Role In Malaria Research Articles

Alveolar macrophages and monocyte subpopulations during Plasmodium berghei NK65 experimental malaria-associated acute respiratory distress syndrome

Alveolar macrophages (AM) and monocytes (MO) are myeloid cells that play a substantial role in the development and establishment of the innate and adaptive immune response. These cells are crucial for host defense against various pathogens, but their role in malaria is poorly understood. Here, we characterize the dynamics of AMs and recruited leukocytes subpopulations in the airways during experimental Plasmodium berghei NK65-NY (PbNK65). We show that PbNK65 infection induces an increased pulmonary vascular permeability that provides Ly6Clow MOs, neutrophils (NEU), CD4+ and CD8+ lymphocytes in the airways. This inflammatory environment resulted in an increase in the population and alteration of the activation state of the AMs. Taken together, the data presented provide new insights into airway inflammation associated with pulmonary malaria.

Aspecific binding of anti-NK1.1 antibodies on myeloid cells in an experimental model for malaria-associated acute respiratory distress syndrome

BackgroundConventional natural killer (cNK) cells play an important role in the innate immune response by directly killing infected and malignant cells and by producing pro- and anti-inflammatory cytokines. Studies on their role in malaria and its complications have resulted in conflicting results.MethodsUsing the commonly used anti-NK1.1 depletion antibodies (PK136) in an in-house optimized experimental model for malaria-associated acute respiratory distress syndrome (MA-ARDS), the role of cNK cells was investigated. Moreover, flow cytometry was performed to characterize different NK cell populations.ResultsWhile cNK cells were found to be dispensable in the development of MA-ARDS, the appearance of a NK1.1+ cell population was observed in the lungs upon infection despite depletion with anti-NK1.1. Detailed characterization of the unknown population revealed that this population consisted of a mixture of monocytes and macrophages that bind the anti-NK1.1 antibody in an aspecific way. This aspecific binding may occur via Fcγ receptors, such as FcγR4. In contrast, in vivo depletion using anti-NK1.1 antibodies was proved to be specific for cNK cells.ConclusioncNK cells are dispensable in the development of experimental MA-ARDS. Moreover, careful flow cytometric analysis, with a critical mindset in relation to potential aspecific binding despite the use of commercially available Fc blocking reagents, is critical to avoid misinterpretation of the results.

Biologic Functions of Hydroxychloroquine in Disease: From COVID-19 to Cancer.

Chloroquine (CQ) and Hydroxychloroquine (HCQ), initially utilized in the treatment of malaria, have now developed a long list of applications. Despite their clinical relevance, their mechanisms of action are not clearly defined. Major pathways by which these agents are proposed to function include alkalinization of lysosomes and endosomes, downregulation of C-X-C chemokine receptor type 4 (CXCR4) expression, high-mobility group box 1 protein (HMGB1) inhibition, alteration of intracellular calcium, and prevention of thrombus formation. However, there is conflicting data present in the literature. This is likely the result of the complex overlapping pathways between these mechanisms of action that have not previously been highlighted. In fact, prior research has focused on very specific portions of particular pathways without describing these in the context of the extensive CQ/HCQ literature. This review summarizes the detailed data regarding CQ/HCQ's mechanisms of action while also providing insight into the overarching themes. Furthermore, this review provides clinical context to the application of these diverse drugs including their role in malaria, autoimmune disorders, cardiovascular disease, thrombus formation, malignancies, and viral infections.

The striking mimics between COVID-19 and malaria: A review.

ObjectivesCOVID-19 is a transmissible illness triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its onset in late 2019 in Wuhan city of China, it continues to spread universally, leading to an ongoing pandemic that shattered all efforts to restrain it. On the other hand, in Africa, the COVID-19 infection may be influenced by malaria coinfection. Hence, in this review article, we aimed to give a comprehensive account of the similarities between COVID-19 and malaria in terms of symptoms, clinical, immunological, and molecular perspectives.MethodologyIn this article, we reviewed over 50 research papers to highlight the multilayered similarities between COVID-19 and malaria infections that might influence the ontology of COVID-19.ResultsDespite the poor health and fragile medical system of many sub-Saharan African countries, they persisted with a statistically significantly low number of COVID-19 cases. This was attributed to many factors such as the young population age, the warm weather, the lack of proper diagnosis, previous infection with malaria, the use of antimalarial drugs, etc. Additionally, population genetics appears to play a significant role in shaping the COVID-19 dynamics. This is evident as recent genomic screening analyses of the angiotensin-converting enzyme 2 (ACE2) and malaria-associated-variants identified 6 candidate genes that might play a role in malaria and COVID-19 incidence and severity. Moreover, the clinical and pathological resemblances between the two diseases have made considerable confusion in the diagnosis and thereafter curb the disease in Africa. Therefore, possible similarities between the diseases in regards to the clinical, pathological, immunological, and genetical ascription were discussed.ConclusionUnderstanding the dynamics of COVID-19 infection in Sub-Saharan Africa and how it is shaped by another endemic disease like malaria can provide insights into how to tailor a successful diagnostic, intervention, and control plans that lower both disease morbidity and mortality.

Neutrophils in malaria: A double-edged sword role.

Neutrophils are the most abundant leukocytes in human peripheral blood. They form the first line of defense against invading foreign pathogens and might play a crucial role in malaria. According to World Health Organization (WHO), malaria is a globally significant disease caused by protozoan parasites from the Plasmodium genus, and it’s responsible for 627,000 deaths in 2020. Neutrophils participate in the defense response against the malaria parasite via phagocytosis and reactive oxygen species (ROS) production. Neutrophils might also be involved in the pathogenesis of malaria by the release of toxic granules and the release of neutrophil extracellular traps (NETs). Intriguingly, malaria parasites inhibit the anti-microbial function of neutrophils, thus making malaria patients more susceptible to secondary opportunistic Salmonella infections. In this review, we will provide a summary of the role of neutrophils during malaria infection, some contradicting mouse model neutrophil data and neutrophil-related mechanisms involved in malaria patients’ susceptibility to bacterial infection.

Nutrient Deficiencies and Potential Alteration in Plasma Levels of Naturally Acquired Malaria-Specific Antibody Responses in Tanzanian Children.

Immunoglobulin G (IgG) subclasses have been suggested to confer naturally acquired immunity to Plasmodium falciparum malaria. Cytophilic IgG1 and IgG3 with their potential for opsonization, phagocytosis, and antibody-dependent cellular inhibition in association with monocytes have been suggested to have a critical role in malaria. The potential for production of antibodies is influenced by micronutrient status. This study aimed at exploring the effect of micronutrients, particularly zinc status, on the profiles of IgG subclasses in 304 Tanzanian children aged ≤ 5 years. An enzyme-linked immunosorbent assay was performed using whole asexual blood stage malaria antigens to determine plasma malaria-specific antibody titers. This baseline cross-sectional study was done from 2005 – 2010 prior to the larger randomized control trial of the Micronutrient and Child Health (MACH) Study. Plasma concentrations of zinc and magnesium were measured by inductively coupled plasma atomic emission spectrometry and results correlated with plasma IgG subclass levels. The findings reveal zinc deficiency to possibly influence the production of IgM, total IgG, and several IgG subclasses in a malaria status-dependent manner. Among IgG subclasses, IgG3 and partly IgG2 displayed a remarkable association with zinc deficiency, particularly IgG3 which was predominant in children with malaria. Nevertheless, zinc, magnesium, and malaria status did not influence the association between IgG3 and IgG4. The study leads to the conclusion that, under conditions of micronutrient deficiency and malaria status, an imbalance in IgG subclass production may occur leading to predominantly higher levels of IgG3 and IgG2 that may not confer sufficient protection from infection. The profile of both cytophilic and non-cytophilic IgG subclasses has been shown to be variably influenced by zinc status; the effects vary with age at least in under-fives. These results provide insight for inclusion of micronutrients, particularly precise amounts of zinc, in future malaria interventional programs in endemic areas.

Prevalence and Dynamic Changes in Lung Ultrasound Findings among Adults with Uncomplicated Malaria and Controls in the Amazon Basin, Brazil.

Malaria patients are at risk of cardiopulmonary complications but diagnosis and management can be difficult in resource-limited settings. B-lines on lung ultrasound (LUS) mark changes in lung density; however, little is known about their role in malaria. We aimed to examine the prevalence of B-lines in adults with malaria at baseline and follow-up compared with controls in the Amazon Basin. We also examined the relationship between B-lines and left ventricular ejection fraction. We performed eight-zone LUS, echocardiography, and blood smears in 94 adults (mean age 40 years, 54% men) with uncomplicated malaria and 449 controls without heart failure, renal insufficiency or lung disease (mean age 41 years, 38% men). Examinations of adults with malaria were repeated after antimalarial treatment, corresponding to a median of 30 days (interquartile range [IQR] 27-39). Adults with malaria suffered from Plasmodium vivax (N = 70, median 2,823 [IQR 598-7,698] parasites/μL) or P. falciparum (N = 24, median 1,148 [IQR 480-3,128] parasites/μL). At baseline, adults with malaria more frequently had ≥ 3 B-lines (summed across eight zones) compared with controls (30% versus 2%, P value < 0.001), indicating higher lung density. When examinations were repeated, only 6% of adults with malaria had ≥ 3 B-lines at follow-up, which was significant lower compared with baseline (median reduction 3 B-line; P value < 0.001). B-lines were not significantly associated with left ventricular ejection fraction in adults with malaria. In conclusion, B-lines detected by LUS were more frequent in adults with uncomplicated malaria compared with controls and decreased after completed antimalarial treatment.

Eryptosis as a New Insight in Malaria Pathogenesis.

Eryptosis is a programmed cell death-like process that occurs in red blood cells. Although the red blood cells are anucleated, there are similarities between eryptosis and apoptosis, such as increased calcium efflux, calpain activation, phosphatidylserine exposure, cell blebbing and cell shrinkage. Eryptosis occurs physiologically in red blood cells, as a consequence of the natural senescence process of these cells, but it can also be stimulated in pathological situations such as metabolic syndromes, uremic syndromes, polycythemia vera, anemias such as sickle cell anemia and thalassemia, and infectious processes including Plasmodium infection. Infection-induced eryptosis is believed to contribute to damage caused by Plasmodium, but it’s still a topic of debate in the literature. In this review, we provided an overview of eryptosis mechanisms and its possible pathogenic role in malaria.

Neutrophils in malaria: The good, the bad or the ugly?

Neutrophils are the most abundant circulating leukocytes in human peripheral blood. They are often the first cells to respond to an invading pathogen and might therefore play an important role in malaria. Malaria is a globally important disease caused by Plasmodium parasites, responsible for more than 400,000 deaths each year. Most of these deaths are caused by complications, including cerebral malaria, severe malarial anaemia, placental malaria, renal injury, metabolic problems and malaria-associated acute respiratory distress syndrome. Neutrophils contribute in the immune defence against malaria, through clearance of parasites via phagocytosis, production of reactive oxygen species and release of neutrophil extracellular traps (NETs). However, Plasmodium parasites diminish antibacterial functions of neutrophils, making patients more susceptible to other infections. Neutrophils might also be involved in the development of malaria complications, for example via the release of toxic granules and NETs. However, technical pitfalls in the determination of the roles of neutrophils have caused contradicting results. Further investigations need to consider these pitfalls, in order to elucidate the role of neutrophils in malaria complications.

STK35L1 regulates host cell cycle-related genes and is essential for Plasmodium infection during the liver stage of malaria

Protein kinases of both the parasite and the host are crucial in parasite invasion and survival and might act as drug targets against drug-resistant malaria. STK35L1 was among the top five hits in kinome-wide screening, suggesting its role in malaria's liver stage. However, the role of host STK35L1 in malaria remains elusive. In this study, we found that STK35L1 was highly upregulated during the infection of Plasmodium berghei (P. berghei) in HepG2 cells and mice liver, and knockdown of STK35L1 remarkably suppressed the sporozoites' infection in HepG2 cells. We showed that STAT3 is upregulated and phosphorylated during P. berghei sporozoites' infection, and STAT3 activation is required for both the upregulation of STK35L1 and STAT3. Furthermore, we found that ten cell cycle genes were upregulated in the sporozoite-infected hepatocytes. Knockdown of STK35L1 inhibited the basal expression of these genes except CDKN3 and GTSE1 in HepG2 cells. Thus, we identified STK35L1 as a host kinase that plays an obligatory role in malaria's liver stage and propose that it may serve as a potential drug target against drug-resistant malaria.

How Genetics Might Explain the Unusual Link Between Malaria and COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated coronavirus disease 2019 (COVID-19) pandemic has been the subject of a large number of studies in recent times. Here, starting from the evidence that in Italy, the areas with the lowest number of COVID-19 cases were those with the highest incidence of malaria in the early 1900's, we explore possible inverse relationships between malaria and COVID-19. Indeed, some genetic variants, which have been demonstrated to give an advantage against malaria, can also play a role in the incidence and severity of SARS-CoV-2 infections (e.g., the ACE2 receptor). To verify this scientific hypothesis, we here use public data from whole-genome sequencing (WGS) experiments to extrapolate the genetic information of 46 world populations with matched COVID-19 data. In particular, we focus on 47 genes, including ACE2 and genes which have previously been reported to play a role in malaria. Only common variants (>5%) in at least 30% of the selected populations were considered, and, for this subset, we correlate the intra-population allele frequency with the COVID-19 data (cases/million inhabitants), eventually pinpointing meaningful variants in 6 genes. This study allows us to distinguish between positive and negative correlations, i.e., variants whose frequency significantly increases with increasing or decreasing COVID-19 cases. Finally, we discuss the possible molecular mechanisms associated with these variants and advance potential therapeutic options, which may help fight and/or prevent COVID-19.

Malaria link of hypertension: a hidden syndicate of angiotensin II, bradykinin and sphingosine 1-phosphate.

In malaria-endemic countries, the burden of hypertension is on the rise. Although malaria and hypertension seem to have no direct link, several studies in recent years support their possible link. Three bioactive molecules such as angiotensin II (Ang II), bradykinin (BK) and sphingosine 1-phosphate (S1P) are crucial in regulating blood pressure. While the increased level of Ang II and S1P are responsible for inducing hypertension, BK is arthero-protective and anti-hypertensive. Therefore, in the present review, based on available literatures we highlight the present knowledge on the production and bioavailability of these molecules, the mechanism of their regulation of hypertension, and patho-physiological role in malaria. Further, a possible link between malaria and hypertension is hypothesized through various arguments based on experimental evidence. Understanding of their mechanisms of blood pressure regulation during malaria infection may open up avenues for drug therapeutics and management of malaria in co-morbidity with hypertension.

Multiparameter Flow Cytometry Analysis of the Human Spleen Applied to Studies of Plasma-Derived EVs From Plasmodium vivax Patients.

The spleen is a secondary lymphoid organ with multiple functions including the removal of senescent red blood cells and the coordination of immune responses against blood-borne pathogens, such as malaria parasites. Despite the major role of the spleen, the study of its function in humans is limited by ethical implications to access human tissues. Here, we employed multiparameter flow cytometry combined with cell purification techniques to determine human spleen cell populations from transplantation donors. Spleen immuno-phenotyping showed that CD45+ cells included B (30%), CD4+ T (16%), CD8+ T (10%), NK (6%) and NKT (2%) lymphocytes. Myeloid cells comprised neutrophils (16%), monocytes (2%) and DCs (0.3%). Erythrocytes represented 70%, reticulocytes 0.7% and hematopoietic stem cells 0.02%. Extracellular vesicles (EVs) are membrane-bound nanoparticles involved in intercellular communication and secreted by almost all cell types. EVs play several roles in malaria that range from modulation of immune responses to vascular alterations. To investigate interactions of plasma-derived EVs from Plasmodium vivax infected patients (PvEVs) with human spleen cells, we used size-exclusion chromatography (SEC) to separate EVs from the bulk of soluble plasma proteins and stained isolated EVs with fluorescent lipophilic dyes. The integrated cellular analysis of the human spleen and the methodology employed here allowed in vitro interaction studies of human spleen cells and EVs that showed an increased proportion of T cells (CD4+ 3 fold and CD8+ 4 fold), monocytes (1.51 fold), B cells (2.3 fold) and erythrocytes (3 fold) interacting with PvEVs as compared to plasma-derived EVs from healthy volunteers (hEVs). Future functional studies of these interactions can contribute to unveil pathophysiological processes involving the spleen in vivax malaria.

Protection against COVID-19 in African Population: Immunology, Genetics, and Malaria Clues for Therapeutic Targets

Background: There is a marked discrepancy between SARS-CoV-2 seroprevalence and COVID-19 cases and deaths in Africa. Main: SARS-CoV-2 stimulates humoral and cellular immunity systems, as well as mitogen-activated protein kinase (MAPK) and nuclear NF-kB signaling pathways, which regulate inflammatory gene expression and immune cell differentiation. The result is pro-inflammatory cytokines release, hyperinflammatory condition, and cytokine storm, which provoke severe lung alterations that can lead to multi-organ failure in COVID-19. Multiple genetic and immunologic factors may contribute to the severity of COVID-19 in African individuals when compared to the rest of the global population. In this article, the role of malaria, NF-kB and MAPK pathways, caspase-12 expression, high level of LAIR-1-containing antibodies, and differential glycophorins (GYPA/B) expression in COVID-19 are discussed. Conclusion: Understanding pathophysiological mechanisms can help identify target points for drugs and vaccines development against COVID-19. To our knowledge, this is the first study that explores this link and proposes a biological and molecular answer to the epidemiologic discrepancy in COVID-19 in Africa.

Comorbidities and the COVID-19 pandemic dynamics in Africa.

The debate around the COVID‐19 response in Africa has mostly focused on effects and implications of public health measures, in light of the socio‐economic peculiarities of the continent. However, there has been limited exploration of the impact of differences in epidemiology of key comorbidities, and related healthcare factors, on the course and parameters of the pandemic. We summarise what is known about (a) the pathophysiological processes underlying the interaction of coinfections and comorbidities in shaping prognosis of COVID‐19 patients, (b) the epidemiology of key coinfections and comorbidities, and the state of related healthcare infrastructure that might shape the course of the pandemic, and (c) implications of (a) and (b) for pandemic management and post‐pandemic priorities. There is a critical need to generate empirical data on clinical profiles and the predictors of morbidity and mortality from COVID‐19. Improved protocols for acute febrile illness and access to diagnostic facilities, not just for SARS‐CoV‐2 but also other viral infections, are of urgent importance. The role of malaria, HIV/TB and chronic malnutrition on pandemic dynamics should be further investigated. Although chronic non‐communicable diseases account for a relatively lighter burden, they have a significant effect on COVID‐19 prognosis, and the fragility of care delivery systems implies that adjustments to clinical procedures and re‐organisation of care delivery that have been useful in other regions are unlikely to be feasible. Africa is a large region with local variations in factors that can shape pandemic dynamics. A one‐size‐fits‐all response is not optimal, but there are broad lessons relating to differences in epidemiology and healthcare delivery factors, that should be considered as part of a regional COVID‐19 response framework.

Evaluating fidelity of community health worker roles in malaria prevention and control programs in Livingstone District, Zambia-A bottleneck analysis

BackgroundCommunity Health Workers (CHWs) are an important human resource in improving community malaria intervention coverages and success in reducing malaria incidence has been attributed to them. However, despite this attribution, malaria resurgence cases have been reported in various countries including Zambia. This study aims to evaluate the implementation fidelity of CHW roles in malaria prevention and control programs in Livingstone through performance and service quality assessment.MethodsA mixed method concurrent cross-sectional study based on quantitative and qualitative approaches was used to evaluate performance and service quality of the CHW roles for selected catchments areas in Livingstone district. For the quantitative approach, (34) CHWs were interviewed and a community survey was also done with 464 community participants. For qualitative approach, two focused group discussions with CHWs and three key informant interviews from the CHW supervisors were done.ResultsOverall implementation fidelity to the CHW roles was low with only 5(14.7%) of the CHWs having good performance and least good quality service while 29 (85.3%) performed poorly with substandard service. About 30% of house-holds reported having experienced malaria cases but CHWs had low coverage in testing with RDT (27%) for malaria index case service response with treatment at 14% coverage and provision of health education at 23%. For other households without malaria cases, only 27% had received malaria health education and 15% were screened for malaria. However, ITN distribution, sensitization for IRS were among other CHW services received by the community but were not documented in CHW registers for evaluation. Factors that shaped fidelity were being married, record for reports, supervision, and work experience as significant factors associated with performance. Lack of supplies, insufficient remuneration and lack of ownership by the supervising district were reported to hinder ideal implementation of the CHW strategy.ConclusionFidelity to the malaria CHW roles was low as performance and quality of service was poor. A systems approach for malaria CHW facilitation considering supervision, stock supply and recruiting more CHWs on a more standardized level of recognition and remuneration would render an effective quality implementation of the CHW roles in malaria.

Assessment of Antiplasmodial and Antioxidant Activities, Total Phenolics and Flavonoids Content, and Toxicological Profile of Cola millenii K. shum (Malvaceae)

Aims: This study was designed to assess antiplasmodial and antioxidant activities in relation to phytochemical contents and toxicological profile of crude extracts of Cola millenii leaves.&#x0D; Place and Duration of Study: The study was carried out from April 2015 to November 2018 at University of Abomey-Calavi, Laboratory of Biochemistry and Bioactives Natural Products and Laboratory of Infectious Vector-borne Diseases.&#x0D; Methodology: Phytochemical screening of aqueous and ethanolic crude extracts was performed using standard methods. Estimation of total phenolics contains (TPC) and total flavonoids contains (TFC) was done using colorimetric methods. Antioxidant activity was assessed in vitro by 2,2-diphenyl-1-picrylhydrazyl (DPPH) Radical-Scavenging, Reducing power, superoxide radical scavenging and Hydrogen peroxide scavenging assay. Antiplasmodial activity was investigated in vitro using both field isolate and laboratory 3D7 strains of P. falciparum using Plasmodium lactate dehydrogenase (pLDH) assay. Hemoglobin release was measured spectrophotometrically to assess hemolytic power. Acute oral toxicity of extracts was evaluated on rats according to OECD 423 guideline.&#x0D; Results: Flavonoids, anthraquinones, coumarins, and triterpenes were recorded in both extracts while tannins were recorded only in ethanolic extract. High TPC and TFC were recorded with ethanolic extract with significate difference (P &lt;0.01) when compared to aqueous extract. Ethanolic extract exhibited the highest parasite growth inhibition against both field isolate (41.62±1.78%) and 3D7 (45.89±1.66%) strains at 100 µg/mL. Both extracts exhibited strong antioxidant activity according to different methods used. Toxicological profile revealed no hemolytic effect on human red blood cells as well as acute toxicity signs in rats.&#x0D; Conclusion: This study demonstrated strong antioxidant and moderate antiplasmodial activities of C. millenii extracts without toxicity effect on rats and human erythrocytes. It would play an important role in malaria and oxidative damage control.

A More Granular View of Neutrophils in Malaria

Neutrophils are abundant innate immune cells with crucial roles in immunity and vascular inflammation. Recent evidence indicates that neutrophils have a dual role in malaria, contributing to both pathogenesis and control of Plasmodium. We discuss emerging mechanisms behind these opposing functions and identify key outstanding questions.

Cyclooxygenase-2 haplotypes influence the longitudinal risk of malaria and severe malarial anemia in Kenyan children from a holoendemic transmission region.

Cyclooxygenase-2 [(COX-2) or prostaglandin endoperoxide H2 synthase-2 (PTGS-2)] induces the production of prostaglandins as part of the host-immune response to infections. Although a number of studies have demonstrated the effects of COX-2 promoter variants on autoimmune and inflammatory diseases, their role in malaria remains undefined. As such, we investigated the relationship between four COX-2 promoter variants (COX-2 -512 C > T, -608 T > C, -765 G > C, and -1195 A > G) and susceptibility to malaria and severe malarial anemia (SMA) upon enrollment and longitudinally over a 36-month follow-up period. All-cause mortality was also explored. The investigation was carried out in children (n = 1081, age; 2-70 months) residing in a holoendemic Plasmodium falciparum transmission region of western Kenya. At enrollment, genotypes/haplotypes (controlling for anemia-promoting covariates) did not reveal any strong effects on susceptibility to either malaria or SMA. Longitudinal analyses showed decreased malaria episodes in children who inherited the -608 CC mutant allele (RR = 0.746, P = 1.811 × 10-4) and -512C/-608T/-765G/-1195G (CTGG) haplotype (RR = 0.856, P = 0.011), and increased risk in TTCA haplotype carriers (RR = 1.115, P = 0.026). Over the follow-up period, inheritance of the rare TTCG haplotype was associated with enhanced susceptibility to both malaria (RR = 1.608, P = 0.016) and SMA (RR = 5.714, P = 0.004), while carriage of the rare TTGG haplotype increased the risk of malaria (RR = 1.755, P = 0.007), SMA (RR = 8.706, P = 3.97 × 10-4), and all-cause mortality (HR = 110.000, P = 0.001). Collectively, these results show that SNP variations in the COX-2 promoter, and their inherited combinations, are associated with the longitudinal risk of malaria, SMA, and all-cause mortality among children living in a high transmission area for P. falciparum.

Is there a role for bedside ultrasound in malaria? A survey of the literature.

Point-of-care ultrasound (POCUS) has proven utility in the evaluation and treatment of many tropical diseases. Its role in malaria has been studied, but its value for the clinician at the bedside is unclear. Our review aimed at summarizing the existing studies to assess the usefulness, if any, of POCUS in treating malaria. We used Boolean operators using keywords "malaria", "acoustic", "ultrasound", "echography", and "ultrasonography" to search PubMed, Scopus, and Science Direct in three languages (Italian, French, and English). We found 22 eligible references. Organs explored include the liver, spleen, heart, optic nerve sheath diameter (ONSD), kidney, lungs, and cerebral vasculature. Multiple pathologic findings by ultrasound are reported, but few demonstrate clinical utility. Current studies involve small numbers of patients, and a few trends emerge when studies are compared. The ability to combine study results is limited due to the significant heterogeneity that exists between studies in regards to both methods of evaluation and the reporting of organ pathology and malaria severity. A review of the current literature indicates that the use of ultrasound by clinicians adds little to the diagnostic evaluation of patients with malaria. Our review did find that measurements of the spleen, lungs, optic nerve sheath diameter, and cerebral blood flow have potential utility in specific patient populations. Further studies are needed to evaluate whether this utility persists when a larger sample size is used.