Challenges of managing HIV cytomegalovirus co-infection in the presence of pancytopenia

A 60-year-old male patient who presented with generalized weakness and low-grade fever was diagnosed to be human immunodeficiency virus (HIV) positive with a CD4 count of 17. Routine laboratory investigations revealed pancytopenia. Serum cytomegalovirus (CMV) DNA polymerase chain reaction (PCR) was positive and fundoscopy showed CMV retinitis in the right eye. The patient was started on tablet valganciclovir. After 2 weeks, the patient was brought back in an altered sensorium. He was found to have hyponatremia which was corrected. He was started on antiretroviral therapy and tablet valganciclovir was continued. The patient came back again after one and a half months with a urinary tract infection and fissure-in-ano. He was found to have severe neutropenia. Valganciclovir was stopped. He was started on injection granulocyte colony-stimulating factor. The patient clinically improved and his hematological parameters became normal. Patients having HIV and CMV co-infection with pre-existing pancytopenia have to be closely monitored as the medicines used for treatment can exacerbate the existing conditions.

Síndrome de Evans asociada a infección por citomegalovirus en una niña de 13 meses / Evans Syndrome Associated With Cytomegalovirus Infection In A 13-Month-Old Girl

Introducción: El síndrome de Evans es un desorden autoinmune poco frecuente, caracterizado por el descenso de al menos dos líneas celulares hemáticas. Las publicaciones del síndrome de Evans e infección por citomegalovirus resultan escasas. Objetivo: Examinar el caso de una niña con síndrome de Evans e infección activa por citomegalovirus que respondió favorablemente a la terapia antiviral. Presentación del caso: Niña de 13 meses con antecedentes de prematuridad y bajo peso al nacer, que acudió a consulta por presentar palidez y equimosis en tórax, abdomen y extremidades. En los exámenes de laboratorio se encontró trombocitopenia y anemia severa con prueba de Coombs directo positiva. Recibió pulsos de metilprednisolona con respuesta desfavorable. La carga viral resultó positiva para citomegalovirus (4019 copias de ADN) y recibió valganciclovir con evolución favorable en el seguimiento. Conclusiones: El síndrome de Evans asociado a infección por CMV es infrecuente. El tratamiento con valganciclovir podría ser beneficioso para cierto grupo de pacientes; sin embargo, hacen falta más estudios que demuestren la eficacia y seguridad de este tratamiento en este síndrome; más aún si está asociado a una elevada carga viral(AU)

Introduction: Evans syndrome is a rare autoimmune disorder, characterized by the descent of at least two blood cell lines. Publications of Evans syndrome and cytomegalovirus infection are scarce. Objective: To examine the case of a girl with Evans syndrome and active cytomegalovirus infection who responded favorably to antiviral therapy. Case presentation: A 13-month-old girl with a history of prematurity and low birth weight, who attended the consultation for presenting pallor and ecchymosis in the thorax, abdomen and extremities. Laboratory tests found thrombocytopenia and severe anemia after a positive direct Coombs test. She received pulses of methylprednisolone with unfavorable response. The viral load was positive for cytomegalovirus (4019 copies of DNA) and received valganciclovir with favorable evolution at follow-up. Conclusions: Evans syndrome associated with CMV infection is uncommon. Treatment with valganciclovir may be beneficial for a certain group of patients. However, more studies are needed to demonstrate the efficacy and safety of this treatment in this syndrome; even more so if it is associated with a high viral load(AU)

Oral valganciclovir in human immunodeficiency virus-positive patients suffering from cytomegalovirus retinitis at a tertiary care hospital in North India

Purpose: To study clinical efficacy of valganciclovir in cytomegalovirus retinitis (CMVR) in human immunodeficiency virus (HIV)?positive?positive patients in a tertiary care clinic in a developing nation. Methods: In a retrospective study, systemic and ocular records of HIV patients suffering from CMVR and treated with valganciclovir, were analyzed. Primary outcome measures were involvement of the other eye, incidence of retinal detachment, systemic involvement, and mortality encountered. Secondary outcome measures included change in BCVA. Results: Out of nine patients who were included, two patients developed CMVR in the other eye and only one patient (11.11%) developed retinal detachment during the course of the study. No patient developed any systemic manifestations or had mortality during the course of the study. The change in BCVA was not statistically significant. Conclusion: Use of oral valganciclovir showed good outcome and was found to be a better alternative compared to the use of intravitreal ganciclovir in the literature. Introduction of valganciclovir at an affordable price in developing nations can decrease disease burden

Application of redox reactions for the determination of valganciclovir hydrochloride in pharmaceuticals

Two simple, selective and sensitive spectrophotometric methods were developed and validated for the determination of valganciclovir hydrochloride (VLGH) in pure drug and tablets. The first method was based on the reduction of iron(III) to iron(II) by VLGH and subsequent formation of iron(III)-ferricyanide complex (Prussian blue) in acid medium which was measured at 730 nm (method A). In the second method (method B), permanganate was reduced by VLGH to bluish green manganate in alkaline medium and the absorbance was measured at 610 nm. The absorbance measured in each case was related to VLGH concentration. The experimental conditions were carefully studied and optimized. Beer's law was obeyed over the concentration ranges of 2.5-20.0 and 2.0-40.0 µg mL-1 for method A and method B, respectively, with corresponding molar absorptivity values of 1.28×104 and 6.88×103 L mol-1 cm-1. The limits of detection (LOD) and quantification (LOQ) were 0.11 and 0.33 µg mL-1 (method A) and 0.21 and 0.64 µg mL-1 (method B). Within-day and between-day relative standard deviations (%RSD) at three different concentrations levels were < 2.4%, and the respective relative errors (%RE) were ≤ 3%. The proposed methods were successfully applied to the determination of VLGH in tablets, and the results confirmed that the proposed methods were equally precise and accurate as the official method.

Incidencia y características clínicas de pacientes trasplantados renales con infección y enfermedad por citomegalovirus en un centro de trasplante / Incidence and clinical characteristics of renal transplanted patients with infection and disease by cytomegalovirus in a transplant center

Resumen Introducción: la infección viral más importante postrasplante renal es la infección por citomegalovirus (CMV), hay discrepancia entre centros y países en datos de incidencia de infección-enfermedad en esta población de pacientes. Diseño: se realiza un estudio observacional analítico, tomando una cohorte retrospectiva de pacientes mayores de 18 años, trasplantados renales de donante vivo o cadavérico entre el 2004 y 2015 con al menos seis meses de seguimiento. Material y métodos: se realiza muestreo no probabilístico por conveniencia, se toman los datos de las historias clínicas de los pacientes trasplantados renales, calculando la densidad de incidencia de infección-enfermedad por CMV y se describen las características clínicas y demográficas de los pacientes que presentaron estas patologías. Resultados: se analizaron 252 pacientes, encontrando 92.4% receptores con riesgo intermedio para CMV y 7.5% con riesgo alto, ninguno fue de riesgo bajo. Se identificaron 19 casos, 13 con infección (5.1%) y seis con enfermedad (2.3%). El compromiso gastrointestinal fue el más frecuente. El tiempo promedio desde el momento del trasplante hasta la aparición de la infección-enfermedad fue de 417 (±479) y 650 días (±481), respectivamente. La tasa de infección fue de 10.08 casos por 1000 pacientes/año y la tasa de enfermedad de 5.88 por 1000 pacientes/año. Conclusiones: la densidad de incidencia de infección-enfermedad por CMV en pacientes trasplantados renales fue de 10.08 casos y 5.88 casos por 1000 pacientes/año, respectivamente. Estas tasas son menores a las reportados en la literatura. Dada la baja frecuencia de eventos, no fue posible establecer factores de asociación.

Abstract Introduction: the most important viral infection after renal transplantation is cytomegalovirus (CMV) infection. There is a discrepancy between centers and countries in terms of incidence data of infection-disease in this population of patients. Design: an analytical observational study was conducted, taking a retrospective cohort of patients older than 18 years old, kidney transplant recipients of living or cadaveric donors between 2004 and 2015, with at least 6 months of follow-up. Material and methods: non-probability convenience sampling was done; data from the clinical records of the kidney transplant patients were taken, calculating the incidence density of CMV infection-disease and the clinical and demographic characteristics of the patients who presented these pathologies were described. Results: 252 patients were analyzed; 92.4% of recipients with intermediate risk for CMV and 7.5% with high risk were found. None of them had low risk. 19 cases were identified, 13 with infection (5.1%) and 6 with disease (2.3%). Gastrointestinal involvement was the most frequent. The average time from the time of transplant to the onset of the infection-disease was 417 (± 479) and 650 days (± 481), respectively. The infection rate was 10.08 cases per 1000 patients / year and the disease rate was 5.88 per 1000 patients/year. Conclusions: the incidence density of CMV infection-disease in renal transplant patients was 10.08 cases and 5.88 cases per 1000 patients / year, respectively. These rates are lower than those reported in the literature. Given the low frequency of events, it was not possible to establish association factors. (Acta Med Colomb 2018; 43: 20-23).

Clinical characteristics and treatment courses for cytomegalovirus-associated thrombocytopenia in immunocompetent children after neonatal period

BACKGROUND: Cytomegalovirus (CMV) causes severe diseases in premature infants and immunocompromised hosts, and antiviral therapy is often required for disease control. However, the clinical manifestations and treatment courses for CMV-associated thrombocytopenia in immunocompetent children are unclear. METHODS: Medical records of the children who suffered from thrombocytopenia, and showed positive CMV polymerase chain reaction and CMV-like symptoms were retrospectively analyzed at three university hospitals in Daegu from January 2000 to March 2017. Patients suffering from leukemia, immunodeficiency, and other infections were excluded. RESULTS: Among 1,065 children with thrombocytopenia, 29 (2.7%) displayed CMV-associated thrombocytopenia. The median age at diagnosis was 15 months and the median platelet count was 26,000/µL. They were classified into the CMV-induced thrombocytopenia (23/29) and CMV-related secondary immune thrombocytopenia (ITP, 6/29) groups. Fourteen subjects had hepatic dysfunction, four had Evans syndrome, two had pneumonitis, and one had gastritis. IVIG was used for 21 patients, and six patients among them showed recurrence, for whom IVIG or antiviral therapy was used. All, except one, recurrent or chronic cases belonged to the CMV-induced thrombocytopenia group. Antiviral therapy was used more frequently for the CMV-induced thrombocytopenia group (8/23, 34.8%) than for the CMV-related secondary ITP group (0/6); however, the results were not statistically significant (P=0.148). CONCLUSION: CMV is a rare but unique etiology of thrombocytopenia, and observed even in healthy children after the neonatal period. About one-third patients need antiviral therapy for disease control. Further, CMV-induced thrombocytopenia is more complex than CMV-related secondary ITP.

Como promover a desospitalização devido ao transplante de órgãos sólidos? Panorama atual no Brasil e profilaxia da infecção pelo citomegalovírus com valganciclovir / How to promote deinstitutionalization due to solid organ transplantation? Current landscape in Brazil and cytomegalovirus infection prophylaxis with valganciclovir

Objetivo: O estudo teve o objetivo de avaliar o panorama dos transplantes de órgãos sólidos (TOS) no Brasil e compreender as diferenças entre a profilaxia oral com valganciclovir e o tratamento preemptivo intravenoso com ganciclovir em pacientes de alto risco para desenvolvimento da doença pelo citomegalovírus (CMV) (D+/R-), e seu potencial impacto na desospitalização. Métodos: Por meio do Sistema de Informações Hospitalares do SUS (SIH/SUS), uma análise retrospectiva foi realizada para avaliar os principais centros de transplantes brasileiros e obter os TOS realizados em 2014. Os cálculos foram baseados na permanência hospitalar média por TOS, tempo de internação para cada abordagem farmacológica e número de pacientes D+/R-. A permanência hospitalar para tratamento preemptivo e profilaxia foram baseadas em diretrizes de uma instituição brasileira de referência. A taxa de infecção de CMV foi obtida de uma revisão da literatura. O desenvolvimento da doença pelo CMV após tratamento preemptivo ou profilaxia não foi considerado. Resultados:Em 2014, os centros de transplante avaliados realizaram um total de 6.912 TOS. O valganciclovir profilático proporcionou anualmente 21 dias a menos de hospitalização por paciente. A partir da relação do valor incremental (21 dias) entre a utilização de ganciclovir e valganciclovir e a média geral de permanência hospitalar no SUS para qualquer procedimento (5,6 dias), sugere-se que 3,75 novas internações por qualquer causa poderiam ocorrer por cada paciente em profilaxia. Conclusão: O valganciclovir profilático para pacientes D+/R- submetidos a TOS é potencialmente capaz de promover a desospitalização, permitindo maior comodidade ao paciente transplantado e utilização racional de recursos pela instituição

Objective: The study aimed to assess the landscape of solid organ transplants (SOT) in Brazil and understand differences between oral prophylaxis with valganciclovir and intravenous preemptive treatment with ganciclovir in patients at high risk for developing disease by cytomegalovirus (D+/R-), and their potential impact on deinstitutionalization. Methods: Based on the Brazilian Hospital Information System (SIH/SUS) database, a retrospective analysis was performed to assess the main Brazilian transplantation centers and obtain the SOT performed in 2014. The analysis was based on time of hospitalization according to SOT, LOS (Length of Stay) of each pharmacological approach and number of D+/R- patients. LOS for preemptive treatment and prophylaxis was taken from a Brazilian reference institution guideline. The CMV infection rate was obtained from a literature review. Development of CMV disease after both prophylaxis and preemptive treatment was not considered in the analysis. Results: In 2014, the transplant centers performed a total of 6,912 SOT. The valganciclovir prophylaxis resulted in reduction of 21 days of LOS per patient. Based on the ratio of incremental daily between the use of ganciclovir and valganciclovir (21 days) and overall mean hospital stay in the SUS to any procedure (5.6 days), it may be suggested that 3.75 new admissions for any cause could occur in addition, for each patient treated with prophylactic valganciclovir. Conclusion: Valganciclovir prophylaxis for patients D+ /R- undergoing TOS ispotentially able to promote deinstitutionalization, allowing greater convenience to patients transplanted and promoting the rational use of resources by the institution.

Valganciclovir en la púrpura trombopénica asociada a infección por Citomegalovirus / Valganciclovir in thrombocitopenic purpura associated with Cytomegalovirus infection

Se presenta el caso de un lactante de 24 meses de edad diagnosticado de púrpura trombopénica corticodependiente, en el que se confirmó infección activa por citomegalovirus mediante serología y aislamiento del virus en orina. Ante la mala evolución de la enfermedad y sospechando relación causal con el virus, se inició valganciclovir vía oral hasta un total de 5 meses, obteniendo excelente respuesta con resolución simultánea de ambos procesos y sin efectos secundarios reseñables.

We report a case of a 24 months old child, diagnosed with corticodependent thrombocytopenia in which active cytomegalovirus infection was confirmed sustituir resaltado por: by means of serology and viris isolation in urine.. Due to the patient's worsening, we suspected a link between both processes and started oral valganciclovir, given for a total of 5 months. We documented excellent simultaneous response in both pathologies, and without relevant side effects.

Infección congénita por citomegalovirus. Primer reporte nacional de tratamiento con valganciclovir vía oral en recién nacidos / Congenital cytomegalovirus infection. First national report treatment with oral valganciclovir in neonates

La infección congénita por citomegalovirus (CMV) es la principal etiología de hipoacusia neurosensorial de causa no genética. El uso de valganciclovir, un profármaco del ganciclovir con buena biodisponibilidad oral, es utilizado a nivel internacional como parte del tratamiento farmacológico. La indicación de tratamiento incluye a los recién nacidos sintomáticos con compromiso neurológico o con enfermedad órgano focal severa, dentro de los primeros 30 días de vida. El mayor beneficio del tratamiento en neonatos es la reducción del deterioro de la audición evitando la peoría de los umbrales auditivos, así como la mejoría en el neurodesarrollo. Un tratamiento inicial con ganciclovir, seguido de valganciclovir vía oral, ha demostrado mejor desempeño del desarrollo auditivo que el uso de terapia a corto plazo. Se reportan dos casos de citomegalovirus congénito, de diferente presentación clínica, en el período setiembre-octubre 2013. Se reporta mejoría sintomática tras el tratamiento con ganciclovir-valganciclovir en ambos casos. En el seguimiento con carga viral en orina, se observó una disminución mantenida de la misma durante el tratamiento. El principal efecto adverso fue la apariciónde anemia...

Profilaxis de citomegalovirus en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos / Prophylaxis against cytomegalovirus infection in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation

CMV is one of the main infectious problems for SOT and HSCT. The severity of the complications are mainly associated with the type of transplant and immune status against the virus of the transplant donor and the transplant recipient. It is important to prevent exposure, using safe blood transfusion CMV seronegative donors (B1) and/or use of blood leucocytes-depleted by filtration (Al). In addition to preventing exposure, there are two widely used prevention strategies: universal prophylaxis with antiviral therapy or "pre-emptive" strategy based on the use of antivirals only to the early detection of CMV replication in blood. The first option is most used in the SOT management, especially for those identified as the high risk group of CMV disease: R (+), with D (+) or D (-) (Al), where the recommended drug is ganciclovir or valganciclovir . The second approach is preferable for HSCT, which recommends weekly monitoring for CMV viral load from day 10 to 100 post transplant (A3). This strategy requires having a viral laboratory support (A2). The selected antiviral in the case of pre emptive therapy is intravenous ganciclovir (A1).

La infección y enfermedad por CMV son problemas comunes en pacientes con TOS y TPH. La gravedad de las complicaciones asociadas a este virus dependen fundamentalmente del tipo de trasplante y de la experiencia inmunológica previa contra el virus del donante y el receptor. Es importante prevenir la exposición, utilizando transfusiones de sangre segura para CMV con donantes seronegativos (B1) y/o uso de sangre leuco-depletada por iltración (A1). Además de prevenir la exposición, existen dos estrategias de prevención ampliamente utilizadas: La proilaxis universal con antivirales y la terapia adelantada o estrategia "pre-emptive" basada en el uso de antivirales sólo ante la detección precoz de replicación del CMV en sangre. La primera opción es de mayor uso en TOS, especialmente para aquellos binomios identficados como de mayor riesgo de enfermedad por CMV: R (+), con D (+) o D (-) (A1), siendo el medicamento recomendado ganciclovir o valganciclovir. La segunda opción es de elección en TPH, en cuyo caso se recomienda monitoreo semanal con carga viral para CMV desde el día 10 al 100 post trasplante (A3), lo que implica contar con un laboratorio de apoyo en diagnóstico virológico (A2). El antiviral de elección en este caso es ganciclovir iv (A1).

Hidrops fetal por infección congénita por citomegalovirus: tratamiento posneonatal prolongado con valganciclovir / Hydrops fetalis due to congenital cytomegalovirus infection: prolonged postneonatal treatment with valganciclovir

El citomegalovirus (CMV) es la infección viral congénita más frecuente con una prevalencia de 0,5% al nacimiento. La primoinfección aparece entre el 1-4% de las gestantes seronegativas. El 40% de estos fetos se infectan y un 10% presentan síntomas al nacimiento. Presentamos un caso de infección congénita por CMV con hidrops fetal, con afectación neonatal del sistema nervioso central. Se trató con ganciclovir intravenoso y posteriormente con valganciclovir oral hasta los 6 meses, con buenos resultados al año de vida. Se realiza una revisión bibliográfica del diagnóstico y pronóstico de los recién nacidos con infección congénita por CMV y las expectativas y experiencia actual del tratamiento con ganciclovir y valganciclovir.

Cytomegalovirus (CMV) is the leading cause of congenital infection affecting 0.5% of all live births. Primary CMV infection occurs in 1-4% of seronegative woman during pregnancy and may be transmitted to the fetus in 40%. Up to 10% of intrauterine CMV infections result in symptomatic congenital disease at birth. We present a case of congenital CMV infection in the third trimester of gestation with central nervous disease involvement, who was treated with intravenosus ganciclovir followed by oral valganciclovir for six months with successful results in the first year of life. We review the literature on the diagnosis and prognosis of newborns with congenital CMV infection and the expectations and current experience of treatment with ganciclovir and valganciclovir.

Acute retinal necrosis / Necrosis retiniana aguda: informe de un caso

Purpose: Clinical features in a case of acute retinal necrosis are described as well as its diagnostic approach and response to early treatment. Methods: This is a descriptive and retrospective study case report of a 26 year old male patient who arrived to the emergency room with a three day history of sudden visual loss in the right eye (RE). At initial evaluation a visual acuity of hand movements in the RE, 20/15 in the left eye (LE) and a right relative afferent pupillary defect were found. Fundoscopy revealed profuse soft exudates and hemorrhages involving posterior pole, inferior hemiretina and superotemporal periphery. Infectious workup and fluoresceinic angiography were made and positive serologies for herpes virus types 1 and 2, without HIV, were found. A diagnosis of acute retinal necrosis was made and treatment with intravenous valgancyclovir for two weeks and intra-vitreous triamcinolone for severe vasculitis, was given. Then a 3 months treatment with oral antiviral agents was prescribed. Results: Patient’s evolution showed improvement with treatment and at two and a half months of follow up, visual acuity was 20/50 in the right eye, normal slit lamp examination, tonometry of 12 mm Hg and fundoscopy improved when compared to initial pictures. Conclusions: A high index of suspicion is needed for diagnosing ARN taking into account clinical findings. Prompt intravenous and intra-vitreous treatments are needed to achieve good clinical and functional outcomes and to avoid central nervous system complications.

Objetivo: Describir un caso de necrosis retiniana aguda, las características clínicas, el enfoque diagnóstico y la respuesta al tratamiento. Método: Se realiza un estudio descriptivo, retrospectivo tipo informe de caso en un paciente de sexo masculino, 26 años de edad, que consulta al Servicio de Urgencias con historia de pérdida visual del ojo derecho (OD) de 3 días de evolución. Al examen de ingreso se encontró una agudeza visual del OD de movimiento de manos y defecto pupilar aferente, y 20/15 en el ojo izquierdo (OI). En el estudio del fondo de ojo derecho se encontraron exudados blandos abundantes y hemorragias que comprometen todo el polo posterior, la hemirretina inferior y la periferia supero temporal. En los exámenes para clínicos se evidenciaron serologías positivas para herpes tipo 1 y 2 en ausencia de VIH y a la angiografía con fluoresceína cambios vasculares con zonas de no perfusión. Se llega al diagnóstico de necrosis retiniana aguda y se decide manejar con valganciclovir endovenoso durante dos semanas, triamcinolona intravítrea y fotocoagulación retiniana con laser para el manejo de la vasculitis severa y zonas isquémicas; luego se continuó con antivirales orales por 3 meses. Resultados: Después de 2 meses y medio de seguimiento, hay una agudeza visual de 20/50 del OD, un examen biomicroscópico normal, presión intraocular de 12 mm Hg y el fondo de ojo muestra mejoría del cuadro al compararlo con las fotos iniciales.Conclusiones: Al diagnóstico de NRA se llega con la sospecha clínica, de acuerdo con los signos del examen; se requiere un manejo endovenoso e intravítreo oportuno, para lograr buenos resultados tanto clínicos como funcionales y evitar complicaciones a nivel del sistema nervioso central.

A Case of Valganciclovir Treatment for Cytomegalovirus Retinitis

PURPOSE: To report a case of a patient with cytomegalovirus (CMV) retinitis who was treated with oral valganciclovir. CASE SUMMARY: A 34-year-old man who had undergone anti-cancer chemotherapy for Non-Hodgkin lymphoma was referred to the ophthalmologic oncology clinic because of decreased vision in both eyes. Fundus examination showed white, opaque, and granular retinal lesions in both eyes, and a serologic test showed a positive response to CMV antibody IgG and a negative response to CMV antibody IgM. The patient received induction therapy with intravenous ganciclovir and maintenance therapy with oral valganciclovir 900 mg once daily. CMV retinitis reactivated 4 weeks after maintenance therapy was discontinued. At that point, the patient received induction therapy with oral valganciclovir 900 mg twice daily for 3 weeks and maintenance therapy with 900 mg once daily for 5 weeks. The retinal lesion disappeared and did not recur after oral administration of valganciclovir. The patient discontinued valganciclovir after 5 weeks of maintenance therapy, and CMV retinitis did not reactivate during 6 months of follow-up. CONCLUSIONS: Oral valganciclovir was clinically effective in the treatment of CMV retinitis in a patient who was treated with anti-cancer chemotherapy for non-Hodgkin lymphoma.