Parents' Awareness of Infectious Diseases Epidemiology in Poland and Ukraine.

BACKGROUND: There has been a decline in vaccine-related confidence in Ukraine over the past few years, resulting in high rates of infectious diseases. Due to the arrival of a large number of refugees in Poland following the outbreak of war in Ukraine in February 2022, the risk of infectious diseases in Poland among children and adults has increased. The present study aimed to analyze the relationship between parents' knowledge of the epidemiological situation of infectious diseases in Poland and Ukraine and socio-demographic factors and their attitudes towards vaccination. MATERIAL AND METHODS: A cross-sectional survey study was designed. Data were collected through an online questionnaire between November 2022 and January 2023, where the inclusion criteria was having a child under 18 years of age. Study participants' stratification was based on responses to seven knowledge questions; those who answered all questions correctly were allocated to group 1, and the others to group 2 for further analysis. RESULTS: A total of 547 parents were included. Their median age was 34 years [IQR: 31-39]. There were 233 (42.60%) participants who answered all the knowledge questions correctly. Respondents from group 1 were older (p = 0.033), were more likely to be in favor of recommended vaccination (p = 0.040), to be vaccinated with four doses against SARS-CoV-2 (p = 0.014), to have their children vaccinated against SARS-CoV-2 (p < 0.001), and to believe that the influx of migrants from Ukraine would increase the incidence rate of infectious diseases in Poland in the future (p < 0.001). They also declared awareness of the impact of migration on the epidemiological situation in Poland (p < 0.001) more often. According to the logistic regression model, older parents (OR = 1.31, p = 0.029), those who were willing to receive additional vaccinations due to migration (OR = 4.29, p = 0.003), those who were aware of the impact of migration on the epidemiological situation (OR = 2.38, p < 0.001), and those who believed that migration would have affected the incidence rate of infectious diseases in Poland (OR = 2.28, p = 0.003) were significantly more likely to belong to group 1. However, parents who were willing to vaccinate their children with additional vaccinations due to migration were significantly less likely to answer all the questions correctly (OR = 0.21, p = 0.002). CONCLUSIONS: Awareness of the epidemiological situation in Poland and Ukraine among parents is related to a greater awareness of the impact of migration and the use of recommended vaccinations and those against SARS-CoV-2. Additional vaccinations should be further promoted among both Poles and migrants.

Impact of COVID-19 Pandemic on the Clinical Course and Complications of Varicella-A Retrospective Cohort Study.

In this study, we aimed to characterize a cohort of children hospitalized due to varicella before and after the outbreak of the COVID-19 pandemic. Medical charts of all children hospitalized in the Regional Hospital of Infectious Diseases in Warsaw due to varicella in the years 2019 and 2022 were retrospectively analyzed and compared. In total, 221 children were included in the analysis; 59 of them were hospitalized in 2019, whereas 162 were hospitalized in 2022. Children hospitalized in 2022 were older than those reported in 2019 (median 4.0 vs. 3.0 years, p = 0.02). None of the hospitalized children received complete varicella vaccination. The most common complication in both years was bacterial superinfection of skin lesions, found in 156/221 (70.6%) of patients. This complication rate was higher in 2022 (50.8% in 2019 vs. 77.8% in 2022, p = 0.0001), OR = 3.38, 95% CI: 1.80-6.35. Moreover, skin infections in 2022 more often manifested with cellulitis (in 2022 13.6% vs. 3.4% in 2019, p = 0.03), OR = 4.40, 95% CI: 1.00-19.33. Sepsis as a complication of varicella was almost five-fold more prevalent in 2022 than in 2019 (p = 0.009), OR = 5.70, 95% CI: 1.31-24.77. Antibiotic use increased between 2019 and 2022 (71.2% vs. 85.2%, p = 0.01). Furthermore, patients were treated more frequently with the combination of two different antibiotics simultaneously (only 3.4% of patients in 2019 compared to 15.4% in 2022, p = 0.01). Primary infections with varicella zoster virus in 2022 led to a more severe course of the disease.

Effectiveness and Safety of Direct-acting Antivirals for Treatment of Adolescents With HCV/HIV Coinfection: Real-world Data From Europe.

We evaluated the effectiveness and safety of direct-acting antivirals in adolescents with hepatitis C (HCV)/HIV coinfection using pooled individual patient-level data from 5 European cohorts. Of 122 participants in follow-up from November 2013 to August 2021, 19 were treated <18 years of age; of 15 with HCV RNA available at/after 12 weeks post-treatment, all had sustained virologic response with acceptable safety. This evidence addresses an important gap in knowledge of treatment outcomes in adolescents with HCV/HIV coinfection in real-life settings.

Health-related quality of life in patients aged 6-18 years with chronic hepatitis C treated with sofosbuvir/velpatasvir.

BACKGROUND & AIMS: The aim of this study was to assess the effect of treatment with sofosbuvir/velpatasvir (SOF/VEL) on the health-related quality of life (HRQL) of children with chronic hepatitis C. METHODS: In the non-commercial, non-randomized, open-label PANDAA-PED study, 50 children aged 6-18 years with chronic hepatitis C were treated with a fixed dose of SOF/VEL. All patients achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Evaluation of HRQL was performed twice: at baseline (before the treatment) and during the SVR12 analysis using the KIDSCREEN-27 questionnaires, which included 5 dimensions of HRQL, for child self-reporting and parent proxy reporting. The normal range for the population was set to T values of 50 ± 10 points. Child-parent agreement was analysed using the intra-class correlation coefficient (ICC) and Bland-Altman test. RESULTS: Mean T values were within the normal range for all dimensions, both before and after treatment. There was a significant improvement in physical well-being based on the children's self-assessment (from 48.53 to 51.21, p = .03). In addition, a trend towards better scores in the 'social support & peers' part of the parent proxy evaluation (from 45.98 to 48.66, p = .06) was noticed. After the treatment, the proportion of children self-assessing their physical well-being as below normal significantly decreased from 17% to 5% (p = .007). HRQL scores were not associated with patients' sex, but in most cases, younger age correlated with better HRQL. Evaluation of the ICC for child self-reports versus parent proxy reports revealed poor to moderate agreement for most single measures. Bland-Altman analysis showed that in all dimensions, both before and after treatment, the limits of agreement (LoAs) exceeded ±5 points (half of the SD and considered a maximum allowed difference). CONCLUSIONS: A significant proportion of children with chronic hepatitis C have decreased HRQL in all dimensions, but effective treatment with SOF/VEL leads to an improvement in some areas of well-being. As the effect of HCV on HRQL is more pronounced in older patients, treatment of younger children should be indicated to prevent them from experiencing decreased HRQL due to ongoing HCV infection in the future.

Real-World Efficacy and Safety of an 8-Week Glecaprevir/Pibrentasvir Regimen in Children and Adolescents with Chronic Hepatitis C-Results of a Multicenter EpiTer-2 Study.

The aim of the study was to analyze the effectiveness and safety of anti-HCV treatment based on a pangenotypic direct-acting antiviral (DAA) regimen with glecaprevir/pibrentasvir (GLE/PIB) in children. The multi-center study was conducted in HCV-infected children who were treated in the period from November 2022 to January 2023. The analysis included 23 pediatric patients with a mean (SD) age of 9.61 (3.68) years. The cohort included 13 girls and 10 boys. The most common HCV genotypes were GT1b (n = 9, 39.1%), GT1a (n = 6, 26.1%) and GT3 (n = 5, 21.7%). The SVR was assessed at 12 weeks after the end of treatment and was 100% for both girls and boys. The conducted study showed a very good tolerance of the treatment in the entire analyzed group and confirmed a very high efficacy and safety for 8-week treatment with GLE/PIB in children over three years of age. It seems that our study is the first on the real-world use of an 8-week GLE/PIB pangenotypic therapy in a group of children aged 3-12 years and the first in Europe for adolescents aged 12-17.

Ukrainian War Refugee Children With Particularly Severe Viral Infections: A Case Series Report.

The humanitarian crisis in Ukraine in 2022 led to a massive migration of refugees to Poland. Immigrant children, living in overcrowded humanitarian hubs, were exposed to multiple stressful factors likely affecting their immune systems. This case series study aimed to describe a particularly severe course of common viral infections, in Ukrainian refugee children. We present 2 case series of Ukrainian refugee children: 5 hospitalized due to either adenovirus (AdV) and 8 with rotavirus (RV) infection, admitted within 3 months in each case series, recruited retrospectively. Most patients lived in humanitarian hubs and were neglected on admission (dehydrated, with poor hygiene and anxious). All RV infection cases had symptoms of severe gastroenteritis requiring intravenous rehydration. Metabolic acidosis was present in 6 children, and hypoglycemia in 4 participants. None of them were vaccinated against RV. All children with AdV infection had prolonged fever, dyspnea requiring oxygen therapy and hyperinflammation. In 2 AdV infection cases with no clinical improvement and increasing inflammatory markers, intravenous immunoglobulins and glucocorticosteroids were used. The combination of stressful factors and living in overcrowded hubs during the high prevalence of viral infections led to a particularly severe course of viral infections in Ukrainian refugee children.

Differences in Clinical Presentation of COVID-19 in Children Hospitalized During Domination of Early (BA.1, BA.2) and Late (BA.5, BA.2.75, BQ.1 and XBB.1.5) SARS-CoV-2 Omicron Subvariants.

This study analyzed data for 1098 children: 575 diagnosed with COVID-19 between January and June 2022 (early Omicron) and 523 hospitalized from July 2022 to April 2023 (late Omicron). New Omicron subvariants lead to similar recovery rates without deaths and acute respiratory distress syndrome in children as BA.1 and BA.2, however, they more often cause fever and croup. Children suffering from comorbidities, presenting with pulmonary lesions and older, may be prone to a more severe consequences of COVID-19 in terms of the currently dominating Omicron subvariants.

Key Considerations during the Transition from the Acute Phase of the COVID-19 Pandemic: A Narrative Review.

The COVID-19 pandemic has been met with an unprecedented response from the scientific community, leading to the development, investigation, and authorization of vaccines and antivirals, ultimately reducing the impact of SARS-CoV-2 on global public health. However, SARS-CoV-2 is far from being eradicated, continues to evolve, and causes substantial health and economic burdens. In this narrative review, we posit essential points on SARS-CoV-2 and its responsible management during the transition from the acute phase of the COVID-19 pandemic. As discussed, despite Omicron (sub)variant(s) causing clinically milder infections, SARS-CoV-2 is far from being a negligible pathogen. It requires continued genomic surveillance, particularly if one considers that its future (sub)lineages do not necessarily have to be milder. Antivirals and vaccines remain the essential elements in COVID-19 management. However, the former could benefit from further development and improvements in dosing, while the seasonal administration of the latter requires simplification to increase interest and tackle vaccine hesitancy. It is also essential to ensure the accessibility of COVID-19 pharmaceuticals and vaccines in low-income countries and improve the understanding of their use in the context of the long-term goals of SARS-CoV-2 management. Regardless of location, the primary role of COVID-19 awareness and education must be played by healthcare workers, who directly communicate with patients and serve as role models for healthy behaviors.

Parents' Attitudes towards Vaccinations Regarding the Ukrainian Migration to Poland in 2022.

Background: Russia's aggression against Ukraine in early 2022 resulted in a large migration of refugees to many countries, including Poland. Vaccination coverage for some infectious diseases in Ukraine is lower than in Poland; consequently, the incidence of infectious diseases-including measles, poliomyelitis, tuberculosis, and COVID-19-is higher. We aimed to investigate whether the migration of Ukrainians had influenced decisions of Polish parents on having their children vaccinated and to examine their attitudes towards vaccinations. Material and methods: A cross-sectional online survey study was designed. Data on parents' demographics, attitudes toward vaccination, and knowledge of the current epidemiological situation in Poland were collected. Parents participating in the study were divided into two subgroups for further analysis according to their decisions to have their children vaccinated. Results: A total of 568 questionnaires were collected, of which 21 did not meet the inclusion criteria for the analysis (respondents were not parents). The Ukrainian immigrants' influx affected 54 (9.87%) participants in their decision of having their children vaccinated. Respondents in this group were more likely to have a positive attitude toward recommended vaccinations (p = 0.0428); in addition, they more often had their children vaccinated with recommended vaccinations (p = 0.0063), believed the vaccination coverage with mandatory vaccinations was higher in Poland than in Ukraine (p = 0.0014), and believed the incidence of diseases covered by mandatory (p = 0.0472) and recommended (p = 0.0097) vaccinations was higher in Ukraine. In addition, parents who declared that the migration had affected their decision regarding their children's vaccinations had more often been vaccinated due to the influx of Ukrainian immigrants (p < 0.00001) and were more likely to be aware of how migration had impacted the current epidemiological situation in Poland (p = 0.0021). Moreover, the survey more often made these participants think about getting additional vaccinations for themselves (p < 0.0001) and their children (p < 0.0001). Conclusions: The Ukrainian immigrants' influx affected nearly one tenth of surveyed parents in their decision of having their children vaccinated. This group was more aware of the differences between infectious diseases' epidemiology in Poland and Ukraine. In addition, they also had a more positive attitude toward vaccinations.

Efficacy and safety of treatment with sofosbuvir/velpatasvir in patients aged 6-18 years with chronic hepatitis C-Results of the PANDAA-PED study.

BACKGROUND AND AIMS: The aim of this non-commercial, open-label, real-life, non-randomized clinical trial was to analyse the efficacy and safety of a pangenotypic regimen sofosbuvir/velpatasvir (SOF/VEL) in patients aged 6-18 years with chronic hepatitis C virus (HCV) infection. METHODS: Fifty patients qualified for the 12-week treatment were divided into two weight groups: 15 children weighting between 17 and <30 kg received a fixed dose of 200/50 mg of SOF/VEL (tablet) once daily, and 35 patients weighting ≥30 kg were treated with 400/100 mg SOF/VEL. The primary endpoint of the study was efficacy defined as sustained viral response (undetectable HCV RNA using an real-time polymerase chain reaction method) at 12 weeks posttreatment (SVR12). RESULTS: Median age of the participants was 10 (IQR 8-12) years, 47 were infected vertically, and 3 patients were previously ineffectively treated with pegylated interferon and ribavirin. Thirty-seven participants were infected with HCV genotype 1, 10 with HCV genotype 3 and the remaining 3 with genotype 4. There was no case of cirrhosis. SVR12 was 100%. Thirty-three reported adverse events (AEs) were considered related to the administration of SOF/VEL, all of them were mild or moderate. Children presenting with AEs were older compared to these without AEs: 12 (9.5-13) versus 9 (IQR 8-11) years (p = 0.008). CONCLUSIONS: Results of the PANDAA-PED study indicated a 100% effectiveness of a 12-week therapy with SOF/VEL in children aged 6-18 years with chronic HCV infection and its good safety profile, in particular in younger patients.

The clinical course of herpes zoster is similar in immunocompetent and immunocompromised paediatric patients.

AIM: We aimed to compare the clinical manifestation of HZ in immunocompetent and immunocompromised children. METHODS: Medical charts of all consecutive children hospitalized and/or consulted in the Regional Hospital for Infectious Diseases in Warsaw due to HZ were retrospectively analysed. Age, history of varicella, time interval between varicella and HZ, underlying diseases, immunosuppresive therapy, dermatome involvement and HZ complications were analyzed in both groups. RESULTS: In total 152 children were included in the analysis, 56 (36.84%) of them were hospitalsed, whereas 96 (63.16%) were consulted and discharged home due to good general condition. The median age was 10 years (IQR 5.75-12), there were 73 (48.03%) boys and 79 (51.97%) girls. In 16/152 (10.5%) one or more complications occurred, including: skin bacterial superinfection (16/17, 94.2%), sepsis (1/17, 5.9%), meningitis (1/17, 5.9%). Thoracic dermatomes were the most commonly affected (81/152, 53.29%). Most of the children didn't have any immunodeficiencies 118/152 (77.6%), and 34/152 (22.4%) of them were immunocompromised (and had been treated with intravenous acyclovir). The clinical picture of the disease was similar in both groups (Table 1). However, immunocompromised children more often had sacral dermatomes affected (5/35, 14.3% vs. 1/117, 0.9%, p < 0.001), and less often thoracic dermatomes were involved in this group (12/35, 34.3% vs. 69/117, 59%, p = 0.0102). CONCLUSIONS: To conclude, herpes zoster occurs in both immunocompetent and immunocompromised children. Clinical manifestations are similar. Serious complications, although uncommon, affect not only immunocompromised patients but also otherwise healthy children.

Epstein Barr Virus Hepatitis-A Mild Clinical Symptom or a Threat?

The present study aimed to characterize pediatric patients diagnosed with hepatitis associated with primary Epstein-Barr Virus (EBV) infection. We described the changes in liver aminotransferases activity during the disease, and we analyzed the results of abdominal ultrasonography. A retrospective study was performed by analyzing the medical records of 166 immunocompetent children diagnosed with primary EBV hepatitis hospitalized at the Department of Children's Infectious Diseases, Medical University of Warsaw, Regional Hospital of Infectious Diseases in Warsaw, between August 2017 and March 2023. Elevated alanine aminotransferase (ALT) activity was noted in the first three weeks of the disease. In 46.3% of patients, ALT values exceeded five times the upper limit of the laboratory norm in the first week of illness. Aspartate aminotransferase activity increased from the first to fourth week from the onset of symptoms and showed two peaks in the first and third weeks. The changes over time of mean AST activity demonstrated significance. Transient cholestatic liver disease was the predominant type of hepatic involvement in 10.8% of children; 66.6% of them were older than 15 years. Clinical and ultrasound criteria of acute acalculous cholecystitis (AAC) were met in three female patients over 16 years of age. Hepatitis associated with primary EBV infection is usually a mild and self-limiting condition. Significantly elevated values of liver enzymes with features of cholestatic liver disease may occur in patients with a more severe course of the infection.

Clinical Course and Severity of COVID-19 in 940 Infants with and without Comorbidities Hospitalized in 2020 and 2021: The Results of the National Multicenter Database SARSTer-PED.

This study aimed to analyze the differences in severity and clinical characteristics of COVID-19 in infants hospitalized in Poland in 2021, when the dominance of variants of concern (VOCs) alpha and delta was reported, compared to 2020, when original (wild) SARS-CoV-2 was dominant (III-IV vs. I-II waves of the pandemic, respectively). In addition, the influence of the presence of comorbidities on the clinical course of COVID-19 in infants was studied. This multicenter study, based on the pediatric part of the national SARSTer database (SARSTer-PED), included 940 infants with COVID-19 diagnosed between March 1, 2020, and December 31, 2021, from 13 Polish inpatient centers. An electronic questionnaire, which addressed epidemiological and clinical data, was used. The number of hospitalized infants was significantly higher in 2021 than in 2020 (651 vs. 289, respectively). The analysis showed similar lengths of infant hospitalization in 2020 and 2021, but significantly more children were hospitalized for more than 7 days in 2020 (p < 0.009). In both analyzed periods, the most common route of infection for infants was household contact. There was an increase in the percentage of comorbidities, especially prematurity, in children hospitalized in 2021 compared to 2020. Among the clinical manifestations, fever was predominant among children hospitalized in 2021 and 2020. Cough, runny nose, and loss of appetite were significantly more frequently observed in 2021 (p < 0.0001). Severe and critical conditions were significantly more common among children with comorbidities. More infants were hospitalized during the period of VOCs dominance, especially the delta variant, compared to the period of wild strain dominance, even though indications for hospitalization did not include asymptomatic patients during that period. The course of COVID-19 was mostly mild, characterized mainly by fever and respiratory symptoms. Comorbidities, particularly from the cardiovascular system and prematurity, were associated with a more severe course of the disease in infants.

The Influence of SARS-CoV-2 Variants B.1.1.7 and B.1.617.2 on a Different Clinical Course and Severity of COVID-19 in Children Hospitalized in 2021 Compared With 2020.

BACKGROUND: This study aimed to analyze the differences in the epidemiologic and clinical characteristics of coronavirus disease 2019 (COVID-19) in children hospitalized in 2021, when the severe acute respiratory syndrome coronavirus 2 variants B.1.1.7 (alpha) and B.1.617.2 (delta) dominated, compared with 2020. METHODS: In this multicenter study based on the pediatric part of the national SARSTer register (SARSTer-PED), we included 2771 children (0-18 years) with COVID-19 diagnosed between March 1, 2020, and December 31, 2021, from 14 Polish inpatient centers. An electronic questionnaire, which addressed epidemiologic and clinical data, was used. RESULTS: Children hospitalized in 2021 were younger compared with those reported in 2020 (mean 4.1 vs. 6.8 years, P = 0 .01). Underlying comorbidities were reported in 22% of the patients. The clinical course was usually mild (70%). A significant difference in the clinical course assessment between 2020 and 2021 was found, with more asymptomatic patients in 2020 and more severely ill children in 2021. In total, 5% of patients were severely or critically ill, including <3% of the participants in 2020 and 7% in 2021. The calculated mortality rate was 0.1% in general and 0.2% in 2021. CONCLUSION: Infections with severe acute respiratory syndrome coronavirus 2 variants alpha and delta lead to a more severe course of COVID-19 with more pronounced clinical presentation and higher fatality rates than infection with an original strain. Most of the children requiring hospitalization due to COVID-19 do not have underlying comorbidities.

HBV and HCV Infection in Children and Adolescents.

Hepatitis B (HBV) and C (HCV) infections are the major causes of chronic liver disease and are associated with significant morbidity and mortality [...].

The influence of steroid therapy of complications of infectious mononucleosis on the course of Epstein-Barr virus hepatitis.

Aim of the study: The purpose of the study was to characterize the differences in the course of Epstein-Barr virus (EBV) primary infection-induced hepatitis between patients treated with steroids due to complications of infectious mononucleosis (IM) and those not receiving such therapy. Material and methods: We analyzed the changes in the activity of liver enzymes and differences in abdominal ultrasound results. The study was based on reviewing the medical records of children hospitalized for primary EBV infection at the Department of Children's Infectious Diseases, Medical University of Warsaw, Regional Hospital of Infectious Diseases in Warsaw, between August 2017 and March 2023. The study population was divided into two groups: patients treated with steroids (Group 1) and children not receiving steroids (Group 2). Results: Significant differences were obtained for alanine aminotransferase activity only in the first week of IM (205.34 ±115.40 vs. 288.82 ±170.16 IU/l for Group 1 and 2, respectively; p = 0.024), and for aspartate aminotransferase in the first (170.63 ±159.47 vs. 218.85 ±128.22 IU/l for Group 1 and 2, respectively; p = 0.009) and the third week (151.09 ±138.57 vs. 235.50 ±170.27 IU/l for Group 1 and 2, respectively; p = 0.016). The analysis of the results of laboratory tests for the diagnosis of cholestasis (γ-glutamyl transferase and total serum bilirubin concentrations with fractions) did not show significant differences between the groups. Conclusions: Our results indicated that the two cohorts of patients may differ in the course of hepatitis associated with primary EBV infection, especially at the beginning of the disease, when the laboratory features of hepatitis were less pronounced in children treated with steroids.

Comparison of the prevalence of risk factors for Toxoplasma Gondii infection among pregnant women in rural and urban areas in Poland.

Introduction: Toxoplasma gondii is a protozoan parasite. While this infection typically exhibits no symptoms in humans, it poses a potential threat to the developing fetus in pregnant women. Several risk factors contribute to toxoplasmosis infection. Adherence to hygiene protocols and avoiding the consumption of raw meat, unwashed vegetables, and fruits may mitigate the risk of this disease. Objective: This study aimed to compare the prevalence of toxoplasmosis risk factors among pregnant women suspected of toxoplasmosis living in rural areas with those residing in urban areas. Materials and methods: A retrospective observational study was conducted by analyzing data from the medical records of pregnant women suspected of toxoplasmosis. These women were consulted at the Provincial Infectious Diseases Hospital between September 2019 and March 2020. The analysis encompassed patients' demographic data and information concerning toxoplasmosis risk factors. A total of 273 women's data were included in the analysis. Diagnosis relied on serological verification using the VIDAS® analyzer (bioMérieux, Lyon, France). Results: Women residing in rural areas were less likely to report a good socio-economic status (p=0.0064), and toxoplasmosis infection was less frequently ruled out (p=0.0023). In comparison to women living in urban areas, pregnant women from rural regions were more likely to have confirmed primary toxoplasmosis (p=0.0164). Additionally, they were more prone to working in gardens without gloves (p<0.0001), consuming unwashed vegetables (p=0.0025), eating raw meat during pregnancy (p=0.0008), and cats caregiving during pregnancy (p=0.0002). This exposure included both care for domestic cats before and during pregnancy (p=0.0069) and interactions with wild cats (p<0.0001). Conclusions: Pregnant women living in rural areas exhibited significantly higher exposure to toxoplasmosis risk factors. They also displayed a higher incidence of primary infections during pregnancy and a lower rate of excluded infections.