Antirelapse Efficacy of Various Primaquine Regimens for Plasmodium vivax

Abstract

Background. Efficacy of standard dose of primaquine (PQ) as antirelapse for P. vivax has decreased. We aimed to assess efficacy of different PQ regimens. Methods. It was an open label, randomized, controlled, parallel group, assessor blind study comparing antirelapse efficacy of 3 PQ regimens (B = 15 mg/day × 14 days, C = 30 mg/day × 7 days, and D = 30 mg/day × 14 days) with no PQ group (A) in P. vivax patients. Paired primary and recurrence samples were subjected to 3 methods: (i) month of recurrence and genotyping, (ii) by PCR-RFLP, and (iii) PCR sequencing, to differentiate relapse and reinfection. The rates of recurrence relapse and reinfection were compared. Methods were compared for concordance between them. Results. The recurrence rate was 16.39%, 8.07%, 10.07%, and 6.62% in groups A, B, C, and D, respectively (P = 0.004). The relapse rate was 6.89%, 1.55%, 4%, and 3.85% as per the month of recurrence; 8.2%, 2%, 4.58%, and 3.68% (P = 0.007) as per PCR-RFLP; and 2.73%, 1.47%, 1.55%, and 1.53% as per PCR sequencing for groups A, B, C, and D, respectively. The concordance between methods was low, 45%. Conclusion. The higher recurrence rate in no PQ as compared to PQ groups documents PQ antirelapse activity. Regimens tested were safe. However, probable resistance to PQ warrants continuous monitoring and low concordance and limitations in the methods warrant caution in interpreting.

Prospective Study of Plasmodium vivax Malaria Recurrence after Radical Treatment with a Chloroquine-Primaquine Standard Regimen in Turbo, Colombia

“…Moreover, it is highly unlikely that these recurrences were recrudescence by therapeutic failure to CQ since all participants had a negative PCR for malaria on day 28 posttreatment. Results from similar studies in other parts of the world reported a cumulative incidence of recurrence between 0% and 13.5% after treatment with 0.25 mg/kg/day PQ for 14 days and a follow-up time between 180 and 210 days, which is much lower than what was found in this study (38)(39)(40)(41)(42)(43).…”

“…It is not clear if any such variation in the genetic background of this population could account for this observation. In addition, it has been shown that when higher doses of PQ, such as 0.5 mg/kg for 14 days, are used as recommended by the CDC (53), lower incidences of recurrence are reported (between 1.9% and 6.6% during 180 to 365 days) (43,54,55). However, no direct comparison had been made between a PQ regimen of 0.5 mg/kg for 14 days and the standard regimen in countries where malaria is endemic (9).…”

Eficacia terapéutica de esquemas de Primaquina usados como alternativa al tratamiento estándar en la prevención de recaídas por Plasmodium vivax: Una revisión sistemática y meta-análisis

“…376 were duplicated and 251 articles were screened, out of which 229 were excluded. Twenty-three articles were fully read for review in the second phase, out of which 9 clinical trials met with the eligibility criteria; 7 studies for the qualitative systematic review of the primary objective 15 - 21 , out of these, 4 studies made a comparison with the standard regimen and were included in the meta-analysis 15 , 17 , 19 , 20 , the other 3 did not compare with the standard regimen 16 , 18 , 21 . Three studies for the secondary objective were identified 19 , 22 , 23 , one of which was also included in the primary objective; only one study made a comparison with the standard regimen 19, therefore, no studies for the quantitative synthesis of this objective were included ( Fig.…”

“…Table 1 shows the main characteristics of the studies. Three studies were conducted in Brazil 15 , 16 , 18 , two in Peru 17 , 20 , one in Colombia 21 , one in India 19 , one in Pakistan 22 , and one in Indonesia 23 . Only one study was conducted in a non-endemic region where reinfection during the follow-up was not possible 23 .…”

Prevalence and association of malaria with ABO blood group and hemoglobin levels in individuals visiting Mekaneeyesus Primary Hospital, Estie District, northwest Ethiopia: A cross-sectional study

“…The dominance of P. vivax over P. falciparum attributed to one or more of the following: the ambient temperature of the study area that might have affected P. falciparum within the vector, active case detection, and early treatment of P. falciparum cases by artimisinin based therapy. The predominance of P. vivax over P. falciparum could also be due to the spreading of chloroquine resistance of P. vivax strains, its peculiarity in relapsing, and decrease in the efficacy of standard dose of primaquine as antirelapse for P. vivax [43]. However, the present finding contradicts the reports of Alelign and Dejene [44] from south and Deressa [45] from south central parts of Ethiopia that reported predominance of the P. falciparum species over P. vivax species.…”