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The Lancet. Global Health Apr 2024The geographical, demographic, and socioeconomic distributions of malaria and malnutrition largely overlap. It remains unknown whether malnutrition affects the efficacy... (Meta-Analysis)
Meta-Analysis
Does acute malnutrition in young children increase the risk of treatment failure following artemisinin-based combination therapy? A WWARN individual patient data meta-analysis.
BACKGROUND
The geographical, demographic, and socioeconomic distributions of malaria and malnutrition largely overlap. It remains unknown whether malnutrition affects the efficacy of WHO-recommended artemisinin-based combination therapies (ACTs). A previous systematic review was inconclusive as data were sparse and heterogeneous, indicating that other methodological approaches, such as individual patient data meta-analysis, should be considered. The objective of this study was to conduct such a meta-analysis to assess the effect of malnutrition (wasting and stunting) on treatment outcomes in children younger than 5 years treated with an ACT for uncomplicated falciparum malaria.
METHODS
We conducted a meta-analysis of individual patient data from studies identified through a systematic review of literature published between 1980 and 2018 in PubMed, Global Health, and Cochrane Libraries (PROSPERO CRD42017056934) and inspection of the WorldWide Antimalarial Resistance Network (WWARN) repository for ACT efficacy studies, including children younger than 5 years with uncomplicated falciparum malaria. The association of either acute (wasting) or chronic (stunting) malnutrition with day 42 PCR-adjusted risk of recrudescence (ie, return of the same infection) or reinfection after therapy was investigated using Cox regression, and with day 2 parasite positivity using logistic regression.
FINDINGS
Data were included from all 36 studies targeted, 31 from Africa. Of 11 301 eligible children in 75 study sites, 11·5% were wasted (weight-for-height Z score [WHZ] <-2), and 31·8% were stunted (height-for-age Z score [HAZ] <-2). Decrease in WHZ was associated with increased risk of day 2 positivity (adjusted odds ratio 1·12, 95% CI 1·05-1·18 per unit; p=0·0002), treatment failure (adjusted hazard ratio [AHR] 1·14, 95% CI 1·02-1·26, p=0·016), and reinfection after therapy (AHR 1·09, 1·04-1·13, p=0·0003). Children with milder wasting (WHZ -2 to -1) also had a higher risk of recrudescence (AHR 1·85, 1·29-2·65, p=0·0008 vs WHZ ≥0). Stunting was not associated with reduced ACT efficacy.
INTERPRETATION
Children younger than 5 years with acute malnutrition and presenting with uncomplicated falciparum malaria were at higher risk of delayed parasite clearance, ACT treatment failure, and reinfections. Stunting was more prevalent, but not associated with changes in ACT efficacy. Acute malnutrition is known to impact medicine absorption and metabolism. Further study to inform dose optimisation of ACTs in wasted children is urgently needed.
FUNDING
Bill & Melinda Gates Foundation.
TRANSLATION
For the French translation of the abstract see Supplementary Materials section.
Topics: Child; Humans; Child, Preschool; Antimalarials; Reinfection; Artemisinins; Malaria, Falciparum; Malaria; Treatment Failure; Malnutrition; Recurrence; Growth Disorders
PubMed: 38485430
DOI: 10.1016/S2214-109X(24)00003-2 -
The Lancet. Global Health May 2024WHO has proposed elimination of transmission of onchocerciasis (river blindness) by 2030. More than 99% of cases of onchocerciasis are in sub-Saharan Africa. Vector... (Meta-Analysis)
Meta-Analysis
Elimination of transmission of onchocerciasis (river blindness) with long-term ivermectin mass drug administration with or without vector control in sub-Saharan Africa: a systematic review and meta-analysis.
BACKGROUND
WHO has proposed elimination of transmission of onchocerciasis (river blindness) by 2030. More than 99% of cases of onchocerciasis are in sub-Saharan Africa. Vector control and mass drug administration of ivermectin have been the main interventions for many years, with varying success. We aimed to identify factors associated with elimination of onchocerciasis transmission in sub-Saharan Africa.
METHODS
For this systematic review and meta-analysis we searched for published articles reporting epidemiological or entomological assessments of onchocerciasis transmission status in sub-Saharan Africa, with or without vector control. We searched MEDLINE, PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, African Index Medicus, and Google Scholar databases for all articles published from database inception to Aug 19, 2023, without language restrictions. The search terms used were "onchocerciasis" AND "ivermectin" AND "mass drug administration". The three inclusion criteria were (1) focus or foci located in Africa, (2) reporting of elimination of transmission or at least 10 years of ivermectin mass drug administration in the focus or foci, and (3) inclusion of at least one of the following assessments: microfilarial prevalence, nodule prevalence, Ov16 antibody seroprevalence, and blackfly infectivity prevalence. Epidemiological modelling studies and reviews were excluded. Four reviewers (NM, AJ, AM, and TNK) extracted data in duplicate from the full-text articles using a data extraction tool developed in Excel with columns recording the data of interest to be extracted, and a column where important comments for each study could be highlighted. We did not request any individual-level data from authors. Foci were classified as achieving elimination of transmission, being close to elimination of transmission, or with ongoing transmission. We used mixed-effects meta-regression models to identify factors associated with transmission status. This study is registered in PROSPERO, CRD42022338986.
FINDINGS
Of 1525 articles screened after the removal of duplicates, 75 provided 282 records from 238 distinct foci in 19 (70%) of the 27 onchocerciasis-endemic countries in sub-Saharan Africa. Elimination of transmission was reported in 24 (9%) records, being close to elimination of transmission in 86 (30%) records, and ongoing transmission in 172 (61%) records. I was 83·3% (95% CI 79·7 to 86·3). Records reporting 10 or more years of continuous mass drug administration with 80% or more therapeutic coverage of the eligible population yielded significantly higher odds of achieving elimination of transmission (log-odds 8·5 [95% CI 3·5 to 13·5]) or elimination and being close to elimination of transmission (42·4 [18·7 to 66·1]) than those with no years achieving 80% coverage or more. Reporting 15-19 years of ivermectin mass drug administration (22·7 [17·2 to 28·2]) and biannual treatment (43·3 [27·2 to 59·3]) were positively associated with elimination and being close to elimination of transmission compared with less than 15 years and no biannual mass drug administration, respectively. Having had vector control without vector elimination (-42·8 [-59·1 to -26·5]) and baseline holoendemicity (-41·97 [-60·6 to -23·2]) were associated with increased risk of ongoing transmission compared with no vector control and hypoendemicity, respectively. Blackfly disappearance due to vector control or environmental change contributed to elimination of transmission.
INTERPRETATION
Mass drug administration duration, frequency, and coverage; baseline endemicity; and vector elimination or disappearance are important determinants of elimination of onchocerciasis transmission in sub-Saharan Africa. Our findings underscore the importance of improving and sustaining high therapeutic coverage and increasing treatment frequency if countries are to achieve elimination of onchocerciasis transmission.
FUNDING
The Bill & Melinda Gates Foundation and Neglected Tropical Diseases Modelling Consortium, UK Medical Research Council, and Global Health EDCTP3 Joint Undertaking.
TRANSLATIONS
For the Swahili, French, Spanish and Portuguese translations of the abstract see Supplementary Materials section.
Topics: Humans; Onchocerciasis; Ivermectin; Onchocerciasis, Ocular; Mass Drug Administration; Seroepidemiologic Studies; Africa South of the Sahara
PubMed: 38484745
DOI: 10.1016/S2214-109X(24)00043-3 -
Mass Testing and Treatment to Accelerate Malaria Elimination: A Systematic Review and Meta-Analysis.The American Journal of Tropical... Apr 2024In regions where malaria transmission persists, the implementation of approaches aimed at eliminating parasites from the population can effectively decrease both burden... (Meta-Analysis)
Meta-Analysis
In regions where malaria transmission persists, the implementation of approaches aimed at eliminating parasites from the population can effectively decrease both burden of disease and transmission of infection. Thus, mass strategies that target symptomatic and asymptomatic infections at the same time may help countries to reduce transmission. This systematic review assessed the potential benefits and harms of mass testing and treatment (MTaT) to reduce malaria transmission. Searches were conducted in March 2021 and updated in April 2022 and included cluster-randomized controlled trials (cRCTs) as well as nonrandomized studies (NRSs) using malaria infection incidence, clinical malaria incidence, or prevalence as outcomes. The risk of bias was assessed with Cochrane's risk of bias (RoB2) tool and Risk of Bias Tool in Nonrandomized Studies - of Interventions (ROBINS-I), and the certainty of evidence (CoE) was graded for each outcome. Of 4,462 citations identified, seven studies (four cRCTs and three NRSs) contributed outcome data. The analysis revealed that MTaT did not reduce the incidence (risk ratio [RR]: 0.95, 95% CI: 0.87-1.04; 1,181 participants; moderate CoE) or prevalence (RR: 0.83, 95% CI: 0.67-1.01; 7,522 participants; moderate CoE) of malaria infection but resulted in a small reduction in clinical malaria (RR: 0.82; 95% CI: 0.70-0.95; 334,944 participants; moderate CoE). Three studies contributing data on contextual factors concluded that MTaT is an acceptable, feasible, and cost-effective intervention. Mathematical modeling analyses (n = 10) suggested that MTaT effectiveness depends on the baseline transmission level, diagnostic test performance, number of rounds, and other co-interventions. Based on the limited evidence available, MTaT has little to no impact on reducing malaria transmission.
Topics: Humans; Malaria; Prevalence; Incidence; Bias; Sugar Alcohols
PubMed: 38471168
DOI: 10.4269/ajtmh.23-0127 -
The American Journal of Tropical... Apr 2024As countries approach elimination of malaria, groups with increased exposure to malaria vectors or poor access to health services may serve as important human reservoirs...
As countries approach elimination of malaria, groups with increased exposure to malaria vectors or poor access to health services may serve as important human reservoirs of infection that help maintain transmission in the community. Parasitological testing and treatment targeted to these groups may reduce malaria transmission overall. This systematic review assessed the effectiveness of targeted testing and treatment (TTaT) to reduce malaria transmission, the contextual factors, and the results of modeling studies that estimated the intervention's potential impact. Bibliographic searches were conducted in March 2021 and updated in April 2022, and a total of 1,210 articles were identified. Three studies were included for outcome data: one factorial cluster randomized controlled trial (cRCT) in Kenya (5,233 participants), one cRCT in Ghana (3,046 participants), and one controlled before-and-after cohort study in schoolchildren in Malawi (786 participants). Nine reports were included for contextual factors, and two were included for mathematical modeling. Data on outcomes from the three studies suggested that at the community level, TTaT would result in little to no difference in the incidence of malaria infection (measured via active surveillance), adverse events, and severe AEs. In contrast, the effects of TTaT on prevalence (malaria parasitemia) among those targeted by the intervention were found to include a short-term impact on reducing transmission but little to no impact on transmission for extended periods. Future iterations of this review should ensure consideration for populations proven to host the vast majority of the reservoir of infection in lower-transmission settings to determine the effectiveness of the intervention.
Topics: Humans; Child; Cohort Studies; Malaria; Kenya; Ghana; Malawi
PubMed: 38471159
DOI: 10.4269/ajtmh.23-0097 -
BMC Public Health Mar 2024Malaria is a widespread and prevalent disease that affects human population globally, particularly in tropical countries. Malaria is a major health issue in sub-Saharan...
Malaria is a widespread and prevalent disease that affects human population globally, particularly in tropical countries. Malaria is a major health issue in sub-Saharan Africa and it contributes to morbidity and mortality among individuals in Africa. Pregnant women have been also reported as high risk of people been infected with malaria. This review attempted to evaluate the various methods used for health education programs and the effectiveness of the programs in improving ITNs among pregnant women.Methods The search involved various databases; EBCOHOST, MEDLINE, CINAHL, Cochrane library, ScienceDirect, PubMed, SAGE, Sringer link, Web of Science and Wiley Online Library. It was limited to full text research articles that report intervention studies, written in English Language, published between 2003 to 2022. The key words were "malaria", "malaria prevention", "health education", "insecticide-treated nets", "utilization", "pregnant women".Results A total of eleven articles met the inclusion criteria and included in the review. Six studies reported randomized controlled trials (RCTs) while five reported non-randomized controlled trials (NRCT).Conclusions There are evidences from the results which showed that health education programs were improved among pregnant women due to the use of ITNs and LLINS utilization. Furthermore, additional interventions directed at significant others need to be implemented, considering their important role in determining pregnant women's use of ITNs.
Topics: Pregnancy; Female; Humans; Insecticides; Insecticide-Treated Bednets; Malaria; Health Education; Africa South of the Sahara; Mosquito Control
PubMed: 38468243
DOI: 10.1186/s12889-024-17650-7 -
The Lancet. Microbe Apr 2024Accurate diagnosis is pivotal for implementing strategies for surveillance, control, and elimination of schistosomiasis. Despite their low sensitivity in low-endemicity... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accurate diagnosis is pivotal for implementing strategies for surveillance, control, and elimination of schistosomiasis. Despite their low sensitivity in low-endemicity areas, microscopy-based urine filtration and the Kato-Katz technique are considered as reference diagnostic tests for Schistosoma haematobium and Schistosoma mansoni infections, respectively. We aimed to collate all available evidence on the accuracy of other proposed diagnostic techniques.
METHODS
In this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane Library, and LILACS for studies published from database inception to Dec 31, 2022, investigating the sensitivity and specificity of diagnostic tests for S haematobium and S mansoni infections against Kato-Katz thick smears or urine microscopy (reference tests) involving adults (aged ≥18 years), school-aged children (aged 7 to 18 years), or preschool-aged children (aged 1 month to 7 years). We extracted raw data on true positives, true negatives, false positives, and false negatives for the diagnostic tests and data on the number of participants, study authors, publication year, journal, study design, participants' age and sex, prevalence of Schistosoma infection, and treatment status. To account for imperfect reference tests, we used a hierarchical Bayesian latent class meta-analysis to model test accuracy.
FINDINGS
Overall, we included 121 studies, assessing 28 different diagnostic techniques. Most studies (103 [85%] of 121) were done in Africa, 14 (12%) in South America, one (1%) in Asia, and one (1%) in an unknown country. Compared with the reference test, Kato-Katz thick smears, circulating cathodic antigen urine cassette assay version 1 (CCA1, 36 test comparisons) had excellent sensitivity (95% [95% credible interval 88-99]) and reasonable specificity (74% [63-83]) for S mansoni. ELISA-based tests had a performance comparable to circulating cathodic antigen, but there were few available test comparisons. For S haematobium, proteinuria (42 test comparisons, sensitivity 73% [62-82]; specificity 94% [89-98]) and haematuria (75 test comparisons, sensitivity 85% [80-90]; specificity 96% [92-99]) reagent strips showed high specificity, with haematuria reagent strips having better sensitivity. Despite limited data, nucleic acid amplification tests (NAATs; eg, PCR or loop-mediated isothermal amplification [LAMP]) showed promising results with sensitivity estimates above 90%. We found an unclear risk of bias of about 70% in the use of the reference or index tests and of 50% in patient selection. All analyses showed substantial heterogeneity (I>80%).
INTERPRETATION
Although NAATs and immunological diagnostics show promise, the limited information available precludes drawing definitive conclusions. Additional research on diagnostic accuracy and cost-effectiveness is needed before the replacement of conventional tests can be considered.
FUNDING
WHO and Luxembourg Institute of Health.
Topics: Child; Child, Preschool; Adult; Animals; Humans; Adolescent; Schistosoma mansoni; Schistosoma haematobium; Hematuria; Reagent Strips; Microscopy; Bayes Theorem; Feces; Antigens, Helminth; Urinalysis; Schistosomiasis haematobia; Diagnostic Tests, Routine
PubMed: 38467130
DOI: 10.1016/S2666-5247(23)00377-4 -
PLoS Neglected Tropical Diseases Mar 2024Cholangiohydatidosis (CH) is an evolutionary complication of hepatic cystic echinococcosis, associated with increased morbidity and mortality. The aim of this study was...
BACKGROUND
Cholangiohydatidosis (CH) is an evolutionary complication of hepatic cystic echinococcosis, associated with increased morbidity and mortality. The aim of this study was to describe the available evidence regarding clinical characteristics of CH, postoperative complications and hospital mortality.
METHODOLOGY/PRINCIPAL FINDINGS
Systematic review. Studies related to CH with no language or publication restriction were included. Sensitive searches were performed in Trip Database, SciELO, BIREME-BVS, WoS, PubMed, EMBASE and SCOPUS. MeSH and free terms were used, including articles up to April 2023. The main outcome variables were postoperative complications and hospital mortality; the secondary ones were publication year, origin and design of primary studies, main clinical manifestation, anatomical location and type of cysts, hospital stay, surgical procedure performed, reinterventions; and methodological quality of primary studies, which was assessed using MInCir-T and MInCir-P scales. Descriptive statistics, calculation of weighted averages and their comparison by least squares logistic regression were applied. 446 studies were retrieved from the searches performed, 102 of which met the inclusion and exclusion criteria. The studies analyzed represent 1241 patients. The highest proportion of articles was published in the last decade (39.2%). Reports are mainly from Turkey (28.4%), Greece (9.8%), Morocco and Spain (8.8% each). With a weighted mean of 14.3 days of hospital stance; it was verified that 26.2% of patients developed postoperative complications (74,3% Clavien y Dindo III y IV), 6.7% needed re-interventions, and 3.7% died. When comparing the variables age, postoperative complications, hospital mortality, and reinterventions in two periods of time (1982-2006 vs. 2007-2023), no statistically significant differences were found. When applying the MInCir-T and MInCir-P scales, the methodological quality of the primary studies was 9.6±1.1 and 14.5±4.3 points, respectively.
CONCLUSION/SIGNIFICANCE
CH is associated with severe postoperative complications and significant hospital mortality, independent of the development of therapeutic support associated with the passage of time.
Topics: Humans; Hospital Mortality; Postoperative Complications; Echinococcosis, Hepatic; Morbidity
PubMed: 38452054
DOI: 10.1371/journal.pntd.0011558 -
PLoS Neglected Tropical Diseases Mar 2024Visceral leishmaniasis (VL), or kala-azar, is a vector-borne tropical disease caused by a group of intracellular hemoflagellate protozoa belonging to the family of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Visceral leishmaniasis (VL), or kala-azar, is a vector-borne tropical disease caused by a group of intracellular hemoflagellate protozoa belonging to the family of Trypanosomatide and the genus Leishmania. The disease is distributed around the world and transmitted via the bite of infected female Phlebotomine sandflies, and there is variation in the diagnostic accuracy. Therefore, this systematic review and meta-analysis aimed to determine the pooled global sensitivity and specificity of the rk-39 test and to evaluate if there is a difference between the different parts of the world.
METHODS
A systematic review and meta-analysis have been conducted on the diagnostic accuracy of dermoscopy. After setting eligibility criteria, literature was searched in four databases and one searching engine. Articles were screened, critically appraised, and extracted independently by two reviewers, and any disagreements were resolved with the involvement of a third person. The quality of the included studies had been assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS 2) tool. Pooled sensitivity and specificity were determined by bivariate random effect analysis. Heterogeneity was assessed by Higgins's I2, and when it was present, mitigation was conducted by using sensitivity analysis.
RESULT
A total of 409 studies were identified, and finally 18 articles were eligible for the review with a total sample size of 5, 253. The bivariate random effect meta-analysis of the 7 diagnostic accuracy studies showed a pooled sensitivity of 0.89 (0.76-0.95) and specificity of 0.86 (0.72-0.94). The +LR was 6.32 (95% CI: 2.85-14.02), the-LR was 0.13 (95% CI: 0.06-0.30), and the diagnostic odds ratio (DOR) was 47.8 (95% CI: 11.3-203.2). Abdel-Latif (2018) was both an outlier and influential for sensitivity, and Walter (2011) was both an outlier and influential for specificity, and removing them from sensitivity and specificity, respectively, was beneficial for reducing the heterogeneity.
CONCLUSION
Rk-39 is found to have highly accurate measures in the diagnosis of visceral leishmaniasis. Both sensitivity and specificity were found to be highly accurate in the diagnosis of leishmaniasis, with a pooled sensitivity of 0.91 (0.88-0.93) and a pooled specificity of 0.89 (0.85-0.91).
ETHICAL CONSIDERATION
As we will use secondary data for the systematic review and meta-analysis, ethical concerns are not necessary.
Topics: Humans; Leishmaniasis, Visceral; Odds Ratio; Serologic Tests
PubMed: 38446789
DOI: 10.1371/journal.pntd.0011938 -
Bulletin of the World Health... Mar 2024To explore the impact of mosquito collection methods, sampling intensity and target genus on molecular xenomonitoring detection of parasites causing lymphatic filariasis. (Review)
Review
OBJECTIVE
To explore the impact of mosquito collection methods, sampling intensity and target genus on molecular xenomonitoring detection of parasites causing lymphatic filariasis.
METHODS
We systematically searched five databases for studies that used two or more collection strategies for sampling wild mosquitoes, and employed molecular methods to assess the molecular xenomonitoring prevalence of parasites responsible for lymphatic filariasis. We performed generic inverse variance meta-analyses and explored sources of heterogeneity using subgroup analyses. We assessed methodological quality and certainty of evidence.
FINDINGS
We identified 25 eligible studies, with 172 083 mosquitoes analysed. We observed significantly higher molecular xenomonitoring prevalence with collection methods that target bloodfed mosquitoes compared to methods that target unfed mosquitoes (prevalence ratio: 3.53; 95% confidence interval, CI: 1.52-8.24), but no significant difference compared with gravid collection methods (prevalence ratio: 1.54; 95% CI: 0.46-5.16). Regarding genus, we observed significantly higher molecular xenomonitoring prevalence for anopheline mosquitoes compared to culicine mosquitoes in areas where species are the primary vector (prevalence ratio: 6.91; 95% CI: 1.73-27.52). One study provided evidence that reducing the number of sampling sites did not significantly affect molecular xenomonitoring prevalence. Evidence of differences in molecular xenomonitoring prevalence between sampling strategies was considered to be of low certainty, due partly to inherent limitations of observational studies that were not explicitly designed for these comparisons.
CONCLUSION
The choice of sampling strategy can significantly affect molecular xenomonitoring results. Further research is needed to inform the optimum strategy in light of logistical constraints and epidemiological contexts.
Topics: Humans; Animals; Elephantiasis, Filarial; Wuchereria bancrofti; Prevalence; Mosquito Vectors; Anopheles
PubMed: 38420575
DOI: 10.2471/BLT.23.290424 -
Microorganisms Jan 2024Febrile neutropenia (FN) is a complication of hematologic malignancy therapy. An early diagnosis would allow optimization of antimicrobials. The F-FDG-PET-CT may be... (Review)
Review
Febrile neutropenia (FN) is a complication of hematologic malignancy therapy. An early diagnosis would allow optimization of antimicrobials. The F-FDG-PET-CT may be useful; however, its role is not well established. We analyzed retrospectively patients with hematological malignancies who underwent F-FDG-PET-CT as part of FN management in our university hospital and compared with conventional imaging. In addition, we performed a systematic review of the literature assessing the usefulness of F-FDG-PET-CT in FN. A total of 24 cases of FN underwent F-FDG-PET-CT. In addition, 92% had conventional CT. In 5/24 episodes (21%), the fever was of infectious etiology: two were bacterial, two were fungal, and one was parasitic. When compared with conventional imaging, F-FDG-PET-CT had an added value in 20 cases (83%): it diagnosed a new site of infection in 4 patients (17%), excluded infection in 16 (67%), and helped modify antimicrobials in 16 (67%). Antimicrobials could be discontinued in 10 (41.6%). We identified seven publications of low quality and one randomized trial. Our results support those of the literature. The available data suggest that F-FDG-PET-CT is useful in the management of FN, especially to diagnose fungal infections and rationalize antimicrobials. This review points out the low level of evidence and indicates the gaps in knowledge.
PubMed: 38399711
DOI: 10.3390/microorganisms12020307