention. We do not know the effect of spatial repellents on malaria prevention (RR 0.24, 95% CI 0.03 to 1.72, very low certainty evidence). There was large heterogeneity between studies and one study had high risk of bias.
AUTHORS' CONCLUSIONS
There is insufficient evidence to conclude topical or spatial repellents can prevent malaria. There is a need for better designed trials to generate higher certainty of evidence before well-informed recommendations can be made. Adherence to daily compliance remains a major limitation. Insecticide-treated clothing may reduce risk of malaria infection in the absence of insecticide-treated nets; further studies on insecticide-treated clothing in the general population should be done to broaden the applicability of the results.
Topics: Animals; Culicidae; Incidence; Insect Repellents; Insecticide-Treated Bednets; Malaria, Falciparum; Malaria, Vivax; Protective Clothing; Randomized Controlled Trials as Topic
PubMed: 29405263
DOI: 10.1002/14651858.CD011595.pub2 -
PLoS Neglected Tropical Diseases May 2016Soil-transmitted helminths (STH) have acute and chronic manifestations, and can result in lifetime morbidity. Disease burden is difficult to quantify, yet quantitative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Soil-transmitted helminths (STH) have acute and chronic manifestations, and can result in lifetime morbidity. Disease burden is difficult to quantify, yet quantitative evidence is required to justify large-scale deworming programmes. A recent Cochrane systematic review, which influences Global Burden of Disease (GBD) estimates for STH, has again called into question the evidence for deworming benefit on morbidity due to STH. In this narrative review, we investigate in detail what the shortfalls in evidence are.
METHODOLOGY/PRINCIPAL FINDINGS
We systematically reviewed recent literature that used direct measures to investigate morbidity from STH and we critically appraised systematic reviews, particularly the most recent Cochrane systematic review investigating deworming impact on morbidity. We included six systematic reviews and meta-analyses, 36 literature reviews, 44 experimental or observational studies, and five case series. We highlight where evidence is insufficient and where research needs to be directed to strengthen morbidity evidence, ideally to prove benefits of deworming.
CONCLUSIONS/SIGNIFICANCE
Overall, the Cochrane systematic review and recent studies indicate major shortfalls in evidence for direct morbidity. However, it is questionable whether the systematic review methodology should be applied to STH due to heterogeneity of the prevalence of different species in each setting. Urgent investment in studies powered to detect direct morbidity effects due to STH is required.
Topics: Anemia; Animals; Anthelmintics; Ascariasis; Ascaris lumbricoides; Chronic Disease; Cost of Illness; Helminthiasis; Humans; Prevalence; Soil
PubMed: 27196100
DOI: 10.1371/journal.pntd.0004566 -
The Lancet. Global Health Feb 2019Global migration from regions where strongyloidiasis and schistosomiasis are endemic to non-endemic countries has increased the potential individual and public health... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Global migration from regions where strongyloidiasis and schistosomiasis are endemic to non-endemic countries has increased the potential individual and public health effect of these parasitic diseases. We aimed to estimate the prevalence of these infections among migrants to establish which groups are at highest risk and who could benefit from screening.
METHODS
We did a systematic review and meta-analysis of strongyloidiasis and schistosomiasis prevalence among migrants born in endemic countries. Original studies that included data for the prevalence of Strongyloides or Schistosoma antibodies in serum or the prevalence of larvae or eggs in stool or urine samples among migrants originating from countries endemic for these parasites and arriving or living in host countries with low endemicity-specifically the USA, Canada, Australia, New Zealand, Israel, and 23 western European countries-were eligible for inclusion. Pooled estimates of the prevalence of strongyloidiasis and schistosomiasis by stool or urine microscopy for larvae or eggs or serum antibodies were calculated with a random-effects model. Heterogeneity was explored by stratification by age, region of origin, migrant class, period of study, and type of serological antigen used.
FINDINGS
88 studies were included. Pooled strongyloidiasis seroprevalence was 12·2% (95% CI 9·0-15·9%; I 96%) and stool-based prevalence was 1·8% (1·2-2·6%; 98%). Migrants from east Asia and the Pacific (17·3% [95% CI 4·1-37·0]), sub-Saharan Africa (14·6% [7·1-24·2]), and Latin America and the Caribbean (11·4% [7·8-15·7]) had the highest seroprevalence. Pooled schistosomiasis seroprevalence was 18·4% (95% CI 13·1-24·5; I 97%) and stool-based prevalence was 0·9% (0·2-1·9; 99%). Sub-Saharan African migrants had the highest seroprevalence (24·1·% [95% CI 16·4-32·7]).
INTERPRETATION
Strongyloidiasis affects migrants from all global regions, whereas schistosomiasis is focused in specific regions and most common among sub-Saharan African migrants. Serological prevalence estimates were several times higher than stool estimates for both parasites. These data can be used to inform screening decisions for migrants and support the use of serological screening, which is more sensitive and easier than stool testing.
FUNDING
None.
Topics: Africa South of the Sahara; Australia; Canada; Caribbean Region; Emigrants and Immigrants; Endemic Diseases; Europe; Asia, Eastern; Feces; Humans; Israel; Latin America; Mass Screening; New Zealand; Pacific Islands; Prevalence; Schistosomiasis; Seroepidemiologic Studies; Serologic Tests; Strongyloidiasis; United States
PubMed: 30683241
DOI: 10.1016/S2214-109X(18)30490-X -
Pathogens and Global Health Oct 2017Toxoplasmosis is an infection caused by the intracellular protozoan parasite Toxoplasma gondii, and is associated with clinically significant infection in... (Review)
Review
Toxoplasmosis is an infection caused by the intracellular protozoan parasite Toxoplasma gondii, and is associated with clinically significant infection in immunocompromised individuals. Vertical transmission during pregnancy can manifest as congenital toxoplasmosis in the neonate, and can have serious consequences. This review aims to describe the modalities for prophylaxis of toxoplasmosis in susceptible populations, and focuses on the following: (1) prophylaxis of congenital toxoplasmosis; (2) prophylaxis of toxoplasmosis in patients with HIV/AIDS; and (3) prophylaxis of toxoplasmosis in transplant recipients.
Topics: HIV Infections; Humans; Infectious Disease Transmission, Vertical; Toxoplasmosis; Transplant Recipients
PubMed: 28948861
DOI: 10.1080/20477724.2017.1370528 -
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 -
PloS One 2017Zoonotic enteric parasites are ubiquitous and remain a public health threat to humans due to our close relationship with domestic animals and wildlife, inadequate water,... (Review)
Review
INTRODUCTION
Zoonotic enteric parasites are ubiquitous and remain a public health threat to humans due to our close relationship with domestic animals and wildlife, inadequate water, sanitation, and hygiene practices and diet. While most communities are now sedentary, nomadic and pastoral populations still exist and experience unique exposure risks for acquiring zoonotic enteric parasites. Through this systematic review we sought to summarize published research regarding pathogens present in nomadic populations and to identify the risk factors for their infection.
METHODS
Using systematic review guidelines set forth by PRISMA, research articles were identified, screened and summarized based on exclusion criteria for the documented presence of zoonotic enteric parasites within nomadic or pastoral human populations. A total of 54 articles published between 1956 and 2016 were reviewed to determine the pathogens and exposure risks associated with the global transhumance lifestyle.
RESULTS
The included articles reported more than twenty different zoonotic enteric parasite species and illustrated several risk factors for nomadic and pastoralist populations to acquire infection including; a) animal contact, b) food preparation and diet, and c) household characteristics. The most common parasite studied was Echinococcosis spp. and contact with dogs was recognized as a leading risk factor for zoonotic enteric parasites followed by contact with livestock and/or wildlife, water, sanitation, and hygiene barriers, home slaughter of animals, environmental water exposures, household member age and sex, and consumption of unwashed produce or raw, unprocessed, or undercooked milk or meat.
CONCLUSION
Nomadic and pastoral communities are at risk of infection with a variety of zoonotic enteric parasites due to their living environment, cultural and dietary traditions, and close relationship to animals. Global health efforts aimed at reducing the transmission of these animal-to-human pathogens must incorporate a One Health approach to support water, sanitation, and hygiene development, provide education on safe food handling and preparation, and improve the health of domestic animals associated with these groups, particularly dogs.
Topics: Animals; Humans; Intestinal Diseases, Parasitic; Risk Factors; Zoonoses
PubMed: 29190664
DOI: 10.1371/journal.pone.0188809 -
Malaria Journal Aug 2023Malaria affects 24 million children globally, resulting in nearly 500,000 child deaths annually in low- and middle-income countries (LMICs). Recent studies have provided... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Malaria affects 24 million children globally, resulting in nearly 500,000 child deaths annually in low- and middle-income countries (LMICs). Recent studies have provided evidence that severe malaria infection results in sustained impairment in cognition and behaviour among young children; however, a formal meta-analysis has not been published. The objective was to assess the association between severe malaria infection with cognitive and behavioural outcomes among children living in LMICs.
METHODS
Six online bibliographic databases were searched and reviewed in November 2022. Studies included involved children < 18 years of age living in LMICs with active or past severe malaria infection and measured cognitive and/or behaviour outcomes. The quality of studies was assessed. Definitions of severe malaria included cerebral malaria, severe malarial anaemia, and author-defined severe malaria. Results from all studies were qualitatively summarized. For studies with relevant data on attention, learning, memory, language, internalizing behaviour and externalizing behaviour, results were pooled and a meta-analysis was performed. A random-effects model was used across included cohorts, yielding a standardized mean difference between the severe malaria group and control group.
RESULTS
Out of 3,803 initial records meeting the search criteria, 24 studies were included in the review, with data from 14 studies eligible for meta-analysis inclusion. Studies across sub-Saharan Africa assessed 11 cohorts of children from pre-school to school age. Of all the studies, composite measures of cognition were the most affected areas of development. Overall, attention, memory, and behavioural problems were domains most commonly found to have lower scores in children with severe malaria. Meta-analysis revealed that children with severe malaria had worse scores compared to children without malaria in attention (standardized mean difference (SMD) -0.68, 95% CI -1.26 to -0.10), memory (SMD -0.52, 95% CI -0.99 to -0.06), and externalizing behavioural problems (SMD 0.45, 95% CI 0.13-0.78).
CONCLUSION
Severe malaria is associated with worse neuropsychological outcomes for children living in LMICs, specifically in attention, memory, and externalizing behaviours. More research is needed to identify the long-term implications of these findings. Further interventions are needed to prevent cognitive and behavioural problems after severe malaria infection.
TRIAL REGISTRATION
This systematic review was registered under PROSPERO: CRD42020154777.
Topics: Child; Child, Preschool; Humans; Developing Countries; Cognition; Malaria, Cerebral; Africa South of the Sahara
PubMed: 37537555
DOI: 10.1186/s12936-023-04653-9 -
The Lancet. Infectious Diseases Mar 2023The neglected zoonosis cystic echinococcosis affects mainly pastoral and rural communities in both low-income and upper-middle-income countries. In Europe, it should be... (Review)
Review
The neglected zoonosis cystic echinococcosis affects mainly pastoral and rural communities in both low-income and upper-middle-income countries. In Europe, it should be regarded as an orphan and rare disease. Although human cystic echinococcosis is a notifiable parasitic infectious disease in most European countries, in practice it is largely under-reported by national health systems. To fill this gap, we extracted data on the number, incidence, and trend of human cases in Europe through a systematic review approach, using both the scientific and grey literature and accounting for the period of publication from 1997 to 2021. The highest number of possible human cases at the national level was calculated from various data sources to generate a descriptive model of human cystic echinococcosis in Europe. We identified 64 745 human cystic echinococcosis cases from 40 European countries. The mean annual incidence from 1997 to 2020 throughout Europe was 0·64 cases per 100 000 people and in EU member states was 0·50 cases per 100 000 people. Based on incidence rates and trends detected in this study, the current epicentre of cystic echinococcosis in Europe is in the southeastern European countries, whereas historical endemic European Mediterranean countries have recorded a decrease in the number of cases over the time.
Topics: Animals; Humans; Incidence; Zoonoses; Echinococcosis; Europe; Rural Population
PubMed: 36427513
DOI: 10.1016/S1473-3099(22)00638-7 -
Malaria Journal Jul 2022Interleukin (IL)-4 had been linked to malaria severity, but the findings are controversial, and the evidence is inconsistent and imprecise. In the current investigation,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Interleukin (IL)-4 had been linked to malaria severity, but the findings are controversial, and the evidence is inconsistent and imprecise. In the current investigation, data on IL-4 levels in patients with severe and uncomplicated malaria were compiled.
METHODS
The systematic review was registered at PROSPERO (CRD42022323387). Searches for relevant articles on IL-4 levels in patients with severe malaria and studies that examined IL-4 levels in both uncomplicated malaria and healthy controls were performed in PubMed, Embase, and Scopus using the search strategy without limitation to publication years or language. The quality of all included studies was evaluated using The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: standards for reporting observational studies. Qualitative and quantitative data syntheses were performed. The random-effects model, which weights each study according to its between- and within-study variance, was used to pool the mean difference (MD) of individual studies. The degree of heterogeneity was determined using Cochran's Q and I statistics. Additionally, meta-regression and subgroup analyses were perfomed to investigate possible sources of heterogeneity. The outliers were identified using the leave-one-out method and assessed publication bias using funnel plots, Egger's test, and a contour-enhanced funnel plot.
RESULTS
A total of 2300 studies were identified through database searches, and 36 were included for analyses. The meta-analysis results showed lower mean IL-4 levels in severe malaria (434 cases) than in uncomplicated malaria (611 cases) (P = 0.01, pooled MD: -3.36 pg/mL, 95% confidence intervals CI -5.55 to -1.16 pg/mL, I: 98.15%, 11 studies). The meta-analysis results showed no difference in mean IL-4 levels between cerebral malaria (96 cases) and noncerebral severe malaria (108 cases) (P = 0.71, pooled MD: 0.86 pg/mL, 95% CI -3.60 to 5.32 pg/mL, I 92.13%, four studies). Finally, no difference was found in mean IL-4 levels between uncomplicated malaria (635 cases) and healthy controls (674 cases) (P = 0.57, pooled MD: 0.79 pg/mL, 95% CI -1.92 to 3.50 pg/mL, I: 99.89%, 11 studies).
CONCLUSION
The meta-analysis revealed lower IL-4 levels in patients with severe malaria than in those with uncomplicated malaria, though a trend toward comparable IL-4 levels between both groups was more likely because several sources of heterogeneities were observed. Based on the limited number of studies included in the meta-analysis, until additional investigations have been conducted, IL-4 consideration as an alternative prognostic factor for malaria severity is not warranted.
Topics: Humans; Interleukin-4; Malaria, Cerebral
PubMed: 35820892
DOI: 10.1186/s12936-022-04237-z