Falciparum Parasitaemia Research Articles

Efficacy of Malaria Symptoms as an Indicator of Malaria Infection among Students of a Tertiary Institution in Ogun State Nigeria

Malaria is a life-threatening disease caused by the parasite Plasmodium, which is transmitted through the bite of an infected female Anopheles mosquito. Asymptomatic Plasmodium falciparum parasitemia refers to the presence of the parasite in the absence of fever or malaria-related symptoms. In Ijebu-Igbo, Ogun State, Nigeria, a study was conducted to ascertain the frequency of asymptomatic malaria among students attending higher education institutions and determine the efficacy of malaria symptoms as an indicator of malaria infection. A total of 115 students who consented to participate in the study were enrolled, and only a total of 93 of the respondents were recruited for the study, having met the inclusion criteria. A structured questionnaire was used to obtain data on socio-demographic characteristics, signs and symptoms of malaria, and malaria prevention strategy using Insecticide Treated Nets (ITN). Blood samples were collected from the respondents and diagnosed for malaria using Rapid Diagnostic Tests (RDT) kit. Of the 93 respondents, 32 (34%) were males while 61 (66%) were females. Analysis of the result showed that 77% of the respondents had malaria parasites, 38.7% of the respondents indicated that they do feel feverish sometimes while 47.3% responded that they rarely feel feverish, those who rarely show symptoms were observed to be asymptomatic as the result of the RDT was positive for malaria. On the use of Insecticide Treated Net (ITN) for both categories of students, those who are not using the net had a higher prevalence (64.5%) of malaria infection. The result of this study shows that malaria symptoms is not a good diagnostic tool for determining treatment. Asymptomatic malaria was a risk factor among the students therefore measures to reduce the prevalence are advocated.

One Haemolytic Anaemia May Hide Another: Paroxysmal Nocturnal Haemoglobinuria Masquerading As Plasmodium Falciparum Infection.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, genetic and acquired haematologic disease that causes complement-mediated intravascular haemolytic anaemia, thrombosis and bone marrow failure. A 27-year-old migrant patient attended the emergency department in a context of fever and chills over the previous few days as well as chronic fatigue, dyspnoea and chest pain. His medical history included chronic anaemia and erectile dysfunction. Initial biology showed a haemoglobin of 6.3 g/dl, platelets of 25,000/μl, total leucocytes of 3,500/μl with 1,500 neutrophils. B12 vitamin, folic acid, ferritin and thyroid stimulating hormone were normal. Lactate dehydrogenase levels were high and haptoglobin was non-measurable. C-reactive protein was 46.1 mg/l. A thick blood smear revealed Plasmodium falciparum infection with 0.1% parasitaemia. The patient was treated with an oral combination of artemether and lumefantrine. Three weeks later, the patient consulted the infectious disease department given the lack of clinical improvement. The cytopenias worsened, and lactate dehydrogenase (LDH) and reticulocytes increased. Tests for schistocytes, a thick blood smear for malaria and a direct Coombs test were negative; a myelogram was reassuring. An abdominal, pelvic and thoracic CT scan showed a mild hepatomegaly with no focal lesion and no splenomegaly or adenomegaly. A 12-colour flow cytometry unveiled a PNH clone on 90.9545% of neutrophils and 80.7371% of monocytes. PNH patients can be vulnerable to parasites infection (such as P. falciparum) as it may trigger breakthrough haemolysis through uncontrolled resurgence of activity of the complement system. In our patient, P. falciparum infection was a confounding factor, as it commonly causes haemolytic anaemia and thrombocytopenia, and patients living in malaria-endemic regions can carry low parasitaemia while being slightly symptomatic or asymptomatic. Plasmodium falciparum infection can cause breakthrough haemolysis in patients with paroxysmal nocturnal haemoglobinuria.Low P. falciparum parasitemia in patients living in malaria-endemic regions is not always significant as these patients often carry acquired immunity.Patients from malaria-endemic regions presenting with severe sickness and low P. falciparum parasitemia must be assessed for other diseases, as it cannot explain heavy illness.Patients presenting with haemolytic anaemia, no schistocytes, a negative direct Coombs test and other unexplained cytopenia such as thrombocytopenia/neutropenia and other unexplained clinical manifestations such as dyspnoea, chest pain or erectile dysfunction should be assessed for paroxysmal nocturnal haemoglobinuria.

The Significance of TNF-α, CRP, and Hematological Parameters in the Prediction of Plasmodium Falciparum Parasitemia

Malaria remains a significant public health concern in Sudan, with Plasmodium falciparum (P. falciparum) infection having widespread indirect consequences. Effective identification of infection severity is crucial for preventing complications. This study aimed to assess the predictive value of Tumor Necrosis Factor Alpha (TNF-α), C-reactive protein (CRP), and hematological parameters in P. falciparum parasitemia. The three-month cross-sectional study involved 54 P. falciparum-positive patients at Bashaire Teaching Hospital Khartoum, Sudan, along with an equal number of P. falciparum-negative individuals. Participants underwent Antigen Rapid Diagnostic Test (RDT), TNFα, CRP, and Complete Blood Count (CBC) assessments. The infected group comprised 68.5% male patients, with a mean age of 22.3 years. Significant variations were observed between the infected and uninfected groups in TNFα, CRP, Total White Blood Cells (TWBCs), and neutrophil levels, with infected individuals showing higher values. Conversely, infected individuals had lower hemoglobin, Red Blood Cells (RBCs), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC), platelets, and lymphocytes. The study revealed a noteworthy association between MCV and parasitemia, while TNFα, CRP, Hb, RBCs, MCH, and MCHC showed no significant correlation. Hematological parameters should be considered in malaria patients.

Subclinical Inflammation in Asymptomatic Schoolchildren With Plasmodium falciparum Parasitemia Correlates With Impaired Cognition.

Subclinical inflammation and cognitive deficits have been separately associated with asymptomatic Plasmodium falciparum infections in schoolchildren. However, whether parasite-induced inflammation is associated with worse cognition has not been addressed. We conducted a cross-sectional pilot study to better assess the effect of asymptomatic P. falciparum parasitemia and inflammation on cognition in Kenyan schoolchildren. We enrolled 240 children aged 7-14 years residing in high malaria transmission in Western Kenya. Children performed five fluid cognition tests from a culturally adapted NIH toolbox and provided blood samples for blood smears and laboratory testing. Parasite densities and plasma concentrations of 14 cytokines were determined by quantitative PCR and multiplex immunoassay, respectively. Linear regression models were used to determine the effects of parasitemia and plasma cytokine concentrations on each of the cognitive scores as well as a composite cognitive score while controlling for age, gender, maternal education, and an interaction between age and P. falciparum infection status. Plasma concentrations of TNF, IL-6, IL-8, and IL-10 negatively correlated with the composite score and at least one of the individual cognitive tests. Parasite density in parasitemic children negatively correlated with the composite score and measures of cognitive flexibility and attention. In the adjusted model, parasite density and TNF, but not P. falciparum infection status, independently predicted lower cognitive composite scores. By mediation analysis, TNF significantly mediated ~29% of the negative effect of parasitemia on cognition. Among schoolchildren with PCR-confirmed asymptomatic P. falciparum infections, the negative effect of parasitemia on cognition could be mediated, in part, by subclinical inflammation. Additional studies are needed to validate our findings in settings of lower malaria transmission and address potential confounders that could affect both inflammation and cognitive performance.

Recombinant Full-length Plasmodium falciparum Circumsporozoite Protein-Based Vaccine Adjuvanted With Glucopyranosyl Lipid A-Liposome Quillaja saponaria 21: Results of Phase 1 Testing With Malaria Challenge.

Malaria is preventable yet causes >600 000 deaths annually. RTS,S, the first marketed malaria vaccine, has modest efficacy, but improvements are needed for eradication. We conducted an open-label, dose escalation phase 1 study of a full-length recombinant circumsporozoite protein vaccine (rCSP) administered with adjuvant glucopyranosyl lipid A-liposome Quillaja saponaria 21 formulation (GLA-LSQ) on days 1, 29, and 85 or 1 and 490 to healthy, malaria-naive adults. The primary end points were safety and reactogenicity. The secondary end points were antibody responses and Plasmodium falciparum parasitemia after homologous controlled human malaria infection. Participants were enrolled into 4 groups receiving rCSP/GLA-LSQ: 10 µg × 3 (n = 20), 30 µg × 3 (n = 10), 60 µg × 3 (n = 10), or 60 µg × 2 (n = 9); 10 participants received 30 µg rCSP alone × 3, and there were 6 infectivity controls. Participants experienced no serious adverse events. Rates of solicited and unsolicited adverse events were similar among groups. All 26 participants who underwent controlled human malaria infection 28 days after final vaccinations developed malaria. Increasing vaccine doses induced higher immunoglobulin G titers but did not achieve previously established RTS,S benchmarks. rCSP/GLA-LSQ had favorable safety results. However, tested regimens did not induce protective immunity. Further investigation could assess whether adjuvant or schedule adjustments improve efficacy. NCT03589794.

Asymptomatic Plasmodium falciparum carriage at the end of the dry season is associated with subsequent infection and clinical malaria in Eastern Gambia.

Chronic carriage of asymptomatic low-density Plasmodium falciparum parasitaemia in the dry season may support maintenance of acquired immunity that protects against clinical malaria. However, the relationship between chronic low-density infections and subsequent risk of clinical malaria episodes remains unclear. In a 2-years study (December 2014 to December 2016) in eastern Gambia, nine cross-sectional surveys using molecular parasite detection were performed in the dry and wet season. During the 2016 malaria transmission season, passive case detection identified episodes of clinical malaria. Among the 5256 samples collected, 444 (8.4%) were positive for P. falciparum. A multivariate model identified village of residence, male sex, age ≥ 5 years old, anaemia, and fever as independent factors associated with P. falciparum parasite carriage. Infections did not cluster over time within the same households or recurred among neighbouring households. Asymptomatic parasite carriage at the end of dry season was associated with a higher risk of infection (Hazard Ratio, HR = 3.0, p < 0.0001) and clinical malaria (HR = 1.561, p = 0.057) during the following transmission season. Age and village of residence were additional predictors of infection and clinical malaria during the transmission season. Chronic parasite carriage during the dry season is associated with an increased risk of malaria infection and clinical malaria. It is unclear whether this is due to environmental exposure or to other factors.

Association between malaria parasite density and hematological profile in malaria infected children at a Nigerian Private hospital.

The correct association between Plasmodium falciparum parasite density and the cellular constituents of blood is not known in entirety in Nigerian children. Thus, we decided to study the association between cellular blood constituents and malaria parasite density in malaria infected children attending a Nigerian hospital. A study of all children diagnosed with malaria fever at the Pediatric out-patient clinic, Cedar Crest Hospital, Abuja, Nigeria, was conducted. Packed cell volume, white blood cells with differentials and platelet counts and malaria parasite densities obtained from blood samples were studied. Malaria parasite densities more than 2 pluses were classified as significant parasitemia and 1 plus as non-significant. Information obtained was recorded and analysed with SPSS 22 software. A total 143 children (74 boys and 69 girls) diagnosed with malaria of ages between 5 months to 17 years (mean 5.24 ±4.60) were studied. The majority of 141 (98.6%) had non-significant P. falciparum parasitemia, while 2 (2.4%) had significant parasitemia. Of the 143 children with malaria, 116 (81.1%) had a normal leucocyte count. All children with significant parasitemia had a normal leucocyte count. Of the 143 children, 11 (7.7%) had anemia and 10 (7.0%) thrombocytopenia. Anemia, monocytosis and thrombocytopenia were significantly associated with significant malaria parasitemia (p<0.05). Mean platelet counts was significantly less amongst those with significant parasitemia (p<0.01). All patients with significant malaria parasitemia had normal leucocyte count. Significant malaria parasitemia is significantly associated with anemia, thrombocytopenia and monocytosis. Blood film appearances showing these changes are suggestive of significant malaria parasitemia.

Malaria Infection in Patients with Sickle Cell Disease in Nigeria: Association with Markers of Hyposplenism.

Malaria is considered an important cause of morbidity and mortality among people living with sickle cell disease (SCD). This has partly been attributed to the loss of splenic function that occurs early in the disease process. We conducted a cross-sectional study and determined the frequency of malaria infection among SCD patients and explored the association with spleen's presence on ultrasonography and spleen function assessed using the frequency of Howell-Jolly bodies (HJBs). A total of 395 participants consisting of 119 acutely-ill SCD patients, 168 steady-state SCD controls, and 108 healthy non-SCD controls were studied. The prevalence of Plasmodium falciparum parasitemia was 51.3% in acutely-ill SCD patients, 31.7% in steady-state SCD controls, and 11.0% in the healthy non-SCD controls; however, the mean parasite density was significantly higher in the non-SCD controls compared to both SCD groups (p = 0.0001). Among the acutely-ill SCD patients, the prevalence of clinical malaria and severe malaria anemia were highest in children <5 years of age. The prevalence of parasitemia (p = 0.540) and parasite density (p = 0.975) showed no association with spleen presence or absence on ultrasonography. Similarly, the frequency of HJB red cells was not associated with the presence of parasitemia (p = 0.183). Our study highlights the frequency and role of malaria infection in acutely-ill SCD patients, especially in those younger than five years. Although we have found no evidence of an increased risk of malaria parasitemia or parasite density with markers of hyposplenism, the role played by an underlying immunity to malaria among SCD patients in malaria-endemic region is not clear and needs further studies.

Erythrocyte Indices Variations In Under Five Children As A Result Of High Plasmodium Falciparum Parasitaemia

Nigeria accounts for 31% of the 619,000 malaria-related deaths recorded worldwide, according to the World Malaria Report 2022. Malaria caused by Plasmodium falciparum causes significant changes in haematological parameters and indices. The study aimed to observe erythrocyte indices and haemoglobin concentration variations in children with Plasmodium falciparum parasitaemia, evaluate the correlation between parasite count and indices, and assess their predictive roles. We analysed 194 children (≤ 5 years old) suspected of malaria and collected 5 ml of whole blood samples for analysis. The samples were used to prepare thin and thick blood films for qualitative and quantitative assays. A CBC was carried out to estimate HGB concentration and erythrocyte indices. The case and control group had a mean difference statistically significant at (P&lt;0.001). MCV [case group (72.26±4.83), control group (85.00±4.48)]; MCH [case group (23.82±2.51), control group (28.85±2.02)] and HGB [case group (100.78±14.84), control group (135.65±9.95). Pearson correlation showed weak negative statistical significance at (P&lt;0.05) for MCV, MCH, MCHC and HGB in the range of (-0.38) – (-0.218). Regression analysis indicated that parasite count predicted MCV, MCH, MCHC and HGB at (P&lt;0.05); R values at (0.283, 0.272, 0.326 and 0.308, respectively). When considering age and parasite count as predictive variables, we obtained R values of 0.285, 0.282, 0.326, and 0.328 for MCV, MCH, MCHC, and HGB, respectively. Research results show a significant relationship between Plasmodium falciparum parasitaemia and variations in erythrocyte indices with haemoglobin concentration in children at significant levels.

Estimation of parasitaemia in imported falciparum malaria using the results of a combined rapid diagnostic test. No big help from haematological parameters

BackgroundMicroscopy continues to be the mainstay for the evaluation of parasitaemia in malaria but requires laboratory support and microbiological experience. Other fast and simple methods are necessary.MethodsA retrospective observational study of imported malaria treated from July-2007 to December-2020 was carried out to evaluate the association between the degree of parasitaemia and both rapid diagnostic tests (RDT) reactivity patterns and haematological parameters. Plasmodium falciparum monoinfections diagnosed by peripheral blood smear and/or polymerase chain reaction (PCR),which also had a positive RDT result in the same blood sample, were included in the study.ResultsA total of 273 patients were included. Most of them were male (n = 256; 93.8%) and visiting friends and relatives (VFR) travellers (n = 252; 92.3%). Patients with plasmodial lactate dehydrogenase (pLDH) or aldolase and histidine-rich protein 2 (HRP-2) co-reactivity (Pan/Pf pattern) had a parasitaemia range between 0 and 37% while those with just HRP-2 reactivity (P. falciparum pattern) had ranges between 0 and 1%. Not a single case of P. falciparum pattern was found for parasitaemia ranges greater than 1%, showing a negative predictive value of 100% for high parasitaemia. All the correlations between haematological parameters and parasitaemia resulted to be weak, with a maximum rho coefficient of -0.35 for lymphocytes and platelets, and of 0.40 for neutrophils-to-lymphocytes count ratio. Multivariate predictive models were constructed reflecting a poor predictive capacity.ConclusionsThe reactivity pattern of RDT allows a rapid semi-quantitative assessment of P. falciparum parasitaemia in travellers with imported malaria, discriminating patients with lower parasite loads. Haematological parameters were not able to estimate parasitaemia with sufficient precision.

Variation in neutrophil levels and artemisinin-based combination therapy efficacy in West-Africa.

Polymorphonuclear neutrophils (PMN) are involved in pathogen clearance by phagocytosis. However, the role of PMNs in the efficacy of artemisinin-based combination therapy (ACT) is poorly understood. In a prospective longitudinal in vivo study, neutrophil rates were compared with malaria carriage after treatment with different ACTs: Artemether - lumefantrine (AL), Artesunate - amodiaquine (ASAQ), Dihydroartemisinin - piperaquine (DP) or Pyronaridine artesunate (PA). The study cases were classified as having neutropenia, normal neutrophil levels or neutrophilia depending on the level of neutrophils in the blood. This study included 3148 patients and was analyzed using R. On day 7, only four patients in the neutropenia group and treated with AL had a malaria positive blood smear based on microscopy. On day 28, the rate of recurrent parasitemia in the AL arm was significantly higher in neutropenia patients (50.9%) than in patients with normal rates of neutrophils (43.1%) or in those with neutrophilia (6.0%) (p < 0.001). In ASAQ arm, the rate of recurrent Plasmodium falciparum parasitemia was 58.8% in the neutropenia group versus 29.4% in patients with normal rates of neutrophils and 11.8% in patients with neutrophilia (p < 0.001). No patient treated with DP with normal neutrophil counts or neutrophilia was carrying malaria parasites on day 28. Among the 15 patients with parasitemia on day 28 in the PA arm, 11 (73.33%) had neutropenia while 4 (26.67%) had a normal neutrophil count (p < 0.001). Patients with neutropenia had higher rates of recurrent P. falciparum parasitemia after ACT.

Increasing Prevalence of Artemisinin-Resistant HRP2-Negative Malaria in Eritrea

BackgroundAlthough the clinical efficacy of antimalarial artemisinin-based combination therapies in Africa remains high, the recent emergence of partial resistance to artemisinin in Plasmodium falciparum on the continent is troubling, given the lack of alternative treatments.MethodsIn this study, we used data from drug-efficacy studies conducted between 2016 and 2019 that evaluated 3-day courses of artemisinin-based combination therapy (artesunate–amodiaquine or artemether–lumefantrine) for uncomplicated malaria in Eritrea to estimate the percentage of patients with day-3 positivity (i.e., persistent P. falciparum parasitemia 3 days after the initiation of therapy). We also assayed parasites for mutations in Pfkelch13 as predictive markers of partial resistance to artemisinin and screened for deletions in hrp2 and hrp3 that result in variable performance of histidine rich protein 2 (HRP2)–based rapid diagnostic tests for malaria.ResultsWe noted an increase in the percentage of patients with day-3 positivity from 0.4% (1 of 273) in 2016 to 1.9% (4 of 209) in 2017 and 4.2% (15 of 359) in 2019. An increase was also noted in the prevalence of the Pfkelch13 R622I mutation, which was detected in 109 of 818 isolates before treatment, from 8.6% (24 of 278) in 2016 to 21.0% (69 of 329) in 2019. The odds of day-3 positivity increased by a factor of 6.2 (95% confidence interval, 2.5 to 15.5) among the patients with Pfkelch13 622I variant parasites. Partial resistance to artemisinin, as defined by the World Health Organization, was observed in Eritrea. More than 5% of the patients younger than 15 years of age with day-3 positivity also had parasites that carried Pfkelch13 R622I. In vitro, the R622I mutation conferred a low level of resistance to artemisinin when edited into NF54 and Dd2 parasite lines. Deletions in both hrp2 and hrp3 were identified in 16.9% of the parasites that carried the Pfkelch13 R622I mutation, which made them potentially undetectable by HRP2-based rapid diagnostic tests.ConclusionsThe emergence and spread of P. falciparum lineages with both Pfkelch13-mediated partial resistance to artemisinin and deletions in hrp2 and hrp3 in Eritrea threaten to compromise regional malaria control and elimination campaigns. (Funded by the Bill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry numbers, ACTRN12618001223224, ACTRN12618000353291, and ACTRN12619000859189.)

Changes in oxygen delivery during experimental models of cerebral malaria

Cerebral malaria (CM) is a severe manifestation of malaria that commonly occurs in children and is hallmarked by neurologic symptoms and significant Plasmodium falciparum parasitemia. It is currently hypothesized that cerebral hypoperfusion from impaired microvascular oxygen transport secondary to parasitic occlusion of the microvasculature is responsible for cerebral ischemia and thus disease severity. Animal models to study CM, are known as experimental cerebral malaria (ECM), and include the C57BL/6J infected with Plasmodium berghei ANKA (PbA), which is ECM-susceptible, and BALB/c infected with PbA, which is ECM-resistant. Here we sought to investigate whether changes in oxygen (O2) delivery, O2 flux, and O2 utilization are altered in both these models of ECM using phosphorescence quenching microscopy (PQM) and direct measurement of microvascular hemodynamics using the cranial window preparation. Animal groups used for investigation consisted of ECM-susceptible C57BL/6 (Infected, n = 14) and ECM-resistant BALB/c (Infected, n = 9) mice. Uninfected C57BL/6 (n = 6) and BALB/c (n = 6) mice were included as uninfected controls. Control animals were manipulated in the exact same way as the infected mice (except for the infection itself). C57BL/6 ECM animals at day 6 of infection were divided into two cohorts: Early-stage ECM, presenting mild to moderate drops in body temperature (>34 < 36 °C) and Late-stage ECM, showing marked drops in body temperature (<33 °C). Data taken from new experiments conducted with these animal models were analyzed using a general linear mixed model. We constructed three general linear mixed models, one for total O2 content, another for total O2 delivery, and the third for total O2 content as a function of convective flow. We found that in both the ECM-susceptible C57BL/6J model and ECM-resistant BALB/c model of CM, convective and diffusive O2 flux along with pial hemodynamics are impaired. We further show that concomitant changes in p50 (oxygen partial pressure for 50% hemoglobin saturation), only 5 mmHg in the case of late-stage CM C57BL/6J mice, and O2 diffusion result in insufficient O2 transport by the pial microcirculation, and that both these changes are required for late-stage disease. In summary, we found impaired O2 transport and O2 affinity in late-stage ECM, but only the former in either early-stage ECM and ECM-resistant strains.

Circulating platelets and malaria severity: two sides of the same coin among inhabitants of a tropical savannah region, Nigeria.

Changes in circulating platelets during different grades of malaria are of major concerns, and its etiology is poorly understood. We appraised and evaluated the role of circulating platelets in the determination of the severity of malaria among a cohort of outpatients living in Ilorin, Nigeria. A hospital-based case-control study of outpatients visiting public health facilities within the locality voluntarily enrolled for this study. Blood samples from 1162 malaise patients were screened using routine microscopy for Plasmodium parasite species identification, and their respective circulating platelet levels were determined. Seven hundred and seventy-five individuals (775, 66.7%, p<0.001) were malaria-positive. Samples from 387 (33.3%) uninfected healthy individuals were used as controls. Individuals with uncomplicated malaria (UCM) and complicated malaria (CM) across age group were notable (p<0.05). Children ≤5 years had the highest number of individuals with CM (103, 45.2%) with a relative risk ratio of 4.005 (95% CI: 2.964-5.413). UCM (471, 40.5%) occurred more than CM (304, 26.2%) (p>0.05) across the groups. The geometric mean, 95% CI, median, and IQR of populations with malaria thrombocytopenia were higher (181, 110.94±2.207, 106.59-115.30, 118.00, and 39.00) than thrombocytosis (78, 624.64±13.131, 598.49-650.79, 623.00, and 208). Seemingly, health controls recorded insignificant morbidity with respect to platelet counts. High P. falciparum parasitemia is inversely correlated with platelet count, and its' morbidity is associated with the manifestation of several malaria pathogenesis. Thrombocytopenia is a silent pathophysiological attribute that can trigger other cofactors during severe malaria disease. Although further studies are pertinent in order to specifically clarify its relevance to clinical disease spectrum.

Exploring the host factors affecting asymptomatic Plasmodium falciparum infection: insights from a rural Burkina Faso study

BackgroundAsymptomatic Plasmodium falciparum parasitaemia forms a reservoir for the transmission of malaria disease in West Africa. Certain haemoglobin variants are known to protect against severe malaria infection. However, data on the potential roles of haemoglobin variants and nongenetic factors in asymptomatic malaria infection is scarce and controversial. Therefore, this study investigated the associations of iron homeostasis, inflammation, nutrition, and haemoglobin mutations with parasitaemia in an asymptomatic cohort from a P. falciparum-endemic region during the high transmission season.MethodsA sub-study population of 688 asymptomatic individuals (predominantly children and adolescents under 15 years, n = 516) from rural Burkina Faso previously recruited by the NOVAC trial (NCT03176719) between June and October 2017 was analysed. Parasitaemia was quantified with conventional haemocytometry. The haemoglobin genotype was determined by reverse hybridization assays targeting a selection of 21 HBA and 22 HBB mutations. Demographics, inflammatory markers (interleukins 6 and 10, hepcidin), nutritional status (mid upper-arm circumference and body mass index), and anaemia (total haemoglobin, ferritin, soluble transferrin receptor) were assessed as potential predictors through logistic regression.ResultsMalaria parasites were detected in 56% of subjects. Parasitaemia was associated most strongly with malnutrition. The effect size increased with malnutrition severity (OR = 6.26, CI95: 2.45–19.4, p < 0.001). Furthermore, statistically significant associations (p < 0.05) with age, cytokines, hepcidin and heterozygous haemoglobin S were observed.ConclusionsAccording to these findings, asymptomatic parasitaemia is attenuated by haemoglobin S, but not by any of the other detected genotypes. Aside from evidence for slight iron imbalance, overall undernutrition was found to predict parasitaemia; thus, further investigations are required to elucidate causality and inform strategies for interventions.

IMPACT OF Plasmodium falciparum PARASITAEMIA ON SOME HEMATOLOGICAL PROFILES AMONG CHILDREN 6-59 MONTHS: A CASE STUDY OF SELECTED HOSPITALS IN MAIDUGURI, BORNO STATE

Plasmodium falciparum is responsible for millions of deaths globally, with children under five (5) years old the most vulnerable. It is associated with some haematological changes. As a result, this study was carried out to evaluate the effects of P. falciparum parasitaemia on certain haematological parameters in Malaria-affected Children in Maiduguri. To ascertain the prevalence and haematological alterations brought on by infection, blood samples were taken from 421 kids during the months of December 2021 and June 2022 (7 months). Overall results show 182 (43.23%) patients were positive to malaria while 239 (56.77%) were negative. Similarly, the PCV, RBC and thrombocytes count respectively (23.95%, 2.94x10-9/µL and 346.23X10-9/µL and 147.15X10-9/µL) of the malaria positives subjects were significantly (p=0.05) lower compared to the malaria negative (34.69%, 4.0 X10-9/µL and 346.23 X10-9/µL) subjects. Furthermore, the mean WBC, lymphocytes and neutrophils respectively of the malaria positive subjects were significantly higher compared (18.67 x10-9/µL, 59.88% and 66,05%) to the infected ones (12.92 x10-9/µl, 37.69% and 47.05%). The result also shows the mean of sex comparison of haematological parameters of children infected with malaria, with the PCV and thrombocytes of male positive subject been significantly lower than that of the female negative children (24.40% and 145.98X10-9/µ) versus (34.82% and 337.00X10-9/µl) appropriately (p=0.05), whereas the mean WBC, lymphocytes and neutrophils were significantly higher compared to female positive subjects (17.48X10_9/µl, 59.46% and 63.95%) versus (18.64 x10-9/µl, 60.48% and 69.04%), (p=0.01, 0.05). In conclusion, malaria is highly prevalent among children, 21-30 months old in Maiduguri and it is associated...

DHEA Induces Sex-Associated Differential Patterns in Cytokine and Antibody Levels in Mice Infected with Plasmodium berghei ANKA.

Malaria is the most lethal parasitic disease worldwide; the severity of symptoms and mortality are higher in men than in women, exhibiting an evident sexual dimorphism in the immune response; therefore, the contribution of 17β-estradiol and testosterone to this phenomenon has been studied. Both hormones differentially affect several aspects of innate and adaptive immunity. Dehydroepiandrosterone (DHEA) is the precursor of both hormones and is the sexual steroid in higher concentrations in humans, with immunomodulatory properties in different parasitic diseases; however, the involvement of DHEA in this sexual dimorphism has not been studied. In the case of malaria, the only information is that higher levels of DHEA are associated with reduced Plasmodium falciparum parasitemia. Therefore, this work aims to analyze the DHEA contribution to the sexual dimorphism of the immune response in malaria. We assessed the effect of modifying the concentration of DHEA on parasitemia, the number of immune cells in the spleen, cytokines, and antibody levels in plasma of CBA/Ca mice infected with Plasmodium berghei ANKA (P. berghei ANKA). DHEA differentially affected the immune response in males and females: it decreased IFN-γ, IL-2 and IL-4 concentrations only in females, whereas in gonadectomized males, it increased IgG2a and IgG3 antibodies. The results presented here show that DHEA modulates the immune response against Plasmodium differently in each sex, which helps to explain the sexual dimorphism present in malaria.

Association between hemoglobin variants and laboratory outcomes in patients infected with P. falciparum from South West Uganda.

We assess the relationship between various hemoglobin variants and some hematological parameters packed cell volume, white blood cells (PCV, WBC) and parasitemia level of patients with malaria in the southwestern, Uganda. Patient were enrolled by rapid diagnostic tests (RDTs), confirmed by microscopy, and laboratory outcomes were determined. Patients positive for malaria RDTs were 155, microscopic-confirmed P. falciparum parasites were 95(61.29%) having hemoglobin variants HbAA andHbAS; 75(78.95%) and13(13.68%), respectively. The laboratory outcomes showed mean, PCV(32.19±4.83), WBC(5831.66±2888.29) and P. falciparum parasitaemia density (32,605.45±14031), while the hemoglobin variants mean values AA(39,008.85±31,261.56), AC(15908±10173.48), AS(16,561.46±15,380.93), SC(30,524±0.000) and SS(1652±0.000) were significantly different from the total population (34,321.5±21,924.26) parasite-density. Patients with hemoglobin variants HbAA had asignificantly higher parasite-carrying capacity and PCV levels.

Protocol for a cluster randomised placebo-controlled trial of adjunctive ivermectin mass drug administration for malaria control on the Bijagós Archipelago of Guinea-Bissau: the MATAMAL trial

IntroductionAs malaria declines, innovative tools are required to further reduce transmission and achieve elimination. Mass drug administration (MDA) of artemisinin-based combination therapy (ACT) is capable of reducing malaria transmission where...

The Dantu blood group prevents parasite growth in vivo: Evidence from a controlled human malaria infection study.

The long co-evolution of Homo sapiens and Plasmodium falciparum has resulted in the selection of numerous human genetic variants that confer an advantage against severe malaria and death. One such variant is the Dantu blood group antigen, which is associated with 74% protection against severe and complicated P. falciparum malaria infections in homozygous individuals, similar to that provided by the sickle haemoglobin allele (HbS). Recent in vitro studies suggest that Dantu exerts this protection by increasing the surface tension of red blood cells, thereby impeding the ability of P. falciparum merozoites to invade them and reducing parasite multiplication. However, no studies have yet explored this hypothesis in vivo. We investigated the effect of Dantu on early phase P. falciparum (Pf) infections in a controlled human malaria infection (CHMI) study. 141 sickle-negative Kenyan adults were inoculated with 3.2 × 103 aseptic, purified, cryopreserved Pf sporozoites (PfSPZ Challenge) then monitored for blood-stage parasitaemia for 21 days by quantitative polymerase chain reaction (qPCR)analysis of the 18S ribosomal RNA P. falciparum gene. The primary endpoint was blood-stage P. falciparum parasitaemia of ≥500/μl while the secondary endpoint was the receipt of antimalarial treatment in the presence of parasitaemia of any density. On study completion, all participants were genotyped both for Dantu and for four other polymorphisms that are associated with protection against severe falciparum malaria: α+-thalassaemia, blood group O, G6PD deficiency, and the rs4951074 allele in the red cell calcium transporter ATP2B4. The primary endpoint was reached in 25/111 (22.5%) non-Dantu subjects in comparison to 0/27 (0%) Dantu heterozygotes and 0/3 (0.0%) Dantu homozygotes (p=0.01). Similarly, 49/111 (44.1%) non-Dantu subjects reached the secondary endpoint in comparison to only 7/27 (25.9%) and 0/3 (0.0%) Dantu heterozygotes and homozygotes, respectively (p=0.021). No significant impacts on either outcome were seen for any of the other genetic variants under study. This study reveals, for the first time, that the Dantu blood group is associated with high-level protection against early, non-clinical, P. falciparum malaria infections in vivo. Learning more about the mechanisms involved could potentially lead to new approaches to the prevention or treatment of the disease. Our study illustrates the power of CHMI with PfSPZ Challenge for directly testing the protective impact of genotypes previously identified using other methods. The Kenya CHMI study was supported by an award from Wellcome (grant number 107499). SK was supported by a Training Fellowship (216444/Z/19/Z), TNW by a Senior Research Fellowship (202800/Z/16/Z), JCR by an Investigator Award (220266/Z/20/Z), and core support to the KEMRI-Wellcome Trust Research Programme in Kilifi, Kenya (203077), all from Wellcome. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. NCT02739763.