Evidence for histidine-rich protein 2 immune complex formation in symptomatic patients in Southern Zambia.

Abstract

BACKGROUND:

Rapid diagnostic tests based on histidine-rich protein 2 (HRP2) detection are the primary tools used to detect Plasmodium falciparum malaria infections. Recent conflicting reports call into question whether α-HRP2 antibodies are present in human host circulation and if resulting immune complexes could interfere with HRP2 detection on malaria RDTs. This study sought to determine the prevalence of immune-complexed HRP2 in a low-transmission region of Southern Zambia.

METHODS:

An ELISA was used to quantify HRP2 in patient sample DBS extracts before and after heat-based immune complex dissociation. A pull-down assay reliant on proteins A, G, and L was developed and applied for IgG and IgM capture and subsequent immunoprecipitation of any HRP2 present in immune complexed form. A total of 104 patient samples were evaluated using both methods.

RESULTS:

Immune-complexed HRP2 was detectable in 17% (18/104) of all samples evaluated and 70% (16/23) of HRP2-positive samples. A majority of the patients with samples containing immune-complexed HRP2 had P. falciparum infections (11/18) and were also positive for free HRP2 (16/18). For 72% (13/18) of patients with immune-complexed HRP2, less than 10% of the total HRP2 present was in immune-complexed form. For the remaining samples, a large proportion (≥ 20%) of total HRP2 was complexed with α-HRP2 antibodies.

CONCLUSIONS:

Endogenous α-HRP2 antibodies form immune complexes with HRP2 in the symptomatic patient population of a low-transmission area in rural Southern Zambia. For the majority of patients, the percentage of HRP2 in immune complexes is low and does not affect HRP2-based malaria diagnosis. However, for some patients, a significant portion of the total HRP2 was in immune-complexed form. Future studies investigating the prevalence and proportion of immune-complexed HRP2 in asymptomatic individuals with low HRP2 levels will be required to assess whether α-HRP2 antibodies affect HRP2 detection for this portion of the transmission reservoir.

• Authors: Christine F Markwalter, Lwiindi Mudenda, Mindy Leelawong, Danielle W Kimmel, Armin Nourani, Saidon Mbambara, Philip E Thuma, David W Wright
• Journal: Malaria journal (Malar J) Vol. 17 Issue 1 Pg. 256 (Jul 09 2018) ISSN: 1475-2875 [Electronic] England
• PMID: 29986725 (Publication Type: Journal Article)

Chemical References

• Antigen-Antibody Complex
• Antigens, Protozoan
• HRP-2 antigen, Plasmodium falciparum
• Protozoan Proteins

Topics

• Antigen-Antibody Complex (immunology)
• Antigens, Protozoan (immunology)
• Enzyme-Linked Immunosorbent Assay (methods)
• Humans
• Malaria, Falciparum (epidemiology, immunology)
• Plasmodium falciparum (physiology)
• Prevalence
• Protozoan Proteins (immunology)
• Sensitivity and Specificity
• Zambia (epidemiology)