Christopher J. Gregory

Dengue outbreak in Key West, Florida, USA, 2009.

After 3 dengue cases were acquired in Key West, Florida, we conducted a serosurvey to determine the scope of the outbreak. Thirteen residents showed recent infection (infection rate 5%; 90% CI 2%–8%), demonstrating the reemergence of dengue in Florida. Increased awareness of dengue among health care providers is needed.

Outbreak of Carbapenem-Resistant Klebsiella pneumoniae in Puerto Rico Associated with a Novel Carbapenemase Variant

BACKGROUND Carbapenem-resistant Klebsiella pneumoniae (CRKP) is resistant to almost all antimicrobial agents, and CRKP infections are associated with substantial morbidity and mortality. OBJECTIVE To describe an outbreak of CRKP in Puerto Rico, determine risk factors for CRKP acquisition, and detail the successful measures taken to control the outbreak. DESIGN Two case-control studies. SETTING A 328-bed tertiary care teaching hospital. PATIENTS Twenty-six CRKP case patients identified during the outbreak period of February through September 2008, 26 randomly selected uninfected control patients, and 26 randomly selected control patients with carbapenem-susceptible K. pneumoniae (CSKP) hospitalized during the same period. METHODS We performed active case finding, including retrospective review of the hospitals microbiology database and prospective perirectal surveillance culture sampling in high-risk units. Case patients were compared with each control group while controlling for time at risk. We sequenced the bla(KPC) gene with polymerase chain reaction for 7 outbreak isolates and subtyped these isolates with pulsed-field gel electrophoresis. RESULTS In matched, multivariable analysis, the presence of wounds (hazard ratio, 19.0 [95% confidence interval {CI}, 2.5-142.0]) was associated with CRKP compared with no K. pneumoniae. Transfer between units (adjusted odds ratio [OR], 7.5 [95% CI, 1.8-31.1]), surgery (adjusted OR, 4.0 [95% CI, 1.0-15.7]), and wounds (adjusted OR, 4.9 [95% CI, 1.1-21.8]) were independent risk factors for CRKP compared to CSKP. A novel K. pneumoniae carbapenemase variant (KPC-8) was present in 5 isolates. Implementation of active surveillance for CRKP colonization and cohorting of CRKP patients rapidly controlled the outbreak. CONCLUSIONS Enhanced surveillance for CRKP colonization and intensified infection control measures that include limiting the physical distribution of patients can reduce CRKP transmission during an outbreak.

Clinical and Laboratory Features That Differentiate Dengue from Other Febrile Illnesses in an Endemic Area—Puerto Rico, 2007–2008

Dengue infection can be challenging to diagnose early in the course of infection before severe manifestations develop, but early diagnosis can improve patient outcomes and promote timely public health interventions. We developed age-based predictive models generated from 2 years of data from an enhanced dengue surveillance system in Puerto Rico. These models were internally validated and were able to differentiate dengue infection from other acute febrile illnesses with moderate accuracy. The accuracy of the models was greater than either the current World Health Organization case definition for dengue fever or a proposed modification to this definition, while requiring the collection of fewer data. In young children, thrombocytopenia and the absence of cough were associated with dengue infection; for adults, rash, leucopenia, and the absence of sore throat were associated with dengue infection; in all age groups, retro-orbital pain was associated with dengue infection.

Dengue Deaths in Puerto Rico: Lessons Learned from the 2007 Epidemic

Background The incidence and severity of dengue in Latin America has increased substantially in recent decades and data from Puerto Rico suggests an increase in severe cases. Successful clinical management of severe dengue requires early recognition and supportive care. Methods Fatal cases were identified among suspected dengue cases reported to two disease surveillance systems and from death certificates. To be included, fatal cases had to have specimen submitted for dengue diagnostic testing including nucleic acid amplification for dengue virus (DENV) in serum or tissue, immunohistochemical testing of tissue, and immunoassay detection of anti-DENV IgM from serum. Medical records from laboratory-positive dengue fatal case-patients were reviewed to identify possible determinants for death. Results Among 10,576 reported dengue cases, 40 suspect fatal cases were identified, of which 11 were laboratory-positive, 14 were laboratory-negative, and 15 laboratory-indeterminate. The median age of laboratory-positive case-patients was 26 years (range 5 months to 78 years), including five children aged <15 years; 7 sought medical care at least once prior to hospital admission, 9 were admitted to hospital and 2 died upon arrival. The nine hospitalized case-patients stayed a mean of 15 hours (range: 3–48 hours) in the emergency department (ED) before inpatient admission. Five of the nine case-patients received intravenous methylprednisolone and four received non-isotonic saline while in shock. Eight case-patients died in the hospital; five had their terminal event on the inpatient ward and six died during a weekend. Dengue was listed on the death certificate in only 5 instances. Conclusions During a dengue epidemic in an endemic area, none of the 11 laboratory-positive case-patients who died were managed according to current WHO Guidelines. Management issues identified in this case-series included failure to recognize warning signs for severe dengue and shock, prolonged ED stays, and infrequent patient monitoring.

Reduced evolutionary rate in reemerged Ebola virus transmission chains.

Surveillance of Ebola virus disease flare-ups uncovers a reduced rate of Ebola virus evolution during persistent infections. On 29 June 2015, Liberia’s respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak (“flare-up”) of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over.

Update: Interim Guidance for Health Care Providers Caring for Pregnant Women with Possible Zika Virus Exposure - United States (Including U.S. Territories), July 2017.

CDC has updated the interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure in response to 1) declining prevalence of Zika virus disease in the World Health Organizations Region of the Americas (Americas) and 2) emerging evidence indicating prolonged detection of Zika virus immunoglobulin M (IgM) antibodies. Zika virus cases were first reported in the Americas during 2015-2016; however, the incidence of Zika virus disease has since declined. As the prevalence of Zika virus disease declines, the likelihood of false-positive test results increases. In addition, emerging epidemiologic and laboratory data indicate that, as is the case with other flaviviruses, Zika virus IgM antibodies can persist beyond 12 weeks after infection. Therefore, IgM test results cannot always reliably distinguish between an infection that occurred during the current pregnancy and one that occurred before the current pregnancy, particularly for women with possible Zika virus exposure before the current pregnancy. These limitations should be considered when counseling pregnant women about the risks and benefits of testing for Zika virus infection during pregnancy. This updated guidance emphasizes a shared decision-making model for testing and screening pregnant women, one in which patients and providers work together to make decisions about testing and care plans based on patient preferences and values, clinical judgment, and a balanced assessment of risks and expected outcomes.

Utility of the tourniquet test and the white blood cell count to differentiate dengue among acute febrile illnesses in the emergency room.

Dengue often presents with non-specific clinical signs, and given the current paucity of accurate, rapid diagnostic laboratory tests, identifying easily obtainable bedside markers of dengue remains a priority. Previous studies in febrile Asian children have suggested that the combination of a positive tourniquet test (TT) and leucopenia can distinguish dengue from other febrile illnesses, but little data exists on the usefulness of these tests in adults or in the Americas. We evaluated the diagnostic accuracy of the TT and leucopenia (white blood cell count <5000/mm3) in identifying dengue as part of an acute febrile illness (AFI) surveillance study conducted in the Emergency Department of Saint Lukes Hospital in Ponce, Puerto Rico. From September to December 2009, 284 patients presenting to the ED with fever for 2–7 days and no identified source were enrolled. Participants were tested for influenza, dengue, leptospirosis and enteroviruses. Thirty-three (12%) patients were confirmed as having dengue; 2 had dengue co-infection with influenza and leptospirosis, respectively. An infectious etiology was determined for 141 others (136 influenza, 3 enterovirus, 2 urinary tract infections), and 110 patients had no infectious etiology identified. Fifty-two percent of laboratory-positive dengue cases had a positive TT versus 18% of patients without dengue (P<0.001), 87% of dengue cases compared to 28% of non-dengue cases had leucopenia (P<0.001). The presence of either a positive TT or leucopenia correctly identified 94% of dengue patients. The specificity and positive predictive values of these tests was significantly higher in the subset of patients without pandemic influenza A H1N1, suggesting improved discriminatory performance of these tests in the absence of concurrent dengue and influenza outbreaks. However, even during simultaneous AFI outbreaks, the absence of leucopenia combined with a negative tourniquet test may be useful to rule out dengue.

Acute febrile illness surveillance in a tertiary hospital emergency department: comparison of influenza and dengue virus infections.

In 2009, an increased proportion of suspected dengue cases reported to the surveillance system in Puerto Rico were laboratory negative. As a result, enhanced acute febrile illness (AFI) surveillance was initiated in a tertiary care hospital. Patients with fever of unknown origin for 2-7 days duration were tested for Leptospira, enteroviruses, influenza, and dengue virus. Among the 284 enrolled patients, 31 dengue, 136 influenza, and 3 enterovirus cases were confirmed. Nearly half (48%) of the confirmed dengue cases met clinical criteria for influenza. Dengue patients were more likely than influenza patients to have hemorrhage (81% versus 26%), rash (39% versus 9%), and a positive tourniquet test (52% versus 18%). Mean platelet and white blood cell count were lower among dengue patients. Clinical diagnosis can be particularly difficult when outbreaks of other AFI occur during dengue season. A complete blood count and tourniquet test may be useful to differentiate dengue from other AFIs.

Investigation of Elevated Case-Fatality Rate in Poliomyelitis Outbreak in Pointe Noire, Republic of Congo, 2010

BACKGROUND Multiple cases of paralysis, often resulting in death, occurred among young adults during a wild poliovirus (WPV) type 1 outbreak in Pointe Noire, Republic of Congo, in 2010. We conducted an investigation to identify factors associated with fatal outcomes among persons with poliomyelitis in Pointe Noire. METHODS Polio cases were defined as acute flaccid paralysis (AFP) cases reported from 7 October to 7 December 2010 with either a stool specimen positive for WPV or clinically classified as polio-compatible. Data were obtained from medical records, hospital databases, AFP case investigation forms and, when possible, via interviews with persons with polio or surrogates using a standard questionnaire. RESULTS A total of 369 polio cases occurred in Pointe Noire between 7 October and 7 December 2010. Median age was 22 years for nonsurvivors and 18 years for survivors (P = .01). Small home size, as defined by ≤2 rooms, use of a well for drinking water during a water shortage, and age ≥15 years were risk factors for death in multivariate analysis. CONCLUSIONS Consideration should be given during polio risk assessment planning and outbreak response to water/sanitation status and potential susceptibility to polio in older children and adults. Serosurveys to estimate immunity gaps in older age groups in countries at high risk of polio importation might be useful to guide preparedness and response planning.

Co-infection with dengue virus and pandemic (H1N1) 2009 virus.

To the Editor: Dengue is a mosquito-borne viral infection caused by 4 related dengue viruses. Each of these viruses is capable of causing classic dengue fever or dengue hemorrhagic fever (DHF), but may also cause nonspecific febrile illnesses. As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (1). Concurrent outbreaks of influenza and dengue have been reported (2,3); this circumstance often leads to delayed recognition of the presence of one or other disease in the community. In April 2009, a new strain of influenza A virus known as pandemic (H1N1) 2009 virus was first detected in the United States (4). Pandemic (H1N1) 2009 infections were first detected in Puerto Rico in June 2009, and 59 deaths caused by the virus have been confirmed to date. This influenza outbreak coincided with the typical dengue season in Puerto Rico, which led to diagnostic difficulties; both infections disproportionately affected young persons, who often had similar, nonspecific symptoms. We describe a case of laboratory-confirmed co-infection of dengue virus and pandemic (H1N1) 2009, and discuss the difficulties in distinguishing the 2 illnesses clinically. A 33-year-old woman (healthcare worker) in Ponce, Puerto Rico, sought treatment at an emergency department of a hospital in the southern part of the island with a 3-day history of febrile illness. Her symptoms began with throat irritation and earache; subsequently, cough, fever, and headache developed. She reported palpitations and generalized malaise but no other symptoms. The patient had no notable medical history and denied taking any medicines apart from over-the-counter antipyretics. She reported recent exposure to influenza at work and multiple recent mosquito bites. On physical examination, she had a temperature of 37°C, a heart rate of 91 bpm, and blood pressure of 125/82 mm Hg. A tourniquet test result was positive. Her pharynx was erythematous without exudate, and she had rhinorrhea. She had no lymphadenopathy, rash, petechiae, or purpura. Several small, red papules, which the patient described as recent mosquito bites, were on her legs. The remainder of her examination showed no unusual findings. Laboratory studies showed a leukocyte count of 5,300 cells/mm3 with a normal differential count, hematocrit 35.2%, and thrombocyte count of 239,000 cells/dL. Results of a chest radiograph was unremarkable. A nasopharyngeal swab was positive for influenza A virus by rapid test. Nasopharyngeal and serum samples were sent to the Centers for Disease Control and Prevention (Dengue Branch) for influenza and dengue testing. The patient was diagnosed with suspected pandemic (H1N1) 2009 infection and prescribed oseltamivir for 5 days. She returned for a follow-up visit 12 days after the onset of symptoms. She reported having 2 more days of fever after her initial visit, but had no rash, petechiae, bleeding, or progression of respiratory symptoms. A second serum specimen was obtained during this visit. The initial serum specimen was positive for dengue virus by serotype-specific, singleplex, real-time reverse transcription–PCR (5). Her nasopharyngeal specimen was positive by PCR for pandemic (H1N1) 2009 influenza. The second, convalescent-phase, serum specimen was negative for dengue immunoglobulin (Ig) M by IgM antibody–capture ELISA. The acute-phase and convalescent-phase samples were positive for IgG against dengue by ELISA (6), which indicated a secondary dengue infection. IgG titers exceeded the limits of the test for acute-phase and convalescent-phase samples, showing unusually elevated levels of IgG against dengue. Distinguishing dengue and influenza by clinical features alone can be difficult. In an investigation of simultaneous dengue and influenza A outbreaks in Puerto Rico in 1977, similar percentages of persons with confirmed dengue and confirmed influenza had classic dengue symptoms (2). Hemorrhagic manifestations, like those typically seen in DHF, have been reported with influenza A in prior outbreaks (7,8) and with pandemic (H1N1) 2009 (Centers for Disease Control and Prevention, unpub. data). Previous influenza A outbreaks were initially believed to be outbreaks of DHF until careful laboratory investigation proved otherwise (8). Our patient did not have the typical signs and symptoms of dengue (rash, eye pain, thrombocytopenia, arthralgia, petechiae, or bleeding) that would differentiate her condition from that of patients with other febrile illnesses. She did have a positive tourniquet test result and fever, which have been advocated as screening criteria for dengue infection in children, at the time of initial examination (9). Data for the specificity and sensitivity of these criteria in adults are sparse, however, and some studies have shown a high incidence of positive tourniquet test results in patients with laboratory-confirmed influenza (7,8). Our report demonstrates that co-infection with dengue virus and pandemic (H1N1) 2009 can occur. Previous studies also have shown cases of probable co-infection with seasonal influenza and dengue (1,10), including 1 fatal case (1). Because many dengue-endemic countries are experiencing pandemic (H1N1) 2009 outbreaks, providers should consider the possibility of viral co-infection, especially in severe cases, and should consider testing for both viruses.