We retrospectively enrolled 93 eligible patients, 49 treated with IVA and 44 treated with IVA + IVQ.
Eleven patients were enrolled in AOUC-FI, 19 in AOUM-FI and 63 in SC-BS. All patients fully recovered.
In total, 45 adult patients (26 treated with IVA and 19 with IVA + IVQ) were analyzed. Patients were predominantly male (30/45, 66.7%), with a median age of 43 (IQR 34–50). A large majority of patients had parasitemia > 2% (39, 86.7%) as criteria for severe malaria, according to 2010 WHO classification. Clinical features of severe malaria were found in a minority of patients: 16 with jaundice (35.5%), 4 with haemoglobinuria (8.9%), 4 with abnormal bleeding (8.9%), 4 with prostration (8.9%), 1 with respiratory failure (2.2%), 1 with impaired consciousness (2.2%). All of them were likely to have acquired the infection in Sub-Saharan Africa, with Nigeria the most represented country (10, 22.2%). In most cases, visiting relatives and friends (VRF) was the travel reason (33, 73.3%). P. falciparum was the species involved in all cases. Baseline characteristics of the two groups are described in Table 1.
The two groups did not show any difference regarding sex, weight, use of chemoprophylaxis in last 12 weeks, laboratory values (LDH, Hb, parasitaemia on admission), days from symptoms onset and fever on admission. Regarding epidemiologic features, the IVA group had a significantly higher CMI (median 1 vs 0, p = 0.003) and was older (median 46 vs 36 years old, p < 0.006). Regarding clinical features, jaundice was more frequent in the IVA group (46.2% vs 21.1%, p = 0.118), whereas AKI and fever on admission were equally distributed.
Patients in the IVA + IVQ group received antibiotics more frequently (47.4% vs 19.2%, p = 0.057).
Clinical and parasitological outcomes are listed in Table 2. The median FCT was similar in both groups (median 48 h, p = 0.19) but number of patients who reached apyrexia within 48 h (FCT48) was significantly higher in IVA group (83.3%, p = 0.04) as shown in Fig. 1. This finding was confirmed in the multivariate analysis (Supplementary Table 1). Eight patients (17.8%) presented with AEs. Most of them were probably due to IVQ (6, 75%): they were all early-onset AE and discontinuation was necessary in all cases; there were no cases of hypoglycemia. IVA was deemed responsible for PADH in two patients (25%), a median 13 days after administration: one of them required blood transfusion (Table 3). Adverse events were more common in the combination treatment group (31.6 vs 7.7%, p = 0.055) but this finding was not confirmed in the multivariate analysis (Supplementary Table 2). PCT did not differ between the two groups (median 48 h in both groups, p = 0.669). No difference in length of hospitalization was observed (median 6 days, p = 0.402).
In total, 48 cases (23 treated with IVA and 25 with IVA + IVQ combined therapy) were analyzed. All cases were classified as severe malaria according to WHO 2010 criteria: most of them presented parasitemia > 2% (42, 87.5%). A smaller part of patients presented clinical features typical of severe malaria: prostration in 9 (18.8%), coma was described in 4 patients (8.3%), jaundice in 3 (6.3%), circulatory collapse in 1 (2.1%). All infections were acquired in Sub-Saharan Africa, being Burkina Faso the most represented country (12, 25%). All patients were VRF. P. falciparum was the species involved in all patients: in particular, two patients (4.2%) presented mixed infection with P. falciparum and P. vivax. Baseline characteristics of the two groups are described in Table 4. As for epidemiological features, the two groups appeared homogeneous: they didn’t show differences for age (median 6 in both groups), gender (males were 56.5% in IVA group vs 64% in IVA + IVQ), and comorbidities. Regarding laboratory values, the two groups didn’t show significant differences: baseline parasitemia was similar in both groups (median 5% in IVA vs 4% in IVA + IVQ). Clinical features (fever at admission, jaundice, AKI) were similar in both groups. There was a not significant difference on the QTc at baseline (median 426 in IVA group vs 391.5 in IVA + IVQ, p = 0.185). Antibiotic therapy was administered to 76% of cases in IVA + IVQ group vs 17.4% in the IVA monotherapy group (p < 0.001).
Clinical and parasitological outcomes are listed in Table 5. PCT and admission to ICU differed between the two groups. PCT was higher in IVA + IVQ group (median 72 vs 48 h, p = 0.002). Likewise, PCT48 was lower in IVA + IVQ group, in comparison with IVA group (48% vs 90%, respectively, p < 0.004) (Fig. 2). Sixteen (69.6%) patients were admitted to ICU in IVA group vs 4 (16%) in IVA + IVQ group (p = 0.023). FCT and AEs were not significantly different between the two groups. The median of FCT was 30 h in IVA group vs 48 in IVA + IVQ group (p = 0.5). The AEs reported were represented by 2 cases of PADH, one in each group, with an average time of onset of 12 days. The watch and wait management was the strategy adopted in both cases. No difference in length of hospitalization was observed (p = 0.505).