Clinical Characteristics, Histopathology, and Tissue Immunolocalization of Chikungunya Virus Antigen in Fatal Cases.

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 reverse transcriptase-polymerase chain reaction in a pre- or postmortem 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 (0.8/100 000 population). The median age was 61 years (range: 6 days-86 years), and 19 (63%) were male. Death occurred a median of 4 days (range: 1-29) after illness onset. Nearly all (93%) had at least 1 comorbidity, most frequently hypertension, diabetes, or obesity. Nine had severe comorbidities (eg, chronic heart or kidney disease, sickle cell anemia) or coinfection (eg, 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 2 patients. CONCLUSIONS: Evaluation of tissue specimens provided insights into the pathogenesis of CHIKV, which may rarely result in septic shock and other severe manifestations.

Postmortem Findings in Patient with Guillain-Barré Syndrome and Zika Virus Infection.

Postmortem examination results of a patient with Guillain-Barré syndrome and confirmed Zika virus infection revealed demyelination of the sciatic and cranial IV nerves, providing evidence of the acute demyelinating inflammatory polyneuropathy Guillain-Barré syndrome variant. Lack of evidence of Zika virus in nervous tissue suggests that pathophysiology was antibody mediated without neurotropism.

Surveillance for Chikungunya and Dengue During the First Year of Chikungunya Virus Circulation in Puerto Rico.

After chikungunya virus (CHIKV) transmission was detected in Puerto Rico in May 2014, multiple surveillance systems were used to describe epidemiologic trends and CHIKV-associated disease. Of 28 327 cases reported via passive surveillance, 6472 were tested for evidence of CHIKV infection, and results for 4399 (68%) were positive. Of 250 participants in household cluster investigations, 70 (28%) had evidence of recent CHIKV infection. Enhanced surveillance for chikungunya at 2 hospitals identified 1566 patients who tested positive for CHIKV, of whom 10.9% were hospitalized. Enhanced surveillance for fatal cases enabled identification of 31 cases in which CHIKV was detected in blood or tissue specimens. All surveillance systems detected a peak incidence of chikungunya in September 2014 and continued circulation in 2015. Concomitant surveillance for dengue demonstrated low incidence, which had decreased before CHIKV was introduced. Multifaceted chikungunya surveillance in Puerto Rico resolved gaps in traditional passive surveillance and enabled a holistic description of the spectrum of disease associated with CHIKV infection.

Pathology of congenital Zika syndrome in Brazil: a case series.

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.

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).

Contact investigation of melioidosis cases reveals regional endemicity in Puerto Rico.

BACKGROUND: Melioidosis results from infection with Burkholderia pseudomallei and is associated with case-fatality rates up to 40%. Early diagnosis and treatment with appropriate antimicrobials can improve survival rates. Fatal and nonfatal melioidosis cases were identified in Puerto Rico in 2010 and 2012, respectively, which prompted contact investigations to identify risk factors for infection and evaluate endemicity. METHODS: Questionnaires were administered and serum specimens were collected from coworkers, neighborhood contacts within 250 m of both patients' residences, and injection drug user (IDU) contacts of the 2012 patient. Serum specimens were tested for evidence of prior exposure to B. pseudomallei by indirect hemagglutination assay. Neighborhood seropositivity results guided soil sampling to isolate B. pseudomallei. RESULTS: Serum specimens were collected from contacts of the 2010 (n = 51) and 2012 (n = 60) patients, respectively. No coworkers had detectable anti-B. pseudomallei antibody, whereas seropositive results among neighborhood contacts was 5% (n = 2) for the 2010 patient and 23% (n = 12) for the 2012 patient, as well as 2 of 3 IDU contacts for the 2012 case. Factors significantly associated with seropositivity were having skin wounds, sores, or ulcers (odds ratio [OR], 4.6; 95% confidence interval [CI], 1.2-17.8) and IDU (OR, 18.0; 95% CI, 1.6-194.0). Burkholderia pseudomallei was isolated from soil collected in the neighborhood of the 2012 patient. CONCLUSIONS: Taken together, isolation of B. pseudomallei from a soil sample and high seropositivity among patient contacts suggest at least regional endemicity of melioidosis in Puerto Rico. Increased awareness of melioidosis is needed to enable early case identification and early initiation of appropriate antimicrobial therapy.

Intestinal intussusception associated with adenovirus infection in Mexican children.

Formalin-fixed intestinal tissue specimens from 12 Mexican pediatric patients with intussusception were examined for the presence of adenovirus. Four patients (33%) had detectable adenovirus antigen in epithelial cells as determined by using immunohistochemical analysis. Two of the patients with positive immunohistochemical results had antigens in dendritic and mononuclear inflammatory cells, and 3 patients had positive results for species C adenovirus by in situ hybridization using adenovirus species-specific probes (A-F). A real-time polymerase chain reaction assay specific for species C (nonenteric) adenoviruses was used to confirm immunohistochemical results and to amplify adenovirus DNA for sequencing. A sequence similar to that for adenovirus serotype 1 was found in 1 patient, serotype 2 in another, and serotype 6 in a third; in the fourth patient, the sequence was indeterminate between serotypes 2 and 6. The assays used in this study proved useful for the identification of species C adenoviruses in formalin-fixed specimens from Mexican pediatric patients with intussusception.