30.11.2020

Dynamics of activity of persistent infections

Persistent infection can cause a range of diseases. Some of them are characterized by severe clinical course, especially at an early age. In Russia, unfortunately, there is a high level of pediatric infectious diseases [1]. It is known that most transmission is in the first few years of life, sometimes in utero. So, infection with herpes viruses human 1-2 and 4-6 types in most cases implemented in under two years.

The source of infection is often the immediate environment of the child, which in the first two years of his life represented by family members and/or staff (nannies, Tutors, etc.). Over the past five years has increased the number of children under one year who died of generalized viral infections [2]. Thus, according to the literature, in children, the markers of active persistent infection detected more frequently than in adults [3].

One of the factors contributing to the high level of replication of infectious agents, is the immaturity of the immune system at an early age [4]. Despite the abundance of scientific works, devoted to the problem of persistent infections, the question of specific dynamics of their activity remains open.

Object and research materials

The subject of analysis was the data obtained in the examination of children and adolescents who were hospitalized in the clinic of the Moscow research Institute of Pediatrics and pediatric surgery (in recent years – a structural subdivision of research clinical Institute of Pediatrics named. Acad. Y. E. Veltishev of the Russian national research medical University them. N. I. Pirogov) of the Ministry of health, and their parents.

Analyzed the results of a survey of 1079 patients, of which 1064 (98,6%) were children and adolescents aged 2 months to 17 years and 15 (1.4 per cent) adults aged 23 to 52 years.

Every patient is examined from one to three samples of different biological materials, only 2051 sample. Of these, precipitation of the urine – 877 (42,8%); boccalini scrapings – 104 (5,1%); the combined material comprising the residue of urine and buccally scraping, – 901 (43,9%); blood – 169 (8.2 per cent) (table. 1).

Research methods

DNA of persistent infections in the studied materials were identified by polymerase chain reaction, the production of which used full sets of reagents (kits) for laboratory diagnostics in vitro production of “BCM”, “Diasan” and “Gentekh”, Moscow, Russia. Used monospecificity sets, complete deliverydiovan sopernikami, ready to eat, frozen and stored at temperatures from -25 to -28 °C. According to our data, the use of such sets allows us to achieve the highest quality results.

Evaluated the replication activity of the following microorganisms: Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, cytomegalovirus, Epstein–Barr, herpes simplex virus 1-2 types.

Among patients girls and women was 56.7% of patients, boys and men of 43.3%.

Age characteristics of the patients are shown in table. 2: the age of most patients ranged from two to 16 years.

In determining the periods of active replication persistent infections depending on the age of a piece of research included data obtained during the examination of 876 patients.

The main selection criterion was the simultaneous study material at least 3 infections (herpes viruses types 4-6 and/or obligate intracellular parasites). For each patient, respectively, examined 3 or 6 infections. This approach allowed to reduce the selectivity of the sample at one or another infection.

The results of the study and their discussion

Revealed the following patterns (Fig. 1):

  1. The highest frequency of detection of DNA Chlamydia trachomatis accounts for the age of two years, from 8 to 12 years, from 14 to 16 years, and adult patients. In children, these periods correspond to the congenital and perinatal infections, time in the active interpersonal contacts and first sexual experience. In children aged 0.2-8 years number of positive samples gradually decreases. The most likely reasons for this: a) maturation of the immune system and, consequently, improving the control over the reproduction of microorganisms; b) stabilization of contacts with the older children and adults, which reduces the likelihood of primary contamination. Upon reaching school age and at puberty the number of contacts, by inducing the primary infection, increases dramatically.
  2. The most active Mycoplasma hominis was under the age of two years, from 4 to 6, 8 to 12 and from 16 to 18 years. The reasons for such regularities is not as obvious as for Chlamydia trachomatis. We can only state that the maximum frequency of the high replication activity is necessary at a time manifestations of congenital and perinatal infections, pre-school socialization and adolescent.
  3. As with Chlamydia trachomatis, the detection rate of active replication Ureaplasma urealyticum gradually decreases by the age of 8 to 10 years. Then steadily increasing, exceeding in adolescence and in adults the indicators in childhood, by more than two times. The frequency of detection of DNA Ureaplasma urealyticum in children older than 12 years were higher than expected – from 23.5% to 39.5%, and the activity of replication Ureaplasma urealyticum and Mycoplasma hominis were high and mostly consistent with 2-4 points.

A clear pattern is shown for cytomegalovirus: detection rate of DNA in the samples decreases steadily to 0 in the examined adults, which can be considered as evidence based on active replication of cytomegalovirus from the maturity of the immune system (Fig. 2).

A similar, although less pronounced changes in the frequency of active replication, depending on the age can be traced to viruses Epstein–Barr and herpes simplex virus 1-2 types.

To answer the question whether there are seasonal changes in activity, persistent infections, we analyzed the frequency of positive samples within two full years; has been surveyed 871 patients.

The chart shows the patterns of change in the number of positive samples of Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum in the course of the year (Fig. 3).

Contrary to expectations, the most active Chlamydia trachomatis accounts for the period from April to June. There are significant fluctuations in the index in the first half of the year with maximum in June and minimum in March and consistently low rates in the second half.

The period of greatest activity of the replication of Mycoplasma hominis was from March to June. In General, during the first half of the year recorded a high level of positive samples, with the exception of February. In the second half of the number of positive samples is reduced and remains stable throughout the period, with the exception of October.

The frequency of detection of DNA Ureaplasma urealyticum is extremely unstable, from December to June, and in July decreases sharply and remains at a relatively low level until November. In December, the index value increases, reaching the maximum. Thus, the total for the studied intracellular parasites is instability and higher values of the index in the first half (for Ureaplasma urealyticum from December to June) and, in contrast, relatively low and stable number of positive samples in the second half. It is possible that the reduction and stabilization of this indicator in the period from July to December due to the improved metabolism, and hence adaptive immunity in late summer and autumn.

For persistent herpes viruses any clear seasonal patterns were not identified, however, the frequency of detection of DNA of herpes simplex virus 1-2 types has been steadily increasing in may, reaching a maximum and then decreases to the end of the year to the minimum value (Fig. 4).

Insights

Our research allowed us to draw the following conclusions:

  • In the analysis of dynamics of activity persistent infections depending on the age shows that the highest frequency of detection of DNA Chlamydia trachomatis is noted before the age of two years, from 8 to 12 years, from 14 to 16 years and over 18 years of age. In the period from 0.2 to 8 years, the number of positive samples gradually decreases.
  • The most active Mycoplasma hominis noted at the age of two, from 4 to 6, 8 to 12 and from 16 to 18 years.
  • The activity of Ureaplasma urealyticum is reduced to 8-10 years, then steadily increases in adolescence and in adults more than twice exceeding the figures registered in the childhood.
  • The frequency of samples, including DNA herpes viruses, with age, is steadily declining. To the greatest extent, such a pattern is characteristic of CMV.

In the study of seasonal activity of all obligate intracellular parasites revealed substantial variability in the first half of the year with maximum in June and a relative decrease and stabilization in the second half.

  • The high replication activity of Chlamydia trachomatis was from April to June, Mycoplasma hominis – from March to June, and Ureaplasma urealyticum in December.
  • Clear patterns of seasonal dynamics of activity of cytomegalovirus and Epstein–Barr have not been identified.
  • The frequency of detection of DNA of herpes simplex virus is seasonal from the beginning of the year has been steadily increasing in may, peaking, and by the end of the year are reduced to the minimum value.

Literature

  1. Mazankova L. N., Zakharova I. N. // ROS. West. perinat. and Pediatrics. 2010. No. 5. Pp. 8-11.
  2. Lobzin Y. V. Problems of childhood infections at the present stage // Infectious diseases. 2009. No. 2. S. 7-12.
  3. Uchaikin V. F., Nisevich N. I., shamsheva O. V. Infectious diseases and vaccination in children. M.: GEOTAR-media. 2006. 688 p
  4. Shalagina L. A., Kruglov I. V. Age peculiarities of the immune system in children // RMJ. No. 23, 2009, p. 1564

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