FACTORS ASSOCIATED WITH SEVERE PLASMODIUM VIVAX MALARIA:A 15-YEAR RETROSPECTIVE STUDY

Abstract

There has been a shift in the predominant species causing malaria in Thailand from Plasmodium falciparum to Plasmodium vivax due to malaria elimination efforts.  In this study we aimed to determine the proportion of adult patients with severe P. vivax malaria admitted to the Hospital for Tropical Diseases, Bangkok, Thailand, during 1 January 2009 - 31 May 2023 and to identify the clinical factors significantly associated with malaria severity, in order to inform current treatment of P. vivax malaria at the study hospital.  Inclusion criteria for study subjects were being aged ≥18 years, being admitted to the study hospital during the study period and being infected with P. vivax malaria mono-infection.  Exclusion criteria for study subjects were having a co-infection with another species of malaria or a coinfection with another infectious disease and having incomplete medical records.  The minimum number of subjects calculated to be needed for the study was 752.  We retrospectively reviewed the medical records of each subject.  Subjects were classified as having severe malaria infection using 2023 World Health Organization criteria.  We used logistic regression analysis to identify factors significantly associated with severity.  A total of 551 subjects were included in the study, fewer than the minimum number calculated to be needed, since these were all the subjects that met the inclusion and exclusion criteria during the study period at the study hospital.  Of these, 478 (86.8%) were male.  The mean (±standard deviation (SD)) age of the study subjects was 30.8 (±11.6) (range: 18-76) years.  Of the total of 551 subjects 78 (14.2%) had severe P. vivax malaria. Twenty-one factors were significantly associated with severe infection on univariate analysis, 7 of these were removed due to multicollinearity or clinical irrelevance.  Therefore, 14 factors were included in multivariable analysis.  After eliminating confounding factors, the following factors were significantly positively associated with severe P. vivax malaria: glucose-6-phosphate dehydrogenase (G6PD) deficiency (adjusted odds ratio (aOR) = 5.68, 95% confidence interval (CI): 2.41-13.35, p<0.001), fever on admission (aOR = 2.28, 95%CI: 1.19-4.38, p=0.013), gametocytemia (aOR = 2.30, 95%CI: 1.11-4.78, p=0.025), severe anemia (hemoglobin <8 g/dl) (aOR = 9.30, 95%CI: 1.81-47.77, p=0.008), an albumin level <3 mg/dl (aOR = 3.66, 95%CI: 1.19-11.25, p=0.023) and an elevated serum aspartate aminotransferase (AST) level 1-3 times greater than the upper normal limit (aOR = 2.42, 95%CI: 1.26-4.66, p=0.008).  The following factor was significantly negatively associated with severe infection: male gender (aOR = 0.36, 95%CI: 0.15-0.84, p=0.018).  In summary, 14.2% of subjects had severe infection and the factors significantly positively associated with severe infection were: having G6PD deficiency, having a fever on admission, having gametocytemia, having severe anemia, having a low serum albumin level and having a high AST level.  The factor significantly negatively associated with severe malaria was being male.  We conclude, subjects with these factors and who do not yet have a severe infection on admission should be monitored more carefully for deterioration and managed accordingly.  Further studies are need to determine if there are interventions that can prevent non-severe patients with these risk factors from deteriorating to severe infection.