How radical is radical cure? Site-specific biases in clinical trials underestimate the effect of radical cure on Plasmodium vivax hypnozoites
Abstract Background Plasmodium vivax blood-stage relapses originating from re-activating hypnozoites are a major barrier for control and elimination of this disease. Radical cure is a form of therapy capable of addressing this problem. Recent clinical trials of radical cure have yielded efficacy est...
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ftdoajarticles:oai:doaj.org/article:2733c2a2f4884a59a2e5550058dd4ded 2023-05-15T15:13:53+02:00 How radical is radical cure? Site-specific biases in clinical trials underestimate the effect of radical cure on Plasmodium vivax hypnozoites John H. Huber Cristian Koepfli Guido España Narimane Nekkab Michael T. White T. Alex Perkins 2021-12-01T00:00:00Z https://doi.org/10.1186/s12936-021-04017-1 https://doaj.org/article/2733c2a2f4884a59a2e5550058dd4ded EN eng BMC https://doi.org/10.1186/s12936-021-04017-1 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-04017-1 1475-2875 https://doaj.org/article/2733c2a2f4884a59a2e5550058dd4ded Malaria Journal, Vol 20, Iss 1, Pp 1-15 (2021) Plasmodium vivax Radical cure Clinical trials Bias Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2021 ftdoajarticles https://doi.org/10.1186/s12936-021-04017-1 2022-12-31T15:47:41Z Abstract Background Plasmodium vivax blood-stage relapses originating from re-activating hypnozoites are a major barrier for control and elimination of this disease. Radical cure is a form of therapy capable of addressing this problem. Recent clinical trials of radical cure have yielded efficacy estimates ranging from 65 to 94%, with substantial variation across trial sites. Methods An analysis of simulated trial data using a transmission model was performed to demonstrate that variation in efficacy estimates across trial sites can arise from differences in the conditions under which trials are conducted. Results The analysis revealed that differences in transmission intensity, heterogeneous exposure and relapse rate can yield efficacy estimates ranging as widely as 12–78%, despite simulating trial data under the uniform assumption that treatment had a 75% chance of clearing hypnozoites. A longer duration of prophylaxis leads to a greater measured efficacy, particularly at higher transmission intensities, making the comparison between the protection of different radical cure treatment regimens against relapse more challenging. Simulations show that vector control and parasite genotyping offer two potential means to yield more standardized efficacy estimates that better reflect prevention of relapse. Conclusions Site-specific biases are likely to contribute to variation in efficacy estimates both within and across clinical trials. Future clinical trials can reduce site-specific biases by conducting trials in low-transmission settings where re-infections from mosquito bite are less common, by preventing re-infections using vector control measures, or by identifying and excluding likely re-infections that occur during follow-up, by using parasite genotyping methods. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 20 1 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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Plasmodium vivax Radical cure Clinical trials Bias Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Plasmodium vivax Radical cure Clinical trials Bias Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 John H. Huber Cristian Koepfli Guido España Narimane Nekkab Michael T. White T. Alex Perkins How radical is radical cure? Site-specific biases in clinical trials underestimate the effect of radical cure on Plasmodium vivax hypnozoites |
topic_facet |
Plasmodium vivax Radical cure Clinical trials Bias Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Plasmodium vivax blood-stage relapses originating from re-activating hypnozoites are a major barrier for control and elimination of this disease. Radical cure is a form of therapy capable of addressing this problem. Recent clinical trials of radical cure have yielded efficacy estimates ranging from 65 to 94%, with substantial variation across trial sites. Methods An analysis of simulated trial data using a transmission model was performed to demonstrate that variation in efficacy estimates across trial sites can arise from differences in the conditions under which trials are conducted. Results The analysis revealed that differences in transmission intensity, heterogeneous exposure and relapse rate can yield efficacy estimates ranging as widely as 12–78%, despite simulating trial data under the uniform assumption that treatment had a 75% chance of clearing hypnozoites. A longer duration of prophylaxis leads to a greater measured efficacy, particularly at higher transmission intensities, making the comparison between the protection of different radical cure treatment regimens against relapse more challenging. Simulations show that vector control and parasite genotyping offer two potential means to yield more standardized efficacy estimates that better reflect prevention of relapse. Conclusions Site-specific biases are likely to contribute to variation in efficacy estimates both within and across clinical trials. Future clinical trials can reduce site-specific biases by conducting trials in low-transmission settings where re-infections from mosquito bite are less common, by preventing re-infections using vector control measures, or by identifying and excluding likely re-infections that occur during follow-up, by using parasite genotyping methods. |
format |
Article in Journal/Newspaper |
author |
John H. Huber Cristian Koepfli Guido España Narimane Nekkab Michael T. White T. Alex Perkins |
author_facet |
John H. Huber Cristian Koepfli Guido España Narimane Nekkab Michael T. White T. Alex Perkins |
author_sort |
John H. Huber |
title |
How radical is radical cure? Site-specific biases in clinical trials underestimate the effect of radical cure on Plasmodium vivax hypnozoites |
title_short |
How radical is radical cure? Site-specific biases in clinical trials underestimate the effect of radical cure on Plasmodium vivax hypnozoites |
title_full |
How radical is radical cure? Site-specific biases in clinical trials underestimate the effect of radical cure on Plasmodium vivax hypnozoites |
title_fullStr |
How radical is radical cure? Site-specific biases in clinical trials underestimate the effect of radical cure on Plasmodium vivax hypnozoites |
title_full_unstemmed |
How radical is radical cure? Site-specific biases in clinical trials underestimate the effect of radical cure on Plasmodium vivax hypnozoites |
title_sort |
how radical is radical cure? site-specific biases in clinical trials underestimate the effect of radical cure on plasmodium vivax hypnozoites |
publisher |
BMC |
publishDate |
2021 |
url |
https://doi.org/10.1186/s12936-021-04017-1 https://doaj.org/article/2733c2a2f4884a59a2e5550058dd4ded |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 20, Iss 1, Pp 1-15 (2021) |
op_relation |
https://doi.org/10.1186/s12936-021-04017-1 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-021-04017-1 1475-2875 https://doaj.org/article/2733c2a2f4884a59a2e5550058dd4ded |
op_doi |
https://doi.org/10.1186/s12936-021-04017-1 |
container_title |
Malaria Journal |
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20 |
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1 |
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1766344399296397312 |