Malaria Research Articles

Monoamine oxidase-A (MAO-A) low-expression variants and increased risk of Plasmodium vivax malaria relapses.

Primaquine is essential for the radical cure of Plasmodium vivax malaria and must be metabolized into its bioactive metabolites. Accordingly, polymorphisms in primaquine-metabolizing enzymes can impact the treatment efficacy. This pioneering study explores the influence of monoamine oxidase-A (MAO-A) on primaquine metabolism and its impact on malaria relapses. Samples from 205 patients with P. vivax malaria were retrospectively analysed by genotyping polymorphisms in MAO-A and cytochrome P450 2D6 (CYP2D6) genes. We measured the primaquine and carboxyprimaquine blood levels in 100 subjects for whom blood samples were available on the third day of treatment. We also examined the relationship between the enzyme variants and P. vivax malaria relapses in a group of subjects with well-documented relapses. The median carboxyprimaquine level was significantly reduced in individuals carrying low-expression MAO-A alleles plus impaired CYP2D6. In addition, this group experienced significantly more P. vivax relapses. The low-expression MAO-A status was not associated with malaria relapses when CYP2D6 had normal activity. This suggests that the putative carboxyprimaquine contribution is irrelevant when the CYP2D6 pathway is fully active. We found evidence that the low-expression MAO-A variants can potentiate the negative impact of impaired CYP2D6 activity, resulting in lower levels of carboxyprimaquine metabolite and multiple relapses. The findings support the hypothesis that carboxyprimaquine may be further metabolized through CYP-mediated pathways generating bioactive metabolites that act against the parasite.

Transcriptional responses of brain endothelium to Plasmodium falciparum patient-derived isolates in vitro.

Cerebral malaria (CM) is the most prevalent and deadly complication of severe Plasmodium falciparum infection. A hallmark of this disease is sequestration of P. falciparum-infected erythrocytes (IE) in brain microvasculature that ultimately results in breakdown of the blood-brain barrier. Here, we compared the effect of P. falciparum parasites derived from uncomplicated malaria (UM) and CM cases on the relative gene expression of human brain microvascular endothelial cells (HBMECs) for a panel of genes. We observed a significant effect on the endothelial transcriptional response in the presence of IE, yet there is no significant correlation between HBMEC responses and the type of clinical syndrome (UM or CM). Furthermore, there was no correlation between HBMEC gene expression and both binding itself and the level of IE binding to HBMECs. Our results suggest that interaction of IE with endothelial cells induces endothelial responses that are independent of clinical origin and not entirely driven by surface Plasmodium falciparum erythrocyte membrane protein 1 expression.

Chloroquine has shown high therapeutic efficacy against uncomplicated Plasmodium vivax malaria in southern Ethiopia: seven decades after its introduction

BackgroundPlasmodium vivax malaria is a leading cause of morbidity in Ethiopia. The first-line treatment for P. vivax is chloroquine (CQ) and primaquine (PQ), but there have been local reports of CQ resistance. A clinical study was conducted to determine the efficacy of CQ for the treatment of P. vivax malaria in southern Ethiopia.MethodsIn 2021, patients with P. vivax mono-infection and uncomplicated malaria were enrolled and treated with 25 mg/kg CQ for 3 consecutive days. Patients were followed for 28 days according to WHO guidelines. The data were analysed using per-protocol (PP) and Kaplan‒Meier (K‒M) analyses to estimate the risk of recurrent P. vivax parasitaemia on day 28.ResultsA total of 88 patients were enrolled, 78 (88.6%) of whom completed the 28 days of follow-up. Overall, 76 (97.4%) patients had adequate clinical and parasitological responses, and two patients had late parasitological failures. The initial therapeutic response was rapid, with 100% clearance of asexual parasitaemia within 48 h.ConclusionDespite previous reports of declining chloroquine efficacy against P. vivax, CQ retains high therapeutic efficacy in southern Ethiopia, supporting the current national treatment guidelines. Ongoing clinical monitoring of CQ efficacy supported by advanced molecular methods is warranted to inform national surveillance and ensure optimal treatment guidelines.

Acute lung injury is prevented by monocyte locomotion inhibitory factor in an experimental severe malaria mouse model

Acute lung injury caused by severe malaria (SM) is triggered by a dysregulated immune response towards the infection with Plasmodium parasites. Postmortem analysis of human lungs shows diffuse alveolar damage (DAD), the presence of CD8 lymphocytes, neutrophils, and increased expression of Intercellular Adhesion Molecule 1 (ICAM-1). P. berghei ANKA (PbA) infection in C57BL/6 mice reproduces many SM features, including acute lung injury characterized by DAD, CD8+ T lymphocytes and neutrophils in the lung parenchyma, and tissular expression of proinflammatory cytokines and adhesion molecules, such as IFNγ, TNFα, ICAM, and VCAM. Since this is related to a dysregulated immune response, immunomodulatory agents are proposed to reduce the complications of SM. The monocyte locomotion inhibitory factor (MLIF) is an immunomodulatory pentapeptide isolated from axenic cultures of Entamoeba hystolitica. Thus, we evaluated if the MLIF intraperitoneal (i.p.) treatment prevented SM-induced acute lung injury. The peptide prevented SM without a parasiticidal effect, indicating that its protective effect was related to modifications in the immune response. Furthermore, peripheral CD8+ leukocytes and neutrophil proportions were higher in infected treated mice. However, the treatment prevented DAD, CD8+ cell infiltration into the pulmonary tissue and downregulated IFNγ. Moreover, VCAM-1 expression was abrogated. These results indicate that the MLIF treatment downregulated adhesion molecule expression, impeding cell migration and proinflammatory cytokine tissular production, preventing acute lung injury induced by SM. Our findings represent a potential novel strategy to avoid this complication in various events where a dysregulated immune response triggers lung injury.

Perspectives of healthcare professionals on training for quantitative G6PD testing during implementation of tafenoquine in Brazil (QualiTRuST Study).

Effective radical cure of Plasmodium vivax malaria is essential for malaria elimination in Brazil. P. vivax radical cure requires administration of a schizonticide, such as chloroquine, plus an 8-aminoquinoline. However, 8-aminoquinolines cause hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, requiring prior screening to exclude those at risk. Brazil is pioneering the implementation of tafenoquine, a single-dose 8-aminoquinoline indicated for P. vivax patients with >70% of normal G6PD activity. Tafenoquine implementation in Manaus and Porto Velho, two municipalities located in the western Brazilian Amazon, included comprehensive training of healthcare professionals (HCPs) on point-of-care quantitative G6PD testing and a new treatment algorithm for P. vivax radical cure incorporating tafenoquine. Training was initially provided to higher-level facilities (phase one) and later adapted for primary care units (phase two). This study analyzed HCP experiences during training and implementation and identified barriers and facilitators. In-depth interviews and focus discussion groups were conducted 30 days after each training for a purposive random sample of 115 HCPs. Thematic analysis was employed using MAXQDA software, analyzing data through inductive and deductive coding. Analysis showed that following the initial training for higher-level facilities, some HCPs did not feel confident performing quantitative G6PD testing and prescribing the tafenoquine regimen. Modifications to the training in phase two resulted in an improvement in understanding the implementation process of the G6PD test and tafenoquine, as well as in the knowledge acquired by HCPs. Additionally, knowledge gaps were addressed through in situ training, peer communication via a messaging app, and educational materials. Training supported effective deployment of the new tools in Manaus and Porto Velho and increased awareness of the need for pharmacovigilance. A training approach for nationwide implementation of these tools was devised. Implementing quantitative G6PD testing and tafenoquine represents a significant shift in P. vivax malaria case management. Consistent engagement with HCPs is needed to overcome challenges in fully integrating these tools within the Brazilian health system.

Prevalence and Characteristics of Plasmodium vivax Gametocytes in Duffy-Positive and Duffy-Negative Populations across Ethiopia.

Plasmodium parasites replicate asexually in human hosts. The proportion of infections that carries gametocytes is a proxy for human-to-mosquito transmissibility. It is unclear which proportion of Plasmodium vivax infections in Duffy-negative populations carries gametocytes. We determined the prevalence and characteristics of P. vivax gametocytes in Duffy-positive and -negative populations across broad regions of Ethiopia. Finger-prick blood samples were collected for microscopic and molecular screening of Plasmodium parasites and Duffy status of individuals. Molecular screening of Plasmodium species and Duffy blood group genotyping was done using SYBR green and the Taqman quantitative polymerase chain reaction method. Of the 447 febrile patients who were shown to be P. vivax smear positive, 414 (92.6%) were confirmed by molecular screening as P. vivax and 16 (3.9%) of them were from Duffy-negative individuals. Of these, 5 of 16 (31.3%) Duffy-negative P. vivax-infected samples were detected with gametocytes. Of the 398 Duffy-positive P. vivax-infected samples, 150 (37.7%) were detected with gametocytes, slightly greater than that in Duffy-negative samples. This study highlights the presence of P. vivax gametocytes in Duffy-negative infections, suggestive of human-to-mosquito transmissibility. Although P. vivax infections in Duffy-negative individuals were commonly associated with low parasitemia, some of these infections were shown to have relatively high parasitemia and may represent a prominent erythrocyte invasion capability of P. vivax, and hidden reservoirs that can contribute to transmission. A better understanding of P. vivax transmission biology and gametocyte function particularly in Duffy-negative populations would aid future treatment and management of P. vivax malaria in Africa.

Challenges of Severe Malaria Management in Patient Returning from Jayapura, Indonesia Presented with Severe Anemia: A Case Report

We report a 55-year-old woman who presented to the hospital with intermittent fever for a month. The patient had a history of living in a malaria endemic area (Jayapura, Papua Province, Indonesia) for approximately 15 years. The hemoglobin level was very low (4.2 mg/dL). Furthermore, we conducted a follow-up supporting examination, Malaria Rapid Diagnostic Test (RDT), the result was positive for malaria tropica (Plasmodium falciparum). Blood smear test was also carried out to confirm the diagnosis, the result was that immature trophozoites (ring shape) were found. Thus, the patient was diagnosed with severe malaria tropica with clinical manifestations indicative of severe anemia. The patient was treated for 3 days with anti-malarial drugs and supportive drugs according to the symptoms in the hospital and was advised to follow up 7 days later. This case report describe the challenges of severe malaria management in patient returning from Jayapura with severe anemia.

Autochthonous Plasmodium vivax Infections, Florida, USA, 2023.

During May-July 2023, a cluster of 7 patients at local hospitals in Florida, USA, received a diagnosis of Plasmodium vivax malaria. Whole-genome sequencing of the organism from 4 patients and phylogenetic analysis with worldwide representative P. vivax genomes indicated probable single parasite introduction from Central/South America.

DELAYED DIAGNOSIS OF IMPORTED PLASMODIUM VIVAX MALARIA MIMICKING REFRACTORY MIGRAINE

Malaria is referred to as imported malaria in countries outside malaria-endemic areas such as Morocco. The aim of our study was to highlight the importance of epidemiological data for the diagnosis of imported malaria. A 29-year-old moroccan female, presenting with a 3-month history of headache unresolved with usual analgesics, for which she was put on antidepressants and neuroleptics. She then presented to the emergency department with nausea, vomiting, abdominal pain, and fever. History and clinical examination revealed only mild abdominal pain with fever. Blood count showed anemia at 10.4 g/dl, MCHC at 34, MCH at 32, MCV at 90 fl and reticulocytes at 157920.Symptomatic treatment was given and the patient was referred to the haematology department for etiological diagnosis of her regenerative normocytic normochromic anaemia.Patient was then referred to Internal Medicine, the patient reported having visited Pakistan 1 year previously.In view of this situation, and taking into account the fact that she had travelled to a malaria-endemic area, a thin blood smear (TBS) and a thick blood smear stained with MGG were carried out urgently. A diagnosis of P. vivax malaria was established. Results were communicated immediately to the attending physician, and treatment was administered in an outpatient setting.

Examining the paradox: increased malaria risk in children under 5 in female-headed households in Nigeria

BackgroundNigeria is facing a severe malaria crisis, accounting for a significant proportion of global cases and deaths of malaria. This study aimed to investigate the differences between female-headed households (FHHs) and male-headed households (MHHs) and their impact on malaria risk among children under five (U5) in Nigeria.MethodsData from the 2021 Nigeria Malaria Indicator Survey (NMIS) were used for this cross-sectional study. A representative sample of 10,988 households was analysed, with key variables subjected to frequency calculations, descriptive statistics, and bivariate analyses using t-tests and chi-square analyses to compare the differences between FHHs and MHHs.ResultsAmong all participants, 92.1% (N = 10,126) reported residing in male-headed households, while 7.8% (N = 862) reported living in female-headed households. MHHs were significantly more likely to own insecticide-treated bed nets (ITNs) than FHHs (64.7% vs. 53.6%, P < 0.001). U5 children in MHHs had a greater likelihood of sleeping under a bed net the night before the survey than U5 children in FHHs (35.3% vs. 30.0%, P < 0.05). The prevalence of fever in the previous two weeks among U5 children was similar in MHHs and FHHs (35.4% vs. 31.4%), and the testing rates for malaria among U5 children who experienced febrile episodes were higher in MHHs than FHHs (22.4% vs. 15.4%, P < 0.05). Although not statistically significant, FHHs exhibited a higher percentage of U5 children testing positive for malaria compared to MHHs (87.8% vs. 78.9%). On the other hand, FHHs had higher education levels, overall wealth index scores, and a larger presence in urban areas compared to MHHs (P < 0.001). Moreover, FHHs reported higher adherence to malaria prevention awareness (P < 0.001).ConclusionIn Nigeria, FHHs enjoy relatively better socioeconomic conditions and stronger awareness of malaria prevention compared to their male-headed counterparts. Contrary to expectations, FHHs are at an increased risk of malaria in children under 5 years old. This phenomenon is associated with entrenched gender inequality and the challenges women face in accessing critical assets. As women in FHHs bear the responsibility of income generation while caring for their children, it is crucial to prioritize interventions that address malaria management in FHHs to reduce both malaria incidence and mortality rates.Graphical

Health workers’ adherence to malaria case management protocols in Northern Sudan: a qualitative study

BackgroundNonadherence to national standards for malaria diagnosis and treatment has been reported in Sudan. In this study, qualitative research examined the clinical domains of nonadherence, factors influencing nonadherent practices and health workers’ views on how to improve adherence.MethodsIn September 2023, five Focus Group Discussions (FGDs) were undertaken with 104 health workers from 42 health facilities in Sudan’s Northern State. The participants included medical assistants, doctors, nurses, laboratory personnel, pharmacists and public health officers. The FGDs followed a semi-structured guide reflecting the national malaria case management protocol. Qualitative thematic analysis was performed.ResultsNonadherent practices included disregarding parasitological test results, suboptimal paediatric artemether–lumefantrine (AL) dosing, lack of counselling, use of prohibited artemether injections for uncomplicated and severe malaria, artesunate dose approximations and suboptimal preparations, lack of AL follow on treatment for severe malaria; and rare use of primaquine for radical Plasmodium vivax treatment and dihydroartemisinin-piperaquine as the second-line treatment for uncomplicated malaria. Factors influencing nonadherence included stock-outs of anti-malarials and RDTs; staff shortages; lack of training, job aids and supervision; malpractice by specialists; distrust of malaria microscopy and RDTs; and patient pressure for diagnosis and treatment. Health workers recommended strengthening the supply chain; hiring personnel; providing in-service protocol training including specialists; establishing external quality assurance for malaria diagnosis; and providing onsite supportive supervision and public health campaigns.ConclusionsThis study revealed a broad spectrum of behavioural and systemic challenges in malaria management among frontline health workers in Northern Sudan, including nonadherence to protocols due to resource shortages, training gaps, a lack of supportive supervision and patient pressure. These insights, including health workers’ views about improvements, will inform evidence-based interventions by Sudan’s National Malaria Control Programme to improve health systems readiness and the quality of malaria case management.

Tafenoquine for Relapsing Babesiosis: A Case Series.

Relapsing babesiosis often occurs in highly immunocompromised patients and has been attributed to the acquisition of resistance against drugs commonly used for treatment such as atovaquone, azithromycin, and clindamycin. Tafenoquine, which is approved for malaria prophylaxis and presumptive antirelapse treatment of Plasmodium vivax malaria, has shown activity against Babesia microti in several animal models of acute infection and in a single human case of relapsing babesiosis. Here, we report 5 cases of relapsing babesiosis treated with tafenoquine, including the previous case, and begin to define the conditions for optimal use of tafenoquine in relapsing babesiosis. A definitive diagnosis of babesiosis was made by microscopic examination of Giemsa-stained thin blood smears or a real-time polymerase chain reaction (PCR) that targets the parasite 18S rRNA gene. Clearance of B. microti infection was ascertained by use of blood smear and real-time PCR. Tafenoquine was initiated with a loading dose of 600 mg. A weekly maintenance dose consisted of 200 mg or 300 mg; the lower dose was associated with a delayed clearance of B. microti. In 2 cases, all antimicrobial agents but tafenoquine were discontinued prior to clearance of infection. In 2 other cases, clearance was achieved while tafenoquine was administered along with other antimicrobial agents. In 3 of these 4 cases, tafenoquine was used in combination with atovaquone-proguanil. Other agents included atovaquone, azithromycin, and/or clindamycin. In 1 case, tafenoquine was administered alone and failed to prevent relapse. Tafenoquine can be a useful adjunct for the treatment of highly immunocompromised patients experiencing relapsing babesiosis caused by B. microti.

Might procalcitonin help predict imported falciparum malaria in children?

BackgroundProcalcitonin (PCT) has been proposed as a marker for malaria severity in adults, with a threshold of 10 ng/ml for severe falciparum disease. Whether PCT is useful in children is debated. Patients & methodsA retrospective case-control study was conducted to compare initial PCT levels in children with uncomplicated malaria and a control group, and between children with uncomplicated and severe malaria. ResultsResults showed significantly higher PCT levels in malaria cases compared to the control group and in malaria severe cases compared to uncomplicated cases. A Receiving Operator Characteristic curve established a PCT threshold of 0.65 ng/ml with a negative predictive value of 98.8 % based on a prevalence of 10 %. Analyzing the pooled results of five studies suggested a threshold of 6.17 ng/ml for differentiating uncomplicated and severe malaria. ConclusionPCT might be a useful tool to help rule out malaria and predict potential disease severity in returning travelers.

Clinical and haematological parameters in malaria caused by different plasmodium species in children

Background: Malaria is a disease of global importance and affects more than ninety countries in both the tropical and subtropical regions. Clinical and haematological parameters vary with type of malaria, although data relating to different species of malaria in children is limited. This study aims to understand the clinical and haematological profile of malaria and to correlate these with different malarial species among children. Methods: This is a descriptive cross-sectional study involving 130 proven malaria cases done over 18 months from October 2014 to April 2016. A detailed history and clinical examination along with haematological parameters were analysed and correlated with different types of malaria. Results: Among 130 children, 97 children were vivax positive, 4 were falciparum and 27 were mixed malaria. Fever was present in all, whilst other symptoms were chills and rigors (86.15%), vomiting (39.52%), headache (19%), pain abdomen (6.84%), myalgia (4.56%) and convulsions (1.52%). Clinical signs were pallor (29.64%), icterus (0.76%), splenomegaly (65.36%), hepatomegaly (23.56%) and hepatosplenomegaly (21.28%).75% of children with falciparum malaria had splenomegaly and pallor whereas hepatomegaly was observed in 34% of mixed malaria cases. Haematological parameters observed were anaemia (47.6%), severe anaemia (2%), leucocytosis (11.5%), leukopenia (39.2%), thrombocytopenia (87%) and severe thrombocytopenia (30%). Severe thrombocytopenia was seen with vivax malaria (70%). No mortality was noted in the studied population. Conclusions: Fever and splenomegaly are important clinical features, whereas anaemia and thrombocytopenia are the most noted haematological parameters in malaria. The parameters vary with different species of malaria knowledge of clinical and haematological parameters aid us in early diagnosis and prompt initiation of treatment and prevention of associated complications.

Longitudinal associations of plasma amino acid levels with recovery from malarial coma.

Disordered amino acid metabolism is observed in cerebral malaria (CM). We sought to determine whether abnormal amino acid concentrations were associated with level of consciousness in children recovering from coma. We quantified 21 amino acids and coma scores longitudinally and analyzed data for associations. In a prospective observational study, we enrolled 42 children with CM. We measured amino acid levels at entry and at frequent intervals thereafter and assessed consciousness by Blantyre Coma Scores (BCS). Thirty-six healthy children served as controls for in-country normal amino acid ranges. We employed logistic regression using a generalized linear mixed-effects model to assess associations between out-of-range amino acid levels and BCS. At entry 16/21 amino acid levels were out-of-range. Longitudinal analysis revealed 10/21 out-of-range amino acids were significantly associated with BCS. Elevated phenylalanine levels showed the highest association with low BCS. This finding held when out-of-normal-range data were analyzed at each sampling time. We provide longitudinal data for associations between abnormal amino acid levels and recovery from CM. Of 10 amino acids significantly associated with BCS, we propose that elevated phenylalanine may be a surrogate for impaired clearance of ether lipid mediators of inflammation contributing to CM pathogenesis.

A novel locus in CSMD1 gene is associated with increased susceptibility to severe malaria in Malian children

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.

Malaria epidemiology, surveillance and response for elimination in Lao PDR

BackgroundLao PDR has made significant progress in malaria control. The National Strategic Plans outline ambitious targets, aiming for the elimination of Plasmodium falciparum and P. vivax malaria from all northern provinces by 2025 and national elimination by 2030. This article presents an overview of malaria epidemiology, surveillance, and response systems in Lao PDR, emphasizing experiences and achievements in transmission reduction.MethodsData on surveillance, monitoring and evaluation systems, human resources, infrastructure, and community malaria knowledge during 2010–2020 were systematically gathered from the national program and relevant documents. The collected information was synthesized, and discussions on challenges and future prospects were provided.ResultsMalaria control and elimination activities in Lao PDR were implemented at various levels, with a focus on health facility catchment areas. There has been significant progress in reducing malaria transmission throughout the country. Targeted interventions, such as case management, vector control, and community engagement, using stratification of control interventions by catchment areas have contributed to the decline in malaria cases. In elimination areas, active surveillance strategies, including case and foci investigation, are implemented to identify and stop transmission. The surveillance system has facilitated timely detection and response to malaria cases, enabling these targeted interventions in higher-risk areas.ConclusionsThe malaria surveillance and response system in Lao PDR has played a crucial role in reducing transmission and advancing the country towards elimination. Challenges such as importation, drug resistance, and sustaining support require ongoing efforts. Further strengthening surveillance, improving access to services, and addressing transmission determinants are key areas of focus to achieve malaria elimination and enhance population health in Lao PDR.

#862 Prevalence and surrogate predictors of acute kidney injury in tropical infections in eastern India

Abstract Background and Aims Acute kidney injury (AKI) in tropical countries is strikingly different from the other countries with a temperate climate. The epidemiology of AKI is largely influenced by environmental factors and climatic conditions and differ significantly its outcome and the surrogate predictors are not much studied. 1. To observe the spectrum and estimate the prevalence of AKI in tropical infections. 2. To evaluate the outcome and surrogate predictor of tropical AKI. Method This was a tertiary level single centre prospective observational study. All patients admitted with tropical infections associated AKI (KDIGO) were enrolled in two years and underwent complete history taking, clinical examinations and necessary laboratory investigations according to situations.. All patients were followed up more than 6 month. All data recorded were analysed in suitable statistical tool. Univariate analysis is followed by multivariate analysis was done for predictors followed by hazards ratio and Neglekers test. Results Out of 132 patients with Tropical AKI M:F was 1.5:1. Mean age was 42.3 ± 14.4 year, About 35.6% had Malaria,31.1% Dengue, 17% Scrub typhus, 10.4% Leptospira, and 5.9% patients had Typhoid fever. Malaria was the most common causative factor followed by Dengue. study reflecting the high dengue incidence occurring in the months of August, September, October &amp; November. Among Malaria AKI (MAKI) 43.75% (21) had Falciparum malaria, 50% (24) had Vivax malaria and 6.25% (3) had dual infection. Out of 132 patients with Tropical AKI about 60% totally recovered at the time of discharge. 40% patients had Shock. Among them 60% Dengue AKI, 33.3% Malarial AKI 5 (21.7%) Scrub typhus, 4 (28.6%) Leptospira AKI &amp; 3 (37%) Typhoid AKI patients had Shock. About 23% patients required RRT. Among them 8 (25%) patients died, 5 (15.6%) patients had CKD progression compared to non-RRT group where only 3 (2.9%) patients died, and 2 (1.94%) patients had progression to CKD. Total 11 (8.1%) patients died during hospital stay and only 7 (6.2%) patients had progressed to CKD. The mean Hospital stay was 5.51 ± 3.8 days. S hock at presentation, requirement of ICU support ( in form of ionotropic and ventilatory support), Need of RRT, prolong hospital stay, late referral was the bad prognostic predictor in terms of death. Though not statistically significant, presence of anaemia, hyponatraemia, deranged liver function &amp; hypoalbuminemia were more in patients who died compared to survival group. Limitations: Small enrolments. non inclusion of all cause including snake bite, less biopsy in this study. Conclusion There are wide spectrum of tropical AKI with high mortality and morbidity. A greater awareness and early intervention is necessary for prompt diagnosis, treatment and favourable outcome.

Impact of the Introduction of Artesunate on the Management of Severe Malaria in Casamance (Senegal): A Comparative Analysis of Data From 2016 and 2020

Background: the implementation of different control strategies, including the treatment of severe forms with injectable artesunate, has made it possible to significantly reduce malaria in Senegal. Despite everything, malaria remains a concern in Senegal, especially in the southern regions, hence the interest in studying these characteristics and their evolution over time. Objectives: describe the epidemiological, clinical and evolving aspects of severe malaria before and after implementation of artesunate treatment. Patients and methods: retrospective, cross-sectional, descriptive and analytical study focusing on cases of severe malaria admitted in two health structures in the Vélingara district in 2016 and 2020. The severity of diagnosis was made based on the current criteria of the WHO and confirmation made by thick blood smear and/or HRP2 rapid diagnostic test. The data was entered into Excel and analyzed with Epi-info version 7.2.6. Results: In 2016, 357 cases of serious malaria were recorded from January 1st to December 31st, with 75.6% in October and December. The average age is 16.2 ± 12.9 years, with a predominance of the age group 6-15 years (38,94%). There was a male predominance and the sex ratio was 1.01. Coma (57%), convulsions (34%) and jaundice (14%) were the most common signs of severity. Under treatment with quinine salts (97%) and artemether (3%), the lethality was 5%. Factors significantly associated with death were rural origin (p:0.009), coma (p:0.000), hepatomegaly (p:0.03) and diffuse hemorrhages (p:0.03). In 2020, 456 cases were collected from July 1st to December 31st, with 75.44% in October and November. The average age was 15.38±15.36 years (1 to 85 years) with a predominance of age group 6 to 15 years (46.49%). There was a male predominance and the sex ratio was 1.06. The signs of severity were dominated by prostration (52.63%), repeated convulsions (17.11%), coma (7.9%) and jaundice (7.2%). All patients were treated with injectable artesunate with a lethality of 3.5%. Death was significantly associated with coma (p:0.000) and the occurrence of respiratory failure (p:0.000). Conclusion: severe malaria remained a childhood pathology with neurological manifestations predominating in Vellingara. A drop in lethality is observed with the generalization of artesunate-based treatment.

Household-level effects of seasonal malaria chemoprevention in the Gambia.

In 2022 the WHO recommended the discretionary expansion of the eligible age range for seasonal malaria chemoprevention (SMC) to children older than 4 years. Older children are at lower risk of clinical disease and severe malaria so there has been uncertainty about the cost-benefit for national control programmes. However, emerging evidence from laboratory studies suggests protecting school-age children reduces the infectious reservoir for malaria and may significantly impact on transmission. This study aimed to assess whether these effects were detectable in the context of a routinely delivered SMC programme. In 2021 the Gambia extended the maximum eligible age for SMC from 4 to 9 years. We conducted a prospective population cohort study over the 2021 malaria transmission season covering 2210 inhabitants of 10 communities in the Upper River Region, and used a household-level mixed modelling approach to quantify impacts of SMC on malaria transmission. We demonstrate that the hazard of clinical malaria in older participants aged 10+ years ineligible for SMC decreases by 20% for each additional SMC round per child 0-9 years in the same household. Older inhabitants also benefit from reduced risk of asymptomatic infections in high SMC coverage households. Spatial autoregression tests show impacts are highly localised, with no detectable spillover from nearby households. Evidence for the transmission-reducing effects of extended-age SMC from routine programmes implemented at scale has been previously limited. Here we demonstrate benefits to the entire household, indicating such programmes may be more cost-effective than previously estimated.