Matthew J. Hepburn

Long-term sequelae after Ebola virus disease in Bundibugyo, Uganda: a retrospective cohort study

BACKGROUND The limited data available for long-term Ebola virus disease health outcomes suggest that sequelae persist for longer than 1 year after infection. The magnitude of the present outbreak in west Africa necessitates a more complete understanding of the health effects and future medical needs of these patients. METHODS We invited adult survivors of the 2007 Bundibugyo Ebola virus outbreak in Uganda and their contacts to take part in an observational study roughly 29 months after the outbreak. We collected information about health status, functional limitations, and demographics. We collected blood samples for clinical chemistry, haematology, and filovirus antibodies using ELISA. Analyses were restricted to probable and confirmed survivors and their seronegative contacts. FINDINGS We recruited 70 survivors of the 2007 Bundibugyo Ebola virus and 223 contacts. We did analyses for 49 probable and confirmed survivors and 157 seronegative contacts. Survivors of the Bundibugyo Ebola virus were at significantly increased risk of ocular deficits (retro-orbital pain [RR 4·3, 95% CI 1·9-9·6; p<0·0001], blurred vision [1·9, 1·1-3·2; p=0·018]), hearing loss (2·3, 1·2-4·5; p=0·010), difficulty swallowing (2·1, 1·1-3·9; p=0·017), difficulty sleeping (1·9, 1·3-2·8; p=0·001), arthralgias (2·0, 1·1-3·6; p=0·020), and various constitutional symptoms controlling for age and sex. Chronic health problems (prevalence ratio [PR] 2·1, 95% CI 1·2-3·6; p=0·008) and limitations due to memory loss or confusion (PR 5·8, 1·5-22·4; p=0·010) were also reported more frequently by survivors of Bundibugyo Ebola virus. INTERPRETATION Long-term sequelae persist for more than 2 years after Ebola virus disease. Definition of health consequences related to Ebola virus disease could improve patient care for survivors and contribute to understanding of disease pathogenesis. FUNDING Chemical Biological Technologies Directorate, Defense Threat Reduction Agency.

The changing pattern of human brucellosis: clinical manifestations, epidemiology, and treatment outcomes over three decades in Georgia

BackgroundBrucellosis is an endemic infection in Georgia. We conducted a review of patient records with a suspected or confirmed diagnosis of brucellosis over three decades at the central referral hospital for brucellosis cases, the Institute of Parasitology and Tropical Medicine (IPTM) in Tbilisi. The purpose was to describe the demographic profile and clinical characteristics as well as diagnostic and treatment strategies in patients with brucellosis.MethodsData were abstracted from randomly selected patient records at the IPTM. In total, 300 records were reviewed from three time periods: 1970-73, 1988-89, and 2004-2008.ResultsThe age distribution of patients shifted from a median age of 40 years in the first time period to 20 years in the third time period. Azeri ethnicity was an increasing proportion of the total number of cases. The frequency of relapsed infection was 14.7% (44 cases). A total of 50 patients received vaccine therapy, and although the vaccine produced immune responses, demonstrated by an increase in agglutination titers, it was not associated with improved outcome.ConclusionThe demographics of brucellosis in Georgia fit a profile of persons that tend sheep. Osteoarticular complications were commonly detected, especially in children. The changing pattern of brucellosis in Georgia suggests clinicians should be updated about different trends in brucellosis in their country.

Real-time Monitoring of Cardiovascular Function in Rhesus Macaques Infected With Zaire ebolavirus

Nine rhesus macaques were implanted with multisensor telemetry devices and internal jugular vein catheters before being infected with Zaire ebolavirus. All animals developed viremia, fever, a hemorrhagic rash, and typical changes of Ebola hemorrhagic fever in clinical laboratory tests. Three macaques unexpectedly survived this usually lethal disease, making it possible to compare physiological parameters in lethally challenged animals and survivors. After the onset of fever, lethal illness was characterized by a decline in mean arterial blood pressure, an increase in pulse and respiratory rate, lactic acidosis, and renal failure. Survivors showed less pronounced change in these parameters. Four macaques were randomized to receive supplemental volumes of intravenous normal saline when they became hypotensive. Although those animals had less severe renal compromise, no apparent survival benefit was observed. This is the first report of continuous physiologic monitoring in filovirus-infected nonhuman primates and the first to attempt cardiovascular support with intravenous fluids.

Outcomes of community-acquired, methicillin-resistant Staphylococcus aureus, soft tissue infections treated with antibiotics other than vancomycin.

Community-acquired, methicillin-resistant Staphylococcus aureus (cMRSA), soft tissue infections are becoming increasingly prevalent in the outpatient setting. Few studies have been specifically designed to examine the efficacy of oral antibiotic therapy for these infections. We performed an observational study to determine the effect of alternative, orally administered antibiotics on cMRSA soft tissue infections. Consecutive patients between January 2001 and March 2004 who had skin or soft tissue infections from which cMRSA was isolated and who had never received vancomycin were studied through retrospective and concurrent review. Primary outcome measures were improvement or resolution of infection 5 and 14 days after initiation of treatment with orally administered antibiotics and rates of recurrence within 30 days after completion of treatment. Thirty subjects met the inclusion criteria. Twenty-one subjects received either clindamycin, trimethoprim/sulfamethoxazole, doxycycline/minocycline, or a fluoroquinolone. Five subjects received a beta-lactam antibiotic with abscess drainage, and four subjects underwent abscess drainage alone. Improvement was noted for all subjects at 5 days, complete resolution of infection occurred for all subjects by 14 to 17 days, and in no case did relapse occur within 30 days. cMRSA skin and soft tissue infections can be successfully treated with orally administered antibiotics to which the organism has demonstrable in vitro susceptibility.

Seroprevalence of Tularemia in Rural Azerbaijan

A representative, two-stage probability sampling design was used to select 40 villages in northern Azerbaijan with populations of <500 people to screen for evidence of prior infection with Francisella tularensis. Informed consent was provided, and samples were obtained from 796 volunteers and tested for the presence of immunoglobulin G antibodies using enzyme-linked immunosorbent assay. F. tularensis seropositivity was prevalent (15.5% of volunteers), but there was minimal reporting of signs and symptoms consistent with clinical tularemia, suggesting that mild or asymptomatic infection commonly occurs. Frequently seeing rodents around the home was a risk factor for seropositivity (POR = 1.6, p = 0.03), controlling for age and gender. Geospatial analysis identified associations between village-level tularemia prevalence and suitable tick habitats, annual rainfall, precipitation in the driest quarter, and altitude. This study contributes to the growing understanding of the geographic distribution of tularemia and provides further information on the climatic and landscape conditions that increased the potential for exposure to this pathogen. The potential occurrence of asymptomatic or mild F. tularensis infection warrants further study.

Crimean-Congo Hemorrhagic Fever in Man, Republic of Georgia, 2009

To the Editor: Crimean-Congo hemorrhagic fever (CCHF) virus is widely distributed in the southwestern regions of the former Soviet Union, the Balkans, the Middle East, western People’s Republic of China, and Africa (1). Public health officials in the Republic of Georgia have long suspected that CCHF occurs in this country, but laboratory confirmation by using molecular diagnostic techniques has not been possible there until recently.

Generation of heterogeneous memory T cells by live attenuated tularemia vaccine in humans

There is very limited evidence concerning the phenotype, function, and homing characteristics of memory T (T(M)) cells elicited by vaccination against intracellular bacteria in humans. Here we studied T(M) subsets elicited by exposure to Francisella tularensis in humans as a model of immunity to intracellular bacteria. To this end, T(M) cells were evaluated in two groups: (1) subjects immunized with live attenuated tularemia vaccine by skin scarification and (2) tularemia naturally infected subjects. In both groups the immune responses were mediated by CD4(+) and CD8(+) effector T(M) cells, mostly CD45RA(-)CD62L(-) and CD45RA(+)CD62L(-). Based on the expression of CD27, integrins alpha(4)/beta(7,) and alpha(4)/beta(1), it is likely that some of these T(M) cells have lytic potential and the ability to enter both mucosal and non-mucosal sites. Thus, regardless of whether by immunization or natural exposure, tularemia antigens elicited a broad spectrum of specific T(M) subsets with diverse homing characteristics.

Hantavirus infection in the Republic of Georgia.

We describe a laboratory-confirmed case of hantavirus infection in the Republic of Georgia. Limited information is available about hantavirus infections in the Caucasus, although the infection has been reported throughout Europe and Russia. Increasing awareness and active disease surveillance contribute to our improved understanding of the geographic range of this pathogen.

Live Vaccine Strain Francisella tularensis Is Detectable at the Inoculation Site but Not in Blood after Vaccination against Tularemia

INTRODUCTION Live vaccine strain (LVS) Francisella tularensis is a live, attenuated investigational tularemia vaccine that has been used by the US Army for decades to protect laboratory workers. Postvaccination bacterial kinetic characteristics of LVS at the inoculation site and in the blood are unknown and, therefore, were assessed in a prospective study. LVS vaccination of laboratory workers provided the opportunity to compare culture with polymerase chain reaction (PCR) for the detection of F. tularensis in human clinical samples. METHODS Blood and skin swab samples were prospectively collected from volunteers who received the LVS tularemia vaccine at baseline (negative controls) and at 5 specified time points (days 1, 2, 7 or 8, 14 or 15, and 35 after vaccination). Bacterial culture and PCR of whole blood samples (17 volunteers) and inoculation site swabs (41 volunteers) were performed. RESULTS The culture and PCR results of all blood samples were negative. Results of real-time PCR from the inoculation site samples were positive for 41 (100%) of 41 volunteers on day 1, for 40 (97.6%) of 41 volunteers on day 2, for 24 (58.5%) of 41 on day 7 or 8, for 6 (16.7%) of 36 on day 14 or 15, and for 0 (0%) of 9 on day 35. Positive results of bacterial cultures of the inoculation site samples occurred significantly less frequently, compared with PCR testing, with 4 (9.8%) of 41 volunteers having positive results on day 1 (P<.001) and 4 (9.8%) of 41 on day 2 (P<.001); all results from subsequent days were negative. CONCLUSIONS F. tularensis LVS genomic DNA was detected in the majority of samples from the inoculation site up to 1 week after LVS vaccination, with real-time PCR being more sensitive than culture. Our data suggest that bacteremia does not occur after LVS vaccination in normal, healthy human volunteers.

Expansion of brucellosis detection in the country of Georgia by screening household members of cases and neighboring community members

BackgroundBrucellosis is considered as endemic zoonotic disease in the country of Georgia. However, the burden of the disease on a household level is not known. Therefore, this study sought to determine the benefits of active surveillance coupled to serological screening for the early detection of brucellosis among close contacts of brucellosis cases.MethodsWe used an active surveillance approach to estimate the rate of seropositivity among household family members and neighboring community members of brucellosis index cases. All participants were screened using the serum tube agglutination test (SAT). Blood cultures were performed, obtained isolates were identified by a bacteriological algorithm, and confirmed as Brucella spp. using real-time PCR. Further confirmation of Brucella species was done using the AMOS PCR assay.ResultsA total of 141 participants enrolled. Of these, 27 were brucellosis index cases, 86 were household family members, and 28 were neighboring community members. The serological evidence of brucellosis in the household member group was 7% and the rate at the household level was 21%. No screened community members were Brucella seropositive. Majority of brucellosis cases were caused by B. melitensis; only one index case was linked to B. abortus.ConclusionWe found evidence of brucellosis infection among household family members of brucellosis index cases. B. melitensis was the most common species obtained. Findings of this active surveillance study highlight the importance of screening household family members of brucellosis cases and of the use of culture methods to identify Brucella species in the country of Georgia.