Medicine / Pediatrics , Dermatology

Sirazitdinova Victoria Feliksovna - MD, PhD, Department of Dermatovenereology TashPMI

Tashkent Pediatric Medical Institute

For herpes infections in young children

                   Large spread of acute viral infections in the population growth indicates a decline in the incidence of antiviral immunity . Under the influence of debilitating factors ( influenza, SARS , AIDS and other diseases , immunosuppressive treatment ) viruses are reactivated with the formation of various forms of the disease , changing during the infection process , forming immunodeficiency [1].

Atualnost problems due to poor knowledge of current patterns of development and persistence of herpesvirus latency in the human body , growth of relapsing forms of the disease and not always satisfactory results of treatment. In recent years, increased interest in the issue of prenatal and perinatal viral infections , among which a special place is given to HSV infection (HSV-1 and 2- types). It is one of the leading causes of stillbirth , miscarriage , premature birth , neonatal morbidity . Newborn can get herpes infection in utero , during delivery or postnatally , and that happens in 75-80% of cases . Intrauterine infection caused by the herpes simplex virus (HSV ) are relevant for the pro ¬ lems of modern obstetrics , perinatology and pediatrics in general. According to several authors , their frequency varies from 2 % to 65.5 % [ 2] . Significance of the problem is determined by the fact that when intrauterine infection often diagnosed cases of children born prematurely , with low birth weight , intrauterine growth or stillbirth. Importantly value changes such as the formation of brain malformation , dysplasia organs dysfunction systems. Intrauterine HSV infection is often the real cause of such widespread diagnoses as " intrauterine hypoxia ", " asphyxia ", " birth trauma " [3,4] Researchers stated widespread perinatal transmission , including among clinically healthy newborns.

Increase in incidence is largely associated with the prevalence of asymptomatic and undiagnosed form of the disease , but this is an objective process , unfortunately, is not accompanied by radical changes in relation to the disease both physicians and the public [5 , 6].

Maximum risk of intrauterine infection of the fetus and the development of severe forms of the disease observed in cases where the pregnant woman carries a primary HSV infection. Intrauterine infection (IUI ) in women with primary HSV infection during late pregnancy in 50-65 % of cases may cause a lightning disseminated infection in the newborn , often with fatal outcome [5]. Neonatal herpes manifests itself in three clinical forms : local, with damage to the skin and mucous membranes - the most mild form of herpes , is 20-45 % of all cases , the local form with CNS - herpetic encephalitis, meningoencephalitis . Is about 30 % of all cases ; disseminated form of herpes infection with CNS , liver, lung , adrenal , DIC [6 , 7]. The influence of unfavorable factors in the ante - and perinatal forms of fetal malnutrition , accompanied by a delay of physical development , and processes of tissue differentiation , especially nerve and bone , blood vessels, skeletal muscle , myocardium , brain [8,9]. Clinical diagnosis of HSV infection in newborns marked skin lesions, eye and mucous membrane of the mouth, which are the first signs of infection , then there may be a development of encephalitis [10 , 11]. However, it may be born and healthy child , ie without symptoms but manifestations associated with IUI can be diagnosed much later [12 , 13].

Materials and methods . We observed 84 children aged 1-6 months. Of these, 62.5 % - 37.5 % and boys - girls , consonant with the position of population genetics , according to which particular male genotype determine a lower level of reserve capacity of the organism under the influence of stress factors. Studied a group of children (n = 84) were selected by the expert sample. Analyzed according to maternal obstetric and gynecological history , pregnancy and delivery , as well as analysis of the newborn on the specifics of neonatal adaptation , physical, physical and neurological development . For this purpose cards for pregnant women , birth stories , stories of child development, follow-up for children.

 A thorough analysis of a number of anamnestic data , pregnancy and childbirth, chronic genital and extragenital diseases , maternal age and social class .

 The age structure of the observed women represented groups " U20 " (P - 0 ), " 21-30 years " (R- 1), " 30 years or more " (R- 2). Maximum number of mothers in the control group were in the most active reproductive function , namely, between the ages of 20 to 30 years (P - 0 , 57.1 %). A high percentage of mothers of infected children is in the range of " under 20 and over 30 years " (R- 1 - 19.0% , 16.7 % , P -2 - 28.6% , 45.7 %, p < 0 , 05). Relative risk (RR ) infection in children depending on the age of the mother in the range of " 20 years younger " was OR = 1.47 and OR = 2.88 , in the range of " 30 years and older ."

 These data also have significant practical importance , namely women aged younger than 20 and older than 30 years should be the object of most attention from physicians and obstetricians - gynecologists during pregnancy . However, the test results may lay the basis for the development of specific planning programs of healthy families and reduce the likelihood of infection with HSV children to mothers aged " under 20 years" by 1.7 times and 4.7 times at the age of " over 30 years."

HSV , like several other agents of viral diseases is trudnokultiviruemym culture and diagnosis of diseases in public health practice is not applicable . Cultures are sometimes used for research purposes and in large medical centers . The methods for the rapid diagnosis of culture . From other methodologies are widely used in molecular biology - in Russia is mainly PCR and enzyme-linked immunosorbent assay - ELISA (Ig M, Ig G), complex application which in most cases make it possible to verify the diagnosis of herpes and co-infections .

Follow-up of children held up to 1.5 - 3 years of age. Studied a group of children (n = 84) were selected by the expert sample. Analyzed according to maternal obstetric and gynecological history , pregnancy and delivery , as well as analysis of the newborn on the specifics of neonatal adaptation , physical, physical and neurological development . For this purpose cards for pregnant women , birth stories , stories of child development, follow-up for children.

 In accordance with the purpose and objectives of the study the grouping observations conducted taking into account the presence of markers of infection by herpes simplex virus :

P -0 - group control , uninfected (n = 32);

R-1 - infected postnatally (n = 27);

          P- 2 - the main group , infected in utero (n = 25).

All children are routinely conducted BP measurement , inspection of narrow specialists - neurologist , ophthalmologist , gastroenterologist, allergist , pulmonologist , nephrologist, pediatric gynecologist .

          Physical development of the child was assessed by calculation ratio of head circumference and chest (PS) by registering low frequency (PS < 0.95) , medium (PS 0,95-1,0 ) and high values of the (PS > 1,0) , body weight and length -for-age , and also in terms of weight - a growth index (IRI ) .

1. Laboratory studies included a complete blood count, urine, feces , bacterial seeding urine, feces , blood chemistry with the determination of iron , calcium and inorganic phosphorus . Levels of iron and calcium in the blood serum was determined by photometry using reagent kits firm «BIO-LA-TEST» ( Czech Republic) . The inorganic phosphorus in serum were determined using reagents «UV-TEST CYPRESS» Diagnostics ( Belgium) .

 2 . To determine whether HSV intrauterine infection in children aged one month was used Polymerase chain reaction ( PCR). As a material used for the study venous blood. Formulation of the test and interpretation of the results was carried out strictly in accordance with instructions for use of the test system .

3 . Immunosorbent assay ( ELISA) for detection of specific anti-viral (anti - IgM and IgG HSV types 1 and 2 ) antibodies to HSV was held in the Institute of Immunology, RU, using a test system «Vector -Best" (Novosibirsk) . Formulation of the test and interpretation of the results was carried out strictly in accordance with instructions for use .

To differentiate primary infection from latent , in this work we used a modified version of an enzyme immunoassay with the definition of the index of avidity IgG- antibodies ( avidity - the index of the strength of antigen-antibody binding ) . Accounting for the ELISA was a quantitative method using a test system for the detection of antibodies to HSV -1 , 2 ( NGO "Diagnostic Systems", IFA - ANTI- HSV -G- avidity ", Nizhny Novgorod) using the principle of detection of low avidity immunoglobulin G.

Results:

ntrauterine infection was confirmed in 25 ( 30 %) children months of age (P -2 group) positive results of PCR and the presence of low avidity of immunoglobulins IgG (> 25%) and negative results for the presence of IgM, indicating a subclinical course of HSV infection in this group children. Apparently , the symptoms of infectious disease were disguised as perinatal CNS , as evidenced by the results of our research.

In 32 (38%) children in the age of one month recorded negative readings DNA PCR and virus -specific IgM ELISA and positive for IgG, indicating the presence of blood in their maternal antibodies. Analyzing the results obtained by PCR and ELISA (IgM, IgG - considering avidity ) to the group R -O (children up to 1 month). Found that at low values of the PCR and ELISA for IgM, IgG detected in 20 cases of 32 , and with high avidity . This can be viewed as a manifestation of the strong ties complementary antibody molecule with an antigen that is the herpes simplex virus mother persists in the body of the child. At the age of 1 year were marked as negative results of PCR analysis and ELISA for IgG and IgM data and children in the control group ( P-O , uninfected ) .

In group P -2 (children under 1 month and over 3 years ) (n = 25, 30 % ), similar results were obtained : PCR -positive , IgM- negative in all cases. Differences concerned IgG: positive low avidity in n / a group of children under the age of 1 month , and in n / a group of children older than 1 year - vysokoavidnye that can testify in favor of the development of intrauterine infection .

         Postnatally infected group consisted of children (n = 27, 32 %) with negative PCR and ELISA studies on IgM, as well as a positive result in the ELISA IgG months of age . Do these children one year of age and older were recorded positive results of PCR and ELISA , which indicated the presence of viral agent in the blood of the child and the appropriate immune response.

Of all the surveyed children were born from the first pregnancy 15 ( 18%) children from the second - 26 (31%) children from the third and more - 43 ( 51%) of the child.

          From full-term pregnancy were born 57 children (68%) , 27 ( 32%) children were born with gestational age 32-36 weeks .

Birthweight 2500 g. had 25 newborns ( 30 %), from 2500 to 3600 c. - 37 (44% ) and more than 3600 g. - 22 (26 %) infants.

Breastfed children were 36.9% , combined - 23.1% , artificial - 40 % of children.

Most of the children had premorbid condition and comorbidities , namely : iron deficiency anemia grade I-II (48,1 ± 4,9%), ENT diseases (30,8 ± 4,5%), rickets (65.4 ± 4,7%), functional bowel disorders (33,6 ± 4,6%), parasitic infestation (12,5 ± 3,2%). 32,7 ± 4,6% of the children had changes in the cardiovascular system . At 27,9 ± 4,4% of children observed tachycardia, muffled heart tones (8,7 ± 2,8%), systolic murmur (13,5 ± 3,2%).

          Bronchial obstruction registered in 34,6 ± 4,6%, allergodermatichesky syndrome in 28,8 ± 4,4% of cases.

         Dysfunctional disorders and signs of lesions of pathological activity according neurosonography and electroencephalography defined in 51,0 ± 4,9% of cases , clinically confirmed recording frequency of perinatal CNS syndromes as cerebroasthenic syndrome (36,5 ± 4,7%), syndrome movement disorders (22,1 ± 4,1%), syndrome of vegetative- visceral dysfunction (30,8 ± 4,5%).

          Conclusions .

1.This study suggests that about half of the total number of examined patients are children born to a third or more pregnancy , which confirms the inverse relationship with the index pregnancy rates newborn health during postnatal adaptation , creating preconditions for the formation of the critical situation in the body when adverse impact of stress factors.

2 . Intrauterine infection of children with herpes simplex virus is associated with maladjustment postnatally predetermining index decreased health and lag in development with the formation of the " sickly children " and with chronic diseases later in life .

3 . Comprehensive laboratory study of mothers and children must provide for PCR and ELISA diagnostics for the detection of antigen and antibody response in view of IgG avidity , which allows to verify the diagnosis of herpes infection and optimize therapeutic approaches .

Literature :

1. Khaldin AA Epidemiological aspects of diseases caused by herpes simplex virus. Vestn. Postgraduate . honey . education. 2009 , 1 : 67-68 .

2 . Sidorova , S., I. Chernienko Russian Bulletin perinatology and pediatrics. 1998 , 3: 7-13 .

3 . Isakov VA Herpesvirus infections in man . M. 2006 , 309.

4 . Drobotko LN, Yu Strakhov Clinical features, diagnosis and treatment of acute herpetic stomatitis in children. The attending physician . 2000 , 8 : 22-26 .

5 . Elizarova VM Drobotko LN, Yu Strakhov Acute herpetic stomatitis in children. Medical Assistance . 2001 : 4; 27-29 .

6. Antonov PV, SP Vydumkina Meaning of intrauterine infection of the central nervous system by herpes simplex viruses in the development of encephalopathy in infants : a scientific publication . Archives of Pathology , 2003 : 4 .

7. Lavrov DB, GA Samsygina Etiology and indicators of high risk of intrauterine infection of the fetus. Pediatriya.1997 3 : 94-99 .

8. Zhabborov UU Optimizing management of women with recurrent genital herpes and reproductive losses in history : Author ... MD Tashkent . 2009 , 18 .

9. Alexander A., NI Kudashov Clinical and immunological features of HSV infection in newborns . Ross . vestn.perinatol . and pediatrii.1999 , 5 : 19-22 .

10 . Kravchenko LV The immune system in infants living with herpes infection : a scientific publication . Pediatrics them . GN Speranskii . 2008 , 1 : 52-58 .

11. Baringer J.R. Herpes simplex infections of the nervous system. Neurol. Clin. 2008 , 3: 657-674 .

12. National Standard " Herpetic infection of genitals and urinary tract ." Moscow, 2008 , 68 .

13. Brown Z. Preventing herpes simplex virus transmission to the neonate. Herpes. 2004 ; .11: 175A-186A.