TY - JOUR
T1 - Reducing the risk of Plasmodium vivax after falciparum infections in co-endemic areas—a randomized controlled trial (PRIMA)
AU - Thriemer, Kamala
AU - Degaga, Tamiru Shibru
AU - Christian, Michael
AU - Alam, Mohammad Shafiul
AU - Ley, Benedikt
AU - Hossain, Mohammad Sharif
AU - Kibria, Mohammad Golam
AU - Tego, Tedla Teferi
AU - Abate, Dagimawie Tadesse
AU - Weston, Sophie
AU - Karahalios, Amalia
AU - Rajasekhar, Megha
AU - Simpson, Julie A.
AU - Rumaseb, Angela
AU - Mnjala, Hellen
AU - Lee, Grant
AU - Anose, Rodas Temesgen
AU - Kidane, Fitsum Getahun
AU - Woyessa, Adugna
AU - Baird, Kevin
AU - Sutanto, Inge
AU - Hailu, Asrat
AU - Price, Ric N.
N1 - Funding Information:
Funding for this project is provided by the Australian Academy of Science, on behalf of the Department of Industry, Innovation and Science. The Regional Collaborations Programme is supported by the Australian Government under the National Innovation and Science Agenda. This work is also supported, in part, by the Bill & Melinda Gates Foundation INV-010504 and the Australian National Health and Medical Research Council (NHMRC) Program grant (APP1132975).
PY - 2022/12
Y1 - 2022/12
N2 - Background: Plasmodium vivax forms dormant liver stages that can reactivate weeks or months following an acute infection. Recurrent infections are often associated with a febrile illness and can cause a cumulative risk of severe anaemia, direct and indirect mortality, and onward transmission of the parasite. There is an increased risk of P. vivax parasitaemia following falciparum malaria suggesting a rationale for universal use of radically curative treatment in patients with P. falciparum malaria even in the absence of detectable P. vivax parasitaemia in areas that are co-endemic for both species. Methods: This is a multicentre, health care facility-based, randomized, controlled, open-label trial in Bangladesh, Indonesia and Ethiopia. Patients with uncomplicated falciparum malaria, G6PD activity of ≥70% of the adjusted male median (AMM) and haemoglobin levels ≥8g/dl are recruited into the study and randomized to either receive standard schizonticidal treatment plus 7-day high dose primaquine (total dose 7mg/kg) or standard care in a 1:1 ratio. Patients are followed up weekly until day 63. The primary endpoint is the incidence risk of any P. vivax parasitemia on day 63. Secondary endpoints include incidence risk on day 63 of symptomatic P. vivax malaria and the risk of any P. falciparum parasitaemia. Secondary safety outcomes include the proportion of adverse events and serious adverse events, the incidence risk of severe anaemia (Hb<5g/dl and <7g/dl) and/or the risk for blood transfusion, the incidence risk of ≥ 25% fall in haemoglobin with and without haemoglobinuria, and the incidence risk of ≥ 25% fall in haemoglobin to under 7g/dl with and without haemoglobinuria. Discussion: This study evaluates the potential benefit of a universal radical cure for both P. vivax and P. falciparum in different endemic locations. If found safe and effective universal radical cure could represent a cost-effective approach to clear otherwise unrecognised P. vivax infections and hence accelerate P. vivax elimination. Trial registration: NCT03916003. Registered on 12 April 2019.
AB - Background: Plasmodium vivax forms dormant liver stages that can reactivate weeks or months following an acute infection. Recurrent infections are often associated with a febrile illness and can cause a cumulative risk of severe anaemia, direct and indirect mortality, and onward transmission of the parasite. There is an increased risk of P. vivax parasitaemia following falciparum malaria suggesting a rationale for universal use of radically curative treatment in patients with P. falciparum malaria even in the absence of detectable P. vivax parasitaemia in areas that are co-endemic for both species. Methods: This is a multicentre, health care facility-based, randomized, controlled, open-label trial in Bangladesh, Indonesia and Ethiopia. Patients with uncomplicated falciparum malaria, G6PD activity of ≥70% of the adjusted male median (AMM) and haemoglobin levels ≥8g/dl are recruited into the study and randomized to either receive standard schizonticidal treatment plus 7-day high dose primaquine (total dose 7mg/kg) or standard care in a 1:1 ratio. Patients are followed up weekly until day 63. The primary endpoint is the incidence risk of any P. vivax parasitemia on day 63. Secondary endpoints include incidence risk on day 63 of symptomatic P. vivax malaria and the risk of any P. falciparum parasitaemia. Secondary safety outcomes include the proportion of adverse events and serious adverse events, the incidence risk of severe anaemia (Hb<5g/dl and <7g/dl) and/or the risk for blood transfusion, the incidence risk of ≥ 25% fall in haemoglobin with and without haemoglobinuria, and the incidence risk of ≥ 25% fall in haemoglobin to under 7g/dl with and without haemoglobinuria. Discussion: This study evaluates the potential benefit of a universal radical cure for both P. vivax and P. falciparum in different endemic locations. If found safe and effective universal radical cure could represent a cost-effective approach to clear otherwise unrecognised P. vivax infections and hence accelerate P. vivax elimination. Trial registration: NCT03916003. Registered on 12 April 2019.
KW - Co-endemic
KW - Falciparum malaria
KW - Radical cure
KW - Randomized controlled trial
KW - Universal radical cure
KW - Vivax elimination
KW - Vivax malaria
UR - http://www.scopus.com/inward/record.url?scp=85130263942&partnerID=8YFLogxK
U2 - 10.1186/s13063-022-06364-z
DO - 10.1186/s13063-022-06364-z
M3 - Article
C2 - 35585641
AN - SCOPUS:85130263942
SN - 1745-6215
VL - 23
SP - 1
EP - 12
JO - Trials
JF - Trials
IS - 1
M1 - 416
ER -
