Infectious diseases with the dominant involvement of skin: erysipelas, felinosis (cat-scratch fever). Erysipelas suis (erysipeloid). Rat-bite fever (sodoku). TORCH-infections. Toxoplasmosis. Hospital (-acquired) or nosocomial infections.

http://intranet.tdmu.edu.ua/data/books/And-INF.pdf

TORCH Syndrome (Chronic Congenital Infection Syndrome)

TORCH syndrome has come to be a widely used preliminary diagnosis to describe a newborn infant who has one or more abnormalities which can occur as a result of an intrauterine infection . The term was originally coined as a mnemonic to emphasize that herpes simplex virus could produce effects similar to those already recognized as due to other agents. The word TORCH is an acronym for Toxoplasma, Other (especially syphilis), Rubella, Cytomegalovirus, Herpes. STORCHES is another acronym where HE stands for herpes and S for syphilis and serum hepatitis.

TORCH syndrome is a phrase likely to remain in common usage because it is much less cumbersome than the phrase “chronic congenital infection syndrome”, a phrase that is practically synonymous with TORCH syndrome.

A chronic congenital infection can be defined as an infection which has apparently been present for more than a month, with the manifestations still present at birth. Some chronic congenital infections arc active; that is, associated with evidence of an active inflammatory response, as well as recovery of the infectious agent from the infant. Other chronic congenital infections are probably inactive or “burnt out” with only the congenital anomaly or damaged organ remaining as evidence of past congenital infection.

Clinical Diagnosis

The TORCH syndrome should be suspected when any of the three following general findings are present.

1.    Intrauterine growth retardation.  Intrauterine growth retardation is defined as a low birth weight for the period of gestation (small for gestational age), as estimated by dates and by physical examination. It is particularly suggestive of congenital rubella infection but also can occur with other congenital infections or noninfectious maternal or fetal diseases.

2.    Congenital defects, indicating teratogenesis or damaged organs. Those defects which are most frequently associated with congenital infections are congenital heart disease (especially patent ductus arteriosus or pulmonic stenosis), CNS abnormalities (especially microcephaly, hydrocephalus, psychomotor retardation), eye abnormalities (especially cataracts, glaucoma, chorioretinitis), and deafness.

3.    Signs suggesting chronic active infection. Several clinical patterns should suggest the possibility of an active congenital infection.

a.      Jaundice with hepatosplenomegaly suggests infection involving the liver.

b.      Thrombocytopenic purpura suggests infection involving the bone marrow.

с. Other signs suggesting active infection include petechial, pustular, or bullous rash, CSF pleocytosis, lytic bone lesions, pneumonitis, myocarditis, rhinitis, vomiting, or diarrhea.

Many combinations of the above findings have been observed in chronic congenital infections. Occasionally, a single malformation or a transient sign of active infection is observed. The presence of one of the above findings should stimulate the clinician to look for other signs of congenital infection.

Asymptomatic infection with no detectable abnormalities can occur with most of these congenital infections. Some of the abnormalities most frequently associated with specific congenital infections are described below.

Possible Etiologies

Rubella Virus http://emedicine.medscape.com/article/968523-overview (Fig. 1). Congenital rubella infection can be classified into several major patterns.

Fig. 1. Rubella virus in RK-13 cells. Electron microscopy.

1.      Classical congenital rubella syndrome was originally described before rubella virus could be cultured in the laboratory. The major features are congenital heart disease (particularly patent ductus arteriosus or pulmonic stenosis) and eye defects (particularly cataracts, glaucoma, or microphthalmia)(Fig. 2-4). Microcephaly or deafness may also be present.

Fig. 2. Congenital rubella. Cataract.

Fig. 3.Congenital rubella. Corneal caligo.

Fig. 4. Congenital rubella. Haemorrhagic rash and hepatosplenomegaly.

2.      Expanded congenital rubella syndrome was defined in the severe epidemic in the United States in 1964, when a number of other manifestations were clearly recognized for the first time. These included intrauterine growth retardation, jaundice with hepatosplenomegaly, thrombocytopenic purpura, encephalitis and myocarditis, observed in various combinations. The term “blueberry muffin” baby was coined to describe the yellow baby with purple spots, be cause of jaundice and purpura or dermal erythropoesis. Other manifestations may include a large anterior fontanelle, transient longitudinal bone radiolucencies, failure to grow well, unusual dermatoglyphics and dental enamel defects. Retinitis manifested by excessive pigmentation or depigmentation was not progressive or associated with decreased vision.

3. Late-onset rubella syndrome. Congenital rubella infection sometimes results in minimal symptoms at birth, but after 3 to 6 months may present with an acute severe multisystem disease, with interstitial pneumonia, skin rash, diarrhea, hypogammaglobulinemia, and circulating immune complexes. Aseptic meningitis, hepatosplenomegaly, thrombocytopenia, and Pneumocystis pneumonia may also occur.

Diabetes mellitus has been observed later in childhood in follow-up studies of some infants with congenital rubella infection. Hypotonia or convulsions or a chronic progressive panence-phalitis also can occur in later childhood.

4. Isolated defects can occur, particularly language retardation, strabismus, deafness, and neonatal hepatitis.

New Proposed Criteria. In 1980 new definitions were proposed for classification of congenital rubella syndrome (CRS) cases because of the difficulty in some situations. The Center for Disease Control has recommended the following classification:

I. CRS Confirmed

Defects present and 1 or more of the following:

Rubella virus isolated

Rubella-specific IgM present

Rubella hemagglutination-inhibition (HI) titer in the infant г 3 months of age persisting above and beyond that expected from passive transfer of maternal antibody (i.e., rubella HI titer in the infant which does not fall off at the expected rate of one 2-fold dilution per month)

II. CRS Probable

Clinical documentation of lab data insufficient for confirmation

Any 2 complications listed in A or 1 from A and 1 from В

A.     Cataracts/congenital glaucoma (either or both count as 1), congenital heart disease, loss of hearing, pigmentary retinopathy

B.     Purpura, splenomegaly, jaundice with onset beginning 24 hours after birth, microcephaly, mental retardation, meningoencephalitis, radiolucent bone disease

III. CRS Possible

Compatible clinical findings which do not fulfill the above criteria for a probable case

IV.    Congenital Rubella Infection Only No defects present and Lab evidence of infection (see criteria for confirmed category)

V.     Not CRS

1 or more of any of the following inconsistent lab findings in child without evidence of an immunodeficiency disease

Rubella HI titer absent in a child < 24 months

Rubella HI titer absent in mother

Rubella HI titer decline in an infant a 3 months of age consistent with the normal decline of passively transferred maternal antibody after birth (the expected rate of decline of maternal antibodies is one 2-fold dilution per month)

 

Toxoplasmosis. http://emedicine.medscape.com/article/229969-overview Several clinical patterns of toxoplasmosis can be defined (Fig. 5).

Fig. 5. Trophosoids of toxoplasma (painting by Leishman).

http://www.cdc.gov/parasites/toxoplasmosis/

1. Jaundice with hepatosplenomegaly may occur, without evidence of blood group incompatibility. Fever, rash, lymphadenopathy, pneumoni-tis, vomiting or diarrhea may also be present. This acute pattern has also been called the generalized form of congenital toxoplasmosis. The patient may also have some neurologic manifestations.

2. Neurologic malformations may occur in various combinations and include hydrocephalus or microcephaly, cerebral calcifications (Fig. 6), choriore-tinitis, and convulsions. These abnormalities are ofteot recognized until the child is several months of age but occasionally may be noted in infants with the jaundice pattern.

Fig. 6. Encephalitis in case of toxoplasmosis. MRT.

3. Isolated defects, particularly mental retardation, deafness, or microphthalmia (Fig. 7), may occur. Repeated abortions, resulting from congenital toxoplasmosis, have been described. Repeated congenital newborn disease in infants (Fig. 8, 9) born to the same woman has been reported but is rare.

Fig. 7. Toxoplasmous chorioretinitis – acute and chronic.

Fig. 8. Congenative hydrocephaly in toxoplasmosis.

Fig. 9. Congenative toxoplasmosis. Intracranial calcinates.

Toxoplasmosis is caused by infection with the protozoan Toxoplasma gondii, an obligate intracellular parasite. The infection produces a wide range of clinical syndromes in humans, land and sea mammals, and various bird species. T gondii has been recovered from locations throughout the world, except Antarctica (see the image below).

Toxoplasmosis. Toxoplasma gondii tachyzoites (Giemsa stain).

Nicolle and Manceaux first described the organism in 1908, after they observed the parasites in the blood, spleen, and liver of a North African rodent, Ctenodactylus gondii. The parasite was named Toxoplasma (arclike form) gondii (after the rodent) in 1909. In 1923, Janku reported parasitic cysts in the retina of an infant who had hydrocephalus, seizures, and unilateral microphthalmia. Wolf, Cowan, and Paige (1937-1939) determined that these findings represented the syndrome of severe congenital T gondii infection.

There are 3 major genotypes (type I, type II, and type III) of T gondii. These genotypes differ in their pathogenicity and prevalence in people. In Europe and the United States, type II genotype is responsible for most cases of congenital toxoplasmosis.^[1]

T gondii infects a large proportion of the world’s population (perhaps one third) but uncommonly causes clinically significant disease.^[2] However, certain individuals are at high risk for severe or life-threatening toxoplasmosis. Individuals at risk for toxoplasmosis include fetuses, newborns, and immunologically impaired patients. (See Etiology and Pathophysiology and Epidemiology.)

Congenital toxoplasmosis is usually a subclinical infection. Among immunodeficient individuals, toxoplasmosis most often occurs in those with defects of T-cell–mediated immunity, such as those with hematologic malignancies, bone marrow and solid organ transplants, or acquired immunodeficiency syndrome (AIDS).In most immunocompetent individuals, primary or chronic (latent) T gondii infection is asymptomatic. A small percentage of these patients eventually develop retinochoroiditis, lymphadenitis, or, rarely, myocarditis and polymyositis. (SeePresentation and Workup.)

Patient education

Educate the public in toxoplasmosis-prevention methods, eg, protecting children’s play areas from cat litter. Mothers with toxoplasmosis must be completely informed of the disease’s potential consequences to the fetus.[#Etiology]

Etiology and Pathophysiology

Life cycle of Toxoplasma gondii

T gondii has 2 distinct life cycles. The sexual cycle occurs only in cats, the definitive host. The asexual cycle occurs in other mammals (including humans) and various strains of birds. It consists of 2 forms: tachyzoites (the rapidly dividing form observed in the acute phase of infection) and bradyzoites (the slowly growing form observed in tissue cysts).

A cat becomes infected with T gondii by eating contaminated raw meat, wild birds, or mice. The organism’s sexual cycle then begins in the cat’s gastrointestinal (GI) tract. Macrogametocytes and microgametocytes develop from ingested bradyzoites and fuse to form zygotes. The zygotes then become encapsulated within a rigid wall and are shed as oocysts. The zygote sporulates and divides to form sporozoites within the oocyst. Sporozoites become infectious 24 hours or more after the cat sheds the oocyst via feces.

During a primary infection, the cat can excrete millions of oocysts daily for 1-3 weeks. The oocysts are very strong and may remain infectious for more than one year in warm humid environments.

T gondii oocysts, tachyzoites, and bradyzoites can cause infection in humans. Infection can occur by ingestion of oocysts following the handling of contaminated soil or cat litter or through the consumption of contaminated water or food sources (eg, unwashed garden vegetables). Transmission of tachyzoites to the fetus can occur via the placenta following primary maternal infection.

Rarely, infection by tachyzoites occurs from ingestion of unpasteurized milk or by direct entry into the bloodstream through a blood transfusion or laboratory accident. Transmission can also occur via ingestion of tissue cysts (bradyzoites) in undercooked or uncooked meat or through transplantation of an organ that contains tissue cysts. (Slaughterhouse workers and butchers may be at increased risk of infection.) In Europe and the United States, pork is the major source of T gondii infection in humans.

The seroprevalence of T gondii antibodies in the human population varies geographically, with prevalence rates approaching 90% in some European countries, while seropositivity rates in the United States have been estimated to fall between 10% and 15%.^{[3, 4]} Infection with the human immunodeficiency virus (HIV) does not seem to effect T gondii seropositivity, and there does not appear to be any difference in the rate of toxoplasmosis infection among patients with AIDS with and without cats.^[4]

Cellular invasion

As previously stated, T gondii oocysts are ingested in material contaminated by feces from infected cats. Oocysts may also be transported to food by flies and cockroaches. When T gondii is ingested, bradyzoites are released from cysts or sporozoites are released from oocysts, and the organisms enter gastrointestinal cells. Host cell receptors consisting of laminin, lectin, and SAG1 are involved in T gondii tachyzoite attachment and penetration. Tachyzoites multiply, rupture cells, and infect contiguous cells. They are transported via the lymphatics and are disseminated hematogenously throughout the tissues.

The ability of T gondii to actively penetrate host cells results in formation of a parasitophorous vacuole that is derived from the plasma membrane, which is entirely distinct from a normal phagocytic or endocytic compartment.^[5] Following apical attachment, the parasite rapidly enters the host cell in a process that is significantly faster than phagocytosis. The vacuole is formed primarily by invagination of the host cell plasma membrane, which is pulled over the parasite through the concerted action of the actin-myosin cytoskeleton of the parasite. During invasion, the host cell is essentially passive and no change is detected in membrane ruffling, the actin cytoskeleton, or phosphorylation of host cell proteins. (See the images below.)

Toxoplasmosis. Toxoplasma gondii tachyzoites in cell line. Toxoplasma gondii in infected monolayers of HeLa cells (Giemsa stain).

Tachyzoites proliferate, producing necrotic foci surrounded by a cellular reaction. Upon the development of a normal immune response, tachyzoites disappear from tissues. In immunodeficient individuals and in some apparently immunologically healthy patients, the acute infection progresses, resulting in potentially lethal consequences such as pneumonitis, myocarditis, and necrotizing encephalitis.

Tissue cysts form as early as 7 days after infection and remain for the lifespan of the host. The tissue cysts are up to 60μm in diameter, each containing up to 60,000 organisms. They produce little or no inflammatory response but cause recrudescent disease in immunocompromised patients or retinochoroiditis in congenitally infected older children.

Changes in T-lymphocyte levels

Alterations in subpopulations of T lymphocytes are profound and prolonged during acute acquired T gondii infection. These have been correlated with disease syndromes but not with disease outcome. Some patients with prolonged fever and malaise have lymphocytosis, increased suppressor T-cell counts, and a decreased helper-to-suppressor T-cell ratio. These patients may have fewer helper cells even when they are asymptomatic.

In some patients with lymphadenopathy, helper-cell counts are diminished for more than 6 months after infection onset. Ratios of T-cell subpopulations may also be abnormal in asymptomatic patients. Some patients with disseminated toxoplasmosis have a very marked reduction in T cells and a marked depression in the ratio of helper to suppressor T lymphocytes. Depletion of inducer T lymphocytes in patients with AIDS may contribute to the severe manifestations of toxoplasmosis observed in these patients.

Retinochoroiditis

Retinochoroiditis usually results from reactivation of congenital infection, although cases have been recorded that were part of acute infection.^{[6, 7]}

There are 5 hypotheses related to the inflammatory process of ocular toxoplasmosis, as follows^[8] :

• Infection and inflammatory response after spontaneous cyst rupture
• Parasitic toxic mediators released from T gondii
• Lytic effect of inflammatory mediators
• Delayed-type hypersensitivity reaction to antigens of T gondii
• Cell-mediated immunity against retinal antigens

When the organism reaches the eye through the bloodstream, depending on the host’s immune status, a clinical or subclinical focus of infection begins in the retina. As the host’s immune system responds and the tachyzoites convert themselves into bradyzoites, the cyst forms. The cyst is extremely resistant to the host’s defenses, and a chronic, latent infection ensues. If a subclinical infection is present, no funduscopic changes are observed. The cyst remains in the normal-appearing retina. Whenever the host’s immune function declines for any reason, the cyst wall may rupture, releasing organisms into the retina, and the inflammatory process restarts. If an active clinical lesion is present, healing occurs as a retinochoroidal scar. The cyst often remains inactive within or adjacent to the scar. (See the image below.)

Inactive retinochoroidal scar secondary to toxoplasmosis

Toxoplasma parasites are rarely identified in aqueous humor samples from patients with active ocular toxoplasmosis.^[9] This suggests that parasite proliferation occurs only during the early phase of infection and that the retinal damages are probably caused by subsequent inflammatory responses.

When human retinal pigment epithelium (RPE) cells are infected with Toxoplasma gondii, there is an increased production of several cytokines, including interleukin 1beta (IL-1ß), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor, and intercellular adhesion molecule (ICAM).^[10] Patients with acquired toxoplasmic retinochoroiditis exhibit higher levels of IL-1 than asymptomatic patients.^[11]

It appears that IL-1 gene polymorphisms, in particular genotypes that are related with a high production of IL-1a, may be associated with recurrence of toxoplasmic retinochoroiditis.^[12] IL-10 polymorphisms associated with a low production of IL-10 also appear to be associated with the occurrence of toxoplasmic retinochoroiditis.^[13] In contrast, tumor necrosis factor (TNF)–alpha gene polymorphism has not been found to be associated with the occurrence or recurrence of toxoplasmic retinochoroiditis.^[14]

Congenital toxoplasmosis

Approximately 10-20% of pregnant women infected with T gondii become symptomatic.^[15] The most common signs of infection are lymphadenopathy and fever. If the mother was infected prior to pregnancy, there is virtually no risk of fetal infection, as long as she remains immunocompetent.^[15]

When a mother is infected with T gondii during gestation, the parasite may be disseminated hematogenously to the placenta. When this occurs, infection may be transmitted to the fetus transplacentally or during vaginal delivery.^{[16, 17]}

If the mother acquires the infection in the first trimester and it goes untreated, the risk of infection to the fetus is approximately 14-17%, and toxoplasmosis in the infant is usually severe. If the mother is infected in the third trimester and it goes untreated, the risk of fetal infection is approximately 59-65%, and involvement is mild or not apparent at birth. These different rates of transmission are most likely related to placental blood flow, the virulence and amount of T gondii acquired, and the immunologic ability of the mother to restrict parasitemia.

The most significant manifestation of toxoplasmosis in the fetus is encephalomyelitis, which may have severe results. Approximately 10% of prenatal T gondii infections result in abortion or neonatal death. In approximately 67-80% of prenatally infected infants, the infection is subclinical and can be diagnosed using only serological and other laboratory methods. Although these infants appear healthy at birth, they may develop clinical symptoms and deficiencies later in life.

Congenital toxoplasmosis caused by atypical genotypes is more severe than that caused by typical genotypes.^[1]

Some infants with more severe congenital infection appear to have Toxoplasma antigen–specific lymphocytic anergy, which may be important in the pathogenesis of their disease. Monoclonal gammopathy of the immunoglobulin G (IgG) class has been described in congenitally infected infants, and IgM levels may be elevated in newborns with congenital toxoplasmosis. Glomerulonephritis with deposits of IgM, fibrinogen, and Toxoplasma antigen has been reported in congenitally infected individuals.

Circulating immune complexes have been detected in sera from an infant with congenital toxoplasmosis and in older individuals with systemic, febrile, and lymphadenopathic forms of toxoplasmosis. However, these complexes did not persist after signs and symptoms resolved. Total serum levels of IgA may be diminished in congenitally infected babies, but no predilection toward associated infections has beeoted. The predilection toward predominant involvement of the central nervous system (CNS) and retina in this congenital infection has not been fully explained.

Infection in immunocompromised patients

Most cases of toxoplasmosis in immunocompromised patients are a consequence of latent infection and reactivation. In patients with AIDS, T gondii tissue cysts can reactivate with CD4 counts of less than 200 cells/μL; with counts of less than 100 cells/μL, clinical disease becomes more likely.^[18] Without adequate prophylaxis or restoration of immune function, patients with CD4 counts of less than 100 cells/μL who are T gondii IgG-antibody positive have a 30% risk of eventually developing reactivation disease.^[19]

Although toxoplasmosis in immunocompromised patients may manifest as retinochoroiditis, reactivation disease in these individuals is typically in the CNS, with brain involvement being common.

Toxoplasmic encephalitis and brain abscess present most commonly as headache, but focal neurologic deficits and seizures are as common. With significant disease, patients may also demonstrate the signs and symptoms of elevated intracranial pressure. Cerebral toxoplasmosis is generally identified on computed tomography (CT) scan as multiple ring-enhancing lesions; however, solitary lesions may be seen, and negative CT or magnetic resonance imaging (MRI) scans should not rule out the diagnosis of CNS toxoplasmosis.^[20]

Aside from CNS toxoplasmosis, other conditions commonly identified in immunocompromised patients include toxoplasmic pneumonitis, myocarditis, and disseminated toxoplasmosis. Toxoplasmic pneumonitis typically presents with symptoms typical for an infectious pulmonary process, including fever, dyspnea, and cough. Chest radiography is ofteonspecific, but findings may have an appearance similar to that of Pneumocystis (carinii) jiroveci pneumonia. Diagnosis is established via bronchoalveolar lavage. Most patients with extra-CNS manifestations of toxoplasmosis will also be noted to have CNS lesions when appropriate radiographic studies have been performed.

Only 10-20% of toxoplasmosis cases in adults and children are symptomatic. Toxoplasmosis is a serious and often life-threatening disease in immunodeficient patients. Congenital toxoplasmosis may manifest as a mild or severe neonatal disease, with onset during the first month of life or with sequelae or relapse of a previously undiagnosed infection at any time during infancy or later in life. Congenital toxoplasmosis has a wide variety of manifestations during the perinatal period.

Acute toxoplasmosis in immunocompetent persons

• Approximately 80-90% of patients are asymptomatic. Symptomatic disease may be characterized as follows:
• Patients may have cervical lymphadenopathy with discrete, usually nontender, nodes smaller than 3cm in diameter
• Fever, malaise, night sweats, and myalgias have been reported
• Patients may have a sore throat
• Retroperitoneal and mesenteric lymphadenopathy with abdominal pain may occur
• Retinochoroiditis is reported

Acute toxoplasmosis in hosts who do not have AIDS but are immunodeficient

The disease in these patients may be newly acquired or a reactivation. It may be characterized as follows:

• CNS toxoplasmosis occurs in 50% of patients – Seizure, dysequilibrium, cranial nerve deficits, altered mental status, focal neurologic deficits, headache
• Patients may have encephalitis, meningoencephalitis, or mass lesions
• Hemiparesis and seizures have been reported
• Patients may report visual changes
• They may have signs and symptoms similar to those observed in immunocompetent hosts.
• Patients may have flulike symptoms and lymphadenopathy
• Myocarditis and pneumonitis are reported.
• Toxoplasmic pneumonitis can occur – Typical symptoms of a pulmonary infection, mirroring in particular P (carinii) jiroveci, including nonproductive cough, dyspnea, chest discomfort, and fever

Symptoms associated with reactivation toxoplasmosis are dependent on the tissue or organ affected.

Clinical manifestations of toxoplasmosis in patients with AIDS

Brain involvement (ie, toxoplasmic encephalitis), with or without focal CNS lesions, is the most common manifestation of toxoplasmosis in individuals with AIDS.

Clinical findings include the following:

• Altered mental state
• Seizures
• Weakness
• Cranial nerve disturbances
• Sensory abnormalities
• Cerebellar signs
• Meningismus
• Movement disorders
• Neuropsychiatric manifestations

The characteristic presentation is usually a subacute onset, with focal neurologic abnormalities in 58-89% of cases. However, in 15-25% of cases, the clinical presentation is more abrupt, with seizures or cerebral hemorrhage. Most commonly, hemiparesis and/or speech abnormality is the major initial manifestation.

Brainstem involvement often produces cranial nerve lesions, and many patients exhibit cerebral dysfunction with disorientation, altered mental state, lethargy, and coma.

Less commonly, parkinsonism, focal dystonia, rubral tremor, hemichorea-hemiballismus, panhypopituitarism, diabetes insipidus, or syndrome of inappropriate antidiuretic hormone secretion may dominate the clinical picture.

In some patients, neuropsychiatric symptoms such as paranoid psychosis, dementia, anxiety, and agitation may be the major manifestations.

Diffuse toxoplasmic encephalitis may develop acutely and can be rapidly fatal; generalized cerebral dysfunction without focal signs is the most common manifestation, and CT scan findings are normal or reveal cerebral atrophy.

Spinal cord involvement manifests as motor or sensory disturbances of single or multiple limbs, bladder or bowel dysfunctions, or both and local pain. Patients may present with clinical findings similar to those of a spinal cord tumor. Cervical myelopathy, thoracic myelopathy, and conus medullaris syndrome have been reported.

Pulmonary toxoplasmosis (pneumonitis) due to toxoplasmosis is increasingly recognized in patients with AIDS who are not receiving appropriate anti-HIV drugs or primary prophylaxis for toxoplasmosis. The diagnosis may be confirmed by demonstrating T gondii in bronchoalveolar lavage fluid.

Pulmonary toxoplasmosis occurs mainly in patients with advanced AIDS (mean CD4⁺ count of 40 cells/µL ±75 standard deviation) and primarily manifests as a prolonged febrile illness with cough and dyspnea. Pulmonary toxoplasmosis may be clinically indistinguishable from P (carinii) jiroveci pneumonia, and the mortality rate, even when treated appropriately, may be as high as 35%.

Extrapulmonary toxoplasmosis develops in approximately 54% of persons with toxoplasmic pneumonitis.

Ocular toxoplasmosis, ie, toxoplasmic retinochoroiditis, is relatively uncommon in patients with AIDS; it commonly manifests as ocular pain and loss of visual acuity. Funduscopic examination usually demonstrates necrotizing lesions, which may be multifocal or bilateral. Overlying vitreal inflammation is often present and may be extensive. The optic nerve is involved in as many as 10% of cases.

Other, uncommon manifestations of toxoplasmosis in patients with AIDS include the following:

• Panhypopituitarism and diabetes insipidus
• Multiple organ involvement, with the disease manifesting as acute respiratory failure and hemodynamic abnormalities similar to septic shock
• Syndrome of inappropriate antidiuretic hormone secretion and possibly orchitis
• Gastrointestinal system invasion of T gondii may result in abdominal pain, diarrhea, and/or ascites (due to involvement of the stomach, peritoneum, or pancreas)
• Acute hepatic failure
• Musculoskeletal involvement
• Parkinsonism
• Focal dystonia
• Rubral tremor
• Hemichorea-hemiballismus

Congenital toxoplasmosis

This is most severe when maternal infection occurs early in pregnancy. Approximately 15-55% of congenitally infected children do not have detectable T gondii –specific IgM antibodies at birth or early infancy. Approximately 67% of patients have no signs or symptoms of infection.

Retinochoroiditis occurs in about 15% of patients, and intracranial calcifications develop in about 10%. Cerebrospinal fluid (CSF) pleocytosis and elevated protein values are present in 20% of patients.

Infected newborns have anemia, thrombocytopenia, and jaundice at birth. Microcephaly has been reported. Affected survivors may have mental retardation, seizures, visual defects, spasticity, or other severe neurologic sequelae.

Ocular toxoplasmosis

Patients develop retinochoroiditis (focal necrotizing retinitis). They have a yellowish white, elevated cotton patch with indistinct margins. The lesions may occur in small clusters. Congenital disease is usually bilateral and acquired disease is usually unilateral.

Symptoms include the following:

• Impaired vision – Either sudden or gradual, depending on the site of infection
• Blurred vision
• Scotoma
• Pain
• Photophobia
• Floaters
• Red eye
• Metamorphopsia

Physical Examination

The acquired infection is usually subclinical and asymptomatic. In 10-20% of cases that become symptomatic, the patient develops a flulike illness characterized by fever, lymphadenopathy, malaise, myalgias, and a maculopapular skin rash that spares the palms and the soles. In individuals who are immunocompetent, the disease is benign and self-limited. Hepatosplenomegaly can also occur. Infrequently, patients develop myocarditis, polymyositis, pneumonitis, hepatitis, or encephalitis

The most common form of symptomatic acute toxoplasmosis in immunocompetent individuals is lymphadenopathy. The typical presentation is painless, firm lymphadenopathy that is confined to 1 chain of nodes, most commonly cervical.

Ophthalmologic examination reveals multiple yellow-white cottonlike patches with indistinct margins located in small clusters in the posterior pole.

A flare-up of congenitally acquired retinochoroiditis is often associated with scarred lesions juxtaposed to the fresh lesion.

Ocular toxoplasmosis (retinochoroiditis)

Symptoms of retinochoroiditis include the following:

• Decreased visual acuity – Other deficits depend on the location of the lesion
• White focal lesions with inflammation of the vitreous humor (the classic “headlight in the fog” appearance) seen on ophthalmoscopic examination
• Recurrent lesions at the border of the retinochoroidal scars

Immunocompromised individuals (AIDS CD4 count < 100 cells/microL)

Host immune function plays an important role in the pathogenicity of toxoplasmosis. Symptoms depend largely on the organ system and tissue involved and may be gradual in onset over a few weeks. They include the following:

• CNS toxoplasmosis – Seizure, mental status change, focal motor deficits, cranial nerve disturbances, sensory disturbances, cerebellar abnormalities, movement disorders, neuropsychiatric findings
• Retinochoroiditis (similar to that seen in immunocompetent individuals)
• Pneumonitis – More common in patients who have undergone bone marrow transplantation and in patients with AIDS; nonproductive cough, blood-tinged sputum, hypoxia (symptoms indistinguishable from P [carinii] jiroveci)
• Septic shock–like presentation

Multifocal, bilateral, and relentlessly progressive lesions characterize the ocular involvement. Because of their immunosuppression, these patients often have problems mounting an inflammatory reaction, which makes the formation of a retinochoroidal scar difficult. Often, the serologic diagnosis is also difficult.

Congenital toxoplasmosis

The classic clinical triad of retinochoroiditis, cerebral calcifications, and convulsions defines congenital toxoplasmosis. Other findings include the following:

• Hydrocephalus
• Microcephaly
• Organomegaly
• Jaundice
• Rash
• Fever
• Psychomotor retardation

Results from basic laboratory studies such as complete blood cell count (CBC), chemistries, and liver function tests (LFTs) are typically normal, although lymphocytosis may be present.

Direct detection

The diagnosis of toxoplasmosis is confirmed with the demonstration of T gondii organisms in blood, body fluids, or tissue. T gondii may be isolated from the blood via either inoculation of human cell lines or mouse inoculation. Mouse inoculation may require a longer time to yield results and also is likely to be more expensive. Isolation of T gondii from amniotic fluid is diagnostic of congenital infection by mouse inoculation.

Polymerase chain reaction assay testing on body fluids, including CSF, amniotic fluid, bronchoalveolar lavage fluid, and blood, may be useful in the diagnosis. However, PCR assay is capable of detecting T gondii deoxyribonucleic acid (DNA) in either an aqueous sample or a vitreous sample in only one third of patients with ocular toxoplasmosis.

Indirect detection

Indirect detection is performed in pregnant women and in immunocompromised patients. Detection of immunoglobulin G (IgG) is possible within 2 weeks of infection using the enzyme-linked immunosorbent assay (ELISA) test, the IgG avidity test, and the agglutination and differential agglutination tests. (Acute and convalescent sera have no role in the indirect detection of toxoplasmosis.)

Procedures

The following diagnostic procedures may be performed for toxoplasmosis:

• Lumbar puncture – After imaging to identify evidence of increased intracranial pressure
• Brain biopsy
• Lymph node biopsy
• Amniocentesis – Perform amniocentesis at 20-24 weeks’ gestation if congenital disease is suggested
• Bronchoalveolar lavage

Tachyzoites may be demonstrated in tissues or smears obtained from biopsy. They also can be seen in CSF. CSF also shows mononuclear pleocytosis and elevated protein level. Tachyzoites demonstrate acute infection, while tissue cysts and bradyzoites are seen in chronic/latent infection (although they may be present in acute infection/reactivation).

Skin tests

Skin tests that show delayed skin hypersensitivity to T gondii antigens may be useful as a screening test.

Testing in pregnancy

Although testing in pregnancy may not be indicated and treatment may not have established literature support, a low index of suspicion is needed to identify acute infection in pregnant patients.

Ophthalmic disease

Antibody titers do not correlate with ophthalmic disease. Antitoxoplasmic antibodies may be very low and should be tested in undiluted (1:1) samples if possible. The absence of antibodies rules out the disease; nevertheless, false-negative results do occur.

Invasive techniques are usually reserved for difficult cases, such as patients who are immunocompromised. Ocular fluids can demonstrate the presence of intraocular antibody production. Polymerase chain reaction assay can detect the causative organism.

Immunoglobulin Testing

Acute systemic toxoplasmosis has traditionally been diagnosed by seroconversion. Anti-Toxoplasma immunoglobulin G (IgG) titers present a 4-fold increase that peak 6-8 weeks following infection and then decline over the next 2 years, although they remain detectable for life. Anti-Toxoplasma IgM appears in the first week of the infection and then declines in the next few months. The presence of anti-Toxoplasma IgA has also been shown to be detectable in acute infection; however, since the titers can last for more than 1 year, its value in helping to diagnose an acute phase is limited.

Detection of IgG is possible within 2 weeks of infection using the ELISA test, the IgG avidity test, and the agglutination and differential agglutination tests. The presence of IgG indicates a likely past infection, while the presence of IgM usually indicates acute infection (particularly in the absence of IgG). However, IgM has, in some cases, been documented to persist for months or years.

Lack of IgG and IgM may exclude infection. IgM alone that then transitions to IgG without IgM or both IgG and IgM indicates likely acute infection. There is a significant rate of false IgM positivity. The sensitivities and specificities of the commercially available IgM and IgG tests vary substantially.

Sabin-Feldman dye test

The Sabin-Feldman dye test is a sensitive and specific neutralization test for toxoplasmosis. It is used to measure primarily IgG antibody and is the standard reference test for toxoplasmosis. However, it requires live T gondii organisms; therefore, it is not available in most laboratories. (It is used primarily as a confirmatory test in reference laboratories.) High titers suggest acute toxoplasmosis.

Fluorescent antibody test

The indirect fluorescent antibody test is used to measure the same antibodies as the dye test. Titers parallel dye test titers. The IgM fluorescent antibody test is used to detect IgM antibodies within the first week of infection, but titers fall within a few months.

Hemagglutination test

The indirect hemagglutination test is easy to perform. However, it usually does not detect antibodies during the acute phase of toxoplasmosis. Titers tend to be higher and remain elevated longer.

ELISA test

The results from a double-sandwich IgM ELISA are more sensitive and specific than the results from other IgM tests.

IgG avidity test

The results of the IgG avidity test may help to differentiate patients with acute infection from those with chronic infection better than do alternative assays, such as assays that measure IgM antibodies. As is true for IgM antibody tests, the avidity test is most useful when performed early in gestation.

IgG produced early in infection is less avid and binds to T gondii antigens more weakly than do antibodies produced later in the course of infection. High antibody avidity indicates an older, earlier infection. This test may be helpful in the setting of pregnancy, as the timing of infection has prognostic value. A long-term pattern occurring late in pregnancy does not exclude the possibility that the acute infection may have occurred during the first months of gestation.

Imaging Studies

Head CT scanning in cerebral toxoplasmosis (general)

In most immunodeficient patients with toxoplasmic encephalitis, CT scans show multiple bilateral cerebral lesions. However, although multiple lesions are more common in persons with toxoplasmosis, they may be solitary. Therefore, a single lesion should not exclude toxoplasmic encephalitis as a diagnostic possibility.

Head CT scanning in cerebral toxoplasmosis (in patients with AIDS)

CT scans in patients with AIDS who have toxoplasmic encephalitis reveal multiple ring-enhancing lesions in 70-80% of cases. In patients with AIDS who have detectable Toxoplasma IgG and multiple ring-enhancing lesions on CT scans or MRIs, the predictive value for toxoplasmic encephalitis is approximately 80%.

Lesions tend to occur at the corticomedullary junction (frequently involving the basal ganglia) and are characteristically hypodense.

The number of lesions is frequently underestimated when assessed using CT scan images, although delayed imaging after a double dose of intravenous (IV) contrast material may improve the sensitivity of this modality. An enlarging, hypodense lesion that does not enhance is a poor prognostic sign.

Single-photon computed tomography

Single-photon computed tomography (SPECT) scanning is useful in distinguishing between CNS lymphoma and infection (ie, toxoplasmosis or any other infection).

PET scanning, radionuclide scanning, and MR techniques

Various positron emission tomography (PET) scanning, radionuclide scanning, and magnetic resonance techniques have been used to evaluate patients with AIDS who have focal CNS lesions and to specifically differentiate between toxoplasmosis and primary CNS lymphoma.

MRI

MRI has superior sensitivity (particularly if gadolinium is used for contrast) to CT scanning, and MRI scans often demonstrate a single or multiple lesion(s) or more extensive disease not apparent on CT scans. One study showed that MRI detected abnormalities in 40% of patients whose abnormalities were not detected on CT.

Toxoplasmic encephalitis lesions on MRIs appear as high-signal abnormalities on T2-weighted studies and have a rim of enhancement surrounding the edema on T1-weighted, contrast-enhanced images.

Hence, MRI should be used as the initial procedure when feasible (and especially if a single lesion is demonstrated on CT scan images). Nevertheless, even characteristic lesions on CT scans or MRIs are not pathognomonic of toxoplasmic encephalitis.

The major differential diagnosis of focal CNS lesions in patients with AIDS is CNS lymphoma, which manifests as multiple enhancing lesions in 40% of cases.

The probability of toxoplasmic encephalitis falls and the probability of lymphoma rises in the presence of single lesions on MRI scans. Therefore, a brain biopsy may be required to obtain a definitive diagnosis in patients with a solitary lesion (especially if confirmed with MRI).

CT scanning abnormalities improve after 2-3 weeks of treatment in approximately 90% of patients with AIDS who have toxoplasmic encephalitis. Complete resolution takes 6 weeks to 6 months; peripheral lesions resolve more rapidly than do deeper ones.

Smaller lesions usually resolve completely within 3-5 weeks as shown on MRI, but lesions with a mass effect tend to resolve more slowly and leave a small residual lesion.

A radiologic response to therapy lags behind the clinical response, with better correlation by the end of acute therapy.

Ultrasonography

Ultrasonographic diagnosis of congenital toxoplasmosis in a fetus is available at 20-24 weeks’ gestation. Fetal or neonatal ultrasonography can be useful in cases of known or suspected maternal acute infection and transplacental infection. Findings are generally nonspecific but include ventriculomegaly and CNS calcifications, particularly in the basal ganglia.

Cytomegalovirus. http://emedicine.medscape.com/article/215702-overview Newborns often acquire cytomegalovirus, as discussed in the section on the differential diagnosis of neonatal sepsis. Several patterns of congenital infection can be defined in addition to low birth weight.

1. Jaundice with marked hepatosplenomegaly may be due to cytomegalovirus infection. Transient hepatosplenomegaly may also occur. Portal hypertension is an uncommon late complication of neonatal cytomegalovirus hepatitis.

2. Thrombocytopenic purpura often occurs with the jaundice pattern. Transient petechiac may also be due to cytomegalovirus infection.

3. Neurologic abnormalities resembling those of toxoplasmosis can occur in various combinations or as isolated defects. These include microcephaly, chorioretinitis, cerebral calcifications, spastic diplegia or psychomotor retardation (Fig. 10). A single such neurologic abnormality may be the only abnormality. One study indicated cytomegalovirus infection accounted for only a small percentage of neurologically handicapped infants. However, such neurologic handicaps are frequent in children, and even asymptomatic infection has a high probability of having a significant impact on the infant’s prognosis.

Fig. 10. Cytomegaloviral encephalitis. MRT.

4.  Persistent interstitial pneumonia can occur as a result of infection acquired before or during birth, or can occur in the newborn period from blood transfusions containing the virus. Acquired neonatal cytomegalovirus pneumonia often is associated with hepatosplenomegaly and atypical lymphocytosis. Chronic interstitial pneumonia is also discussed in the chapters on pneumonia and on infections in patients with chronic disease.

5.  Asymptomatic infection, with excretion of the virus in the urine, occurs in about 1 % to 2 % of newborn infants, who apparently do not develop any sequelae.

 

Syphilis. In the case of syphilis, several clinical patterns can be observed in the newborn period.

1.      Rash is the most common manifestation. Typically, the rash is bullous, sharply demarcated, and involves the face, diaper area, palms or soles. An erythema multiforme rash may also be seen.

2.      Jaundice with hepatosplenomegaly may occur. The serum bilirubin is mostly the direct (conjugated) form.

 3. Monocytosis may be present, with an absolute monocyte count higher than 1500 raonocytes per cubic millimeter.

4. Lytic bone lesions, with periosteal reaction or metaphyseal destruction, may be observed on roentgenogram, which usually is taken because the infant fails to use an arm or leg.

5.      Chronic rhinitis can be a manifestation of syphilis in the newborn period.

6. Nephrotic syndrome may be the major manifestation of congenital syphilis during the new born period.

7. Asymptomatic infection is the most common pattern of congenital syphilis. Routine serologic testing for syphilis is not likely to be done in a normal newborn infant, so that detection of asymptomatic infection usually depends on serologic testing of the mother. The mother’s serology test results should always be transcribed onto the newborn’s record. If the mother’s test was done in early pregnancy, infection late in pregnancy of both mother and infant cannot be excluded, unless a VDRL is done at the time of delivery.

Herpes Simplex Virus. Often the infant is born prematurely if congenital infection has occurred. Herpes simplex virus can infect the infant just before or during delivery, or in the nursery. The infection can be asymptomatic or produce disease of varying severity.

1. Disseminated herpes simplex is the term usually used to describe the generalized form. Skin lesions may be present at birth in infants infected in utero, or may not appear until 1 or 2 weeks after birth in infants infected during delivery. Clinical manifestations of disseminated disease include fever, pneumonia with respiratory distress, hepatomegaly and jaundice, and bleeding tendency. Typically the skin lesions are groups of vesicles (Fig. 11-13). These findings are usually regarded as indications for the current chemotherapy, as described below. The vesicles may appear at the site of scalp monitoring electrodes. Congenital vesicles have been demonstrated to contain H. influenzae in one case report.

Fig. 11. Disseminated herpes simplex.

Fig. 12. Herpetic lesions of oral cavity.

Fig. 13. Herpetic lesions of tongue.

Recovery without chemotherapy and without apparent neurologic damage has been reported in a newborn with type 2 herpes simplex virus recovered from the spinal fluid in association with facial palsy and lethargy. Although not all patients with skin lesions will develop disseminated disease, there still is some risk and the consequences are severe. Vidarabine (Ara-A) is effective and recommended in localized disease, but is less effective in treating isolated CNS disease, and even less effective in preventing severe neurologic damage if the disease is already disseminated. A more effective antiherpetic drug is needed.

Usually it is type 2 (genital) herpes simplex virus that is recovered from the newborn, who is usually infected by way of the mother’s genital tract, but disseminated herpes of the newborn and mother’s genitalia caused by the type 1 (oral) strain has been reported.

2. .Skin lesions with isolated organ involvement can occur, including chorioretinitis with motor retardation, or pneumonia.

3.Skin lesions with no apparent damage can also occur Usually the lesions are groups of vesicles which progress to ulcers. The distribution of lesions may be in a dermatome and may resemble zoster. An erythema-multiforme rash may be present in addition to the grouped vesicles, and recurrent skin lesions may occur at the sites of the original lesions.

 

Diagnostic Plan

Serum IgM. Determination of IgM in the ; cord or newborn serum may be useful as a j. screening test, because the IgM is usually more than 20 mg/dl in symptomatic congenital intra-j uterine infections. The usefulness is limited by I the fact that about 10 % of normal newborn inifants have IgM levels above 20 mg/dl. The source of the elevated IgM in the uninfected newborn can be maternal blood which has en-1 the fetal circulation, in which case maternal erythrocytes or other factors should be detectable. Mild illnesses in the first few months of life may result in increased IgM levels. The cord IgM level was usually not elevated in one study of infants with congenital rubella infection unless there were three or more definite abnormalities in the infant. Thus, the IgM is useful if elevated, but a low IgM does not exclude congenital infection. IgM-specific antibodies are more useful, as discussed under the Individual infections later in this chapter.

VDRL. Congenital syphilis should always be excluded by serologic testing whenever there are signs suggesting chronic active infection. Serologic confirmation of congenital syphilis is complicated by the fact that maternal IgG antibodies can pass the placenta, so that even if the mother has been adequately treated, syphilis antibodies may be detected in the infant. Similarly, a negative test early in pregnancy should not deter a physician from obtaining a later test (from either mother or newborn) in any sick newborn. A VDRL test is usually rapidly available and syphilis is an important treatable disease to exclude. Therefore, the VDRL should be done in all infants in whom any congenital disease is suspected, and should be done routinely at birth in high risk groups.

The IgM-specific antibody test for syphilis using a fluorescent antibody method (IgM FTA test), is reasonably accurate if suitably standardized, but recently has been criticized in the United States for lack of standardization, and lack of accuracy, with a recommendation that “there is no substitute for serial VDRL testing” of the suspected newborn infant.

Rubella Titer. Congenital rubella infection can be excluded by a very low rubella HI titer. If the titer is elevated, it may be because of transplacentally acquired maternal antibodies. This can be resolved in several ways. The newborn infant’s serum can be tested immediately for rubella-specific IgM antibodies. If the infant is younger than 2 years of age, serum can be tested for rubella antibodies. A titer higher than the mother’s or continued presence of rubella antibody at 6 months indicates congenital rubella infection, because by this age transplacentally acquired antibodies would have decreased significantly or disappeared.

Toxoplasma Antibodies. A low toxoplasma dye titer (1:100 or lower) is good evidence that there has beeo recent infection. A high dye titer in the infant and the mother cannot be interpreted unless the toxoplasma-specific IgM titer is measured in the infant. Even then, a rise in titer of IgM-specific toxoplasma antibodies is necessary to confirm fetal infection.

The complement-fixation test may also be useful. A new enzyme-linked immunosor-bantassay (ELISA) test also appears promising. Further studies are needed to determine whether difficulties in laboratory detection of congenital toxoplasmosis is related to the sensitivity of the tests or the failure of the infant to form IgM antibody to the parasite.

Specific IgM Antibodies. The IgM is most useful as a screening procedure if it is followed up with determination of IgM-specific antibody, such as for toxoplasmosis, cytomegalovirus, or rubella, for detection and management of subclinical infection.

The detection of the specific antibody can be improved by combining it with fluorescent antibody (FA) techniques. The patient’s serum is allowed to react with the test antigen (toxoplasma, treponema, or cytomegalovirus), and washed off. If there is an attachment of the patient’s IgM specific antibody to the antigen, it can be detected by adding fluorescent-labelled antihuman IgM. Fluorescent antibody techniques are available in very few laboratories for measurement of specific IgM antibodies against toxoplasmosis, cytomegalovirus, and syphilis. Testing for specific IgM antibodies should not be done unless the specific antibody has been demonstrated in the whole serum.

Methods available vary with the reference laboratory involved. Rubella antibodies in the IgM fraction can be calculated after removing IgM by 2-mercaptoethanol. An IgM-specific fluorescent treponema antibody (FTA) combines the specificity of the FTA test with the evidence that the infant has produced this antibody, although its standardization and reliability have been recently controversial. IgM cytomegalovirus antibody determinations are also useful and may be available in research laboratories.

Many new IgM-specific tests for the TORCH syndrome antibodies are now available and are in the process of being evaluated.

Viral Cultures. Recovery of the rubella virus from blood, CSF, lens, or other organ of the infant can be considered a conclusive test. Recovery of rubella virus from the throat of an infant with one of the three clinical patterns of congenital rubella syndrome should also be considered confirmatory.

Culture of herpes simplex virus from skin lesions is easy if facilities for viral cultures are available. A typical cytopathic effect can sometimes be seen in 24 hours but usually takes 2 to 5 days.

Urine is the most useful source for culture for cytomegalovirus. One per cent to 2% of normal infants have cytomegalovirus in the urine, so that recovery of this virus must be interpreted with consideration of the clinical findings. The infectivity of the virus in urine is well preserved for up to a week at 4 °C.

Smear of Lesions. A vesicular or bullous lesion can be scraped at the base and the scrapings stained with Giemsa stain to look for the typical inclusion cells associated with herpes simplex virus. The fluid can be examined under a darkfield microscope for spirochetes.

Serologic Screening for Other Viruses.

In general, serologic screening for antibodies to mumps, influenza, or other respiratory viruses or enteroviruses reveal serum antibodies compatible with maternal transplacentally transferred antibodies. These values can usually not be interpreted except in a negative way to exclude past infection. Since these viruses are not known to be statistically associated with chronic congenital infection, there is no value in obtaining this information, except as part of a controlled research project.

Serologic study for herpes simplex virus antibodies is also of no value, since any antibodies detected may be transplacental antiboides from the mother.

Nonspecific Tests. In a prospective study, the rheumatoid factor test proved to be a useful screening test for cytomegaloviruria, because it was positive in 35 % to 40 % of the cases and there were no false positives.

 

Treatment

 

Syphilis. Immediate treatment of the newborn infant should be given in certain circumstances when syphilis is present. These include:

1. Newborn VDRL is fourfold or greater than the mother.

2.    Newborn VDRL is positive, and mother’s treatment during pregnancy is inadequate or unknown.

3.    Newborn has clinical or radiologic evidence of syphilis and mother’s treatment during pregnancy is inadequate or unknown.

4.    Newborn VDRL is positive and newborn IgM is elevated. Syphilis-specific IgM antibody (IgM-FTA-ABS) caow be measured in many reference laboratories. In some laboratories, it provides a rapid accurate diagnosis on a single serum, but currently its accuracy is controversial.

Elaborate criteria for withholding treatment have been proposed, based on following the VDRL of the infant. However, treatment should usually be given if there is a reasonable possibility of congenital syphilis. Whether or not the baby is proved to be infected is no longer the social issue it once was.

No treatment is necessary if the infant’s VDRL is negative and if the mother is known to have received adequate treatment.

Antibiotic therapy of the newborn infant who is being treated for congenital syphilis should consist of procaine or aqueous penicillin, 25,000 U/kg twice a day over a 10-day period, since neurosyphilis is difficult to exclude. If the infant is in the hospital, the daily dose can be given as crystalline penicillin every 12 hours. The daily dose can be given once a day as procaine penicillin if the infant is an outpatient, but procaine penicillin has a risk of producing a sterile abscess. Failure of this therapy to eradicate severe infection has been reported, although the CSF levels after procaine penicillin are adequate.

Herpes Simplex.

1.    Idoxuridine has been used for disseminated neonatal herpes but has not yet been clearly demonstrated to be of value, and is no longer used. Vidarabine, formerly called adenine arabinoside or ara-A, is currently under investigation, as described earlier.

2.    Interferon inducers. Interferon can be found in patients with disseminated herpesvirus infection, so induction of additional interferon may not be of value. Therapy with interferon inducers has not been adequately tested.

3.    Body temperature. Herpesvirus infection of dogs disseminates only in puppies, apparently because of their lower body temperature. Raising the ambient temperature of mice protects them from disseminated disease, but such therapy has not been studied in human infants.

Cytomegalovirus. Chemotherapy with drugs, such as cytosine arabinoside, is still in the investigational stage.

Rubella. Supportive therapy may include cardiac surgery, enucleation of cataracts, and hearing aids. Newborn infants with congenital rubella are highly contagious.

Congenital Toxoplasmosis. Therapy with sulfadiazine, pyrimethamine, and folinic acid has been advocated in an attempt to diminish any progression of intellectual impairment.

 

 

Erysipelas

Definition

Erysipelas is a distinctive type of superficial border serous or serous-hemorrhagic inflammation of the skin with prominent lymphatic involvement with acute or chronic course of disease.

http://emedicine.medscape.com/article/1052445-overview#showall

Etiology

It is almost always due to group A b–hemolytic streptococci (uncommonly, group С or G). Group В streptococci have produced erysipelas in the newborns.

http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/202300.htm&word=Erysipelas

Epidemiology

Erysipelas is more common in infants, young children, and older adults. Evidence of streptococcal infections (groups A, G, and C) was found in 26 of 27 patients with clinical erysipelas, utilizing the combination of direct immunofluorescence and cultures of punch biopsy specimens along with serologic titers. Very rarely, a similar skin lesion is caused by S. aureus.

 Formerly, the face was most commonly involved, and an antecedent streptococcal respiratory tract infection preceded cutaneous involvement in about one-third of patients even though streptococci might not be found on culture at the time the skin lesion became evident.

Source of disease is sick person with erysipelas and other streptococcal infections (tonsillitis, pneumonia, scarlet fever, streptodermia) and healthy carriers.

Contact mechanism of transmission. Increasing of morbidity in summer-autumn period.

 

Pathogenesis

Most interest has focused on streptococcal pyrogenic exotoxins (SPEs). In edition to mediating the scarlatinal rush, SPE exibit a variety of adverse biologic effects, including the multiorgan damage and lethal shock. There is an amino acid homology of 50 % and immunologic reactivity between SPE A and staphylococcal enterotoxins B and C. SPE of  group A streptococcus is a superantigen and it is a potent inducer of tumor necrosis factor.

The antistreptolysin O response after cutaneous streptococcal infection is wea. There is experimental evidence to suggest that this may be due to local inactivation of streptolysin O by skin lipids. The immune response to antiDNase B is brisk, and antihyaluronidase reactivity is also a useful test in the serodiagnosis of erysipelas.

 

Clinical manifestations

Usual localization of erysipelas: 70-80 % of the lesions on the lower extremities and 5-20 % on the face. Portals of entry are commonly skin ulcers, local trauma or abrasions, psoriatic or eczematous lesions, or fungal infections; in the neonate, erysipelas may develop from an infection of the umbilical stump. Predisposing factors include venous stasis, paraparesis, diabetes mellitus, and alcohol abuse. Patients with the nephrotic syndrome are particularly susceptible. Erysipelas tends to occur in areas of preexisting lymphatic obstruction or edema (after a radical mastectomy). Also, because erysipelas itself produces lymphatic obstruction, it tends to recur in an area of earlier infection. Over a 3-year period, the recurrence rate is about 30 %, predominantly in individuals with venous insufficiency or lymphedema.

Streptococcal bacteremia occurs in about 5 % of patients with erysipelas; group A, C, or G streptococci can be isolated on throat culture from about 20 % of cases.

The face (often bilaterally)(Fig.14), an arm or a leg (Fig.15) is most often involved. The lesion is well demarcated, shiny, red, edematous and tender; vesicles and bullas often develop. Patches of peripheral redness and regional lymphadenopathy are seen occasionally; high fever, chills and malaise are common. Erysipelas may be recurrent and may result in chronic lymph edema. A cause of infection may be an interdigital fungal infection of the foot that may require long-term therapy to prevent recurrent erysipelas.

Uncomplicated erysipelas remains confined primarily to the lymphatics and the dermis. Occasionally, the infection extends more deeply, producing cellulitis, subcutaneous abscess, and necrotizing fasciitis.

Leukocytosis is common with erysipelas. Group A streptococci usually cannot be cultured from the surface of the skin lesion, and only rarely can they be isolated from tissue fluid aspirated from the advancing edge of the lesion. In cases of erysipelas complicating infected ulcers, group A streptococci have been isolated from the ulcerated area in 30 % of patients.

Fig.14. Erysipelas of face

Fig.15. Erysipelas of leg

 

Diagnosis

Diagnosis from the characteristic appearance is usually easy. The causative organism is difficult to culture from the lesion, but it may occasionally be cultured from the blood.

http://emedicine.medscape.com/article/1052445-workup#showall

Therapy

 Mild early cases of erysipelas in the adult may be treated with intramuscular procaine penicillin (600,000 units once or twice daily) or with oral penicillin V (250-500 mg every 6 hours). Erythromycin (250-500 mg orally every 6 hours) is a suitable alternative. For more extensive erysipelas, patients should be hospitalized and receive pare) aqueous penicillin G (600,000-2 millions units every 6 hours).

 

Prophylaxis

Adherense to good regimens of personal hygiene, with special attention to frequent scrubbing with soap and water, is the most effective preventive measure currently available. The in time treatment of streptococcal pharyngitis is of much importance.

Salmonellosis

Salmonellae are widely dispersed in nature, being found in the in the gastrointestinal tracts of domesticated and wild mammals, reptiles, birds, and insects.

May present clinically as gastroenteritis, enteric fever, a bacteremic syndrome, or focal disease. An asymptomatic carrier state may also occur.

http://www.cdc.gov/salmonella/

Historic reference

The  term  “Salmonellosis”  unites  a  large  group  of  diseases, caused  by  multiply  serotypes  of  bacteriums  from genus Salmonellae (more than 2000).

Sallmonellae are named for the pathologist Salmon who first isolated S. cholerae suis from porcine intestine. The antigenic classification or serotyping of Salmonella used today is the result of study of antibody interactions with bacterial surface antigens by Kauffman and White in the 1920s to 1940s. Ames and coworkers in 1973 reported the development of the test that uses S.typhimurium auxotrophic mutants to test the mutagenic activity of chemical compounds.

Salmonellosis is disease of animals and humans. It is characterized by essential damage of gastrointestinal tract, and more rarely by typhus-like or septicopyemic duration.

Etiology

http://www.onlinemedicinetips.com/disease/s/salmonella/Etiology-Of-Salmonella.html

Salmonella are non-spore-forming gram negative rods of the family Enterobacteriaceae. Salmonella are motile by peritrichous flagella. Salmonella strains demonstrate sufficient differences in biochemical reactions, antigenic structure, host adaptations, and geographical distribution to be grouped into 10 distinct subgroups, which have been variously designated in proposed taxonomic schemes. Virtually all strains isolated in clinical laboratories and implicated in disease in humans (more than 700 serotypes)(Fig.9).

 

 

Fig.9. Lactose-negative colonies of salmonella growing on MacConkey agar

 

Like other enterobacteria, salmonella has somatic (0) antigens, which are lipopolysaccharide components of the cell wall, and flagella (H)  antigens, which are proteins. There  may  be  detached  some  serological  groups  on  the  basic of  the  differences  in  structure  of  O-antigens. Salmonella  preserve  viability  in  external environment  for  a  long  time: in  water – 11-120 days, in  the  sea  water – 15-27 days, in  soil – 1-9 months , in  sausage products – 60-130 days, in  the  eggs, vegetables  and  fruits  till  2,5 months. The  optimal  temperature  for  reproduction is  35-37 °C. There  are  serological  groups A, B, C, D, E  and  other.

Salmonella can be differentiated from other Enterobacteriaceae on the basis of certain biochemical reactions, including fermentation reactions with specific sugars.

Salmonella organisms grow readily on simple media in aerobic or anaerobic conditions. Cultures of specimens that are normally sterile, such as blood, joint fluid, or cerebrospinal fluid, can be done on ordinary media such as blood agar. Excretions or secretions, such as feces or sputum, which have high concentrations of  other microorganisms, are usually grown on selective or differential media, such as bismuth sulfate agar or desoxychlorate  agar, which contains inhibitors of growth of non-pathogenic organisms of the normal flora.

Epidemiology

http://www.safe-poultry.com/salmonellaepidemiology.asp

Animals  suffering  from  primary  or  secondary  salmonellosis, water   swimming  birds and  also  human-sick  or  carries are the  main  sources  of infection    in  salmonellosis. Mechanism  of  transmission  of  infection  is  fecal-oral. The factors  of  the transmission  of  the infection  are  food-stuffs  of  animal  origin  and  other  products  which  are polluted  by excretions  of  animals  and  humans. The  promotive  factors  are  violation  of  the  preservation  and  preparing  of  the  food  and  also sanitary.

The  diseases occur  as  separate  sporadic  cases  and  as  outbreaks. Susceptibility  of  human depends  from  the  premorbidal state  of  the  macroorganism and  from  the  quantity  and  variety (serotypes)  of   Salmonella.

Salmonella are primarily pathogens of lower animals. The reservoir of infection in animals constitutes the principal source of nontyphoidal Salmonella organisms that infect man, although infection may be transmitted from person to person, Salmonella have been isolated from almost all animals species, including poultry (chickens, turkeys and ducks), cows, pigs, pets (turtles, cats, dogs, mice, guinea pigs and hamsters), other birds (doves, pigeons, parrots, starlings, sparrows), sheep,  seals, donkeys, lizards and snakes.

The most accurate information on sources of human Salmonellosis is derived from studies of outbreaks. Poultry (chickens, turkeys, ducks) and poultry products (primarily eggs) are the most important sources of human infection and are estimated to be responsible for about one-half of the common – vehicle epidemic. Salmonella in feces of infected hens may contaminate the surface of egg shells or penetrate into the interior of the egg through hairline cracks. In hens with ovarian infection, organism may gain access to the yolk. Meat, especially beef and pork, are quite often implicated, accounting for about 13 % of the outbreaks,  and dairy products, including raw and powdered milk account for about 4 % of the epidemics.

Cross – infection with spread by person – to – person is responsible for virtually all the outbreaks ieonatal nerseries  and in pediatric wards and is important in many outbreaks among hospitalized adults.

The stage is set for cross-infection when Salmonella are introduced into the hospital by admission, or for example, a patient with acute enterocolitis or as asymptomatic carrier with other  medical problem or by the introduction of a contaminated common- course vehicle. Hospital personnel then may carry infection on hands or clothing from patient to patient; in some cases fomites (dust, delivery room, furniture), may be implicated in transmission. Hospital personnel who are excreting Salmonella in stools may also occasionally transmit infection to patient.

Pathogenesis

The development of disease after ingestion of Salmonella is influenced by the number and virulence of the organisms and by multiple host factors.

A large number of Salmonella  must be swallowed in most instances to produce disease in healthy human being. However, in the event of infection with unusually virulent organisms or in patients with reduced resistance, symptomatic infection may result from extremely small inocula. Ingested organisms pass from the mouth to the stomach. In the stomach  Salmonella are exposed to gastric acid and low PH, which reduce the number of viable organisms. Most  Salmonella are perished rapidly at 2,0 PH, which is readily achieved in the normal stomach. Viable bacilli that survive then pass into the small intestine, where the organisms may be further reduced iumber or eliminated entirely. The antimicrobial  activity observed in the small bowel is related at least in part to the normal microbial flora of the intestine, which elaborate short-chain fatty acids and perhaps other substances capable of killing or inhibiting growth of Salmonella. Studies in animals have shown that the increased susceptibility to Salmonella infection produced by administration of antibiotics rapidly reverts to normal with reestablishment of the normal intestinal flora.

Salmonella that survive the antibacterial mechanisms in the stomach and upper small bowel may multiply in the small intestine. Multiplication of Salmonella in the intestinal tract may be asymptomatic, associated only with transient excretion of organism in stools, or symptomatic, associated with clinical manifestations of either enterocolitis (acute gastroenteritis) enteric fever or bacteremia.

Blood stream invasion, which occurs with variable frequency, may lead to localization of infection and suppuration at almost any site.

Local factors in the stomach and upper intestinal tract are important determinants of the disease. Factors that neutralize the low PH of the stomach or decrease the time the pathogen is exposed to stomach acid diminish local bactericidal action and increase the probability that an infections inoculums will reach the small intestine. The importance of gastric acidity as a defense mechanism is emphasized by the increased incidence of severe Salmonella enterocolitis in persons with achlorhydria, prior gastroectomy, gastroenterostomy, or vagotomy, conditions that reduce acidity or cause faster gastric emptying time.

The oral administration of buffering compounds also increases susceptibility to intestinal infection. It has been suggested that ingestion  of organisms in food allows for longer exposure to gastric acid, thereby necessitating the presence of a relatively larger inoculums to produce disease, whereas water or other liquids, which have a fast  gastric transit time, may be less heavily contaminated and still cause disease.

The small intestine provides other protective mechanisms through motility and normal flora. Alteration of the intestinal flora by antibiotics markedly reduces the size of the inoculums required to produce   Salmonella infection in animals and humans and prolongs the convalescent carrier state. Prior antimicrobial   therapy also enhances the possibility of  infection with antibiotic – resistant Salmonella strains.

Age is an important determinant of  disease produced by Salmonella. Salmonella enterocolitis occurs with highest incidence in children less than 5 years old; newborns and infants less one year of age are especially susceptible. The influence of age on incidence may reflect immaturity of humoral and cellular immune mechanisms, diminished antibacterial action of the normal intestinal flora, a high frequently of fecal – oral contamination, or other factors. In some instances, increasing resistance with age is related to immunity consequent to previous exposure to the organism, even though disease has not been produced.

Patient with impaired cellular and humoral immune mechanisms are at increased risk for development of Salmonellosis. Impairments of host defenses caused by malnutrition, malignancy, infection with  human immunodeficiency virus or therapeutic measures such as corticosteroid or immunosuppressive therapy also predispose to infection and disease.

Salmonella causing enterocolitis are thought to produce diarrhea by a true infection with mucosal  invasion and possibly by elaboration of an enterotoxin that acts on upper intestinal transport. Salmonella invasion of intestinal mucosa may lead to local production of inflammatory exudates of mediators that stimulate electrolyte secretion and smooth muscle contraction (Fig.10).

Fig.10. Flask-shaped ulcer with necrosis of epithelium and extrusion of necrotic tissue, fibrin and mucus

There  are  two types of toxins: exotoxins and endotoxins. Exotoxins are the toxic products of bacteria which are actively secreted into environment. Endotoxins are toxic substances which are liberated only during the lysis of microbial cells. The principal factor responsible for development of this disease is endotoxical complex of Salmonella, but we should remember that these bacteria produce even exotoxins. Exotoxins and endotoxins have toxical properties.

Stages of salmonellosis development:

1.     Colonization (setting) of pathogenic organism in the place of the inculcation.

2.     Invasion and reproduction.

3.     Death of the pathogenic bacteria and endotoxins liberation.

Infectious process may stop at the stage of colonization due to unknown reasons. Invasion may be limited by nearest tissues. In majority cases it leads to development of gastrointestinal forms of Salmonellosis. For development of the first stage of pathogenesis of Salmonellosis the factors violating structural and functional state of gastrointestinal tract play important role (dysbacteriosis, hypovitaminosis and other). These conditions may promote to development of the disease even due to small quantity of bacteria in food-stuffs.

In salmonellosis the principal pathologoanatomical changes develop in the place of inoculation of the agent in the small intestine. Data about changes of small intestine in gastrointestinal forms of Salmonellosis may be received only as a result of its biopsy. But biopsy is not used in practice. Investigation of material during biopsy testifies dystrophical changes of epithelium, infiltration of epithelium  of mucous membrane by macrophages. Increased quantity of interepithelial leukocytes, polymorphonuclear leukocytes and macrophages is marked.

Principal  changes develop in lamina propria of mucous membrane of small intestine in Salmonellosis. These changes are accompanied by hyperemia, hemorrhages, edema and intensification of cell infiltration. At the same time  the  changes of the different parts of gastrointestinal tract develop. There is an acute inflammatory process, dystrophic changes of epithelium, edema, hyperemia and cell infiltration in stomach. There are dystrophy, erosions, hyperemia, edema in mucous of large intestine. Changes in all parts of gastrointestinal tract are transient. They are exposed to reverse development in clinical recovery of the patients.

In half of the patients with Salmonellosis nonsharp violations of liver are marked. These changes are considered as compensatory mechanism.

In connection with sufficient efficiency of modern methods of treatment the fatal outcomes are rare. Dystrophic  changes of parenchymatous organs were revealed in autopsy of deceaseds from gastrointestinal forms of Salmonellosis. These changes were direct cause of death. Inrarely, edema of the lungs and brain, hyperplasia of spleen and mesenteric lymph nodes may develop.

Clinical  manifestations

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In connection with considerable variability of clinical duration of Salmonellosis there are multitude classifications of this disease. The next classification is more comfortable for practice use:

1)     Localized (gastrointestinal) forms of Salmonellosis:

a)     Gastritic variant;

b)    Gastroenteritic variant;

c)      Gastroenterocolitic variant.

2)     Generalized forms:

a)     Typhus-like form;

b)    Septic form (septicopyemia).

3)     Carrier state:

a)     Acute carriers;

b)    Chronic carriers;

c)     Transitory carriers.

Clinical symptoms of Salmonellosis are studied sufficiently completely.  Gastrointestinal forms of Salmonellosis are observed in most of cases of the disease. According data of different authors they occur from 79 to 85 %.

Incubation period is from 4-6 hours up to some days. Onset of the disease is an acute. Prodromal period is not typical or very short. Weakness, malaise, and slight chill characterize it. Then temperature increases to subfebrile in moderate and severe forms accordingly.

After ingestion of  contaminated food or water, illness begins in many patients with nausea and vomiting; these symptoms usually resolve within a few hours. Myalgia and headache are common. The cardinal manifestation is diarrhea, which may vary from a few loose stools to fulminate diarrhea. In most cases, stools are loose, of moderate volume,  without blood, swamp-like and bed smell (Fig.11).

Fig.11. Stool in case of salmonellosis

In exceptional cases, the stools may be watery and of great volume (“cholera-like”), or, in other instances, of small volume and associated with tenesmus and gross blood (“shigellosis-like”). Temperature elevations to 38-39 °C are common, as are chills; both appear in the majority of patients in whom  definitive diagnosis is established. Abdominal cramps occur in about two-thirds of the patient and are often localized to the periumbilical region or lower abdominal quadrants. Bowel sounds are increased and abdominal tenderness is present. At microscopic examination, stool show a moderate number of polymorphonuclear leukocytes and, occasionally, red blood cells. Cross blood  is unusual but may be seen in severe cases. Peripheral leukocyte count is usually normal, although neuthrophilia with  a shift to younger forms may be present.

The duration of fever is less than 2 days in the majority of cases. Diarrhea usually persists less than 7 days, although, rarely, gastrointestinal symptoms may last for several weeks. Prolonged fever and diarrhea suggest a complication or a different diagnosis.

Localization of pain in the right lower quadrant of the abdomen in patients with enterocolitis may lead to a diagnosis of acute appendicitis. At surgery, such patients may have normal appendices or occasionally acute appendicitis rarely with perforation.

Clinic of Salmonellosis is characterized by symptoms of damage of cardiovascular system. The basis of these violations is water-electrolytes loss and change of reological properties of the blood.

Changes in organs of respiratory systems are not typical for uncomplicated cases of gastrointestinal forms. But sometimes breathlessness may be observed.

Toxicosis takes place when localized forms of Salmonellosis. It is manifested by headache, pain in the muscles, mild ataxia, asymetric reflexes. Development of toxic encephalitis is possible.

Electrolyte and water depletion may be severe during illness, leading to hypovolemic shock. The disease is more severe in children, in seniors, and in patient with achlorhydria, gastroectomy, gastroenterostomy, sickle cell anemia, or other conditions that impair resistance to infection. The frequency of transient bacteremia  is less than 5 % in adults. It  is increased in children and in persons with severe preceded diseases. Bacteremia has been shown to occur in 8-16 % of infants and children of 3 years age or younger who are hospitalized with Salmonella enterocolitis. Salmonella  intestinal infections has tendency to be prolonged in children, who continue to excrete agent in stool for a longer time than adults after subsidence  of  clinical manifestation of infection.

Salmonella enterocolitis may develop in hospitalized patients. The illness may be a nosocomial infection or it may result of activation of pre-existing  asymptomic intestinal infection by antimicrobial therapy, of surgical diseases  of  abdomen  or  from other  causes.

In one-two third of children over 5 years and adults positive cultures are observed during second or third week from the onset of the disease. In this time majority of the patients have no symptoms of the disease.

Salmonella can produce an illness characterized by fever and sustained bacteremia without manifestations of enterocolitis. This syndrome may be caused by any Salmonella serotypes. The clinical syndrome of Salmonella bacteremia is characterized by a hectic febrile course lasting for days or weeks. The organism is isolated from blood, but stool cultures are ofteegative. More than 70 % of cases of generalized forms of Salmonellosis begin as gastrointestinal form with dyspeptic manifestations. Then, in typhus like variant after subsidence of dyspeptic manifestations the disease acquires signs of typhus infection. The second febrile wave-like or incorrect type continues in most cases during 10-14 days. The principal symptoms of the period of climax of the disease are weakness, adynamia, severe headache, sleeplessness, pains of muscles and joints.

Typical typhus state is not characteristic for this variant of Salmonellosis. In majority of the patients enlarged liver and spleen, distantion of abdomen are observed.

Approximately, in 25 % of the patients scanty rose sports are observed. Rash  appears on 4-10 day, sometimes later. In peripheral blood leukocytosis is observed only in early period of the disease. Then leukopenia is marked, but with neutrophilosis. Sometimes typhus like variant may be without appearances of gastroenteritis. The principal symptoms of beginning period in that cases are fever, chill, headache, weakness. In the period of climax adynamia, pale skin, injections of scleras are observed.

There are single rose spots on the skin of abdomen and chest. In this variant of generalized form of Salmonellosis relapses may observed, and rarely, complications, which are typical for typhus fever. Typhus like variant may be with temperate manifestations of intoxication and dyspeptic appearances, with short duration fever. There is marked catarrh, hyperemia of pharynx, laryngotracheobronchitis in these patients rarely.

Septic variant (septicopyemia) is sepsis of Salmonella etiology. The development of sepsis is evoked by sharp decrease of the immuneprotective strengths of the organism of the patient. This variant of generalized of Salmonellosis is characterized by acyclic development of the disease, prolonged fever, chills, sweating, hepatosplenomegaly, sometimes development of jaundice, plural purulent metastases in different organs and tissues.

Usually, the disease begins from manifestations of gastroenteritis. Then typical septicopyemia develops with hectic fever. The signs of influence of intoxication on central nervous system are marked from the first days of the disease. They are manifested by irritation, violations of sleep, motive trouble, sometimes delirium. The skin is pale. Rash may appear on the skin (petechias or large hemorrhages).

The  secondary  purulent  focuses  may  be  in  any  organs  and  tissues. Localization  of  infection  may  be  in  thyroid, brain membranes, bones, heart, lungs, kidneys, adrenals, pancreas, spleen, liver, pericardium  and soft  tissues.

Meningitis is a rare complication of Salmonella infection and occur almost exclusively in infants, particularly neonates. Even epidemics of meningitis have been reported during outbreaks of Salmonella infection in hospital nurseries. Clinical manifestations are the same as those of any bacterial meningitis in this age group. The clinical course is usually long and marked by relapse. Acute neurologic complications are common and include subdural empyema, cerebral abscesses, and ventriculitis. Acute or chronic hydrocephalus may occur. Mortality is high, despite appropriate antimicrobial therapy.

Pleuropulmonary disease. Pneumonia or empyema, the predominant types of serious respiratory diseases, occur usually in elderly patients or in patients with underlying diseases such as diabetes mellitus, malignancy, cardiovascular disease, or pulmonary disease. Mortality is high.

Arthritis. Salmonella infection may be with localization in major vessels, including the thoracic and abdominal aortas, coronary arteries, peripheral arteries. Atherosclerotic intrarenal aortic aneurysms are by far the most common vascular sites of localization. The risk of endothelial infection is high in persons over the age of 50 years who have Salmonella bacteremia.

The mechanism of arterial infection is through to be direct implantation at a site of endothelial injury in the bacteremia patient on to extension from an adjacent inflammatory lesion, such as vertebral osteomyelitis. Mortality is high.

Osteomyelitis and Arthritis. Osteomyelitis can develop iormal bone but especially likely to occur in patient with sickle – cell hemoglobinopathies, systemic lupus erythematosus, immunosuppressive therapy, bone surgery or trauma. Salmonella, not Staphylococcus, is the most common cause of osteomyelitis in patients with sickle-cell anemia.

Salmonella may cause a metastatic supportive arthritis. Pyogenic arthritis is much less frequent than reactive arthritis.

Splenic Abscess and Hepatic Abscess. Splenic abscess is a rare complication of Salmonella infection. Localization occurs after bacteremia in posttraumatic subcapsular hematomas or splenic cysts. The clinical manifestation is one of left upper  quadrant tenderness, fever and leukocytosis.

Salmonella liver abscesses may occur. Usually, the patients have pre- existing liver disease including amebic abscesses, ecchinococcal  cysts, and hematomas. Association with biliary tract disease exists in occasional cases.

Urogenital Tract. Salmonella in stools of carriers or persons with acute illness may gain access to the urinary tract to produce cystitis or pyelonephritis. Localization of Salmonella blood  form with abscess formation in kidneys, testicles, or ovaries is also occasionally reported.

Bacteriocarriering of Salmonella is developed after disease. There are acute, chronic and transitory carriers. Acute and chronic carriers are divided depending on duration of excretion of Salmonella. Acute  carrier has the duration of excretion of Salmonella from 15 days till 3 months after clinical recovery. The persons, excreting Salmonella over a year, are chronic carriers. The conditions of development of transitory carrier are insignificant dose of the agent and its avirulence.

Complications  and  outcomes

Complications and outcomes of Salmonellosis, as and multiple clinical forms are exposed to wide oscillations. Even gastrointestinal forms of Salmonellosis with favorable duration are not finished clinical recovery.

Generalized form of Salmonellosis, as rule, is accompanied by complications. Exceeding expression of symptoms of Salmonellosis frequently leads to collapse (1.5-6 % of the cases). Collapse may develop at the first day of the disease on the altitude of clinical manifestations before dehydration. Endotoxinemia plays leading role in development of collapse. It is a manifestation of infectious-toxic shock.

Besides expressive hypodynamic disorders acute renal insufficiency, edema of brain, edema of lungs and hemorrhagic syndromes develop. The development of dysbacteriosis is connected with large doses of antibiotics use at any clinical forms of Salmonellosis. Dysbacteriosis may be compensated  or latent.

Outcomes of salmonellosis depend on premorbidal state, age, clinical forms, timely diagnostics and treatment.

Diagnosis

Diagnostics of salmonellosis is performed on the basis of epidemiological, clinical and laboratory data. Bacteriological and serological methods are used  for confirmation of salmonellosis. The main materials for bacteriological  investigation  are vomiting masses, water after irrigation of stomach, stool, blood, urine.

Serological investigations are used. These are reaction of agglutination (RA) (7-8^th day of the disease) and indirect hemagglutination (RIHA). RIHA is more  sensitive. It gives  positive results on the 5^th day of the disease. Diagnostical titer is 1:200. Serological investigation should be done in dynamics of the disease.

Rentgenology investigation shows the increasing of thick intestin (Fig.12).

Fig.12. Tension and swelling of sigmoid colon

Differential diagnosis

Differential diagnosis of salmonellosis is perform with other intestinal diseases – shigellosis, toxic food-borne infections, esherichiasis, cholera; with surgical diseases – appendicitis, pancreatitis, cholecyctitis, thrombosis of mesenterial vessels; gynecological pathology and with therapeutic pathology (myocardial infarction, chronic gastritis aggravation, enterocolitis, ulcerous disease), with acute gastroenteritis of viral origin (enteroviral, rotaviral etiology), poisoning by organic and inorganic poisons, poisoning by mushrooms.

Generalized forms of salmonellosis is necessary to differentiate from sepsis of different etiology, pneumonia, malaria, acute pyelonephritis, tuberculosis.

Treatment

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The volume of medical actions depends on the clinical form and a stage of gravity of disease. At gastrointestinal form immediately wash out stomach and intestine with boiled water (isotonic solution of Sodium chloridum is the best) then give sorbents per os and give a warm drink. For restoration of hydro-electrolityc balance and normalization of circulatory disorders there should be indicated per os Glucosole or Rehydroni. Infusion therapy is indicated at expressed dehydration – Trisol, Quartasol, Lactasol. At severe stage of dehydratation one of the specified solutions is infused in vein with rate 80-120 mL/min, 5-10 L of solution is necessary on course of treatment. If hypotension and toxicosis are marked Prednisolon and Hidrocortizon, Polyglucin, Reopoliglycin are infused in vein. Pathogenetically 5 % solution of glucose is indicated with desintoxication purpose and restoration of power balance, a solution of sodium hydrocarbonat for acidosis correction, Heparin for improvement of reologic properties of blood, preparations of antiallergic action – calcii chloridi, Dimedrol, Tavegil, Indomethacin are proved at severe diarrhea (for downstroke of Prostaglandines synthesis), calcium gluconate. Antibiotics at gastrointestinal form of salmonellosis are not used.

However at syndrome  of hemocolitis and lingering diarrhea Furazolidon is  indicated in combination with fermental preparations – Festal, Panzynorm, Pancreatin, Mezym forte, Pancitrat, Vobensim. The broths of herbs has anti-inflammatory, disinfectant and astringent properties, and also properties raising organism reactivity. They are vitamin preparations, Pentoxyl, Methyluracil, Thymalin, Enterol-250 also indicated. Bificol, Colibacterin, Bifidumbacterin, Linex is used at intestinal dysbacteriosis.

At generalized form simultaneously with pathogenetic therapy there are  indicated antibiotics – Levomycetin, Ampicillin, Monomycin, Gentamycini sulfas, Cefazolin (Kefzol), Cefotaxim (Claforan). At the septic form of disease antibiotics are better to infuse parenteraly.  For sanitation of chronic carriers of salmonelas the specified antibiotics use in average therapeutic doses in combination with preparations stimulating nonspecific and immunological reactivity (Pentoxyl, Methyluracil, Splenin, Thymalin, T- activin).

Prophylaxis

The  measures  of  prophylaxis  are  veterinary-surveillance upon  animals  and  production  of  meat  and   dairy industry, laboratory  control  of  food  stuffs.

It is  necessary  to  reveal  carriers  on  milk  farms,  in foods, children’s and medical establishments. The  maintenance  of  the  rules  of  personal  hygiene  and  rules  of  food’s  cooking  plays  an  important  role  in  prophylaxis  of Salmonellosis.