Towards malaria elimination: a case-control study to assess associated factors to malaria relapses in the extra-Amazon Region of Brazil from 2008 to 2019.

Background: Malaria is an infectious disease caused by the Plasmodium species and is a global burden. When not treated correctly, it can reemerge as a relapse or recrudescence. Malaria relapse cases can contribute to maintaining active transmission chains and can influence the patient to develop severe malaria, potentially leading to hospitalization or death. The objective of this study is to estimate the number of malaria relapse cases in the extra-Amazon region of Brazil and to investigate the associated factors.

Methods: This is a case-control study that analyses malaria infections caused by Plasmodium vivax, as reported in Notifiable Diseases Information System (Sinan) for the Brazilian extra-Amazon region (an area not endemic for the disease) from 2008 to 2019. For the identification of relapse cases, deduplication record linkage processes in R software were used. Malaria relapses were defined as the case group, and new malaria infections were defined as the control group. Logistic regression models were used to assess associated factors.

Results: Of the 711 malaria relapses, 589 (82.8%) were first relapses. Most relapses (71.6%) occurred between 30 and 120 days after the previous infection. Malaria relapses are spread throughout the extra-Amazon region, with a higher concentration near big cities. Driver occupation was found to be a common risk factor compared to other occupations, along with asymptomatic individuals. Other associated factors were: being infected in the Brazilian Amazon region, having follow-ups for malaria relapses, and having parasite density of the previous infection higher than 10,000 parasites per mm.

Conclusions: This study provides evidence that allows malaria health surveillance services to direct their efforts to monitor cases of malaria in the highest risk segments identified in this study, particularly in the period between 30 and 120 days after being infected and treated. Relapses were associated to driver occupation, absence of symptoms, infection in endemic areas of Brazil, being detected through active surveillance or routine follow-up actions, and with parasitaemia greater than 10,000 parasites per mm in the previous infection. Improving cases follow-up is essential for preventing relapses.