Malaria Journal最新文献

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.

Background: Foreign migrant workers from malaria-endemic regions play a critical factor in the transmission of malaria to non-endemic areas, mainly due to their mobility while seeking employment opportunities. This risk is particularly heightened in areas where malaria vectors are present.

Methods: This study aimed to investigate the malaria vectors in two sub-districts in Khon Kaen Province, known for their factory areas and the significant presence of Myanmar migrant worker communities. The collection was carried out from June 2020 to May 2021. The black light traps (BLT) operated continuously from 6:00 pm to 6:00 am (12 h) and Kelambu trap (KT) were set up from 6:00 pm to 9:00 pm, with both traps set up once a month. A total of 679 female Anopheles mosquitoes were collected near the workplaces and dormitories of these workers. Subsequently, the collected female mosquitoes underwent morphological identification using Standard Thailand keys and polymerase chain reaction analysis with rDNA ITS2 primers.

Results: Morphological identification revealed that 201 (29.6%) belonged to the Barbirostris complex. The remaining Anopheles mosquitoes are in the subgroup Cellia, comprised 437 (64.4%) Anopheles vagus, 39 (5.7%) Anopheles subpictus, and 2 (0.3%) Anopheles annularis. To distinguish the Barbirostris complex, multiplex PCR based on ITS-2 sequences was conducted. Out of the 201 specimens examined, 153 (76.1%) as Anopheles campestris, 36 (17.9%) as Anopheles wejchoochotei, and 12 (6%) as Anopheles dissidens. Additionally, the subgroup Anopheles Cellia was confirmed using specific primers based on ITS-2 sequences.

Conclusions: From the obtained results, An. campestris, An. wejchoochotei, An. vagus and An. annularis are reported as the malaria vectors in Thailand. The findings emphasized the important of addressing the presence of Anopheles malaria vectors, especially in the substantial migrant worker population originating from endemic areas. This situation raises concerns regarding the potential transmission of malaria infections to regions not traditionally affected by the disease. Epidemiological studies on malaria vectors should not solely concentrate on endemic regions but also extend to non-endemic areas because of the mobility of migrant workers throughout the country. This broader approach is crucial for implementing an effective malaria surveillance strategy.

Background: Low malaria parasitaemia is a diagnostic challenge in pregnancy, leading to false negative microscopy and rapid diagnostic test (RDT) results. However, these submicroscopic or subpatent infections could cause adverse pregnancy outcomes. Thus, evaluating the diagnostic performance of microscopy, RDT, and multiplex qPCR in pregnancy is vital for informed decisions.

Methods: A total of 835 peripheral blood and 372 placental blood samples were collected from 835 pregnant women attending first antenatal care or admitted for delivery at selected health facilities in northwest Ethiopia between November 2021 and July 2022. In multiplex qPCR, all microscopy and/or RDT positive samples were extracted and amplified individually, whereas all samples negative by both RDT and microscopy were extracted after pooling ten samples together and tested for Plasmodium genus. The diagnostic performance of microscopy, RDT, and multiplex qPCR in pregnancy was compared and evaluated against each other.

Results: Using multiplex qPCR as a reference test, microscopy had a sensitivity of 73.8% (95% confidence interval (CI): 65.9-80.7) and 62.2% (95% CI: 46.5-76.2) to detect Plasmodium parasites in peripheral and placental blood samples, respectively, with a 100% (95% CI: 98.9-100) specificity in both samples. Similarly, the RDT had a sensitivity of 67.6% (95% CI: 59.3-75.1) and a specificity of 96.5% (95% CI: 94.9-97.8) for Plasmodium infection diagnosis in peripheral blood and a sensitivity of 62.2% (95% CI: 46.5-76.2) and a specificity of 98.8% (95% CI: 96.9-99.7) in placental blood samples. Considering microscopy as a reference test, multiplex qPCR showed a sensitivity of 100% (95% CI: 96.6-100) and a specificity of 94.8% (95% CI: 93.0-96.3) to diagnose Plasmodium infections in both peripheral and placental blood samples. Pooled multiplex qPCR detected 34 peripheral and 12 placental blood Plasmodium infections from microscopy and RDT negative samples. The pooled assay obviated about half of the reactions and its testing costs. Microscopy showed almost perfect agreement (κ = 0.823) with multiplex qPCR for detecting malaria parasites in pregnancy, whereas the RDT showed a substantial agreement (κ = 0.684).

Conclusion: Multiplex qPCR had a better performance for Plasmodium infection diagnosis in pregnancy compared to microscopy and RDT. Pooled multiplex qPCR could be a sensitive and resource-efficient strategy for epidemiological surveillance of Plasmodium infections in pregnancy.

Malaria remains a significant public health challenge, particularly in low- and middle-income countries, despite ongoing efforts to eradicate the disease. Recent advancements, including the rollout of malaria vaccines, such as RTS,S/AS01 and R21/Matrix-M™, offer new avenues for prevention. However, the rise of resistance to anti-malarial medications necessitates innovative strategies. This review explores the potential integration of CRISPR/Cas9 gene drive technology with malaria vaccination efforts to enhance vector control and reduce transmission. By employing gene drive mechanisms for population suppression and replacement of malaria-transmitting Anopheles mosquitoes, combined with the immunogenic properties of vaccines, a synergistic approach can be established. This paper discussed the need for integrated strategies to address the biological complexities of malaria and socio-economic factors influencing its prevalence. Challenges such as regulatory hurdles, community acceptance, ecological impacts, and sustainable funding are examined, alongside strategies for implementation within existing malaria control programmes. This integrated approach could significantly contribute to achieving the World Health Organization's targets for malaria reduction by 2030, ultimately enhancing public health outcomes and supporting broader socio-economic development.

Background: Global progress toward malaria elimination and eradication goals has stagnated in recent years, with many African countries reporting increases in malaria morbidity and mortality. Insecticide-treated nets and indoor residual spraying are effective, but the emergence and increased intensity of insecticide resistance and the challenge of outdoor transmission are undermining their impact. New tools are needed to get back on track towards global targets. This Perspective explores the major challenges hindering wider-scale implementation of larviciding in Africa and identifies potential solutions and opportunities to overcome these barriers.

Larviciding in africa: OVERVIEW, CHALLENGES, AND SOLUTIONS: Larviciding is a valuable vector control tool with strong potential for regional scale-up. There is considerable evidence of its effectiveness, and the World Health Organization (WHO) recommends it as a supplemental intervention. However, malaria programmes hoping to implement larviciding face significant barriers, including (1) poor global technical, policy, and funding support; (2) fragmented implementation and experience; (3) high complexity of delivery and impact evaluation; and (4) limited access to the full range of WHO prequalified larvicide products. Strategic barriers related to global policy and donor hesitancy can be overcome through a coordinated demonstration of cost-effectiveness. Technological advancements and strengthened operational capacity have already overcome technical barriers related to larvicide delivery, targeting, coverage, and evaluation. Developing a Community of Practice platform for larviciding has strong potential to consolidate efforts, addressing the challenge of fragmented implementation and experience. Such a platform can serve as a resource center for African malaria programmes, collating and disseminating technical guidance, facilitating the exchange of best practices, and aiding malaria programmes and partners in designing and evaluating larviciding projects.

Conclusion: The global shift toward targeted and adaptive interventions enables the incorporation of larviciding into an expanded vector control toolbox. As more African countries implement larvicide programmes, establishing a regional Community of Practice platform for exchanging experiences and best practices is necessary to strengthen the evidence base for cost-effective implementation, advocate for support, and inform policy recommendations, thus supporting Africa's progress toward malaria elimination.

Background: Acceptability of malaria chemoprevention interventions by caregivers is crucial for overall programme success. This study assessed coverage and acceptability of Seasonal Malaria Chemoprevention (SMC) in selected communities in the Northern part of Ghana.

Methods: An analytical cross-sectional design was conducted from "July 23rd to August 4th, 2020-a 12-day period that covered 5 days of the first SMC implementation cycle and 7 days post-implementation. Using a stratified multi-stage sampling technique, a total of 495 caregivers providing care for 569 eligible children aged 3-59 months from randomly selected households in the study communities were enrolled into the study. Acceptability of SMC was assessed on a set of 19 questionnaire items-8 of the items measured caregivers' perceptions and 11 items measured children's reaction to administered medicines. Univariable and stepwise multivariable logistic regression analyses were performed to assess the predictors of acceptability of SMC at a 95% confidence interval and a p-value of 0.05.

Results: SMC coverage was 95.1% (541/569). Caregivers had a good level of knowledge of SMC (n = 475; 96.0%; 95% CI 94.2-97.7%) and a good perception of SMC (n = 471; 95.2%; 95% CI 93.3-97.0). Seven out of ten caregivers (70.9%; 95% CI 66.9-74.9%) had good acceptability of SMC. For 7 out of 28 children who did not receive the SMC intervention, their caregivers intentionally refused them the intervention. Of those that received the treatment, 17.2% (n = 85; 95%CI 13.8-20.5%) of caregivers had at least one leftover amodiaquine tablet after the third day of treatment. Caregivers who practice Christianity or Islam had better acceptability than caregivers who practice African traditional religion (p < 0.001).

Conclusion: Health authorities and stakeholders can work towards bridging the gap between knowledge and SMC treatment practices of caregivers through continuous education, adherence counseling, and effective monitoring of SMC practices in malaria-endemic countries.