Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-18 (of 18 Records) |
Query Trace: Keating MK [original query] |
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Fatal systemic fungal infection in eastern bongo antelope (Tragelaphus eurycerus isaaci): Six cases
Garner MM , Fredholm DVE , Citino SB , Keating MK , Ritter JM , Lockart S , Lysen C , Bradway DS , Koons AR , Newton J . J Zoo Wildl Med 2023 54 (1) 102-110 Over a span of 6 yr, six adult eastern bongo antelope (Tragelaphus eurycerus isaaci) from a single institution died due to systemic mycotic infections. All animals were of the same genetic lineage and in good body condition at the time of death. Gross findings in all cases included multifocal white-to-tan nodules up to 10 cm in diameter that were most numerous in the heart, lung, and kidney. Histologic examination identified these nodules as foci of granulomatous inflammation containing branching, septate, broad, undulating fungal elements. Identification of the fungal species was pursued using PCR with sequencing, immunohistochemistry, and culture. Multiple fungal species were identified using the various modalities, and commonality of species identification was limited to Cladosporium sp. in four of the cases. The clinical and postmortem findings in these cases were identical and were considered to be the same infectious disease. The Cladosporium sp. was considered a candidate as an emerging fatal infectious agent in this population of bongo antelopes. In all of these cases, death was attributed to conduction abnormalities associated with the cardiac lesions or euthanasia. |
Postmortem Study of Cause of Death Among Children Hospitalized With Respiratory Illness in Kenya
Njuguna HN , Zaki SR , Roberts DJ , Rogena EA , Walong E , Fligner CL , Keating MK , Gachii AK , Maleche-Obimbo E , Irimu G , Mathaiya J , Orata N , Lopokoiyit R , Michuki J , Emukule GO , Onyango CO , Gikunju S , Owuor C , Muturi PK , Bunei M , Gloria Carvalho M , Fields B , Mott JA , Widdowson MA , Chaves SS . Pediatr Infect Dis J 2021 40 (8) 715-722 BACKGROUND: In resource-limited settings, acute respiratory infections continue to be the leading cause of death in young children. We conducted postmortem investigations in children <5 years hospitalized with a clinical diagnosis of respiratory disease at Kenya's largest referral hospital. METHODS: We collected respiratory and other tissues postmortem to examine pathologic processes using histology, molecular and immunohistochemistry assays. Nasopharyngeal, trachea, bronchi and lung specimens were tested using 21-target respiratory pathogen real-time reverse transcription polymerase chain reaction assays deployed on Taqman Array Cards. Expert panels reviewed all findings to determine causes of death and associated pathogens. RESULTS: From 2014 to 2015, we investigated 64 pediatric deaths (median age 7 months). Pneumonia was determined as cause of death in 70% (42/52) of cases where death was associated with an infectious disease process. The main etiologies of pneumonia deaths were respiratory syncytial virus (RSV) (n = 7, 19%), Pneumocystis jirovecii (n = 7, 19%), influenza A (n = 5, 14%) and Streptococcus pneumoniae (n = 5, 14%)-10% of cases had multi-pathogen involvement. Among the other 10 deaths associated with a nonpneumonia infectious process, 4 did not have an etiology assigned, the others were associated with miliary tuberculosis (2), cerebral thrombosis due to HIV (1), Enterobacteriaceae (1), rotavirus (1), and 1 case of respiratory infection with severe hypokalemia associated with RSV. CONCLUSIONS: In spite of well-established vaccination programs in Kenya, some deaths were still vaccine preventable. Accelerated development of RSV monoclonal antibodies and vaccines, introduction of seasonal influenza vaccination, and maintenance or improved uptake of existing vaccines can contribute to further reductions in childhood mortality. |
Clinical characteristics, histopathology, and tissue immunolocalization of chikungunya virus antigen in fatal cases
Sharp TM , Keating MK , Shieh WJ , Bhatnagar J , Bollweg BC , Levine R , Blau DM , Torres JV , Rivera A , Perez-Padilla J , Munoz-Jordan J , Sanabria D , Fischer M , Garcia BR , Tomashek KM , Zaki SR . Clin Infect Dis 2020 73 (2) e345-e354 BACKGROUND: Death in patients with chikungunya is rare, and has been associated with encephalitis, hemorrhage, and septic shock. We describe clinical, histologic and immunohistochemical findings in individuals who died following chikungunya virus (CHIKV) infection. METHODS: We identified individuals who died in Puerto Rico during 2014 following an acute illness, and had CHIKV RNA detected by RT-PCR in a pre- or post-mortem blood or tissue specimen. We performed histopathology and immunohistochemistry (IHC) for CHIKV antigen on tissue specimens and collected medical data via record review and family interviews. RESULTS: Thirty CHIKV-infected fatal cases were identified (0.8 per 100,000 population). Median age was 61 years (range: 6 days-86 years), and 19 (63%) were male. Death occurred a median of four days (range: 1-29) after illness onset. Nearly all (93%) had at least one co-morbidity, most frequently hypertension, diabetes, or obesity. Nine had severe co-morbidities (e.g., chronic heart or kidney disease, sickle cell anemia) or co-infection (e.g., leptospirosis). Among 24 fatal cases with tissue specimens, 11 (46%) were positive by IHC. CHIKV antigen was most frequently detected in mesenchymal tissues and mononuclear cells including tissue macrophages, blood mononuclear cells, splenic follicular dendritic cells, and Kupffer cells. Common histopathologic findings were intra-alveolar hemorrhage and edema in the lung, chronic or acute tenosynovitis, and increased immunoblasts in the spleen. CHIKV infection likely caused fatal septic shock in two patients. CONCLUSIONS: Evaluation of tissue specimens provided insights into the pathogenesis of CHIKV, which may rarely result in septic shock and other severe manifestations. |
Comparison of minimally invasive tissue sampling with conventional autopsy to detect pulmonary pathology among respiratory deaths in a resource-limited setting
Roberts DJ , Njuguna HN , Fields B , Fligner CL , Zaki SR , Keating MK , Rogena E , Walong E , Gachii AK , Maleche-Obimbo E , Irimu G , Mathaiya J , Orata N , Lopokoiyit R , Michuki J , Emukule GO , Onyango CO , Gikunju S , Owuor C , Muturi PK , Bunei M , Widdowson MA , Mott JA , Chaves SS . Am J Clin Pathol 2019 152 (1) 36-49 OBJECTIVES: We compared minimally invasive tissue sampling (MITS) with conventional autopsy (CA) in detection of respiratory pathology/pathogens among Kenyan children younger than 5 years who were hospitalized with respiratory disease and died during hospitalization. METHODS: Pulmonary MITS guided by anatomic landmarks was followed by CA. Lung tissues were triaged for histology and molecular testing using TaqMan Array Cards (TACs). MITS and CA results were compared for adequacy and concordance. RESULTS: Adequate pulmonary tissue was obtained by MITS from 54 (84%) of 64 respiratory deaths. Comparing MITS to CA, full histologic diagnostic concordance was present in 23 (36%) cases and partial concordance in 19 (30%), an overall 66% concordance rate. Pathogen detection using TACs had full concordance in 27 (42%) and partial concordance in 24 (38%) cases investigated, an overall 80% concordance rate. CONCLUSIONS: MITS is a viable alternative to CA in respiratory deaths in resource-limited settings, especially if combined with ancillary tests to optimize diagnostic accuracy. |
Determining the cause of death among children hospitalized with respiratory illness in Kenya: Protocol for Pediatric Respiratory Etiology Surveillance Study (PRESS)
Njuguna HN , Zaki SR , Roberts DJ , Fligner CL , Keating MK , Rogena E , Walong E , Gachii AK , Maleche-Obimbo E , Irimu G , Mathaiya J , Orata N , Lopokoiyit R , Maina J , Emukule GO , Onyango CO , Gikunju S , Owuor C , Kinuthia P , Bunei M , Fields B , Widdowson MA , Mott JA , Chaves SS . JMIR Res Protoc 2019 8 (1) e10854 BACKGROUND: In sub-Saharan Africa, where the burden of respiratory disease-related deaths is the highest, information on the cause of death remains inadequate because of poor access to health care and limited availability of diagnostic tools. Postmortem examination can aid in the ascertainment of causes of death. This manuscript describes the study protocol for the Pediatric Respiratory Etiology Surveillance Study (PRESS). OBJECTIVE: This study protocol aims to identify causes and etiologies associated with respiratory disease-related deaths among children (age 1-59 months) with respiratory illness admitted to the Kenyatta National Hospital (KNH), the largest public hospital in Kenya, through postmortem examination coupled with innovative approaches to laboratory investigation. METHODS: We prospectively followed children hospitalized with respiratory illness until the end of clinical care or death. In case of death, parents or guardians were offered grief counseling, and postmortem examination was offered. Lung tissue specimens were collected using minimally invasive tissue sampling and conventional autopsy where other tissues were collected. Tissues were tested using histopathology, immunohistochemistry, and multipathogen molecular-based assays to identify pathogens. For each case, clinical and laboratory data were reviewed by a team of pathologists, clinicians, laboratorians, and epidemiologists to assign a cause of and etiology associated with death. RESULTS: We have enrolled pediatric cases of respiratory illness hospitalized at the KNH at the time of this submission; of those, 14.8% (140/945) died while in the hospital. Both analysis and interpretation of laboratory results and writing up of findings are expected in 2019-2020. CONCLUSIONS: Postmortem studies can help identify major pathogens contributing to respiratory-associated deaths in children. This information is needed to develop evidence-based prevention and treatment policies that target important causes of pediatric respiratory mortality and assist with the prioritization of local resources. Furthermore, PRESS can provide insights into the interpretation of results using multipathogen testing platforms in resource-limited settings. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/10854. |
Outbreak of Tattoo-Associated Nontuberculous Mycobacterial Skin Infections.
Griffin I , Schmitz A , Oliver C , Pritchard S , Zhang G , Rico E , Davenport E , Llau A , Moore E , Fernandez D , Mejia-Echeverry A , Suarez J , Noya-Chaveco P , Elmir S , Jean R , Pettengill JB , Hollinger KA , Chou K , Williams-Hill D , Zaki S , Muehlenbachs A , Keating MK , Bhatnagar J , Rowlinson MC , Chiribau C , Rivera L . Clin Infect Dis 2018 69 (6) 949-955 BACKGROUND: On April 29, 2015, the Florida Department of Health in Miami-Dade County (DOH-Miami-Dade) was notified by a local dermatologist of three patients with suspect nontuberculous mycobacterial (NTM) infection after receiving tattoos at a local tattoo studio. METHODS: DOH-Miami-Dade conducted interviews and offered testing, described below, to tattoo studio clients reporting rashes. Culture of clinical isolates and identification were performed at the Florida Bureau of Public Health Laboratories (BPHL). Characterization of NTM was performed by the Centers for Disease Control and Prevention (CDC) and the United States Food and Drug Administration (FDA), respectively. Whole-genome sequencing (WGS) and single-nucleotide polymorphism (SNP) analyses were used to construct a phylogeny among 21 Mycobacterium isolates at FDA. RESULTS: Thirty-eight of 226 interviewed clients were identified as outbreak-associated cases. Multivariate logistic regression revealed individuals who reported grey tattoo ink in their tattoos were 8.2 times as likely to report a rash [95% CI: 3.07-22.13]. Multiple NTM species were identified in clinical and environmental specimens. Phylogenetic results from environmental samples and skin biopsies indicated that two M. fortuitum isolates (greywash ink and a skin biopsy) and 11 M. abscessus isolates (five from the implicated bottle of greywash tattoo ink, two from tap water, and four from skin biopsies) were indistinguishable. In addition, M. chelonae was isolated from five unopened bottles of greywash ink provided by two other tattoo studios in Miami-Dade County. CONCLUSIONS: WGS and SNP analyses identified the tap water and the bottle of greywash tattoo ink as the sources of the NTM infections. |
Pathology in practice
Edwards EE , Birch SM , Hoppes SM , Keating MK , Stoica G . J Am Vet Med Assoc 2018 253 (4) 423-426 A 7-month-old 370-g (0.81-lb) sexually intact female common marmoset (Callithrix jacchus) that was kept as a pet was taken to a referring veterinarian after a sudden onset of lethargy and inappetence. A diagnosis of pulmonary consolidation and colic was made, and the owners were instructed to administer supportive treatments to the marmoset at home. The next day, the animal's condition slowly worsened with development of neurologic signs including disorientation, trembling, and ataxia. The marmoset was brought to the Zoological Medicine Service at Texas A&M University on an emergency basis but died during hospitalization the next day, approximately 72 hours following the initial onset of clinical signs. The marmoset was submitted for necropsy. The marmoset lived with an 11-month-old male marmoset and had access to an outdoor porch allowing for indirect contact with a feral cat. Human contact with the marmoset was limited to the 2 owners and the referring veterinarian and veterinary staff. According to the owner, not long after the death of the female marmoset, the male marmoset from the household developed similar clinical signs and died shortly thereafter. A necropsy was not performed on that animal. |
Prototheca zopfii colitis in inherited CARD9 deficiency
Sari S , Dalgic B , Muehlenbachs A , DeLeon-Carnes M , Goldsmith CS , Ekinci O , Jain D , Keating MK , Vilarinho S . J Infect Dis 2018 218 (3) 485-489 Human protothecosis is a rare microalgae infection, and its dissemination typically occurs in immunocompromised individuals, but no specific immune defect has been reported. Here, we describe an 8-year-old daughter of a consanguineous union with abdominal pain and bloody diarrhea for 3 months who was found to have pancolitis with numerous microalgae identified as Prototheca zopfii. In the absence of a known immunodeficiency, exome sequencing was performed, which uncovered a novel recessive frameshift mutation in CARD9 (p.V261fs). This report highlights that CARD9 deficiency should be investigated in patients with unexplained systemic/visceral protothecosis and suggests a new mechanistic insight into anti-Prototheca immunity. |
A Case of Prototheca zopfii Genotype 1 Infection in a Dog (Canis lupus familiaris).
Silveira CS , Cesar D , Keating MK , DeLeon-Carnes M , Armien AG , Luhers M , Riet-Correa F , Giannitti F . Mycopathologia 2018 183 (5) 853-858 Protothecosis is a rare disease caused by environmental algae of the genus Prototheca. These are saprophytic, non-photosynthetic, aerobic, colorless algae that belong to the Chlorellaceae family. Seven different species have been described. Prototheca zopfii genotype 2 and P. wickerhamii are most commonly involved in pathogenic infections in humans and animals. The objective of this work is to describe, for the first time, a case of protothecosis caused by P. zopfii genotype 1 in a dog. The dog, a 4-year-old mix bred male, was presented to a veterinary clinic in Montevideo, Uruguay, with multiple skin nodules, one of which was excised by surgical biopsy. The sample was examined histologically and processed by PCR, DNA sequencing, and restriction fragments length polymorphisms for the detection and genotyping of P. zopfii. In addition, transmission electron microscopy and scanning electron microscopy were performed. Histology showed severe ulcerative granulomatous dermatitis and panniculitis with myriads of pleomorphic algae. Algal cells were 4-17 microm in size, with an amphophilic, 2-4-microm-thick wall frequently surrounded by a clear halo, contained flocculant material and a deeply basophilic nucleus, and internal septae with daughter cells (endospores) consistent with endosporulation. Ultrastructurally, algal cells/endospores at different stages of development were found within parasitophorous vacuoles in macrophages. Prototheca zopfii genotype 1 was identified by molecular testing, confirming the etiologic diagnosis of protothecosis. |
Candida pneumonia with severe clinical course, recovery with antifungal therapy and unusual pathologic findings: A case report
Dermawan JKT , Ghosh S , Keating MK , Gopalakrishna KV , Mukhopadhyay S . Medicine (Baltimore) 2018 97 (2) e9650 BACKGROUND: Candida is frequently isolated from the respiratory tract and usually reflects airway colonization. True Candida pneumonia is rare. Our aim is to document a case of Candida pneumonia confirmed by cultures, molecular techniques, and surgical lung biopsy, and to highlight a previously unreported pathologic manifestation of this infection. CASE SUMMARY: A 59-year-old man with a history of chronic obstructive pulmonary disease (COPD) presented with dry cough, low-grade fever, and progressive dyspnea. He was eventually diagnosed with sarcoidosis based on bilateral lung infiltrates and granulomas in a transbronchial biopsy. His condition worsened after immunosuppression, prompting surgical lung biopsy, which revealed suppurative granulomas containing Candida albicans, confirmed by cultures and polymerase chain reaction. Despite multiple episodes of respiratory failure and a prolonged course in intensive care, he recovered fully after antifungal therapy and is currently alive with COPD-related dyspnea 3 years after his initial presentation. CONCLUSION: Candida can rarely cause clinically significant pneumonia in adults, and should be considered in the differential diagnosis of suppurative granulomas in the lung. |
Evaluation of placental and fetal tissue specimens for Zika virus infection - 50 states and District of Columbia, January-December, 2016
Reagan-Steiner S , Simeone R , Simon E , Bhatnagar J , Oduyebo T , Free R , Denison AM , Rabeneck DB , Ellington S , Petersen E , Gary J , Hale G , Keating MK , Martines RB , Muehlenbachs A , Ritter J , Lee E , Davidson A , Conners E , Scotland S , Sandhu K , Bingham A , Kassens E , Smith L , St George K , Ahmad N , Tanner M , Beavers S , Miers B , VanMaldeghem K , Khan S , Rabe I , Gould C , Meaney-Delman D , Honein MA , Shieh WJ , Jamieson DJ , Fischer M , Zaki SR . MMWR Morb Mortal Wkly Rep 2017 66 (24) 636-643 Zika virus infection during pregnancy can cause congenital microcephaly and brain abnormalities (1), and detection of Zika virus RNA in clinical and tissue specimens can provide definitive laboratory evidence of recent Zika virus infection. Whereas duration of viremia is typically short, prolonged detection of Zika virus RNA in placental, fetal, and neonatal brain tissue has been reported and can provide key diagnostic information by confirming recent Zika virus infection (2). In accordance with recent guidance (3,4), CDC provides Zika virus testing of placental and fetal tissues in clinical situations where this information could add diagnostic value. This report describes the evaluation of formalin-fixed paraffin-embedded (FFPE) tissue specimens tested for Zika virus infection in 2016 and the contribution of this testing to the public health response. Among 546 live births with possible maternal Zika virus exposure, for which placental tissues were submitted by the 50 states and District of Columbia (DC), 60 (11%) were positive by Zika virus reverse transcription-polymerase chain reaction (RT-PCR). Among 81 pregnancy losses for which placental and/or fetal tissues were submitted, 18 (22%) were positive by Zika virus RT-PCR. Zika virus RT-PCR was positive on placental tissues from 38/363 (10%) live births with maternal serologic evidence of recent unspecified flavivirus infection and from 9/86 (10%) with negative maternal Zika virus immunoglobulin M (IgM) where possible maternal exposure occurred >12 weeks before serum collection. These results demonstrate that Zika virus RT-PCR testing of tissue specimens can provide a confirmed diagnosis of recent maternal Zika virus infection. |
Crimean-Congo hemorrhagic fever in humanized mice reveals glial cells as primary targets of neurological infection
Spengler JR , Keating MK , McElroy AK , Zivcec M , Coleman-McCray JD , Harmon JR , Bollweg BC , Goldsmith CS , Bergeron E , Keck JG , Zaki SR , Nichol ST , Spiropoulou CF . J Infect Dis 2017 216 (11) 1386-1397 Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral hemorrhagic disease seen exclusively in humans. Central nervous system (CNS) infection and neurological involvement have also been reported in CCHF. Here we inoculated NSGTM-SGM3 mice engrafted with human hematopoietic CD34+ stem cells with low passage CCHF virus strains isolated from human patients. Humanized mice develop lethal disease characterized by histopathological change in the liver and brain. To date, targets of neuroinfection and neuropathology have not been investigated in CCHF. CNS disease in humanized mice was characterized by gliosis, meningitis and meningoencephalitis, and glial cells were identified as principal targets of infection. Humanized mice represent a novel lethal model for studies of CCHF countermeasures, and CCHF-associated CNS disease. Our data suggests a role for astrocyte dysfunction in neurologic disease, and distinguish key regions of infection in the CNS for future investigations of CCHF. |
Zika Virus RNA Replication and Persistence in Brain and Placental Tissue.
Bhatnagar J , Rabeneck DB , Martines RB , Reagan-Steiner S , Ermias Y , Estetter LB , Suzuki T , Ritter J , Keating MK , Hale G , Gary J , Muehlenbachs A , Lambert A , Lanciotti R , Oduyebo T , Meaney-Delman D , Bolanos F , Saad EA , Shieh WJ , Zaki SR . Emerg Infect Dis 2017 23 (3) 405-414 Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections. |
Assessment of domestic goats as models for experimental and natural infection with the North American isolate of Rickettsia slovaca
Lukovsky-Akhsanov N , Keating MK , Spivey P , Lathrop GW Jr , Powell N , Levin ML . PLoS One 2016 11 (10) e0165007 Rickettsia slovaca is a tick-borne human pathogen that is associated with scalp eschars and neck lymphadenopathy known as tick-borne lymphadenopathy (TIBOLA) or Dermacentor-borne necrosis erythema and lymphadenopathy (DEBONEL). Originally, R. slovaca was described in Eastern Europe, but since recognition of its pathogenicity, human cases have been reported throughout Europe. European vertebrate reservoirs of R. slovaca remain unknown, but feral swine and domestic goats have been found infected or seropositive for this pathogen. Recently, a rickettsial pathogen identical to R. slovaca was identified in, and isolated from, the American dog tick, Dermacentor variabilis. In previous experimental studies, this organism was found infectious to guinea pigs and transovarially transmissible in ticks. In this study, domestic goats (Capra hircus) were experimentally inoculated with the North American isolate of this R. slovaca-like agent to assess their reservoir competence-the ability to acquire the pathogens and maintain transmission between infected and uninfected ticks. Goats were susceptible to infection as demonstrated by detection of the pathogen in skin biopsies and multiple internal tissues, but the only clinical sign of illness was transient fever noted in three out of four goats, and reactive lymphoid hyperplasia. On average, less than 5% of uninfected ticks acquired the pathogen while feeding upon infected goats. Although domestic goats are susceptible to the newly described North American isolate of R. slovaca, they are likely to play a minor role in the natural transmission cycle of this pathogen. Our results suggest that goats do not propagate the North American isolate of R. slovaca in peridomestic environments and clinical diagnosis of infection could be difficult due to the brevity and mildness of clinical signs. Further research is needed to elucidate the natural transmission cycle of R. slovaca both in Europe and North America, as well as to identify a more suitable laboratory model. |
Pathology of congenital Zika syndrome in Brazil: a case series
Martines RB , Bhatnagar J , de Oliveira Ramos AM , Davi HP , Iglezias SD , Kanamura CT , Keating MK , Hale G , Silva-Flannery L , Muehlenbachs A , Ritter J , Gary J , Rollin D , Goldsmith CS , Reagan-Steiner S , Ermias Y , Suzuki T , Luz KG , de Oliveira WK , Lanciotti R , Lambert A , Shieh WJ , Zaki SR . Lancet 2016 388 (10047) 898-904 BACKGROUND: Zika virus is an arthropod-borne virus that is a member of the family Flaviviridae transmitted mainly by mosquitoes of the genus Aedes. Although usually asymptomatic, infection can result in a mild and self-limiting illness characterised by fever, rash, arthralgia, and conjunctivitis. An increase in the number of children born with microcephaly was noted in 2015 in regions of Brazil with high transmission of Zika virus. More recently, evidence has been accumulating supporting a link between Zika virus and microcephaly. Here, we describe findings from three fatal cases and two spontaneous abortions associated with Zika virus infection. METHODS: In this case series, formalin-fixed paraffin-embedded tissue samples from five cases, including two newborn babies with microcephaly and severe arthrogryposis who died shortly after birth, one 2-month-old baby, and two placentas from spontaneous abortions, from Brazil were submitted to the Infectious Diseases Pathology Branch at the US Centers for Disease Control and Prevention (Atlanta, GA, USA) between December, 2015, and March, 2016. Specimens were assessed by histopathological examination, immunohistochemical assays using a mouse anti-Zika virus antibody, and RT-PCR assays targeting the NS5 and envelope genes. Amplicons of RT-PCR positive cases were sequenced for characterisation of strains. FINDINGS: Viral antigens were localised to glial cells and neurons and associated with microcalcifications in all three fatal cases with microcephaly. Antigens were also seen in chorionic villi of one of the first trimester placentas. Tissues from all five cases were positive for Zika virus RNA by RT-PCR, and sequence analyses showed highest identities with Zika virus strains isolated from Brazil during 2015. INTERPRETATION: These findings provide strong evidence of a link between Zika virus infection and different congenital central nervous system malformations, including microcephaly as well as arthrogryposis and spontaneous abortions. FUNDING: None. |
Notes from the field: evidence of Zika virus infection in brain and placental tissues from two congenitally infected newborns and two fetal losses - Brazil, 2015
Martines RB , Bhatnagar J , Keating MK , Silva-Flannery L , Muehlenbachs A , Gary J , Goldsmith C , Hale G , Ritter J , Rollin D , Shieh WJ , Luz KG , Ramos AM , Davi HP , Kleber de Oliveria W , Lanciotti R , Lambert A , Zaki S . MMWR Morb Mortal Wkly Rep 2016 65 (6) 159-160 Zika virus is a mosquito-borne flavivirus that is related to dengue virus and transmitted primarily by Aedes aegypti mosquitoes, with humans acting as the principal amplifying host during outbreaks. Zika virus was first reported in Brazil in May 2015 (1). By February 9, 2016, local transmission of infection had been reported in 26 countries or territories in the Americas.* Infection is usually asymptomatic, and, when symptoms are present, typically results in mild and self-limited illness with symptoms including fever, rash, arthralgia, and conjunctivitis. However, a surge in the number of children born with microcephaly was noted in regions of Brazil with a high prevalence of suspected Zika virus disease cases. More than 4,700 suspected cases of microcephaly were reported from mid-2015 through January 2016, although additional investigations might eventually result in a revised lower number (2). In response, the Brazil Ministry of Health established a task force to further investigate possible connections between the virus and brain anomalies in infants (3). |
Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in United Arab Emirates, April 2014
Ng DL , Al Hosani F , Keating MK , Gerber SI , Jones TL , Metcalfe MG , Tong S , Tao Y , Alami NN , Haynes LM , Mutei MA , Abdel-Wareth L , Uyeki TM , Swerdlow DL , Barakat M , Zaki SR . Am J Pathol 2016 186 (3) 652-8 Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti-MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans. |
Diagnosing Balamuthia mandrillaris Encephalitis With Metagenomic Deep Sequencing.
Wilson MR , Shanbhag NM , Reid MJ , Singhal NS , Gelfand JM , Sample HA , Benkli B , O'Donovan B , Ali IK , Keating MK , Dunnebacke TH , Wood MD , Bollen A , DeRisi JL . Ann Neurol 2015 78 (5) 722-30 OBJECTIVE: Identification of a particular cause of meningoencephalitis can be challenging due to the myriad bacteria, viruses, fungi, and parasites that can produce overlapping clinical phenotypes, frequently delaying diagnosis and therapy. Metagenomic deep sequencing (MDS) approaches to infectious disease diagnostics are known for their ability to identify unusual or novel viruses and thus are well suited for investigating possible etiologies of meningoencephalitis. METHODS: We present the case of a 74 year-old woman with endophthalmitis followed by meningoencephalitis. MDS of her cerebrospinal fluid (CSF) was performed to identify an infectious agent. RESULTS: Sequences aligning to Balamuthia mandrillaris ribosomal RNA genes were identified in the CSF via MDS. Polymerase chain reaction (PCR) subsequently confirmed the presence of B. mandrillaris in CSF, brain tissue, and vitreous fluid from the patient's infected eye. B. mandrillaris serology and immunohistochemistry for free-living amoebas on the brain biopsy tissue were positive. INTERPRETATION: The diagnosis was made using MDS after the patient had been hospitalized for several weeks and subjected to costly and invasive testing. MDS a powerful diagnostic tool with the potential for rapid and unbiased pathogen identification leading to early therapeutic targeting. |
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