BACKGROUND: On 20 September 2022, Uganda declared its fifth Sudan virus disease (SVD) outbreak, culminating in 142 confirmed and 22 probable cases. The reproductive rate (R) of this outbreak was 1.25. We described persons who were exposed to the virus, became infected, and they led to the infection of an unusually high number of cases during the outbreak. METHODS: In this descriptive cross-sectional study, we defined a super-spreader person (SSP) as any person with real-time polymerase chain reaction (RT-PCR) confirmed SVD linked to the infection of ≥ 13 other persons (10-fold the outbreak R). We reviewed illness narratives for SSPs collected through interviews. Whole-genome sequencing was used to support epidemiologic linkages between cases. RESULTS: Two SSPs (Patient A, a 33-year-old male, and Patient B, a 26-year-old male) were identified, and linked to the infection of one probable and 50 confirmed secondary cases. Both SSPs lived in the same parish and were likely infected by a single ill healthcare worker in early October while receiving healthcare. Both sought treatment at multiple health facilities, but neither was ever isolated at an Ebola Treatment Unit (ETU). In total, 18 secondary cases (17 confirmed, one probable), including three deaths (17%), were linked to Patient A; 33 secondary cases (all confirmed), including 14 (42%) deaths, were linked to Patient B. Secondary cases linked to Patient A included family members, neighbours, and contacts at health facilities, including healthcare workers. Those linked to Patient B included healthcare workers, friends, and family members who interacted with him throughout his illness, prayed over him while he was nearing death, or exhumed his body. Intensive community engagement and awareness-building were initiated based on narratives collected about patients A and B; 49 (96%) of the secondary cases were isolated in an ETU, a median of three days after onset. Only nine tertiary cases were linked to the 51 secondary cases. Sequencing suggested plausible direct transmission from the SSPs to 37 of 39 secondary cases with sequence data. CONCLUSION: Extended time in the community while ill, social interactions, cross-district travel for treatment, and religious practices contributed to SVD super-spreading. Intensive community engagement and awareness may have reduced the number of tertiary infections. Intensive follow-up of contacts of case-patients may help reduce the impact of super-spreading events.

Rabies perpetuates in Nigeria despite initiatives like the Regional Disease Surveillance System Enhancement Project, with evidence indicating suboptimal canine vaccination rates as a contributing factor. To inform effective planning of mass dog vaccination campaigns, it is crucial to understand the factors associated with variation in canine vaccination rates. We conducted a cross-sectional study in 2022 to understand factors associated with canine vaccination. We used stratified random sampling of the streets and dog-owning households to survey 4162 households from three states and the Federal Capital Territory (FCT). We then built a joint probabilistic model to understand factors associated with dog vaccination and non-vaccination. First, we modelled rabies knowledge as a latent variable indirectly measured with several targeted survey questions. This method allowed a respondent's unobserved understanding of rabies to be estimated using their responses to a collection of survey questions that targeted different aspects of rabies epidemiology and took various possible response distributions (i.e., ordinal, categorical, binary). Second, we modelled factors influencing pet owners' decisions to vaccinate their dogs against rabies and barriers to dog vaccination among dog owners whose dogs were not vaccinated against rabies. Posterior distributions revealed that the probability of dog vaccination was positively associated with the owner's latent knowledge of rabies, civil servant service employment, residence in the FCT, ownership of a single dog, providing care to dogs, and a preference for contemporary treatment following a dog bite. Conversely, non-vaccination was positively associated with private employment, residing in Anambra and Enugu states, owning multiple dogs, allowing dogs to search for leftovers, and a preference for traditional treatment after a dog bite. Cost was the primary barrier against vaccination for dog owners in Anambra and Enugu, while mistrust posed a major challenge for those in the FCT. Owners in areas with veterinary establishments cited cost as a barrier, while those without a veterinary establishment cited access as the primary barrier. Our study underscores the need to enhance rabies knowledge, tailor vaccination campaigns to specific demographics, address financial and access barriers, and combat hesitancy to improve rabies vaccination rates in Nigeria. © 2024 The Authors

BACKGROUND: The reported incidence of acute hepatitis C virus (HCV) infection is increasing among persons of childbearing age in the United States. Infants born to pregnant persons with HCV infection are at risk for perinatal HCV acquisition. In 2020, the United States Preventive Services Task Force and Centers for Disease Control and Prevention recommended that all pregnant persons be screened during each pregnancy for hepatitis C. However, there are limited data on trends in hepatitis C testing during pregnancy. OBJECTIVE: We estimated hepatitis C testing rates in a large cohort of patients with Medicaid and commercial insurance who gave birth during 2015-2019 and described demographic and risk-based factors associated with testing. METHODS: Medicaid and commercial insurance claims for patients aged 15-44 years and who gave birth between 2015 and 2019 were included. Birth claims were identified using procedure and diagnosis codes for vaginal or cesarean delivery. Hepatitis C testing was defined as an insurance claim during the 42 weeks before delivery. Testing rates were calculated among patients who delivered and among the subset of patients who were continuously enrolled for 42 weeks before delivery. We also compared the timing of testing relative to delivery among patients with commercial or Medicaid insurance. Multivariable logistic regression was used to identify factors associated with testing. RESULTS: Among 1,142,770 Medicaid patients and 1,207,132 commercially insured patients, 175,223 (15.3%) and 221,436 (18.3%) were tested for hepatitis C during pregnancy, respectively. Testing rates were 89,730 (21.8%) and 187,819 (21.9%) among continuously enrolled Medicaid and commercially insured patients, respectively. Rates increased from 2015 through 2019 among Medicaid (from 20,758/108,332, 19.2% to 13,971/52,330, 26.8%) and commercially insured patients (from 38,308/211,555, 18.1% to 39,152/139,972, 28%), respectively. Among Medicaid patients, non-Hispanic Black (odds ratio 0.73, 95% CI 0.71-0.74) and Hispanic (odds ratio 0.53, 95% CI 0.51-0.56) race or ethnicity were associated with lower odds of testing. Opioid use disorder, HIV infection, and high-risk pregnancy were associated with higher odds of testing in both Medicaid and commercially insured patients. CONCLUSIONS: Hepatitis C testing during pregnancy increased from 2015 through 2019 among patients with Medicaid and commercial insurance, although tremendous opportunity for improvement remains. Interventions to increase testing among pregnant persons are needed.

Approximately 2.4 million adults were estimated to have hepatitis C virus (HCV) infection in the United States during 2013-2016 (1). Untreated, hepatitis C can lead to advanced liver disease, liver cancer, and death (2). The Viral Hepatitis National Strategic Plan for the United States calls for ≥80% of persons with hepatitis C to achieve viral clearance by 2030 (3). Characterizing the steps that follow a person's progression from testing to viral clearance and subsequent infection (clearance cascade) is critical for monitoring progress toward national elimination goals. Following CDC guidance (4), a simplified national laboratory results-based HCV five-step clearance cascade was developed using longitudinal data from a large national commercial laboratory throughout the decade since highly effective hepatitis C treatments became available. During January 1, 2013-December 31, 2021, a total of 1,719,493 persons were identified as ever having been infected with HCV. During January 1, 2013-December 31, 2022, 88% of those ever infected were classified as having received viral testing; among those who received viral testing, 69% were classified as having initial infection; among those with initial infection, 34% were classified as cured or cleared (treatment-induced or spontaneous); and among those persons, 7% were categorized as having persistent infection or reinfection. Among the 1.0 million persons with evidence of initial infection, approximately one third had evidence of viral clearance (cured or cleared). This simplified national HCV clearance cascade identifies substantial gaps in cure nearly a decade since highly effective direct-acting antiviral (DAA) agents became available and will facilitate the process of monitoring progress toward national elimination goals. It is essential that increased access to diagnosis, treatment, and prevention services for persons with hepatitis C be addressed to prevent progression of disease and ongoing transmission and achieve national hepatitis C elimination goals.

During 2013-2016, an estimated 2.4 million people in the United States were living with hepatitis C virus (HCV) infection.1 With the availability of curative treatment since 2013, the United States has established a goal of eliminating hepatitis C as a public health threat by 2030.2 HCV clearance cascades (hereinafter, HCV cascades) are an important tool to track progress toward elimination, across jurisdictions and at a national level, and to identify disparities in access to testing and treatment. HCV cascades are a sequence of steps that follow progression from testing and treatment to clearance and subsequent infection and can be used to inform public health interventions to facilitate progression along the cascade. | Many HCV cascades are developed in a single or regional health system in which both treatment and laboratory data are available. However, an important goal for health departments is to develop population-level cascades that capture data on HCV infection status for all people living in a jurisdiction who might seek care across various health settings. In the absence of treatment information, which is not always readily available in health department surveillance systems, HCV laboratory results can be used to develop HCV cascades. Here, we describe a standardized, laboratory result–based HCV cascade developed by the Centers for Disease Control and Prevention (CDC) as a guide for health departments (Figure 1, Supplemental Material).

The study evaluates the effect of the 2020 Centers for Disease Control and Prevention and U.S. Preventive Services Task Force recommendations on hepatitis C virus (HCV) screening among pregnant persons nationally and by health insurance type. The study included 5,048,428 pregnant persons aged 15-44 years with either Medicaid or commercial health insurance who had obstetric panel testing performed by Quest Diagnostics, January 2011-June 2021. Antibody screening for HCV infection increased before and accelerated after the updated recommendations in early 2020. Disparities in HCV testing by health insurance status were substantial over the entire study period. Despite substantial progress in the proportion of pregnant persons screened for HCV infection, current testing rates fall short of universal recommendations.

Post-exposure prophylaxis (PEP) is highly effective in preventing disease progression of rabies when used in timely and appropriate manner. The key treatment for PEP is infiltration of rabies immune globulin (RIG) into lesion site after bite exposure, besides wound care and vaccination. Unfortunately, however, RIG is expensive and its supply is limited. Currently, several anti-rabies virus monoclonal antibody (mAb) products are under development as alternatives to RIG, and two recently received regulatory approval in India. In this study, fully human mAbs that recognize different rabies virus glycoprotein conformational antigenic site (II and III) were created from peripheral blood mononuclear cells of heathy vaccinated subjects. These mAbs neutralized a diverse range of lyssavirus types. As at least two anti-rabies virus mAbs are recommended for use in human PEP to ensure broad coverage against diverse lyssaviruses and to minimize possible escape variants, two most potent mAbs, NP-19-9 and 11B6, were selected to be used as cocktail treatment. These two mAbs were broadly reactive to different types of lyssaviruses isolates, and were shown to have no interference with each other. These results suggest that NP-19-9 and 11B6 are potent candidates to be used for PEP, suggesting further studies involving clinical studies in human.

INTRODUCTION: The proportion of individuals infected with hepatitis C virus that receive direct-acting antiviral treatment is unclear. METHODS: The proportion of commercially or Medicaid-insured patients receiving hepatitis C virus treatment was estimated using administrative claims data obtained from MarketScan and Multi-State Medicaid obtained on January 6, 2020. Validated algorithms derived from standardized procedures and International Classification of Diseases diagnosis codes were used to identify enrollees with chronic hepatitis C; analysis (performed November 30, 2020) was restricted to adults continuously enrolled with prescription drug coverage for >6 months before and after their index hepatitis C viral load test claim date from January 2014 through December 2018. Prescription drug claims using National Drug Codes were used for hepatitis C virus drugs. The proportion of treated patients by demographic and clinical characteristics was described, and associations with treatment were modeled using multivariable-adjusted hazard ratios and 95% CIs by insurance status. RESULTS: Of patients with chronic hepatitis C, 12,090 of 17,562 (69%) with commercial insurance and 8,112 of 27,328 (30%) with Medicaid were treated. Commercially insured patients with opioid use disorder (hazard ratio=0.78, 95% CI=0.72, 0.85), alcohol use disorder (hazard ratio=0.85, 95% CI=0.79, 0.91), severe mental illness (hazard ratio=0.92, 95% CI=0.87, 0.98), chronic kidney disease (hazard ratio=0.75, 95% CI=0.69, 0.82), or HIV infection (hazard ratio=0.74, 95% CI=0.66, 0.82) were less likely to be treated. Medicaid patients with opioid (hazard ratio=0.64, 95% CI=0.61, 0.68) or alcohol use disorders (hazard ratio=0.83, 95% CI=0.79, 0.88) were less likely to be treated. CONCLUSIONS: Hepatitis C virus treatment gaps were identified using administrative claims data among patients with commercial and Medicaid insurance.

INTRODUCTION: The COVID-19 pandemic has disrupted healthcare services, reducing opportunities to conduct routine hepatitis C virus antibody screening, clinical care, and treatment. Therefore, people living with undiagnosed hepatitis C virus during the pandemic may later become identified at more advanced stages of the disease, leading to higher morbidity and mortality rates. Further, unidentified hepatitis C virus-infected individuals may continue to unknowingly transmit the virus to others. METHODS: To assess the impact of the COVID-19 pandemic, data were evaluated from a large national reference clinical laboratory and from national estimates of dispensed prescriptions for hepatitis C virus treatment. Investigators estimated the average number of hepatitis C virus antibody tests, hepatitis C virus antibody-positive test results, and hepatitis C virus RNA-positive test results by month in January-July for 2018 and 2019, compared with the same months in 2020. To assess the impact of hepatitis C virus treatment, dispensed hepatitis C virus direct-acting antiretroviral medications were examined for the same time periods. Statistical analyses of trends were performed using negative binomial models. RESULTS: Compared with the 2018 and 2019 months, hepatitis C virus antibody testing volume decreased 59% during April 2020 and rebounded to a 6% reduction in July 2020. The number of hepatitis C virus RNA-positive results fell by 62% in March 2020 and remained 39% below the baseline by July 2020. For hepatitis C virus treatment, prescriptions decreased 43% in May, 37% in June, and 38% in July relative to the corresponding months in 2018 and 2019. CONCLUSIONS: During the COVID-19 pandemic, continued public health messaging, interventions and outreach programs to restore hepatitis C virus testing and treatment to prepandemic levels, and maintenance of public health efforts to eliminate hepatitis C infections remain important.

BACKGROUND: Rabies is a viral disease of animals and people causing fatal encephalomyelitis if left untreated. Although effective pre- and post-exposure vaccines exist, they are not widely available in many endemic countries within Africa. Since many individuals in these countries remain at risk of infection, post-exposure healthcare-seeking behaviors are crucial in preventing infection and warrant examination. METHODOLOGY: A rabies knowledge, attitudes, and practices survey was conducted at 24 geographically diverse sites in Uganda during 2013 to capture information on knowledge concerning the disease, response to potential exposure events, and vaccination practices. Characteristics of the surveyed population and of the canine-bite victim sub-population were described. Post-exposure healthcare-seeking behaviors of canine-bite victims were examined and compared to the related healthcare-seeking attitudes of non-bite victim respondents. Wealth scores were calculated for each household, rabies knowledge was scored for each non-bitten survey respondent, and rabies exposure risk was scored for each bite victim. Logistic regression was used to determine the independent associations between different variables and healthcare-seeking behaviors among canine-bite victims as well as attitudes of non-bitten study respondents. RESULTS: A total of 798 households were interviewed, capturing 100 canine-bite victims and a bite incidence of 2.3 per 100 person-years. Over half of bite victims actively sought medical treatment (56%), though very few received rabies post-exposure prophylaxis (3%). Bite victims who did not know or report the closest location where PEP could be received were less likely to seek medical care (p = 0.05). Respondents who did not report having been bitten by a dog with higher knowledge scores were more likely to respond that they would both seek medical care (p = 0.00) and receive PEP (p = 0.06) after a potential rabies exposure event. CONCLUSIONS: There was varying discordance between what respondents who did not report having been bitten by a dog said they would do if bitten by a dog when compared to the behaviors exhibited by canine-bite victims captured in the KAP survey. Bite victims seldom elected to wash their wound or receive PEP. Having lower rabies knowledge was a barrier to theoretically seeking care and receiving PEP among not bitten respondents, indicating a need for effective and robust educational programs in the country.

OBJECTIVES: Monitoring care and treatment for persons with chronic hepatitis B (CHB) is essential for demonstrating progress in achieving national elimination goals. We sought to evaluate insurance claims data as a source for monitoring progression along the CHB care cascade. STUDY DESIGN: Longitudinal evaluation from diagnosis to treatment among commercially insured enrollees with CHB. METHODS: We used standardized procedure and diagnosis codes to identify enrollees (≥ 18 years) with CHB in large insurance claims databases to describe the CHB care cascade from 2008 to 2016. Linkage to care was defined as procedure codes for liver fibrosis assessment (alanine aminotransferase in conjunction with either hepatitis B virus DNA or hepatitis B e-antigen) more than 12 months after CHB diagnosis. Treatment was defined as a claim for any CHB prescription. We analyzed factors associated with linkage to care and treatment using unadjusted logistic regression and evaluated rates of diagnosis, linkage to care, and treatment over time. RESULTS: Of 16,644 individuals with CHB, 6004 (36%) were linked to care and 2926 (18%) were treated. Persons coinfected with HIV (odds ratio [OR], 0.46; 95% CI, 0.36-0.59) or hepatitis C (OR, 0.50; 95% CI, 0.34-0.73) were less likely to be linked to care, and persons coinfected with HIV (OR, 0.29; 95% CI, 0.19-0.44) were less likely to be treated. From 2009 to 2015, there was a significant decrease in CHB diagnoses but no change in the proportion linked to care and treatment. CONCLUSIONS: We identified gaps in linkage to care and treatment in commercially insured adults with CHB.

Using questionnaires and serologic testing, we evaluated bat and lyssavirus exposure among persons in an area of Nigeria that celebrates a bat festival. Bats from festival caves underwent serologic testing for phylogroup II lyssaviruses (Lagos bat virus, Shimoni bat virus, Mokola virus). The enrolled households consisted of 2,112 persons, among whom 213 (10%) were reported to have ever had bat contact (having touched a bat, having been bitten by a bat, or having been scratched by a bat) and 52 (2%) to have ever been bitten by a bat. Of 203 participants with bat contact, 3 (1%) had received rabies vaccination. No participant had neutralizing antibodies to phylogroup II lyssaviruses, but >50% of bats had neutralizing antibodies to these lyssaviruses. Even though we found no evidence of phylogroup II lyssavirus exposure among humans, persons interacting with bats in the area could benefit from practicing bat-related health precautions.

Hepatitis C virus (HCV) infection is a public health threat. The electronic health record (EHR) can be used to monitor patients along the HCV cure cascade and highlight opportunities for interventions to improve cascade outcomes. We developed an HCV patient registry using data from Grady Health System's (GHS) EHR and performed a cross sectional analysis of 72,745 GHS patients who received anti-HCV testing from 2004-2016. We created a testing cascade: 1) anti-HCV reactive, 2) HCV RNA tested, and 3) HCV RNA detectable; and a cure cascade: 1) HCV RNA detectable, 2) engaged in care, 3) treatment prescribed, 4) sustained virologic response (SVR) tested, and 5) SVR documented. 9,893 (14%) had reactive anti-HCV tests of 72,745 patients tested, 5,109 (52%) of these had HCV RNA tested, and 4,224 (43%) were HCV RNA detectable. 2,738 (65%) of 4,224 with detectable RNA were engaged in care, 909 (22%) were prescribed antiviral therapy, and 354 (8%) achieved SVR. Factors associated with HCV treatment included cirrhosis, tobacco use, depression, diabetes, obesity, alcohol use, male gender, black race, and Medicare insurance. Uninsured patients were significantly less likely to be prescribed HCV treatment. In conclusion, Using EHR data, we identified high anti-HCV prevalence and noted gaps in HCV RNA testing, linkage to care, and treatment. The EHR can be used to evaluate the effectiveness of targeted interventions to overcome these gaps.

BACKGROUND: Hepatitis B virus (HBV) infection testing among persons with hepatitis C virus (HCV) infection is necessary to appropriately care for these patients, yet uptake of HBV testing and vaccination in this population is suboptimal. METHODS: In a retrospective cohort analysis, we describe the prevalence of hepatitis B testing, linkage to hepatitis B care, and hepatitis B vaccination in patients with HCV infection within a large urban safety-net health system. Using a registry of HCV-infected patients with patient-level electronic health record data, that included demographic, clinical, and laboratory information from 2004 to 2016 from Grady Health System in Atlanta, GA, we describe (1) The prevalence of hepatitis B testing (hepatitis B surface antigen [HBsAg], core antibody [anti-HBc], surface antibody [anti-HBs]); (2) The proportion of HBsAg-positive persons receiving HBV DNA and e-antigen (HBeAg) as indicators for linkage to hepatitis B-directed care; and (3) The proportion of persons receiving hepatitis B vaccine. RESULTS: Of 4224 HCV-infected patients, 3629 (86%) had test results for HBsAg and 43 (1.2%) were HBsAg-positive. Of 2342 (55%) with test results for all three HBV serological markers, median age was 60 years, 67% were male, and 83% were African-American, 789 (34%) anti-HBc positive only, 678 (29%) anti-HBc/anti-HBs positive, 190 (8.1%) anti-HBs positive only, and 642 (27%) were HBV-susceptible. Of HBsAg-positive patients, 21% received HBV DNA and 40% HBeAg testing. The proportion of HBV-susceptible patients receiving at least 1 dose of hepatitis B vaccine was 322/642 (50%). CONCLUSIONS: In a large cohort of HCV-infected patients, we found a high prevalence of current or past HBV infection, but there were gaps in complete hepatitis B testing, hepatitis B-directed care, and hepatitis B vaccination. Strategies are needed to increase hepatitis B testing, linkage to care, and administration of the hepatitis B vaccine for HCV-infected persons in this healthcare system.

Electronic medical record data structure prevents easy population-level monitoring of hepatitis C virus (HCV) treatment uptake and cure. Using an HCV registry from a public hospital system in Atlanta, Georgia, we developed multiple algorithms using serial HCV RNA test results as proxy measures for direct acting antiviral (DAA) treatment initiation and sustained virologic response (SVR). We calculated sensitivity and positive predictive values by comparing the algorithms to the DAA initiation and SVR results from the registry. From December 2013 - August 2016, 1,807 persons actively infected with HCV were identified in the registry. Of those, 698 initiated DAA treatment based on medical record abstraction; of 442 patients with treatment start and/or end dates, 314 had documented SVR. Treatment algorithm 2 (detectable HCV RNA result followed by 2 sequential HCV RNA tests results) and treatment algorithm 5 (detectable HCV RNA result followed by 2 sequential HCV RNA tests results > 6 weeks apart) had the highest sensitivity (87% and 85% respectively) and positive predictive value (80% and 82% respectively) combinations. Four SVR algorithms relied on fulfilling treatment algorithm definitions and having an undetectable HCV RNA test result >/= 12 weeks after the last HCV RNA result; sensitivity for all was 79% and positive predictive value was 92-93%. Algorithms using serial quantitative HCV RNA results can serve as proxy measures for evaluating population-level DAA treatment and SVR outcomes.

Twice a year in southwestern Nigeria, during a traditional bat festival, community participants enter designated caves to capture bats, which are then consumed for food or traded. We investigated the presence of Bartonella species in Egyptian fruit bats (Rousettus aegyptiacus) and bat flies (Eucampsipoda africana) from these caves and assessed whether Bartonella infections had occurred in persons from the surrounding communities. Our results indicate that these bats and flies harbor Bartonella strains, which multilocus sequence typing indicated probably represent a novel Bartonella species, proposed as Bartonella rousetti. In serum from 8 of 204 persons, we detected antibodies to B. rousetti without cross-reactivity to other Bartonella species. This work suggests that bat-associated Bartonella strains might be capable of infecting humans.

The highest rate of human rabies deaths reported in the Americas is in Haiti, and most of these deaths result from rabies virus infections that occur after individuals are bitten by infected dogs and do not receive rabies post-exposure prophylaxis. One barrier to rabies prevention in Haiti is a lack of knowledge about this disease among healthcare professionals and community members. During the past 4 years, The US Centers for Disease Control and Prevention has collaborated with public health officials and partners to develop, test and refine educational materials aimed at filling this need for rabies education. This report summarizes the use of feedback from knowledge, attitudes and practises surveys; key informant interviews; and focus groups to develop culturally appropriate rabies prevention materials for community members, health officials, clinicians, laboratory professionals, veterinary professionals, government officials and national and local district leaders about ways to prevent rabies. These formative research methods were critically important in ensuring that the materials would be culturally appropriate and would stand the greatest likelihood of motivating Haitians to protect themselves from rabies. Centers for Disease Control and Prevention is using lessons learned in Haiti to develop and test materials in other countries with high rates of canine rabies.

Haiti, a Caribbean country of 10.5 million people, is estimated to have the highest burden of canine-mediated human rabies deaths in the Western Hemisphere, and one of the highest rates of human rabies deaths in the world. Haiti is also the poorest country in the Western Hemisphere and has numerous economic and health priorities that compete for rabies-control resources. As a result, primary rabies-control actions, including canine vaccination programs, surveillance systems for human and animal rabies, and appropriate postbite treatment, have not been fully implemented at a national scale. After the 2010 earthquake that further hindered the development of public health program infrastructure and services, the U.S. Centers for Disease Control and Prevention worked with the Ministry of Public Health and Population and key health development partners (including the Pan-American Health Organization) to provide technical expertise and funding for general disease surveillance systems, laboratory capacity, and selected disease control programs; including rabies. In 2011, a cross-ministerial rabies consortium was convened with participation from multiple international rabies experts to develop a strategy for successful rabies control in Haiti. The consortium focused on seven pillars: 1) enhancement of laboratory diagnostic capacity, 2) development of comprehensive animal surveillance system, 3) development of comprehensive human rabies surveillance system, 4) educational outreach, 5) sustainable human rabies biologics supply, 6) achievement of sustained canine vaccination rates of ≥ 70%, and 7) finalization of a national rabies control strategy. From 2010 until 2015, Haiti has seen improvements in the program infrastructure for canine rabies control. The greatest improvements were seen in the area of animal rabies surveillance, in support of which an internationally recognized rabies laboratory was developed thereby leading to an 18-fold increase in the detection of rabid animals. Canine rabies vaccination practices also improved, from a 2010 level of approximately 12% to a 2015 dog population coverage level estimated to be 45%. Rabies vaccine coverage is still below the goal of 70%, however, the positive trend is encouraging. Gaps exist in the capacity to conduct national surveillance for human rabies cases and access to human rabies vaccine is lacking in many parts of the country. However, control has improved over the past 5 years as a result of the efforts of Haiti's health and agriculture sectors with assistance from multiple international organizations. Haiti is well situated to eliminate canine-mediated human rabies deaths in the near future and should serve as a great example to many developing countries struggling with similar barriers and limitations.

Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG) have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC). Two kinds of chimeric human antibodies (chimeric #7 and #17) were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse models and show low risk for adverse immunogenicity.

In the USA, rabies vaccines (RVs) are licensed for intramuscular (IM) use only, although RVs are licensed for use by the intradermal (ID) route in many other countries. Recent limitations in supplies of RV in the USA reopened discussions on the more efficient use of available biologics, including utilization of more stringent risk assessments, and potential ID RV administration. A clinical trial was designed to compare the immunogenic and adverse effects of a purified chicken embryo cell (PCEC) RV administered ID or IM. Enrollment was designed in four arms, ID Pre-Exposure Prophylaxis (Pre-EP), IM Pre-EP, ID Booster, and IM Booster vaccination. Enrollment included 130 adult volunteers. The arms with IM administration received vaccine according to the current ACIP recommendations: Pre-EP, three 1mL (2.5 I.U.) RV doses, each on day 0, 7, and 21; or a routine Booster, one 1ml dose. The ID groups received the same schedule, but doses administered were in a volume of 0.1mL (0.25 I.U.). The rate of increase in rabies virus neutralizing antibody titers 14-21days after vaccination were similar in the ID and correspondent IM groups. The GMT values for ID vaccination were slightly lower than those for IM vaccination, for both naive and booster groups, and these differences were statistically significant by t-test. Fourteen days after completing vaccination, all individuals developed RV neutralizing antibody titers over the minimum arbitrary value obtained with the rapid fluorescent focus inhibition test (RFFIT). Antibodies were over the set threshold until the end of the trial, 160days after completed vaccination. No serious adverse reactions were reported. Most frequent adverse reactions were erythema, induration and tenderness, localized at the site of injection. Multi use of 1mL rabies vaccine vials for ID doses of 0.1 was demonstrated to be both safe and inmunogenic.

BACKGROUND: Rabies is a neglected disease despite being responsible for more human deaths than any other zoonosis. A lack of adequate human and dog surveillance, resulting in low prioritization, is often blamed for this paradox. Estimation methods are often employed to describe the rabies burden when surveillance data are not available, however these figures are rarely based on country-specific data. METHODS: In 2013 a knowledge, attitudes, and practices survey was conducted in Uganda to understand dog population, rabies vaccination, and human rabies risk factors and improve in-country and regional rabies burden estimates. Poisson and multi-level logistic regression techniques were conducted to estimate the total dog population and vaccination coverage. RESULTS: Twenty-four villages were selected, of which 798 households completed the survey, representing 4 375 people. Dog owning households represented 12.9% of the population, for which 175 dogs were owned (25 people per dog). A history of vaccination was reported in 55.6% of owned dogs. Poverty and human population density highly correlated with dog ownership, and when accounted for in multi-level regression models, the human to dog ratio fell to 47:1 and the estimated national canine-rabies vaccination coverage fell to 36.1%. This study estimates there are 729 486 owned dogs in Uganda (95% CI: 719 919 - 739 053). Ten percent of survey respondents provided care to dogs they did not own, however unowned dog populations were not enumerated in this estimate. 89.8% of Uganda's human population was estimated to reside in a community that can support enzootic canine rabies transmission. CONCLUSIONS: This study is the first to comprehensively evaluate the effect of poverty on dog ownership in Africa. These results indicate that describing a dog population may not be as simple as applying a human: dog ratio, and factors such as poverty are likely to heavily influence dog ownership and vaccination coverage. These modelled estimates should be confirmed through further field studies, however, if validated, canine rabies elimination through mass vaccination may not be as difficult as previously considered in Uganda. Data derived from this study should be considered to improve models for estimating the in-country and regional rabies burden.

Bats provide vital ecologic services that humans benefit from, such as seed dispersal and pest control, and are a food source for some human populations. However, bats also are reservoirs for a number of high-consequence zoonoses, including paramyxoviruses, filoviruses, and lyssaviruses. The variety of viruses that bats harbor might be related to their evolutionary diversity, ability to fly large distances, long lifespans, and gregarious roosting behaviors. Every year a festival takes place in Idanre, Nigeria, in which males of all ages enter designated caves to capture bats; persons are forbidden from entering the caves outside of these festivities. Festival participants use a variety of techniques to capture bats, but protective equipment rarely is used, placing hunters at risk for bat scratches and bites. Many captured bats are prepared as food, but some are transported to markets in other parts of the country for sale as bushmeat. Bats also are presented to dignitaries in elaborate rituals. The health consequences of contact with these bats are unknown, but a number of viruses have been previously identified among Nigerian bats, including lyssaviruses, pegiviruses, and coronaviruses. Furthermore, the caves are home to Rousettus aegyptiacus bats, which are reservoirs for Marburg virus in other parts of Africa.

Although there are over 1,150 bat species worldwide, the diversity of viruses harbored by bats has only recently come into focus as a result of expanded wildlife surveillance. Such surveys are of importance in determining the potential for novel viruses to emerge in humans, and for optimal management of bats and their habitats. To enhance our knowledge of the viral diversity present in bats, we initially surveyed 415 sera from African and Central American bats. Unbiased high-throughput sequencing revealed the presence of a highly diverse group of bat-derived viruses related to hepaciviruses and pegiviruses within the family Flaviridae. Subsequent PCR screening of 1,258 bat specimens collected worldwide indicated the presence of these viruses also in North America and Asia. A total of 83 bat-derived viruses were identified, representing an infection rate of nearly 5%. Evolutionary analyses revealed that all known hepaciviruses and pegiviruses, including those previously documented in humans and other primates, fall within the phylogenetic diversity of the bat-derived viruses described here. The prevalence, unprecedented viral biodiversity, phylogenetic divergence, and worldwide distribution of the bat-derived viruses suggest that bats are a major and ancient natural reservoir for both hepaciviruses and pegiviruses and provide insights into the evolutionary history of hepatitis C virus and the human GB viruses.

Enhancing DNA vaccine effectiveness remains a challenge, especially if the desired goal is immunization efficacy after a single dose. The glycoprotein gene from the rabies virus Evelyn-Rokitnicki-Abelseth (ERA) strain was modified by mutation at amino acid residue 333 from arginine to glutamine. The modified and original unmodified glycoprotein genes were cloned separately and developed as DNA vaccines for immunization in mice. The intramuscular (IM) route using a single dose (100 microg) of a modified DNA vaccine showed virus neutralizing antibody induction by d30, and 80% of the mice survived a challenge in which 100% of unvaccinated controls succumbed. Similar results were obtained using a single dose (10 microg) by the intradermal (ID) route with one-tenth amount of the DNA administered. Administration of single dose of DNA vaccine with unmodified G did not result in the production of detectable levels of virus neutralizing antibody by d30. The results of the IM and the ID routes of administration were statistically significant (P<0.01). Based on these preliminary results, a modified glycoprotein gene from the ERA rabies virus strain may be an ideal candidate for DNA vaccine efficacy enhancement.