Peripheral blood count disorders at the beginning of icteric phase of hepatitis A in adults according to clinical form.

AIM: Hepatitis A remains a common cause of morbidity in developing countries, sometimes affecting adults. The aim of this study was to determine the age and sex distribution of adult hepatitis A patients, the seasonal appearance of disease and the possible peripheral blood count (PBC) disorders at the beginning of the icteric phase in different clinical forms of the disease. METHODS: The retrospective study was carried out during 1987-1990, with 106 adult hepatitis A patients assigned to 1 of 3 subgroups: typical (74 patients), prolonged (28 patients) and cholestatic forms of hepatitis A (4 patients) whose PBC was analysed at the beginning of the icteric phase of the disease. The hypothesis of the study was that there were significant differences between mean values of PBC in different subgroups. In data analysis, Student's ''t''-test was performed where appropriate. RESULTS: Fifteen (53.8%) males and 49 (46.2%) females were involved in the study (median age 24.7 years). Most of them were hospitalized at the end of Summer and Autumn. Significant differences were observed neither in mean values of red blood count (RBC) nor platelet count among studied groups. Mild leucopenia was found in the vast majority of patients. In the differential count, only the monocyte count showed a slightly significant difference between prolonged form (4%) and typical form (3%), (t=2.35, p<0.05). CONCLUSIONS: There is no single reason to use peripheral blood count as a specific diagnostic marker in setting the diagnosis of hepatitis A, except for its importance as a relative laboratory indicator of infection of viral origin.

[Primary varicella-zoster virus infection--current knowledge, diagnostic and therapeutic approaches]. / Primoinfekcija virusom varicele zoster--savremena saznanja i dijagnosticko-terapijski pristup.

INTRODUCTION: It is well known that varicella, a clinical entity of primary varicella-zoster virus infection, is most commonly a mild, benign disease of preschool and school children. However, in spite of progress in diagnostic approach and up-to-date treatment based on specific antiviral agents, many clinicians face cases of life-threatening varicella with uncertain course and prognosis, in adult and immunocompromised patients predominantly. ETIOPATHOGENESIS AND HISTOPATHOLOGY: Varicella-zoster virus (VZV) is a member of the Herpesviridae family. The portal of entry is nasopharyngeal mucosa, sometimes conjunctiva. VZV causes a generalized infection and has dermal tropism. Histopathological findings include degenerative changes of epithelial cells such as ballooning, multinucleated giant cells and eosinophilic intranuclear inclusions. CLINICAL FEATURES AND COMPLICATIONS: The evolution of varicella includes 3 stages of disease and is characterized by gradual onset, constitutional symptoms, signs of upper respiratory tract and polymorphous rash. According to the severity of clinical presentation, there is a number of mild forms and severe, even life-threatening forms of varicella. According to etiology, varicella complications are divided in viral and bacterial ones. Immunocompromised patients often develop serious, life-threatening forms of varicella. Especially the prognosis of visceral dissemination commonly followed by liver and brain involvement is dubious. The course of varicella in pregnancy may be severe because of changed immune response and more frequent appearance of complications in adults. The probability of vertical transmission of VZV is 25%. The early infection of embryo may lead to abortion. The symptomatic intrauterine infection appears in about 3% of all cases of varicella of pregnant women and is called a "congenital varicella syndrome". Vertical transmission of VZV in the late pregnancy may result in preterm delivery or perinatal varicella (varicella in the newborn). DIAGNOSIS: The diagnosis is made by history and physical examination. Atypical cases of varicella require laboratory confirmation of diagnosis including virus/viral antigen detection, virus isolation and identification or serological diagnosis (detection of specific anti-VZV antibodies in patient's sera). PREVENTION: Prevention of varicella includes active and passive immunization. Passive immunization is based on the use of varicella-immunoglobulin (VZIG). A live, attenuated vaccine was developed by Takahashi and colleagues in Japan. This vaccine is recommended, first of all, to seronegative immunodeficient children. Vaccine virus is sensitive to acyclovir and is not transmissible to non-vaccinated children. The duration of vaccine-induced immunity is at least 6-10 years in the majority of vaccinees. THERAPY: Hygiene is the most important principle in the management of varicella, particularly bathing and use of a stringent soaks to avoid secondary bacterial skin infection. The patient should be isolated in a well-ventilated room with regular change of bed, linen and light food should be provided. Indications for, acyclovir (and other antiviral agents) treatment are, individuals who have suffered from severe forms of varicella and those, belonging to the high-risk group of patients (adults, viral, complications, immunocompromised host).

[Reactivation of herpes zoster infection by varicella-zoster virus]. / Reaktivacija herpes zoster infekcije varicela-zoster virusom.

HISTORY: There has been considerable interest in varicella-zoster virus in the middle of the twentieth century. Virus isolation in 1958 had made it possible to find out the complete DNA sequence of the varicella-zoster virus. Molecular identify of the causative agents of varicella and shingles had been proved. ETIOPATHOGENESIS AND HISTOPATHOLOGY: Varicella-zoster virus is a member of the Herpesviridae family. After primary infection which results in varicella, the virus becomes latent in the cerebral or posterior root ganglia. Some of these individuals develop shingles after several decades because of virus reactivation. It is caused by decline of cellular immune response. Circumstances such as old age, hard work, using of steroids or malignancies contribute to the appearance of shingles. Histopathological findings include degenerative changes of epithelial cells such as ballooning, multinucleated giant cells and eosinophilic intranuclear inclusions. EPIDEMIOLOGY: Shingles occur sporadically, mainly among the elderly who have had varicella. There is no seasonal appearance of shingles. Individuals suffering from shingles may be sometimes contagious for susceptible children because of enormous amount of virus particles in vesicle fluid. CLINICAL FEATURES: Clinically, shingles is characterized at first by pain or discomfort in involved dermatome, usually without constitutional symptoms. Local edema and erythema appear before developing of rash. Maculopapular and vesicular rash evolves into crusts. The most commonly involved ganglia are: lumbar, thoracic, sacral posterior root ganglia, then geniculate ganglion of the VIIth cranial nerve and the trigeminal ganglion. The most common complication, postherpetic neuralgia, may last for as long as two or three weeks, sometimes even one year or more. Other complications that may be seen in shingles, but more rarely, are ocular (keratitis, iridocyclitis, secondary glaucoma, loss of sight), neurological (various motor neuropathies, encephalitis, Guillain-Barre syndrome), secondary bacterial infection of vesicles. Immunocompromised patients often develop more severe disease lasting up to two weeks, skin lesions are more numerous and often with hemorrhagic base and there is a high possibility for cutaneous dissemination and visceral involvement including viral pneumonia, encephalitis and hepatitis. Chronic shingles may also be found in immunocompromised hosts, particularly in those with a diagnosis of HIV infection. In patients with HIV infection, shingles is often characterised by radicular pain and itching several days before appearance of skin lesions. Those patients may have two or more dermatomes involved and recurrences of shingles cannot be quite infrequent in those patients. But visceral involvement is rarer than in other immunocompromised patients. Shingles may occur in the second half of pregnancy and usually have a mild course. However, congenital abnormalities has been described in few cases. DIAGNOSIS: The diagnosis of shingles is usually made by history and physical examination. Exceptionally, for example in zoster sine herpete and atypical forms of shingles, virus isolation and serological tests must be used. DIFFERENTIAL DIAGNOSIS: Some other diseases may cause similar skin lesions and rash (varicella, erysipelas, impetigo, enteroviral infections, herpes simplex infections). These diseases are excluded by using detailed history taking and physical examination, laboratory findings, virus isolation and commercially available serological tests. THERAPY: The vast majority of immunocompetent persons with shingles should be treated only by symptomatic therapy. Predominantly it is directed toward reduction of fever and avoiding secondary bacterial skin infection in immunocompetent hosts. Acute neuritis and post-herpetic neuralgia require administration of various analgesics, even like amitriptyline hydrochloride and fluphenazine hydrochloride. Acyclovir therapy is limited to ophthal

[Primary infection with varicella-zoster virus in risk groups]. / Primoinfekcija virusom varicele zoster kod rizicnih grupa.

INTRODUCTION: Chickenpox represents the primary form of Varicella-zoster virus (VZV) infection and appears most commonly in preschool and school children. The clinical course of chickenpox in immunocompetent children is mainly mild and complications are rare (1-5). Adults and immunocompromised patients are considered to be risk groups for development of serious and even life-threatening complications. The most frequent bacterial complications include secondary bacterial skin infections, angina, sinusitis, otitis and bronchopneumonia. Central nervous system complications, visceral dissemination, pneumonitis and myocarditis are the major viral complications (6,7). Acyclovir is approved for treatment of chickenpox in risk groups to reduce the frequency of viral complications and to treat those ones which have already appeared (7,8). The treatment of bacterial complications is based on the examination results of the bacterial sensitivity to antibiotics. MATERIAL AND METHODS: In our study patients with the diagnosis of chickenpox based on the history of disease, clinical features and clinical course and data on intimate contact with individuals suffering from chickenpox, were clinically followed-up. Sedimentation rate, blood count and urine samples were analyzed. A unique questionnaire was designed to follow-up the following data: sex, age, course of the disease, occurrence of complications in immunocompetent patients and those belonging to risk groups and effects of acyclovir therapy. RESULTS: During a three-year period 48 patients with chickenpox treated at the Clinic of Infectious and Dermatovenereology Diseases have been observed. 64.6% of them were males and 35.4% were females. 29.2% were infants under 1 year of age, 29.2% were 2-13 years of age and 41.6% were 14-50 years of age. According to the clinical course, patients were divided into two groups: the first one included patients who developed complications of chickenpox (54.1%), the second one consisted of those without complications (45.1%). 72.7% of all complications occurred in patients belonging to risk group (14-50 years of age). Among viral complications in risk groups the most common were pneumonia (44.4%) and haemorrhagic rash (44.4%), only one patient (11.1%) developed a mild, viral meningitis. Bacterial complications were also present in risk group as secondary bacterial skin infections (71.4%) and otitis media (28.6%). Viral complications were treated successfully by 750 mg intravenous acyclovir given 3 times a day, or by 800 mg oral acyclovir given 5 times a day during 7-10 days. Adequate antibiotics were used in the treatment of bacterial complications. A case of chickenpox associated with the meningitis caused by Haemophilus influenzae was also reviewed. DISCUSSION: In this study the majority of observed patients had a mild, clinical form of chickenpox that is in accordance with the other available clinical data (1-4). Complications developed more frequently in the adults and usually were of viral etiology. All patients were on time treated with acyclovir and visceral dissemination did not occur in any of them. Complications had a favourable evolution and VZV meningitis was healed without sequelae. Many authors have written about successful use of acyclovir in the treatment of chickenpox. However, acyclovir is not recommended to immunocompetent persons without chickenpox viral complications who do not belong to risk groups (1,3,4,9-11). CONCLUSION: Our findings lead to the conclusion that chickenpox in adults may have an uncertain outcome because of a more severe clinical course and susceptibility to complications. In our study application of acyclovir in that age group provided good results as for prevention and treatment of complications of chickenpox if already manifested.

[Congenital toxoplasmosis]. / Kongenitalna toksoplazmoza.

INTRODUCTION: Toxoplasma gondii is a ubiquitous parasite of all species of mammals and birds (1). Most often the infection in the immunocompetent persons is asymptomatic. Symptoms (if present) are usually mild and self-limited. Infection in the fetus and immunodeficient patients may lead up to clinically severe and often fatal toxoplasmosis (2). ETIOLOGY: Toxoplasma exists in three forms: oocysts, tissue cysts and tachyzoites. The definitive hosts of Toxoplasma are members of the cat family. They shed unsporulated oocysts in the feces. After sporulation oocysts become infectious. Tachyzoites are crescent-shaped forms responsible for manifestations of acute Toxoplasma infection in the intermediate hosts (6,7). Cysts are formed, particularly in brain, heart muscle and skeletal muscles. The cyst forms of the parasite are seen in the latent stage of the infection. Postnatally acquired toxoplasmosis is a consequence of infection from cysts (by ingestion of undercooked meat of infected animals), oocysts (by ingestion of soil, fruits, vegetables contaminated by cat feces) and tachyzoites (by blood transfusion). Congenital Toxoplasma infection causes congenital toxoplasmosis. PATHOGENESIS: Some authors represented the concept that latent (chronic) infection with Toxoplasma during pregnancy can result in congenital infection in the offspring (8-11). Now it is generally agreed that congenital transmission of Toxoplasma occurs only when the infection is acquired during gestation (6,7, 12-16). More than half of the fetuses escape infection, one-third are definitely infected, and the infection is more often subclinical than clinically obvious (15). The fetus is infected hematogenously from inflammatory foci in the placenta formed during parasitemia in the mother. CLINICAL MANIFESTATIONS: Approximately 75% of congenitally infected newborns are asymptomatic. Wilson's study indicates that nearly all such children will develop adverse sequelae (neurologic, intellectual, audiologic and ophthalmologic) 21). Severe forms of congenital toxoplasmosis occur only in 10% of infected offsprings. Clinical manifestations of congenital toxoplasmosis are different. Clinical findings in patients with congenital toxoplasmosis may include: chorioretinitis and other ocular findings, central nervous system abnormalities (such as microcephaly, hydrocephalus, encephalomyelitis, seizures and mental retardation), icterus, hepatosplenomegaly, rash, anemia, erythroblastosis, thrombopenia. INCIDENCE: Incidence of human congenital toxoplasmosis is different in different countries. The incidence in Britain is 0.6 subclinical infection and 0.09 severe illnesses per 1000 births (22). The incidence in USA is between 1/1000 and 1/8000 live births (23). In France the incidence is 1/2000. In Slovenia the incidence is 2.3 cases per 1000 births (25). DIAGNOSIS: Diagnostic methods are: 1. Isolation of the parasite from the placenta, blood, body fluids (by inoculation of specimens into mice or tissue cultures). 2. Histologically by demonstration of tachyzoites in tissue sections or smears of body fluids. 3. Serologic diagnosis. The most important diagnostic methods are serologic tests. For diagnosis of congenital toxoplasmosis determination of IgM antibody (in the serum of newborn infant) has the greatest importance. The fetus is able to produce IgM specific antibody. The presence of IgM antibodies in serum obtained from the neonate is an evidence of fetus infection in utero. Maternal IgM antibodies do not pass the placenta. IgM antibodies may be demonstrable by indirect fluorescent antibody test (IgM-IFA), enzyme linked immunosorbent assay (IgM-ELISA), double sendwich IgM enzyme-linked immunosorbent assay (DS-IgM-ELISA), IgM immunosorbent agglutination assay (IgM-ISAGA) and reversed enzyme immunoassay (REI). For diagnosis of congenital toxoplasmosis the next tests are also applied: Sabin-Feldman Dye test, indirect fluorescent antibody test for IgG antibodies (IgG-IFA) and enzyme

[Herpes zoster--treatment with acyclovir]. / Herpes zoster--lecenje aciklovirom.

We investigated the effect of acyclovir to the evolution of cutaneous changes and acute herpetic neuralgia at the time of herpes zoster infection. The examined group of 47 patients predominantly consisted of women in older ages, with anamnestic data usually referring to the chronic disease or stress as a provoking factor. In case of 19 patients the therapy was initiated in the phase of maculopapular changes, in 24 patients it was in the phase of vesicular changes and in 4 patients in the phase of encrustation. The evolution of cutaneous changes was accelerated under the acyclovir therapy regardless of the phase in which it was initiated. The intensity and duration of acute herpetic neuralgia directly depended on the time of therapy initiation. The patients who were given the therapy in time (not later than 6 days after the disease onset) reported the pain of lower intensity which completely ceased at the time of hospital discharge.

[Serologic diagnosis of infectious mononucleosis]. / Seroloska dijagnostika infektivne mononukleoze.

9,249 persons were examined by Paul-Bunnell-Davidson test and in 329 heterophile antibodies were established in titre > 1/40 which enables, with corresponding clinical-laboratory parameters, diagnosis of infectious mononucleosis caused by Epstein-Barr virus. In 271 persons diagnosis could not be established by testing only one sample of serum and performing only one test. That is why Epstein-Barr virus specific tests were recommended and their diagnostic possibilities in certain stages of Epstein-Barr virus infection have been theoretically considered.

[Hemorrhagic fever with renal syndrome in Vojvodina]. / Hemoragijska groznica s bubreznim sindromom u Vojvodini.

This paper presents 4 serologically confirmed cases of hemorrhagic fever with kidney syndrome. The objective of this study was to point to occurrence of unexpected hemorrhagic fever with kidney syndrome, to different clinical pictures and differential-diagnostic difficulties as well as to therapeutic procedures of serious cases. The disease had a sudden onset with general signs of infection in all our patients. 3 out of 4 patients had had a dominant symptomatology in regard to gastrointestinal tract, whereas signs of acute renal insufficiency appeared later. In 3 patients there was a complete recovery without consequences, while one female patient died on the twelfth day of the disease.

[Lyme disease--neuroborreliosis]. / Lajmska bolest--neuroborelioza.

Lyme disease is an infective disease caused by Borrelia burgdorferi transmitted by ticks of the Ixodes ricinus. The disease usually has three stages whereas the last, because of domination of neurologic symptomatology is called "neuroborreliosis". This is a case report of a female patient with neuroborreliosis in whom, due to lack of symptoms and signs which characterize the first stage of Lyme disease as well as lack of evidence about the tick, nobody assumed such an etiology. Lyme disease was not confirmed by serologic evaluation until the third stage of the disease occurred. This case points to the conclusion that by differential diagnosis of meningeal syndrome accompanied by maintenance and progredience of neurologic deficit and disorders in mental sphere one should think of the Lyme disease.

[The Epstein-Barr virus and chronic fatigue syndrome]. / Epstein-Barrov virus i sindrom hronicnog umora.

Lately discovered chronic fatigue syndrome is associated with Epstein-Barr virus infection. The objective of this paper was to detect this syndrome in our patients. 31 patients with cured acute infective mononucleosis were examined by questionnaire, physical check-up and laboratory analyses in order to detect disorders characteristic for chronic fatigue syndrome. Six months after they had been cured, out of 7 patients 5 patients complained of frequent sore throat, fatigue and exhaustion, and a year later, all 5 patients were sleepy and tired all the time. More than a year after the acute illness 19 patients were examined and in 5.6% frequent sore throat and enlarged neck lymph nodes occurred. The gathered results point to disorders characteristic for chronic fatigue syndrome in a high percentage. This pilot study should only be the beginning of examinations of this kind.