Epidemiological, clinical and pathological features of canine parvovirus 2c infection in dogs from southern Brazil / Aspectos epidemiológicos, clínicos e patológicos da infecção pelo parvovirus canino 2c em cães do Sul do Brasil

Canine parvovirus type 2c (CPV-2c) emerged in Europe in the early 2000's and rapidly spread out worldwide. Clinical and molecular data have demonstrated its circulation in Brazilian dogs, yet detailed descriptions of cases are still lacking. This article describes the epidemiological, clinical and pathological features of 24 cases of CPV-2c-associated disease in dogs submitted to veterinary clinics and laboratory diagnosis in southern Brazil (2014-2016). Most affected dogs presented signs/lesions suggestive of parvovirus enteritis: diarrhea, vomiting, hyperemia and hemorrhage of the serous membrane of the small intestine, diffuse segmental granulation, atrophy of the villi, necrosis and fusion of crypts, squamous metaplasia and epithelial syncytia. A number of cases presented features divergent from the classical presentations, including a wide variation in the color of feces (reddish and/or yellowish, light-brownish, orange-brown and brownish), involvement of adults (4/24) and vaccinated dogs (12/24), extensive involvement of the small intestine (8/20) and the presence of pulmonary edema (7/24) and convulsions (3/24). Feces and intestinal fragments submitted to PCR for the CPV-2 VP2 gene and to virus isolation in cell culture yielded positive results in 100% and 58.3% (14/24) of the cases, respectively. Nucleotide sequencing revealed a high nucleotide identity in VP2 (99.4 to 100%) and a consistent mutation at amino acid 426 (asparagine to glutamic acid), considered a signature of CPV-2c. These results confirm the involvement of CPV-2c in the described cases and demonstrate the importance of CPV-2c infection among Brazilian dogs, calling attention of veterinarians to correctly diagnose the disease, mainly considering the frequent atypical presentations.(AU)

O parvovírus canino tipo 2c (CPV-2c) surgiu na Europa no início do ano 2000 e rapidamente se espalhou pelas populações de cães ao redor do mundo. Dados clínicos e moleculares demonstraram a sua circulação em cães brasileiros, porém descrições detalhadas desses casos ainda são escassas. Este artigo descreve os aspectos epidemiológicos, clínicos e patológicos de 24 casos de doença gastroentérica associada com a infecção pelo CPV-2c em cães atendidos em clínicas veterinárias e submetidos ao diagnóstico laboratorial no Sul do Brasil (2014-2016). A maioria dos cães afetados apresentaram sinais e/ou lesões sugestivas de enterite por parvovírus: diarreia, vômitos, hiperemia e hemorragia na membrana serosa do intestino delgado, granulação segmentar difusa, atrofia das vilosidades, necrose e fusão de criptas, metaplasia escamosa e sincícios epiteliais. Alguns casos apresentaram características divergentes das apresentações clássicas, incluindo uma grande variação na cor das fezes (avermelhada e/ou amarelada, marrom-claro, marrom-alaranjada ou amarronzada), a participação dos adultos (4/24) e cães vacinados (12/24), um amplo envolvimento do intestino delgado (8/20), a presença de edema pulmonar (7/24) e convulsões (3/24). As fezes e fragmentos intestinais foram submetidos ao teste de PCR para o gene VP2 do CPV-2, e ao isolamento do vírus em cultura de células produziram resultados positivos em 100% e 58,3% (14/24) dos casos, respectivamente. O sequenciamento dos nucleótidos revelou uma alta identidade de nucleótidos na VP2 (99,4-100%) e uma mutação no aminoácido 426 (asparagina para ácido glutâmico), considerada uma assinatura de CPV-2c. Estes resultados confirmam o envolvimento do CPV-2c nos casos descritos e demonstra a importância da infecção pelo CPV-2c entre os cães do Brasil, chamando a atenção de veterinários para diagnosticar corretamente a doença, principalmente considerando-se as apresentações atípicas frequentes.(AU)

Epidemiological, clinical and pathological features of canine parvovirus 2c infection in dogs from southern Brazil / Aspectos epidemiológicos, clínicos e patológicos da infecção pelo parvovirus canino 2c em cães do Sul do Brasil

Canine parvovirus type 2c (CPV-2c) emerged in Europe in the early 2000's and rapidly spread out worldwide. Clinical and molecular data have demonstrated its circulation in Brazilian dogs, yet detailed descriptions of cases are still lacking. This article describes the epidemiological, clinical and pathological features of 24 cases of CPV-2c-associated disease in dogs submitted to veterinary clinics and laboratory diagnosis in southern Brazil (2014-2016). Most affected dogs presented signs/lesions suggestive of parvovirus enteritis: diarrhea, vomiting, hyperemia and hemorrhage of the serous membrane of the small intestine, diffuse segmental granulation, atrophy of the villi, necrosis and fusion of crypts, squamous metaplasia and epithelial syncytia. A number of cases presented features divergent from the classical presentations, including a wide variation in the color of feces (reddish and/or yellowish, light-brownish, orange-brown and brownish), involvement of adults (4/24) and vaccinated dogs (12/24), extensive involvement of the small intestine (8/20) and the presence of pulmonary edema (7/24) and convulsions (3/24). Feces and intestinal fragments submitted to PCR for the CPV-2 VP2 gene and to virus isolation in cell culture yielded positive results in 100% and 58.3% (14/24) of the cases, respectively. Nucleotide sequencing revealed a high nucleotide identity in VP2 (99.4 to 100%) and a consistent mutation at amino acid 426 (asparagine to glutamic acid), considered a signature of CPV-2c. These results confirm the involvement of CPV-2c in the described cases and demonstrate the importance of CPV-2c infection among Brazilian dogs, calling attention of veterinarians to correctly diagnose the disease, mainly considering the frequent atypical presentations.(AU)

O parvovírus canino tipo 2c (CPV-2c) surgiu na Europa no início do ano 2000 e rapidamente se espalhou pelas populações de cães ao redor do mundo. Dados clínicos e moleculares demonstraram a sua circulação em cães brasileiros, porém descrições detalhadas desses casos ainda são escassas. Este artigo descreve os aspectos epidemiológicos, clínicos e patológicos de 24 casos de doença gastroentérica associada com a infecção pelo CPV-2c em cães atendidos em clínicas veterinárias e submetidos ao diagnóstico laboratorial no Sul do Brasil (2014-2016). A maioria dos cães afetados apresentaram sinais e/ou lesões sugestivas de enterite por parvovírus: diarreia, vômitos, hiperemia e hemorragia na membrana serosa do intestino delgado, granulação segmentar difusa, atrofia das vilosidades, necrose e fusão de criptas, metaplasia escamosa e sincícios epiteliais. Alguns casos apresentaram características divergentes das apresentações clássicas, incluindo uma grande variação na cor das fezes (avermelhada e/ou amarelada, marrom-claro, marrom-alaranjada ou amarronzada), a participação dos adultos (4/24) e cães vacinados (12/24), um amplo envolvimento do intestino delgado (8/20), a presença de edema pulmonar (7/24) e convulsões (3/24). As fezes e fragmentos intestinais foram submetidos ao teste de PCR para o gene VP2 do CPV-2, e ao isolamento do vírus em cultura de células produziram resultados positivos em 100% e 58,3% (14/24) dos casos, respectivamente. O sequenciamento dos nucleótidos revelou uma alta identidade de nucleótidos na VP2 (99,4-100%) e uma mutação no aminoácido 426 (asparagina para ácido glutâmico), considerada uma assinatura de CPV-2c. Estes resultados confirmam o envolvimento do CPV-2c nos casos descritos e demonstra a importância da infecção pelo CPV-2c entre os cães do Brasil, chamando a atenção de veterinários para diagnosticar corretamente a doença, principalmente considerando-se as apresentações atípicas frequentes.(AU)

Molecular detection of chicken parvovirus in broilers with enteric disorders presenting curving of duodenal loop, pancreatic atrophy, and mesenteritis.

Enteric disorders are an important cause of economic losses in broiler chickens worldwide. Several agents have been associated with enteric problems, such as viruses, bacteria, and parasites. In this study, broiler chickens showing signs of enteric disorders were subjected to molecular diagnosis for several viral agents and also for pathological examination for elucidating this problem. Thus, the chickens were screened for avian nephritis virus (ANV), chicken astrovirus (CAstV), avian rotavirus (ArtV), avian reovirus (AReoV), infectious bronchitis virus (IBV), fowl adenovirus group I (FAdV-1), and chicken parvovirus (ChPV). Postmortem examinations revealed a curving of the duodenal loop (J-like appearance) and intestines filled with liquid and gaseous content. Histopathological analysis of the duodenal loop showed pancreatic atrophy, acute mesenteritis, and enteritis. PCR results showed that ChPV was the sole viral agent detected in samples with lesions such as the curved duodenal loop and pancreatic atrophy. Molecular characterization of the nucleotide and deduced amino acid sequences revealed a high similarity with other strains of ChPV from Brazil, Canada, United States, Europe, and Asia. These findings suggest an association between ChPV and the development of enteritis, pancreatitis, and pancreatic atrophy, which may lead to curling of the duodenal loop. Together, these alterations may disrupt the normal functioning of the digestive system, diminishing digestion and the absorption of dietary nutrients and consequently leading to reduced weight gain, flock impairment, dwarfism, and an elevated feed conversion rate.

Isolation and molecular characterisation of chicken parvovirus from Brazilian flocks with enteric disorders.

1. The presence of parvovirus in chickens with enteric disease was investigated in commercial flocks in Brazil. 2. The intestinal contents of chickens exhibiting clinical signs of diarrhoea, weight loss or mortality were examined, and chicken parvovirus (chPV) was identified using a polymerase chain reaction (PCR) assay. The samples were sequenced and inoculated into specific-pathogen-free (SPF) embryonated eggs to isolate the virus. 3. Necropsies showed that the embryos were dwarfish, haemorrhagic and oedematous. The presence of chPV was confirmed by PCR and DNA sequencing. 4. The molecular characterisation of chPV strains circulating in the Brazilian flocks showed that they were genetically related to sequences from North America, Europe and Asia. Phylogenetic analyses clustered the Brazilian chPV sequences with those from Europe (Croatia, Hungary) and Asia (South Korea). 5. This study is the first report of the molecular characterisation of chPV circulating in the commercial flocks in Brazil and indicates high genetic similarity with chPV sequences from around the world.

Parvovirus among patients with cytopenia of unknown origin in Brazil: a case-control study.

The molecular prevalence of human parvovirus B19V (B19V) in bone marrow (BM) samples from 120 cases with cytopenias of unknown etiology was compared with that in samples from 45 BM donors (control group 1) and 120 oncohematological patients (control group 2) to determine the role that B19V genotypes may play in unexplained cytopenias. Of the 285 participants, the BM samples of 39 (13.7%) contained B19V DNA (21 with genotype 1, 5 with genotype 2, and 13 with genotype 3). The prevalences of B19V were similar between case and control subjects (15.0% versus 12.7%, respectively). Genotypes 2 and 3 were associated with older age and were detected in similar proportions between case and control group 2 subjects. The results of this study do not support a role for B19V genotype variants in the etiology of unexplained cytopenias.

Detection of parvovirus B19 infection in formalin-fixed and paraffin-embedded placenta and fetal tissues.

Parvovirus B19 infection was first discovered in 1975 and it is implicated in fetal death from hydrops fetalis the world over. Diagnosis is usually made through histological identification of the intranuclear inclusion in placenta and fetal organs. However, these cells may be scarce or uncharacteristic, making definitive diagnosis difficult. We analyzed histologically placentas and fetal organs from 34 cases of non-immune hydrops fetalis, stained with Hematoxylin and Eosin (HE) and submitted to immunohistochemistry and polymerase chain reaction (PCR). Of 34 tissue samples, two (5.9%) presented typical intranuclear inclusion in circulating normoblasts seen in Hematoxylin and Eosin stained sections, confirmed by immunohistochemistry and PCR. However, PCR of fetal organs was negative in one case in which the placenta PCR was positive. We concluded that parvovirus B19 infection frequency is similar to the literature and that immunohistochemistry was the best detection method. It is highly specific and sensitive, preserves the morphology and reveals a larger number of positive cells than does HE with the advantage of showing cytoplasmic and nuclear positivity, making it more reliable. Although PCR is more specific and sensitive in fresh or ideally fixed material it is not so in formalin-fixed paraffin-embedded tissues, frequently the only one available in such cases.

Detection of parvovirus B19 infection in formalin-fixed and paraffin-embedded placenta and fetal tissues

Parvovirus B19 infection was first discovered in 1975 and it is implicated in fetal death from hydrops fetalis the world over. Diagnosis is usually made through histological identification of the intranuclear inclusion in placenta and fetal organs. However, these cells may be scarce or uncharacteristic, making definitive diagnosis difficult. We analyzed histologically placentas and fetal organs from 34 cases of non-immune hydrops fetalis, stained with Hematoxylin and Eosin (HE) and submitted to immunohistochemistry and polymerase chain reaction (PCR). Of 34 tissue samples, two (5.9 percent) presented typical intranuclear inclusion in circulating normoblasts seen in Hematoxylin and Eosin stained sections, confirmed by immunohistochemistry and PCR. However, PCR of fetal organs was negative in one case in which the placenta PCR was positive. We concluded that parvovirus B19 infection frequency is similar to the literature and that immunohistochemistry was the best detection method. It is highly specific and sensitive, preserves the morphology and reveals a larger number of positive cells than does HE with the advantage of showing cytoplasmic and nuclear positivity, making it more reliable. Although PCR is more specific and sensitive in fresh or ideally fixed material it is not so in formalin-fixed paraffin-embedded tissues, frequently the only one available in such cases.

O parvovírus B19 foi detectado em 1975 e desde sua descoberta tem se mostrado um agente infeccioso importante em seres humanos, cujo diagnóstico pode ser feito pelo exame histológico através do encontro de inclusão nuclear em tecidos fetais ou placentários. No entanto, estas células podem ser escassas ou não apresentarem características típicas, dificultando o diagnóstico. Analisamos placentas e órgãos fetais de 34 casos de hidropisia fetal não-imune corados com Hematoxilina e Eosina (HE) e submetidos à reação em cadeia da polimerase (PCR) e imuno-histoquímica (IH). Em dois casos (5,9 por cento) houve positividade na placenta pelo HE, IH e PCR. No entanto, PCR dos órgãos fetais foi negativa em um destes casos enquanto que a identificação pôde ser feita por IH e histologia. Concluímos que a freqüência do parvovírus B19 é similar à literatura e a reação IH foi o melhor método de detecção, com identificação mais específica e segura, permitindo identificação citoplasmática, o que não é possível pelo exame histopatológico. A PCR pode apresentar falsa negatividade, provavelmente pela fixação, não identifica as células e é mais dispendiosa. Embora mais específica e sensível em material a fresco ou idealmente fixado isto não ocorre com tecidos fixados em formalina e embebidos em parafina, freqüentemente os únicos disponíveis.

Erythrovirus B19 infection in acquired immunodeficiency syndrome: screening by histopathology, immunohistochemistry, and in situ hybridization.

Erythrovirus B19 infects erythrocytic progenitors, transiently interrupting erythropoiesis. In AIDS patients it causes chronic anemia amenable to treatment. We looked for evidences of B19 infection in stored bone marrow material from patients with acquired immunodeficiency syndrome. Histological sections were made from stored paraffin blocks from 33 autopsies (39 blocks) and 35 biopsies (45 blocks, 30 patients) performed from 1988 to 2002. They were examined after hematoxylin-eosin (HE) staining, immunohistochemical (IHC), and in situ hybridization. HE revealed intra-nuclear inclusion bodies ("lantern cells") suggesting B19 infection in 19 sections corresponding to 19 of 63 patients examined with this test. Seven of 78 sections subjected to immunohistochemistry were positive, corresponding to 7 of 58 patients examined with this test. Fourteen sections corresponding to 13 of the 20 HE and/or IHC positive patients were subjected to in situ hybridization, with six positives results. Among the 13 patients subjected to the three techniques, only one gave unequivocal positive results in all and was considered a true positive. The frequency of B19 infection (1/63 patients) in the material examined can be deemed low.

Erythrovirus B19 infection in acquired immunodeficiency syndrome: screening by histopathology, immunohistochemistry, and in situ hybridization

Erythrovirus B19 infects erythrocytic progenitors, transiently interrupting erythropoiesis. In AIDS patients it causes chronic anemia amenable to treatment. We looked for evidences of B19 infection in stored bone marrow material from patients with acquired immunodeficiency syndrome. Histological sections were made from stored paraffin blocks from 33 autopsies (39 blocks) and 35 biopsies (45 blocks, 30 patients) performed from 1988 to 2002. They were examined after hematoxylin-eosin (HE) staining, immunohistochemical (IHC), and in situ hybridization. HE revealed intra-nuclear inclusion bodies ("lantern cells") suggesting B19 infection in 19 sections corresponding to 19 of 63 patients examined with this test. Seven of 78 sections subjected to immunohistochemistry were positive, corresponding to 7 of 58 patients examined with this test. Fourteen sections corresponding to 13 of the 20 HE and/or IHC positive patients were subjected to in situ hybridization, with six positives results. Among the 13 patients subjected to the three techniques, only one gave unequivocal positive results in all and was considered a true positive. The frequency of B19 infection (1/63 patients) in the material examined can be deemed low.

[Tubulointerstitial nephritis associated with parvovirus beta19 infection]. / Nefritis tubulo intersticial asociada a parvovirus B19.

A previously healthy 9 year old girl developed nephrotic syndrome with hypertension, microhematuria and normal renal function. The patient evolved as steroid resistant nephrotic syndrome whose initial renal biopsy was consistent with diffuse proliferative mesangial glomerulonephritis with focal segmental glomerulosclerosis. At the time of cyclophosphamide and prednisone treatment, she developed a prolonged febrile syndrome. She also had severe anemia following an aplastic crisis induced by human parvovirus B19 infection and acute renal failure secondary to a severe tubulointersticial disease. Bone marrow and renal tissue, tested by polimerase chain reaction were positive for parvovirus, while the patient's blood was negative. The renal involvement did not improve requiring chronic dialysis support. We believe that the initial glomerular disease could have been due to a parvovirus infection followed by un unexpected acute tubular interstitial nephritis, rapidly progressing to chronic renal disease. This case represents, to our knowledge, the first time that a direct relationship between parvovirus infection and acute tubulointerstitial disease has been demonstrated.

Parvovirus B19: another agent associated with remitting seronegative symmetrical synovitis with pitting edema.

A number of conditions have been associated with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) and the controversy of whether this should be considered a syndrome rather than a disease continues. There are few reports on the role of infectious agents in the etiology of RS3PE, and human parvovirus B19 has not previously been linked to this syndrome. We describe a patient with RS3PE syndrome in association with positive serology and viremia for parvovirus B19. A 9-year followup failed to uncover another cause for RS3PE.

Nefritis tubulo intersticial asociada a parvovirus b19 / Tubulointerstitial nephritis associated with parvovirus beta19 infection

Paciente de 9 años, previamente sana, que ingresa en anasarca con síndrome nefrótico clínico y humoral, asociado a hipertensión arterial y microhematuria, con función renal normal y se comporta como corticorresistente. Se realiza 1º biopsia renal que informa glomerulonefritis proliferativa mesangial difusa con esclerosis focal y segmentaria. En tratamiento con ciclofosfamida y corticoides, presenta síndrome febril prolongado con anemia secundaria a crisis aplásica de la serie roja

Nefritis tubulo intersticial asociada a parvovirus b19 / Tubulointerstitial nephritis associated with parvovirus beta19 infection

Paciente de 9 años, previamente sana, que ingresa en anasarca con síndrome nefrótico clínico y humoral, asociado a hipertensión arterial y microhematuria, con función renal normal y se comporta como corticorresistente. Se realiza 1° biopsia renal que informa glomerulonefritis proliferativa mesangial difusa con esclerosis focal y segmentaria. En tratamiento con ciclofosfamida y corticoides, presenta síndrome febril prolongado con anemia secundaria a crisis aplásica de la serie roja, asociada con una infección aguda por parvovirus B19, e insuficiencia renal aguda secundaria a nefritis tubulointersticial severa. La PCR para parvovirus B19 DNA fue positiva en tejido renal y médula ósea. La paciente evoluciona a insuficiencia renal crónica terminal. No se puede descartar que desde su inicio, el síndrome nefrótico estuviera asociado al daño glomerular por la infección viral, que comenzó como síndrome nefrótico con componentes nefríticos y que evoluciona inesperadamente a una nefritis tubulointersticial. Este sería el primer caso en el que se documenta como causa de insuficiencia renal crónica terminal, un daño tubulointersticial secundario a parvovirus B19.

Etiopatogênese da infecção por parvovírus humano B19 e relação com leucemias agudas da infância / Human parvovirus B19: etiopathogenesis and relation with leukaemias

O parvovírus humano B19 (B19V) é o agente causador do eritema infeccioso em crianças, há muito conhecidocomo "quinta doença". Esta infecção foi descrita inicialmente há mais de 100 anos, no entanto há apenas 30 anoso vírus tornou-se conhecido dos cientistas. Apesar de se resolver sem maiores complicações, em indivíduosnormais (imunocompetentes), alguns grupos de pacientes merecem especial atenção quando acometidos por esteparvovírus, tendo em vista as sérias complicações que podem vir a apresentar no futuro. Entre tais pacientesencontram-se os portadores de hemoglobinopatias, imunocomprometidos e fetos. Especula-se que a infecção porB19 está associada a etiopatogênese de leucemias agudas. Atualmente, modernas técnicas vêm sendo empregadaspara o diagnóstico desta doença, incluindo a dosagem sérica de imunoglobulinas e a detecção do vírus. O tratamento,por outro lado, continua sintomático na maior parte dos casos. No entanto novas abordagens terapêuticas com usoanti-retroviral vêm sendo utilizadas, especialmente nas complicações que o parvovírus provoca. O objetivo destetrabalho é apresentar uma revisão enfocando os principais aspectos clínicos, imunocelulares e terapêuticos destadoença exantemática comumente subestimada.

Feto-placentary pathology in human parvovirus B19 infection.

In view of the scarce references concerning the histological data in congenital parvovirus human B19 infection, we intend to provide a description of the pathological features observed in six autopsies. The virus was detected by DNA hybridization (ISH-DBH), PCR and electronmicroscopy (EM) in paraffin-embedded feto-placentary tissues. These cases constitute a subset from 86 Non Immunologic Hydrops Fetalis (NIHF) cases, in which a systemic complex of inflammatory/degenerative lesions of unknown etiology was visualized by optical microscopy. In one case a syphilitic process was detected, typefying a double infection. All fetuses showed a similar pathology--hydrops, hepato-splenomegaly, lung hypoplasia and erythroblastemia, the specific histological feature being the presence of intranuclear inclusions in the erythroid progenitors, in the erythropoietic visceral tissue and in blood marrow. Complex cardiopathy allied to abnormal lung lobulation and polisplenia were observed once; in 2 cases endocardial fibroelastosis was diagnosed. The pulmonary lesions were represented by dysmaturity allied to interstitial mononuclear infiltration. The hepatic consisted of cholestasis, portal fibrosis, canalicular proliferation, hemossiderosis, focal necroses and giant cell transformation. The central nervous system lesions were predominantly anoxic although the autolysis impaired a correct diagnosis.

Feto-placentary pathology in human parvovirus B (19) infection

Sao escassas as referencias aos dados histologicos relativos a infeccao congenita pelo parvovirus humano B(19). Apresentamos estudo morfologico de seis autopsias em que o virus foi detectado por hibridizacao DNA (HIS-HDB), PCR e microscopia eletronica (ME) em tecidos feto-placentarios fixados em formol e incluidos em parafina. Estas autopsias integravam um grupo de 86 Hidropisias Fetais nao Imunologicas (HFNI) que apresentaram a microscopia optica complexo lesional sistemico inflamatorio/degenerativo de causa indeterminada. Em uma crianca detectou-se processo sifilitico multivisceral com microorganismos, caracterizando infeccao dupla. Os fetos exibiram quadro semelhante: hidropisia, hepato-esplenomegalia, hipoplasia pulmonar e eritroblastemia...

Síndrome hemofagocítico asociado a parvovirus B19 y citomegalovirus / Parvovirus associated hemophagocytic syndrome B19 citomegalovirus

El síndrome hemofagocítico asociado a virus está caracterizado por fiebre elevada, hepatoesplenomegalia, anormalidades de la coagulación, linfadenopatías, pancitopenia y una proliferación histiocítica benigna con hemofagocitos en médula ósea, ganglios linfáticos, bazo e higado. Los virus del grupo herpes han sido los más frecuentementes identificados como agentes causantes. Se presenta el caso de un varón de 5 meses de edad con síndrome hemofagocítico y evidencia serológica de infección reciente por parvovirus B19 y citomegalovirus; con evolución tórpida sin respuesta al tratamiento con antivirales, inmunoglobulina y quimioterapia. Destacamos la importancia de la infección por parvovirus B19 en el diagnóstico diferencial de los niños con hepatoesplenomegalia y alteraciones hematológicas. Asimismo, se trata del segundo caso reportado en la literatura de síndrome hemofagocítico secundario e infección por parvovirus B19