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Query: UMLS:C0021051 (immunodeficiency)
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The objective of this study was to assess the response of the feline thymus to fetal infection with feline immunodeficiency virus (FIV), an animal model for human immunodeficiency virus infection. Thirteen feline embryos from four litters were directly inoculated with FIV during the sixth week postbreeding, a period corresponding to the late second trimester of pregnancy. Thymus tissue was collected and analyzed from randomly selected kittens at 2, 4, and 16 weeks postinoculation (PI) and compared to age-matched control kittens that did not receive fetal inoculations. Of three kittens evaluated at 2 weeks PI (week 8 of gestation), neither thymus:body weight ratio nor histologic structure differed from five age-matched control animals. However, analysis of thymocyte subpopulations by flow cytometry revealed a significant (P = 0.011) reduction in the percentage of cluster of differentiation (CD)4+/CD8+ cells from an average of 66% in control fetuses to 45% in infected fetuses. FIV RNA transcription, assessed by in situ hybridization using an FIVgag RNA probe, was widely distributed throughout the thymus in patterns suggestive of both stromal and parenchymal infection. By 4 weeks PI (week 1 postpartum), the thymus:body weight ratio was significantly reduced (P = 0.007) from 0.36% in five control kittens to 0.13% in four fetal inoculates. Severely atrophied thymus lobules supported minimal virus transcription and mean CD4+/CD8+ thymocyte percentages were lower (P = 0.021) in infected kittens (15%) compared to age-matched controls (66%). By 16 weeks PI (week 12 postpartum), thymus:body weight ratios of six inoculated kittens were not significantly different from six age-matched controls, suggesting that partial postnatal thymus regeneration had occurred. However, despite similar size, the regenerative thymus contained reduced percentages of CD4+/CD8+ thymocytes (infected: 40% versus control: 76%; P = 0.009) and increased percentages of CD4+/CD8- (11% versus 5%; P = 0.002) and CD4-/CD8+ (16% versus 9%; P = 0.035) lymphocytes. These changes were associated with widespread FIV transcription within thymic lymphocytes. Thus, the thymus of kittens infected with FIV during late fetal development is characterized by two distinct changes: neonatal atrophy and postnatal regeneration. Despite a recovery in thymus weight, thymus regeneration ineffectively restores the normal phenotypic distribution of thymocytes and supports FIV transcription.
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PMID:Biphasic thymus response by kittens inoculated with feline immunodeficiency virus during fetal development. 959 82

Syphilis, a sexually transmitted infection, has a major impact on the disease burden worldwide. Globally, an estimated 12 million new cases of sexually acquired syphilis occurred in 1997. Developing countries in Africa, Southeast Asia and regions of the former Soviet Union are mainly affected. With rising numbers of human immunodeficiency virus-infected pregnant women and an increase in gonorrhoea in some areas, the incidence of syphilis is expected to increase again. As a consequence of migration from Eastern bloc countries to Europe after the breakdown of the former Soviet Union, the resurgence of syphilis will also affect Germany. Therefore, we present the clinical picture of syphilis as well as review the current recommendations of the German STD Society, the Centers of Disease Control (CDC), USA, and the Clinical Effectiveness Group (CEG), England, for diagnosis and treatment of syphilis with special emphasis on pregnancy. Considering the current epidemiological situation, physicians should include syphilis in their differential diagnosis. Although recommended therapy regimens differ, penicillin is the treatment of choice. Pregnant patients who are allergic to penicillin should be desensitized and treated with penicillin. Early recognition and timely treatment of syphilis are essential to prevent or treat potentially fatal fetal infection.
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PMID:[Syphilis in pregnancy]. 1219 89

The guidance in this report is for evaluation and treatment of patients with complications from smallpox vaccination in the preoutbreak setting. Information is also included related to reporting adverse events and seeking specialized consultation and therapies for these events. The frequencies of smallpox vaccine-associated adverse events were identified in studies of the 1960s. Because of the unknown prevalence of risk factors among today's population, precise predictions of adverse reaction rates after smallpox vaccination are unavailable. The majority of adverse events are minor, but the less-frequent serious adverse reactions require immediate evaluation for diagnosis and treatment. Agents for treatment of certain vaccine-associated severe adverse reactions are vaccinia immune globulin (VIG), the first-line therapy, and cidofovir, the second-line therapy. These agents will be available under Investigational New Drug (IND) protocols from CDC and the U.S. Department of Defense (DoD). Smallpox vaccination in the preoutbreak setting is contraindicated for persons who have the following conditions or have a close contact with the following conditions: 1) a history of atopic dermatitis (commonly referred to as eczema), irrespective of disease severity or activity; 2) active acute, chronic, or exfoliative skin conditions that disrupt the epidermis; 3) pregnant women or women who desire to become pregnant in the 28 days after vaccination; and 4) persons who are immunocompromised as a result of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies. Additional contraindications that apply only to vaccination candidates but do not include their close contacts are persons with smallpox vaccine-component allergies, women who are breastfeeding, those taking topical ocular steroid medications, those with moderate-to-severe intercurrent illness, and persons aged < 18 years. In addition, history of Darier disease is a contraindication in a potential vaccinee and a contraindication if a household contact has active disease. In the event of a smallpox outbreak, outbreak-specific guidance will be disseminated by CDC regarding populations to be vaccinated and specific contraindications to vaccination. Vaccinia can be transmitted from a vaccinee's unhealed vaccination site to other persons by close contact and can lead to the same adverse events as in the vaccinee. To avoid transmission of vaccinia virus (found in the smallpox vaccine) from vaccinees to their close contacts, vaccinees should wash their hands with warm soapy water or hand rubs containing > or = 60% alcohol immediately after they touch their vaccination site or change their vaccination site bandages. Used bandages should be placed in sealed plastic bags and can be disposed of in household trash. Smallpox vaccine adverse reactions are diagnosed on the basis of clinical examination and history, and certain reactions can be managed by observation and supportive care. Adverse reactions that are usually self-limited include fever, headache, fatigue, myalgia, chills, local skin reactions, nonspecific rashes, erythema multiforme, lymphadenopathy, and pain at the vaccination site. Other reactions are most often diagnosed through a complete history and physical and might require additional therapies (e.g., VIG, a first-line therapy and cidofovir, a second-line therapy). Adverse reactions that might require further evaluation or therapy include inadvertent inoculation, generalized vaccinia (GV), eczema vaccinatum (EV), progressive vaccinia (PV), postvaccinial central nervous system disease, and fetal vaccinia. Inadvertent inoculation occurs when vaccinia virus is transferred from a vaccination site to a second location on the vaccinee or to a close contact. Usually, this condition is self-limited and no additional care is needed. Inoculations of the eye and eyelid require evaluation by an ophthalmologist and might require therapy with topical antiviral or antibacterial medications, VIG, or topical steroids. GV is characterized by a disseminated maculopapular or vesicular rash, frequently on an erythematous base, which usually occurs 6-9 days after first-time vaccination. This condition is usually self-limited and benign, although treatment with VIG might be required when the patient is systemically ill or found to have an underlying immunocompromising condition. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. EV occurs among persons with a history of atopic dermatitis (eczema), irrespective of disease severity or activity, and is a localized or generalized papular, vesicular, or pustular rash, which can occur anywhere on the body, with a predilection for areas of previous atopic dermatitis lesions. Patients with EV are often systemically ill and usually require VIG. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. PV is a rare, severe, and often fatal complication among persons with immunodeficiencies, characterized by painless progressive necrosis at the vaccination site with or without metastases to distant sites (e.g., skin, bones, and other viscera). This disease carries a high mortality rate, and management of PV should include aggressive therapy with VIG, intensive monitoring, and tertiary-level supportive care. Anecdotal experience suggests that, despite treatment with VIG, persons with cell-mediated immune deficits have a poorer prognosis than those with humoral deficits. Infection-control precautions should be used to prevent secondary transmission and nosocomial infection. Central nervous system disease, which includes postvaccinial encephalopathy (PVE) and postvaccinial encephalomyelitis (or encephalitis) (PVEM), occur after smallpox vaccination. PVE is most common among infants aged < 12 months. Clinical symptoms of central nervous system disease indicate cerebral or cerebellar dysfunction with headache, fever, vomiting, altered mental status, lethargy, seizures, and coma. PVE and PVEM are not believed to be a result of replicating vaccinia virus and are diagnoses of exclusion. Although no specific therapy exists for PVE or PVEM, supportive care, anticonvulsants, and intensive care might be required. Fetal vaccinia, resulting from vaccinial transmission from mother to fetus, is a rare, but serious, complication of smallpox vaccination during pregnancy or shortly before conception. It is manifested by skin lesions and organ involvement, and often results in fetal or neonatal death. No known reliable intrauterine diagnostic test is available to confirm fetal infection. Given the rarity of congenital vaccinia among live-born infants, vaccination during pregnancy should not ordinarily be a reason to consider termination of pregnancy. No known indication exists for routine, prophylactic use of VIG in an unintentionally vaccinated pregnant woman; however, VIG should not be withheld if a pregnant woman develops a condition where VIG is needed. Other less-common adverse events after smallpox vaccination have been reported to occur in temporal association with smallpox vaccination, but causality has not been established. Prophylactic treatment with VIG is not recommended for persons or close contacts with contraindications to smallpox vaccination who are inadvertently inoculated or exposed. These persons should be followed closely for early recognition of adverse reactions that might develop, and clinicians are encouraged to enroll these persons in the CDC registry by calling the Clinician Information Line at 877-554-4625. To request clinical consultation and IND therapies for vaccinia-related adverse reactions for civilians, contact your state health department or CDC's Clinician Information Line (877-554-4625). Clinical evaluation tools are available at http.//www.bt.cdc.gov/agent/smallpox/vaccination/clineval. Clinical specimen-collection guidance is available at http://www.bt.cdc.gov/agent/smallpox/vaccination/vaccinia-specimen-collection.asp. Physicians at military medical facilities can request VIG or cidofovir by calling the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at 301-619-2257 or 888-USA-RIID.
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PMID:Smallpox vaccination and adverse reactions. Guidance for clinicians. 1261 10

Diagnosis of fetal infection has depended on identification of pathogens by means of microbiological cultures, immunologic techniques, and special molecular biology techniques that can identify organisms known or suspected of being associated with adverse outcomes of pregnancy. Rubella, cytomegalovirus (CMV), herpes simplex virus (HSV), and human immunodeficiency virus (HIV), for example, are capable of gaining access to the amniotic cavity and producing fetal infection, even when amniotic membranes are intact. Intrauterine invasion by viruses can be associated with maternal symptoms of infection or can be completely silent. In many instances extensive fetal compromise with irreversible structural damage or fetal death will have occurred by the time infection is confirmed by culture or other histopathological methods. The evidence of fetal infection may be as subtle as nascent intrauterine growth restriction (IUGR), mildly inappropriate calcification of fetal organs, placenta, cord, and membranes, and failure to adequately develop fetal fat reserves. The evidence of infection may be as dramatic as obvious fetal malformation, severe central nervous system structural damage, or fetal death. Sonography is capable of detecting most of the grave alterations and some of the subtle effects that are typical of fetal infection.
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PMID:Ultrasound markers of fetal infection part 1: viral infections. 1634 48

In utero transmission of feline immunodeficiency virus (FIV) occurs frequently in queens experimentally infected with FIV-B-2542 and other FIV isolates. Fetal infection has been detected as early as 3-4 weeks gestation, and the incidence of fetal infection increases with progressing gestation. Reproductive failure occurs commonly, including fetal resorptions and developmentally-arrested fetuses, demonstrating that fetal demise occurs early in gestation. Precise, temporal immunomodulation within the placenta is essential for successful pregnancy. Placental Th1 and Th2 cytokines must be appropriately balanced, typically favoring Th2 cytokines at the maternal-fetal interface. Abnormal inflammatory cytokine expression often accompanies miscarriage. Regulatory T cells (Tregs) play an essential role in maternal tolerance of the semi-allogeneic fetus by suppressing inflammation. We are using the FIV-infected cat to examine the relationship between lentivirus-induced placental immunopathology and reproductive outcome. Using TaqMan real time reverse transcriptase (RT)-PCR, we measured relative expression of key immunomodulators in the placentas of FIV-B-2542-infected and control cats, including placentas from both viable and nonviable pregnancies. Our data associate significantly-increased expression of inflammatory cytokines with failed pregnancies, identify Treg markers in the placentas, and provide preliminary evidence that Tregs or other cells bearing similar activation markers may be involved in pregnancy maintenance. Our data suggest that placental inflammation in the FIV-infected cat may compromise pregnancy.
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PMID:Placental immunopathology in the FIV-infected cat: a role for inflammation in compromised pregnancy? 1989 19

Cytomegalovirus (CMV) is recognized as the most common congenital viral infection in humans and an important cause of morbidity and mortality in immunocompromised hosts. This recognition of the clinical importance of invasive CMV disease in the setting of immunodeficiency and in children with congenital CMV infection has led to the development of new diagnostic procedures for the rapid identification of CMV. Diagnosis of acute maternal CMV infection by the presence of immunoglobulin (Ig)M and low-avidity IgG requires confirmation of fetal infection, which is typically performed using polymerase chain reaction (PCR) assays for CMV on amniotic fluid. Viral culture of the urine and saliva obtained within the first two weeks of life continues to be the gold standard for diagnosis of congenitally-infected infants. PCR assays of dried blood spots from newborns have been shown to lack sufficient sensitivity for the identification of most neonates with congenital CMV infection for universal screening purposes. However, saliva PCR assays are currently being assessed as a useful screening method for congenital CMV infection. In the immunocompromised host, newer rapid diagnostic assays, such as phosphoprotein 65 antigenemia and CMV real-time PCR of blood or plasma have allowed for preemptive treatment, reducing morbidity and mortality. However, lack of standardized real-time PCR protocols hinders the comparison of data from different centers and the development of uniform guidelines for the management of invasive CMV infections in immunocompromised individuals.
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PMID:Overview of the diagnosis of cytomegalovirus infection. 2182 33

Aerobic vaginitis (AV) is the name given in 2002 to a vaginal infectious entity which was not recognized as such before. It is characterized by abnormal (dysbiotic) vaginal microflora containing aerobic, enteric bacteria, variable levels of vaginal inflammation and deficient epithelial maturation. Although AV and bacterial vaginosis (BV) share some characteristics, such as a diminished number or absence of lactobacilli, increased discharge (fishy smelling in BV, while in severe forms of AV, a foul, rather rotten smell may be present) and increased pH (often more pronounced in AV), there are also striking differences between the two. There is no inflammation in women with BV, whereas the vagina of women with AV often appears red and edematous, and may even display small erosions or ulcerations. The color of the discharge in BV is usually whitish or gray and of a watery consistency, whereas in AV it is yellow to green and rather thick and mucoid. Women with BV do not have dyspareunia, while some women with severe AV do. Finally, the microscopic appearance differs in various aspects, such as the presence of leucocytes and parabasal or immature epithelial cells in AV and the absence of the granular aspect of the microflora, typical of BV. Despite all these differences, the distinction between AV and BV was not recognized in many former studies, leading to incomplete and imprecise diagnostic workouts and erroneous management of patients in both clinical and research settings. The prevalence of AV ranges between 7 and 12%, and is therefore less prevalent than BV. Although still largely undiagnosed, many researchers and clinicians increasingly take it into account as a cause of symptomatic vaginitis. AV can co-occur with other entities, such as BV and candidiasis. It can be associated with dyspareunia, sexually transmitted infections (such as human papilloma virus, human immunodeficiency virus, Trichomonas vaginalis and Chlamydia trachomatis), chorioamnionitis, fetal infection, preterm birth and cervical dysplasia. Many other possible pathological associations are currently under investigation. The diagnosis of AV is made using wet mount microscopy, ideally using phase contrast. An AV score is calculated, according to: lactobacillary grade, presence of inflammation, proportion of toxic leucocytes, characteristics of the microflora and presence of immature epithelial cells. To circumvent the hurdle of microscopic investigation, some groups have begun to develop nucleic-acid-based and enzymatic diagnostic tests, but the detailed information obtained with phase contrast microscopy is irreplaceable. The best treatment is not yet fully determined, but it must be tailored according to the microscopic findings and the patient's needs. There is a role for local estrogen therapy, corticosteroids, antimicrobials and probiotics. Further research will reveal more precise data on diagnosis, pathogenesis, management and prevention.
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PMID:Aerobic vaginitis: no longer a stranger. 2850 74

Congenital toxoplasmosis is a zoonosis caused by the intracellular Apicomplexa protozoan Toxoplasma gondii. This infection causes subclinical or clinical lesions, such as retinochoroiditis and central nervous system lesions. The severity of fetal infection is related to the stage of pregnancy and the efficacy of the gestational treatment on fetal infection, whether it is achieved, or if it starts early. South America is the region with the highest burden of congenital toxoplasmosis and the most pathogenic genotypes. Here, we present the results of a comprehensive systematic review and meta-analysis of the congenital toxoplasmosis in Brazil. PubMed, Web of Science, and CAPES databases were used to search for relevant studies that were published between 1 January 2007 and 31 December 2018. The final searching process yielded 21 papers. The studies accounted for 469 children with congenital toxoplasmosis. Of these, 269 (57%) had a diagnosis in the postnatal period. Concerning mothers, 209 (44.6%) underwent prenatal care, but 47 (22.5%) did not receive any drug for toxoplasmosis treatment. There were 226 (48.2%) children with retinochoroiditis; 83 (17.7%) with brain calcifications; 9 (1.9%) with neurosensory auditory dysfunction; and 2 (0.42%) with human immunodeficiency virus coinfection. A total of 460 (98%) children had a medical and multidisciplinary follow-up for at least one year and the most frequent genotype was #11(BRII), found in seven children. There was a statistical correlation between the mother's treatment and asymptomatic children. The gestational treatment seems to protects the fetus since children of mothers who received anti-T. gondii medications have a better prognosis. The retinochoroiditis was the main finding among children, followed by brain calcifications.
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PMID:The congenital toxoplasmosis burden in Brazil: Systematic review and meta-analysis. 3261 81

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