2,434 results on '"Severe Malaria"'
Search Results
2. Platelet-Directed Whole Blood Transfusion Strategy for Malaria (PLATFORM)
- Author
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Johns Hopkins University, Tropical Diseases Research Centre, University of California, San Francisco, and University of Maryland
- Published
- 2024
3. Study to Compare Feasibility of 1-step Injectable Artesunate vs. Conventional 2-step Injectable Artesunate (1STEP-AS)
- Author
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Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd., University of Kinshasa, and National Institute for Medical Research, Tanzania
- Published
- 2024
4. Host Immune and Metabolic Determinants of Sexual Conversion in Plasmodium Parasites IMMETASEX (IMMETASEX)
- Author
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Instituto Nacional de Saúde, Mozambique, Clinical Research Unit of Nanoro (CRUN), Burkina Faso, Barcelona Institute for Global Health, Leiden University Medical Center, and KU Leuven
- Published
- 2024
5. Perceived barriers and opportunities for the introduction of post-discharge malaria chemoprevention (PDMC) in five sub-Saharan countries: a qualitative survey amongst malaria key stakeholders.
- Author
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Audibert, Céline and Rietveld, Hans
- Subjects
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TREND setters , *MALARIA , *CHEMOPREVENTION , *LEGAL evidence , *CLINICAL trials - Abstract
Background: Post-discharge malaria chemoprevention (PDMC) is an intervention aimed at reducing morbidity and mortality in patients hospitalized with severe anaemia, with its effectiveness established in several clinical trials. The aim of this study was to better understand factors that would influence the scale up of this intervention, and to identify preferences for two delivery mechanisms, facility-based or community-based. Methods: Forty-six qualitative individual interviews were conducted in five sub-Saharan countries amongst malaria key opinion leaders and national decision makers. Findings were analysed following a thematic inductive approach. Results: Half of participants were familiar with PDMC, with a satisfactory understanding of the intervention. Although PDMC was perceived as beneficial by most respondents, there was some unclarity on the target population. Both delivery approaches were perceived as valuable and potentially complementary. From an adoption perspective, relevant evidence generation, favorable policy environment, and committed funding were identified as key elements for the scale up of PDMC. Conclusions: The findings suggest that although PDMC was perceived as a relevant tool to prevent malaria, further clarification was needed in terms of the relevant patient population, delivery mechanisms, and more evidence should be generated from implementation research to ensure policy adoption and funding. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
6. Improving adherence to severe malaria treatment guidelines in children at a Ugandan regional hospital: assessment of a quality improvement initiative.
- Author
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Moffitt, Cynthia A., Olupot-Olupot, Peter, Wamulugwa, Joan, Abeso, Julian, Muszynski, Jennifer A., and O'Brien, Nicole
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BLOOD testing , *HOSPITAL care of children , *FISHER exact test , *MALARIA , *CHILDREN'S hospitals - Abstract
Background: Malaria is the leading cause of hospitalizations and death in Uganda, particularly in children under the age of five. Studies have shown that adherence to the World Health Organization (WHO) guidelines for the management of severe malaria reduces mortality in hospitalized children. This study aimed to determine the impact of targeted interventions on adherence to the WHO severe malaria treatment guidelines in children at a Ugandan hospital as part of a quality improvement initiative. Methods: Interventions included workflow changes, such as obtaining patient blood samples for diagnostic testing by the admitting healthcare provider as well as utilizing patient caregivers to assist nursing staff in timing medications. An additional intervention was the use of an admission checklist sticker. The post-intervention sample was compared to the baseline assessment. The primary outcome was the proportion of patients receiving care consistent with all aspects of the WHO guidelines. Secondary outcomes included the proportion of patients receiving malaria diagnostic testing, those receiving at least 3 doses of artesunate, the timely administration of artesunate, and adherence to other guideline components. Statistical analyses were conducted using GraphPad PRISM 9.0. Comparisons between groups were analysed using Chi-square or Fisher's exact test for categorical variables and Mann–Whitney test for continuous variables. Results: The post-intervention group included 230 patients with a median age of 5 years [4–8], and 58% of patients were male. Adherence to all aspects of the WHO guidelines was achieved in 10% of patients in the post-intervention group compared to 3% of patients in the baseline (P = 0.007). Appropriate malaria diagnostic testing was performed in 85% of patients post-intervention compared to 66% of patients in the baseline (P < 0.0001). Patients in the post-intervention group were more likely to receive the minimum 3 doses of artesunate (86%) than in the baseline (74%) (P = 0.008). Patients in the post-intervention group were more likely to receive artesunate doses on time than in the baseline (dose 2 P = 0.02, dose 3 P = 0.003). Conclusions: Targeted, low-cost interventions led to improvement in adherence to severe malaria treatment guidelines. The most notable changes were in malaria diagnostic testing and antimalarial administration. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
- View/download PDF
7. Non-falciparum malaria infections in Uganda, does it matter? A review of the published literature.
- Author
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Ranjbar, Mansour and Tegegn Woldemariam, Yonas
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MALARIA , *MIXED infections , *SYMPTOMS , *DEATH rate , *PLASMODIUM falciparum - Abstract
Background: Plasmodium falciparum is the dominant malaria species in the sub-Saharan Africa and the main cause of severe disease and death. Notwithstanding, severe malaria and death due to non-falciparum infections have been reported, but at much lower rates than P. falciparum infections. Following increasing use of molecular detection techniques in epidemiological studies, a higher prevalence of non-falciparum species has been reported in the region than previously thought. This article reviews the literature on the prevalence of non-falciparum malaria species in Uganda and the clinical figures of their severe diseases. It aims to elucidate the extent to which mono non-falciparum malaria infections in a highly malaria-endemic country contribute to malaria mortality and outline its policy implications on malaria case management. Methods: The available English-language published peer-reviewed literature up to March 2024 was sought via PubMed and Google Scholar. The keywords used were severe malaria, AND P. falciparum, P. malariae, P. vivax, P. ovale spp., mixed infections AND Uganda. The review encompassed 53 articles. Articles using molecular diagnosis methods were accounted for analysis. Results: The literature reported a substantial prevalence of non-falciparum infections in Uganda. Plasmodium malariae and Plasmodium ovale spp. were the second and third most prevalent reported malaria species respectively after P. falciparum as dominant species. Non-falciparum malaria infections often occur as mixed infections rather than mono-infections. Besides, molecular diagnostics revealed that 21% of initially reported mono-infections of P. falciparum were, in fact, mixed infections. No article was found on the prevalence of severe malaria or case fatality rate due to mixed or non-falciparum infections. Conclusion: A critical knowledge gap exists regarding the impact of mixed and non-falciparum species on severe malaria and death in Uganda. Robust evidence on prevalence, recurrent parasitaemia, and severe clinical manifestations of mixed and non-falciparum malaria infections is crucial for evidence-based and effective policymaking regarding malaria case management. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
- View/download PDF
8. Whole-genome surveillance identifies markers of Plasmodium falciparum drug resistance and novel genomic regions under selection in Mozambique
- Author
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Coonahan, Erin, Gage, Hunter, Chen, Daisy, Noormahomed, Emilia Virginia, Buene, Titos Paulo, de Sousa, Irina Mendes, Akrami, Kevan, Chambal, Lucia, Schooley, Robert T, Winzeler, Elizabeth A, and Cowell, Annie N
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Microbiology ,Clinical Sciences ,Medical Microbiology ,Vaccine Related ,Infectious Diseases ,Genetics ,Orphan Drug ,Emerging Infectious Diseases ,Biotechnology ,Prevention ,Human Genome ,Rare Diseases ,Malaria ,Vector-Borne Diseases ,Immunization ,Infection ,Good Health and Well Being ,Animals ,Humans ,Plasmodium falciparum ,Mozambique ,Antimalarials ,Parasites ,Genomics ,Drug Resistance ,Malaria ,Falciparum ,severe malaria ,whole-genome sequencing ,selective whole genome amplification ,antimalarial drug resistance ,genetic variation ,positive selection ,Biochemistry and cell biology ,Medical microbiology - Abstract
ImportanceMalaria is a devastating disease caused by Plasmodium parasites. The evolution of parasite drug resistance continues to hamper progress toward malaria elimination, and despite extensive efforts to control malaria, it remains a leading cause of death in Mozambique and other countries in the region. The development of successful vaccines and identification of molecular markers to track drug efficacy are essential for managing the disease burden. We present an analysis of the parasite genome in Mozambique, a country with one of the highest malaria burdens globally and limited available genomic data, revealing current selection pressure. We contribute additional evidence to limited prior studies supporting the effectiveness of SWGA in producing reliable genomic data from complex clinical samples. Our results provide the identity of genomic loci that may be associated with current antimalarial drug use, including artemisinin and lumefantrine, and reveal selection pressure predicted to compromise the efficacy of current vaccine candidates.
- Published
- 2023
9. Perceived barriers and opportunities for the introduction of post-discharge malaria chemoprevention (PDMC) in five sub-Saharan countries: a qualitative survey amongst malaria key stakeholders
- Author
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Céline Audibert and Hans Rietveld
- Subjects
Severe anaemia ,Severe malaria ,Post-discharge malaria chemoprevention ,Sub-Saharan Africa ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Post-discharge malaria chemoprevention (PDMC) is an intervention aimed at reducing morbidity and mortality in patients hospitalized with severe anaemia, with its effectiveness established in several clinical trials. The aim of this study was to better understand factors that would influence the scale up of this intervention, and to identify preferences for two delivery mechanisms, facility-based or community-based. Methods Forty-six qualitative individual interviews were conducted in five sub-Saharan countries amongst malaria key opinion leaders and national decision makers. Findings were analysed following a thematic inductive approach. Results Half of participants were familiar with PDMC, with a satisfactory understanding of the intervention. Although PDMC was perceived as beneficial by most respondents, there was some unclarity on the target population. Both delivery approaches were perceived as valuable and potentially complementary. From an adoption perspective, relevant evidence generation, favorable policy environment, and committed funding were identified as key elements for the scale up of PDMC. Conclusions The findings suggest that although PDMC was perceived as a relevant tool to prevent malaria, further clarification was needed in terms of the relevant patient population, delivery mechanisms, and more evidence should be generated from implementation research to ensure policy adoption and funding.
- Published
- 2024
- Full Text
- View/download PDF
10. Improving adherence to severe malaria treatment guidelines in children at a Ugandan regional hospital: assessment of a quality improvement initiative
- Author
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Cynthia A. Moffitt, Peter Olupot-Olupot, Joan Wamulugwa, Julian Abeso, Jennifer A. Muszynski, and Nicole O’Brien
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Malaria ,Severe malaria ,Guidelines ,Case management ,Adherence ,Uganda ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Malaria is the leading cause of hospitalizations and death in Uganda, particularly in children under the age of five. Studies have shown that adherence to the World Health Organization (WHO) guidelines for the management of severe malaria reduces mortality in hospitalized children. This study aimed to determine the impact of targeted interventions on adherence to the WHO severe malaria treatment guidelines in children at a Ugandan hospital as part of a quality improvement initiative. Methods Interventions included workflow changes, such as obtaining patient blood samples for diagnostic testing by the admitting healthcare provider as well as utilizing patient caregivers to assist nursing staff in timing medications. An additional intervention was the use of an admission checklist sticker. The post-intervention sample was compared to the baseline assessment. The primary outcome was the proportion of patients receiving care consistent with all aspects of the WHO guidelines. Secondary outcomes included the proportion of patients receiving malaria diagnostic testing, those receiving at least 3 doses of artesunate, the timely administration of artesunate, and adherence to other guideline components. Statistical analyses were conducted using GraphPad PRISM 9.0. Comparisons between groups were analysed using Chi-square or Fisher’s exact test for categorical variables and Mann–Whitney test for continuous variables. Results The post-intervention group included 230 patients with a median age of 5 years [4–8], and 58% of patients were male. Adherence to all aspects of the WHO guidelines was achieved in 10% of patients in the post-intervention group compared to 3% of patients in the baseline (P = 0.007). Appropriate malaria diagnostic testing was performed in 85% of patients post-intervention compared to 66% of patients in the baseline (P
- Published
- 2024
- Full Text
- View/download PDF
11. Haemoglobin genotype of children with severe malaria seen at the University of Benin Teaching Hospital, Benin city, Nigeria
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Nwaneri DU and Ibadin MO
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children ,genotype ,haemoglobin ,mortality ,severe malaria ,Medicine - Abstract
Introduction: Types of haemoglobin (Hb) genotype have been found to be crucial to the rate of red blood cell parasite invasion, multiplication, and destruction as well as outcome of malaria disease. In a bid to provide more information on the relationship between Hb genotype and level of protection conferred by genotype against severe forms of malaria, this study was undertaken. This is done through evaluation of forms of Hb genotype in children with severe malaria seen in University of Benin Teaching Hospital (UBTH), Benin City. Patients and methods: This crosssectional study was carried out on children (6 - 60 months old) admitted for severe malaria using standard World Health Organization (WHO) guidelines. Diagnosis of malaria was by microscopic demonstration of parasitaemia or serology (in those with negative parasitaemia). Hb genotype was done using the Hb electrophoresis. Results: Ninety-six well nourished children; (56(58.3%) males and 40 (41.7%) females) mean age (± SD) 29.22 ± 16.02 months were recruited for the study. Sixty-eight (73.4%) of the 92 subjects had Hb genotype AA while 24(26.1%) Had abnormal Hb genotype. Prevalence of severe malaria in children with abnormal Hb was 20/24 (83.3%) as against 58/68(85.3%) observed in those with HbAA. Significantly fewer incidence of heavy malaria parasitaemia (3+ and 4+) was observed in children with abnormal Hb genotype. Heavy parasite density was the most important features of severe malaria in children with HbAA (p= 0.013) as against altered sensorium, prostration, and haemoglobinuria in children with abnormal Hb genotype (p = 0.003, 0.041, and 0.023 respectively). Children with HbAA were also about 3 times more likely to die from severe malaria (p = 0.567, O.R = 2.96) when compared with their counterparts with abnormal Hb. Conclusion: Study supports a higher prevalence of severe malaria in children with HbAA when compared with those with abnormal Hb genotype. Altered sensorium, prostration and haemoglobinuria were the significant presenting features of severe malaria in children with abnormal Hb genotype in this study.
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- 2024
12. Effects of probiotic saccharomyces bourlardii on cytokine levels and outcomes of childhood severe malaria: Study protocol for a randomized controlled trial
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Abiodun Moses Temidayo, Onyiriuka Alphonsus N, Enato Ehijie FO, and Osarogiagbon Wilson O
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probiotic saccharomyces bourladii ,severe malaria ,cytokines ,outcomes ,Medicine - Abstract
Background: Severe malaria is acute malaria with signs of organ dysfunction and/or hyper- parasitaemia. About 90% of the world’s severe and fatal malaria is estimated to affect young children in sub-Sahara Africa. Systemic complications and neuropathology in severe malaria include ‘cytokine storm hypothesis’. Probiotic immunomodulation may show therapeutic benefits in severe malaria. Aim: This study aims to evaluate the effects of probiotic saccharomyces bourladii on serum cytokine levels (IL-6 and TNF), clinical course and outcome of children with severe malaria. Methods: Participants shall be recruited based on WHO diagnostic criteria for severe malaria and their clinical-demographic data shall be obtained with a pretested questionnaire. The study design is randomized controlled trial (RCT); participants shall be randomized into two study sub-groups (intervention vs. control). All participants shall receive standard anti-malarial therapies. In addition, probiotic saccharomyces bourladii 250mg twice a day shall be administered to those in the intervention sub-group for 3 days. There after, their serum CC –BY 4.0 cytokines (IL-6 and TNF) shall be measured quantitatively by a Sandwich enzyme-linked immunosorbent assay (ELISA) technique. Primary outcomes shall be cytokine levels and length of stay (LOS) while secondary measures shall be coma scores, seizure, neurological deficits and mortality. The data shall be analyzed using SPSS version 26.0 statistical software for Windows. Both ‘intention-to-treat analysis’ and ‘analysis as per protocol’ shall be done. P-value< 0.05 shall be considered significant in all tests. Discussion: At the end of this clinical trial, it is expected that the potential benefits of probiotic saccharomyces bourladii in modulating pro-inflammatory cytokines, averting systemic complications and reducing mortality in childhood severe malaria would have been verified. Protocol No: ADM/E22/A/VOL.VII/148312145; University of Benin Teaching Hospital’s Health Research Ethics Committee Approval; August 5th, 2022.
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- 2024
13. Non-falciparum malaria infections in Uganda, does it matter? A review of the published literature
- Author
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Mansour Ranjbar and Yonas Tegegn Woldemariam
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Severe malaria ,Non-falciparum ,Mixed infections ,P. ovale spp. ,P. malariae ,P. vivax ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Plasmodium falciparum is the dominant malaria species in the sub-Saharan Africa and the main cause of severe disease and death. Notwithstanding, severe malaria and death due to non-falciparum infections have been reported, but at much lower rates than P. falciparum infections. Following increasing use of molecular detection techniques in epidemiological studies, a higher prevalence of non-falciparum species has been reported in the region than previously thought. This article reviews the literature on the prevalence of non-falciparum malaria species in Uganda and the clinical figures of their severe diseases. It aims to elucidate the extent to which mono non-falciparum malaria infections in a highly malaria-endemic country contribute to malaria mortality and outline its policy implications on malaria case management. Methods The available English-language published peer-reviewed literature up to March 2024 was sought via PubMed and Google Scholar. The keywords used were severe malaria, AND P. falciparum, P. malariae, P. vivax, P. ovale spp., mixed infections AND Uganda. The review encompassed 53 articles. Articles using molecular diagnosis methods were accounted for analysis. Results The literature reported a substantial prevalence of non-falciparum infections in Uganda. Plasmodium malariae and Plasmodium ovale spp. were the second and third most prevalent reported malaria species respectively after P. falciparum as dominant species. Non-falciparum malaria infections often occur as mixed infections rather than mono-infections. Besides, molecular diagnostics revealed that 21% of initially reported mono-infections of P. falciparum were, in fact, mixed infections. No article was found on the prevalence of severe malaria or case fatality rate due to mixed or non-falciparum infections. Conclusion A critical knowledge gap exists regarding the impact of mixed and non-falciparum species on severe malaria and death in Uganda. Robust evidence on prevalence, recurrent parasitaemia, and severe clinical manifestations of mixed and non-falciparum malaria infections is crucial for evidence-based and effective policymaking regarding malaria case management.
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- 2024
- Full Text
- View/download PDF
14. An epidemiological analysis of severe imported malaria infections in Sri Lanka, after malaria elimination
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Shilanthi Seneviratne, Deepika Fernando, Rajitha Wickremasinghe, Sujai Senarathne, Pubudu Chulasiri, Nethmini Thenuwara, Champa Aluthweera, Iromi Mohotti, Shamila Jayakuru, Thilan Fernando, Anula Wijesundara, Rohini Fernandopulle, and Kamini Mendis
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Severe malaria ,Imported malaria ,Sri Lanka ,Prevention of re-establishment ,Management ,Delay in diagnosis ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Imported malaria continues to be reported in Sri Lanka after it was eliminated in 2012, and a few progress to life-threatening severe malaria. Methods Data on imported malaria cases reported in Sri Lanka from 2013 to 2023 were extracted from the national malaria database maintained by the Anti Malaria Campaign (AMC) of Sri Lanka. Case data of severe malaria as defined by the World Health Organization were analysed with regard to patients’ general characteristics and their health-seeking behaviour, and the latter compared with that of uncomplicated malaria patients. Details of the last three cases of severe malaria in 2023 are presented. Results 532 imported malaria cases were diagnosed over 11 years (2013–2023); 46 (8.6%) were severe malaria, of which 45 were Plasmodium falciparum and one Plasmodium vivax. Most severe malaria infections were acquired in Africa. All but one were males, and a majority (87%) were 26–60 years of age. They were mainly Sri Lankan nationals (82.6%). Just over half (56.5%) were treated at government hospitals. The average time between arrival of the person in Sri Lanka and onset of illness was 4 days. 29 cases of severe malaria were compared with 165 uncomplicated malaria cases reported from 2015 to 2023. On average both severe and uncomplicated malaria patients consulted a physician equally early (mean = 1 day) with 93.3% of severe malaria doing so within 3 days. However, the time from the point of consulting a physician to diagnosis of malaria was significantly longer (median 4 days) in severe malaria patients compared to uncomplicated patients (median 1 day) (p = 0.012) as was the time from onset of illness to diagnosis (p = 0.042). All severe patients recovered without sequelae except for one who died. Conclusions The risk of severe malaria among imported cases increases significantly beyond 5 days from the onset of symptoms. Although patients consult a physician early, malaria diagnosis tends to be delayed by physicians because it is now a rare disease. Good access to expert clinical care has maintained case fatality rates of severe malaria at par with those reported elsewhere.
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- 2024
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- View/download PDF
15. Defining the next generation of severe malaria treatment: a target product profile
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Jane Achan, Aïssata Barry, Didier Leroy, George Kamara, Stephan Duparc, Wiweka Kaszubska, Preetam Gandhi, Bénédicte Buffet, Patrick Tshilab, Bernhards Ogutu, Terrie Taylor, Sanjeev Krishna, Naomi Richardson, Hanu Ramachandruni, and Hans Rietveld
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Severe malaria ,Drug development ,Translational medicine ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Severe malaria is a life-threatening infection, particularly affecting children under the age of 5 years in Africa. Current treatment with parenteral artemisinin derivatives is highly efficacious. However, artemisinin partial resistance is widespread in Southeast Asia, resulting in delayed parasite clearance after therapy, and has emerged independently in South America, Oceania, and Africa. Hence, new treatments for severe malaria are needed, and it is prudent to define their characteristics now. This manuscript focuses on the target product profile (TPP) for new treatments for severe malaria. It also highlights preparedness when considering ways of protecting the utility of artemisinin-based therapies. Target product profile Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. They should also have a low potential for drug resistance selection, given the high parasite burden in patients with severe malaria. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed. These should be advanced to at least phase 2 clinical trials, enabling rapid progression to patient use should current treatment fail clinically. New drug combinations for severe malaria should be available as injectable formulations for rapid and effective treatment, or as rectal formulations for pre-referral intervention in resource-limited settings. Conclusion Defining the TPP is a key step to align responses across the community to proactively address the potential for clinical failure of artesunate in severe malaria. In the shorter term, artemisinin-based combination therapies should be developed using approved or novel drugs. In the longer term, novel combination treatments should be pursued. Thus, this TPP aims to direct efforts to preserve the efficacy of existing treatments while improving care and outcomes for individuals affected by this life-threatening disease.
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- 2024
- Full Text
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16. Severe malaria intervention status in Nigeria: workshop meeting report
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Emmanuel Shekarau, Miriam Uzoanya, Nnenna Ogbulafor, and Severe Malaria Working Group
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Severe malaria ,Pre-referral intervention ,Guidelines ,Referral system ,Nigeria ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Nigeria accounts for 39% of global malaria deaths in children under 5 years of age and the effective management of severe malaria is a health priority. The Annual Nigeria Severe Malaria Stakeholders Workshop, held on the 5–6th of July 2023 in Abuja, Nigeria brought together representatives from 36 States, the Federal Capital Territory, and other key stakeholders to address the management of severe malaria across all levels of the health service. Aims were to provide updates and review progress on severe malaria activities, the burden of disease, commodity logistics management, and pre-referral national policy implementation as well as to disseminate research findings. Two roundtable discussions were conducted to identify the challenges, barriers, and facilitators to the effective management of severe malaria in Nigeria. A key challenge was the limited awareness of updated guidelines and strategic documents among frontline health workers, leading to the misuse of non-recommended medications, like α-β-arteether. Further to this, the need to ensure appropriate treatments during pregnancy and the adoption of the WHO directive on the use of rectal artesunate were highlighted. To address these issues, innovative dissemination channels for guideline awareness were recommended and collaboration with professional organizations to enrich training materials emphasized. Other areas for improvement considered the processes involved in severe malaria management, with insufficient coordination among government agencies, inadequate referral linkages, and inadequate human resources identified as barriers. Recommendations focused on practical measures to minimize wastage of injectable artesunate, enhance data management through scaling up electronic medical records, and strengthen referral systems. The extension of severe malaria surveillance to patients older than 5 years was also proposed. To deliver these changes, actionable plans for sustained recruitment and training are needed, as well as committed advocacy at all levels to ensure timely fund disbursement and institutional support. A key overarching theme from the workshop was that a multifaceted approach was needed to address severe malaria in Nigeria, emphasizing collaborative efforts, evidence-based practices, and strategic resource allocation. With the largest malaria burden globally, the potential impact of addressing the challenges of severe malaria management in Nigeria cannot be understated and must be urgently addressed.
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- 2024
- Full Text
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17. Predictors of poor outcome in children with severe malaria at a tertiary health facility in Northern Nigeria
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Abubakar Sani Lugga, Olayinka Rasheed Ibrahim, Nuraddeen Ibrahim, Olumide B. Ajide, Ashurah Armayau Abubakar, Olajide Aladesua, Mohammed Bashir, Fatima F. Nasir, Amina O. Ibrahim, Sakiru Abiodun Yekinni, Lawal Magaji Ibrahim, Bello M. Suleiman, and Muutassim Ibrahim
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children ,hospitalization outcome ,predictors of poor outcome ,severe malaria ,Medicine - Abstract
Background: Malaria is a major cause of mortality among children. Objective: This study determines the clinical profile, outcome (discharge and death), and factors associated with poor outcome in children with severe malaria in a tertiary health facility in Northern Nigeria. Methods: We conducted a descriptive retrospective study of all children (≤14 years) admitted with severe malaria based on positive malaria parasite on thick film and or rapid diagnostic test and the World Health Organization guideline for severe malaria. We extracted relevant data from patients’ case files and departmental records and analyzed with the Statistical Package for the Social Sciences (SPSS) for Windows, version 20.0. (IBM Corp, Armonk, NY). Results: A total of 483 children with severe malaria were admitted with median age interquartile range of 4.0 (2.5–8.0) years. Males were 261 (54.0%). Underfives were 258 (53.4%). Common forms of presentation were cerebral malaria 169 (35.0%), prostration (102; 21.1%), and multiple convulsion (86; 17.8%). Cerebral malaria and prostration were significantly higher among children aged 5 years and older. The mortality rate was 4.3% (21). Multivariate logistic regression analyses showed that impaired consciousness (adjusted odds ratio [aOR] 8.5, 95% confidence interval [CI]: 2.345, 30.484), hypoglycemia (aOR: 21.4, 95% CI: 2.766, 165.410), presence of two or more components (aOR: 4.5, 95% CI: 1.630, 12.522), and duration of hospitalization of 24 h or less (aOR: 4.6, 95% CI: 1.621, 12.782) were independent predictors of poor outcome. Conclusion: Our study showed that cerebral malaria was the most common form of severe malaria with a significant burden in children above 5 years. The presence of impaired consciousness, hypoglycemia, multiple components, and duration of
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- 2024
- Full Text
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18. An epidemiological analysis of severe imported malaria infections in Sri Lanka, after malaria elimination.
- Author
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Seneviratne, Shilanthi, Fernando, Deepika, Wickremasinghe, Rajitha, Senarathne, Sujai, Chulasiri, Pubudu, Thenuwara, Nethmini, Aluthweera, Champa, Mohotti, Iromi, Jayakuru, Shamila, Fernando, Thilan, Wijesundara, Anula, Fernandopulle, Rohini, and Mendis, Kamini
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EPIDEMIOLOGY , *MALARIA , *DELAYED diagnosis , *PUBLIC hospitals , *RARE diseases - Abstract
Background: Imported malaria continues to be reported in Sri Lanka after it was eliminated in 2012, and a few progress to life-threatening severe malaria. Methods: Data on imported malaria cases reported in Sri Lanka from 2013 to 2023 were extracted from the national malaria database maintained by the Anti Malaria Campaign (AMC) of Sri Lanka. Case data of severe malaria as defined by the World Health Organization were analysed with regard to patients' general characteristics and their health-seeking behaviour, and the latter compared with that of uncomplicated malaria patients. Details of the last three cases of severe malaria in 2023 are presented. Results: 532 imported malaria cases were diagnosed over 11 years (2013–2023); 46 (8.6%) were severe malaria, of which 45 were Plasmodium falciparum and one Plasmodium vivax. Most severe malaria infections were acquired in Africa. All but one were males, and a majority (87%) were 26–60 years of age. They were mainly Sri Lankan nationals (82.6%). Just over half (56.5%) were treated at government hospitals. The average time between arrival of the person in Sri Lanka and onset of illness was 4 days. 29 cases of severe malaria were compared with 165 uncomplicated malaria cases reported from 2015 to 2023. On average both severe and uncomplicated malaria patients consulted a physician equally early (mean = 1 day) with 93.3% of severe malaria doing so within 3 days. However, the time from the point of consulting a physician to diagnosis of malaria was significantly longer (median 4 days) in severe malaria patients compared to uncomplicated patients (median 1 day) (p = 0.012) as was the time from onset of illness to diagnosis (p = 0.042). All severe patients recovered without sequelae except for one who died. Conclusions: The risk of severe malaria among imported cases increases significantly beyond 5 days from the onset of symptoms. Although patients consult a physician early, malaria diagnosis tends to be delayed by physicians because it is now a rare disease. Good access to expert clinical care has maintained case fatality rates of severe malaria at par with those reported elsewhere. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
19. Severe malaria intervention status in Nigeria: workshop meeting report.
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Shekarau, Emmanuel, Uzoanya, Miriam, Ogbulafor, Nnenna, Ntadom, Godwin, Ijezie, Simon Ntomchukwu, Uzoanya, Miriam Ihuoma, Seye, Babatunde, Fashanu, Chizoba, Eze, Nwamaka, Nwidae, Lekia, Mokuolu, Olugbenga, Nwokenna, Uchenna, Nglass, Iniabasi, Ishola-Gbenla, Olusesan, Okouzi, Methodius, Fagbola, Motunrayo, Oresanya, Olusola, Getachew, Dawit, Chukwumerije, Jennifer, and Erinle, Victoria
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MALARIA , *ADULT education workshops , *ELECTRONIC health records , *CHILD death - Abstract
Nigeria accounts for 39% of global malaria deaths in children under 5 years of age and the effective management of severe malaria is a health priority. The Annual Nigeria Severe Malaria Stakeholders Workshop, held on the 5–6th of July 2023 in Abuja, Nigeria brought together representatives from 36 States, the Federal Capital Territory, and other key stakeholders to address the management of severe malaria across all levels of the health service. Aims were to provide updates and review progress on severe malaria activities, the burden of disease, commodity logistics management, and pre-referral national policy implementation as well as to disseminate research findings. Two roundtable discussions were conducted to identify the challenges, barriers, and facilitators to the effective management of severe malaria in Nigeria. A key challenge was the limited awareness of updated guidelines and strategic documents among frontline health workers, leading to the misuse of non-recommended medications, like α-β-arteether. Further to this, the need to ensure appropriate treatments during pregnancy and the adoption of the WHO directive on the use of rectal artesunate were highlighted. To address these issues, innovative dissemination channels for guideline awareness were recommended and collaboration with professional organizations to enrich training materials emphasized. Other areas for improvement considered the processes involved in severe malaria management, with insufficient coordination among government agencies, inadequate referral linkages, and inadequate human resources identified as barriers. Recommendations focused on practical measures to minimize wastage of injectable artesunate, enhance data management through scaling up electronic medical records, and strengthen referral systems. The extension of severe malaria surveillance to patients older than 5 years was also proposed. To deliver these changes, actionable plans for sustained recruitment and training are needed, as well as committed advocacy at all levels to ensure timely fund disbursement and institutional support. A key overarching theme from the workshop was that a multifaceted approach was needed to address severe malaria in Nigeria, emphasizing collaborative efforts, evidence-based practices, and strategic resource allocation. With the largest malaria burden globally, the potential impact of addressing the challenges of severe malaria management in Nigeria cannot be understated and must be urgently addressed. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Defining the next generation of severe malaria treatment: a target product profile.
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Achan, Jane, Barry, Aïssata, Leroy, Didier, Kamara, George, Duparc, Stephan, Kaszubska, Wiweka, Gandhi, Preetam, Buffet, Bénédicte, Tshilab, Patrick, Ogutu, Bernhards, Taylor, Terrie, Krishna, Sanjeev, Richardson, Naomi, Ramachandruni, Hanu, and Rietveld, Hans
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MALARIA , *RESOURCE-limited settings , *ARTEMISININ derivatives , *DRUG resistance , *ARTEMISININ - Abstract
Background: Severe malaria is a life-threatening infection, particularly affecting children under the age of 5 years in Africa. Current treatment with parenteral artemisinin derivatives is highly efficacious. However, artemisinin partial resistance is widespread in Southeast Asia, resulting in delayed parasite clearance after therapy, and has emerged independently in South America, Oceania, and Africa. Hence, new treatments for severe malaria are needed, and it is prudent to define their characteristics now. This manuscript focuses on the target product profile (TPP) for new treatments for severe malaria. It also highlights preparedness when considering ways of protecting the utility of artemisinin-based therapies. Target product profile: Severe malaria treatments must be highly potent, with rapid onset of antiparasitic activity to clear the infection as quickly as possible to prevent complications. They should also have a low potential for drug resistance selection, given the high parasite burden in patients with severe malaria. Combination therapies are needed to deter resistance selection and dissemination. Partner drugs which are approved for uncomplicated malaria treatment would provide the most rapid development pathway for combinations, though new candidate molecules should be considered. Artemisinin combination approaches to severe malaria would extend the lifespan of current therapy, but ideally, completely novel, non-artemisinin-based combination therapies for severe malaria should be developed. These should be advanced to at least phase 2 clinical trials, enabling rapid progression to patient use should current treatment fail clinically. New drug combinations for severe malaria should be available as injectable formulations for rapid and effective treatment, or as rectal formulations for pre-referral intervention in resource-limited settings. Conclusion: Defining the TPP is a key step to align responses across the community to proactively address the potential for clinical failure of artesunate in severe malaria. In the shorter term, artemisinin-based combination therapies should be developed using approved or novel drugs. In the longer term, novel combination treatments should be pursued. Thus, this TPP aims to direct efforts to preserve the efficacy of existing treatments while improving care and outcomes for individuals affected by this life-threatening disease. [ABSTRACT FROM AUTHOR]
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- 2024
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21. A novel locus in CSMD1 gene is associated with increased susceptibility to severe malaria in Malian children.
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Damena, Delesa, Barry, Amadou, Morrison, Robert, Gaoussou, Santara, Mahamar, Almahamoudou, Attaher, Oumar, Issiaka, Djibrilla, Dicko, Yahia, Dicko, Alassane, Duffy, Patrick, and Fried, Michal
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MALARIA ,SINGLE nucleotide polymorphisms ,GENOME-wide association studies ,LINKAGE disequilibrium ,GENETIC polymorphisms ,LOGISTIC regression analysis - Abstract
Background: Plasmodium falciparum malaria is still a leading cause of child mortality in sub-Saharan Africa. The clinical manifestations of malaria range from asymptomatic infection to severe disease. The variation in clinical presentation is partly attributed to host genetic factors with estimated narrow-sense heritability of 23%. Here, we investigate the associations between candidate gene polymorphisms and the likelihood of severe malaria (SM) in a cohort of Malian children. Methods: Based on our previous genome-wide association studies (GWAS) analysis, candidate genes were selected for in-depth analysis using several criteria including gene-level GWAS scores, functional overlap with malaria pathogenesis, and evidence of association with protection or susceptibility to other infectious or inflammatory diseases. Single Nucleotide Polymorphisms (SNPs) residing within these genes were selected mainly based on p-values from previous severe malaria susceptibility GWAS studies and minor allele frequency (MAF) in West African populations. Results: Of 182 candidate genes reported in our previous study, 11 genes and 22 SNPs residing in these genes were selected. The selected SNPs were genotyped using KASP technology in 477 DNA samples (87 SM and 390 controls). Logistic regression analysis revealed that a common intron variant, rs13340578 in CUB and Sushi Multi Domain (CSMD1) gene, is associated with increased odds of SM in recessive mode of inheritance (MAF = 0.42, OR = 1.8, 95% CI = [1.78, 1.84], p = 0.029). The SNP is in linkage disequilibrium (LD) with multiple variants with regulatory features. Conclusion: Taken together, the current study showed that an intron variant rs13340578, residing in CSMD1 gene, is associated with increased susceptibility to malaria. This finding suggests that modified regulation of complement may contribute to malaria disease severity. Further studies are needed to identify the causal variants and the underlying molecular mechanisms. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Severe malaria-related disability in Ethiopian children from the perspectives of caregivers: an interpretive description study.
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Engeda, Eshetu Haileselassie, Aldersey, Heather M., Davison, Colleen M., Gelaye, Kassahun Alemu, and Fayed, Nora
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RISK assessment , *DISABILITIES , *CHILDREN with disabilities , *QUALITATIVE research , *RESEARCH funding , *MALARIA , *INTERVIEWING , *JUDGMENT sampling , *SOUND recordings , *THEMATIC analysis , *RESEARCH methodology , *QUALITY of life , *CONCEPTUAL structures , *CAREGIVER attitudes , *WELL-being , *DISEASE complications , *CHILDREN - Abstract
This study explored severe malaria-related disability in children from the perspectives of their caregivers. The interpretive description qualitative approach was employed. The participants were selected using the purposive sampling technique considering the child's history of severe malaria, age (0–10 years), and location (urban/rural). Data were collected through face-to-face interviews with sixteen caregivers. Reflexive thematic data analysis was utilized. Through prolonged engagement, reflective journaling, an audit trail, and co-authors' review, trustworthiness was enhanced. The study generated five themes from the interviews: mitigators of disability, contributors of disability, impact on body function, impact on activities and participation, and uncertainties about future well-being. The findings revealed previously unstudied social components of disability and environmental factors. Furthermore, the research uncovered health-related quality of life aspects that are out of the scope of the current comprehensive disability framework. The study contributes to a deeper understanding of severe malaria-related disability in children from the biopsychosocial perspective. The findings could help policymakers, researchers, and clinicians who want to design rehabilitation interventions for the affected children or examine the components of disability on a large scale using quantitative methods. Various contextual factors interacted with severe malaria and influenced functioning either as facilitators or barriers, implying disability related to malaria can be prevented or created. The long-term impacts of severe malaria are not limited to functioning and disability but also affect the health-related quality of life of children who survive severe malaria. Rehabilitation professionals should consider applying comprehensive functioning and disability frameworks such as the ICF when designing (or applying) screening tools, planning interventions, and evaluating the outcomes of intervention for children with severe malaria-related disability. Rehabilitation interventions for children with severe malaria-related disability should consider patient– or caregiver–reported outcomes (components of disability). [ABSTRACT FROM AUTHOR]
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- 2024
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23. sTREM-1: A Biomarker of Mortality in Severe Malaria Impacted by Acute Kidney Injury.
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Mufumba, Ivan, Kazinga, Caroline, Namazzi, Ruth, Opoka, Robert O, Batte, Anthony, Bond, Caitlin, John, Chandy C, and Conroy, Andrea L
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ACUTE kidney failure , *CLINICAL decision support systems , *MALARIA , *BIOMARKERS , *MORTALITY - Abstract
Background Malaria is an important cause of mortality in African children. Identification of biomarkers to identify children at risk of mortality has the potential to improve outcomes. Methods We evaluated 11 biomarkers of host response in 592 children with severe malaria. The primary outcome was biomarker performance for predicting mortality. Biomarkers were evaluated using receiver operating characteristic (ROC) curve analysis comparing the area under the ROC curve (AUROC). Results Mortality was 7.3% among children in the study with 72% of deaths occurring within 24 hours of admission. Among the candidate biomarkers, soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) had the highest AUROC (0.78 [95% confidence interval,.70–.86]), outperforming several other biomarkers including C-reactive protein and procalcitonin. sTREM-1 was the top-performing biomarker across prespecified subgroups (malaria definition, site, sex, nutritional status, age). Using established cutoffs, we evaluated mortality across sTREM-1 risk zones. Among children with acute kidney injury, 39.9% of children with a critical-risk sTREM-1 result had an indication for dialysis. When evaluated relative to a disease severity score, sTREM-1 improved mortality prediction (difference in AUROC, P =.016). Conclusions sTREM-1 is a promising biomarker to guide rational allocation of clinical resources and should be integrated into clinical decision support algorithms, particularly when acute kidney injury is suspected. [ABSTRACT FROM AUTHOR]
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- 2024
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24. SEVUparin as a potential Adjunctive Treatment in children with severe malaria: A phase I trial safety and dose finding trial (SEVUSMAART) [version 2; peer review: 2 approved, 1 approved with reservations]
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Mainga Hamaluba, Thomas N. Williams, Christabel Mogoka, Luc Kambale Kamavu, Mike Chaponda, Sam Miti, Nick White, Nick Day, Nchafatso Obonyo, Diana M. Gibb, Elizabeth C. George, Arjen Dondorp, Kathryn Maitland, Roisin Connon, A. Sarah Walker, Jonathan Jonathan Gwasupika, and Emmanuel Oguda
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severe malaria ,adjunctive therapy ,children ,Africa ,clinical trial ,heparin-like molecule ,eng ,Medicine ,Science - Abstract
Background Even on the best antimalarial treatments (injectable artesunate) African children with severe malaria have poor outcomes with most deaths occurring early in the course of hospital admission ( 2mmol/l). Three intravenous doses will be given at admission (0 hours), 8 and 16 hours. APPT will be measured 1 hour after each dose (to assess maximum toxicity). Studying 20 children will allow sufficient data on safety to be generated across a range of doses to identify the maximum tolerated dose (MTD) using the Continual Reassessment Method, which adapts or informs subsequent doses for each child based on the data from previously enrolled children. The MTD will be identified based on the dose-toxicity model updated by each previous patient’s APTT results using standard methods. Conclusions The results of the Phase I trial will identify the final dose to be tested in a Phase II trial in terms of both efficacy and safety outcomes. Registration PACTR number: 202007890194806 (date 20/07/2020) ISRCTN32271864 (date 28/07/2021)
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- 2024
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25. Not all severe malaria cases are severe: Is it time to redefine severity criteria for malaria in non-endemic regions?
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Leire Balerdi-Sarasola, Jose Muñoz, Pedro Fleitas, Natalia Rodriguez-Valero, Alex Almuedo-Riera, Alba Antequera, Carme Subirà, Ignacio Grafia-Perez, Maria Ortiz-Fernández, Tessa de Alba, Miriam J. Álvarez-Martínez, M Eugenia Valls, Claudio Parolo, Pedro Castro, and Daniel Camprubí-Ferrer
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Severe malaria ,Imported malaria ,Travel medicine ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Background: The current definition of severe malaria in non-endemic areas follows WHO criteria, which mainly target children in malaria-endemic areas, potentially misclassifying cases in non-endemic regions. We assessed the performance of a modified severe malaria classification criteria within our patient cohort. Methods: A cohort study of patients managed for malaria in a non-endemic setting (2005–2023) was analyzed. We classified patients into severe malaria (SM) using WHO 2013 criteria except for hyperparasitemia, where 2 % threshold was applied. Patients with SM were distinguished as very severe malaria (VSM) when presenting at least one of the following conditions: parasitemia >10 %, pulmonary edema, impaired consciousness, seizures, renal failure, metabolic acidosis or hyperlactatemia, shock or hypoglycemia. In patients with SM and no criteria for VSM, less severe malaria (LSM) was defined by: 2–10 % parasitemia, hyperbilirubinemia, prostration, anemia or minor bleeding. The primary composite outcome was death or the need for a life-saving intervention, as analyzed in the three comparative groups. Secondary outcome was the prevalence of co-infections. Results: Among 506 patients with malaria, 176 (34.8 %) presented with SM. A total of 37 (7.3 %) patients developed a life-threatening condition, namely death (n = 4) and/or the need for life-saving interventions (n = 34). All fatalities and 33 out of the 34 life-saving interventions occurred in the VSM group. Patients in LSM group did not develop any life-threatening conditions. As to co-infections, 28 (5.5 %) patients had a community-acquired co-infection, with no differences between groups (p = 0.763). Conclusions: Severity criteria definitions would benefit from a review when assessing patients with malaria in non-endemic areas. Within the spectrum of SM, patients reclassified as LSM have a low risk of developing a life-threatening condition and present low co-infection incidence and could benefit from management out of intensive care units and a restrictive use of empirical antibiotics.
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- 2024
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26. An elevated level of interleukin-17A in a Senegalese malaria cohort is associated with rs8193038 IL-17A genetic variant
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Fatou Thiam, Gora Diop, Cedric Coulonges, Celine Derbois, Alassane Thiam, Abou Abdallah Malick Diouara, Mame Ndew Mbaye, Mamadou Diop, Cheikh Momar Nguer, Yakhya Dieye, Babacar Mbengue, Jean-Francois Zagury, Jean-Francois Deleuze, and Alioune Dieye
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Plasmodium falciparum ,Cytokines ,Single nucleotide polymorphism ,Severe malaria ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Malaria infection is a multifactorial disease partly modulated by host immuno-genetic factors. Recent evidence has demonstrated the importance of Interleukin-17 family proinflammatory cytokines and their genetic variants in host immunity. However, limited knowledge exists about their role in parasitic infections such as malaria. We aimed to investigate IL-17A serum levels in patients with severe and uncomplicated malaria and gene polymorphism’s influence on the IL-17A serum levels. In this research, 125 severe (SM) and uncomplicated (UM) malaria patients and 48 free malaria controls were enrolled. IL-17A serum levels were measured with ELISA. PCR and DNA sequencing were used to assess host genetic polymorphisms in IL-17A. We performed a multivariate regression to estimate the impact of human IL-17A variants on IL-17A serum levels and malaria outcomes. Elevated serum IL-17A levels accompanied by increased parasitemia were found in SM patients compared to UM and controls (P
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- 2024
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27. A machine learning approach for early identification of patients with severe imported malaria
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Alessandra D’Abramo, Francesco Rinaldi, Serena Vita, Riccardo Mazzieri, Angela Corpolongo, Claudia Palazzolo, Tommaso Ascoli Bartoli, Francesca Faraglia, Maria Letizia Giancola, Enrico Girardi, and Emanuele Nicastri
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Imported malaria ,Machine learning ,Severe malaria ,Risk factors ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background The aim of this study is to design ad hoc malaria learning (ML) approaches to predict clinical outcome in all patients with imported malaria and, therefore, to identify the best clinical setting. Methods This is a single-centre cross-sectional study, patients with confirmed malaria, consecutively hospitalized to the Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy from January 2007 to December 2020, were recruited. Different ML approaches were used to perform the analysis of this dataset: support vector machines, random forests, feature selection approaches and clustering analysis. Results A total of 259 patients with malaria were enrolled, 89.5% patients were male with a median age of 39 y/o. In 78.3% cases, Plasmodium falciparum was found. The patients were classified as severe malaria in 111 cases. From ML analyses, four parameters, AST, platelet count, total bilirubin and parasitaemia, are associated to a negative outcome. Interestingly, two of them, aminotransferase and platelet are not included in the current list of World Health Organization (WHO) criteria for defining severe malaria. Conclusion In conclusion, the application of ML algorithms as a decision support tool could enable the clinicians to predict the clinical outcome of patients with malaria and consequently to optimize and personalize clinical allocation and treatment.
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- 2024
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28. Diagnosis and management of malaria in the intensive care unit
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George Akafity, Nicholas Kumi, and Joyce Ashong
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Malaria ,Intensive care unit ,Severe malaria ,Antimicrobial resistance ,Antimalarials ,Artemisinin-based combination therapy ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Malaria is responsible for approximately three-quarters of a million deaths in humans globally each year. Most of the morbidity and mortality reported are from Sub-Saharan Africa and Asia, where the disease is endemic. In non-endemic areas, malaria is the most common cause of imported infection and is associated with significant mortality despite recent advancements and investments in elimination programs. Severe malaria often requires intensive care unit admission and can be complicated by cerebral malaria, respiratory distress, acute kidney injury, bleeding complications, and co-infection. Intensive care management includes prompt diagnosis and early initiation of effective antimalarial therapy, recognition of complications, and appropriate supportive care. However, the lack of diagnostic capacities due to limited advances in equipment, personnel, and infrastructure presents a challenge to the effective diagnosis and management of malaria. This article reviews the clinical classification, diagnosis, and management of malaria as relevant to critical care clinicians, highlighting the role of diagnostic capacity, treatment options, and supportive care.
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- 2024
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29. Effect of Paracetamol on Kidney Function in Severe Malaria (PROTECtS)
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Mahidol Oxford Tropical Medicine Research Unit, Kinshasa Medical Oxford Research Unit, and Katherine Plewes, MD PhD, Principal Investigator
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- 2023
30. An elevated level of interleukin-17A in a Senegalese malaria cohort is associated with rs8193038 IL-17A genetic variant.
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Thiam, Fatou, Diop, Gora, Coulonges, Cedric, Derbois, Celine, Thiam, Alassane, Diouara, Abou Abdallah Malick, Mbaye, Mame Ndew, Diop, Mamadou, Nguer, Cheikh Momar, Dieye, Yakhya, Mbengue, Babacar, Zagury, Jean-Francois, Deleuze, Jean-Francois, and Dieye, Alioune
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GENETIC variation , *MALARIA , *PARASITIC diseases , *GENETIC polymorphisms , *GENE expression - Abstract
Malaria infection is a multifactorial disease partly modulated by host immuno-genetic factors. Recent evidence has demonstrated the importance of Interleukin-17 family proinflammatory cytokines and their genetic variants in host immunity. However, limited knowledge exists about their role in parasitic infections such as malaria. We aimed to investigate IL-17A serum levels in patients with severe and uncomplicated malaria and gene polymorphism's influence on the IL-17A serum levels. In this research, 125 severe (SM) and uncomplicated (UM) malaria patients and 48 free malaria controls were enrolled. IL-17A serum levels were measured with ELISA. PCR and DNA sequencing were used to assess host genetic polymorphisms in IL-17A. We performed a multivariate regression to estimate the impact of human IL-17A variants on IL-17A serum levels and malaria outcomes. Elevated serum IL-17A levels accompanied by increased parasitemia were found in SM patients compared to UM and controls (P < 0.0001). Also, the IL-17A levels were lower in SM patients who were deceased than in those who survived. In addition, the minor allele frequencies (MAF) of two IL-17A polymorphisms (rs3819024 and rs3748067) were more prevalent in SM patients than UM patients, indicating an essential role in SM. Interestingly, the heterozygous rs8193038 AG genotype was significantly associated with higher levels of IL-17A than the homozygous wild type (AA). According to our results, it can be concluded that the IL-17A gene rs8193038 polymorphism significantly affects IL-17A gene expression. Our results fill a gap in the implication of IL-17A gene polymorphisms on the cytokine level in a malaria cohort. IL-17A gene polymorphisms also may influence cytokine production in response to Plasmodium infections and may contribute to the hyperinflammatory responses during severe malaria outcomes. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Exploring adjunctive therapies for cerebral malaria.
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Bensalel, Johanna and Gallego-Delgado, Julio
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CEREBRAL malaria ,CHILD patients ,MALARIA ,PARASITEMIA ,DRUG target - Abstract
Cerebral malaria (CM) is one of the most severe complications of malaria infection characterized by coma and neurological effects. Despite standardized treatment of malaria infection with artemisinin-based combination therapies (ACT), the mortality rate is still high, and it primarily affects pediatric patients. ACT reduces parasitemia but fails to adequately target the pathogenic mechanisms underlying CM, including blood-brain-barrier (BBB) disruption, endothelial activation/dysfunction, and hyperinflammation. The need for adjunctive therapies to specifically treat this form of severe malaria is critical as hundreds of thousands of people continue to die each year from this disease. Here we present a summary of some potential promising therapeutic targets and treatments for CM, as well as some that have been tested and deemed ineffective or, in some cases, even deleterious. Further exploration into these therapeutic agents is warranted to assess the effectiveness of these potential treatments for CM patients. [ABSTRACT FROM AUTHOR]
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- 2024
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32. A machine learning approach for early identification of patients with severe imported malaria.
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D'Abramo, Alessandra, Rinaldi, Francesco, Vita, Serena, Mazzieri, Riccardo, Corpolongo, Angela, Palazzolo, Claudia, Ascoli Bartoli, Tommaso, Faraglia, Francesca, Giancola, Maria Letizia, Girardi, Enrico, and Nicastri, Emanuele
- Abstract
Background: The aim of this study is to design ad hoc malaria learning (ML) approaches to predict clinical outcome in all patients with imported malaria and, therefore, to identify the best clinical setting. Methods: This is a single-centre cross-sectional study, patients with confirmed malaria, consecutively hospitalized to the Lazzaro Spallanzani National Institute for Infectious Diseases, Rome, Italy from January 2007 to December 2020, were recruited. Different ML approaches were used to perform the analysis of this dataset: support vector machines, random forests, feature selection approaches and clustering analysis. Results: A total of 259 patients with malaria were enrolled, 89.5% patients were male with a median age of 39 y/o. In 78.3% cases, Plasmodium falciparum was found. The patients were classified as severe malaria in 111 cases. From ML analyses, four parameters, AST, platelet count, total bilirubin and parasitaemia, are associated to a negative outcome. Interestingly, two of them, aminotransferase and platelet are not included in the current list of World Health Organization (WHO) criteria for defining severe malaria. Conclusion: In conclusion, the application of ML algorithms as a decision support tool could enable the clinicians to predict the clinical outcome of patients with malaria and consequently to optimize and personalize clinical allocation and treatment. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
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33. Perturbations de l'hémogramme au cours du paludisme grave de l'enfant au centre hospitalier et universitaire (CHU) de Bouaké (Côte d'Ivoire).
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Yeboua, R.K.Y., Yenan, J.P., Yao, K.C., Akanji, I.A., Aka-Tanoh, K.A.-H., Avi-Siallou, C.H., Adou, L.R., Sahi, G.J.L., Amani, E.A.E., and Assé, K.V.
- Abstract
L'anémie sévère est la seule anomalie à l'hémogramme définie comme critère de gravité du paludisme. Cependant, il existe d'autres perturbations à l'hémogramme non encore décrites au CHU de Bouaké. L'objectif était d'étudier les anomalies observées à l'hémogramme au cours du paludisme grave de l'enfant pour l'amélioration du pronostic. Étude transversale menée dans le service de pédiatrie du CHU de Bouaké de janvier à mars 2021. Les cas de paludisme grave avec bilan paraclinique comportant au moins un hémogramme ont été inclus. Les paramètres d'étude étaient sociodémographiques, cliniques et biologiques. La comparaison des variables était faite avec le test de Chi2 ou le test exact de Fisher au seuil de significativité p < 0,05. Deux cent huit cas de paludisme grave dont 203 avec une anomalie à l'hémogramme sur au moins une lignée sanguine soit une fréquence des anomalies de 97,60 %. Le sex-ratio était de 1,74 avec un âge médian de 29 mois [6–144 mois]. Les motifs d'admission étaient dominés par : fièvre (83,17 %), vomissements (50,48 %) et anémie (49,04 %). La parasitémie moyenne était de 13 321,92 trophozoïtes/μL [800–150 000]. Les formes de gravité étaient : anémie sévère (79,81 %), formes neurologiques (10,10 %), formes neuro-anémiques (5,29 %), hyperparasitémie (4,80 %). Les principales anomalies à l'hémogramme étaient l'anémie (97,6 %), la thrombopénie (82,69 %), la lymphopénie (68,75 %) et l'hyperleucocytose (63,94 %). La létalité était de 4,81 %. Les facteurs significativement associés au décès étaient la thrombopénie profonde < 25 000/μL (p < 0,000001), l'anémie sévère < 5 g/dL (p < 0,001) et la densité parasitaire ≥ 50 000 trophozoïtes/μL (p < 0,006). La thrombopénie et la lymphopénie sont aussi fréquentes au cours du paludisme grave de l'enfant. La thrombopénie profonde est un facteur de mauvais pronostic d'où l'intérêt d'études complémentaires afin de la retenir éventuellement comme critère de gravité. Severe anemia is the only blood count abnormality defined as a criterion of malaria severity. However, there are other blood count abnormalities that have not yet been described at Bouaké University Hospital. The aim of this study was to investigate the blood count abnormalities observed in severe malaria in children with a view to improving the prognosis. Cross-sectional study conducted in the Paediatrics Department of the Bouaké University Hospital from January to March 2021. Cases of severe malaria with a paraclinical work-up including at least one blood count were included. The study parameters were sociodemographic, clinical and biological. Variables were compared using the Chi2 test or Fisher's exact test at a significance level of p < 0.05. Two hundred and eight cases of severe malaria, including 203 with a blood count abnormality in at least one blood line, i.e. a frequency of abnormalities of 97.60%. The sex ratio was 1.74 with a median age of 29 months [6–144 months]. Reasons for admission were dominated by fever (83.17%), vomiting (50.48%) and anemia (49.04%). Mean parasitaemia was 13,321.92 trophozoites/μL [800–15,000]. The forms of severity were: severe anemia (79.81%), neurological forms (10.10%), neuro-anemic forms (5.29%), hyperparasitemia (4.80%). The main blood count abnormalities were anemia (97.6%), thrombocytopenia (82.69%), lymphopenia (68.75 %) and hyperleukocytosis (63.94%). Case fatality was 4.81%. Factors significantly associated with death were profound thrombocytopenia < 25,000/μL (p < 0.000001), severe anemia < 5 g/dL (p < 0.001) and parasite density ≥ 50,000 trophozoites/μL (p < 0.006). Thrombocytopenia and lymphopenia are also common in severe malaria in children. Profound thrombocytopenia is a poor prognostic factor, hence the need for further studies to determine whether it should be included as a criterion of severity. [ABSTRACT FROM AUTHOR]
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- 2024
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34. Continúa la controversia: exanguinotransfusión para pacientes con malaria grave.
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Chediack, Viviana, Cini, Paula V., Gregori Sabelli, Rosana, Saúl, Pablo, Cunto, Eleonora, and Gonzalez, Carlos A.
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DRUG therapy for malaria ,EXTRACORPOREAL membrane oxygenation ,BLOOD transfusion ,PARASITEMIA - Abstract
Copyright of Revista Argentina de Terapia Intensiva is the property of Sociedad Argentina de Terapia Intensiva (SATI) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
35. Severe malaria-related disability in African children: a scoping review.
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Engeda, Eshetu Haileselassie, Aldersey, Heather M., Davison, Colleen M., Gelaye, Kassahun Alemu, Abebe, Abey Bekele, Chala, Mulugeta Bayisa, and Fayed, Nora
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CINAHL database , *PSYCHOLOGY of children with disabilities , *MEDICAL information storage & retrieval systems , *SYSTEMATIC reviews , *MALARIA , *LITERATURE reviews , *MEDLINE , *DISEASE complications , *CHILDREN - Abstract
Disability is a consequence of severe malaria for a significant proportion of African children. This scoping review aims to describe the impact of severe malaria on African children according to current literature using an international biopsychical classification and framework of disability and functioning. MEDLINE, EMBASE, Global Health, and CINHAL databases were searched for original research conducted on African children aged 0–18 using terms related to severe malaria and components of disability. Independent and dependent variables were extracted and classified using the World Health Organization's International Classification of Functioning, Disability, and Health-Children and Youth version (ICF-CY) using standardized coding methods. Seventy-two percent of the measured variables in the 34 included studies were coded as "body functions," (i.e., impairments), such as mental, neuromusculoskeletal, movement, and sensory functions, and 23.3% of variables were coded as "activities and participation" (i.e., activity limitations/participation restrictions), such as difficulties with general tasks and demands, communication, mobility, interpersonal interactions, and relationships. "Environment" variables such as family support, health access, education, or societal attitudes were not found in the included studies. Existing peer-reviewed quantitative research of severe malaria-related disability is focused on neurological sequelae, with less research about activity limitations and participation restrictions. Promoting the use of a comprehensive biopsychosocial disability framework and classification system for severe malaria will provide a framework that other researchers, policymakers, and rehabilitation professionals can consider when looking at the best ways to support outcomes for children with severe malaria. Using a framework of the ICF-CY, we have highlighted the need for better research into child functioning outcomes in severe malaria research, especially within the domain of child participation. Policymakers should be encouraged to support better holistic evaluation, support, and rehabilitation of children who have had severe malaria. [ABSTRACT FROM AUTHOR]
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- 2024
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36. Clinico-epidemiological profiles & outcome of severe malaria in children under-five in the tribal area of Kalahandi, Odisha.
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Edassery, Aquinas, Meher, Ajay Kumar, Gupta, Vanshika, and Rodriguez, Rashmi
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- 2024
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37. A Phase I trial of Non-invasive Ventilation and seizure prophylaxis with levetiracetam In Children with Cerebral Malaria Trial (NOVICE-M Trial) [version 1; peer review: 2 approved]
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Mainga Hamaluba, Diana M. Gibb, Elizabeth C. George, Symon M. Kariuki, Kathryn Maitland, Roisin Connon, Nchafasto Obonyo, Christabel Mogaka, Thomas N. Williams, Emmanuel Ogoda, A. Sarah Walker, and Charles Newton
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severe malaria ,prophylactic anticonvulsants ,children ,Africa ,clinical trial ,non invasive ventilation ,eng ,Medicine ,Science - Abstract
Background African children with cerebral malaria and seizures caused Plasmodium falciparum are at greater risk of poor outcomes including death and neurological sequelae. The agonal events are severe hypoventilation and respiratory arrest often triggered by seizures. We hypothesised that prophylactic anti-seizure medication (ASM) could avert ‘spikes’ of intracranial pressure during or following seizures and that adequate ventilation could be supported by biphasic Cuirass Ventilation (BCV) which requires no intubation. Methods A Phase I trial conducted in Kilifi, Kenya designed to provide data on safety, feasibility and preliminary data on seizure control using prophylactic ASM (levetiracetam) and BCV as non-invasive ventilatory support in children with cerebral malaria. Children aged 3 months to 12-years hospitalised with P falciparum malaria (positive rapid diagnostic test or a malaria slide), a Blantyre Coma Score ≤2 and a history of acute seizures in this illness are eligible for the trial. In a phased evaluation we will study i) BCV alone for respiratory support (n=10); ii) prophylactic LVT: 40mg/kg loading dose then 30mg/kg every 12 hours given via nasogastric tube for 72 hours (or until fully conscious) plus BCV support (n=10) and; iii) prophylactic LVT: 60mg/kg loading dose then 45mg/kg every 12 hours given via nasogastric tube for 72 hours (or until fully conscious) plus BCV support (n=10). Primary outcome measure: cumulative time with a clinically detected seizures or number of observed seizures over 36 hours. Secondary outcomes will be assessed by feasibility or ability to implement BCV, and recovery from coma within 36 hours. Safety endpoints include: aspiration during admission; death at 28 days and 180 days; and de-novo neurological impairments at 180 days. Conclusions This is a Phase I trial largely designed to test the feasibility, tolerability and safety of using non-invasive ventilatory support and LVT prophylaxis in cerebral malaria. Registration ISRCTN76942974 (5.02.2019); PACTR202112749708968 (20.12.2021).
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- 2024
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38. A novel locus in CSMD1 gene is associated with increased susceptibility to severe malaria in Malian children
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Delesa Damena, Amadou Barry, Robert Morrison, Santara Gaoussou, Almahamoudou Mahamar, Oumar Attaher, Djibrilla Issiaka, Yahia Dicko, Alassane Dicko, Patrick Duffy, and Michal Fried
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candidate gene ,snps ,severe malaria ,complement control ,CSMD1 ,Genetics ,QH426-470 - Abstract
BackgroundPlasmodium falciparum malaria is still a leading cause of child mortality in sub-Saharan Africa. The clinical manifestations of malaria range from asymptomatic infection to severe disease. The variation in clinical presentation is partly attributed to host genetic factors with estimated narrow-sense heritability of 23%. Here, we investigate the associations between candidate gene polymorphisms and the likelihood of severe malaria (SM) in a cohort of Malian children.MethodsBased on our previous genome-wide association studies (GWAS) analysis, candidate genes were selected for in-depth analysis using several criteria including gene-level GWAS scores, functional overlap with malaria pathogenesis, and evidence of association with protection or susceptibility to other infectious or inflammatory diseases. Single Nucleotide Polymorphisms (SNPs) residing within these genes were selected mainly based on p-values from previous severe malaria susceptibility GWAS studies and minor allele frequency (MAF) in West African populations.ResultsOf 182 candidate genes reported in our previous study, 11 genes and 22 SNPs residing in these genes were selected. The selected SNPs were genotyped using KASP technology in 477 DNA samples (87 SM and 390 controls). Logistic regression analysis revealed that a common intron variant, rs13340578 in CUB and Sushi Multi Domain (CSMD1) gene, is associated with increased odds of SM in recessive mode of inheritance (MAF = 0.42, OR = 1.8, 95% CI = [1.78, 1.84], p = 0.029). The SNP is in linkage disequilibrium (LD) with multiple variants with regulatory features.ConclusionTaken together, the current study showed that an intron variant rs13340578, residing in CSMD1 gene, is associated with increased susceptibility to malaria. This finding suggests that modified regulation of complement may contribute to malaria disease severity. Further studies are needed to identify the causal variants and the underlying molecular mechanisms.
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- 2024
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39. Association of Diabetes and Metabolic Syndrome With Severe Malaria in Cameroon
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University of Dschang and Katja Wyss, prinicpal investigator
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- 2023
40. Assessing caregivers’ perceptions of treatment-seeking for suspected severe malaria in the Democratic Republic of the Congo
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Jean Okitawutshu, Antoinette Tshefu, Jean-Claude Kalenga, Giulia Delvento, Christian Burri, Manuel W. Hetzel, Christian Lengeler, and Aita Signorell
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Severe malaria ,Malaria infection ,Rectal artesunate ,Treatment-seeking ,Knowledge, attitude and practice ,Democratic Republic of the Congo ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Malaria remains a major public health issue in the Democratic Republic of the Congo (DRC), accounting for 44% deaths among outpatient visits in children
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- 2023
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41. Prophylaxis Failure and Successful Management of Delayed-Onset Malaria with Renal Complications: A Case Report with Oral Artemether-Lumefantrine Treatment.
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Tolaj, Ilir, Bunjaku, Gramoz, Mehmeti, Murat, and Begolli, Yllka
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ORAL drug administration , *MALARIA , *LOSS of consciousness , *BLOOD parasites , *PARENTERAL therapy - Abstract
This case report presents a critical clinical scenario involving a 55-year-old patient who developed severe Plasmodium falciparum malaria with renal complications despite receiving doxycycline prophylaxis while traveling in a malaria-endemic region. The case emphasizes the potential failure of doxycycline prophylaxis and highlights the importance of considering malaria in patients with a history of travel to endemic areas, even if they have adhered to prophylactic treatment. The patient's clinical presentation included fever, extreme fatigue, and loss of consciousness, leading to hospitalization. Laboratory findings revealed severe anemia, elevated liver enzymes, and impaired renal function, consistent with the criteria for severe malaria. The diagnosis was confirmed by the presence of Plasmodium falciparum parasites on thin blood smears. Due to limited access to parenteral antimalarial medications in Kosovo, the patient received oral artemether-lumefantrine, resulting in clinical improvement. Supportive care and dialysis played a vital role in the patient's recovery. This case report underscores the need for increased awareness of prophylaxis failure, the challenges of managing severe malaria in non-endemic countries, and the importance of timely and appropriate interventions to improve outcomes in severe malaria cases, particularly those with renal involvement. [ABSTRACT FROM AUTHOR]
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- 2023
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42. Trends in clinical features and severity of Plasmodium vivax malaria among children at tertiary care center in North India.
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Arya, Aditi, Meena, Shyam Sundar, Matlani, Monika, Chaudhry, Shewta, and Singh, Vineeta
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DAY care centers , *PLASMODIUM vivax , *CEREBRAL malaria , *MALARIA , *ADULT respiratory distress syndrome , *INSECTICIDE resistance - Abstract
Background Malaria is a significant cause of morbidity and mortality in adults and children. Plasmodium falciparum is the primary cause of severe malaria, but recently Plasmodium vivax is also recognized to cause severe malaria-associated morbidity and mortality. The study focuses on determining the mortality related to severity parameters in individuals under 12 years and their critical presentation in P.vivax malaria-infected children. Methods A prospective cross-sectional hospital-based study was conducted at Safdarjung Hospital, New Delhi, and ICMR-NIMR, New Delhi. All clinically suspected cases were admitted for screening. Exclusion criteria (rapid malaria antigen test, microscopy and medication history) were applied to all the admitted patients (n = 221) to obtain P.vivax patients only. Patients aged ≤ 12 years were included in the study. DNA was extracted from dried blood spots and amplified by nested PCR, followed by visualization on gel electrophoresis. Result A total of 221 clinically suspected cases of malaria were screened for P.vivax. After implementing various exclusion criteria, 45/221 cases were enrolled for the study, among which 44.4% (20/45) of children had the symptoms of severe malaria in terms of cerebral malaria, thrombocytopenia, anemia, pancytopenia, acute respiratory distress syndrome and hemophagocytic lymphohistiocytosis. Conclusion Plasmodium vivax mono-infection can cause severe manifestation and must be treated as P.falciparum without any delay because it may lead to increased morbidity and mortality. A changing trend in clinical symptoms has shown in P.vivax which was an earlier phenomenon of P.falciparum. [ABSTRACT FROM AUTHOR]
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- 2023
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43. Implementation of the Revised National Malaria Control Guidelines: Compliance and Challenges in Public Health Facilities in a Southern Nigerian State.
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Akpan, Ubong, Edet, Ekpo, Arogundade, Kazeem, Akpanika, Chinyere, Ekott, Mabel, and Etuk, Saturday
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Background: There has been a concerted effort to reduce malaria burden and bring malaria related mortality to zero. The objectives of this survey were to assess the level of adherence to the current revised malaria control guidelines in the public health facilities in Cross River State of Nigeria and to identify the challenges as well as suggest ways for improvement in treatment outcomes. Methods: This was a mixed observational and qualitative survey conducted in 32 public health facilities from 21st to 25th June 2022. Treatment records on malaria were assessed for adherence to the National guidelines. In-depth interviews were conducted with 36 key informants and 4 purposefully selected stakeholders to identify the successes and challenges. Quantitative data were summarized and presented in simple proportions and percentages while qualitative information was recorded, the transcripts thematically coded, analyzed and presented using NVivo 11 software. Results: The survey revealed that vector control program was poorly implemented across the state. For case management, presumptive treatment was frequently practiced especially at secondary health facilities for uncomplicated malaria. More than 60% of uncomplicated malaria were being treated with parenteral artemether instead of oral artemisinin combination therapy (ACTs) as recommended. Severe malaria were not treated with Intravenous (IV) Artesunate as first line drug in about 40% of the secondary health facilities. Key successes were noted in malaria management in pregnancy. Major challenges identified include: stock out of commodities, shortage of clinical man power, and low trust in parasitological diagnosis. Conclusion: The survey showed that adherence to the key recommendations in various categories of malaria control among health care providers in the public health facilities was below expectation. Malaria preventive treatment in pregnancy with SP fared better perhaps because of its inclusion in ANC packages. [ABSTRACT FROM AUTHOR]
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- 2023
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44. The association of intraleucocytic malaria pigment and disease severity in Papua New Guinean children with severe P. falciparum malaria.
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Lufele, Elvin, Manning, Laurens, Lorry, Lina, Warrel, Jonathan, Aipit, Susan, Robinson, Leanne J, and Laman, Moses
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MALARIA ,COMA ,SYMPTOMS ,ACIDOSIS ,PLATELET count ,PLASMODIUM falciparum - Abstract
Background Plasmodium falciparum pigment-containing leucocytes (PCLs) are associated with adverse clinical manifestations of severe malaria in African children. However, limited data exist on the association of PCLs in settings outside of Africa. Methods Thin films on peripheral blood slides obtained from children ages 6 months–10 y with severe malaria were examined for PCLs. The intraleucocytic pigment data were correlated with clinical phenotypic data such as severe anaemia, metabolic acidosis and coma to determine the association of PCLs with clinical phenotypes of severe malaria and outcome. Results Of the 169 children with severe P. falciparum malaria confirmed by microscopy, 76% (129/169) had PCLs. Compared with children without PCLs, the presence (adjusted odds ratio [AOR] 3.2 [95% confidence interval {CI} 1.5 to 6.9], p≤0.01) and quantity (AOR 1.0 [95% CI 1.0 to 1.1], p=0.04) of pigment-containing monocytes (PCMs) was significantly associated with severe anaemia, while the quantity of both PCMs (AOR 1.0 [95% CI 1.0 to 1.1], p≤0.01) and pigment-containing neutrophils (AOR 1.0 [95% CI 1.0 to 1.1], p=0.01) was significantly associated with metabolic acidosis. Plasma P. falciparum histidine-rich protein-2 level negatively correlated with the platelet count (r=−0.5, p≤0.01) in patients with PCLs and no PCLs. Conclusions In Papua New Guinean children with severe P. falciparum malaria, the presence and quantity of PCLs are predictors of disease severity, severe anaemia and metabolic acidosis. [ABSTRACT FROM AUTHOR]
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- 2023
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45. Antibody to Plasmodium falciparum Variant Surface Antigens, var Gene Transcription, and ABO Blood Group in Children With Severe or Uncomplicated Malaria.
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Barua, Priyanka, Duffy, Michael F, Manning, Laurens, Laman, Moses, Davis, Timothy M E, Mueller, Ivo, Haghiri, Ali, Simpson, Julie A, Beeson, James G, and Rogerson, Stephen J
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ABO blood group system , *CELL surface antigens , *PLASMODIUM falciparum , *BLOOD groups , *IMMUNOGLOBULIN G , *BLOOD group incompatibility - Abstract
Background Antibodies to variant surface antigens (VSAs) such as Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) may vary with malaria severity. The influence of ABO blood group on antibody development is not understood. Methods Immunoglobulin G antibodies to VSAs in Papua New Guinean children with severe (n = 41) or uncomplicated (n = 30) malaria were measured by flow cytometry using homologous P falciparum isolates. Isolates were incubated with ABO-matched homologous and heterologous acute and convalescent plasma. RNA was used to assess var gene transcription. Results Antibodies to homologous, but not heterologous, isolates were boosted in convalescence. The relationship between antibody and severity varied by blood group. Antibodies to VSAs were similar in severe and uncomplicated malaria at presentation, higher in severe than uncomplicated malaria in convalescence, and higher in children with blood group O than other children. Six var gene transcripts best distinguished severe from uncomplicated malaria, including UpsA and 2 CIDRα1 domains. Conclusions ABO blood group may influence antibody acquisition to VSAs and susceptibility to severe malaria. Children in Papua New Guinea showed little evidence of acquisition of cross-reactive antibodies following malaria. Var gene transcripts in Papua New Guinean children with severe malaria were similar to those reported from Africa. [ABSTRACT FROM AUTHOR]
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- 2023
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46. Assessing caregivers' perceptions of treatment-seeking for suspected severe malaria in the Democratic Republic of the Congo.
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Okitawutshu, Jean, Tshefu, Antoinette, Kalenga, Jean-Claude, Delvento, Giulia, Burri, Christian, Hetzel, Manuel W., Lengeler, Christian, and Signorell, Aita
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CAREGIVER attitudes , *MALARIA , *PUBLIC health , *CAREGIVERS , *HAZARD signs - Abstract
Background: Malaria remains a major public health issue in the Democratic Republic of the Congo (DRC), accounting for 44% deaths among outpatient visits in children < 5 years of age, and 22% of facility deaths. Understanding determinants of caregivers' treatment-seeking patterns and decision-making is crucial in reducing the malaria burden. Methods: In the frame of the Community Access to Rectal Artesunate for Malaria (CARAMAL) project, cross-sectional household surveys that randomly sampled villages and households were carried-out in three rural DRC health zones prior to the rollout of pre-referral Rectal Artesunate (RAS) and then 9 and 19 months after RAS rollout (post-RAS). Data were captured electronically through face-to-face interviews with the main caregivers of children < 5 years. Capillary blood samples of the children were tested for malaria and anaemia. The main study outcome was whether caregiver "sought treatment outside home" when the child had fever. Multilevel mixed effects logistic regression models using village as random effect and health zone as a fixed effect was performed to assess treatment-seeking predictors. Results: 2439 household interviews were completed (pre-RAS 888 and post-RAS 1551), including 316 and 653 treatment-seeking interviews. Overall, 3499 children < 5 years were tested for malaria and anaemia (pre-RAS 1,315 and post-RAS 2184). Caregiver's recognition of severe malaria signs was poor, while knowledge of symptoms of uncomplicated malaria seemed high. Despite this, danger signs significantly increased the odds of seeking treatment (aOR = 2.12, 95%CI 1.03–4.38), the same was found for the "least poor" quintile (aOR = 3.01, 95%CI 1.03–8.82), as well as residents of Kingandu (aOR = 2.78, 95%CI 1.01–7.65). "Doing something at home" against fever negatively affected treatment-seeking in both study phases. RAS acceptance was high, at almost 100%. Malaria prevalence was higher post-RAS (45.2%) compared to pre-RAS (34.4%), p = 0.003, but anaemia, although high (≥ 75%), was similar in both study phases (p = 0.92). Conclusion: In remote communities with high malaria prevalence in the DRC, malaria remains a major problem. Improving the recognition of danger signs of severe disease and introducing pre-referral RAS may improve treatment-seeking and contribute to reducing malaria-related mortality among children—if quality of care can be guaranteed. [ABSTRACT FROM AUTHOR]
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- 2023
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47. Exploring adjunctive therapies for cerebral malaria
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Johanna Bensalel and Julio Gallego-Delgado
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cerebral malaria ,severe malaria ,adjunctive therapy ,endothelium ,child mortality ,Microbiology ,QR1-502 - Abstract
Cerebral malaria (CM) is one of the most severe complications of malaria infection characterized by coma and neurological effects. Despite standardized treatment of malaria infection with artemisinin-based combination therapies (ACT), the mortality rate is still high, and it primarily affects pediatric patients. ACT reduces parasitemia but fails to adequately target the pathogenic mechanisms underlying CM, including blood-brain-barrier (BBB) disruption, endothelial activation/dysfunction, and hyperinflammation. The need for adjunctive therapies to specifically treat this form of severe malaria is critical as hundreds of thousands of people continue to die each year from this disease. Here we present a summary of some potential promising therapeutic targets and treatments for CM, as well as some that have been tested and deemed ineffective or, in some cases, even deleterious. Further exploration into these therapeutic agents is warranted to assess the effectiveness of these potential treatments for CM patients.
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- 2024
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48. Spatiotemporal dynamics of malaria in Banmauk Township, Sagaing region of Northern Myanmar: characteristics, trends, and risk factors
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Aung, Pyae Linn, Soe, Myat Thu, Oo, Thit Lwin, Aung, Kyaw Thu, Lin, Kyaw Kyaw, Thi, Aung, Menezes, Lynette, Parker, Daniel M, Cui, Liwang, and Kyaw, Myat Phone
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Malaria ,Clinical Research ,Infectious Diseases ,Orphan Drug ,Rare Diseases ,Prevention ,Pediatric ,Vector-Borne Diseases ,2.4 Surveillance and distribution ,Aetiology ,Infection ,Good Health and Well Being ,Aged ,Child ,Child ,Preschool ,Humans ,Malaria ,Falciparum ,Malaria ,Vivax ,Male ,Myanmar ,Plasmodium falciparum ,Plasmodium vivax ,Risk Factors ,Epidemiology ,Annual Parasite incidence ,Spatial distribution ,Severe malaria ,Risk factor ,Northern Myanmar ,Microbiology ,Clinical Sciences ,Medical Microbiology - Abstract
BackgroundWhile national malaria incidence has been declining in Myanmar, some subregions within the nation continue to have high burdens of malaria morbidity and mortality. This study assessed the malaria situation in one of these regions, Banmauk Township, located near the Myanmar-India border. Our goal was to provide a detailed description of the malaria epidemiology in this township and to provide some evidence-based recommendations to formulate a strategy for reaching the national malaria elimination plan. Banmauk consistently has one of the highest malaria burdens in Myanmar.MethodsWith the implementation of strengthened malaria control and surveillance activities after the endorsement of a national malaria elimination plan in 2015, detailed incidence data were obtained for 2016-2018 for Banmauk Township. The data include patient demographics, parasite species, disease severity, and disease outcome. Data were analyzed to identify characteristics, trends, distribution, and risk factors.ResultsDuring 2016-2018, 2,402 malaria cases were reported, with Plasmodium falciparum accounting for 83.4% of infections. Both P. falciparum and P. vivax were transmitted more frequently during the rainy season (May-October). Despite intensified control, the annual parasite incidence rate (API) in 2017 (11.0) almost doubled that in 2016 (6.5). In total, 2.5% (59/2042) of the cases, of which 54 P. falciparum and 5 P. vivax, were complicated cases, resulting in 5 deaths. Malaria morbidity was high in children
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- 2022
49. Severe Malaria in the ICU
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Díaz-Rodríguez, Cristina, Canas-Pérez, Isabel, Pérez-Torres, David, Cecconi, Maurizio, Series Editor, De Backer, Daniel, Series Editor, Pérez-Torres, David, editor, Martínez-Martínez, María, editor, and Schaller, Stefan J., editor
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- 2023
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50. Severe Fungal and Parasitic Infections in the Intensive Care Unit
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Lakbar, Ines, Pérez-Torres, David, Cecconi, Maurizio, Series Editor, De Backer, Daniel, Series Editor, Pérez-Torres, David, editor, Martínez-Martínez, María, editor, and Schaller, Stefan J., editor
- Published
- 2023
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