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.

In 2017, Puerto Rico sustained extensive damage from Hurricane Maria, increasing the risk of fires and carbon monoxide (CO) poisonings. Using a population-based, in-person survey of households with children less than 6 years old in Puerto Rico, we collected data in 2010 concerning the presence of smoke alarms and CO alarms in these households. We generated national estimates by extrapolating the number of households in each stratum using data from the 2010 Census. We determined which household characteristics predicted the presence of these alarms. Of 355 households analyzed, 31% had functional smoke alarms, or an estimated 109,773 households territory wide. The presence of smoke alarms was associated with living in multifamily housing and no child in the household receiving government medical insurance. Public housing or publicly subsidized housing, as compared to owner-occupied housing and unsubsidized rental housing, was associated with having a functional smoke alarm in households with children aged less than 6 years. Based on only six houses having CO alarms, we estimated only 7685 (2%) households had CO alarms. The low prevalence of functional smoke or CO alarms 7 years before Hurricane Maria is unfortunate and should be remedied by ensuring that such alarms are widely installed in current rebuilding activities.

On December 1, 2015, the Puerto Rico Department of Health (PRDH) was notified by a local hospital of a suspected human rabies case. The previous evening, a Puerto Rican man aged 54 years arrived at the emergency department with fever, difficulty swallowing, hand paresthesia, cough, and chest tightness. The next morning the patient left against medical advice but returned to the emergency department in the afternoon with worsening symptoms. The patient's wife reported that he had been bitten by a mongoose during the first week of October, but had not sought care for the bite. While being transferred to the intensive care unit, the patient went into cardiac arrest and died. On December 3, rabies was confirmed from specimens collected during autopsy. PRDH conducted an initial rapid risk assessment, and five family members were started on rabies postexposure prophylaxis (PEP).

On July 16 2015, the Puerto Rico Department of Health (PRDH) was notified of a case of malaria, diagnosed by a hospital parasitology laboratory in a student who had traveled to Punta Cana, Dominican Republic, during late June for a school-organized graduation trip. Malaria is a mosquito-borne parasitic infection, characterized by fever, shaking chills, headaches, muscle pains, nausea, general malaise, and vomiting. Malaria can be clinically difficult to distinguish from other acute febrile illnesses, and a definitive diagnosis requires demonstration of malaria parasites using microscopy or molecular diagnostic tests. The student's initial diagnosis on July 10 was suspected dengue virus infection. Puerto Rico eliminated local malaria transmission during the mid-1950s; however, reintroduction remains a risk because of the presence of a competent vector (Anopheles albimanus) and ease of travel to areas where the disease is endemic, including Hispaniola, the island shared by the Dominican Republic and Haiti, and the only island in the Caribbean with endemic malaria. During 2014, the Dominican Republic reported 496 confirmed malaria cases and four associated deaths; Haiti reported 17,662 confirmed cases and nine deaths. During 2000-2014, Puerto Rico reported a total of 35 imported malaria cases (range = 0-7 per year); three cases were imported from Hispaniola. During June-August 2015, eight confirmed malaria cases among travelers to the Dominican Republic were reported to CDC's National Malaria Surveillance System (CDC, unpublished data, 2015).

Serum specimens from free-ranging but nonnative patas monkeys (Erythrocebus patas) and rhesus macaques (Macaca mulatta) in southwestern Puerto Rico (PR) were tested for antibodies to infection with dengue viruses (DENVs), West Nile virus (WNV), Leptospira species, and Burkholderia pseudomallei by microneutralization, plaque reduction neutralization, microscopic agglutination, and indirect hemagglutination, respectively. Of 23 animals (21 E. patas and two M. mulatta) tested, all had evidence of prior DENV infection, and of 17 animals tested for WNV, nine (53%) had evidence of prior infection. Of 24 (22 E. patas, two M. mulatta) tested for Leptospira spp., 10 (42%) had evidence of prior exposure, and one patas monkey had antibodies against B. pseudomallei. The acquisition of pathogens endemic among humans in PR by resident nonhuman primates merits further study to define modes of acquisition.

Chikungunya and dengue are mosquito-borne, viral, acute febrile illnesses that can be difficult to distinguish clinically. Whereas dengue is endemic in many countries in the Caribbean and the Americas, the first locally acquired chikungunya case in the Western Hemisphere was reported from the Caribbean island of St. Martin in December 2013 and was soon followed by cases in many parts of the region. In January 2014, the Puerto Rico Department of Health (PRDH) and CDC initiated chikungunya surveillance by building on an existing passive dengue surveillance system. To assess the extent of chikungunya in Puerto Rico, the severity of illnesses, and the health care-seeking behaviors of residents, PRDH and CDC analyzed data from passive surveillance and investigations conducted around the households of laboratory-positive chikungunya patients. Passive surveillance indicated that the first locally acquired, laboratory-positive chikungunya case in Puerto Rico was in a patient with illness onset on May 5, 2014. By August 12, a total of 10,201 suspected chikungunya cases (282 per 100,000 residents) had been reported. Specimens from 2,910 suspected cases were tested, and 1,975 (68%) were positive for chikungunya virus (CHIKV) infection. Four deaths were reported. The household investigations found that, of 250 participants, 70 (28%) tested positive for current or recent CHIKV infection, including 59 (84%) who reported illness within the preceding 3 months. Of 25 laboratory-positive participants that sought medical care, five (20%) were diagnosed with chikungunya and two (8%) were reported to PRDH. These investigative efforts indicated that chikungunya cases were underrecognized and underreported, prompting PRDH to conduct information campaigns to increase knowledge of the disease among health care professionals and the public. PRDH and CDC recommended that health care providers manage suspected chikungunya cases as they do dengue because of the similarities in symptoms and increased risk for complications in dengue patients that are not appropriately managed. Residents of and travelers to the tropics can minimize their risk for both chikungunya and dengue by taking standard measures to avoid mosquito bites.

Co-infection with pathogens that cause acute febrile illness creates a diagnostic challenge as a result of overlapping clinical manifestations. Here, we describe four fatal cases of Leptospira species/dengue virus co-infection in Puerto Rico. Although all patients sought care early, antibiotic administration was delayed for most. Steroids were administered to all patients, in most cases before antibiotics. These cases show the need for clinicians evaluating patients in or recently returned from the tropics with acute febrile illness to consider both dengue and leptospirosis. Furthermore, they illustrate the need for nucleic acid- or antigen-based rapid diagnostic tests to enable timely patient diagnosis and management. In particular, antibiotic therapy should be initiated early for patients with suspected leptospirosis, and steroids should not be administered to patients with suspected dengue.