Crimean-Congo Hemorrhagic fever (CCHF) is an important zoonotic disease transmitted to humans both by tick vectors and contact with fluids from an infected animal or human. Although animals are not symptomatic when infected, they are the main source of human infection. Uganda has reported sporadic human outbreaks of CCHF in various parts of the country since 2013. We designed a nationwide epidemiological study to investigate the burden of CCHF in livestock. A total of 3181 animals were sampled; 1732 cattle (54.4%), 1091 goats (34.3%), and 358 sheep (11.3%) resulting in overall livestock seropositivity of IgG antibodies against CCHF virus (CCHFV) of 31.4% (999/3181). Seropositivity in cattle was 16.9% and in sheep and goats was 48.8%. Adult and juvenile animals had higher seropositivity compared to recently born animals, and seropositivity was higher in female animals (33.5%) compared to male animals (24.1%). Local breeds had higher (36.8%) compared to exotic (2.8%) and cross breeds (19.3%). Animals that had a history of abortion or stillbirth had higher seropositivity compared to those without a history of abortion or stillbirth. CCHFV seropositivity appeared to be generally higher in northern districts of the country, though spatial trends among sampled districts were not examined. A multivariate regression analysis using a generalized linear mixed model showed that animal species, age, sex, region, and elevation were all significantly associated with CCHFV seropositivity after adjusting for the effects of other model predictors. This study shows that CCHFV is actively circulating in Uganda, posing a serious risk for human infection. The results from this study can be used to help target surveillance efforts for early case detection in animals and limit subsequent spillover into humans.

In 2016, an outbreak of Rift Valley fever was reported in the Kabale District in Uganda for the first time in 48 years. Three human cases were confirmed by polymerase chain reaction, and subsequent serological investigations revealed an overall IgG seropositivity of 13% in humans and 13% in animals. In response to this reemergence, we designed a countrywide survey to determine the seropositivity of anti-Rift Valley fever virus (RVFV) IgG antibodies in livestock. Samples were collected from 27 districts and tested for RVFV anti-IgG antibodies. A total of 3,181 livestock samples were tested, of which 54.4% were cattle (1,732 of 3,181), 34.3% were goats (1,091 of 3,181), and 11.3% were sheep (358 of 3,181). Overall RVFV seropositivity was 6.9% (221 of 3,181). Seroprevalence was greater in cattle (10.7%) compared with goats (2.6%) and sheep (2.0%), among females (7.5%) compared with males (5.2%), and among adults (7.6%) compared with juveniles (4.9%) and nurslings (6.4%). Exotic breeds and animals with a history of abortion or stillbirth also had greater odds of RVFV seropositivity. Animals grazed under tethering and paddocking had greater RVFV seropositivity compared with animals that grazed communally, and livestock in the western and eastern regions had the greatest seroprevalence. In a multivariate regression model, animal species (odds ratio [OR], 6.4; 95% CI, 3.5-11.4) and age (OR, 2.3; 95% CI, 1.4-3.6) were associated significantly with RVFV seropositivity. This study could be important in developing risk-based surveillance for early outbreak detection to limit the spread of RVFV in both human and animal populations.

Importance Reported cases of SARS-CoV-2 infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected.Objective To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the United States.Design Serologic testing of convenience samples using residual sera obtained for routine clinical testing by two commercial laboratory companies.Setting Connecticut (CT), south Florida (FL), Missouri (MO), New York City metro region (NYC), Utah (UT), and Washington State’s (WA) Puget Sound region.Participants Persons of all ages with serum collected during intervals from March 23 through May 3, 2020.Exposure SARS-CoV-2 virus infection.Main outcomes and measures We estimated the presence of antibodies to SARS-CoV-2 spike protein using an ELISA assay. We standardized estimates to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). We estimated the number of infections in each site by extrapolating seroprevalence to site populations. We compared estimated infections to number of reported COVID-19 cases as of last specimen collection date.Results We tested sera from 11,933 persons. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein ranged from 1.13% (95% confidence interval [CI] 0.70-1.94) in WA to 6.93% (95% CI 5.02-8.92) in NYC (collected March 23-April 1). For sites with later collection dates, estimates ranged from 1.85% (95% CI 1.00-3.23, collected April 6-10) for FL to 4.94% (95% CI 3.61-6.52) for CT (April 26-May 3). The estimated number of infections ranged from 6 to 24 times the number of reported cases in each site.Conclusions and relevance Our seroprevalence estimates suggest that for five of six U.S. sites, from late March to early May 2020, >10 times more SARS-CoV-2 infections occurred than the number of reported cases. Seroprevalence and under-ascertainment varied by site and specimen collection period. Most specimens from each site had no evidence of antibody to SARS-CoV-2. Tracking population seroprevalence serially, in a variety of specific geographic sites, will inform models of transmission dynamics and guide future community-wide public health measures.Question What proportion of persons in six U.S. sites had detectable antibodies to SARS-CoV-2, March 23-May 3, 2020?Findings We tested 11,933 residual clinical specimens. We estimate that from 1.1% of persons in the Puget Sound to 6.9% in New York City (collected March 23-April 1) had detectable antibodies. Estimates ranged from 1.9% in south Florida to 4.9% in Connecticut with specimens collected during intervals from April 6-May 3. Six to 24 times more infections were estimated per site with seroprevalence than with case report data.Meaning For most sites, evidence suggests >10 times more SARS-CoV-2 infections occurred than reported cases. Most persons in each site likely had no detectable SARS-CoV-2 antibodies.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was funded by the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This protocol underwent review by CDC human subjects research officials, who determined that the testing represented non-research activity in the setting of a public health response to the COVID-19 pandemic.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any su h study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesA limited dataset will be made publicly available at a later time.

Spillovers of Nipah virus (NiV) from Pteropus bats to humans occurs frequently in Bangladesh, but the risk for spillover into other animals is poorly understood. We detected NiV antibodies in cattle, dogs, and cats from 6 sites where spillover human NiV infection cases occurred during 2013-2015.

BACKGROUND: Long-term persistence of Ebola virus (EBOV) in immunologically-privileged sites has been implicated in recent outbreaks of Ebola Virus Disease (EVD) in Guinea and the Democratic Republic of Congo. This study was designed to understand how the acute course of EVD, convalescence, and host immune and genetic factors may play a role in prolonged viral persistence in semen. METHODS: A cohort of 131 male EVD survivors in Liberia were enrolled in a case-case study. "Early clearers" were defined as those with two consecutive negative EBOV semen tests by real-time reverse transcriptase polymerase chain reaction (rRT-PCR) at least two weeks apart within 1 year after discharge from the Ebola Treatment Unit (ETU) or acute EVD. "Late clearers" had detectable EBOV RNA by rRT-PCR over one year following ETU discharge or acute EVD. Retrospective histories of their EVD clinical course were collected by questionnaire, followed by complete physical exams and blood work. RESULTS: Compared to early clearers, late clearers were older (median 42.5 years, p = 0.0001) and experienced fewer severe clinical symptoms (median 2, p = 0.006). Late clearers had more lens opacifications (OR 3.9, 95%CI 1.1-13.3, p = 0.03), after accounting for age, higher total serum IgG3 titers (p = 0.007) and increased expression of the HLA-C*03:04 allele (OR 0.14, 95% CI 0.02-0.70, p = 0.007). CONCLUSIONS: Older age, decreased illness severity, elevated total serum IgG3 and HLA-C*03:04 allele expression may be risk factors for the persistence of EBOV in the semen of EVD survivors. EBOV persistence in semen may also be associated with its persistence in other immunologically protected sites, such as the eye.

INTRODUCTION: Ebola virus (EBOV), species Zaire ebolavirus, may persist in the semen of male survivors of Ebola Virus Disease (EVD). We conducted a study of male survivors of the 2014-2016 EVD outbreak in Liberia and evaluated their immune responses to EBOV. We report here findings from the serologic testing of blood for EBOV-specific antibodies, molecular testing for EBOV in blood and semen, and serologic testing of peripheral blood mononuclear cells (PBMCs) in a subset of study participants. METHODS: We tested for EBOV RNA in blood by qRT-PCR, and for anti-EBOV-specific IgM and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) for 126 study participants. We performed peripheral blood mononuclear cell (PBMC) analysis on a subgroup of 26 IgG-negative participants. RESULTS: All 126 participants tested negative for EBOV RNA in blood by qRT-PCR. The blood of 26 participants tested negative for EBOV-specific IgG antibodies by ELISA. PBMCs were collected from 23/26 EBOV IgG-negative participants. Of these, 1/23 participants had PBMCs which produced anti-EBOV-specific IgG antibodies upon stimulation with EBOV-specific GP and NP antigens. DISCUSSION: The blood of EVD survivors, collected when they did not have symptoms meeting the case definition for acute or relapsed EVD, is unlikely to pose a risk for EBOV transmission. We identified one IgM/IgG negative participant who had PBMCs which produced anti-EBOV-specific antibodies upon stimulation. Immunogenicity following acute EBOV infection may exist along a spectrum and absence of antibody response should not be exclusionary in determining an individual's status as a survivor of EVD.

IMPORTANCE: Reported cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected. OBJECTIVE: To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the US. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study performed serologic testing on a convenience sample of residual sera obtained from persons of all ages. The serum was collected from March 23 through May 12, 2020, for routine clinical testing by 2 commercial laboratory companies. Sites of collection were San Francisco Bay area, California; Connecticut; south Florida; Louisiana; Minneapolis-St Paul-St Cloud metro area, Minnesota; Missouri; New York City metro area, New York; Philadelphia metro area, Pennsylvania; Utah; and western Washington State. EXPOSURES: Infection with SARS-CoV-2. MAIN OUTCOMES AND MEASURES: The presence of antibodies to SARS-CoV-2 spike protein was estimated using an enzyme-linked immunosorbent assay, and estimates were standardized to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). The number of infections in each site was estimated by extrapolating seroprevalence to site populations; estimated infections were compared with the number of reported coronavirus disease 2019 (COVID-19) cases as of last specimen collection date. RESULTS: Serum samples were tested from 16 025 persons, 8853 (55.2%) of whom were women; 1205 (7.5%) were 18 years or younger and 5845 (36.2%) were 65 years or older. Most specimens from each site had no evidence of antibodies to SARS-CoV-2. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein antibodies ranged from 1.0% in the San Francisco Bay area (collected April 23-27) to 6.9% of persons in New York City (collected March 23-April 1). The estimated number of infections ranged from 6 to 24 times the number of reported cases; for 7 sites (Connecticut, Florida, Louisiana, Missouri, New York City metro area, Utah, and western Washington State), an estimated greater than 10 times more SARS-CoV-2 infections occurred than the number of reported cases. CONCLUSIONS AND RELEVANCE: During March to early May 2020, most persons in 10 diverse geographic sites in the US had not been infected with SARS-CoV-2 virus. The estimated number of infections, however, was much greater than the number of reported cases in all sites. The findings may reflect the number of persons who had mild or no illness or who did not seek medical care or undergo testing but who still may have contributed to ongoing virus transmission in the population.

In January 2018, a woman admitted to a Delaware hospital tested positive for New World hantavirus immunoglobulin M (IgM) and immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA). Subsequent testing by CDC’s Viral Special Pathogens Branch detected New World hantavirus by nested reverse transcription–polymerase chain reaction (RT-PCR) and Andes virus by nucleic acid sequencing. This case represents the first confirmed importation of Andes virus infection into the United States; two imported cases have also been reported in Switzerland (1). Before her illness, the patient had traveled to the Andes region of Argentina and Chile from December 20, 2017, to January 3, 2018. She stayed in cabins and youth hostels in reportedly poor condition. No rodent exposures were reported. After returning to the United States on January 10, she developed fever, malaise, and myalgias on January 14. On January 17, while ill, she traveled on two commercial domestic flights. She was hospitalized during January 20–25 in Delaware and discharged to her home after clinical recovery.

Heat stress, an environmental and occupational hazard, is associated with a spectrum of heat-related illnesses, including heat stroke, which can lead to death. CDC's National Institute for Occupational Safety and Health (NIOSH) publishes recommended occupational exposure limits for heat stress (1). These limits, which are consistent with those of the American Conference of Governmental Industrial Hygienists (ACGIH) (2), specify the maximum combination of environmental heat (measured as wet bulb globe temperature [WBGT]) and metabolic heat (i.e., workload) to which workers should be exposed. Exposure limits are lower for workers who are unacclimatized to heat, who wear work clothing that inhibits heat dissipation, and who have predisposing personal risk factors (1,2). These limits have been validated in experimental settings but not at outdoor worksites. To determine whether the NIOSH and ACGIH exposure limits are protective of workers, CDC retrospectively reviewed 25 outdoor occupational heat-related illnesses (14 fatal and 11 nonfatal) investigated by the Occupational Safety and Health Administration (OSHA) from 2011 to 2016. For each incident, OSHA assessed personal risk factors and estimated WBGT, workload, and acclimatization status. Heat stress exceeded exposure limits in all 14 fatalities and in eight of 11 nonfatal illnesses. An analysis of Heat Index data for the same 25 cases suggests that when WBGT is unavailable, a Heat Index screening threshold of 85 degrees F (29.4 degrees C) could identify potentially hazardous levels of workplace environmental heat. Protective measures should be implemented whenever the exposure limits are exceeded. The comprehensive heat-related illness prevention program should include an acclimatization schedule for newly hired workers and unacclimatized long-term workers (e.g., during early-season heat waves), training for workers and supervisors about symptom recognition and first aid (e.g., aggressive cooling of presumed heat stroke victims before medical professionals arrive), engineering and administrative controls to reduce heat stress, medical surveillance, and provision of fluids and shady areas for rest breaks.

Nipah virus (NiV) is a paramyxovirus, and Pteropus spp. bats are the natural reservoir. From December 2010 through March 2014, hospital-based encephalitis surveillance in Bangladesh identified 18 clusters of NiV infection. The source of infection for case-patients in 3 clusters in 2 districts was unknown. A team of epidemiologists and anthropologists investigated these 3 clusters comprising 14 case-patients, 8 of whom died. Among the 14 case-patients, 8 drank fermented date palm sap (tari) regularly before their illness, and 6 provided care to a person infected with NiV. The process of preparing date palm trees for tari production was similar to the process of collecting date palm sap for fresh consumption. Bat excreta was reportedly found inside pots used to make tari. These findings suggest that drinking tari is a potential pathway of NiV transmission. Interventions that prevent bat access to date palm sap might prevent tari-associated NiV infection.

Marburg virus (family Filoviridae) causes sporadic outbreaks of severe hemorrhagic disease in sub-Saharan Africa. Bats have been implicated as likely natural reservoir hosts based most recently on an investigation of cases among miners infected in 2007 at the Kitaka mine, Uganda, which contained a large population of Marburg virus-infected Rousettus aegyptiacus fruit bats. Described here is an ecologic investigation of Python Cave, Uganda, where an American and a Dutch tourist acquired Marburg virus infection in December 2007 and July 2008. More than 40,000 R. aegyptiacus were found in the cave and were the sole bat species present. Between August 2008 and November 2009, 1,622 bats were captured and tested for Marburg virus. Q-RT-PCR analysis of bat liver/spleen tissues indicated approximately 2.5% of the bats were actively infected, seven of which yielded Marburg virus isolates. Moreover, Q-RT-PCR-positive lung, kidney, colon and reproductive tissues were found, consistent with potential for oral, urine, fecal or sexual transmission. The combined data for R. aegyptiacus tested from Python Cave and Kitaka mine indicate low level horizontal transmission throughout the year. However, Q-RT-PCR data show distinct pulses of virus infection in older juvenile bats ( approximately six months of age) that temporarily coincide with the peak twice-yearly birthing seasons. Retrospective analysis of historical human infections suspected to have been the result of discrete spillover events directly from nature found 83% (54/65) events occurred during these seasonal pulses in virus circulation, perhaps demonstrating periods of increased risk of human infection. The discovery of two tags at Python Cave from bats marked at Kitaka mine, together with the close genetic linkages evident between viruses detected in geographically distant locations, are consistent with R. aegyptiacus bats existing as a large meta-population with associated virus circulation over broad geographic ranges. These findings provide a basis for developing Marburg hemorrhagic fever risk reduction strategies.

The first known Ebola hemorrhagic fever (EHF) outbreak caused by Bundibugyo Ebola virus occurred in Bundibugyo District, Uganda, in 2007. Fifty-six cases of EHF were laboratory confirmed. Although signs and symptoms were largely nonspecific and similar to those of EHF outbreaks caused by Zaire and Sudan Ebola viruses, proportion of deaths among those infected was lower ( approximately 40%).

In July and September 2007, miners working in Kitaka Cave, Uganda, were diagnosed with Marburg hemorrhagic fever. The likely source of infection in the cave was Egyptian fruit bats (Rousettus aegyptiacus) based on detection of Marburg virus RNA in 31/611 (5.1%) bats, virus-specific antibody in bat sera, and isolation of genetically diverse virus from bat tissues. The virus isolates were collected nine months apart, demonstrating long-term virus circulation. The bat colony was estimated to be over 100,000 animals using mark and re-capture methods, predicting the presence of over 5,000 virus-infected bats. The genetically diverse virus genome sequences from bats and miners closely matched. These data indicate common Egyptian fruit bats can represent a major natural reservoir and source of Marburg virus with potential for spillover into humans.