Clinical Manifestations of an Outbreak of Monkeypox Virus in Captive Chimpanzees in Cameroon, 2016.

Monkeypox virus (MPXV) is a reemerging virus of global concern. An outbreak of clade I MPXV affected 20 captive chimpanzees in Cameroon in 2016. We describe the epidemiology, virology, phylogenetics, and clinical progression of this outbreak. Clinical signs included exanthema, facial swelling, perilaryngeal swelling, and eschar. Mpox can be lethal in captive chimpanzees, with death likely resulting from respiratory complications. We advise avoiding anesthesia in animals with respiratory signs to reduce the likelihood of death. This outbreak presented a risk to animal care staff. There is a need for increased awareness and a One Health approach to preparation for outbreaks in wildlife rescue centers in primate range states where MPXV occurs. Control measures should include quarantining affected animals, limiting human contacts, surveillance of humans and animals, use of personal protective equipment, and regular decontamination of enclosures.

Outbreak of Mycobacterium orygis in a Shipment of Cynomolgus Macaques Imported from Southeast Asia - United States, February-May 2023.

Nonhuman primates (NHP) can become infected with the same species of Mycobacteria that cause human tuberculosis. All NHP imported into the United States are quarantined and screened for tuberculosis; no confirmed cases of tuberculosis were diagnosed among NHP during CDC-mandated quarantine during 2013-2020. In February 2023, an outbreak of tuberculosis caused by Mycobacterium orygis was detected in a group of 540 cynomolgus macaques (Macaca fascicularis) imported to the United States from Southeast Asia for research purposes. Although the initial exposure to M. orygis is believed to have occurred before the macaques arrived in the United States, infected macaques were first detected during CDC-mandated quarantine. CDC collaborated with the importer and U.S. Department of Agriculture's National Veterinary Services Laboratories in the investigation and public health response. A total of 26 macaques received positive test results for M. orygis by culture, but rigorous occupational safety protocols implemented during transport and at the quarantine facility prevented cases among caretakers in the United States. Although the zoonotic disease risk to the general population remains low, this outbreak underscores the importance of CDC's regulatory oversight of NHP importation and adherence to established biosafety protocols to protect the health of the United States research animal population and the persons who interact with them.

Review of CDC's Suspension of and Advance Written Approval Process for Dogs Entering the United States from Egypt - May 2019-December 2020.

Dog-maintained rabies virus variant (DMRVV) was eliminated in the United States in 2007. During 2015­2019, three dogs with rabies were imported into the United States from Egypt, where DMRVV is endemic. CDC developed a risk mitigation strategy, in consultation with a diverse group of subject matter experts, that permitted 296 dogs to be imported from Egypt during May 10, 2019­December 31, 2020, minimizing the risk for future rabid dog importations. The broadly vetted risk mitigation strategy, which included serologic testing for rabies antibody titer, improved CDC's ability to ensure that imported dogs from Egypt posed no public health risk in the United States. This strategy could be used to guide future policy decisions regarding dog importations.

Rabies in a Dog Imported from Azerbaijan - Pennsylvania, 2021.

On June 16, 2021, rabies virus infection was confirmed in a dog included in a shipment of rescue animals imported into the United States from Azerbaijan. A multistate investigation was conducted to prevent secondary rabies cases, avoid reintroduction of a dog-maintained rabies virus variant (DMRVV), identify persons who might have been exposed and would be recommended to receive rabies postexposure prophylaxis, and investigate the cause of importation control failures. Results of a prospective serologic monitoring (PSM) protocol suggested that seven of 32 (22%) animals from the same shipment as the dog with confirmed rabies virus infection and who had available titer results after rabies vaccine booster had not been adequately vaccinated against rabies before importation. A requirement for rabies vaccination certificates alone will not adequately identify improper vaccination practices or fraudulent paperwork and are insufficient as a stand-alone rabies importation prevention measure. Serologic titers before importation would mitigate the risk for importing DMRVV.

Public Health Actions to Control Measles Among Afghan Evacuees During Operation Allies Welcome - United States, September-November 2021.

On August 29, 2021, the United States government oversaw the emergent establishment of Operation Allies Welcome (OAW), led by the U.S. Department of Homeland Security (DHS) and implemented by the U.S. Department of Defense (DoD) and U.S. Department of State (DoS), to safely resettle U.S. citizens and Afghan nationals from Afghanistan to the United States. Evacuees were temporarily housed at several overseas locations in Europe and Asia* before being transported via military and charter flights through two U.S. international airports, and onward to eight U.S. military bases,† with hotel A used for isolation and quarantine of persons with or exposed to certain infectious diseases.§ On August 30, CDC issued an Epi-X notice encouraging public health officials to maintain vigilance for measles among Afghan evacuees because of an ongoing measles outbreak in Afghanistan (25,988 clinical cases reported nationwide during January-November 2021) (1) and low routine measles vaccination coverage (66% and 43% for the first and second doses, respectively, in 2020) (2).

Vital Signs: Trends in Human Rabies Deaths and Exposures - United States, 1938-2018.

INTRODUCTION: Each year, rabies causes approximately 59,000 deaths worldwide, including approximately two deaths in the United States. Before 1960, dogs were a common reservoir of rabies in the United States; however, increasingly, species of wildlife (e.g., bats, raccoons) are the main reservoirs. This report characterizes human rabies deaths, summarizes trends in rabies mortality, and highlights current rabies risks in the United States. METHODS: Rabies trends in the United States during 1938-2018 were analyzed using national rabies surveillance data. Data from the Healthcare Cost and Utilization Project for 2006-2014 were used to estimate the number of postexposure prophylaxis (PEP) visits per 100,000 persons during 2017-2018. The Centers for Medicare & Medicaid Services' average sales price data were used to estimate PEP costs. RESULTS: From 1960 to 2018, a total of 125 human rabies cases were reported in the United States; 36 (28%) were attributed to dog bites during international travel. Among the 89 infections acquired in the United States, 62 (70%) were attributed to bats. In 2018, approximately 55,000 persons sought PEP after contact with a potentially rabid animal. CONCLUSIONS AND COMMENTS: In the United States, wildlife rabies, especially in bats, continues to pose a risk to humans. Travelers also might be exposed to canine rabies in countries where the disease is still present; increased awareness of rabies while traveling abroad is needed. Vaccinating pets, avoiding contact with wildlife, and seeking medical care if one is bitten or scratched by an animal are the most effective ways to prevent rabies. Understanding the need for timely administration of PEP to prevent death is critical.

Rabies Vaccine Hesitancy and Deaths Among Pregnant and Breastfeeding Women - Vietnam, 2015-2016.

Human rabies deaths are preventable through prompt administration of postexposure prophylaxis (PEP) with rabies immune globulin and rabies vaccine after exposure to a rabid animal (1); there are no known contraindications to receiving PEP (1,2). Despite widespread availability of PEP in Vietnam, in 2015 the Ministry of Health (MoH) received reports of pregnant and breastfeeding women with clinically diagnosed rabies. MoH investigated factors associated with these rabies cases. MoH found that, during 2015-2016, among 169 cases reported in Vietnam, two probable cases of rabies were reported in breastfeeding mothers and four in pregnant women, all of whom had been bitten by dogs. All six patients died. Three of the four pregnant women had cesarean deliveries. One of the three newborns died from complications believed to be unrelated to rabies; the fourth pregnant woman contracted rabies too early in pregnancy for the fetus to be viable. Two of the patients sought care from a medical provider or traditional healer; however, none sought PEP after being bitten. In each case, families reported the patient's fear of risk to the fetus or breastfed child as the primary barrier to receiving PEP. These findings highlight the need for public health messaging about the safety and effectiveness of PEP in preventing rabies among all persons with exposures, including pregnant and breastfeeding women.

Notes from the Field: Assessment of Health Facilities for Control of Canine Rabies - Gondar City, Amhara Region, Ethiopia, 2015.

Rabies is an encephalitic disease that is nearly always fatal after onset of illness. Worldwide, rabies kills an estimated 59,000 humans each year (95% confidence interval [CI] = 25,000-159,000); the majority of the deaths are caused by the rabies virus variant that circulates in dogs (1,2). Canine rabies is endemic in Ethiopia, with an estimated 2,771 human deaths annually (CI = 1,116-12,660) (1-3). Annual rabies-associated livestock losses are estimated at >$50 million (USD), making rabies important to both human and animal health (1).

Q Fever Outbreak Among Travelers to Germany Who Received Live Cell Therapy--United States and Canada, 2014.

During September­November 2014, the New York State Department of Health (NYSDOH) was notified of five New York state residents who had tested seropositive for Coxiella burnetii, the causative agent of Q fever. All five patients had symptoms compatible with Q fever (e.g., fever, fatigue, chills, and headache) and a history of travel to Germany to receive a medical treatment called "live cell therapy" (sometimes called "fresh cell therapy") in May 2014. Live cell therapy is the practice of injecting processed cells from organs or fetuses of nonhuman animals (e.g., sheep) into human recipients. It is advertised to treat a variety of health conditions. This practice is unavailable in the United States; however, persons can travel to foreign locations to receive injections. Local health departments interviewed the patients, and NYSDOH notified CDC and posted a report on CDC's Epidemic Information Exchange to solicit additional cases. Clinical and exposure information for each patient was reported to the Robert Koch Institute in Germany, which forwarded the information to local health authorities. A Canada resident who also received live cell therapy in May 2014 was diagnosed with Q fever in July 2014. Clinicians should be aware of health risks, such as Q fever and other zoonotic diseases, among patients with a history of receiving treatment with live cell therapy products.

Dogs on the move: Estimating the risk of rabies in imported dogs in the United States, 2015-2022.

BACKGROUND: Dog-mediated rabies virus variant (DMRVV), a zoonotic pathogen that causes a deadly disease in animals and humans, is present in more than 100 countries worldwide but has been eliminated from the United States since 2007. In the United States, the U.S. Centers for Disease Control and Prevention has recorded four instances of rabies in dogs imported from DMRVV-enzootic countries since 2015. However, it remains uncertain whether the incidence of DMRVV among imported dogs from these countries significantly surpasses that of domestically acquired variants among domestic U.S. dogs. AIM: This evaluation aimed to estimate the number of dogs imported from DMRVV-enzootic countries and compare the risk of rabies between imported dogs and the U.S. domestic dog population. MATERIALS AND METHODS: Data from the CDC's dog import permit system (implemented during 2021 under a temporary suspension of dog importation from DMRVV-enzootic countries) and U.S. Customs and Border Protection's Automated Commercial Environment system, each of which records a segment of dogs entering the U.S. from DMRVV-enzootic countries, was analysed. Additionally, we estimated the incidence rate of rabies in dogs imported from DMRVV-enzootic countries and compared it to the incidence rate within the general U.S. dog population, due to domestically acquired rabies variants, over the eight-year period (2015-2022). RESULTS: An estimated 72,589 (range, 62,660-86,258) dogs were imported into the United States annually between 2015 and 2022 from DMRVV-enzootic countries. The estimated incidence rate of rabies was 16 times higher (range, 13.2-19.4) in dogs imported from DMRVV-enzootic countries than that estimated for domestically acquired rabies in the general U.S. dog population. CONCLUSIONS: Preventing human exposure to dogs with DMRVV is a public health priority. The higher risk of rabies in dogs imported from DMRVV-enzootic countries supports the need for importation requirements aimed at preventing the reintroduction of DMRVV into the United States.

Human exposures to Brucella canis from a pregnant dog during an international flight: Public health risks, diagnostic challenges and future considerations.

AIMS: This report documents the exposure of passengers and crew of a commercial international flight to the zoonotic pathogen Brucella canis after an infected dog aborted in the passenger cabin of the aircraft. This case demonstrates the challenges associated with brucellosis screening and the risks that airline personnel, airport employees and travellers face when animals with unrecognized zoonotic infections are transported. METHODS/RESULTS: The public health investigation of this case was conducted by the Centers for Disease Control, the Illinois Department of Health and the Illinois Department of Agriculture, in collaboration with a local veterinary clinic and several academic and federal diagnostic laboratories. It included an extensive diagnostic evaluation of the dam and aborted foetuses to confirm a diagnosis of canine brucellosis. Passengers, airline personnel and staff from the veterinary clinic where the dogs were treated underwent risk assessments, and clinic staff also received detailed guidance regarding infection prevention practices. CONCLUSIONS: Animal shelters and breeding programs are recommended to screen dogs routinely for brucellosis, but it is not unusual for domestic or imported animals to have unknown health histories, including the dog's brucellosis status, at the time of purchase, adoption, or re-homing. Testing recommendations and requirements vary by state, making it challenging for state public health and animal health agencies to monitor and respond appropriately. This case highlights the importance of Brucella spp. screening in sexually intact dogs prior to breeding, purchase, or domestic or international transportation of the dogs. The transportation of pregnant dogs may present a previously unrecognized public health threat in addition to contributing to unnecessary stress and health risks for pregnant animals.

Comparing the genetic typing methods for effective surveillance and rabies control in Georgia.

A full nucleoprotein gene sequencing of 68 isolates collected from passive rabies surveillance system in Georgia between 2015 and 2016 identified two distinct dog rabies phylogroups, GEO_V1 and GEO_V2, which both belonged to the cosmopolitan dog clade. GEO_V1 was found throughout the country and was further divided into four sub-phylogroups that overlapped geographically; GEO_V2 was found in the southeast region and was closely related to dog rabies in Azerbaijan. A sequence analysis of the full N gene, partial nucleoprotein gene of N-terminal and C-terminal, and the amplicon sequences of pan-lyssavirus RT-qPCR LN34 showed that all four sequencing approaches provided clear genetic typing results of canine rabies and could further differentiate GEO_V1 and GEO_V2. The phylogenetic analysis results vary and were affected by the length of the sequences used. Amplicon sequencing of the LN34 assay positive samples provided a rapid and cost-effective method for rabies genetic typing, which is important for improving rabies surveillance and canine rabies eradication globally.

Measles virus transmission patterns and public health responses during Operation Allies Welcome: a descriptive epidemiological study.

BACKGROUND: On Aug 29, 2021, Operation Allies Welcome (OAW) was established to support the resettlement of more than 80 000 Afghan evacuees in the USA. After identification of measles among evacuees, incoming evacuee flights were temporarily paused, and mass measles vaccination of evacuees aged 6 months or older was introduced domestically and overseas, with a 21-day quarantine period after vaccination. We aimed to evaluate patterns of measles virus transmission during this outbreak and the impact of control measures. METHODS: We conducted a measles outbreak investigation among Afghan evacuees who were resettled in the USA as part of OAW. Patients with measles were defined as individuals with an acute febrile rash illness between Aug 29, 2021, and Nov 26, 2021, and either laboratory confirmation of infection or epidemiological link to a patient with measles with laboratory confirmation. We analysed the demographics and clinical characteristics of patients with measles and used epidemiological information and whole-genome sequencing to track transmission pathways. A transmission model was used to evaluate the effects of vaccination and other interventions. FINDINGS: 47 people with measles (attack rate: 0·65 per 1000 evacuees) were reported in six US locations housing evacuees in four states. The median age of patients was 1 year (range 0-26); 33 (70%) were younger than 5 years. The age distribution shifted during the outbreak towards infants younger than 12 months. 20 (43%) patients with wild-type measles virus had rash onset after vaccination. No fatalities or community spread were identified, nor further importations after flight resumption. In a non-intervention scenario, transmission models estimated that a median of 5506 cases (IQR 10-5626) could have occurred. Infection clusters based on epidemiological criteria could be delineated into smaller clusters using phylogenetic analyses; however, sequences with few substitution count differences did not always indicate single lines of transmission. INTERPRETATION: Implementation of control measures limited measles transmission during OAW. Our findings highlight the importance of integration between epidemiological and genetic information in discerning between individual lines of transmission in an elimination setting. FUNDING: US Centers for Disease Control and Prevention.

Risk factors for death and illness in dogs imported into the United States, 2010-2018.

CDC estimates 1 million dogs are imported into the United States annually. With the movement of large numbers of animals into the United States the risk of disease importation, especially emerging diseases, and animal welfare issues are of concern. Dogs that arrive to the United States ill or dead are investigated by public health authorities to ensure dogs are not infected with diseases of concern (such as rabies). We identified factors associated with illness and death in imported dogs and estimated the initial investigation cost to public health authorities. Dog importation data from the CDC's Quarantine Activity Reporting System were reviewed from 2010 to 2018. The date of entry, country of origin, port of entry, transportation method and breed were extracted to examine factors associated with illness and death in dogs during international travel. Costs for public health investigations were estimated from data collected by the Bureau of Labor Statistics and Office of Personal Management. Death or illness was more likely to occur in brachycephalic breeds (aOR = 3.88, 95%CI 2.74-5.51). Transportation of dogs via cargo (aOR = 2.41, 95%CI 1.57-3.70) or as checked baggage (aOR = 5.74, 95%CI 3.65-9.03) were also associated with death or illness. On average, 19 dog illnesses or deaths were reported annually from 2010 to 2018. The estimated annual cost to public health authorities to conduct initial public health assessments ranged from $2,071 to $104,648. Current regulations do not provide adequate resources or mechanisms to monitor the rates of morbidity and mortality of imported dogs. There are growing attempts to assess animal welfare and communicable disease importation risks. However, because the responsibility for dogs' health and wellbeing is overseen by multiple agencies it is challenging to coordinate implementation and enforcement measures. A joint federal agency approach to identify interventions that reduce dog morbidity and mortality during flights while continuing to protect US borders from public health and foreign animal disease threats could be beneficial.

Roles of traditional medicine and traditional healers for rabies prevention and potential impacts on post-exposure prophylaxis: A literature review.

INTRODUCTION: Globally, traditional medicine is widely used to treat a variety of injuries and illnesses, including dog bites, and exposures that are risky for rabies. However, efficacy of most traditional remedies used for rabies prevention or treatment has not been demonstrated in controlled trials or proven in community-based surveys. METHODS: Six databases were searched including the terms rabies, traditional treatment, traditional remedy, traditional therapy, traditional medicine, and medicinal treatment to review traditional remedies used in the prevention and treatment of rabies. In addition, published literature of rabies transmission dynamics was used to estimate statistical likelihood of dog bite victims developing rabies to provide clarity as to why traditional healers have a high apparent success rate when preventing death from rabies in victims bitten by suspected rabid dogs. RESULTS: Literature review yielded 50 articles, including three controlled experiments, that described use of traditional remedies for rabies prevention and treatment. Traditional remedies for rabies ranged from plant- or animal-based products to spiritual rituals; however, only a few controlled mice trials were conducted, and none of these trials demonstrated efficacy in preventing or treating rabies. Risk of dying from rabies after a bite from a dog with unknown rabies status is low, 1.90% (0.05%-29.60%). Therefore, traditional healers had a 98.10% (70.40%-99.95%) apparent success rate in preventing death from suspected rabid dog bites despite inefficaciousness of herbal remedies. CONCLUSION: There was no universal plant species or route of administration that was consistently used for rabies prevention or treatment across countries. No traditional remedy was efficacious in the prevention or treatment of rabies in randomized controlled experiments. Understanding the cultural context under which traditional remedies are used may facilitate collaboration of traditional healers with the modern medical system to ensure timely and appropriate use of proven therapies for prevention and clinical management of rabies.

Heterogeneity in dog population characteristics contributes to chronic under-vaccination against rabies in Guatemala.

Guatemala has held dog rabies mass vaccination campaigns countrywide since 1984, yet the virus remains endemic. To eliminate dog-mediated human rabies, dog vaccination coverage must reach at least 70%. The Guatemala rabies program uses a 5:1 human:dog ratio (HDR) to estimate the vaccination coverage; however, this method may not accurately reflect the heterogeneity of dog ownership practices in Guatemalan communities. We conducted 16 field-based dog population estimates in urban, semi-urban and rural areas of Guatemala to determine HDR and evaluate the standard 5:1. Our study-derived HDR estimates varied from 1.7-11.4:1 (average 4.0:1), being higher in densely populated sites and lowest in rural communities. The community-to-community heterogeneity observed in dog populations could explain the persistence of rabies in certain communities. To date, this is the most extensive dog-population evaluation conducted in Guatemala, and can be used to inform future rabies vaccination campaigns needed to meet the global 2030 rabies elimination targets.

A country classification system to inform rabies prevention guidelines and regulations.

BACKGROUND: Assessing the global risk of rabies exposure is a complicated task requiring individual risk assessments, knowledge of rabies epidemiology, surveillance capacity and accessibility of rabies biologics on a national and regional scale. In many parts of the world, availability of this information is limited and when available is often dispersed across multiple sources. This hinders the process of making evidence-based health and policy recommendations to prevent the introduction and spread of rabies. METHODS: CDC conducted a country-by-country qualitative assessment of risk and protective factors for rabies to develop an open-access database of core metrics consisting of the presence of lyssaviruses (specifically canine or wildlife rabies virus variants or other bat lyssaviruses), access to rabies immunoglobulins and vaccines, rabies surveillance capacity and canine rabies control capacity. Using these metrics, we developed separate risk scoring systems to inform rabies prevention guidance for travelers and regulations for the importation of dogs. Both scoring systems assigned higher risk to countries with enzootic rabies (particularly canine rabies), and the risk scoring system for travelers also considered protective factors such as the accessibility of rabies biologics for post-exposure prophylaxis. Cumulative scores were calculated across the assessed metrics to assign a risk value of low, moderate or high. RESULTS: A total of 240 countries, territories and dependencies were assessed, for travelers, 116 were identified as moderate to high risk and 124 were low or no risk; for canine rabies virus variant importation, 111 were identified as high-risk and 129 were low or no risk. CONCLUSIONS: We developed a comprehensive and easily accessible source of information for assessing the rabies risk for individual countries that included a database of rabies risk and protective factors based on enzootic status and availability of biologics, provided a resource that categorizes risk by country and provided guidance based on these risk categories for travelers and importers of dogs into the United States.

Influenza-Like Illness Among Personnel Responding to U.S. Quarantine of Cruise Ship Passengers Exposed to SARS-CoV-2.

OBJECTIVES: Before community transmission of COVID-19 was recognized in the United States, cruise ship passengers with high risk for exposure to SARS-CoV-2 were repatriated and quarantined. We describe cases of influenza-like illness (ILI) among responders. METHODS: We reviewed situation reports and responder illness reports to characterize ill responders, including illness onset date, symptoms, fever, diagnostic tests, potential breaches in PPE use, and return to work status. RESULTS: Among 339 responders, nine (3%) reported ILI. No breaches in PPE were reported. Three responders with ILI were tested for both SARS-CoV-2 infection and influenza A; none tested positive for SARS-CoV-2 infection and two tested positive for influenza A. CONCLUSIONS: Despite an outbreak of ILI among responders, none were diagnosed with COVID-19, suggesting preventive measures in place might have been sufficient to prevent responders from SARS-CoV-2 exposure.