Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure

Rodríguez-Barraquer, Isabel; Arinaitwe, Emmanuel; Jagannathan, Prasanna; Kamya, Moses R.; Rosenthal, Phillip; Rek, John; Dorsey, Grant; Nankabirwa, Joaniter I.; Staedke, Sarah G.; Kilama, Maxwell; Drakeley, Chris; Ssewanyana, Isaac; Smith, David L.; Greenhouse, Bryan

doi:10.7554/elife.35832

Cited by 105 publications

(95 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Effects of RBC variants on two components of anti-malarial immunity, anti-parasite immunity (ability to control parasite densities upon infection) and anti-disease immunity (ability to tolerate higher parasite density without developing fever) were also investigated. To model these outcomes, generalized additive models (GAMS) were used as previously described [38]. The outcome of interest in the antiparasite immunity model was the log10 parasite density in parasite positive visits, and the outcome of interest in the anti-disease model was the measured temperature, adjusted for parasite density.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study

Kakande

Greenhouse

Bajunirwe

et al. 2020

Malar J

Self Cite

View full text Add to dashboard Cite

Background: Multiple red blood cell (RBC) variants appear to offer protection against the most severe forms of Plasmodium falciparum malaria. Associations between these variants and uncomplicated malaria are less clear. Methods: Data from a longitudinal cohort study conducted in 3 sub-counties in Uganda was used to quantify associations between three red blood cell variants Hb [AA, AS, S (rs334)], alpha thalassaemia 3.7 kb deletion, and glucose-6-phosphate dehydrogenase deficiency A-(G6PD 202A genotype) and malaria incidence, parasite prevalence, parasite density (a measure of anti-parasite immunity) and body temperature adjusted for parasite density (a measure of anti-disease immunity). All analyses were adjusted for age, average household entomological inoculation rate, and study site. Results for all variants were compared to those for wild type genotypes. Results: In children, HbAS was associated, compared to wild type, with a lower incidence of malaria (IRR = 0.78, 95% CI 0.66-0.92, p = 0.003), lower parasite density upon infection (PR = 0.66, 95% CI 0.51-0.85, p = 0.001), and lower body temperature for any given parasite density (− 0.13 ℃, 95% CI − 0.21, − 0.05, p = 0.002). In children, HbSS was associated with a lower incidence of malaria (IRR = 0.17, 95% CI 0.04-0.71, p = 0.02) and lower parasite density upon infection (PR = 0.31, 95% CI 0.18-0.54, p < 0.001). α−/αα thalassaemia, was associated with higher parasite prevalence in both children and adults (RR = 1.23, 95% CI 1.06-1.43, p = 0.008 and RR = 1.52, 95% CI 1.04-2.23, p = 0.03, respectively). G6PD deficiency was associated with lower body temperature for any given parasite density only among male hemizygote children (− 0.19 ℃, 95% CI − 0.31, − 0.06, p = 0.003). Conclusion: RBC variants were associated with non-severe malaria outcomes. Elucidation of the mechanisms by which they confer protection will improve understanding of genetic protection against malaria.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Study procedures and follow up have been described in detail [36][37][38]. Briefly, all participants were given an insecticide treated bed net at enrollment and were followed for all their healthcare needs at dedicated study clinics open 7 days each week.…”

Section: Study Procedures and Follow-upmentioning

confidence: 99%

Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study

Kakande

Greenhouse

Bajunirwe

et al. 2020

Malar J

Self Cite

View full text Add to dashboard Cite

show abstract

“…That is because the immunity towards Plasmodium increases with age [16], and the anti-parasite ability of children is lower than adults. It would lead to a higher parasite density of childhood malaria infection if other conditions are the same [17].…”

Section: Viewpoints Papersmentioning

confidence: 99%

High value of rapid diagnostic tests to diagnose malaria within children: A systematic review and meta-analysis

Zhu

Ling

Shang

et al. 2020

Journal of Global Health

View full text Add to dashboard Cite

High value of rapid diagnostic tests to diagnose malaria within children: A systematic review and meta-analysis Background Children aged under five years accounted for 61% of all malaria deaths worldwide in 2017, and quicker differential diagnosis of malaria fever is vital for them. Rapid diagnostic tests (RDTs) are strips to detect Plasmodium-specific antigens promptly and are helpful in resource-limited areas. Thus, our aim is to assess the diagnostic accuracy of RDTs for malaria in children against the gold standard. Methods MEDLINE, Web of Science, EMBASE, Cochrane Library, the China National Knowledge Infrastructure, Wanfang, and Sinomed databases were systematically searched on August 23, 2019. Studies that compared RDTs with microscopy or polymerase chain reaction in malaria diagnoses for children were eligible. Relevant data were extracted. The quality of studies was evaluated using the revised Quality Assessment of Diagnostic Accuracy Studies instrument. Meta-analyses were carried out to calculate the pooled estimates and 95% confidence intervals of sensitivity and specificity. Results 51 articles were included. For diagnostic accuracy, the pooled estimates of the sensitivity and specificity of RDTs were 0.93 (95% confidence interval (CI) = 0.90, 0.95) and 0.93 (95% CI = 0.90, 0.96) respectively. Studies were highly heterogeneous, and subgroup analyses showed that the application of RDTs in high malaria transmission areas had higher sensitivity but lower specificity than those in low-to-moderate areas. Conclusions RDTs have high accuracy for malaria diagnosis in children, and this characteristic is more prominent in high transmission areas. As they also have the advantages of rapid-detection, are easy-to-use, and can be cost-effective, it is recommended that the wider usage of RDTs should be promoted, especially in resource-limited areas. Further research is required to assess their performance in WHO SouthEast Asia and Americas Region. Electronic supplementary material: The online version of this article contains supplementary material.

show abstract

“…Thick blood smears were performed on all children who reported fever in the previous 24 hours or who were febrile (>38.0°C) at the sick visit. Parasitemia was determined based on microscopy and parasite density was calculated as previously described (23). Those with symptomatic malaria were treated with the first line treatment in Uganda, artemether-lumefantrine.…”

Section: Resultsmentioning

confidence: 99%

Inhibitory KIR ligands are associated with higherP. falciparumparasite prevalence

Digitale

Callaway

Martin

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Killer cell immunoglobulin-like receptors (KIR) and their HLA ligands influence the outcome of many infectious diseases. Data from a longitudinal cohort comprised of three study sites in Uganda with varying malaria transmission intensity show that presence of the HLA-C2 and HLA-Bw4 ligands for inhibitory KIR2DL1 and KIR3DL1, respectively, increase the likelihood of Plasmodium falciparum (Pf) parasitemia in an additive manner. For KIR2DL1/2/3, parasite prevalence was highest among individuals with KIR/HLA-C ligand pairs that are capable of the greatest cellular inhibition. Individuals homozygous for HLA-C2, which mediates strong inhibition via the near ubiquitous KIR2DL1 receptor, had the highest odds of parasitemia, while HLAC1/C2 heterozygotes had intermediate odds, and individuals homozygous for HLA-C1, which mediates weaker inhibition through KIR2DL2/3, had the lowest odds of parasitemia. A higher risk of parasitemia was also observed in the pairing of HLA-C1 with its receptor KIR2DL2 compared to its less inhibitory receptor KIR2DL3. Additionally, higher surface expression of HLA-C, the ligand for KIR2DL1/2/3, was associated with a higher likelihood of parasitemia. Together these data indicate that stronger KIR-mediated inhibition confers a higher risk of Pf parasitemia and suggest that KIR-expressing effector cells play a role in mediating anti-parasite immunity.

show abstract

Quantification of anti-parasite and anti-disease immunity to malaria as a function of age and exposure

Cited by 105 publications

References 25 publications

Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study

Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study

High value of rapid diagnostic tests to diagnose malaria within children: A systematic review and meta-analysis

Inhibitory KIR ligands are associated with higherP. falciparumparasite prevalence

Contact Info

Product

Resources

About