CC BY
2"CHILDREN WITH RECURRENT INFECTIONS" AS A MANIFESTATION OF PRIMARY IMMUNODEFICIENCY
1Matkarimova A.A., 2Jiemuratova G.K., 3Kurbanova A.A., 4Tajieva Z.U., 5Jadigerova L.S.
i,3,4,5Republican Children's Multidisciplinary Medical Center, Nukus 2Nukus Branch of the Institute of Human Immunology and Genomics, Academy of Sciences of
Uzbekistan https://doi.org/10.5281/zenodo.12360778
Abstract. In modern pediatrics, children with recurrent infections are commonly referred to as frequently ill. Factors contributing to the development of frequently ill children, as described in various literature, include delayed development of the immune system, anatomical and physiological features of the respiratory tract in children (structural characteristics of the bronchi), nutrition, and living conditions. It is believed that frequently recurring or persistent infectious conditions are the main manifestation of primary immunodeficiency.
The aim of the study is to assess the clinicalfeatures, possible complications, and outcomes of recurrent infections in frequently ill children.
Materials and Methods. The study observed frequently ill children receiving inpatient treatment at the Republican Children's Multidisciplinary Medical Center. We conducted a study on 180 frequently ill children with acute respiratory infections occurring 6 times or more per year, who also had foci of secondary infection. The vast majority of children were found to have combined pathology of the upper respiratory tract, including frequent episodes of acute respiratory illness (more than 6 times a year), adenoid hypertrophy, tracheobronchitis, rhinosinusitis, pharyngotonsillitis, otitis, and tubootitis.
Results. Among the recurrent respiratory tract infections, acute recurrent otitis media, pharyngitis, sinusitis, bronchiolitis, stenosing laryngitis, and community-acquired pneumonia were common. The frequency of their recurrence ranged from 4 to 12-14 times a year.
Conclusion. Children with a history of frequent recurrent, severe, or unusual infectious diseases (frequently ill children) require a high degree of vigilance regarding the diagnosis of immunodeficiency. Recurrent or persistent infection is the main manifestation of primary immunodeficiency. Although most children with recurrent infections have normal immunity, it is important to remain vigilant in cases of unusually frequent or severe infections.
Keywords: children, recurrent infection, primary immunodeficiencies (PID), prevalence.
Relevance. In modern pediatrics, children with recurrent infections are commonly referred to as frequently ill [4]. This group under dispensary observation corresponds to the concept of "patients with recurrent acute respiratory infections (ARI)" in foreign literature. Thus, the condition characterized by recurrent infections begins to be perceived as a diagnosis [1,5]. Factors contributing to the formation of frequently ill children, described in various literature, include delayed development of the immune system, anatomical and physiological features of the respiratory tract in children (structural characteristics of the bronchi), nutrition, and living conditions [6,7]. It is believed that frequently recurring or persistent infectious conditions are the main manifestation of primary immunodeficiency.
A tendency towards recurrent respiratory tract infections against the background of suppressed immune responses is characteristic of children living in environmentally unfavorable regions [11,13]. Despite the overall rarity of primary immunodeficiencies in the population, some partial immunodeficiencies, such as selective IgA deficiency or mannose-binding lectin
deficiency, are more common and can clinically manifest as a tendency towards recurrent respiratory infections [12].
The aim of the study is to assess the clinical features, possible complications, and outcomes of recurrent infections in frequently ill children.
Materials and Methods. The study observed frequently ill children receiving inpatient treatment at the Republican Children's Multidisciplinary Medical Center. Recurrent respiratory tract infections or persistent respiratory infections are understood as repeatedly developing specific nosological forms of ARI. Based on medical documentation and results of dispensary observation, we recorded infectious complications and recurrent respiratory viral infections in children, as well as the extent of therapy received. We conducted a study on 180 frequently ill children with acute respiratory infections occurring 6 times or more per year, who also had foci of secondary infection. The vast majority of children were found to have combined pathology of the upper respiratory tract, including frequent episodes of acute respiratory illness (more than 6 times a year), adenoid hypertrophy, tracheobronchitis, rhinosinusitis, pharyngotonsillitis, otitis, and tubootitis.
Results of the Study. Among the recurrent respiratory tract infections, acute recurrent otitis media, pharyngitis, sinusitis, bronchiolitis, stenosing laryngitis, and community-acquired pneumonia were frequently encountered. Figure 1 shows the frequency of their recurrence, ranging from 4 to 12-14 times per year.
Fig.1 Recurrent respiratory tract infections in children (%).
The duration of observation of frequently ill children from the onset of concomitant diseases ranged from 1 to 3 years. In 25 of them (13.8%), concomitant recurrent herpetic infection was detected, characterized by the recurrence of symptoms 5-9 times a year. Moderate manifestations of atopic dermatitis in the form of localized foci were observed in 20 patients (11.1%). The clinical picture was characterized by prolonged fever, intoxication, cough, and 58.2% of children complained of difficulty breathing or a sensation of breathlessness. Oxygen saturation decreased to 90% in 45.5% of cases, and severe respiratory failure developed in 13.6% of children. Radiographic examination of the chest more often revealed bilateral lung involvement (54.6%). In cases of unilateral involvement, the left and right lungs were affected with equal frequency.
Such frequent and recurrent respiratory illnesses contribute to sensitizing the body and lead
to a decrease in immune status, which promotes the formation of chronic inflammatory processes in the respiratory tract [1,3].
In addition to the influenza virus, the most dangerous and widespread pathogen, it is worth mentioning adenoviruses, which are characterized by a wide tissue tropism and can cause a variety of clinical manifestations, especially in children with weakened immune systems; respiratory syncytial virus (RSV), which has a decisive influence on the development of the immune system in children, acting as a trigger for the development of atopic bronchial asthma; parainfluenza viruses, as well as rhinoviruses.
Among the many reasons for insufficient vaccination coverage of children, special attention is given to temporary medical contraindications, which are caused by intercurrent diseases that develop shortly before planned vaccination. Considering that in the overwhelming majority of cases these intercurrent diseases are acute respiratory infections.
Based on the available statistics, asymptomatic and mild forms of the disease are most often detected in children. However, severe forms of the disease also exist, especially in children with concomitant pathologies. In most cases, moderate severity of viral pneumonia was observed in hospitalized children (53.6%), mild forms accounted for 27.5%, and severe forms for 18.8%. Preschool-aged children more often encounter mild forms of the disease, while more severe cases of pneumonia are more frequently registered in infants.
Among these persistent or periodically recurrent respiratory tract infections in children, those associated with primary immunodeficiencies (PID) are encountered. It is not accidental that these recurrent diseases, including recurrent rhinopharyngitis and pharyngitis, are registered not only in early and preschool-aged children, among whom the frequently ill children group is most often formed, but also in children of any age and even in adults. Recurrent otitis media was associated with lower levels of antibodies to certain pneumococcal serotypes compared to healthy children in the same age group. This includes defective neutrophil conversion, moderate decreases in the numbers of CD4, CD8, CD19, and NK cells, altered cytokine production by lymphocytes (IL-4|, IL-10|, IFN-yj, IL-2j), reduced production of immunoglobulin subclasses A, M, G, and decreased production of post-infection specific antibodies. These immune defects, one or, less frequently, 2-3, have either congenital or acquired origins, with the acquired ones being the result of past viral infections.
Thus, frequently recurring or persistent infectious conditions are the main manifestation of primary immunodeficiency. Although most children with recurrent infections have normal immunity, it is important to timely recognize whether the cause of a child's frequent infectious diseases is immune deficiency in order to provide appropriate evaluation and treatment.
Conclusion. Children with a history of frequent recurrent, severe, or unusual infectious diseases (FRID) require a high degree of vigilance regarding the diagnosis of immunodeficiency. Recurrent or persistent infection is the main manifestation of PID. Although most children with recurrent infections have normal immunity, it is important to remain vigilant in cases of unusually frequent or severe infections. Early referral to a clinical immunologist in cases of suspected immunodeficiency plays a key role, as early detection and treatment of PID can prevent significant organ damage and improve survival and long-term prognosis.
REFERENCES
1. Вавилова В.П., Вавилова Т.А., Черкаева А.Х. Рецидивирующие острые респираторные инфекции у детей: эффективность и безопасность фитотерапии. Педиатрическая фармакология. 2015;12(5): 605-608. DOI: 10.15690/pf. v12i5.1463.
2. Геппе Н.А. Острые инфекции дыхательных путей у детей. Диагностика, лечение, профилактика: клиническое руководство. Под ред. Геппе Н.А.М.: МедКом-Про; 2018.
3. Дрынов Г.И. Опыт профилактики и терапии респираторно-вирусных инфекций у больных с аллергическими заболеваниями. РМЖ. 2011:23:1426.
4. Заплатников А.Л., Гирина А.А., Леписева И.В. и др. К вопросу о рациональной терапии острых респираторных инфекций у детей в условиях растущей антибиотикорезистентности. Педиатрия. Приложение к журналу Consilium Medicum. 2018; 4:37-41. DOI: 10.26442/24138460.2018.4.180133.
5. Намазова-Баранова Л.С., Котлярова М.С., Ровенская Ю.В. и др. Сравнение эффективности и безопасности фито- и антибиотикотерапии при лечении острого бронхита у детей: результаты многоцентрового двойного слепого рандомизированного клинического исследования. Педиатрическая фармакология. 2014;11(5):22-29. DOI: 10.15690/pf.v11i5.1161.
6. Сафина А.И. Лечение кашля при острых респираторных инфекциях у часто болеющих детей. Вопросы современной педиатрии. 2014; 13(1):88-91.
7. Хаитов Р.М., Пинегин Б.В., Пащенков М.В. Эпителиальные клетки дыхательных путей как равноправные участники врожденного иммунитета и потенциальные мишени для иммунотропных средств. Иммунология. 2020; 41 (2): 107-113. DOI: 10.33029/02064952-2020-41-2-107-113.
8. Щербина, А. Ю. Первичные иммунодефицитные состояния: вопросы диагностики и лечения /А. Ю. Щербина, Т. Г. Косачева, А. Г. Румянцев //Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2010. Т. 9. № 2. С. 23-32.
9. Chauhan L., Young H., Knepper B. et al. Appropriateness of antibiotic prescriptions for acute sinusitis and pharyngitis in an integrated healthcare system. Infect Control Hosp Epidemiol. 2018;39(8):991-993. DOI: 10.1017/ice.2018.117.
10. Esposito S., Soto-Martinez M.E., Feleszko W. et al. Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence. Curr Opin Allergy Clin Immunol. 2018;18(3):198-209. DOI: 10.1097/ACI.0000000000000433.
11. Wang MY, Zhao R, et al. SARS-CoV-2: Structure, Biology, and Structure-Based Therapeutics Development. Front Cell Infect Microbiol. 2020; 10: 587269. DOI: 10.3389/fcimb.2020.587269.
12. Morgan J.R., Carey K.M., Barlam T.F. et al. nonappropriate Antibiotic Prescribing for Acute Bronchitis in Children and Impact on Subsequent Episodes of Care and Treatment. Pediatr Infect Dis J. 2019;38(3):271-274. DOI: 10.1097/INF.0000000000002117.
13. Zou X Chen, et al. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med. 2020; 14: 185-192. DOI: 10.1016/j. bbrc.2020.03.044.
14. Wei L, Sun S, Xu CH, et al. Pathology of the thyroid in severe acute respiratory syndrome. Hum Pathol. 2007; 38 (1): 95-102. DOI: 10.1016/j.humpath.2006.06.011.
