Epidemiological investigation of hepatitis C virus infections among children in oncohematology departments

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Abstract

The aim of this study was to conduct an epidemiological analysis of hepatitis C infection in children with oncohematological diseases (OHD) using phylogenetic analysis of HCV nucleotide sequences and to analyze the causes and factors of HCV nosocomial transmission.

Materials and methods. A retrospective analysis of HCV genetic isolates obtained from children with oncohematological diseases treated at the «Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology» (the Center) was conducted. The analysis included all children with HCV markers (anti-HCV and/or HCV RNA) identified between 2013 and 2025 during hospitalization and treatment at the Center—a total of 146 children. The children's ages ranged from 0 to 18 years, and from September 1, 2022, to 21 years. Samples were taken from the Center's bacteriology laboratory collection. Genotyping and phylogenetic analysis were performed at the Central Research Institute of Epidemiology of Rospotrebnadzor for 30 patient blood samples containing HCV RNA in quantities sufficient for analysis (at least 1000 IU/mL). To compare the distribution of HCV genotypes, the VGARus database data from 997 individuals was used. The core/E1 region of the HCV genome was sequenced and a phylogenetic analysis was performed. A Bayesian approach was used with the BEAST2 software package. The tree was visualized using FigTree.

Results. In the structure of HCV genotypes isolated from children in the oncohematology departments, genotype 3a was predominant (77%), while 1b accounted for 23%. In contrast to the general population, where genotypes 3a and 1b circulate with equal frequency, the prevalence of genotype 3a among children with OHD indicates a greater involvement of this genotype in cases of nosocomial infection. Phylogenetic analysis revealed three common HCV clusters: 14 children with genotype 3a (13 children from the Amur Region and 1 child from the Altai Krai) and two common clusters with genotype 1b (2 patients each from the Kyrgyz Republic and Uzbekistan). The majority of HCV infection cases in children with OHD (60%) were nosocomial in origin. Cases of HCV infection in children from the Amur Region are associated with a long-standing chronic HCV epidemic in the oncohematology department of the Amur Regional Children's Clinical Hospital. No cases of infection have been identified at the Center. A patient from the Altai Krai region may have been infected at the Center in 2013-2014 during blood collection from a central venous catheter (CVC) due to improper hand sanitization, glove changing, aseptic technique, or work surface zoning. Standardization of procedures, implementation of aseptic non-touch technique (ANTT), training, and monitoring of staff knowledge and skills, widely implemented in the Center's work, have demonstrated high effectiveness, resulting in the absence of HCV transmission cases for over 10 years.

Conclusion. Nosocomial HCV transmission in the OHD departments requires the widespread implementation of modern approaches to preventive and anti-epidemic measures, such as aseptic non-touch technique (ANTT), standardization of procedures, staff training, and knowledge and skills audits.

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Introduction

Children with oncohematological diseases (OHD) are a high-risk group for hepatitis C infection. Given the severity of their underlying disease, the duration of treatment and subsequent rehabilitation, and multiple comorbid conditions, infection with the hepatitis C virus (HCV) significantly complicates their long-term journey to recovery.

In Russia, the literature on infection rates of children with OHD is represented by a single study covering the years 2014–2020, according to which the prevalence rates of HCV, hepatitis B virus (HBV), and HIV infection among children with OHD were 1.7%, 0.2%, and 0.1%, respectively, and exceeded the prevalence rates of HCV, HBV and HIV infection among the country’s population aged 0–19 years by 50, 6, and 3 times, respectively [1]. In foreign sources, information on infection rates among children with OHD in the general population is currently provided by developing countries where the problem remains relevant; for example, in Egypt, the prevalence of OHD among children in the general population was 39.2% [2].

Descriptions of epidemic foci of blood-borne infections in available Russian literature are represented by a single study describing a large chronic epidemic focus of HCV among children in the general population in the Amur Region in 2012–2018, involving 169 children. Possible causes of the widespread transmission of HCV included violations of venous catheter care protocols, including the reuse of non-sterile catheter caps; flushing catheters with a solution drawn from a shared multi-dose vial; possibly, the use of a shared syringe to flush catheters in multiple patients; breaches of instrument sterility during capillary blood collection for laboratory testing; and the administration of various drug solutions drawn from a shared container [3]. Foreign publications describing outbreaks of blood-borne infections in primary healthcare facilities mainly refer to the period prior to 2013, which is due to the lack of outbreak reporting in recent years. The causes of the described outbreaks were multiple violations related to standard preventive measures: separation of “clean” and “dirty” zones, reuse of stopper plugs, violations of hand hygiene protocols, improper waste management, contaminated multi-dose vials of saline solution for flushing venous catheters, and reuse of single-dose vials [4].

High infection rates and the identification of a long-standing HCV outbreak among children with OHD highlight the urgency of this issue in Russia, which necessitates an investigation into the causes and factors contributing to child infections in order to implement modern preventive measures.

Currently, genotyping and phylogenetic analysis are an integral part of epidemiological investigations of HCV infections associated with healthcare settings. Phylogenetic analysis of HCV nucleotide sequences, combined with methods of classical epidemiological analysis, allows for the establishment of epidemiological links between cases of blood-borne infections, the analysis of infection factors, and the implementation of the necessary set of preventive and anti-epidemic measures1. The global experience of successfully applying phylogenetic analysis in investigating cases of HCV transmission during the provision of medical care, including in pediatric OHD departments of general hospitals, spans more than 20 years [5, 6]. The investigation of the aforementioned chronic HCV outbreak in the Amur Region was also conducted using phylogenetic analysis of HCV sequences isolated from the affected children [3].

The aim of this study was to establish an epidemiological link between HCV infection cases among children with OHD who were treated at the Dmitry Rogachev National Medical Research Center for Pediatric Hematology, Oncology and Immunology (the Center) using phylogenetic analysis of HCV nucleotide sequences, and to investigate possible causes and factors of HCV infection among children at the Center.

Materials and methods

A retrospective analysis was conducted of HCV sequences isolated from children with OHD who were treated at the Center. The analysis included all children with HCV markers (anti-HCV and/or HCV RNA) identified between 2013 and 2025 during hospitalization and treatment at the Center—146 children. The ages of the children observed ranged from 0 to 18 years; starting September 1, 2022, the age limit was extended to 21 years. Samples were taken from the Center’s bacteriology laboratory collection, with registration numbers ranging from 1 to 146. The Center is the federal leading pediatric oncohematology institution where children from all regions of the country with hematological and oncological diseases and congenital immune defects undergo examination and treatment, receiving specialized and high-tech care that is unavailable in their place of residence. The Center includes the “Russian Field” Clinical Rehabilitation Research Center (CRRC), where children undergo follow-up observation and rehabilitation.

HCV genotyping and phylogenetic analysis was performed at the Central Research Institute of Epidemiology of Rospotrebnadzor for patient blood samples containing HCV RNA at a concentration of at least 1,000 IU/mL. The analysis included 30 samples suitable for testing; in all other samples, HCV RNA was not detected or its concentration was less than 1,000 IU/mL. Quantitative determination of HCV RNA was performed using the AmpliSens HCV-Monitor-FL reagent kit; HCV genotyping was performed using the AmpliSens HCV-Genotype-FL reagent kit (Central Research Institute of Epidemiology).

To compare the distribution of HCV genotypes among the study cohort and the general Russian population, we used HCV genotyping results from 997 individuals based on the VGARus database of the Reference Center for Viral Hepatitis Monitoring at Rospotrebnadzor. The comparison group consisted of individuals of all ages from various regions of the country.

For the purpose of genetic identification and differentiation of viral genotypes, the HCV core/E1 region of the genome was sequenced, and a phylogenetic analysis was performed based on these sequences. For this purpose, RNA was isolated from 140 μL blood serum samples using the QIAamp Viral RNA Mini Kit (Qiagen). Reverse transcription was performed with random hexamer primers using the MMLV RT reagent kit (Eurogen). The resulting cDNA was amplified by PCR using previously described primers targeting the HCV Core and E1 genomic regions (nucleotide positions 273–1315 according to the reference sequence of HCV 1a strain H77, GenBank No. AF011753) using the Tersus Plus PCR kit (Eurogen) [7]. Negative controls (PCR water) were used at all stages of the PCR procedure (RNA extraction, first and second PCR rounds) to monitor for contamination. The 942-nucleotide amplification product was excised from the gel and isolated from agarose using the QIAquick Gel Extraction kit (Qiagen). Sequencing was performed on a 3500 Genetic Analyzer (ABI) using the Big Dye Terminator v 3.1 Cycle Sequencing Kit.

Phylogenetic analysis of the obtained HCV sequences was performed using a Bayesian approach implemented in the BEAST2 software package. Reference sequences were used to determine the genotype, in accordance with the ICTV recommendations dated March 9, 2022. To determine the relationships among the analyzed samples, all available archived HCV sequences from the working collection, isolated within Russia, were added to the sample set, including 51 sequences from the children’s regions of origin, isolated from patients with no epidemiological link to the children included in the study. Furthermore, 10 sequences from the international GenBank database that showed the highest degree of identity were added to each sample under study. For all sequences, the year and country of collection were known; for Russia, the city/region was also known. The run parameters were as follows: BEAST Model Test, relaxed log-normal clock with an initial mutation rate of 5.58 × 10–4 substitutions/site/year, and a population model of a merging constant population. The length of the Markov chain Monte Carlo simulation was 50 million generations. The selection and refinement of the phylogenetic analysis methodology have been described previously [8]. The reliability of the results was assessed using the Tracer program; the ESS of all parameters was greater than 200. The tree was visualized using the FigTree program.

Based on the results of the phylogenetic analysis, an epidemiological analysis was conducted to identify the causes and factors of infection among children whose HCV sequences formed common clusters. The epidemiological analysis was conducted only for children who were infected at the Center, using the available information specified in the patients’ medical records. The following data from medical records were used: dates of hospitalization, ward of stay, invasive procedures, as well as data from the medical history collected upon admission, namely the dates of hospitalization in other pediatric OHD hospitals and information on detected HCV markers.

Statistical analysis of the obtained data was performed using the R software environment, version 4.4.2. The statistical significance of differences was calculated using the Pearson χ² test, since the frequency values in the contingency table were greater than 5. The frequency of HCV genotype detection was characterized by relative frequency and 95% confidence intervals. The level of statistical significance in this study was set at p ≤ 0.05.

Results

HCV genotyping in samples from children in pediatric OHD departments revealed a predominance of HCV genotype 3a—23 patients, 77% (95% confidence interval (CI) 57–89%); HCV genotype 1b was detected in 7 patients — 23% (95% CI 11–43%). The majority of HCV genotype 3a genetic isolates were from children in the Amur Region, which accounted for 56% of cases of genotype 3a detection (13 out of 23 children) (Table 1).

 

Table 1. Characteristics of HCV-infected children in pediatric OHD departments identified between 2013 and 2025 during their stay at the Center

HCV genotype

Date of the first detection of HCV markers at the Center

Region/country

1b

19.10.2015

Penza Region

1b

19.04.2016

Tver Region

1b

29.06.2016

Orenburg Region

1b

12.09.2018

Penza Region

1b

18.11.2021

Kyrgyz Republic

1b

10.04.2025

Republic of Uzbekistan

1b

03.06.2025

Republic of Uzbekistan

3а

26.11.2013

Amur Region

3а

11.06.2014

Republic of Chuvashia

3а

19.02.2014

Altai Krai

3а

04.12.2014

Moscow Region

3а

06.05.2015

Tver Region

3а

28.05.2015

Amur Region

3а

11.06.2015

Amur Region

3а

17.06.2015

Amur Region

3а

11.11.2015

Krasnodar Krai

3а

10.01.2017

Amur Region

3а

19.09.2017

Amur Region

3а

20.11.2017

Astrakhan Region

3а

21.02.2018

Amur Region

3а

02.02.2017

Amur Region

3а

10.07.2018

Amur Region

3а

06.09.2018

Amur Region

3а

05.10.2018

Amur Region

3а

05.02.2019

Amur Region

3а

06.03.2019

Omsk Region

3а

18.10.2019

Amur Region

3а

21.07.2020

Penza Region

3а

24.08.2021

Novosibirsk Region

3а

21.01.2025

Moscow

 

A comparison was conducted of the distribution of HCV genotypes identified among children in pediatric OHD departments and the general population of Russia, based on data from the VGARus database (n = 997). HCV genotypes 3a and 1b occur with the same frequency in the Russian population—44% (95% CI 41–47%) and 48% (95% CI 45–51%).

A statistically significant difference was found between the frequency of HCV genotypes 3a and 1b among children in pediatric OHD departments and the general population. HCV genotype 3a was more common among children in pediatric OHD departments (77%) than in the general population (χ² = 12.553; p = 0.002), while HCV genotype 1b (23%) was less common (χ² = 7.134; p = 0.013). Thus, HCV genotype 3a predominated among children in pediatric OHD departments included in the study, with a higher detection rate than in the general population (Fig. 1).

 

Fig. 1. The distribution of HCV genotypes among children in pediatric OHD departments and the general population of Russia.

 

Phylogenetic analysis identified three major clusters (Fig. 2). The first cluster consisted of HCV genotype 3a sequences from 13 children in the Amur Region and one sample from the Altai Krai, indicating an epidemiological link between HCV infections in children from pediatric OHD departments in the Amur Region and the child from the Altai Krai. The second general cluster was formed by HCV genotype 1b sequences from 2 children from the Kyrgyz Republic (1 child registered in the Orenburg Region). The third general cluster was formed by HCV genotype 1b sequences from two children in the Republic of Uzbekistan. The remaining sequences were not linked to one another, which does not suggest an epidemiological link between them.

 

Fig. 2. Phylogenetic tree constructed based on the HCV core/E1 region (942 nt, positions 293–1234, numbered relative to the genome of the reference strain H77, GenBank No. AF011753).

The region and year of isolation are indicated for each sequence. Sequences from the present study are marked in red with the region/country of the patient’s origin indicated. Tree branches with a posteriori probability >90% are highlighted in red.

 

The results of the analysis of the causes and factors underlying epidemiologically linked cases of HCV infection among children with OHD are presented below.

First HCV cluster

An analysis of the timing of admission to the Center and the detection of HCV markers revealed that 8 children (Nos. 1, 3, 4, 5, 7, 10, 11, 12) were already infected with HCV at the time of their initial admission to the Center (Fig. 3).

 

Fig. 3. The periods of stay at the Center for 14 children (13 patients from the Amur Region and 1 patient from the Altai Krai) from HCV genotype 3a cluster.

 

All patients, except for child No. 2 from the Altai Krai, had been hospitalized at the Amur Regional Children’s Clinical Hospital (ARCCH) prior to the detection of HCV. Four children (Nos. 8, 9, 13, 14) did not have HCV markers upon initial admission to the Center; however, markers were detected during subsequent hospitalizations, which were preceded by periods of stay at the ARCCH; markers were detected either at the ARCCH or at the Center.

Patient No. 6 stayed at the Center for 4 months before HCV markers were detected; however, during this period, there were no other HCV-infected individuals from the analyzed cluster at the Center.

Thus, all children from the Amur Region were likely infected with HCV at the ARCCH; no cases of infection were identified at the Center among children from the Amur Region. The HCV outbreak involving genotype 3a at the ARCCH affected 169 children; it was chronic in nature and involved an artificial medical transmission route during procedures involving venous catheters [3].

Patient No. 2 from the Altai Krai has had the underlying condition since October 2013. Starting on November 15, 2013, he underwent examination at the Altai Krai Clinical Center for Maternal and Child Health. From November 21, 2013, to February 24, 2016, he underwent examination and treatment at the Center. During examinations upon admission to the Center on November 22, 2013, and subsequently on January 13, 2014, no HCV markers were detected in the patient. HCV RNA was first detected on February 19, 2014; on February 24, 2014, a quantitative HCV RNA analysis was performed, yielding a result of 106,893 copies/mL. On March 4, 2014, a diagnosis of acute viral hepatitis C was established: seronegative form, genotype 3a, moderate severity.

Patient No. 2 from the Altai Krai coincided with Patient No. 1 from the Amur Region in terms of the time and ward of stay at the Center (Fig. 3). No other medical facilities where Patient No. 2 could have been present at the same time as the children from the Amur Region were identified, according to medical records.

Patient No. 1 has had an underlying condition since September 25, 2012, and was admitted to the ARCCH on October 7, 2012. He was admitted to the Center on November 14, 2012, and was discharged on February 18, 2013, in remission; HCV markers were first detected during this hospitalization on November 26, 2012. From 11/06/2013, he continued treatment at ARCCH; however, a recurrence of the primary disease was suspected, and the patient was transferred to the Center on November 24, 2013. During an examination at the Center on November 26, 2013, the patient tested positive for anti-HCV, HCV RNA, and biochemical markers of liver cytolysis; the patient was not receiving antiviral treatment.

Patients No. 1 and No. 2 were in the same ward at the same time during two hospitalizations: from November 24, 2013, to December 28, 2013, and from February 5, 2014, to February 10, 2014. It is likely that the infection occurred during these periods in this ward. No information regarding the children’s shared stay in the same room has been preserved due to the statute of limitations.

An analysis was conducted of overlapping invasive procedures from November 24, 2013, to February 10, 2014. Patients underwent infusion therapy (intravenous administration of medications) via a central venous catheter (CVC), lumbar and bone marrow punctures, intrathecal and intramuscular administration of medications, and diagnostic blood sampling via a CVC. During both periods of concurrent hospitalization, patients had CVCs in place. Among the invasive procedures that coincided in date of performance were diagnostic venous blood sampling, infusion therapy, and CVC flushing with saline. An assessment of the statistical significance of the coincidences, including the calculation of risk ratios, was not performed due to an insufficient sample size (1 case of infection); therefore, the results of the analysis are hypothetical.

During their stay at the Center during the specified period, 13 patients underwent diagnostic venous blood draws on the same date (Table 2). Blood collection from the CVC at the Center was performed using a closed system, so transmission of HCV via contaminated surfaces during blood transfer into tubes is unlikely. HCV transmission during blood collection could have occurred if gloves or syringes were contaminated with blood. Possible causes included violations of hand hygiene protocols, failure to change gloves between patients, poor aseptic technique, inadequate work surface zoning, and the disposal of waste in the clean zone of the work surface, where syringes with open tips and unprotected needles in caps might have been present. Reuse of syringes and tube holders was never practiced at the Center, and it is unlikely that this could have been a factor in HCV transmission. When drawing blood from the CVC, gloves and waste are typically heavily contaminated with blood and pose high infection risks, as blood is always squeezed out of the catheter when a syringe/syringe-tube/tube holder is attached to the cannula (port) and lands on the gloves.

 

Table 2. The duration of children’s concurrent stays in the ward, the dates of their concurrent stays, and the number of concurrent invasive procedures by date (absolute numbers)

Date of admission to the Center ward

Periods of joint stay at the Center

Venous blood sampling from the central venous catheter performed on the same date, number of procedures

рatient No. 1

рatient No. 2

24.11.2013–28.12.2013

26.11.2013 — HCV RNA

21.11.2013–04.01.2014

24.11.2013–28.12.2013

12

05.02.2014–14.02.2014

12.01.2014–10.02.2014

05.02.2014–10.02.2014

1

 

18.02.2014–24.03.2014

19.02.2014 — HCV RNA

  

 

Throughout both periods of the patients’ concurrent stay in the ward, they received continuous infusion therapy. The patients did not receive any medications on the same date, so contamination via a contaminated medication vial could not have occurred. Simultaneously with infusion therapy and blood collection from the CVC, the venous catheter is flushed, which is an integral part of the procedure for performing these manipulations. The patients may have used the same vials of saline solution. The Center uses multi-dose vials of saline solution for flushing catheters with a volume of 0.5–1.0 L; however, the solution is drawn into syringes in a separate room designated solely for this purpose, to which patients and caregivers are prohibited from entering. Therefore, the reuse of syringes and, consequently, contamination of the multi-dose vials is ruled out. The actual catheter procedures—such as administering infusions, drawing blood, and flushing the catheter—were performed in the patient’s room (all rooms are double occupancy) in this ward, so it cannot be ruled out that there may have been other sources of contamination for infusion solutions already drawn into syringes—for example, due to a violation of the work surface zoning described above, or due to a violation of hand hygiene, glove change, and aseptic technique protocols. Reuse of syringes, stoppers, infusion lines, and drug vials was never practiced at the Center and is unlikely to have been a factor in HCV infection.

Thus, the child from the Altai Krai could have been infected in 2013–2014 during blood collection from the CVC if staff failed to follow hand hygiene protocols, glove-changing procedures, aseptic techniques, and work surface zoning.

Second HCV cluster

The first patient underwent examination and treatment at the Center from November 19, 2013, to December 19, 2014, and the second from August 6, 2021, to August 13, 2021. HCV transmission at the Center could not have occurred because the children’s stays were not concurrent. According to their medical histories, both children underwent examination and treatment at their place of residence in the Kyrgyz Republic at the Department of Pediatric Oncology and Hematology of the National Oncology Center of the Kyrgyz Republic: the first patient in September 2013, and the second in November 2016. There were no periods during which the patients were simultaneously present at the clinic where they were treated; furthermore, the pediatric HCV infections occurred over a significant time span — three years elapsed between the probable periods of infection. It can be assumed that the HCV outbreak at the facility where the children were treated is of significant scale. Since the child was not infected at the Center, an analysis of the causes and factors of HCV infection was not conducted.

Third HCV cluster

The first child underwent examination and treatment at the Center from April 9, 2025, to April 11, 2025, and the second from June 2, 2025, to July 1, 2025. HCV infection could not have occurred at the Center because the children’s stays were not concurrent. According to their medical histories, both children underwent examination and treatment at their place of residence in the Republic of Uzbekistan; the first from May 2024 to April 2025 (facility unknown), and the second was treated at the Zangianatin Children’s Hospital from November 2024 to May 2025. The HCV infection cases from the Republic of Uzbekistan coincided in terms of the timing of the patients’ examination and treatment. It is likely that the children became infected with HCV at the Zangianatin Children’s Hospital during their concurrent stay there from November 2024 to April 2025. Since the child was not infected at the Center, an analysis of the causes and factors of HCV infection was not conducted.

Discussion

In contrast to the general population, where genotypes 3a and 1b circulate with equal frequency, a predominance of genotype 3a (77%) was observed among children in the pediatric intensive care units monitored at the Center, indicating that this genotype is more frequently involved in cases of nosocomial transmission. The majority of children with genotype 3a were patients from the Amur Region, which accounted for 56% (13/23) of the identified HCV genotypes 3a. The data obtained characterize only a portion of the analyzed cohort, as samples with low viral loads were not included in the analysis.

Comparable data from the foreign literature are limited in number and primarily relate to an earlier period (before 2000), when the problem of nosocomial HCV transmission was acute against the backdrop of unsafe blood transfusions, and the prevalence of HCV markers among oncohematology patients was 35.7% [9]. Studies conducted among children treated for OHD prior to 2000 indicate a predominance of genotypes 1b and 3a [10–12]. With the introduction of blood donor screening, the prevalence of HCV markers among OHD patients decreased to 5.2% over the following 20 years, and the problem became less relevant [9]. Despite significant progress in blood transfusion safety, the importance of nosocomial HCV transmission remains. There are virtually no recent studies on this topic, which underscores the importance of the present study.

In the phylogenetic analysis, HCV genotype 3a sequences formed a single cluster, which included 13 children from the Amur Region and 1 child from the Altai Krai. HCV genotype 1b sequences formed two common clusters, each comprising 2 patients from the Kyrgyz Republic and the Republic of Uzbekistan. The selection of the HCV genome region for phylogenetic analysis was determined by its length and variability, particularly in the E1 region, which ensures high discriminatory power of the analysis in investigations of nosocomial infection cases, as well as by successful international experience in applying analysis of this genome region to similar tasks [13]. The grouping into a single cluster of HCV sequences isolated from children who received medical care at a single facility in the Amur Region, where a chronic HCV outbreak had previously been reported, confirms the validity of the phylogenetic analysis conducted.

The cases of HCV infection among children in the Amur Region are linked to a long-standing chronic HCV outbreak at the pediatric department of the ARCCH, where, according to an epidemiological investigation conducted by the Federal Service for Supervision of Consumer Rights Protection and Human Well-being in 2018–2019, 169 children were admitted. The causes of infection in children were violations in the use and care of venous catheters (reuse of catheter caps, syringes, and contaminated multi-dose vials) and hand hygiene. The spread of HCV was facilitated by errors in diagnosis, insufficient supplies of disposable materials, antiseptics, and disinfectants, and a shortage of staff [3].

An analysis of the case of a patient from the Altai Krai who may have been infected at the Center by a child from the Amur Region revealed that HCV transmission could have occurred during a blood draw from the CVC if staff failed to follow hand hygiene protocols, change gloves between patients, as well as failure to follow aseptic techniques during invasive procedures and proper zoning of work surfaces. The presumed causes of infection coincide with the causes and factors of blood-borne infection described in the literature during epidemiological analyses of outbreaks, including during the investigation of a chronic epidemic focus of hepatitis C in the General Surgery Department of the ARCCH [3, 4]. In foreign literature sources, the causes of nosocomial outbreaks of blood-borne infections included violations of the zoning of “clean” and “dirty” areas, reuse of venous catheter caps, violations in hand hygiene and waste management, contaminated vials of saline solution for flushing venous catheters, and the reuse of single-dose vials of medications [4].

An analysis of the causes and factors of infection among children from the Kyrgyz Republic and the Republic of Uzbekistan was not within the scope of this study or the Center’s jurisdiction, similar to the other 12 non-clustered cases of HCV infection, the transmission of which is unrelated to the Center.

Thus, 14 (47%) of the 30 cases of HCV infection among children in the pediatric OHD departments who were treated at the Center between 2013 and 2025 were of nosocomial origin.

The infection of a child from the Altai Krai occurred in 2013–2014, prior to the implementation of a comprehensive set of preventive and anti-epidemic measures at the Center, which is currently being successfully implemented.

The Center’s structure includes an Infection Control Department, which brings together infectious disease specialists, epidemiologists, a bacteriological laboratory, a central sterilization unit, and others, and whose tasks include ensuring the infection safety of medical procedures. In 2020, a department for the professional development of nursing staff was established at the Center, headed by an epidemiologist. The department is responsible for developing standard operating procedures (SOPs), practical, methodological, and clinical guidelines, training manuals, and training nursing staff in modern approaches to performing invasive procedures and handling invasive devices. Starting in 2023, the department’s responsibilities were expanded to include auditing nursing procedures. In 2024, an internal quality control department was established at the Center.

In 2019, the Center adopted the aseptic non-touch technique2, developed and proposed by a cancer hospital in England [14], which is now the primary strategy of the Association for Safe Aseptic Practices and the global standard for infection control in invasive procedures worldwide3. A reduction in the incidence of nosocomial infections following the implementation of the aseptic non-touch technique has been demonstrated in many clinics [15–18]. Initially, the aseptic non-touch technique was introduced at the Center for work with venous catheters, then incorporated into all SOPs for invasive procedures; in 2024, a separate SOP for performing the aseptic non-touch technique was created. In 2023, Center staff published the training manual “Venous Catheter: Application, Care, Monitoring, and Complications”4, in 2026, they published “Placement of Peripheral Venous Catheters (Short, Long, and Midline) in Pediatrics.”5. The training manuals covered all aspects of infection control when working with venous catheters. Guidelines for working with venous catheters in 2024–2025 were incorporated into clinical recommendations for the treatment of certain pediatric oncohematological conditions, such as soft tissue sarcomas, neuroblastoma, and hepatoblastoma. In 2026, the Center’s staff published a training manual titled “Aseptic Non-touch Technique (ANTT)”6, which details all infection control guidelines for performing invasive procedures and working with invasive devices, including guidelines for zoning work surfaces, hand hygiene and cleanliness, and the safe use of gloves in the context of aseptic non-touch technique.

The standardization of procedures, training, and assessment of staff knowledge and skills implemented at the Center—which are recommended by medical communities in the field of infection prevention—have demonstrated high effectiveness at the Center and the absence of reported HCV infection cases for over 10 years.

Conclusion

Among children in the pediatric oncohematology departments who were treated at the Dmitry Rogachev National Medical Research Center for Pediatric Hematology, Oncology and Immunology between 2013 and 2025 and included in the study, HCV genotype 3a was the most prevalent (77%). Approximately half (47%) of HCV genotype 3a infections among children in the pediatric OHD departments were of nosocomial origin.

Phylogenetic analysis identified one case of HCV transmission at the Center from a patient who was part of a chronic HCV outbreak at the ARCCH. The HCV infection of the child could have occurred in 2013–2014 during diagnostic blood collection from the central venous catheter if staff failed to follow hand hygiene protocols, change gloves between patients, adhere to aseptic techniques during invasive procedures, or maintain work surface zoning.

The rules for catheter handling and aseptic non-touch techniques implemented at the Dmitry Rogachev National Medical Research Center for Pediatric Hematology, Oncology and Immunology, along with staff training and audits, have demonstrated high effectiveness and the absence of reported nosocomial HCV transmission among children for over 10 years.

 

1 Methodological recommendations MR 3.1.0366-25 "Use of genotyping and phylogenetic analysis in the epidemiological investigation of cases of HIV infection and viral hepatitis C" (approved by the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing on February 19, 2025); Sanitary rules and regulations SanPiN 3.3686-21 "Sanitary and epidemiological requirements for the prevention of infectious diseases" (registered with the Ministry of Justice of Russia on February 15, 2021, No. 62500).

2 Guidance Document. Standardizing the Critical Clinical Competency of Aseptic, Sterile, and Clean Techniques with a Single International Standard: Aseptic Non Touch Technique (ANTT®). Association for Vascular Access. 2019. URL: https://www.antt.org/download/ava-position-statement.pdf

3 Guidelines for the prevention of bloodstream infections and other infections associated with the use of intravascular catheters. Part I: peripheral catheters. Geneva; 2024. URL: https://www.who.int/publications/i/item/9789240093829?ysclid=mnc35ygcr2493100388

4 Satsuk A.V., Solopova G.G., Shchukin V.V., et al. Venous catheter. Use, care, control, complications: a tutorial. Moscow; 2023. 152 p.

5 Satsuk A.V., Solopova G.G., Pimenova O.V., et al. Aseptic Non-Touch Technique (ANTT): a training manual for doctors, residents, postgraduate students, and nurses. Moscow; 2026. 39 p.

6 Satsuk A.V., Solopova G.G., Shchukin V.V. et al. Placement of peripheral venous catheters (short, long, mid) in pediatrics: a tutorial for doctors, residents, postgraduate students, and nurses. Moscow; 2026. 48 p.

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About the authors

Anastasiia V. Satsuk

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology; Central Research Institute of Epidemiology

Author for correspondence.
Email: vnpoemp2@yandex.ru
ORCID iD: 0000-0003-3293-2008

Cand. Sci. (Med.), epidemiologist, Head, Department of training of nursing personnel; senior researcher

Russian Federation, Moscow; Moscow

Galina G. Solopova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Email: galina.solopova@dgoi.ru
ORCID iD: 0000-0002-1680-7269

Cand. Sci. (Med.), hematologist, Deputy chief physician for infection control

Russian Federation, Moscow

Karen K. Kyuregyan

Central Research Institute of Epidemiology

Email: karen-kyuregyan@yandex.ru
ORCID iD: 0000-0002-3599-117X

Dr. Sci. (Biol)., Professor of the RAS, Head, Laboratory of molecular epidemiology of viral hepatitis

Russian Federation, Moscow

Anastasiya A. Karlsen

Central Research Institute of Epidemiology

Email: karlsen12@gmail.com
ORCID iD: 0000-0002-6013-7768

researcher, Laboratory of molecular epidemiology of viral hepatitis

Russian Federation, Moscow

Vera S. Kichatova

Central Research Institute of Epidemiology

Email: kichatova@mail.ru
ORCID iD: 0000-0002-7838-6965

Cand. Sci. (Med.), senior researcher, Laboratory of molecular epidemiology of viral hepatitis

Russian Federation, Moscow

Svetlana V. Begunova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Email: svetlana.begunova@dgoi.ru
ORCID iD: 0000-0002-9736-1712

clinical laboratory diagnostics physician

Russian Federation, Moscow

Elena V. Rozanсeva

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Email: elena.rozantseva@dgoi.ru
ORCID iD: 0000-0002-5269-5508

biologist

Russian Federation, Moscow

Polina E. Emelyanova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Email: polina.emelianova@dgoi.ru
ORCID iD: 0009-0000-7756-5294

medical laboratory technician

Russian Federation, Moscow

Galina A. Novichkova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Email: galina.novichkova@dgoi.ru
ORCID iD: 0000-0003-4911-0553

Dr. Sci. (Med.), Professor, Scientific supervisor

Russian Federation, Moscow

Antonina A. Ploskireva

Central Research Institute of Epidemiology

Email: antoninna@mail.ru
ORCID iD: 0000-0002-3612-1889

Dr. Sci. (Med.), Professor of the RAS, Deputy director for clinical work

Russian Federation, Moscow

Vasiliy G. Akimkin

Central Research Institute of Epidemiology

Email: vgakimkin@yandex.ru
ORCID iD: 0000-0003-4228-9044

Dr. Sci. (Med.), Professor of the RAS, Director

Russian Federation, Moscow

References

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  2. Alkilany L.F., Alkilany S.F., Gaber N., et al. Exploring hepatitis C as a relapse risk factor in pediatric acute lymphoblastic leukemia: a study from a resource-limited Egyptian setting. J. Med. Virol. 2025;97(11):e70683. DOI: https://doi.org/10.1002/jmv.70683
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Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. The distribution of HCV genotypes among children in pediatric OHD departments and the general population of Russia.

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3. Fig. 2. Phylogenetic tree constructed based on the HCV core/E1 region (942 nt, positions 293–1234, numbered relative to the genome of the reference strain H77, GenBank No. AF011753). The region and year of isolation are indicated for each sequence. Sequences from the present study are marked in red with the region/country of the patient’s origin indicated. Tree branches with a posteriori probability >90% are highlighted in red.

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4. Fig. 3. The periods of stay at the Center for 14 children (13 patients from the Amur Region and 1 patient from the Altai Krai) from HCV genotype 3a cluster.

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Copyright (c) 2026 Satsuk A.V., Solopova G.G., Kyuregyan K.K., Karlsen A.A., Kichatova V.S., Begunova S.V., Rozanсeva E.V., Emelyanova P.E., Novichkova G.A., Ploskireva A.A., Akimkin V.G.

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