Malaria JournalPub Date : 2024-11-29DOI: 10.1186/s12936-024-05171-y
Ashenafi Abossie, Hallelujah Getachew, Assalif Demissew, Kassahun Habtamu, Arega Tsegaye, Daibin Zhong, Xiaoming Wang, Teshome Degefa, Ming-Chieh Lee, Guofa Zhou, Christopher L King, James W Kazura, Delenasaw Yewhalaw, Guiyun Yan
{"title":"Profiling vivax malaria incidence, residual transmission, and risk factors using reactive case detection in low transmission settings of Ethiopia.","authors":"Ashenafi Abossie, Hallelujah Getachew, Assalif Demissew, Kassahun Habtamu, Arega Tsegaye, Daibin Zhong, Xiaoming Wang, Teshome Degefa, Ming-Chieh Lee, Guofa Zhou, Christopher L King, James W Kazura, Delenasaw Yewhalaw, Guiyun Yan","doi":"10.1186/s12936-024-05171-y","DOIUrl":"10.1186/s12936-024-05171-y","url":null,"abstract":"<p><strong>Background: </strong>Identification of local Plasmodium vivax transmission foci and its hidden reservoirs are crucial to eliminating residual vivax malaria transmission. This study assessed whether reactive case detection (RCD) could better identify P. vivax cases and infection incidences in Arjo-Didessa, Southwestern Ethiopia.</p><p><strong>Methods: </strong>A RCD survey was conducted from November 2019 to October 2021 in Arjo-Didessa and the surrounding vicinity in southwestern Ethiopia. RCD was performed at 0, 30, and 60 days following reports of P. vivax infections by health facilities to detect further cases and potential transmission networks. Household members of the index case and neighbours living within 200 m of the index household were screened for P. vivax. Households 200-500 m away are considered controls and were also screened for P. vivax. Plasmodium vivax was detected by microscopy, rapid diagnostic testing (RDT), and quantitative polymerase chain reaction (qPCR). Risk factors associated with vivax malaria were analysed using generalized estimating equations (GEE).</p><p><strong>Results: </strong>A total of 3303 blood samples were collected from the index (n = 427), neighbouring (n = 1626), and control (n = 1240) household in the three rounds of follow-up visits for malaria infection, the overall positivity rate of P. vivax malaria was 1.6% (95% CI 1.2-2.2%), 1.9% (95% CI 1.5-2.4), and 3.9% (95% CI 3.2-4.6%) by microscopy, RDT, and qPCR, respectively. Microscopy and RDT detected 41.5% (54 of 130) and 49.1% (64 of 130) of the qPCR-confirmed P. vivax cases, respectively. Of qPCR-positive samples, 77.7% of the total P. vivax infections circulated in the index and neighbouring households, while control households accounted for 23.3% of the infections. Of the P. vivax infections detected 81.0% (95% CI 72.9-87.1%) were asymptomatic. In this study, P. vivax infection incidence was higher in index case households (53.8 cases per 1000 person-months) and (44.0 cases per 1000 person-months) in neighbouring households compared to the control households (25.1 cases per 1000 person-months) with statistical difference (p = 0.02). In index case households, children < 5 years and school-age children were at higher risk of P. vivax infection (AOR: 6.3, 95% CI: 2.24-18.02, p = 0.001 and AOR: 2.7, 95% CI: 1.10-6.64, p = 0.029).</p><p><strong>Conclusions: </strong>This study found clustering of asymptomatic and sub-microscopic P. vivax infections in the index case household and their neighbours using RCD and molecular methods. Children under 5 years and of school age were more likely to have P. vivax infection in index households. Thus, tailored RCD approaches and targeted interventions for interrupting residual P. vivax transmission networks are needed to eliminate P. vivax malaria in low transmission settings.</p>","PeriodicalId":18317,"journal":{"name":"Malaria Journal","volume":"23 1","pages":"362"},"PeriodicalIF":2.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Malaria JournalPub Date : 2024-11-29DOI: 10.1186/s12936-024-05180-x
Eustace Bugase, Paulina Tindana
{"title":"Influence of trust on the acceptance of the RTS,S malaria vaccine in the Kassena-Nankana districts of Ghana.","authors":"Eustace Bugase, Paulina Tindana","doi":"10.1186/s12936-024-05180-x","DOIUrl":"10.1186/s12936-024-05180-x","url":null,"abstract":"<p><strong>Background: </strong>Vaccines have increasingly become some of the most effective public health tools for promoting health and reducing the burden of infectious diseases. The availability of a malaria vaccine for routine use will be a major milestone, nonetheless, trust by the public for the vaccine could pose a major challenge for its acceptance. Documented evidence such as the boycott of the oral polio vaccine in northern Nigeria and the failure of the Ebola vaccine trial in Ghana among others highlight the impact of public trust on vaccine acceptance.</p><p><strong>Methods: </strong>This is an explorative cross-sectional mixed-method study conducted in the Kassena Nankana districts. The study was conducted in the Kassena Nankana Districts between May and December 2020. A total of 390 structured questionnaires were administrated to mothers and caregivers of children under five years of age while 15 in-depth interviews were conducted with mothers and health workers. STATA software Version 16.0 was used to interpret the quantitative data, where bivariate and multivariate regression analysis was performed to determine the influence of trust on vaccine acceptance while QSR NVivo 12 software was used to code the qualitative data to aid the thematic analysis.</p><p><strong>Results: </strong>The results revealed that the level of knowledge of the RTS,S vaccine among participants was high. About 95.4% of the mothers had good knowledge of the malaria vaccine and more than half 61.2% of them got information about the vaccine from the health facility. The level of trust for the malaria vaccine was equally high with 91.4% of the mothers reporting that the vaccine treats childhood malaria. In a bivariate analysis, educational status (P = 0.013), ethnicity (P = 0.008), marital status (P = 0.041), education on the vaccine and perceived ineffectiveness P < 0.05, and trust for the malaria vaccine (P < 0.05) were found to be statistically associated with vaccine acceptance. Compared with participants who agree that vaccines are harmless to children, those who disagree were significantly less likely to accept vaccines (OR = 0.25, 95%CI [0.08, 0.83], p = 0.017). The qualitative data correspondingly revealed that mothers trusted vaccines which thus accounted for the high uptake of the malaria vaccine in the districts.</p><p><strong>Conclusion: </strong>The results of this study suggest that trust in the malaria vaccine is critical for its uptake. Therefore, efforts towards improving acceptance of the vaccine should be focused on building and sustaining trust for the vaccine among mothers and community members.</p>","PeriodicalId":18317,"journal":{"name":"Malaria Journal","volume":"23 1","pages":"365"},"PeriodicalIF":2.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Malaria JournalPub Date : 2024-11-29DOI: 10.1186/s12936-024-05131-6
Jenna Hoyt, Hellen C Barsosio, Isdorah A Odero, Benson Omondi, Florence Achieng, Simon Kariuki, Jenny Hill, Jayne Webster
{"title":"\"If they take it without knowing, they will default…\": perceptions of targeted information transfer to promote adherence to intermittent preventive treatment with dihydroartemisinin-piperaquine for the prevention of malaria in pregnancy in western Kenya.","authors":"Jenna Hoyt, Hellen C Barsosio, Isdorah A Odero, Benson Omondi, Florence Achieng, Simon Kariuki, Jenny Hill, Jayne Webster","doi":"10.1186/s12936-024-05131-6","DOIUrl":"10.1186/s12936-024-05131-6","url":null,"abstract":"<p><strong>Background: </strong>Increasing resistance to sulfadoxine-pyrimethamine (SP) threatens the effectiveness of intermittent preventive treatment (IPTp) to prevent malaria in pregnancy. Dihydroartemisinin-piperaquine (DP) is the most promising candidate to emerge from clinical trials, but requires a multi-day regimen. Despite being a single-dose regimen, coverage of IPTp-SP remains low, fuelling concerns about adherence to multi-day drug options. An implementation feasibility trial in routine antenatal care settings in western Kenya demonstrated that adherence to the multi-day DP regimen was improved when IPTp-DP was delivered with a targeted information transfer intervention that comprised healthcare provider training and communication tools to support delivery and uptake. This study explored healthcare provider and pregnant women perspectives to understand (1) how the targeted information transfer improved adherence to IPTp-DP and (2) if improved adherence to IPTp-DP influenced provider perceptions towards implementation feasibility of multi-day drug regimens for IPTp.</p><p><strong>Methods: </strong>In-depth interviews were conducted with 64 healthcare providers and 64 pregnant women, selected using a convenience sampling approach from across the three trial arms: IPTp-DP+ (with intervention), IPTp-DP, and current standard of care IPTp-SP. Transcripts from healthcare providers and pregnant women were coded in Nvivo-12 using separate a priori frameworks that included components of the consolidated framework for implementation research. Thematic analysis was used to understand how the targeted information transfer affected adherence to IPTp-DP and how concerns about adherence might influence provider perceptions towards multi-day drug regimens for IPTp.</p><p><strong>Results: </strong>Adherence to IPTp-DP doses taken at home was compromised when women experienced unpleasant side effects. Pregnant women valued being given information about IPTp-DP, including potential side effects and how to manage them. Among providers in the IPTp-DP + arm, confidence in advising women on how to manage side effects increased, and they believed this guidance improved adherence. When concerns about adherence were reduced, providers in the IPTp-DP + arm were positive about implementation feasibility, whereas providers in the IPTp-SP arm remained focused on the dosing complexities and were less convinced of the feasibility of implementing IPTp-DP.</p><p><strong>Conclusions: </strong>Healthcare provider confidence in advising women on how to minimize side effects was boosted through targeted information transfer, which was perceived to improve adherence to IPTp-DP. Policy makers are encouraged to consider supportive interventions that enhance provider confidence around adherence should they shift to multi-day drug regimens for IPTp.</p>","PeriodicalId":18317,"journal":{"name":"Malaria Journal","volume":"23 1","pages":"364"},"PeriodicalIF":2.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Malaria JournalPub Date : 2024-11-28DOI: 10.1186/s12936-024-05195-4
Chimezie Igwegbe Nzoputam, Oluwakemi Christie Ogidan, Amadou Barrow, Michael Ekholuenetale
{"title":"What do women in the highest malaria burden country know about ways to prevent malaria? A multi-level analysis of the 2021 Nigeria Malaria Indicator Survey data.","authors":"Chimezie Igwegbe Nzoputam, Oluwakemi Christie Ogidan, Amadou Barrow, Michael Ekholuenetale","doi":"10.1186/s12936-024-05195-4","DOIUrl":"10.1186/s12936-024-05195-4","url":null,"abstract":"<p><strong>Background: </strong>With Nigeria accounting for 31% of the estimated 608,000 deaths due to malaria globally, good knowledge of malaria prevention is essential for effective malaria control. The objective of this study was to examine the knowledge of malaria prevention and its associated factors among Nigerian women.</p><p><strong>Methods: </strong>This study analysed secondary data from the 2021 Nigeria Malaria Indicator Survey. The sample included 14,476 women of reproductive age (15-49 years). A multilevel multivariable logistic regression was used to examine individual, household, and community-level factors associated with having good knowledge of malaria prevention.</p><p><strong>Results: </strong>The weighted prevalence of having good knowledge of malaria prevention was 43.5% (95%CI: 41.7-45.2%). Women with secondary/higher education had 2.35 higher odds of good knowledge of malaria prevention, when compared with those with no formal/primary education (aOR = 2.35; 95% CI: 2.00-2.75). Those exposed to malaria messages had 2.62 higher odds of good knowledge of malaria prevention, when compared with no exposure to malaria messages (aOR = 2.62; 95% CI: 2.31-2.97). Women from non-poor households had 1.42 higher odds of good knowledge of malaria prevention, when compared with those from poor households (aOR = 1.42; 95% CI: 1.17-1.71). Rural dwellers had 39.0% reduction in the odds of good knowledge of malaria prevention, when compared with their urban counterparts (aOR = 0.61; 95% CI: 0.46-0.80). In addition, women from communities with high level of education (aOR = 2.24; 95%CI: 1.38-3.64), moderately exposed to malaria messages (aOR = 1.43; 95%CI: 1.08-1.88) and highly exposed to malaria messages (aOR = 1.71; 95%CI: 1.27-2.30), had higher odds of good knowledge of malaria prevention, when compared with women from communities with low education and low exposure to malaria messages, respectively.</p><p><strong>Conclusion: </strong>The knowledge of malaria prevention was found to be low. The study identified education, religion, exposure to malaria messages, wealth, region, place of residence, community-level poverty, education and exposure to malaria messages as factors associated with the knowledge of malaria prevention. Addressing these factors through targeted interventions, such as improving educational opportunities for women and enhancing media-driven public health campaigns are essential to enhancing malaria knowledge among this critical demographic group.</p>","PeriodicalId":18317,"journal":{"name":"Malaria Journal","volume":"23 1","pages":"361"},"PeriodicalIF":2.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Malaria JournalPub Date : 2024-11-27DOI: 10.1186/s12936-024-05187-4
Joshua Epuitai, Grace Ndeezi, Rose Chalo Nabirye, Lydia Kabiri, David Mukunya, Josephine Tumuhamye, Faith Oguttu, James K Tumwine
{"title":"Prevalence and factors associated with placental malaria in Lira District, Northern Uganda: a cross-sectional study.","authors":"Joshua Epuitai, Grace Ndeezi, Rose Chalo Nabirye, Lydia Kabiri, David Mukunya, Josephine Tumuhamye, Faith Oguttu, James K Tumwine","doi":"10.1186/s12936-024-05187-4","DOIUrl":"10.1186/s12936-024-05187-4","url":null,"abstract":"<p><strong>Background: </strong>Malaria has a stable perennial transmission across Uganda. Placental malaria is associated with adverse maternal, fetal, and neonatal outcomes. The factors associated with placental malaria are poorly understood in the study setting. The aim of the study was to assess the prevalence of placental malaria and to determine its associated factors among parturient women in Lira District, Uganda.</p><p><strong>Methods: </strong>This was a cross-sectional study among 366 pregnant women who delivered at Lira Regional Referral Hospital. Data were collected from December 2018 to February 2019 using an interviewer-administered questionnaire. The variables were socio-demographic, obstetric characteristics, and malaria preventive practices. Standard Diagnostic Bioline Rapid Diagnostic Tests were used to detect placental malaria present in placental blood. Microscopy was used to quantify the grade of placental malaria parasitaemia. Logistic regression was used to assess factors associated with placental malaria.</p><p><strong>Results: </strong>The mean age of the participants was 25.34 years (standard deviation [SD] 5.73). The prevalence of placental malaria was [4.4% (16/366) 95% CI (2.5 to 7.0)]. Of these, only 7/16 were positive on microscopy, with 2/7 having moderate parasitemia and 5/7 having mild parasitaemia. Women aged less than 20 years [AOR 3.48, 95% CI (1.13 to 10.72)], and those not taking iron supplements during pregnancy [AOR = 3.55, 95% CI (1.02 to 12.31)] were associated with an increased likelihood of having placental malaria.</p><p><strong>Conclusion: </strong>The prevalence of placental malaria was low in this setting. This may have reflected the low malaria transmission rates following intensive indoor residual spraying. Placental malaria infection was associated with younger age and not taking iron supplements during pregnancy. Public health measures need to scale up and emphasise adherence to malaria preventive measures during pregnancy especially among teenage mothers.</p>","PeriodicalId":18317,"journal":{"name":"Malaria Journal","volume":"23 1","pages":"360"},"PeriodicalIF":2.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Procedural legitimacy: co-developing a community agreement model for genetic approaches research to malaria control in Africa.","authors":"Naima Sykes, Jude Bigirwenkya, Isabelle Coche, Mouhammed Drabo, Divine Dzokoto, Samantha O'Loughlin, Lea Pare Toe, Alexandre Quach, Delphine Thizy","doi":"10.1186/s12936-024-05160-1","DOIUrl":"10.1186/s12936-024-05160-1","url":null,"abstract":"<p><p>With reductions in the malaria burden stalling in the past years, gene drive holds promise as a novel way of reducing disease transmission. Governance and decision-making processes are pivotal aspects of the legitimate adoption of this technology. Here, the authors explore Target Malaria's journey in developing a community agreement model for the release of non-gene drive genetically modified mosquitoes. They describe the iterative development of the model, including consultations with experts, stakeholder engagement, and alignment with principles of procedural justice. Several challenges were identified during its development, including defining communities, ensuring adequate information, consultation, monitoring, and achieving a common decision between dissenting and consenting viewpoints. They underscore the complexity of developing a legitimate model and emphasize the importance of transparency, procedural legitimacy, and adherence to ethical principles. This paper does not describe the model itself, which will be the subject of another paper. Instead it focuses on the process, to share this experience with other projects-those working with gene drive, or any other projects requiring a community-level decision-making process. The model builds on Target Malaria's experience with the release of genetically modified sterile male mosquitoes, to address the challenges posed by modified mosquitoes which are fertile and would therefore be expected to persist longer in the environment and spread further than the sterile male mosquito strains. While the level of spread and persistence of these non gene drive, but fertile, modified mosquitoes are expected to be substantially lower than those of the gene drive mosquitoes, the process is an essential advance in accommodating the broader geographical and temporal concerns associated with the more permanent spread of gene drive mosquitoes. The work described here constitutes part of the evolution of a community agreement process that could be applied to proposals for releases of gene drive mosquitoes for malaria control. In describing this process, Target Malaria hopes to contribute to the ongoing dialogue on good practices for community agreement engagement in research for genetic vector control approaches and to share the experience of building legitimacy while designing such agreement models.</p>","PeriodicalId":18317,"journal":{"name":"Malaria Journal","volume":"23 1","pages":"359"},"PeriodicalIF":2.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142730108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Malaria JournalPub Date : 2024-11-25DOI: 10.1186/s12936-024-05190-9
Chandni Hayat, Atif Kamil, Asifullah Khan, Aniqa Sayed, Kehkashan Akbar, Sahib Gul Afridi
{"title":"Genetic diversity of Plasmodium falciparum and Plasmodium vivax field isolates from the Nowshera district of Pakistan.","authors":"Chandni Hayat, Atif Kamil, Asifullah Khan, Aniqa Sayed, Kehkashan Akbar, Sahib Gul Afridi","doi":"10.1186/s12936-024-05190-9","DOIUrl":"10.1186/s12936-024-05190-9","url":null,"abstract":"<p><strong>Background: </strong>The genetic diversity of malaria parasites contributes to their ability to adapt to environmental changes, develop drug resistance and circumvent the host immune system. This study aimed to analyse the genetic diversity of the Pfmsp1 and Pfmsp2 genes in Plasmodium falciparum and the Pvmsp-3α gene in Plasmodium vivax isolates from District Nowshera in Pakistan.</p><p><strong>Methods: </strong>Blood samples from 124 consenting patients with uncomplicated malaria presenting to different hospitals from the Nowshera district were collected between March and August 2019, representing 28 P. falciparum and 96 P. vivax isolates. The genomic DNA extracted from the isolates were subjected to nested PCR and allele-specific analysis. Pvmsp-3α amplified fragments were further treated with restriction fragment length polymorphism (RFLP)-based Hha1 restriction enzyme.</p><p><strong>Results: </strong>Of the analyzed P. falciparum, 21 distinct alleles were detected, including 14 alleles for Pfmsp-1 and 7 alleles for Pfmsp-2. The sub-allelic families MAD20 (50%) of Pfmsp-1and FC27 (75%) of Pfmsp-2 were predominant. The multiplicity of infection (MOI) was calculated as 1.4 and 1.2 for Pfmsp-1 and Pfmsp-2, respectively, with an overall mean MOI of 1.34. In P. vivax, 4 allelic variants, Pvmsp-3α types A, B, C and D, were detected, while RFLP digestion of amplicons, detected 9 sub-allelic variants (A1-A4, B1, B2, C1, C2 and D1) at the Pvmsp-3α locus.</p><p><strong>Conclusion: </strong>This first ever report of molecular characterization of P. falciparum and P. vivax genotypes from District Nowshera, Pakistan reveals moderate to high allelic diversity in parasite population from District Nowshera, Pakistan.</p>","PeriodicalId":18317,"journal":{"name":"Malaria Journal","volume":"23 1","pages":"358"},"PeriodicalIF":2.4,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Malaria JournalPub Date : 2024-11-23DOI: 10.1186/s12936-024-05155-y
Gia-Bao Nguyen, Caitlin A Cooper, Olivia McWhorter, Ritu Sharma, Anne Elliot, Anthony Ruberto, Rafael Freitas, Ashutosh K Pathak, Dennis E Kyle, Steven P Maher
{"title":"Screening the Global Health Priority Box against Plasmodium berghei liver stage parasites using an inexpensive luciferase detection protocol.","authors":"Gia-Bao Nguyen, Caitlin A Cooper, Olivia McWhorter, Ritu Sharma, Anne Elliot, Anthony Ruberto, Rafael Freitas, Ashutosh K Pathak, Dennis E Kyle, Steven P Maher","doi":"10.1186/s12936-024-05155-y","DOIUrl":"10.1186/s12936-024-05155-y","url":null,"abstract":"<p><strong>Background: </strong>Malaria, a disease caused by parasites of the genus Plasmodium, continues to impact many regions globally. The rise in resistance to artemisinin-based anti-malarial drugs highlights the need for new treatments. Ideally, new anti-malarials will kill the asymptomatic liver stages as well as the symptomatic blood stages. While blood stage screening assays are routine and efficient, liver stage screening assays are more complex and costly. To decrease the cost of liver stage screening, a previously reported luciferase detection protocol requiring only common laboratory reagents was adapted for testing against luciferase-expressing Plasmodium berghei liver stage parasites.</p><p><strong>Methods: </strong>After optimizing cell lysis conditions, the concentration of reagents, and the density of host hepatocytes (HepG2), the protocol was validated with 28 legacy anti-malarials to show this simple protocol produces a stable signal useful for obtaining quality small molecule potency data similar to that obtained from a high content imaging endpoint. The protocol was then used to screen the Global Health Priority Box (GHPB) and confirm the potency of hits in dose-response assays. Selectivity was determined using a galactose-based, 72 h HepG2 assay to avoid missing mitochondrial-toxic compounds due to the Crabtree effect. Receiver-operator characteristic plots were used to retroactively characterize the screens' predictive value.</p><p><strong>Results: </strong>Optimal luciferase signal was achieved using a lower HepG2 seed density (5 × 10<sup>3</sup> cells/well of a 384-well microtitre plate) compared to many previously reported luciferase-based screens. While producing lower signal compared to a commercial alternative, this luciferase detection method was found much more stable, with a > 3 h half-life, and robust enough for producing dose-response plots with as few as 500 sporozoites/well. A screen of the GHPB resulted in 9 hits with selective activity against P. berghei liver schizonts, including MMV674132 which exhibited 30.2 nM potency. Retrospective analyses show excellent predictive value for both anti-malarial activity and cytotoxicity.</p><p><strong>Conclusions: </strong>This method is suitable for high-throughput screening at a cost nearly 20-fold less than using commercial luciferase detection kits, thereby enabling larger liver stage anti-malarial screens and hit optimization make-test cycles. Further optimization of the hits detected using this protocol is ongoing.</p>","PeriodicalId":18317,"journal":{"name":"Malaria Journal","volume":"23 1","pages":"357"},"PeriodicalIF":2.4,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Malaria JournalPub Date : 2024-11-23DOI: 10.1186/s12936-024-05161-0
Kennedy Zembere
{"title":"The potential for attractive toxic sugar baits to complement core malaria interventions strategies: the need for more evidence.","authors":"Kennedy Zembere","doi":"10.1186/s12936-024-05161-0","DOIUrl":"10.1186/s12936-024-05161-0","url":null,"abstract":"<p><p>Despite its success, the increased use of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) has contributed to the development of insecticide resistance in malaria vectors and shifts in biting patterns of the primary malaria vectors. The limitations portrayed by ITNs and IRS suggest that their use alone will not reduce malaria to elimination levels as the remaining untargeted vectors continue to sustain residual malaria transmission (RMT). RMT is a big challenge to malaria elimination because even at 100% ITN and IRS coverage, malaria transmission persists as outdoor vectors avoid or reduce contact with such interventions. With the recent increase in the outdoor biting Anopheles arabiensis (hard to control using routine tools), in most African countries, including Malawi, novel tools such as the attractive toxic sugar baits (ATSBs), targeting outdoor biting vectors in addition to controlling indoor vectors are greatly needed to complement current tools, and could facilitate sustainable malaria control. The ATSB is one potential tool that has been tested in different settings with promising results, and more trials are ongoing in other African countries. ATSBs have been attributed to reductions of mosquito densities and malaria incidence with over 80% and 50%, respectively, and there is hope that by 2025, ATSBs would be considered for the World Health Organization prequalification listing as a complementary tool for mosquito control. This article highlights evidence that ATSBs can advance malaria elimination by complementing indoor-based tools. However, for effective control programmes and elimination campaigns, the use of ATSBs alone might not be adequate, and this article recommends the combined use of ATSBs with either IRS or ITNs.</p>","PeriodicalId":18317,"journal":{"name":"Malaria Journal","volume":"23 1","pages":"356"},"PeriodicalIF":2.4,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Malaria JournalPub Date : 2024-11-22DOI: 10.1186/s12936-024-05164-x
Calder Glowac, João L Ferrão, Kelly M Searle
{"title":"The association between infrastructure damage in the aftermath of Cyclone Idai and malaria risk in Sofala Province, Mozambique: an ecological study.","authors":"Calder Glowac, João L Ferrão, Kelly M Searle","doi":"10.1186/s12936-024-05164-x","DOIUrl":"10.1186/s12936-024-05164-x","url":null,"abstract":"<p><strong>Background: </strong>In April 2019, Mozambique was hit by Cyclone Idai leaving substantial damage to infrastructure and nearly two million people in need of humanitarian assistance. Malaria risk has been associated with living in a rural setting, vicinity to water, and household structure, all factors which are impacted by severe storms. This study quantified the association between damage to infrastructure (health care facilities and schools) following Cyclone Idai and malaria outcomes: malaria incidence, severe malaria, and administration of intermittent preventative treatment in pregnancy (IPTp) in Sofala Province, Mozambique.</p><p><strong>Methods: </strong>To quantify infrastructure damage, historical satellite imagery was assessed visually using Google Earth Pro<sup>®</sup>. Damage to 66 school and 105 health centres was assessed for severity and duration. Location data was imported to QGIS and joined with district level data on malaria outcomes and environmental covariates. Multivariable Poisson regression models were used to quantify the associations between facility damage and malaria incidence and severe malaria. Generalized linear models were used to determine the association between facility damage and changes in malaria incidence and administration of IPTp from 2018 to 2019.</p><p><strong>Results: </strong>An increase in facility damage was associated with an increase in malaria incidence and severe malaria. An increase in proportion of facilities damaged by 10% was associated with a 7.3% (95% CI 6.8-7.8%) increase in malaria incidence. Risk of severe malaria was 2.16 (95% CI 1.42-3.32) times higher in districts with any damage compared to those with no damage. However, proportional facility damage was associated with decreased malaria incidence and increased access to IPTp from 2018 to 2019, but these were not statistically significant.</p><p><strong>Conclusion: </strong>An increase in proportion of facilities damaged following Cyclone Idai was associated with increased risk of malaria and severe malaria at the district level. This may be a function of decreased access to healthcare and an increased exposure to risk factors for malaria. A non-statistically significant decrease in malaria incidence was also found at the district level from 2018 to 2019, indicating that malaria may have been underreported in 2019, likely again a function of decreased access to healthcare.</p>","PeriodicalId":18317,"journal":{"name":"Malaria Journal","volume":"23 1","pages":"355"},"PeriodicalIF":2.4,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}