Malaria Journal最新文献

Background: The limited efficacy of the two recently approved malaria vaccines, RTS,S/AS01 and R21/Matrix- M™, highlights the need for alternative vaccine candidate genes. Plasmodium falciparum Reticulocyte Binding Protein Homologue 5 (Pfrh5) is a promising malaria vaccine candidate, given its limited polymorphism, its essential role in parasite survival, a lack of immune selection pressure and higher efficacy against multiple parasites strains. This study evaluated the genetic diversity of Pfrh5 gene among parasites from regions with varying malaria transmission intensities in Mainland Tanzania, to generate baseline data for this potential malaria vaccine candidate.

Methods: This study utilized secondary data of 697 whole-genome sequences which were generated by the MalariaGEN Community Network. The samples which were sequenced to generated the data were collected between 2010 and 2015 from five districts within five regions of Mainland Tanzania, with varying endemicities (Morogoro-urban district in Morogoro region, Muheza in Tanga, Kigoma-Ujiji in Kigoma, Muleba in Kagera, and Nachingwea district in Lindi region). Wright's fixation index (F_ST), Wright's inbreeding coefficient (Fws), Principal component analysis (PCA), nucleotide diversity (π), haplotype network, haplotype diversity (Hd), Tajima's D, and Linkage disequilibrium (LD) were used to assess the diversity of the gene.

Results: Of the sequences used in this study, 84.5% (n = 589/697) passed quality control and 313 (53.1%) were monoclonal (contained infections from a single strain of P. falciparum) and were used for haplotype diversity and haplotype network analysis. High within-host diversity (Fws < 0.95) was reported in Kigoma-Ujiji (60.7%), Morogoro-urban (53.1%), and Nachingwea (50.8%), while Muleba (53.9%) and Muheza (61.6%) had low within-host diversity (Fws ≥ 0.95). PCA did not show any population structure and the mean F_ST value was 0.015. Low nucleotide diversity values were observed across the study sites (mean π = 0.00056). A total of 27 haplotypes were observed among the 313 monoclonal samples and under-fives exhibited higher haplotype counts. The Pf3D7 was detected as Hap_1, which occurred in 16/313 (5.1%) monoclonal sequences. Negative Tajima's D values were observed among the parasite populations in all the study sites.

Conclusion: Low levels of polymorphism in the pfrh5 gene were observed based on low nucleotide and haplotype diversity, a lack of population structure and negative Tajima's D values. This study provides essential data on the diversity of the Pfrh5 gene indicating that it can be considered in the development of the next generation malaria vaccines. Robust and intensive studies of this and other candidate genes are crucial to support the prioritization of the Pfrh5 gene for potential inclusion in a broadly cross-protective malaria vaccine.

Background: The World Health Organization conditionally recommends reactive drug administration to reduce malaria transmission in settings approaching elimination. However, few studies have evaluated the impact of reactive focal drug administration (rFDA) in sub-Saharan Africa, and none have evaluated it under programmatic conditions. In 2016, Senegal's national malaria control programme introduced rFDA, the presumptive treatment of compound members of a person with confirmed malaria, and reactive mass focal drug administration (rMFDA), an expanded effort including neighbouring compounds during an outbreak, in 10 low transmission districts in the north of the country. This evaluation sought to measure the impact of rFDA and rMFDA on malaria incidence.

Methods: An interrupted time series analysis was conducted with routine surveillance data on health post-level monthly confirmed malaria case counts from the District Health Information Software (DHIS2). The study evaluated the change in incidence following rFDA and rMFDA rollout (level change), which ranged from August 2016 to November 2019, and monthly thereafter (trend change), using an adjusted negative binomial regression model with data from January 2015 through January 2020. The model was used to estimate the number of cases averted via a counterfactual simulation.

Results: No incidence rate reductions were estimated immediately following rollout (level change: incidence rate ratio (IRR) = 1.00, 95% credible interval (CI) = 0.76, 1.33). However, rFDA and rMFDA were associated with a 4% monthly decline in incidence relative to the baseline trend (trend change: IRR = 0.96, 95% CI = 0.95, 0.98). Over the study period, RFDA and rMFDA were estimated to avert 2,070 (95% CI = 577, 4,367) of 4,108 (95% CI = 2,620, 6,425) malaria cases.

Conclusions: RFDA and rMFDA were associated with reduced malaria incidence in northern Senegal, supporting their use in malaria control in very low transmission areas. However, additional strategies are likely needed to achieve elimination in this setting.

Background: The negative impact of COVID-19 pandemic on healthcare service utilization has been reported in several countries. In Gabon, data on the preparedness for future pandemic are lacking. The aim of the present study was to assess the trends of hospital attendance, malaria and self-medication prevalences as well as ITN use before and during Covid-19 first epidemic waves in a paediatric wards of a sentinel site for malaria surveillance, in Libreville, Gabon.

Methods: This was a retrospective descriptive and hospital-based survey which was conducted at the Regional Hospital of Melen Estuaire (RHME). Census of files of patients below 18 years of age attending for fever management with a result of malaria biological diagnosis from January 2018 to December 2022 was conducted. Comparison of the prevalence of microscopic malaria, ITN use, self-medication and the fever duration prior the screening before and after year 2020 was performed using bivariate and multivariate analysis.

Results: Overall, 14428 febrile participants were screened for malaria. A 15% increase in the number of febrile patients was observed between 2019 and 2020 while this rate was above 100% in 2021 and 2022. The frequency of self-medication significantly doubled in 2020 and 2021 compared to the pre-COVID-19 period (p < 0.01). Previous self-medication was more common during the COVID-19 period compared to the COVID-19 one (aOR = 2.15 [1.91-2.42]) (p < 0.01). Among the 7259 (51.2%) patients screened after 3 days of fever onset, self-anti-malarial treatment was reported for 17.5% of them in 2019 and for more than 30% of them from 2020: 33.3% in 2020, 35.0% in 2021 and 32.3% in 2022 (p < 0.01). The median of fever duration was significantly higher in the group of participants with a previous self-medication (p < 0.01). Positive blood smears frequency was higher in the COVID-19 period (35.6%; n = 3876/10868) compared to the pre-COVID-19 period (23.6%) (OR = 1.79[1.59-2.02], (p < 0.01).

Conclusion: Malaria prevalence and care-seeking behaviours for fever management in children significantly changed during the COVID-19 epidemic phase and subsequent years in the main malaria sentinel surveillance site of Gabon.

Background: Informal Healthcare Providers (IHCPs), including Proprietary Patent Medicine Vendors (PPMVs), drug peddlers, traditional healers, and herbal drug sellers are often the first choice for malaria treatment, especially in urban slums. Unplanned urbanization significantly impacts malaria transmission by creating cities with inadequate safety nets and healthcare access, increasing reliance on IHCPs. While the World Health Organization recognizes IHCP's crucial role and emphasizes integrating them into formal healthcare for improved malaria care, they lack requisite training in malaria management and operate outside official regulations, raising concerns about the quality of care they provide. Understanding IHCPs' perceptions and practices is essential for their proper integration. This study explored the perceived malaria burden, IHCPs' competence in malaria treatment, and reasons for visiting IHCPs in various urban settlements from both community member and provider perspectives.

Methods: This qualitative cross-sectional study was carried out in Ibadan and Kano metropolises. Eighteen Focus Group Discussions among 157 adult community members and twelve Key-Informant Interviews among PPMVs, drug peddlers, traditional healers and herbal drug sellers were conducted in these cities. Participants were drawn purposively from settlements-designated as formal, informal, and slum based on local definitions-in selected wards within the cities. Data were collected using pre-tested guides and analysed thematically.

Results: This study reveals that malaria remains a significant health problem in these Nigerian cities. Patronage of IHCPs generally is driven by affordable treatment, perceived mildness of illness, and access to credit facilities. However, cultural belief was key to patronage of traditional healers and herbal drug sellers, largely among informal and slum residents. Furthermore, while IHCPs had a strong perceived competence in managing malaria cases, inadequate diagnosis and treatment were standard practices.

Conclusions: IHCPs remain consistently patronized across urban settlements. IHCPs are continuously patronized in all urban settlement. Educating and equipping IHCPs with diagnostic tools, enhancing access to affordable healthcare, and raising public awareness is crucial for proper malaria management and promoting collaborations with formal healthcare providers.

Background: Malaria remains a leading cause of death worldwide, claiming over 600,000 lives each year. Over 90% of these deaths, mostly among children under 5 years, occur in sub-Saharan Africa and are caused by Plasmodium falciparum. The merozoites stage of the parasite, crucial for asexual development invade erythrocytes through ligand-receptor interactions. Erythrocyte binding antigen (EBA)-175 is one of the key ligands facilitating invasion via interaction with glycoprotein A (GpA) receptors on the erythrocytes. EBA-175 is known to exist in two dimorphic allelic (F and C) forms with each found to infer different virulence. There is paucity of data on the prevalence of these alleles and their epidemiology in the Ghanaian malaria landscape and hence this study.

Methods: Parasite gDNA was extracted from archived Dried Blood Spots (DBS) prepared from 700 confirmed malaria-infected individuals and analysed for P. falciparum EBA-175 dimorphism. Selective eba-175 gene amplification via nested PCR and allele scoring using agarose gel electrophoresis for F, C and F/C alleles.

Results: Of the total 632 successfully genotyped samples, prevalence of F, C, and F/C allelic forms were 61.2% (n = 387), 20.7% (n = 131), and 18.0% (n = 114), respectively. Seasonality analysis did not reveal a statistically significant difference in the prevalence of dimorphic forms between the wet (n = 475) and dry (n = 157) seasons (p = 0.051). The prevalence ratio (wet/dry) for C, F and F/C were determined to be 1.0, 1.1 and 1.4, respectively. Between 2019 and 2022, the prevalence of the alleles changed significantly (χ² = 6.5427, p = 0.03). Geometric mean parasite density for the C, F, and F/C alleles were 21,477.1 [95%CI 15,749.2 - 29,288.1], 18,308.0 [95%CI 15,149.9-22,124.5] and 22,690.4[95% CI 16,891.9-30,479.2], respectively.

Conclusion: The F-allele was the most prevalent form across all age groups, followed by the C allele and mixed F/C alleles. No significant difference in allele prevalence was observed between the high malaria season (wet) and low malaria season (dry). However, a statistically significant difference in the temporal prevalence of pure alleles (F & C) between two time points was observed. The current study adds to the existing body of knowledge on eba-175 allelic dimorphism and highlights the co-circulation of alleles in high malaria endemic areas in Ghana.

Background: Congenital malaria remains a significant public health challenge in Nigeria, particularly in regions with high malaria endemicity. The increased vertical transmission of malaria is partly associated with the high susceptibility of women to malaria during pregnancy. This systematic review aimed to assess the prevalence, characteristics, and treatment outcomes of congenital malaria in Nigeria.

Methods: Twelve studies were included in this review. Studies were retrieved from multiple electronic databases such as PubMed, EMBASE, Google Scholar, Scopus, Web of Science, African Journals Online (AJOL), and Cochrane Library and subjected to a multistage screening per established eligibility criteria. The study was registered with PROSPERO and was conducted per PRSIMA-established guidelines. Quality assessment of included studies was done using the Critical Appraisal Skills Programme (CASP) framework, while a narrative synthesis synthesized and summarized extracted data.

Results: The prevalence of congenital malaria in Nigeria ranged from as low as 5.1% to as high as 96.3%. Clinical manifestations were often non-specific, with fever being the most common symptom. Treatment regimens included a variety of antimalarial drugs, such as chloroquine, sulfadoxine-pyrimethamine, amodiaquine, quinine, and artemisinin-based combination therapy. While treatment outcomes were generally positive, some studies reported complications and deaths.

Conclusions: The findings highlight the need for improved diagnostic tools, standardized treatment protocols, and targeted interventions in high-burden areas. Further research is required to investigate the long-term health outcomes of neonates with congenital malaria and to evaluate the effectiveness of different treatment strategies. By addressing these gaps, effective prevention and management strategies can be developed to reduce the burden of congenital malaria in Nigeria.

Background: Synergists reduce insecticide metabolism in mosquitoes by competing with insecticides for the active sites of metabolic enzymes, such as cytochrome P450s (CYPs). This increases the availability of the insecticide at its specific target site. The combination of both insecticides and synergists increases the toxicity of the mixture. Given the demonstrated resistance to the classical insecticides in numerous Anopheles spp., the use of synergists is becoming increasingly pertinent. Tropical plants synthesize diverse phytochemicals, presenting a repository of potential synergists.

Methods: Extracts prepared from medicinal plants found in Jamaica were screened against recombinant Anopheles gambiae CYP6M2 and CYP6P3, and Anopheles funestus CYP6P9a, CYPs associated with anopheline resistance to pyrethroids and several other insecticide classes. The toxicity of these extracts alone or as synergists, was evaluated using bottle bioassays with the insecticide permethrin. RNA sequencing and in silico modelling were used to determine the mode of action of the extracts.

Results: Aqueous extracts of Piper amalago var. amalago inhibited CYP6P9a, CYP6M2, and CYP6P3 with IC₅₀s of 2.61 ± 0.17, 4.3 ± 0.42, and 5.84 ± 0.42 μg/ml, respectively, while extracts of Kalanchoe pinnata, inhibited CYP6M2 with an IC₅₀ of 3.52 ± 0.68 μg/ml. Ethanol extracts of P. amalago var. amalago and K. pinnata displayed dose-dependent insecticidal activity against An. gambiae, with LD₅₀s of 368.42 and 282.37 ng/mosquito, respectively. Additionally, An. gambiae pretreated with K. pinnata (dose: 1.43 μg/mosquito) demonstrated increased susceptibility (83.19 ± 6.14%) to permethrin in a bottle bioassay at 30 min compared to the permethrin only treatment (0% mortality). RNA sequencing demonstrated gene modulation for CYP genes in anopheline mosquitoes exposed to 715 ng of ethanolic plant extract at 24 h. In silico modelling showed good binding affinity between CYPs and the plants' secondary metabolites.

Conclusion: This study demonstrates that extracts from P. amalago var. amalago and K. pinnata, with inhibitory properties, IC₅₀ < 6.95 μg/ml, against recombinant anopheline CYPs may be developed as natural synergists against anopheline mosquitoes. Novel synergists can help to overcome metabolic resistance to insecticides, which is increasingly reported in malaria vectors.

Background: Despite significant distribution of insecticide-treated net (ITNs) by the Government of Uganda to refugees, malaria is major cause of mortality and morbidity among children under five years in refugee settlements. This highlights the persistent challenges and complexities surrounding malaria control and prevention efforts in these settings. Studies that focus on the determinants of ITN utilization among children under five years in refugee settlements in Uganda are not available. Using the 2018-2019 Uganda's Malaria Indicator Survey (UMIS) data, analysis of the individual and household factors associated with utilization of ITN among children under five in refugee settlements of Uganda was conducted.

Methods: This study focused on 589 children under five staying in refugee settlements located in Uganda. The extracted variables from the UMIS included social-economic factors associated with ITN utilization. Descriptive analysis was performed to generate summarized statistics, while inferential statistics by way of bivariate analysis were performed to assess the association between the outcome and the independent variables using the chi-square test, and multivariable logistic regression modelling to assess the magnitude of the associations after controlling for other covariates. All analyses considered the survey sampling design and sampling weights, and are conducted in Stata version 18.

Results: The odds of children sleeping under ITN were higher if their mothers had secondary and higher education (8.1 times) as well as primary education (1.5 times). The odds of children sleeping under ITN reduced by 50% if their mothers were pregnant. Interestingly, the odds of children sleeping under ITN were 70% lower if their mothers knew that 'not sleeping in nets' caused malaria. Mothers who were exposed to malaria messages had lower odds of their children sleeping under ITNs.

Conclusions: The results highlight areas of intervention that can increase ITN use in refugee settlements of Uganda. Improving access to education for mothers, providing targeted health education on the importance of ITN, dispelling misconceptions about malaria transmission, facilitating the proper installation of ITNs among others, can all contribute to increased ITN utilization among children under five.

Background: The Plasmodium proteasome emerges as a promising target for anti-malarial drug development due to its potential activity against multiple life cycle stages.

Methods: In this investigation, a comparative analysis was conducted on the structural features of the β5 subunit in the 20S proteasomes of both Plasmodium and humans.

Results: The findings underscore the structural diversity inherent in both proteasomes. The human proteasome β5 subunit reveals a composition rich in β-sheets and adopts a more compact conformation. This structural arrangement limits the ligand binding pocket's capacity to accommodate only small compounds effectively. In contrast, the Plasmodium β5 subunit exhibits a higher prevalence of loop structures, creating a more open and flexible binding pocket. This unique structural characteristic enables the binding of a larger and more diverse array of compounds.

Conclusion: The discernible structural contrast between the human and Plasmodium proteasome β5 subunits holds promise for the identification of Plasmodium-selective compounds. The ability of the Plasmodium proteasome to accommodate a broader range of compounds due to its distinctive structural features opens avenues for drug screening to intending to develop selective anti-malarial agents. This study contributes valuable insights into the structural basis for targeting the Plasmodium proteasome and paves the way for the rational design of compounds with enhanced specificity and efficacy against malaria.

Background: Imported malaria from southern Mozambique drives low levels of disease transmission in KwaZulu-Natal, South Africa. Therefore, the South African Department of Health funded implementation of indoor residual spraying (IRS) in Mozambiquan districts identified as sources of malaria infection for border communities in KwaZulu-Natal. IRS was initiated in districts of Guija, Inharrime, Panda and Zavala. To determine impact of spraying on malaria transmission in these districts, data relating to incidence and prevalence was collected before spraying (2018) and before the second round of spraying was completed (2023). Implementation of IRS was also monitored to ensure optimal spray coverage was achieved.

Methods: The study was a cross-sectional survey conducted in 6 sentinel sites in each of the four afore-mentioned districts, focusing on children 6 months to < 15 years from selected households. There was a baseline and an endline cross-sectional survey. Baseline prevalence took place during March-April 2022 whereas the endline surveys occurred during February-March 2023. One hundred and twenty children from each sentinel site were tested for malaria using rapid diagnostic tests. Monthly malaria cases were obtained from health facilities in each study district. Spray data was obtained from LSDI2 initiative who implemented IRS in the targeted districts.

Results: The study showed a definite impact of IRS on malaria prevalence in the targeted districts. Prevalence for sentinel sites in Guija district indicated that the prevalence of malaria increased slightly from baseline to endline in all sentinel sites in Guija. Overall, there was no significant change in prevalence in Zavala, from baseline to endline (p-value = 0.611). Panda's overall malaria prevalence decreased from 19.20% to 10.82% (p-value < 0.001) whereas overall prevalence in Inharrime, decreased from 27.68% to 19.50% (p-value < 0.001). Malaria prevalence in children younger than 5 years decreased significantly in all four districts. In Panda there was a decrease in numbers of males and females being infected between surveys (p < 0.001), whereas for Inharrime the decrease was significant in females (p < 0.001). High coverage with IRS (> 95%) resulted in greater population protection.

Conclusion: The study revealed that IRS implementation decreased malaria prevalence in Inharrime and Panda but not in Guija and Zavala. To ensure that cross-border movement of people does not result in increased malaria transmission, targeting areas identified as source of infection in travelers is paramount to reaching elimination.