Nyt fra tidsskrifterne
Søgeord (malaria) valgt.
21 emner vises.
BMC Infectious Diseases, 22.10.2024
Tilføjet 22.10.2024
Abstract Malaria is a potentially fatal infective illness caused due to parasites that belong to the Plasmodium genus, which are transferred to humans with the help of the stings of affected female Anopheles mosquitoes, and it persists as a serious public wellness problem worldwide. Cordia myxa is a medicinal plant that possesses various medicinal characteristics like antimicrobial, anti-inflammation, antioxidant, and antidiabetic activities, which makes it an important natural resource for the therapy of different maladies in traditional medicine. In this investigation, a certain network pharmacology method has been utilized to identify the potent active components, possible targets as well as signaling pathways present in C. myxa in relation to malaria therapy. The active compounds were submitted to molecular docking approaches to validate their successful activity against the potential targets. The study concluded that three constituents named cosmosiin, stigmastanol, robinetin, and quercetin were highly active and could regulate the expression of Interleukin 6 (IL6) and Cysteine-aspartic acid protease 3 (CASP3), which may act as a potential therapeutic target for malaria treatment. These analyses are validated by molecular dynamics simulation which reflects on the overall structural stability of the intermolecular conformation and interactions. These results can also be witnessed in simulation-based trajectories binding free energies, which concluded the significant role of electrostatic and van der Waals energies in total intermolecular interactions. Finally, we utilized machine learning to predict the anti-malarial activity of C. myxa compounds, comparing them with approved drugs. Using the Chemprop model and MAIP predictions, we assessed ten compounds, revealing their potential as lead anti-malarial agents. This study establishes a groundwork for comprehending the function of the anti-malaria action of C. myxa.
Læs mere Tjek på PubMedPaul Taconet, Barnabas Zogo, Ludovic P. Ahoua Alou, Alphonsine Amanan Koffi, Roch Kounbobr Dabiré, Cedric Pennetier, Nicolas Moiroux
PLoS One Infectious Diseases, 22.10.2024
Tilføjet 22.10.2024
by Paul Taconet, Barnabas Zogo, Ludovic P. Ahoua Alou, Alphonsine Amanan Koffi, Roch Kounbobr Dabiré, Cedric Pennetier, Nicolas Moiroux Background Understanding how weather and landscape shape the fine-scale distribution and diversity of malaria vectors is crucial for efficient and locally tailored vector control. This study examines the meteorological and landscape determinants of (i) the spatiotemporal distribution (presence and abundance) of the major malaria vectors in the rural region of Korhogo (northern Côte d’Ivoire) and (ii) the differences in vector probability of presence, abundance, and diversity observed between that area and another rural West African region located 300 km away in Diébougou, Burkina Faso. Methods We monitored Anopheles human-biting activity in 28 villages of the Korhogo health district for 18 months (2016 to 2018), and extracted fine-scale environmental variables (meteorological and landscape) from high-resolution satellite imagery. We used a state-of-the-art statistical modeling framework to associate these data and identify environmental determinants of the presence and abundance of malaria vectors in the area. We then compared the results of this analysis with those of a similar, previously published study conducted in the Diébougou area. Results The spatiotemporal distribution of malaria vectors in the Korhogo area was highly heterogeneous and appeared to be strongly determined and constrained by meteorological conditions. Rice paddies, temporary sites filled by rainfall, rivers and riparian forests appeared to be the larval habitats of Anopheles mosquitoes. As in Diébougou, meteorological conditions (temperatures, rainfall) appeared to significantly affect all developmental stages of the mosquitoes. Additionally, ligneous savannas were associated with lower abundance of malaria vectors. Anopheles species diversity was lower in Korhogo compared to Diébougou, while biting rates were much higher. Our results suggest that these differences may be due to the more anthropized nature of the Korhogo region in comparison to Diébougou (less forested areas, more agricultural land), supporting the hypothesis of higher malaria vector densities and lower mosquito diversity in more anthropized landscapes in rural West Africa. Conclusion This study offers valuable insights into the landscape and meteorological determinants of the spatiotemporal distribution of malaria vectors in the Korhogo region and, more broadly, in rural west-Africa. The results emphasize the adverse effects of the ongoing landscape anthropization process in the sub-region, including deforestation and agricultural development, on malaria vector control.
Læs mere Tjek på PubMedMalaria Journal, 21.10.2024
Tilføjet 21.10.2024
Abstract Background Long-lasting insecticidal nets (LLINs) have been a widely used malaria prevention method for decades. In South Sudan, LLINs are typically distributed by volunteers who use paper-based systems to collect distribution data. Paper-based systems are simple to use but have a higher occurrence of data inaccuracies and can hinder the timely use of data for decision-making. In 2022, a digital tool was introduced to collect data during the LLIN campaign in Northern Bahr el Ghazal (NBeG). The tool aimed to improve the accuracy of data entry and enable data to be used in real-time for decision making during the campaign. The digital tool was developed with offline functionality and interoperability with DHIS2 tracker version 2.8 in DHIS2 version 2.38. This study assessed the usability of the tool according to user perspectives. Methods A questionnaire containing open- and closed-ended questions was conducted with users of the digital tool, supervisors and other key stakeholders in five counties of NBeG. The questionnaire was administered using Malaria Consortium’s Projects Results System Android mobile application. Usability was determined through a modified and validated System Usability Scale (SUS) approach. Results A total of 93 participants responded to the usability questionnaire. The mean (± standard deviation) usability score across 10 SUS-scoring items was 60.91 (12.87), indicating a modest level of usability. The majority of users agreed the tool was useful for managing the LLIN distribution workflow, was easy to use, reduced workload, and supported stock management and real-time campaign monitoring. There was no significant difference in the usability scores across genders, roles, and counties. Respondents with experience of both paper-based and the digital tool tended to express a preference for the digital tool over paper-based systems. The majority of respondents also reported they would recommend the digital tool to colleagues. Conclusion Digital tools are perceived to improve data collection during LLIN campaigns, even in remote areas where network coverage is challenging. Additional improvements can be implemented to overcome operational challenges and improve usability of the tool. Further study is needed to assess the impact of the digital tool on data quality and real-time data use.
Læs mere Tjek på PubMedMalaria Journal, 20.10.2024
Tilføjet 20.10.2024
Abstract Background Intense pyrethroid resistance threatens the effectiveness of the primary vector control intervention, insecticide-treated nets (ITNs), in Nigeria, the country with the largest malaria burden globally. In this study, the epidemiological and entomological impact of a new type of ITN (piperonyl-butoxide [PBO] ITNs) distributed in Ebonyi State were evaluated. The epidemiological impact was also compared to the impact of standard pyrethroid-only ITNs in Cross River State. Methods A controlled interrupted time series analysis was conducted on monthly malaria incidence data collected at the health facility level, using a multilevel mixed-effects negative binomial model. Data were analysed two years before and after the PBO ITN campaign in Ebonyi State (December 2017 to November 2021). A pre-post analysis, with no comparison group, was used to assess the impact of PBO ITNs on human biting rates and indoor resting density in Ebonyi during the high transmission season immediately before and after the PBO ITN campaign. Results In Ebonyi, PBO ITNs were associated with a 46.7% decrease (95%CI: -51.5, -40.8%; p
Læs mere Tjek på PubMedMalaria Journal, 19.10.2024
Tilføjet 19.10.2024
Abstract Background Submicroscopic Plasmodium infections can be a source of persistent malaria transmission. The aim of this study was to assess their frequency, distribution, morbidity and associated factors in a pre-elimination malaria setting in sub-Saharan Africa, Guinea-Bissau, where the Plasmodium falciparum is the predominant Plasmodium species. Methods Dried fingerprick whole blood samples from 601 participants in the 2017 national, household-based, cross-sectional survey to estimate malaria prevalence were subjected to DNA extraction. The DNA was used in nested end-point PCR assays targeting genus- and species-specific regions of the Plasmodium 18S rRNA genes. Statistical analysis of socio-demographic, clinical and molecular data was carried out using the Statistical Package for the Social Sciences, version 29. Factors associated with submicroscopic P. falciparum infections and their magnitude were sought using Chi-square test and multiple logistic regression models, respectively. Statistically significant level was considered at P-value
Læs mere Tjek på PubMedMalaria Journal, 19.10.2024
Tilføjet 19.10.2024
Abstract Malaria is preventable, but the burden of disease remains high with over 249 million cases and 608,000 deaths reported in 2022. Historically, the most important protective interventions have been vector control and chemopreventive medicines with over 50 million children receiving seasonal malaria chemoprevention in the year 2023. Two vaccines are approved and starting to be deployed, bringing additional protection for children up to 36 months. However, the impact of these currently available tools is somewhat limited on various fronts. Vaccines exhibit partial efficacy, are relatively costly, and not accessible in all settings. The challenges encountered with chemoprevention are barriers to acceptability and feasibility, including frequency of dosing, and the lack of options in the first trimester of pregnancy and for women living with HIV. Also, the emergence of resistance against chemopreventive medicines is concerning. To address these limitations, a target product profile (TPP) is proposed as a road map to guide innovation and to boost the quest for novel chemopreventive alternatives. This TPP describes the ideal product attributes, while acknowledging potential trade-offs that may be needed. Critically, it considers the target populations most at risk; primarily infants, children, and pregnant women. Malaria control and elimination requires appropriate chemoprevention, not only in areas of high endemicity and transmission, but also in lower transmission areas where immunity is declining, as well as for travellers from areas where malaria has been eliminated. New medicines should show acceptable safety and tolerability, with high and long protective efficacy. Formulations and costs need to support operational adherence, access, and effectiveness. Next generation long-acting oral and injectable drugs are likely to constitute the backbone of malaria prevention. Therefore, the perspectives of front-line experts in malaria prevention, researchers, and those involved in drug development are captured in the TPP. This inclusive approach aims at concentrating efforts and aligning responses across the community to develop new and transformative medicines.
Læs mere Tjek på PubMedMalaria Journal, 19.10.2024
Tilføjet 19.10.2024
Abstract Background Peru is a low-endemic transmission area for malaria, where the majority (84%) of incident malaria cases are localized to the department of Loreto, which is composed of several geographically isolated rural communities. Recent intervention efforts targeting at-risk Indigenous populations that live in riverine communities in Loreto place emphasis on preventive behaviours to decrease transmission. However, malaria related behaviour change is often dependent upon local knowledge, beliefs, and practices, especially in areas where malaria is viewed an embedded and unavoidable aspect of life. Methods This exploratory case study used semi-structured interviews conducted in Spanish between February and March of 2019 to examine the knowledge, attitudes, and practices related to malaria prevention among the Indigenous Maijuna people of Sucusari, Loreto, Peru. Participants who consented were also administered a rapid diagnostic test (RDT) upon the time of interview. Results A total of 33 community members were interviewed, and 31 were tested via malaria rapid diagnostic tests, with RDT filter paper subsequently tested using PCR. All test results were negative for malaria. Themes that emerged included: varying knowledge of methods to prevent malaria, reports of observed changes in malaria incidence over time, confusion surrounding malaria transmission, treatment-seeking as a common behaviour, the belief that medications are effective, and the acceptance of bed nets which were viewed as a lifestyle norm. Conclusion These shared narratives should be used as a foundation for further studies and health interventions among communities in the Peruvian Amazon with limited access to health services where culturally resonant, community-based health programming is essential to improving health. Takeaways regarding confusion surrounding malaria transmission should also be considered.
Læs mere Tjek på PubMedChew, R., Wynberg, E., Liverani, M., Rekol, H., Nguon, C., Dysoley, L., Vanna, M., Callery, J. J., Mishra, A., Adhikari, B., Tripura, R., Chandna, A., Fegan, G., Waithira, N., Maude, R. J., Day, N. P. J., Peto, T. J., Lubell, Y.
BMJ Open, 19.10.2024
Tilføjet 19.10.2024
IntroductionAcute febrile illness (AFI), traditionally attributed to malaria, is a common reason for seeking primary healthcare in rural South and Southeast Asia. However, malaria transmission has declined while health workers are often poorly equipped to manage non-malarial AFIs. This results in indiscriminate antibiotic prescribing and care escalation, which promotes antibiotic resistance and may increase healthcare costs. To address this problem, an electronic clinical decision support algorithm (eCDSA) called ‘Electronic clinical Decision support for Acute fever Management (EDAM)’ has been developed for primary health workers which integrates clinical, epidemiological and vital sign data with simple point-of-care tests to produce a diagnosis and management plan. Methods and analysisThis is a pragmatic cluster-randomised trial aiming to assess the effect of EDAM and related training on antibiotic prescribing rates in rural Cambodian primary health centres (PHCs) as the primary outcome, along with a range of secondary outcomes including safety. Patients with AFI are eligible for recruitment if they are aged ≥1 year. A cluster is defined as a PHC and PHCs will be randomised to control (standard of care) and intervention (EDAM and associated training) arms, with 15 PHCs per arm. Patients will be followed up after 7 days to ascertain the safety profile of EDAM. Each PHC will recruit 152 patients (total 4560), based on a baseline antibiotic prescription rate of 25% and expected reduction to 17.5% with EDAM. Ethics and disseminationResults will be published in international peer-reviewed journals to inform the design of future versions of EDAM and of future trials of similar eCDSAs and other digital health interventions targeted towards rural populations. This study was approved by the Oxford University Tropical Research Ethics Committee (550-23) and the Cambodian National Ethics Committee for Health Research (395-NECHR). Trial registration numberInternational Standard Randomized Controlled Trial Number Registry (ISRCTN15157105).
Læs mere Tjek på PubMedBMC Infectious Diseases, 19.10.2024
Tilføjet 19.10.2024
Abstract Malaria is a potentially fatal infective illness caused due to parasites that belong to the Plasmodium genus, which are transferred to humans with the help of the stings of affected female Anopheles mosquitoes, and it persists as a serious public wellness problem worldwide. Cordia myxa is a medicinal plant that possesses various medicinal characteristics like antimicrobial, anti-inflammation, antioxidant, and antidiabetic activities, which makes it an important natural resource for the therapy of different maladies in traditional medicine. In this investigation, a certain network pharmacology method has been utilized to identify the potent active components, possible targets as well as signaling pathways present in C. myxa in relation to malaria therapy. The active compounds were submitted to molecular docking approaches to validate their successful activity against the potential targets. The study concluded that three constituents named cosmosiin, stigmastanol, robinetin, and quercetin were highly active and could regulate the expression of Interleukin 6 (IL6) and Cysteine-aspartic acid protease 3 (CASP3), which may act as a potential therapeutic target for malaria treatment. These analyses are validated by molecular dynamics simulation which reflects on the overall structural stability of the intermolecular conformation and interactions. These results can also be witnessed in simulation-based trajectories binding free energies, which concluded the significant role of electrostatic and van der Waals energies in total intermolecular interactions. Finally, we utilized machine learning to predict the anti-malarial activity of C. myxa compounds, comparing them with approved drugs. Using the Chemprop model and MAIP predictions, we assessed ten compounds, revealing their potential as lead anti-malarial agents. This study establishes a groundwork for comprehending the function of the anti-malaria action of C. myxa.
Læs mere Tjek på PubMedMalaria Journal, 18.10.2024
Tilføjet 18.10.2024
Abstract Background Despite the application of various tools for the control of vectors of Plasmodium falciparum, malaria remains the major killer disease in sub-Saharan Africa accounting for up to 90% of deaths due to the disease. Due to limitations of the useage of chemical insecticides such as resistance, negative impact on the environment and to nontarget organisms, the World Health Organization (WHO) requires that affected countries find alternative vector control tools. This study evaluated the effectiveness of ( +)-usnic acid (UA) as an insecticide through oral administration to male and female Anopheles gambiae as an alternative or additional active ingredient to be used in toxic sugar bait. Methods ( +)-usnic acid was diluted using acetone at 5, 10, and 15 mg/ml concentrations in three replicates. A 5 ml mixture of 2% food dye and 10% sugar using chlorine-free water mixed with the dilutions of the ( +)-usnic acid and negative control was made containing 2% food dye and 10% sugar solution. The preparations were soaked on a ball of cotton wool and placed over the net of a cup. 5 male and 5 non-blood-fed female newly hatched starved An. gambiae Kisumu strain were introduced together into a cup and monitored for knockdown and mortalities after 4, 24 48, and 72 h. The data were analysed using a multiple linear regression model using the lm function, a base R function and a posthoc test were conducted on the significant main effects and interaction terms using the emmeans function from the emmeans R package. All analyses were performed in RStudio using base R (version 4.3.3). Results There was high mortality of both male and female An. gambiae after ingestion of the toxic sugar bait. 15 mg/ml usnic acid caused the highest mortality (50%) within the first 4 h compared to 5 and 10 mg/ml ( +)-UA. There was a decline in the mortality rate with increased exposure time from 24 to 72 h, however, there was a significant difference in mortality at 5, 10 and 15 mg/ml. Acute toxicity was associated with ingestion of 15 mg/ml after 24 h. 72 h post-mortality was lower in all concentrations than in the control. High mortality was observed among females over the first 4 h (60%) compared to males (40%) due to higher feeding rate of the toxic agent. The proportion of dead males and females was equal after 24 h while after 48 h, the proportion of dead males was high.There was a significantly lower mortality rate after 72 h for both males and females (0 to 13.3%). Compared to all the treatments, high mortality of males was observed. Conclusions The results of this study indicate that ( +)-UA when administered as oral sugar bait to An. gambiae has insecticidal properties and is a suitable ingredient to be used as a toxic agent in the novel attractive toxic sugar bait for the control of malaria vectors. ( +)-UA may be an alternative active ingredient as toxic bait in the effort to reduce and eliminate the transmission of Plasmodium falciparum in Africa.
Læs mere Tjek på PubMedMalaria Journal, 18.10.2024
Tilføjet 18.10.2024
Abstract Background Malaria is an infectious disease caused by the Plasmodium species and is a global burden. When not treated correctly, it can reemerge as a relapse or recrudescence. Malaria relapse cases can contribute to maintaining active transmission chains and can influence the patient to develop severe malaria, potentially leading to hospitalization or death. The objective of this study is to estimate the number of malaria relapse cases in the extra-Amazon region of Brazil and to investigate the associated factors. Methods This is a case–control study that analyses malaria infections caused by Plasmodium vivax, as reported in Notifiable Diseases Information System (Sinan) for the Brazilian extra-Amazon region (an area not endemic for the disease) from 2008 to 2019. For the identification of relapse cases, deduplication record linkage processes in R software were used. Malaria relapses were defined as the case group, and new malaria infections were defined as the control group. Logistic regression models were used to assess associated factors. Results Of the 711 malaria relapses, 589 (82.8%) were first relapses. Most relapses (71.6%) occurred between 30 and 120 days after the previous infection. Malaria relapses are spread throughout the extra-Amazon region, with a higher concentration near big cities. Driver occupation was found to be a common risk factor compared to other occupations, along with asymptomatic individuals. Other associated factors were: being infected in the Brazilian Amazon region, having follow-ups for malaria relapses, and having parasite density of the previous infection higher than 10,000 parasites per mm3. Conclusions This study provides evidence that allows malaria health surveillance services to direct their efforts to monitor cases of malaria in the highest risk segments identified in this study, particularly in the period between 30 and 120 days after being infected and treated. Relapses were associated to driver occupation, absence of symptoms, infection in endemic areas of Brazil, being detected through active surveillance or routine follow-up actions, and with parasitaemia greater than 10,000 parasites per mm3 in the previous infection. Improving cases follow-up is essential for preventing relapses.
Læs mere Tjek på PubMedHabtu Debash, Ermiyas Alemayehu, Melaku Ashagrie Belete, Hussen Ebrahim, Ousman Mohammed, Daniel Gebretsadik, Mihret Tilahun, Agumas Shibabaw, Zewudu Mulatie, Bruktawit Eshetu, Saba Gebremichael, Alemu Gedefie
PLoS One Infectious Diseases, 18.10.2024
Tilføjet 18.10.2024
by Habtu Debash, Ermiyas Alemayehu, Melaku Ashagrie Belete, Hussen Ebrahim, Ousman Mohammed, Daniel Gebretsadik, Mihret Tilahun, Agumas Shibabaw, Zewudu Mulatie, Bruktawit Eshetu, Saba Gebremichael, Alemu Gedefie Background Malaria and undernutrition pose challenges for children in conflict-affected areas. Understanding the prevalence and risk factors for these issues in war-torn communities is important to effectively design aid efforts and select interventions. This study aimed to determine the prevalence and correlates of malaria and undernutrition among febrile children in northeast Ethiopia to help address these problems. Methods A cross-sectional study was conducted from November 2022 to January 2023. Four hundred twenty-two children were enrolled using a systematic random sampling technique. Data on associated factor variables were collected via questionnaire. Capillary blood samples were collected from each child to prepare thick and thin blood films, which were stained with Giemsa and examined microscopically. Height and weight measurements were also taken using a meter and a standard calibrated balance. The data were analyzed in SPSS 26.0 using bivariable and multivariable logistic regression to determine associations between correlates, malaria infection, and undernutrition. Statistical significance was set at p < 0.05. Results The overall malaria prevalence among screened children at temporary sites in the conflict-affected areas of Northeast Ethiopia was 65.9% (278/422). Plasmodium falciparum, P. vivax, and mixed infections accounted for 74.1%, 19.8%, and 6.1% of the cases, respectively. The presence of stagnant water (P
Læs mere Tjek på PubMedMalaria Journal, 17.10.2024
Tilføjet 17.10.2024
Abstract Background Malaria in pregnancy (MiP) is a public health concern especially for pregnant women living in slums. The World Health Organization recommends at least three doses of Sulfadoxine-Pyrimethamine (SP) to prevent MiP. In Ghana, it is recommended that pregnant women receive a minimum of five doses of the medication. This study sought to determine the level of adherence to IPT5 policy and factors associated with adherence among pregnant women in a slum community in Ghana. Methods This was a cross-sectional study involving 232 nursing mothers and four healthcare workers at the St. Martin’s Memorial Hospital, Sukura, Ghana. Sociodemographic characteristics of nursing mothers were obtained using an interview-administered questionnaire. Data on the number of SP doses and other obstetrics characteristics were collected by reviewing the antenatal record books. To obtain information about healthcare and health system factors associated with adherence to the five-dose policy, four healthcare providers were interviewed. A data extraction form was used to obtain information about the availability of SP at the facility. Results The level of adherence to IPT5 was 8.6% (20/232) (95% CI 5.0–12.3) among the participants. Only 8.4% of the participants received their first dose at 16 weeks. Respondents who began ANC in the second trimester were 81% less likely to adhere to IPT5 than those who began in the first trimester (aOR = 0.19, 95% CI 90.01–0.65, p
Læs mere Tjek på PubMedBMC Infectious Diseases, 17.10.2024
Tilføjet 17.10.2024
Abstract Background Malaria remains a significant public health concern, especially for the deadliest parasite, Plasmodium falciparum. During acute malaria, various cytokines, including osteopontin (OPN), regulate the immune response. OPN has been shown to be protective against malaria in mice. Nonetheless, its precise function and potential ability to control parasites during acute malaria in humans remain poorly understood. Results Blood samples were collected from Swedish adults with imported malaria, Ugandan children and adults with symptomatic malaria (including follow-up after 42 days), Ugandans with non-malarial fever and healthy individuals from both Uganda and Sweden. Parasitemia was determined by microscopy. Malaria-negative samples were verified by LAMP. OPN and interferon-γ (IFN- γ) levels were measured using ELISA. In children, OPN levels were significantly higher during acute infection compared to levels after 42 days, whereas Ugandan adults showed no difference. Swedish adults with imported malaria had elevated OPN levels compared to both Swedish controls and Ugandan adults with malaria. Parasitemia was significantly correlated with both OPN and IFN-γ levels across the entire cohort. While a significant correlation between OPN and IFN-γ was evident overall, it remained statistically significant only in Ugandan adults when analyzed by subgroups. This suggests that OPN is not just a general marker of inflammation but may be regulated differently during the development of malaria immunity. Conclusions In acute malaria, elevated OPN levels showed a stronger correlation with lack of immunity than age. These findings underscore the potential importance of OPN in malaria, particularly in non-immune individuals.
Læs mere Tjek på PubMedJulia Zerebinski, David F. Plaza
Trends in Parasitology, 17.10.2024
Tilføjet 17.10.2024
Recent studies by Girgis et al. and de Cesare et al. promise to advance malaria genomic surveillance using inexpensive and portable long-read amplicon-sequencing technologies. These technologies allow rapid characterization of drug-resistance markers, antigenic diversity, and diagnostic target loci from dried blood spots, providing new tools for surveillance in endemic regions and informing interventions to combat malaria more effectively.
Læs mere Tjek på PubMedRitwik Singhal, Isadora O. Prata, Victoria A. Bonnell, Manuel Llinás
Trends in Parasitology, 17.10.2024
Tilføjet 17.10.2024
The regulation of gene expression in Plasmodium spp., the causative agents of malaria, relies on precise transcriptional control. Malaria parasites encode a limited repertoire of sequence-specific transcriptional regulators dominated by the apicomplexan APETALA 2 (ApiAP2) protein family. ApiAP2 DNA-binding proteins play critical roles at all stages of the parasite life cycle. Recent studies have provided mechanistic insight into the functional roles of many ApiAP2 proteins. Two major areas that have advanced significantly are the identification of ApiAP2-containing protein complexes and the role of ApiAP2 proteins in malaria parasite sexual development. In this review, we present recent advances on the functional biology of ApiAP2 proteins and their role in regulating gene expression across the blood stages of the parasite life cycle.
Læs mere Tjek på PubMedMalaria Journal, 16.10.2024
Tilføjet 16.10.2024
Abstract Background Non-inferiority trials are recommended by the World Health Organization (WHO) to demonstrate that health products show comparable efficacy to that of existing standard of care. As part of the WHO Global Malaria Programme (GMP) process of assessment of malaria vector control products, a second-in-class insecticide-treated net (ITN) must be shown to be non-inferior to a first-in-class product based on mosquito mortality. The public health impact of the first-in-class pyrethroid-piperonyl butoxide (PBO) ITN, Olyset® Plus, has been demonstrated in epidemiological trials in areas with insecticide-resistant mosquitoes, but there is a need to determine the efficacy of other pyrethroid-PBO nets to ensure timely market availability of nets in order to increase access to ITNs. The non-inferiority of a deltamethrin-PBO ITN Yorkool® G3 was evaluated entomologically against Olyset® Plus in experimental huts in Tanzania, following WHO guidelines for non-inferiority trials. Methods The trial of the two pyrethroid-PBO ITNs was conducted in experimental huts in Lupiro, Tanzania, using a randomized 7 × 7 Latin square block design. The study ran for 49 nights in 14 huts assessing the mosquito mortality and blood-feeding of wild, free-flying, pyrethroid-resistant Anopheles arabiensis. Using the non-inferiority approach, the comparative efficacy (primary endpoint was mosquito mortality at 24 h and secondary endpoint was blood-feeding) of unwashed and 20 times field-washed pyrethroid-PBO Yorkool® G3 ITNs, were compared with the first-in-class product Olyset® Plus and against a pyrethroid-only ITN, PermaNet® 2.0 ITNs, as a standard comparator. Results The experimental hut trial demonstrated non-inferiority and superiority of Yorkool® G3 to Olyset® Plus based on mosquito mortality [51% vs. 39%, OR 1.68 (95% CI 1.50–1.88)], given that lower 95% CI exceeded 0.74 (delta of 39%) and the margin of no difference (1). Blood-feeding inhibition was high for all treated ITNs (> 90%) and Yorkool® G3 was non-inferior to Olyset® Plus [4% vs. 2%, OR 1.81 (95% CI 1.46–2.39)], given that upper 95% CI was less than 4.85 (delta of 4%). The pyrethroid-PBO ITNs were superior to the pyrethroid-only net, PermaNet® 2.0, as determined by both the proportion of mortality and blood-feeding of mosquitoes (p-value
Læs mere Tjek på PubMedBMC Infectious Diseases, 16.10.2024
Tilføjet 16.10.2024
Abstract Background Malaria remains a significant public health concern, especially for the deadliest parasite, Plasmodium falciparum. During acute malaria, various cytokines, including osteopontin (OPN), regulate the immune response. OPN has been shown to be protective against malaria in mice. Nonetheless, its precise function and potential ability to control parasites during acute malaria in humans remain poorly understood. Results Blood samples were collected from Swedish adults with imported malaria, Ugandan children and adults with symptomatic malaria (including follow-up after 42 days), Ugandans with non-malarial fever and healthy individuals from both Uganda and Sweden. Parasitemia was determined by microscopy. Malaria-negative samples were verified by LAMP. OPN and interferon-γ (IFN- γ) levels were measured using ELISA. In children, OPN levels were significantly higher during acute infection compared to levels after 42 days, whereas Ugandan adults showed no difference. Swedish adults with imported malaria had elevated OPN levels compared to both Swedish controls and Ugandan adults with malaria. Parasitemia was significantly correlated with both OPN and IFN-γ levels across the entire cohort. While a significant correlation between OPN and IFN-γ was evident overall, it remained statistically significant only in Ugandan adults when analyzed by subgroups. This suggests that OPN is not just a general marker of inflammation but may be regulated differently during the development of malaria immunity. Conclusions In acute malaria, elevated OPN levels showed a stronger correlation with lack of immunity than age. These findings underscore the potential importance of OPN in malaria, particularly in non-immune individuals.
Læs mere Tjek på PubMedN. J. WhiteK. Chotivanich1Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand2Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom3Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandFerric C. FangSunil Parikh
Clinical Microbiology Reviews, 16.10.2024
Tilføjet 16.10.2024
Malaria Journal, 16.10.2024
Tilføjet 16.10.2024
Abstract Malaria parasites are haploid within humans, but infections often contain genetically distinct groups of clonal parasites. When the per-infection number of genetically distinct clones (i.e., the multiplicity of infection, MOI) exceeds one, and per-infection genetic data are generated in bulk, important information are obfuscated. For example, the MOI, the phases of the haploid genotypes of genetically distinct clones (i.e., how the alleles concatenate into sequences), and their frequencies. This complicates many downstream analyses, including relatedness estimation. MOIs, parasite sequences, their frequencies, and degrees of relatedness are used ubiquitously in malaria studies: for example, to monitor anti-malarial drug resistance and to track changes in transmission. In this article, MrsFreqPhase methods designed to estimate statistically malaria parasite MOI, relatedness, frequency and phase are reviewed. An overview, a historical account of the literature, and a statistical description of contemporary software is provided for each method class. The article ends with a look towards future method development, needed to make best use of new data types generated by cutting-edge malaria studies reliant on MrsFreqPhase methods.
Læs mere Tjek på PubMedMalaria Journal, 16.10.2024
Tilføjet 16.10.2024
Abstract Background Healthcare providers (HCPs) practice and correct management of suspected malaria (CMSM) are central components of malaria elimination and prevention of re-establishment (POR) in countries in the elimination phase. However, knowledge of malaria surveillance systems and HCPs practices often wanes in countries aiming to eliminate malaria due to the low numbers of cases. The study aimed to implement a valid Simulated Malaria Online Tool (SMOT) for assessment HCP performance in CMSM and POR in a malaria-free area. Methods HCPs were evaluated using SMOT tool based on four criteria including presenting a suspected malaria case for detection of HCPs’ failures in recognition (a), diagnosis (b), appropriate treatment (c), and urgent reporting (d); and compared with simulated patients (SP). Multiple logistic regression analysis was carried out to estimate adjusted odds ratios (ORs) for the risk of HCPs failures. Results The overall failure proportion was 237 (83%), and the majority of failures were in recognition (a). There was no significant difference between the SMOT and SP based on all failure criteria (P > 0.05). The private clinic (93%) and the public specialized clinic (70%) had the highest and lowest failure proportions. After passing the recognition stage (a), the overall failure proportions decreased to 47.8% and 25.0% for total HCPs and infectious disease specialists, respectively. In the final analysis, private sector (AOR = 4.36: 1.25–15.2), not-specialist providers (AOR = 2.84: 1.29–6.25) and HCPs with ≥ 5 years’ experience (AOR = 2.03: 1.01–6.25) increased the risk of failure. Conclusion Findings confirmed the implementation of SMOT tool in settings where malaria transmission is low or interrupted. The tool is able to identify sub-groups of providers needing strengthening, and contributes to the prevention of malaria re-establishment.
Læs mere Tjek på PubMed