Health worker compliance with severe malaria treatment guidelines in the context of implementing pre-referral rectal artesunate in the Democratic Republic of the Congo, Nigeria, and Uganda: An operational study.


Journal

PLoS medicine
ISSN: 1549-1676
Titre abrégé: PLoS Med
Pays: United States
ID NLM: 101231360

Informations de publication

Date de publication:
02 2023
Historique:
received: 22 07 2022
accepted: 02 02 2023
revised: 07 03 2023
pubmed: 23 2 2023
medline: 10 3 2023
entrez: 22 2 2023
Statut: epublish

Résumé

For a full treatment course of severe malaria, community-administered pre-referral rectal artesunate (RAS) should be completed by post-referral treatment consisting of an injectable antimalarial and oral artemisinin-based combination therapy (ACT). This study aimed to assess compliance with this treatment recommendation in children under 5 years. This observational study accompanied the implementation of RAS in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020. Antimalarial treatment was assessed during admission in included referral health facilities (RHFs) in children under 5 with a diagnosis of severe malaria. Children were either referred from a community-based provider or directly attending the RHF. RHF data of 7,983 children was analysed for appropriateness of antimalarials; a subsample of 3,449 children was assessed additionally for dosage and method of ACT provision (treatment compliance). A parenteral antimalarial and an ACT were administered to 2.7% (28/1,051) of admitted children in Nigeria, 44.5% (1,211/2,724) in Uganda, and 50.3% (2,117/4,208) in DRC. Children receiving RAS from a community-based provider were more likely to be administered post-referral medication according to the guidelines in DRC (adjusted odds ratio (aOR) = 2.13, 95% CI 1.55 to 2.92, P < 0.001), but less likely in Uganda (aOR = 0.37, 95% CI 0.14 to 0.96, P = 0.04) adjusting for patient, provider, caregiver, and other contextual factors. While in DRC, inpatient ACT administration was common, ACTs were often prescribed at discharge in Nigeria (54.4%, 229/421) and Uganda (53.0%, 715/1,349). Study limitations include the unfeasibility to independently confirm the diagnosis of severe malaria due to the observational nature of the study. Directly observed treatment was often incomplete, bearing a high risk for partial parasite clearance and disease recrudescence. Parenteral artesunate not followed up with oral ACT constitutes an artemisinin monotherapy and may favour the selection of resistant parasites. In connection with the finding that pre-referral RAS had no beneficial effect on child survival in the 3 study countries, concerns about an effective continuum of care for children with severe malaria seem justified. Stricter compliance with the WHO severe malaria treatment guidelines is critical to effectively manage this disease and further reduce child mortality. ClinicalTrials.gov (NCT03568344).

Sections du résumé

BACKGROUND
For a full treatment course of severe malaria, community-administered pre-referral rectal artesunate (RAS) should be completed by post-referral treatment consisting of an injectable antimalarial and oral artemisinin-based combination therapy (ACT). This study aimed to assess compliance with this treatment recommendation in children under 5 years.
METHODS AND FINDINGS
This observational study accompanied the implementation of RAS in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020. Antimalarial treatment was assessed during admission in included referral health facilities (RHFs) in children under 5 with a diagnosis of severe malaria. Children were either referred from a community-based provider or directly attending the RHF. RHF data of 7,983 children was analysed for appropriateness of antimalarials; a subsample of 3,449 children was assessed additionally for dosage and method of ACT provision (treatment compliance). A parenteral antimalarial and an ACT were administered to 2.7% (28/1,051) of admitted children in Nigeria, 44.5% (1,211/2,724) in Uganda, and 50.3% (2,117/4,208) in DRC. Children receiving RAS from a community-based provider were more likely to be administered post-referral medication according to the guidelines in DRC (adjusted odds ratio (aOR) = 2.13, 95% CI 1.55 to 2.92, P < 0.001), but less likely in Uganda (aOR = 0.37, 95% CI 0.14 to 0.96, P = 0.04) adjusting for patient, provider, caregiver, and other contextual factors. While in DRC, inpatient ACT administration was common, ACTs were often prescribed at discharge in Nigeria (54.4%, 229/421) and Uganda (53.0%, 715/1,349). Study limitations include the unfeasibility to independently confirm the diagnosis of severe malaria due to the observational nature of the study.
CONCLUSIONS
Directly observed treatment was often incomplete, bearing a high risk for partial parasite clearance and disease recrudescence. Parenteral artesunate not followed up with oral ACT constitutes an artemisinin monotherapy and may favour the selection of resistant parasites. In connection with the finding that pre-referral RAS had no beneficial effect on child survival in the 3 study countries, concerns about an effective continuum of care for children with severe malaria seem justified. Stricter compliance with the WHO severe malaria treatment guidelines is critical to effectively manage this disease and further reduce child mortality.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT03568344).

Identifiants

pubmed: 36809247
doi: 10.1371/journal.pmed.1004189
pii: PMEDICINE-D-22-02521
pmc: PMC9990943
doi:

Substances chimiques

Artesunate 60W3249T9M
Antimalarials 0

Banques de données

ClinicalTrials.gov
['NCT03568344']

Types de publication

Observational Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1004189

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright: © 2023 Signorell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Aita Signorell (A)

Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
University of Basel, Basel, Switzerland.

Phyllis Awor (P)

Makerere University School of Public Health, Kampala, Uganda.

Jean Okitawutshu (J)

Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
University of Basel, Basel, Switzerland.
Kinshasa School of Public Health, Kinshasa, Democratic Republic of the Congo.

Antoinette Tshefu (A)

Kinshasa School of Public Health, Kinshasa, Democratic Republic of the Congo.

Elizabeth Omoluabi (E)

Akena Associates, Abuja, Nigeria.

Manuel W Hetzel (MW)

Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
University of Basel, Basel, Switzerland.

Proscovia Athieno (P)

Makerere University School of Public Health, Kampala, Uganda.

Joseph Kimera (J)

Makerere University School of Public Health, Kampala, Uganda.

Gloria Tumukunde (G)

Makerere University School of Public Health, Kampala, Uganda.

Irene Angiro (I)

Makerere University School of Public Health, Kampala, Uganda.

Jean-Claude Kalenga (JC)

Kinshasa School of Public Health, Kinshasa, Democratic Republic of the Congo.

Babatunde K Akano (BK)

Akena Associates, Abuja, Nigeria.

Kazeem Ayodeji (K)

Akena Associates, Abuja, Nigeria.

Charles Okon (C)

Akena Associates, Abuja, Nigeria.

Ocheche Yusuf (O)

Akena Associates, Abuja, Nigeria.

Giulia Delvento (G)

Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
University of Basel, Basel, Switzerland.

Tristan T Lee (TT)

Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
University of Basel, Basel, Switzerland.

Nina C Brunner (NC)

Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
University of Basel, Basel, Switzerland.

Mark J Lambiris (MJ)

Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
University of Basel, Basel, Switzerland.

James Okuma (J)

Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
University of Basel, Basel, Switzerland.

Nadja Cereghetti (N)

Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
University of Basel, Basel, Switzerland.

Valentina Buj (V)

UNICEF, New York, New York, United States of America.

Theodoor Visser (T)

Clinton Health Access Initiative, Boston, Massachusetts, United States of America.

Harriet G Napier (HG)

Clinton Health Access Initiative, Boston, Massachusetts, United States of America.

Christian Lengeler (C)

Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
University of Basel, Basel, Switzerland.

Christian Burri (C)

Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
University of Basel, Basel, Switzerland.

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