RESUMO Objetivo: Analisar e identificar infecções documentadas e possíveis fatores de risco para infecções por Clostridioides difficile em crianças com câncer. Métodos: Estudo retrospectivo caso-controle em um hospital pediátrico oncológico, que abrangeu os anos de 2016–2019. O pareamento foi realizado por idade e doença de base e, para cada caso, o número de controles variou de um a três. Modelos de regressão logística foram utilizados para avaliar os fatores de risco. Resultados: Analisamos 63 casos de infecção documentados por C. difficile e 125 controles. A diarreia esteve presente em todos os casos, acompanhada de febre acima de 38°C em 52,4% dos pacientes. A mortalidade foi semelhante entre casos (n=4, 6,3%) e controles (n=6, 4,8%; p=0,7). No grupo caso, 71% dos pacientes e, no grupo controle, 53% deles receberam antibióticos de amplo espectro antes da infecção. Para uso prévio de vancomicina, a Odds Ratio para infecção por C. difficile foi de 5,4 (intervalo de confiança [IC95%] 2,3–12,5); para meropenem, 4,41 (IC95% 2,1–9,2) e, para cefepima, 2,6 (IC95% 1,3–5,1). Para os agentes antineoplásicos, a razão de chances para carboplatina foi de 2,7 (IC95% 1,2–6,2), para melfalano de 9,04 (IC95% 1,9-42,3), para bussulfano de 16,7 (IC95% 2,1–134,9) e, para asparaginase, de 8,97 (IC95% 1,9–42,9). Conclusões: A infecção sintomática por C. difficile em crianças com câncer associou-se à internação prévia e ao uso de antibióticos como vancomicina, meropenem e cefepime nos últimos três meses. Os quimioterápicos carboplatina, melfalano, bussulfano e asparaginase também foram fatores de risco. Objetivo Métodos casocontrole caso controle oncológico 20162019 2016 2019 2016–2019 Resultados 6 C 12 38C 38 524 52 4 52,4 n=4, n4 n (n=4 6,3% 3 n=6, n6 (n=6 4,8% 48 8 p=0,7. p07 p p=0,7 . 0 7 p=0,7) 71 53 vancomicina 54 5 5, intervalo IC95% IC95 IC [IC95% 2,3–12,5 23125 2 2,3–12,5) 441 41 4,4 (IC95 2,1–9,2 2192 1 9 cefepima 26 2, 1,3–5,1. 1351 1,3–5,1 1,3–5,1) antineoplásicos 27 1,2–6,2, 1262 1,2–6,2 , 1,2–6,2) 904 04 9,0 1,942,3, 19423 1,9 42,3 42 1,9-42,3) 167 16 16, 2,1–134,9 211349 134 897 97 8,9 1,9–42,9. 19429 1,9–42,9 1,9–42,9) Conclusões associouse associou se meses 2016201 201 2016–201 52, n=4 (n= 6,3 n=6 4,8 p0 p=0, IC9 [IC95 2,3–12, 2312 44 4, (IC9 2,1–9, 219 135 1,3–5, 126 1,2–6, 90 9, 942 1,942,3 1942 19 1, 423 42, 1,9-42,3 2,1–134, 21134 13 89 8, 1,9–42, 201620 20 2016–20 n= (n 6, p=0 [IC9 2,3–12 231 (IC 2,1–9 21 1,3–5 1,2–6 94 1,942, 194 1,9-42, 2,1–134 2113 1,9–42 20162 2016–2 p= [IC 2,3–1 23 2,1– 1,3– 1,2– 1,942 1,9-42 2,1–13 211 1,9–4 2016– 2,3– 2,1 1,3 1,2 1,94 1,9-4 2,1–1 1,9– 2,3 1,9-

Abstract Objective: The aim of this study was to analyze and identify documented infections and possible risk factors for Clostridioides difficile infections in children with cancer. Methods: This is a retrospective case-control study, carried out in a pediatric cancer hospital, covering the years 2016–2019. Matching was performed by age and underlying disease, and for each case, the number of controls varied from 1 to 3. Logistic regression models were used to assess risk factors. Results: We analyzed 63 cases of documented infection by C. difficile and 125 controls. Diarrhea was present in all cases, accompanied by fever higher than 38°C in 52.4% of the patients. Mortality was similar among cases (n=4; 6.3%) and controls (n=6; 4.8%; p=0.7). In all, 71% of patients in the case group and 53% in the control group received broad-spectrum antibiotics prior to the infection. For previous use of vancomycin, the Odds Ratio for C. difficile infection was 5.4 (95% confidence interval [95%CI] 2.3–12.5); for meropenem, 4.41 (95%CI 2.1–9.2); and for cefepime, 2.6 (95%CI 1.3–5.1). For the antineoplastic agents, the Odds Ratio for carboplatin was 2.7 (95%CI 1.2–6.2), melphalan 9.04 (95%CI 1.9–42.3), busulfan 16.7 (95%CI 2.1–134.9), and asparaginase 8.97 (95%CI 1.9–42.9). Conclusions: C. difficile symptomatic infection in children with cancer was associated with previous hospitalization and the use of common antibiotics in cancer patients, such as vancomycin, meropenem, and cefepime, in the last 3 months. Chemotherapy drugs, such as carboplatin, melphalan, busulfan, and asparaginase, were also risk factors. Objective Methods casecontrol hospital 20162019 2016 2019 2016–2019 disease Results 6 C 12 38C 38 524 52 4 52.4 n=4 n4 n (n=4 6.3% n=6 n6 (n=6 4.8% 48 8 p=0.7. p07 p p=0.7 . 0 7 p=0.7) 71 53 broadspectrum broad spectrum vancomycin 54 5 5. 95% 95 (95 95%CI 95CI CI [95%CI 2.3–12.5 23125 2 2.3–12.5) meropenem 441 41 4.4 2.1–9.2 2192 9 2.1–9.2) cefepime 26 2. 1.3–5.1. 1351 1.3–5.1 1.3–5.1) agents 27 1.2–6.2, 1262 1.2–6.2 , 1.2–6.2) 904 04 9.0 1.9–42.3, 19423 1.9–42.3 42 1.9–42.3) 167 16 16. 2.1–134.9, 211349 2.1–134.9 134 2.1–134.9) 897 97 8.9 1.9–42.9. 19429 1.9–42.9 1.9–42.9) Conclusions months drugs 2016201 201 2016–201 52. n= (n= 6.3 4.8 p0 p=0. (9 2.3–12. 2312 44 4. 2.1–9. 219 135 1.3–5. 126 1.2–6. 90 9. 1942 1.9–42. 21134 2.1–134. 13 89 8. 201620 20 2016–20 (n 6. p=0 ( 2.3–12 231 2.1–9 21 1.3–5 1.2–6 194 1.9–42 2113 2.1–134 20162 2016–2 p= 2.3–1 23 2.1– 1.3– 1.2– 19 1.9–4 211 2.1–13 2016– 2.3– 2.1 1.3 1.2 1.9– 2.1–1 2.3 1. 1.9

Soroprevalence for Hepatitis C virus is reported as 2.12% in Northern Brazil, with about 50% of the patients exhibiting a sustained virological response (SVR). Aiming to associate polymorphisms in Killer Cell Immunoglobulin-like Receptors (KIR) with chronic hepatitis C and therapy responses we investigated 125 chronic patients and 345 controls. Additionally, 48 ancestry markers were genotyped to control for population stratification. The frequency of the KIR2DL2 and KIR2DL2+HLA-C Asp80 gene and ligand was higher in chronic infected patients than in controls (p < 0.0009, OR = 3.4; p = 0.001, OR = 3.45). In fact, KIR2DL3 is a weaker inhibitor of NK activity than KIR2DL2, which could explain the association of KIR2DL2 with chronic infection. Moreover, KIR2DS2 and KIR2DS2+HLA-C Asp80 (p < 0.0001, OR = 2.51; p = 0.0084, OR = 2.62) and KIR2DS3 (p < 0.0001; OR = 2.57) were associated with chronic infection, independently from KIR2DL2. No differences in ancestry composition were observed between control and patients, even with respect to therapy response groups. The allelic profile KIR2DL2/KIR2DS2/KIR2DS3 was associated with the chronic hepatitis C (p < 0.0001; OR = 3). Furthermore, the patients also showed a higher mean number of activating genes and a lower frequency of the homozygous AA profile, which is likely secondary to the association with non-AA and/or activating genes. In addition, the KIR2DS5 allele was associated with SVR (p = 0.0261; OR = 0.184).The ancestry analysis of samples ruled out any effects of population substructuring and did not evidence interethnic differences in therapy response, as suggested in previous studies.