Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study
Abstract Background To prevent child deaths from severe malaria, early parenteral treatment is essential. Yet, in remote rural areas, accessing facilities offering parenteral antimalarials may be difficult. A randomised controlled trial found pre-referral treatment with rectal artesunate (RAS) to re...
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-022-02541-8 |
| _version_ | 1797853703071334400 |
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| author | Manuel W. Hetzel Jean Okitawutshu Antoinette Tshefu Elizabeth Omoluabi Phyllis Awor Aita Signorell Nina C. Brunner Jean-Claude Kalenga Babatunde K. Akano Kazeem Ayodeji Charles Okon Ocheche Yusuf Proscovia Athieno Joseph Kimera Gloria Tumukunde Irene Angiro Giulia Delvento Tristan T. Lee Mark J. Lambiris Marek Kwiatkowski Nadja Cereghetti Theodoor Visser Harriet G. Napier Justin M. Cohen Valentina Buj Christian Burri Christian Lengeler |
| author_facet | Manuel W. Hetzel Jean Okitawutshu Antoinette Tshefu Elizabeth Omoluabi Phyllis Awor Aita Signorell Nina C. Brunner Jean-Claude Kalenga Babatunde K. Akano Kazeem Ayodeji Charles Okon Ocheche Yusuf Proscovia Athieno Joseph Kimera Gloria Tumukunde Irene Angiro Giulia Delvento Tristan T. Lee Mark J. Lambiris Marek Kwiatkowski Nadja Cereghetti Theodoor Visser Harriet G. Napier Justin M. Cohen Valentina Buj Christian Burri Christian Lengeler |
| author_sort | Manuel W. Hetzel |
| collection | DOAJ |
| description | Abstract Background To prevent child deaths from severe malaria, early parenteral treatment is essential. Yet, in remote rural areas, accessing facilities offering parenteral antimalarials may be difficult. A randomised controlled trial found pre-referral treatment with rectal artesunate (RAS) to reduce deaths and disability in children who arrived at a referral facility with delay. This study examined the effectiveness of pre-referral RAS treatment implemented through routine procedures of established community-based health care systems. Methods An observational study accompanied the roll-out of RAS in the Democratic Republic of the Congo (DRC), Nigeria and Uganda. Children <5 years of age presenting to a community-based health provider with a positive malaria test and signs of severe malaria were enrolled and followed up during admission and after 28 days to assess their health status and treatment history. The primary outcome was death; covariates of interest included RAS use, referral completion, and post-referral treatment. Results Post-roll-out, RAS was administered to 88% of patients in DRC, 52% in Nigeria, and 70% in Uganda. The overall case fatality rate (CFR) was 6.7% (135/2011) in DRC, 11.7% (69/589) in Nigeria, and 0.5% (19/3686) in Uganda; 13.8% (865/6286) of patients were sick on day 28. The CFR was higher after RAS roll-out in Nigeria (16.1 vs. 4.2%) and stable in DRC (6.7 vs. 6.6%) and Uganda (0.7 vs. 0.3%). In DRC and Nigeria, children receiving RAS were more likely to die than those not receiving RAS (aOR=3.06, 95% CI 1.35–6.92 and aOR=2.16, 95% CI 1.11–4.21, respectively). Only in Uganda, RAS users were less likely to be dead or sick at follow-up (aOR=0.60, 95% CI 0.45–0.79). Post-referral parenteral antimalarials plus oral artemisinin-based combination therapy (ACT), a proxy for appropriate post-referral treatment, was protective. However, in referral health facilities, ACT was not consistently administered after parenteral treatment (DRC 68.4%, Nigeria 0%, Uganda 70.9%). Conclusions Implemented at scale to the recommended target group, pre-referral RAS had no beneficial effect on child survival in three highly malaria-endemic settings. RAS is unlikely to reduce malaria deaths unless health system issues such as referral and quality of care at all levels are addressed. Trial registration The study is registered on ClinicalTrials.gov : NCT03568344. |
| first_indexed | 2024-04-09T19:54:59Z |
| format | Article |
| id | doaj.art-2ba73178c9f64d9aba74b45ee7142511 |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-04-09T19:54:59Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medicine |
| spelling | doaj.art-2ba73178c9f64d9aba74b45ee71425112023-04-03T05:30:07ZengBMCBMC Medicine1741-70152022-10-0120111210.1186/s12916-022-02541-8Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational studyManuel W. Hetzel0Jean Okitawutshu1Antoinette Tshefu2Elizabeth Omoluabi3Phyllis Awor4Aita Signorell5Nina C. Brunner6Jean-Claude Kalenga7Babatunde K. Akano8Kazeem Ayodeji9Charles Okon10Ocheche Yusuf11Proscovia Athieno12Joseph Kimera13Gloria Tumukunde14Irene Angiro15Giulia Delvento16Tristan T. Lee17Mark J. Lambiris18Marek Kwiatkowski19Nadja Cereghetti20Theodoor Visser21Harriet G. Napier22Justin M. Cohen23Valentina Buj24Christian Burri25Christian Lengeler26Swiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteKinshasa School of Public HealthAkena AssociatesMakerere University School of Public HealthSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteKinshasa School of Public HealthAkena AssociatesAkena AssociatesAkena AssociatesAkena AssociatesMakerere University School of Public HealthMakerere University School of Public HealthMakerere University School of Public HealthMakerere University School of Public HealthSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteClinton Health Access InitiativeClinton Health Access InitiativeClinton Health Access InitiativeSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteSwiss Tropical and Public Health InstituteAbstract Background To prevent child deaths from severe malaria, early parenteral treatment is essential. Yet, in remote rural areas, accessing facilities offering parenteral antimalarials may be difficult. A randomised controlled trial found pre-referral treatment with rectal artesunate (RAS) to reduce deaths and disability in children who arrived at a referral facility with delay. This study examined the effectiveness of pre-referral RAS treatment implemented through routine procedures of established community-based health care systems. Methods An observational study accompanied the roll-out of RAS in the Democratic Republic of the Congo (DRC), Nigeria and Uganda. Children <5 years of age presenting to a community-based health provider with a positive malaria test and signs of severe malaria were enrolled and followed up during admission and after 28 days to assess their health status and treatment history. The primary outcome was death; covariates of interest included RAS use, referral completion, and post-referral treatment. Results Post-roll-out, RAS was administered to 88% of patients in DRC, 52% in Nigeria, and 70% in Uganda. The overall case fatality rate (CFR) was 6.7% (135/2011) in DRC, 11.7% (69/589) in Nigeria, and 0.5% (19/3686) in Uganda; 13.8% (865/6286) of patients were sick on day 28. The CFR was higher after RAS roll-out in Nigeria (16.1 vs. 4.2%) and stable in DRC (6.7 vs. 6.6%) and Uganda (0.7 vs. 0.3%). In DRC and Nigeria, children receiving RAS were more likely to die than those not receiving RAS (aOR=3.06, 95% CI 1.35–6.92 and aOR=2.16, 95% CI 1.11–4.21, respectively). Only in Uganda, RAS users were less likely to be dead or sick at follow-up (aOR=0.60, 95% CI 0.45–0.79). Post-referral parenteral antimalarials plus oral artemisinin-based combination therapy (ACT), a proxy for appropriate post-referral treatment, was protective. However, in referral health facilities, ACT was not consistently administered after parenteral treatment (DRC 68.4%, Nigeria 0%, Uganda 70.9%). Conclusions Implemented at scale to the recommended target group, pre-referral RAS had no beneficial effect on child survival in three highly malaria-endemic settings. RAS is unlikely to reduce malaria deaths unless health system issues such as referral and quality of care at all levels are addressed. Trial registration The study is registered on ClinicalTrials.gov : NCT03568344.https://doi.org/10.1186/s12916-022-02541-8Severe malariaMalaria treatmentRectal artesunateReferralChild mortalityMalaria mortality |
| spellingShingle | Manuel W. Hetzel Jean Okitawutshu Antoinette Tshefu Elizabeth Omoluabi Phyllis Awor Aita Signorell Nina C. Brunner Jean-Claude Kalenga Babatunde K. Akano Kazeem Ayodeji Charles Okon Ocheche Yusuf Proscovia Athieno Joseph Kimera Gloria Tumukunde Irene Angiro Giulia Delvento Tristan T. Lee Mark J. Lambiris Marek Kwiatkowski Nadja Cereghetti Theodoor Visser Harriet G. Napier Justin M. Cohen Valentina Buj Christian Burri Christian Lengeler Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study BMC Medicine Severe malaria Malaria treatment Rectal artesunate Referral Child mortality Malaria mortality |
| title | Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study |
| title_full | Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study |
| title_fullStr | Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study |
| title_full_unstemmed | Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study |
| title_short | Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study |
| title_sort | effectiveness of rectal artesunate as pre referral treatment for severe malaria in children under 5 years of age a multi country observational study |
| topic | Severe malaria Malaria treatment Rectal artesunate Referral Child mortality Malaria mortality |
| url | https://doi.org/10.1186/s12916-022-02541-8 |
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