The role of complement immune response on artemisinin-based combination therapy in a population from malaria endemic region of Western Kenya
Abstract Background Naturally acquired immunity (NAI), which is characterized by protection against overt clinical disease and high parasitaemia, is acquired with age and transmission intensity. The role of NAI on the efficacy of anti-malarial drugs, including artemisinin-based combinations used as...
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Malaria Journal |
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| Online Access: | http://link.springer.com/article/10.1186/s12936-020-03242-4 |
| _version_ | 1811336958191861760 |
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| author | Christine N. L. Wanjala Elke Bergmann-Leitner Hoseah M. Akala Geoffrey Odhiambo Bernhards R. Ogutu Ben Andagalu Edwin Kamau Daniel Ochiel |
| author_facet | Christine N. L. Wanjala Elke Bergmann-Leitner Hoseah M. Akala Geoffrey Odhiambo Bernhards R. Ogutu Ben Andagalu Edwin Kamau Daniel Ochiel |
| author_sort | Christine N. L. Wanjala |
| collection | DOAJ |
| description | Abstract Background Naturally acquired immunity (NAI), which is characterized by protection against overt clinical disease and high parasitaemia, is acquired with age and transmission intensity. The role of NAI on the efficacy of anti-malarial drugs, including artemisinin-based combinations used as the first-line treatment for uncomplicated Plasmodium falciparum, has not been fully demonstrated. This study investigated the role of NAI in response to artemisinin-based combination therapy (ACT), in symptomatic patients living in western Kenya, a high malaria transmission area. Methods Sera samples from malaria immune participants (n = 105) in a therapeutic efficacy study were assessed for in vitro growth inhibitory activity against the 3D7 strain of P. falciparum using a fluorescent-based growth inhibition assay (GIA). Participants’ age and parasite clearance parameters were used in the analysis. Pooled sera from malaria naïve participants (n = 6) with no Plasmodium infection from malaria non-endemic regions of Kenya was used as negative control. Results The key observations of the study were as follows: (1) Sera with intact complement displayed higher GIA activity at lower (1%) serum dilutions (p < 0.0001); (2) there was significant relationship between GIA activity, parasite clearance rate (p = 0.05) and slope half-life (p = 0.025); and (3) age was a confounding factor when comparing the GIA activity with parasite clearance kinetics. Conclusion This study demonstrates for the first time there is synergy of complement, pre-existing immunity, and drug treatment in younger patients with symptomatic malaria in a high-transmission area. |
| first_indexed | 2024-04-13T17:47:59Z |
| format | Article |
| id | doaj.art-9a2116b22ab44a8184f0870694ff6b43 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-04-13T17:47:59Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-9a2116b22ab44a8184f0870694ff6b432022-12-22T02:36:52ZengBMCMalaria Journal1475-28752020-04-011911810.1186/s12936-020-03242-4The role of complement immune response on artemisinin-based combination therapy in a population from malaria endemic region of Western KenyaChristine N. L. Wanjala0Elke Bergmann-Leitner1Hoseah M. Akala2Geoffrey Odhiambo3Bernhards R. Ogutu4Ben Andagalu5Edwin Kamau6Daniel Ochiel7Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP)Malaria Biologics Branch, Walter Reed Army Institute of ResearchDepartment of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP)Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP)Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP)Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP)Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP)Department of Emerging and Infectious Diseases (DEID), United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)/Walter Reed Project (WRP)Abstract Background Naturally acquired immunity (NAI), which is characterized by protection against overt clinical disease and high parasitaemia, is acquired with age and transmission intensity. The role of NAI on the efficacy of anti-malarial drugs, including artemisinin-based combinations used as the first-line treatment for uncomplicated Plasmodium falciparum, has not been fully demonstrated. This study investigated the role of NAI in response to artemisinin-based combination therapy (ACT), in symptomatic patients living in western Kenya, a high malaria transmission area. Methods Sera samples from malaria immune participants (n = 105) in a therapeutic efficacy study were assessed for in vitro growth inhibitory activity against the 3D7 strain of P. falciparum using a fluorescent-based growth inhibition assay (GIA). Participants’ age and parasite clearance parameters were used in the analysis. Pooled sera from malaria naïve participants (n = 6) with no Plasmodium infection from malaria non-endemic regions of Kenya was used as negative control. Results The key observations of the study were as follows: (1) Sera with intact complement displayed higher GIA activity at lower (1%) serum dilutions (p < 0.0001); (2) there was significant relationship between GIA activity, parasite clearance rate (p = 0.05) and slope half-life (p = 0.025); and (3) age was a confounding factor when comparing the GIA activity with parasite clearance kinetics. Conclusion This study demonstrates for the first time there is synergy of complement, pre-existing immunity, and drug treatment in younger patients with symptomatic malaria in a high-transmission area.http://link.springer.com/article/10.1186/s12936-020-03242-4Malaria antibodyComplementMalaria immunityArtemisinin combination therapyWestern KenyaMalaria holoendemic areas |
| spellingShingle | Christine N. L. Wanjala Elke Bergmann-Leitner Hoseah M. Akala Geoffrey Odhiambo Bernhards R. Ogutu Ben Andagalu Edwin Kamau Daniel Ochiel The role of complement immune response on artemisinin-based combination therapy in a population from malaria endemic region of Western Kenya Malaria Journal Malaria antibody Complement Malaria immunity Artemisinin combination therapy Western Kenya Malaria holoendemic areas |
| title | The role of complement immune response on artemisinin-based combination therapy in a population from malaria endemic region of Western Kenya |
| title_full | The role of complement immune response on artemisinin-based combination therapy in a population from malaria endemic region of Western Kenya |
| title_fullStr | The role of complement immune response on artemisinin-based combination therapy in a population from malaria endemic region of Western Kenya |
| title_full_unstemmed | The role of complement immune response on artemisinin-based combination therapy in a population from malaria endemic region of Western Kenya |
| title_short | The role of complement immune response on artemisinin-based combination therapy in a population from malaria endemic region of Western Kenya |
| title_sort | role of complement immune response on artemisinin based combination therapy in a population from malaria endemic region of western kenya |
| topic | Malaria antibody Complement Malaria immunity Artemisinin combination therapy Western Kenya Malaria holoendemic areas |
| url | http://link.springer.com/article/10.1186/s12936-020-03242-4 |
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