The side effects associated with sirolimus therapy included bronchitis; lymphopenia; elevated AST, ALT and platelets; hyperlipidaemia; opportunistic infection; mild reversible leukopenia; mucositis; fever; pain and skin rash/vomiting and diarrhoea.
Eligible participants for first malaria episode and all retreatment episodes were adults and children aged 6 months and older with microscopically confirmed Plasmodium spp malaria (>0 to <200 000 parasites per μL of blood) and fever or history of fever in the previous 24 h. Individuals with severe or complicated malaria, an alanine aminotransferase concentration of more than twice the upper limit of normal, or a QTc greater than 450 ms were excluded.
Multivariate analysis revealed that advanced age, the absence of fever, a higher Charlson comorbidity score, higher blood urea nitrogen (BUN)/albumin ratios and lower alanine aminotransferase (ALT) levels were all predictors of long-term mortality.
The most common grade 3-4 adverse events in the leucovorin and fluorouracil group were neutropenia without fever (17 [23%]), fatigue (16 [22%]), paraesthesia (14 [19%]), diarrhoea (nine [12%]), and mucositis (seven [10%]); in the gemcitabine group they were neutropenia without fever (12 [32%]), thrombocytopenia (seven [18%]), fatigue (eight [21%]), anaemia (five [13%]), increased alanine aminotransferase and aspartate aminotransferase concentrations (five [13%] for both), and paraesthesia (four [11%]).
Serious adverse events occurring in more than two patients included alanine aminotransferase increase (five [14%]), pyrexia (four [11%]), aspartate aminotransferase increase (three [8%]), and ejection fraction decrease (three [8%]).
Among the first eight patients, four experienced unexpected dose-limiting toxicities: grade 4 sepsis syndrome, grade 4 hypotension with grade 3 rash and fevers, grade 4 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation with fevers, and grade 3 pulmonary infection with grade 3 maculopapular rash.
Three patients developed transient moderate fever after infusion, and there were no significant differences in alanine aminotransferase and aspartate aminotransferase levels before and after treatment in both groups.
The most common adverse events were nasopharyngitis, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST), headache, diarrhea, and pyrexia.
Of the 22 patients, 15 (68%) presented with fever, fewer comorbidities, shorter hospital stays, lower mean creatinine levels (1.10 mg/dL vs. 1.74 mg/dL), lower aspartate aminotransferase levels (29.1 IU/L vs. 79.0 IU/L), and lower alanine aminotransferase levels (16.4 IU/L vs. 67.0 IU/L) when compared to afebrile patients.