TY - JOUR

T1 - Acquired Clinical Immunity to Malaria in Nonhuman Primates Coinfected with Schistosoma and Plasmodium Parasites

AU - Nyakundi, Ruth K.

AU - Hau, Jann

AU - Ogongo, Paul

AU - Nyamongo, Onkoba

AU - Jeneby, Maamum

AU - Akinyi, Mercy

AU - Mulei, Isaac

AU - Nyundo, Fred

AU - Farah, Idle

AU - Malhotra, Indu

AU - Ozwara, Hastings

AU - King, Christopher L.

AU - Kariuki, Thomas

N1 - Funding Information: This work was supported by Public Health service grant 5R01AI075682-01 from the National Institutes of Health (NIH). We thank Simon Kiarie, Peter Mareri, James Ndung’u, Pricilla Kimiti, and the Animal Science department at the IPR for their technical and animal welfare support. Publisher Copyright: © 2022 American Society for Microbiology. All rights reserved.

PY - 2022

Y1 - 2022

N2 - Naturally acquired immunity to malaria develops over several years and can be compromised by concomitant infections. This study explored the influence of chronic schistosomiasis on clinical outcome and immunity to repeated malaria infection. Two groups of baboons (n = 8 each), were infected with Schistosoma mansoni cercariae to establish chronic infections. One of the two groups was treated with praziquantel (PZQ) to eliminate schistosome infection. The two groups plus a new malaria control group (n = 8) were inoculated three times with Plasmodium knowlesi parasites at 1-month intervals. Clinical data and IgG, IgG1, memory T-cell, and monocyte levels were recorded. After three P. knowlesi infections, we observed (i) reduced clinical symptoms in all groups with each subsequent infection, (ii) increased IgG and IgG1 levels in the malaria control (Pk-only) group, (iii) increased IgG, IgG1, CD141, and CD142 CD161 levels in the Schistosoma-treated (Schisto/PZQ1Pk) group, and (iv) significantly lower IgG and IgG1 levels compared to those of the Pk-only group, reduced CD41 CD45RO1 levels, and increased levels of CD142 CD161 cells in the coinfected (Schisto1Pk) group. Chronic S. mansoni infection does not compromise establishment of clinical immunity after multiple malaria infections, with nonclassical monocytes seeming to play a role. Failure to develop robust antibody and memory T cells may have a long-term impact on acquired immunity to malaria infection.

AB - Naturally acquired immunity to malaria develops over several years and can be compromised by concomitant infections. This study explored the influence of chronic schistosomiasis on clinical outcome and immunity to repeated malaria infection. Two groups of baboons (n = 8 each), were infected with Schistosoma mansoni cercariae to establish chronic infections. One of the two groups was treated with praziquantel (PZQ) to eliminate schistosome infection. The two groups plus a new malaria control group (n = 8) were inoculated three times with Plasmodium knowlesi parasites at 1-month intervals. Clinical data and IgG, IgG1, memory T-cell, and monocyte levels were recorded. After three P. knowlesi infections, we observed (i) reduced clinical symptoms in all groups with each subsequent infection, (ii) increased IgG and IgG1 levels in the malaria control (Pk-only) group, (iii) increased IgG, IgG1, CD141, and CD142 CD161 levels in the Schistosoma-treated (Schisto/PZQ1Pk) group, and (iv) significantly lower IgG and IgG1 levels compared to those of the Pk-only group, reduced CD41 CD45RO1 levels, and increased levels of CD142 CD161 cells in the coinfected (Schisto1Pk) group. Chronic S. mansoni infection does not compromise establishment of clinical immunity after multiple malaria infections, with nonclassical monocytes seeming to play a role. Failure to develop robust antibody and memory T cells may have a long-term impact on acquired immunity to malaria infection.

KW - Acquired immunity

KW - Coinfection

KW - Malaria

KW - Schistosomiasis

U2 - 10.1128/iai.00464-21

DO - 10.1128/iai.00464-21

M3 - Journal article

C2 - 34871040

AN - SCOPUS:85124850421

VL - 90

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 2

M1 - e00464-21

ER -