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Malaria Journal Jun 2024Neonatal malaria is defined as the detection of asexual stages of Plasmodium species in the cord blood within the first 28 days of life. It can be congenital or...
BACKGROUND
Neonatal malaria is defined as the detection of asexual stages of Plasmodium species in the cord blood within the first 28 days of life. It can be congenital or acquired through mosquito bites or blood transfusions. Neonates are generally considered to be relatively protected due to the multiple innate and acquired physiological protective effects present in neonates. However, in areas where malaria is endemic, the prevalence of malaria in neonates is high. The predominant clinical feature of malaria in neonates is fever. Other clinical manifestations of neonatal malaria include respiratory distress, pallor and anaemia, hepatomegaly, refusal to feed, jaundice and diarrhoea. Atypical presentations without fever can lead to inaccurate diagnosis and contribute to neonatal morbidity and mortality. Neonates from endemic areas with any of the above symptoms should be screened for malaria.
CASE PRESENTATION
We present a series of three cases of neonatal Plasmodium falciparum malaria that presented atypically without febrile episodes and were diagnosed and managed at Mizan-Tepi University Teaching Hospital between July and September 2023. The first patient presented with vomiting, refusal to feed, pallor, severe anaemia, and splenomegaly. The second patient presented with an inconsolable cry, failure to pass feces, abdominal distention, and anaemia. The third patient presented with vomiting and anaemia. All patients received a 7-day course of intravenous artesunate; the first patient also received a blood transfusion. All patients recovered and were discharged.
CONCLUSIONS
Partial immunity resulting from repeated malaria infections in endemic regions may result in the transfer of high levels of maternal Immunoglobulin G (IgG) antibodies through the placenta and can produce different atypical clinical presentations. In malaria-endemic areas, neonates presenting with any of the presenting signs and symptoms of malaria, including afebrile presentation, require malaria screening to avoid delays in diagnosis.
Topics: Humans; Infant, Newborn; Malaria, Falciparum; Female; Male; Ethiopia; Plasmodium falciparum; Antimalarials; Artesunate
PubMed: 38840266
DOI: 10.1186/s12936-024-04987-y -
Scientific Reports Jun 2024The present cluster-randomised control trial aims to assess the entomological efficacy of pyrethroid-pyriproxyfen and pyrethroid-chlorfenapyr LLINs compared to the... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy of pyrethroid-pyriproxyfen and pyrethroid-chlorfenapyr nets on entomological indicators of malaria transmission: third year of a randomised controlled trial in Benin.
The present cluster-randomised control trial aims to assess the entomological efficacy of pyrethroid-pyriproxyfen and pyrethroid-chlorfenapyr LLINs compared to the standard pyrethroid-only LLINs, in their third year of community usage. Adult mosquito collections were performed every 3 months, in 4 randomly selected houses in each of the 60 trial clusters, using human landing catches. Adult mosquitoes were morphologically identified and Anopheles vectors were molecularly speciated and screened for the presence of the L1014F kdr mutation using PCR. Plasmodium falciparum sporozoite infection was assessed using ELISA. A subset of An. gambiae s.l. was also dissected to examine parity and fertility rates across study arms. There was no evidence of a significant reduction in indoor vector density and entomological inoculation rate by the pyrethroid-pyriproxyfen [DR 0.94 (95% CI 0.46-1.88), p = 0.8527; and RR 1.10 (95% CI 0.44-2.72), p = 0.8380], and pyrethroid-chlorfenapyr [DR 0.74 (95% CI 0.37-1.48), p = 0.3946; and RR 1.00 (95% CI 0.40-2.50), p = 0.9957] LLINs, respectively. The same trend was observed outdoors. Frequencies of the L1014F kdr mutation, as well as parous and fertility rates, were similar between study arms. In the third year after net distribution, entomological indicators show that the two dual active-ingredients nets performed similarly to the standard pyrethroid-only LLIN. To maintain malaria gains, it is crucial that net distribution cycles fit with their operational lifespan.
Topics: Pyrethrins; Animals; Anopheles; Insecticide-Treated Bednets; Humans; Pyridines; Mosquito Control; Benin; Mosquito Vectors; Plasmodium falciparum; Malaria; Insecticides; Malaria, Falciparum; Female; Insecticide Resistance
PubMed: 38839981
DOI: 10.1038/s41598-024-63883-2 -
PloS One 2024Artemisinin resistance threatens malaria control and elimination efforts globally. Recent studies have reported the emergence of Plasmodium falciparum parasites tolerant...
Artemisinin resistance threatens malaria control and elimination efforts globally. Recent studies have reported the emergence of Plasmodium falciparum parasites tolerant to artemisinin agents in sub-Saharan Africa, including Uganda. The current study assessed the day 3 parasite clearance and its correlation with P. falciparum K13 propeller gene (pfkelch13) mutations in P. falciparum parasites isolated from patients with uncomplicated malaria under artemether-lumefantrine (AL) treatment. This study enrolled 100 P. falciparum-positive patients to whom AL was prescribed between 09/September/2022 and 06/November/2022. Blood samples were collected in EDTA tubes before treatment initiation (day 0) and on day 3. Parasitemia was assessed by microscopy from blood smears and quantitative polymerase chain reaction (qPCR) from the DNA extracted. The day 0 parasite K13 gene was sequenced using Sanger sequencing. Sequence data were analysed using MEGA version 11 software. The data were analysed using STATA version 15, and the Mann‒Whitney U test was used to compare PCR parasite clearance on day 3 using the comparative CT value method and pfkelch13 mutations. The prevalence of day 3 parasitaemia was 24% (24/100) by microscopy and 63% (63/100) by qPCR from the AL-treated patients. P. falciparum K13-propeller gene polymorphism was detected in 18.8% (15/80) of the day 0 DNA samples. The K13 mutations found were C469Y, 12.5% (10/80); A675V, 2.5% (2/80); A569S, 1.25%, (1/80), A578S, 1.25%, (1/80) and; F491S, 1.25%, (1/80) a new allele not reported anywhere. The C469Y mutation, compared to the wild-type, was associated with delayed parasite clearance p = 0.0278, Hodges-Lehmann estimation 3.2108 on the log scale, (95%CI 1.7076, 4.4730). There was a high prevalence of day 3 P. falciparum among malaria patients treated using artemether-lumefantrine. We conclude the presence of the K13 mutation associated with artemisinin resistance by P. falciparum in Adjumani district, Uganda, necessitates regular surveillance of the effectiveness and efficacy of artemether-lumefantrine in the country.
Topics: Humans; Plasmodium falciparum; Artemether, Lumefantrine Drug Combination; Uganda; Malaria, Falciparum; Mutation; Antimalarials; Male; Female; Parasitemia; Protozoan Proteins; Adult; Child; Adolescent; Child, Preschool; Young Adult; Drug Resistance; Artemisinins; Middle Aged
PubMed: 38837973
DOI: 10.1371/journal.pone.0305064 -
Antimicrobial Agents and Chemotherapy Jun 2024The human malaria- monkey model has served the malaria research community since its inception in 1966 at the Gorgas Memorial Laboratory (GML) in Panama. Spanning over... (Review)
Review
The human malaria- monkey model has served the malaria research community since its inception in 1966 at the Gorgas Memorial Laboratory (GML) in Panama. Spanning over five decades, this model has been instrumental in evaluating the efficacy and pharmacokinetics of a wide array of candidate antimalarial drugs, whether used singly or in combination. The animal model could be infected with drug-resistant and susceptible and strains that follow a characteristic and reproducible course of infection, remarkably like human untreated and treated infections. Over the years, the model has enabled the evaluation of several synthetic and semisynthetic endoperoxides, for instance, artelinic acid, artesunate, artemether, arteether, and artemisone. These compounds have been evaluated alone and in combination with long-acting partner drugs, commonly referred to as artemisinin-based combination therapies, which are recommended as first-line treatment against uncomplicated malaria. Further, the model has also supported the evaluation of the primaquine analog tafenoquine against blood stages of , contributing to its progression to clinical trials and eventual approval. Besides, the / model at GML has also played a pivotal role in exploring the biology, immunology, and pathogenesis of malaria and in the characterization of drug-resistant and strains. This minireview offers a historical overview of the most significant contributions made by the Panamanian owl monkey () to malaria chemotherapy research.
PubMed: 38837364
DOI: 10.1128/aac.00338-24 -
Frontiers in Immunology 2024Innate immunity is crucial to reducing parasite burden and contributing to survival in severe malaria. Monocytes are key actors in the innate response and, like...
INTRODUCTION
Innate immunity is crucial to reducing parasite burden and contributing to survival in severe malaria. Monocytes are key actors in the innate response and, like macrophages, are plastic cells whose function and phenotype are regulated by the signals from the microenvironment. In the context of cerebral malaria (CM), monocyte response constitutes an important issue to understand. We previously demonstrated that decreased percentages of nonclassical monocytes were associated with death outcomes in CM children. In the current study, we postulated that monocyte phagocytosis function is impacted by the severity of malaria infection.
METHODS
To study this hypothesis, we compared the opsonic and nonopsonic phagocytosis capacity of circulant monocytes from Beninese children with uncomplicated malaria (UM) and CM. For the CM group, samples were obtained at inclusion (D0) and 3 and 30 days after treatment (D3, D30). The phagocytosis capacity of monocytes and their subsets was characterized by flow cytometry and transcriptional profiling by studying genes known for their functional implication in infected-red blood cell (iRBC) elimination or immune escape.
RESULTS
Our results confirm our hypothesis and highlight the higher capacity of nonclassical monocytes to phagocyte iRBC. We also confirm that a low number of nonclassical monocytes is associated with CM outcome when compared to UM, suggesting a mobilization of this subpopulation to the cerebral inflammatory site. Finally, our results suggest the implication of the inhibitory receptors LILRB1, LILRB2, and Tim3 in phagocytosis control.
DISCUSSION
Taken together, these data provide a better understanding of the interplay between monocytes and malaria infection in the pathogenicity of CM.
Topics: Humans; Malaria, Cerebral; Phagocytosis; Monocytes; Male; Child, Preschool; Female; Child; Infant; Plasmodium falciparum; Opsonin Proteins; Erythrocytes; Immunity, Innate
PubMed: 38835780
DOI: 10.3389/fimmu.2024.1358853 -
Journal of Cheminformatics May 2024Drug discovery is an intricate and costly process. Repurposing existing drugs and active compounds offers a viable pathway to develop new therapies for various diseases....
Drug discovery is an intricate and costly process. Repurposing existing drugs and active compounds offers a viable pathway to develop new therapies for various diseases. By leveraging publicly available biomedical information, it is possible to predict compounds' activity and identify their potential targets across diverse organisms. In this study, we aimed to assess the antiplasmodial activity of compounds from the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library using in vitro and bioinformatics approaches. We assessed the in vitro antiplasmodial activity of the compounds using blood-stage and liver-stage drug susceptibility assays. We used protein sequences of known targets of the ReFRAME compounds with high antiplasmodial activity (EC < 10 uM) to conduct a protein-pairwise search to identify similar Plasmodium falciparum 3D7 proteins (from PlasmoDB) using NCBI protein BLAST. We further assessed the association between the compounds' in vitro antiplasmodial activity and level of similarity between their known and predicted P. falciparum target proteins using simple linear regression analyses. BLAST analyses revealed 735 P. falciparum proteins that were similar to the 226 known protein targets associated with the ReFRAME compounds. Antiplasmodial activity of the compounds was positively associated with the degree of similarity between the compounds' known targets and predicted P. falciparum protein targets (percentage identity, E value, and bit score), the number of the predicted P. falciparum targets, and their respective mutagenesis index and fitness scores (R between 0.066 and 0.92, P < 0.05). Compounds predicted to target essential P. falciparum proteins or those with a druggability index of 1 showed the highest antiplasmodial activity.
PubMed: 38831351
DOI: 10.1186/s13321-024-00856-7 -
PLoS Pathogens Jun 2024Asexual replication of Plasmodium falciparum occurs via schizogony, wherein 16-36 daughter cells are produced within the parasite during one semi-synchronized...
Asexual replication of Plasmodium falciparum occurs via schizogony, wherein 16-36 daughter cells are produced within the parasite during one semi-synchronized cytokinetic event. Schizogony requires a divergent contractile ring structure known as the basal complex. Our lab has previously identified PfMyoJ (PF3D7_1229800) and PfSLACR (PF3D7_0214700) as basal complex proteins recruited midway through segmentation. Using ultrastructure expansion microscopy, we localized both proteins to a novel basal complex subcompartment. While both colocalize with the basal complex protein PfCINCH upon recruitment, they form a separate, more basal subcompartment termed the posterior cup during contraction. We also show that PfSLACR is recruited to the basal complex prior to PfMyoJ, and that both proteins are removed unevenly as segmentation concludes. Using live-cell microscopy, we show that actin dynamics are dispensable for basal complex formation, expansion, and contraction. We then show that EF-hand containing P. falciparum Centrin 2 partially localizes to this posterior cup of the basal complex and that it is essential for growth and replication, with variable defects in basal complex contraction and synchrony. Finally, we demonstrate that free intracellular calcium is necessary but not sufficient for basal complex contraction in P. falciparum. Thus, we demonstrate dynamic spatial compartmentalization of the Plasmodium falciparum basal complex, identify an additional basal complex protein, and begin to elucidate the unique mechanism of contraction utilized by P. falciparum, opening the door for further exploration of Apicomplexan cellular division.
Topics: Plasmodium falciparum; Protozoan Proteins; Malaria, Falciparum; Humans; Erythrocytes
PubMed: 38829893
DOI: 10.1371/journal.ppat.1012265 -
PloS One 2024Malaria is a deadly disease that is transmitted through mosquito bites. Microscopists use a microscope to examine thin blood smears at high magnification (1000x) to... (Comparative Study)
Comparative Study
Malaria is a deadly disease that is transmitted through mosquito bites. Microscopists use a microscope to examine thin blood smears at high magnification (1000x) to identify parasites in red blood cells (RBCs). Estimating parasitemia is essential in determining the severity of the Plasmodium falciparum infection and guiding treatment. However, this process is time-consuming, labor-intensive, and subject to variation, which can directly affect patient outcomes. In this retrospective study, we compared three methods for measuring parasitemia from a collection of anonymized thin blood smears of patients with Plasmodium falciparum obtained from the Clinical Department of Parasitology-Mycology, National Reference Center (NRC) for Malaria in Paris, France. We first analyzed the impact of the number of field images on parasitemia count using our framework, MALARIS, which features a top-classifier convolutional neural network (CNN). Additionally, we studied the variation between different microscopists using two manual techniques to demonstrate the need for a reliable and reproducible automated system. Finally, we included thin blood smear images from an additional 102 patients to compare the performance and correlation of our system with manual microscopy and flow cytometry. Our results showed strong correlations between the three methods, with a coefficient of determination between 0.87 and 0.92.
Topics: Humans; Plasmodium falciparum; Parasitemia; Malaria, Falciparum; Retrospective Studies; Microscopy; Erythrocytes; Image Processing, Computer-Assisted; Neural Networks, Computer; Flow Cytometry
PubMed: 38829858
DOI: 10.1371/journal.pone.0304789 -
Frontiers in Cellular and Infection... 2024Recent studies indicate that human spleen contains over 95% of the total parasite biomass during chronic asymptomatic infections caused by . Previous studies have...
Recent studies indicate that human spleen contains over 95% of the total parasite biomass during chronic asymptomatic infections caused by . Previous studies have demonstrated that extracellular vesicles (EVs) secreted from infected reticulocytes facilitate binding to human spleen fibroblasts (hSFs) and identified parasite genes whose expression was dependent on an intact spleen. Here, we characterize the spleen-dependent hypothetical gene (PVX_114580). Using CRISPR/Cas9, PVX_114580 was integrated into 3D7 genome and expressed during asexual stages. Immunofluorescence analysis demonstrated that the protein, which we named (PvSDP1), was located at the surface of infected red blood cells in the transgenic line and this localization was later confirmed in natural infections. Plasma-derived EVs from -infected individuals (PvEVs) significantly increased cytoadherence of 3D7_PvSDP1 transgenic line to hSFs and this binding was inhibited by anti-PvSDP1 antibodies. Single-cell RNAseq of PvEVs-treated hSFs revealed increased expression of adhesion-related genes. These findings demonstrate the importance of parasite spleen-dependent genes and EVs from natural infections in the formation of intrasplenic niches in , a major challenge for malaria elimination.
Topics: Extracellular Vesicles; Plasmodium vivax; Humans; Spleen; Malaria, Vivax; Protozoan Proteins; Erythrocytes; Fibroblasts; Plasmodium falciparum; Cell Adhesion; Host-Parasite Interactions
PubMed: 38828264
DOI: 10.3389/fcimb.2024.1408451 -
Risk Management and Healthcare Policy 2024Malaria is one of the most widespread infections worldwide, particularly in developing countries. Accordingly, Jimma Zone is one of the widely affected areas by malaria...
BACKGROUND
Malaria is one of the most widespread infections worldwide, particularly in developing countries. Accordingly, Jimma Zone is one of the widely affected areas by malaria in Ethiopia. In 2020 woreda health offices have reported the possible malaria epidemic that needs further investigation. Accordingly, this study aims to characterize the scope, pinpoint determinants connected to the Nono Benja woreda malaria outbreak, and implement suitable public health management measures.
METHODS
A descriptive cross-sectional study was followed by an unmatched case-control study with a 1:1 ratio of cases to controls. The sample size of 136 individuals (68 cases and 68 controls) was used. The collected data was imported into Epi-data version 3.1 and analyzed using SPSS version 25.0. By doing multivariate logistic regression association was determined at 95% confidence intervals P value of 5%.
RESULTS
A total of 687 instances were identified, giving an overall attack incidence of 1%. The assault rate ranged from 51.6 per 1000 people in Benja rural to 1.1 per 1000 people in Dhokonu Kebele. But there were no recorded deaths. and were the major types of Plasmodium species reported. From independent variables absence of ITNS [AOR 3.98 (CI = 1.11-24.8)], residing in an unsprayed home [AOR = 3.83 (CI = 1.04-14.08], presence of stagnant water in residential area [AOR = 4.25, CI (1.37-12.24113.10)], and lack of awareness on malaria prevention [AOR = 8.28 (CI 2.31-29.73)] were significantly associated with Malaria outbreak.
CONCLUSION
A number of factors, including lack of ITNS, lack of malaria health education, stagnant water, and IRS (indoor residual spray), were significantly linked with the occurrence of malaria outbreaks. The woreda health office should therefore provide ITNS to the community, use indoor residual spray, and disseminate health information regarding efficient and long-lasting malaria preventive and control techniques.
PubMed: 38828105
DOI: 10.2147/RMHP.S456958