 | Daniel Chandramohan, Issaka Zongo, Issaka Sagara, Matthew Cairns, Rakiswendé-Serge Yerbanga, Modibo Diarra, Frédéric Niki`ema, Amadou Tapily, Frédéric Sompougdou, Djibrilla Issiaka, Charles Zoungrana, Koualy Sanogo, Alassane Haro, Mahamadou Kaya, Abdoul-Aziz Sienou, Seydou Traore, Almahamoudou Mahamar, Ismaila Thera, Kalifa Diarra, Amagana Dolo, Irene Kuepfer, Paul Snell, Paul Milligan, Christian Ockenhouse, Opokua Ofori-Anyinam, Halidou Tinto, Abdoulaye Djimde, Jean-Bosco Ouédraogo, Alassane Dicko, Brian Greenwood Seasonal malaria vaccination with or without seasonal malaria chemoprevention Journal Article In: N. Engl. J. Med., vol. 385, no. 11, pp. 1005–1017, 2021, ISSN: 1533-4406 0028-4793, (Copyright © 2021 Massachusetts Medical Society.
Place: United States
PMID: 34432975). @article{Chandramohan2021-qm,
title = {Seasonal malaria vaccination with or without seasonal malaria chemoprevention},
author = {Daniel Chandramohan and Issaka Zongo and Issaka Sagara and Matthew Cairns and Rakiswend\'{e}-Serge Yerbanga and Modibo Diarra and Fr\'{e}d\'{e}ric Niki`ema and Amadou Tapily and Fr\'{e}d\'{e}ric Sompougdou and Djibrilla Issiaka and Charles Zoungrana and Koualy Sanogo and Alassane Haro and Mahamadou Kaya and Abdoul-Aziz Sienou and Seydou Traore and Almahamoudou Mahamar and Ismaila Thera and Kalifa Diarra and Amagana Dolo and Irene Kuepfer and Paul Snell and Paul Milligan and Christian Ockenhouse and Opokua Ofori-Anyinam and Halidou Tinto and Abdoulaye Djimde and Jean-Bosco Ou\'{e}draogo and Alassane Dicko and Brian Greenwood},
doi = {10.1056/NEJMoa2026330},
issn = {1533-4406 0028-4793},
year = {2021},
date = {2021-09-09},
urldate = {2021-09-09},
journal = {N. Engl. J. Med.},
volume = {385},
number = {11},
pages = {1005--1017},
publisher = {Massachusetts Medical Society},
abstract = {BACKGROUND: Malaria control remains a challenge in many parts of
the Sahel and sub-Sahel regions of Africa. METHODS: We conducted
an individually randomized, controlled trial to assess whether
seasonal vaccination with RTS,S/AS01E was noninferior to
chemoprevention in preventing uncomplicated malaria and whether
the two interventions combined were superior to either one alone
in preventing uncomplicated malaria and severe malaria-related
outcomes. RESULTS: We randomly assigned 6861 children 5 to 17
months of age to receive sulfadoxine-pyrimethamine and
amodiaquine (2287 children [chemoprevention-alone group]),
RTS,S/AS01E (2288 children [vaccine-alone group]), or
chemoprevention and RTS,S/AS01E (2286 children [combination
group]). Of these, 1965, 1988, and 1967 children in the three
groups, respectively, received the first dose of the assigned
intervention and were followed for 3 years. Febrile seizure
developed in 5 children the day after receipt of the vaccine,
but the children recovered and had no sequelae. There were 305
events of uncomplicated clinical malaria per 1000 person-years
at risk in the chemoprevention-alone group, 278 events per 1000
person-years in the vaccine-alone group, and 113 events per 1000
person-years in the combination group. The hazard ratio for the
protective efficacy of RTS,S/AS01E as compared with
chemoprevention was 0.92 (95% confidence interval [CI], 0.84 to
1.01), which excluded the prespecified noninferiority margin of
1.20. The protective efficacy of the combination as compared
with chemoprevention alone was 62.8% (95% CI, 58.4 to 66.8)
against clinical malaria, 70.5% (95% CI, 41.9 to 85.0) against
hospital admission with severe malaria according to the World
Health Organization definition, and 72.9% (95% CI, 2.9 to
92.4) against death from malaria. The protective efficacy of the
combination as compared with the vaccine alone against these
outcomes was 59.6% (95% CI, 54.7 to 64.0), 70.6% (95% CI,
42.3 to 85.0), and 75.3% (95% CI, 12.5 to 93.0), respectively.
CONCLUSIONS: Administration of RTS,S/AS01E was noninferior to
chemoprevention in preventing uncomplicated malaria. The
combination of these interventions resulted in a substantially
lower incidence of uncomplicated malaria, severe malaria, and
death from malaria than either intervention alone. (Funded by
the Joint Global Health Trials and PATH; ClinicalTrials.gov
number, NCT03143218.).},
note = {Copyright © 2021 Massachusetts Medical Society.
Place: United States
PMID: 34432975},
keywords = {Amodiaquine/therapeutic use, Antimalarials/adverse effects/therapeutic use, Burkina Faso/epidemiology, Chemoprevention, Combination, Combined Modality Therapy, Double-Blind Method, Drug Combinations, Drug Therapy, Falciparum/epidemiology/mortality/prevention \& control, Febrile/etiology, Female, Hospitalization/statistics \& numerical data, Humans, Infant, Malaria, Malaria Vaccines/administration \& dosage/adverse effects, Male, Mali/epidemiology, Pyrimethamine/therapeutic use, Seasons, Seizures, Sulfadoxine/therapeutic use},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Malaria control remains a challenge in many parts of
the Sahel and sub-Sahel regions of Africa. METHODS: We conducted
an individually randomized, controlled trial to assess whether
seasonal vaccination with RTS,S/AS01E was noninferior to
chemoprevention in preventing uncomplicated malaria and whether
the two interventions combined were superior to either one alone
in preventing uncomplicated malaria and severe malaria-related
outcomes. RESULTS: We randomly assigned 6861 children 5 to 17
months of age to receive sulfadoxine-pyrimethamine and
amodiaquine (2287 children [chemoprevention-alone group]),
RTS,S/AS01E (2288 children [vaccine-alone group]), or
chemoprevention and RTS,S/AS01E (2286 children [combination
group]). Of these, 1965, 1988, and 1967 children in the three
groups, respectively, received the first dose of the assigned
intervention and were followed for 3 years. Febrile seizure
developed in 5 children the day after receipt of the vaccine,
but the children recovered and had no sequelae. There were 305
events of uncomplicated clinical malaria per 1000 person-years
at risk in the chemoprevention-alone group, 278 events per 1000
person-years in the vaccine-alone group, and 113 events per 1000
person-years in the combination group. The hazard ratio for the
protective efficacy of RTS,S/AS01E as compared with
chemoprevention was 0.92 (95% confidence interval [CI], 0.84 to
1.01), which excluded the prespecified noninferiority margin of
1.20. The protective efficacy of the combination as compared
with chemoprevention alone was 62.8% (95% CI, 58.4 to 66.8)
against clinical malaria, 70.5% (95% CI, 41.9 to 85.0) against
hospital admission with severe malaria according to the World
Health Organization definition, and 72.9% (95% CI, 2.9 to
92.4) against death from malaria. The protective efficacy of the
combination as compared with the vaccine alone against these
outcomes was 59.6% (95% CI, 54.7 to 64.0), 70.6% (95% CI,
42.3 to 85.0), and 75.3% (95% CI, 12.5 to 93.0), respectively.
CONCLUSIONS: Administration of RTS,S/AS01E was noninferior to
chemoprevention in preventing uncomplicated malaria. The
combination of these interventions resulted in a substantially
lower incidence of uncomplicated malaria, severe malaria, and
death from malaria than either intervention alone. (Funded by
the Joint Global Health Trials and PATH; ClinicalTrials.gov
number, NCT03143218.). |
