Detection of IgG Antibodies to Glycosylphosphatidylinositol (GPI) as a Biomarker of Immune Status to Plasmodium species

Finding new ways to eliminate malaria is critical and this would greatly be influenced by developing indicators of exposure as well as distribution of effective vaccines against Plasmodium. This study was aimed at detecting Immunoglobulin G(IgG) antibodies, to glycosylphosphatidylinositol (GPI) as a biomarker of immune status to Plasmodium species. In this study, blood samples were gotten from apparently healthy individuals and patients having symptoms of malaria attending Ahmadu Bello University Teaching Hospital, Zaria. Thick and thin blood smears were prepared and stained with Giemsa stain. The smears were observed microscopically. Parasite densities were estimated on positive slides. Samples positive and some negative for Plasmodium were further tested to detect IgG antibodies to GPI among both the Asymptomatic and Symptomatic participants using ELISA. The prevalence of Plasmodium infection among both asymptomatic and symptomatic participants in this study was 18.9% and the prevalence of asymptomatic malaria was 15.6%. There was a significant association between the level of parasitemia and concentration of IgG antibodies to GPI among the asymptomatic participants and a no significant association among symptomatic participants. Type of housing amongst other risk factors was the only factor significantly associated with malaria in this study. This study suggests PGPI as a biomarker of immunity to Plasmodium and may be a vaccine candidate for programs of malaria control.

The Dynamics of Malaria Clinical Symptoms with very Strong Emphasis on Asymptomatic Malaria

In the developed world, malaria is a dangerous parasite that contributes to high morbidity and mortality. The disease is variable and its clinical presence varies from extreme to complex, normal, and difficult malaria, asymptomatic malaria. Malaria pathogenesis is complex. Our current research was conducted at Mayo Hospital, Lahore from May 2019 to February 2020. Despite several clinical severities trials the disorder is still poorly known for asymptomatic malaria infection. Malaria remains a problem for asymptomatic malaria, as it has a significant impact on the dynamic of transmission. In order to develop various therapeutic results, a thorough understanding of the relationship between hosts and parasites is important. Problems and obstacles to asymptomatic malaria study and management are addressed in this study. Man and parasite are identified and methods for management and recovery are presented for differential clinical outcomes. They are exposed to disease prevention. In the context of prospective studies to create more efficient malaria prevention methods, important lacunae in the understanding of asymptomatic malaria are further illustrated. Keywords: Malaria Clinical Symptoms, Strong Emphasis, Asymptomatic Malaria.

Hepatitis B and Asymptomatic Malaria Infection among Pregnant Women in a Semiurban Community of North-Central Nigeria

Background. The overlap of malaria and Hepatitis B Virus (HBV) infections present a major threat to public health throughout endemic countries of tropical and sub-Saharan Africa. There is a paucity of data on the prevalence and associated factors of malaria and HBV infections among pregnant women in Ejule, a semiurban area of Nigeria. Therefore, the current study was designed to assess the seroprevalence of malaria and HBV among pregnant women attending antenatal clinics in Ejule Metropolis. Materials and Methods. In a hospital-based cross-sectional study, blood samples collected from 200 apparently healthy pregnant women at the Ilemona Clinic were screened for Plasmodium falciparum (P. falciparum) and HBsAg using histidine-rich protein 2 (HRP2) and hepatitis B surface antigen (HBsAg) rapid diagnostic tests (RDTs), respectively. Relevant sociodemographic and putative risk factor information was obtained with structured questionnaires. Results. The prevalence of the infections was 44 (22%), 5 (2.5%), and 1 (0.5%) for P. falciparum monoinfection and HBV monoinfection and coinfection, respectively. Single and concurrent infections peaked at ages 31–40 years but decreased with older ages. High P. falciparum, 31 (59.62%), and HBV 2 (3.85%) infection were observed among those without formal education. Contrary to ages, occupation, and knowledge of infection, malaria parasitemia differed significantly with lower educational qualification ( p ≤ 0.001 ), being single ( p = 0.001 ), and inconsistent use of insecticide-treated bed nets (ITNs) ( p = 0.04 , OR = 5, CI: 0.10–0.47). History of blood donation (OR = 5, p = 0.04 , CI: 1.10–32.80) and multiple sex partners (OR = 11.9, p = 0.01 , CI: 0.01–0.93) were found to be significantly associated with hepatitis B surface antigenemia rate during pregnancy. No evidence of HBV infection was observed in women with a history of HBV vaccination. Conclusions. Malaria is still highly prevalent among pregnant women due to high illiteracy and noncompliance to using ITNs. Therefore, routine screening and educating pregnant mothers are crucial in eliminating malaria in endemic settings. The low rate of hepatitis B and coinfection with malaria shows that further improvement in HBV vaccination could considerably reduce the disease burden among pregnant women.

A cohort study on the duration of Plasmodium falciparum infections during the dry season in The Gambia

Background: In areas where Plasmodium falciparum malaria is highly seasonal, a dry season reservoir of blood-stage infection is essential for initiating transmission during the following wet season, bridging transmission seasons several months apart. Understanding infections during the dry season could thus inform approaches for malaria control. Methods: In The Gambia, a cohort of 42 individuals with qPCR positive P. falciparum infections at the end of the transmission season (December) were followed monthly until the end of the dry season (May) to evaluate the duration of detectable infections. The influence of human host (age, sex, haemoglobin concentration and genotype, and P. falciparum-specific antibodies), and parasitological (parasite density, gametocyte density and genotypic multiplicity of infection) factors was investigated. Results: A large proportion of individuals infected at the end of the wet season had detectable infections until the end of the dry season (40.0%; 16/40), with the majority of these infections also harbouring gametocytes (81.3%; 13/16). 22 infections were classified as persistent (detectable for at least 3 months), 17 were classified as short-lived (undetectable within 2 months), and 3 were treated (due to symptoms). At the start of the dry season, the majority of persistent infections (82%; 18/22) had parasite densities >10 p/uL compared to only 5.9% (1/17) of short-lived infections. Persistent infections (59%; 13/22) were also more likely to be multi-clonal than short-lived infections (5.9%; 1/17), they were most common in 5 to 15 year old children (63%; 12/19), and were associated with individuals having higher levels of P. falciparum-specific antibodies (p = 0.058). Conclusions: Asymptomatic persistent dry season infections in The Gambia were multiclonal with higher parasite densities at the beginning of the dry season, mostly occurring in school age children and adults with higher P. falciparum-specific antibodies. Screening and treating asymptomatic, malaria-infected individuals during the dry season may reduce the human reservoir of malaria responsible initiating transmission in the wet-season.

C-reactive protein as an early biomarker for malaria infection and monitoring of malaria severity: a meta-analysis

This study investigated whether C-reactive protein (CRP) can be used as a marker for the early detection and monitoring of malaria severity. Potentially relevant studies were searched in Medline (PubMed), Scopus, and Web of Science. Differences in CRP between (1) severe malaria and uncomplicated malaria, (2) uncomplicated malaria and asymptomatic malaria, (3) uncomplicated malaria and febrile/healthy controls, and (4) asymptomatic malaria and febrile/healthy controls were estimated using random-effects models. Twenty-nine studies were included for meta-analysis. The results of meta-analysis demonstrated higher mean CRP levels in (1) patients with severe malaria compared with uncomplicated malaria (p < 0.001, standard mean difference [SMD]: 1.52, 95% confidence interval [CI]: 0.91–2.12, I2: 95.1%), (2) patients with uncomplicated malaria than in those with asymptomatic malaria (p: 0.001, SMD: 1.65, 95% CI: 0.67–2.62, I2: 96.7%), (3) patients with uncomplicated malaria compared with febrile/healthy controls (p < 0.001, SMD: 2.38, 95% CI: 1.37–3.40, I2: 98.5%), and (4) patients with asymptomatic malaria compared with febrile/healthy controls (p < 0.001, SMD: 2.55, 95% CI: 1.60–3.50, I2: 99.2%). This study demonstrated CRP levels are a biomarker for the early detection and monitoring of malaria severity.

Baseline malaria prevalence at the targeted pre-elimination districts in Ethiopia

Background Encouraged by the previous success in malaria control and prevention strategies, the Ethiopian ministry of health launched malaria elimination with a stepwise approach by primarily targeting the low-transmission Districts and their adjacent areas/zones in order to shrink the country’s malaria map progressively. Hence, this community survey was conducted to establish baseline malaria information at the preliminary phase of elimination at targeted settings. Methods A community-based cross-sectional survey was conducted at 20 malaria-elimination targeted Districts selected from five Regional states and one city administration in Ethiopia. The GPS-enabled smartphones programmed with Open Data Kit were used to enumerate 9326 study households and collect data from 29,993 residents. CareStart™ Malaria PAN (pLDH) Rapid Diagnostic Tests (RDTs) were used for blood testing at the field level. Armpit digital thermometers were used to measure axillary temperature. Result Overall malaria prevalence by RDTs was 1.17% (339/28973). The prevalence at District levels ranged from 0.0 to 4.7%. The proportion of symptomatic cases (axillary temperature > 37.5oc) in the survey was 9.2% (2760/29993). Among the 2510 symptomatic individuals tested with RDTs, only 3.35% (84/2510) were malaria positive. The 75.2% (255/339) of all malaria positives were asymptomatic. Of the total asymptomatic malaria cases, 10.2% (26/255) were under-five children and 89.8% (229/255) were above 5 years of age. Conclusion The study shows a decrease in malaria prevalence compared to the reports of previous malaria indicator surveys in the country. The finding can be used as a baseline for measuring the achievement of ongoing malaria elimination efforts. Particularly, the high prevalence of asymptomatic individuals (0.88%) in these transmission settings indicates there may be sustaining hidden transmission. Therefore, active case detection with more sensitive diagnostic techniques is suggested to know more real magnitude of residual malaria in the elimination-targeted areas.

Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation

Homeostatic perturbation caused by infection fosters two major defense strategies, resistance and tolerance, which promote the host’s survival. Resistance relates to the ability of the host to restrict the pathogen load. Tolerance minimizes collateral tissue damage without directly affecting pathogen fitness. These concepts have been explored mechanistically in murine models of malaria but only superficially in human disease. Indeed, individuals infected with Plasmodium vivax may present with asymptomatic malaria, only mild symptoms, or be severely ill. We and others have reported a diverse repertoire of immunopathological events that potentially underly susceptibility to disease severity in vivax malaria. Nevertheless, the combined epidemiologic, clinical, parasitological, and immunologic features associated with defining the disease outcomes are still not fully understood. In the present study, we perform an extensive outlining of cytokines and inflammatory proteins in plasma samples from a cohort of individuals from the Brazilian Amazon infected with P. vivax and presenting with asymptomatic (n = 108) or symptomatic (n = 134) disease (106 with mild presentation and 28 with severe malaria), as well as from uninfected endemic controls (n = 128) to elucidate these gaps further. We employ highly multidimensional Systems Immunology analyses using the molecular degree of perturbation to reveal nuances of a unique profile of systemic inflammation and imbalanced immune activation directly linked to disease severity as well as with other clinical and epidemiologic characteristics. Additionally, our findings reveal that the main factor associated with severe cases of P. vivax infection was the number of symptoms, despite of a lower global inflammatory perturbation and parasitemia. In these participants, the number of symptoms directly correlated with perturbation of markers of inflammation and tissue damage. On the other hand, the main factor associated with non-severe infections was the parasitemia values, that correlated only with perturbation of inflammatory markers, such as IL-4 and IL-1β, with a relatively lower number of symptoms. These observations suggest that some persons present severe vivax regardless of pathogen burden and global inflammatory perturbation. Such patients are thus little tolerant to P. vivax infection and show higher susceptibility to disrupt homeostasis and consequently exhibit more clinical manifestations. Other persons are capable to tolerate higher parasitemia with lower inflammatory perturbation and fewer symptoms, developing non-severe malaria. The analytical approach presented here has capability to define in more details the determinants of disease tolerance in vivax malaria.

Cohort profile: the Mâncio Lima cohort study of urban malaria in Amazonian Brazil

PurposeThis population-based open cohort study aims to investigate biological and sociodemographic drivers of malaria transmission in the main urban hotspot of Amazonian Brazil.ParticipantsNearly 20% of the households in the northwestern town of Mâncio Lima were randomly selected and 2690 participants were enrolled since April 2018. Sociodemographic, housing quality, occupational, behavioural and morbidity information and travel histories were collected during consecutive study visits. Blood samples from participants>3 months old were used for malaria diagnosis and human genetic studies; samples from participants with laboratory-confirmed malaria have been cryopreserved for genetic and phenotypic characterisation of parasites. Serology was introduced in 2020 to measure the prevalence and longevity of SARS-CoV-2 IgG antibodies.Findings to dateMalaria prevalence rates were low (up to 1.0% for Plasmodium vivax and 0.6% for P. falciparum) during five consecutive cross-sectional surveys between April–May 2018 and October–November 2020; 63% of infections diagnosed by microscopy were asymptomatic. Malaria risk is heterogeneously distributed, with 20% study participants contributing 86% of the overall burden of P. vivax infection. Adult males are at greatest risk of infection and human mobility across the urban–rural interface may contribute to sustained malaria transmission. Local P. vivax parasites are genetically diverse and fragmented into discrete inbred lineages that remain stable across space and time.Future plansTwo follow-up visits, with similar study protocols, are planned in 2021. We aim to identify high-risk individuals that fuel onwards malaria transmission and represent a priority target for more intensive and effective control interventions.Trial registration numberNCT03689036.

High Prevalence of Asymptomatic Malarial Anemia and Association with Early Conversion from Asymptomatic to Symptomatic Infection in a Plasmodium falciparum Hyperendemic Setting in Cameroon

Asymptomatic malarial parasitemia is highly prevalent in Plasmodium falciparum endemic areas and often associated with increased prevalence of mild to moderate anemia. The aim of this study was to assess the prevalence of anemia during asymptomatic malaria parasitemia and its interplay with persistent infection in highly exposed individuals. A household-based longitudinal survey was undertaken in a malaria hyperendemic area in Cameroon using multiplex nested polymerase chain reaction to detect plasmodial infections. Residents with P. falciparum asymptomatic parasitemia were monitored over a 3-week period with the aid of structured questionnaires and weekly measurements of axillary temperatures. Of the 353 individuals included (median age: 26 years, range 2–86 years, male/female sex ratio 0.9), 328 (92.9%) were positive for malaria parasitemia of whom 266 (81.1%) were asymptomatic carriers. The prevalence of anemia in the study population was 38.6%, of which 69.2% were asymptomatic. Multivariate analyses identified high parasitemia (> 327 parasites/µL) and female gender as associated risk factors of asymptomatic malarial anemia in the population. Furthermore, risk analyses revealed female gender and anemia at the time of enrolment as key predictors of early development of febrile illness (< 3 weeks post enrolment) among the asymptomatic individuals. Together, the data reveal an extremely high prevalence of asymptomatic malaria parasitemia and anemia in the study area, unveiling for the first time the association of asymptomatic malarial anemia with early clinical conversion from asymptomatic to symptomatic infection. Furthermore, these findings underscore the negative impact of asymptomatic malaria parasitemia on individual health, necessitating the development of appropriate control and preventive measures.