Parvovirus B19: un nuevo patógeno emergente en pacientes con SIDA. Presentación de 3 casos / PARVOVIRUS B19: HUMAN PARVOVIRUS B19: A NEW EMERGING DISEASE IN PATIENTS WITH AIDS. REPORT OF THREE PATIENTS

El Parvovirus humano B19 puede presentarse con una amplia variedad de manifestaciones clínicas, con distinto compromiso y evolución según el huésped afectado. En pacientes inmunocomprometidos se asocia con cuadros hematológicos prolongados y graves. Se describen 3 casos de pacientes con antecedentes de infección por virus de la inmunodeficiencia humana (VIH) que desarrollaron infecciones agudas por Parvovirus B19 que se presentaron con síndrome febril, citopenias (anemia, plaquetopenia y disminución de reticulocitos) y esplenomegalia. En todos los casos el diagnóstico se confirmó por la serología específica. Todos recibieron tratamiento con inmunoglobulina humana (Ig) intravenosa (IV); 2 pacientes tuvieron buena respuesta clínica y mejoría de citopenias mientras que el restante falleció. La infección por Parvovirus B19 debe incluirse en el diagnóstico diferencial de los pacientes VIH positivos con fiebre y citopenias, principalmente anemia persistente y compromiso linfoganglionar con esplenomegalia

Human Parvovirus B 19 is presented as a variety of diseases with different compromise and evolution according to the affected host. In immunocompromised patients the acute infection due to Parvovirus B19 is associated with severe and prolonged hematological clinical pictures. Three cases of patients with a history of infection with human immunodeficiency virus (HIV) co-infected with Human Parvovirus B19 are presented. All of they presented with febrile syndrome, cytopenias (anemia, platelet count and reticulocyte reduction) and lymphadenopathy and splenomegaly. In all cases the diagnosis was confirmed by serology. All were treated with intravenous human immunoglobulin (IVI G; 2 patients had good clinical response and better cytopenias while the other died. We consider thinking about Parvovirus B19 infection in HIV immunocompromised hosts with haematological involvement, mainly persistent anemia and lymph node involvement with splenomegaly

Serological and molecular analysis of parvovirus B19 infection in Mayan women with systemic lupus erythematosus in Mexico / Análisis serológico y molecular de la infección por parvovirus B19 en mujeres mayas con lupus eritematoso sistémico en México

Abstract Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that mainly affects women, characterized by the production of autoantibodies. Its causal agent is unknown, but the combination of environmental, hormonal and genetic factors may favor the development of the disease. Parvovirus B19 has been associated with the development of SLE, since it induces the production of anti-single stranded DNA antibodies. It is unknown whether PV-B19 infection is an environmental factor that trigger or reactivate SLE in the Mexican Mayan population. Aim: A preliminary serological and molecular study of PV-B19 infection in Mayan women with established SLE was done. Methods: IgG and IgM anti PV-B19 were evaluated in 66 SLE patients and 66 control subjects, all women of Mayan origin. Viral DNA and viral load were analyzed by qPCR. Results: Insignificant levels of IgM were observed in 14.3% (4/28) of the patients and 11.4% (4/35) of control subjects. IgG was detected in 82.1% (23/28) of the patients and 82.9% (29/35) of control subjects, but were significantly higher in patients. Viral DNA was found in 86.0% (57/66) of the patients and 81.0% (54/66) of control subjects. Viral load, quantified in 28/66 patients and 31/66 controls which were positive for IgM and IgG, was significantly higher in controls. Conclusion: The high prevalence of PV-B19 in Yucatan, and the presence of IgM, IgG, and viral load in Mayan women with established SLE suggest that PV-B19 infection could be an environmental factor to trigger or reactivate SLE.

Resumen Antecedentes: Lupus eritematoso sistémico (LES) es una enfermedad sistemica autoinmune que afecta principalmente a las mujeres, caracterizada por la producción de autoanticuerpos. El agente causaal es desconocido. Pero la combinación de factores ambientales, hormonales y genéticos podría favorecer el desarrollo de la enfermedad. El parvovirus B19 se asoció con el desarrollo de LES, debido a que induce la producción de anticuerpos anti-cadena simple de DNA. Es desconocido si la infección PV-B19 es un factor ambiental que desencadena o reactiva LES en la población mexicana Maya. Objetivo: Se realizó un estudio serológico y molecular preliminar de la infección de PV-B19 en mujeres Mayas con LES. Métodos: Se evaluó IgG and IgM anti PV-B19 en 66 pacientes con LES y 66 controles sanos, todas las mujeres fueron de origen Maya. DNAViral y la carga viral fueron analizadas por qPCR. Resultados: Se determinaron niveles insignificantes de IgM en el 14.3% (4/28) de las pacientes y en el 11.4% (4/35) de los controles. IgG se detectó en el 82.1% (23/28) de los pacients y en el 82.9% (29/35) de los controles. Hubo un alta significancia en los pacientes con LES. DNA viral se encontró en el 86.0% (57/66) de los pacientes y en el 81.0% (54/66) de los controles. La carga viral se cuantifico en 28/66 pacientes y en 31/66 de los controles, la cual fueron positivos para IgM e IgG; fue significativamente mas alta en los controles. Conclusión: La alta prevalencia de PV-B19 en Yucatan y la presencia de IgM, IgG y una carga viral en mujeres Mayas con LES sugiere que la infección con PV-B19 poria ser un factor ambiental que desencadene o reactive el LES

Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group.

Viral markers in patients with hemophagocytosis: A prospective study in a tertiary care hospital.

Background : Hemophagocytic syndrome (HPS) is a rare clinicopathological condition characterized by the activation of macrophages with prominent hemophagocytosis in bone marrow and other reticulo-endothelial systems. HPS can be familial or secondary to infections including viruses. Aim : To study the viral markers in patients with HPS. Materials and Methods : Serum samples of patients with HPS and control group were screened for anti EBV VCA IgM, and IgG, anti-Parvo B19 IgM, and anti-CMV IgM antibodies using commercially available ELISA kits and CMV and ParvoB19 DNA by polymerase chain reaction (PCR). Results and Discussion : The present prospective study reports the profile of viral markers in HPS cases from north India. Among the 14 HPS cases 43% (6/14) were positive for at least one viral marker tested, of which EBV was found to be the most prevalent (3/6: 50%) followed by parvovirus B19(2/6: 33%) and cytomegalovirus (1/6: 17%). Mortality was noted in 33% of virus associated HPS patients. Our study highlights the higher association of Epstein-Barr virus (EBV) with HPS as compared to other viruses along with higher rate of mortality in both parvovirus B 19 and EBV associated HPS.

Novel detection of parvovirus B19 DNA & IgM antibodies in patients with non-occlusive gangrene of stomach & bowel.

Background: Gangrene of stomach or intestines owing to non-occlusive bowel infarction (NOBI) is a rare event with unknown etiolology. Since B19 may cause vasculitis, arteritis, angiopathy and more importantly, localized microvascular thrombi formation hence patients with bowel gangrene were investigated for B19 infection. Methods: Twelve patients (8 male and 4 females; median age 40 yr) of ischemic unexplained gangrene of bowel underwent emergency laparotomy. Eight cases had NOBI while four had occlusive bowel infarction (OBI). Anti-B19 antibodies in sera by ELISA and Western-blot and B19 DNA by PCR in sera and resected tissues were analysed. Results: All patients underwent resection of gangrenous bowel; with exteriorization followed by restoration wherever appropriate. Histopathology showed loss of bowel mucosa and crypts with inflammatory cell infiltration besides fibrin thrombus in gastric vessels. Sera of all 8 patents of NOBI had B19 genome by nested-PCR (VP1 unique) and in 6 by PCR (VP1-VP2). In three patients resected bowel tissues also had B19 DNA besides anti-B19 IgM and IgG antibodies. NOBI patients were reticulocytopenic and anaemic while one had necrotizing vasculitis of skin a year ago. No IgM antibodies to agents causing vasculitis (HTLV-I, HIV-1+2, CMV, HSV1+2, mumps virus and Mycobacterium tuberculosis) nor any abnormality in coagulation profiles were detected. In four OBI cases’s sera and resected bowel tissues and in control bowel tissues (n=36) no anti-B19 IgM antibodies or B19 DNA were detected. Conclusion: Novel finding of active B19 infection in non-occlusive gangrene of the bowel may be causal rather than casual.

Red baby syndrome a new disease due to parvovirus B-19 observed in Kerala.

Red Baby Syndrome is a new disease seen in infants and young children. Dramatic onset of clinical symptoms with high intensity, short duration and lack of similarity with other cutaneous lesions makes it distinct. Of 50 such patients studied over a period of 5 years, half were below one year of age. Abrupt onset of high fever and generalized erythema involving the entire skin, which is swollen and tender is characteristic. These children were highly irritable and had paradoxical cry when cuddled. Rapid resolution of symptoms occurred in 7-10 days with extensive desquamation. Routine investigations were normal, C-reactive protein was raised only in 10 patients. Human Parvo virus B-19 IgM antibodies were positive in 15 out of 24 patients. Real time polymerase chain reaction was positive for human parvovirus B 19 DNA in one. Histopathological changes in the skin biopsy showed post infectious vascular injury pattern.

A pilot study on the seroprevalence of parvovirus B19 infection.

BACKGROUND & OBJECTIVES: Human parvovirus B 19 (PVB 19) causes aplastic crisis in children with congenital haemolytic anaemia, erythema infectiosum, abortion and stillbirth. Since data on PVB 19 prevalence is lacking in India, a pilot study was undertaken to estimate the prevalence of IgG antibody in children and adults. METHODS: The samples were obtained from children attending our hospital and from volunteer blood donors, majority of whom were from south India. They included 45 children aged 1-5 yr, 39 aged 6-10 yr, 42 aged 11-15 yr and 100 healthy blood donors > 15 yr of age. Sera were tested for the presence of antibody to PVB 19 using a commercial enzyme immuno assay (EIA). RESULTS: Of 226 samples tested, 113 (50%) were positive for PVB 19 IgG. The prevalence of antibody increased from 8.9 per cent at 1-5 yr to 70 per cent in those > 15 yr: the median age of infection was between 6 and 15 yr. Sex and domiciliary status did not have significant effect on the prevalence of antibody. The IgG antibody index increased significantly with age, suggesting repeated exposure to the virus. INTERPRETATION & CONCLUSION: This seroprevalence study indicates that large numbers of individuals show exposure to PVB 19 virus. The exposure as indicated by IgG positivity is seen to increase with age. The IgG negative individuals may be considered to be at risk of developing infections due to PVB 19.

Detection of human parvovirus B19 in a patient with hepatitis

Parvovirus B19 has been associated by some investigators with cases of severe hepatitis. The aim of the present study was to determine the presence of active parvovirus B19 infection among 129 Brazilian patients with non-A-E hepatitis. The patients were assayed for antibodies against parvovirus B19, IgM class, by ELISA. In IgM-positive cases, parvovirus B19 DNA was assayed by PCR in serum and liver tissue and parvovirus VP1 antigen in liver tissue was assayed by immunohistochemistry. Antibodies against parvovirus B19, IgM class, were detected in 3 (2.3 percent) of 129 patients with non-A-E hepatitis. Previous surgery and blood transfusions were reported by these 3 patients. One patient was a 56-year-old female with severe hepatitis, with antimitochondrial antibody seropositivity and submassive necrosis at liver biopsy, who responded to corticosteroid therapy. Strong evidence for active parvovirus B19 infection was found in this patient, with parvovirus B19 DNA being detected by PCR in liver tissue. Furthermore, parvovirus VP1 antigen was also detected in liver tissue by immunohistochemistry. The other two IgM-positive patients were chronic hepatitis cases, but active infection was not proven, since neither viral DNA nor antigen were detected in their liver tissues. This and other reports suggest a possible relation between parvovirus B19 infection and some cases of hepatitis

Parvovirus B19 antibodies in immunocompromized children in Thailand.

Parvovirus B19, a non-enveloped single stranded DNA virus is distributed worldwide. Sero-prevalence in adult populations amounts to approximately 50%. Clinical manifestations vary depending on the Immune status of the infected individuals and may include mild childhood Infection as well as hydrops fetalis due to intrauterine infection. To determine the prevalence of this infection among the immunocompromized individuals in Thailand, we determined, by indirect ELISA, levels of IgM and IgG antibodies to the parvovirus B19 in 106 immunocompromized children. These included 49 children who were on chemotherapy for treatment of malignancies, 18 who were receiving immunosuppressive drugs after organ transplantations, 14 who were under a regimen of corticosteroids and 25 who were positive for antibodies to HIV. The average prevalence of IgG antibodies in 106 children was 16.0%; the prevalence of antibodies was 33.3% in post-transplanted group, 16% in children positive for HIV, 12.2% in the group receiving chemotherapy for malignancies and 7.6% in the group treated with corticosteroids. All children were negative for IgM antibodies to parvovirus B19.

Prevalence of antibodies to parvovirus B 19 in Thailand.

Infection with human parvovirus B 19, a single-stranded non-enveloped DNA virus of worldwide distribution, is rather common and displays a broad spectrum of clinical manifestations of varying severity, depending on the patient's immune response. As the target of infection are the erythroid precursor cells, patients can experience an aplastic crisis. Usually, at least in immunocompetent individuals, viremia ceases with the appearance of virus-specific antibodies in the patient's serum whereupon the patients retain lifelong immunity to reinfection. Since data as to the prevalence of this agent has not been established for Thailand, the purpose of the present study was to investigate its frequency among 3 distinct groups, comprising 30 healthy children. 64 children with acute unrelated illness, and 35 voluntary blood donors, respectively, by means of enzyme linked immunosorbent assay. Our results have shown that, as reported for other countries, anti-parvovirus IgG increases in an age-dependent manner and is established at an overall prevalence of 20.16%, inviting the conclusion that the local population is infected by this agent as frequently as those of other countries in the Far East. Further studies need to be undertaken in order to elucidate its prevalence among members of high-risk groups.

Raised IgM antibodies to parvovirus B19 in juvenile rheumatoid arthritis.

To delineate the role of human parvovirus B19 in the etiopathogenesis of juvenile rheumatoid arthritis (JRA), IgM and IgG antibodies specific for parvovirus B19 surface protein antigen(s) were estimated in the sera using commercial ELISA kits. Sera of 69 JRA patients (median age 16 yr, male : female ratio 1.1:1) satisfying the criteria of American Rheumatism Association along with 26 sera of rheumatoid arthritis (RA) and 12 sera of healthy children as disease and normal controls respectively were screened. Of the 69 patients with JRA, 19 (27.5%), 35 (50.7%) and 9 (13%) were positive for IgM, IgG and both IgG and IgM antibodies respectively. Of the 26 disease control sera, 11 (42.3%) were positive for IgG antibodies while none had elevated IgM antibodies. Among 12 healthy controls, 7 (58.3%) were positive for IgG and 1 was positive for both IgG and IgM antibodies. Thus, a statistically significant proportion of children with JRA had evidence of parvovirus B19 infection.

Human parvovirus B19 infections among exanthematic diseases notified as measles

A total of 1397 sera collected from 1095 cases of exanthematic disease notified as measles in ES and RJ states during July 1992 to December 1994 were investigated. These sera were first tested for measles and rubella specific IgM. When they proved negative, they were tested for B19 specific IgM by an enzyme immunoassay. B19 infection was confirmed in 27 (2.5 per cent) of these cases. Sera from 194 negative cases for measles and rubella IgM received from other Brazilian states were also investigated and B19 infection was confirmed for 11 of them. Sera from these 38 IgM positive cases for B19, were tested for anti-B19 IgG by an enzyme immunoassay and for B19 DNA by dot blot hybridization. Anti-B19 IgG antibodies were detected in most of the acute sera. B19 DNA was detected in the acute serum of one patient that had been splenectomized before. As the exanthem caused by human parvovirus infection may be clinically diagnosed as rubella, it could be important to diagnose B19 infection in Brazil since it is becoming prevalent as the cause of rash in countries where rubella is controlled by vaccination.