Epidemic Cycles Research Articles

Influenza Vaccine Effectiveness Assessed at Different Stages of the Epidemic Cycle in Reducing the Frequency of Hospitalization with Influenza

Relevance . Influenza vaccination is considered as the most effective way to prevent this infection. In the past epidemic season in Russia, the main share of influenza vaccines comprised domestically produced vaccines. Aims was to assess the vaccine effectiveness (VE) in preventing severe forms of influenza that require hospitalization. Materials & Methods . To collect clinical and epidemiological data for the epidemic season 2018–2019. an active prospective surveillance approach was used. The study included 6 departments of three infectious diseases hospitals in St. Petersburg. Results It was established that early VE, estimated during the epidemic, was 66.4% for children and 64.7% for adults. Evaluation of VE for the entire study period from week 52 of 2018 to week 13 of 2019, showed that it decreased, the total VE for this period was 48.4%. Conclusions The data obtained in the course of the study indicate a pronounced protective role of vaccination in preventing the development of severe forms of influenza with subsequent hospitalization.

Chikungunya Virus: Role of Vectors in Emergence from Enzootic Cycles.

Chikungunya virus (CHIKV), a re-emerging mosquito-borne arbovirus, has caused millions of cases of severe, often chronic arthralgia during recent outbreaks. In Africa, circulation in sylvatic, enzootic cycles involves several species of arboreal mosquito vectors that transmit among diverse nonhuman primates and possibly other amplifying hosts. Most disease occurs when CHIKV emerges into a human-amplified cycle involving Aedes aegypti and sometimes Aedes albopictus transmission and extensive spread via travelers. Epidemiologic studies suggest that the transition from enzootic to epidemic cycles begins when people are infected via spillover in forests. However, efficient human amplification likely only ensues far from enzootic habitats where peridomestic vector and human densities are adequate. Recent outbreaks have been enhanced by mutations that adapt CHIKV for more efficient infection of Ae. albopictus, allowing for geographic expansion. However, epistatic interactions, sometimes resulting from founder effects following point-source human introductions, have profound effects on transmission efficiency, making CHIKV emergence somewhat unpredictable.

Genetic variants of parvovirus B19 circulating in Belarus during the epidemic cycle of infection (2005–2016)

Human parvovirus infection is characterized by a variety of clinical manifestations. Based on the genetic analysis, genotypes 1a, 1b, 2, 3a, 3b of parvovirus B19 are distinguished, which have different geographical distribution. In the period 2005–2016, in Belarus 210 strains of parvovirus B19 isolated from the patients with various forms of parvovirus infection, mainly erythema infectiosum, were genotyped. All strains, except one, belonged to genotype 1a. One strain belonged to genotype 3b and was isolated from a child with aplastic crisis who arrived in Belarus from Kazakhstan for medical care. On the phylogenetic tree, the strains of genotype 1a formed two groups related to the subtypes 1a1 and 1a2. During the 12-year observation, both subtypes circulated in Belarus, but with varying intensity. In the highest incidence years, as well as one or two years before and after this (2005–2008 and 2013–2016), strains of subtype 1a2 predominated in circulation. During the period of low incidence (2009–2012), the dominant position belonged to subtype 1a1. The average genetic distance inside each subtype was 0.51 % for 1a1 and 0.56 % for 1a2. Between subtypes it was also small – 1.32 %. It can be assumed that subtype 1a2 is more new for Belarus and therefore might be connected with the increase of morbidity.

Detection of the Onset of the Epidemic Period of Respiratory Syncytial Virus Infection in Japan.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children worldwide. An annual epidemic of RSV infection generally begins around autumn, reaching a peak at the end of year in Japan, but in 2017 it started in early July and peaked in September. As the onset timing of RSV season varies, it is important to detect the beginning of an epidemic, to enable the implementation of preventive measures. However, there are currently no specified criteria or methods to determine the onset of RSV season in a timely manner. Therefore, we developed a model to detect the epidemic onset, based on data from the Infectious Diseases Weekly Report from 2012 to 2017. The 47 prefectures of Japan span 11 climate zones, which affect the timing of epidemic onset. Therefore, the onset of RSV season was assessed separately in each prefecture. Non-linear regression analysis was performed to generate a mathematical model of the annual epidemic cycle for each prefecture. A search index was used to determine the onset of RSV season, which was estimated using the number of RSV reports per week within an epidemic period (RSV-reports/w) and the number of reported cases included within an epidemic period relative to the total number of RSV reports (capture rate). A number of RSV-reports/w, which was used as a threshold (a number at onset line) to determine the condition of the onset of RSV season, was then estimated based on the search index. The mean number at the onset of RSV season for 47 prefectures was 29.7 reports/week (median 21.0, range 6.0–121.0 reports/ week). The model also showed that the onset of RSV season in 2017 was more than 1 month earlier than the previous year. In conclusion, the model detected epidemic cycles and their onset conditions in all prefectures, despite the 11 climate zones of Japan. The results are expected to contribute to infant medical care by allowing medical personnel to take preventive measures promptly at the beginning of the epidemic RSV season.

Report on the 2018 Acute Flaccid Myelitis Outbreaks in the USA

An increase in the number of Acute Flaccid Myelitis (AFM) cases reported in the USA was detected in August 2018. The CDC has confirmed 186 cases of AFM in 2018 making this the largest outbreak of AFM reported in the USA. The cause however remains unknown. In this watching brief we review key features of the current outbreak in context, describe what is known about AFM, and consider probable causes. A two-year epidemic cycle of AFM appears to be emerging, and most current evidence implicates both EV-A71 and EV-D68 as the probable cause of the current outbreak yet key questions remain.

Genetic diversity, population structure and rickettsias in Amblyomma ovale in areas of epidemiological interest for spotted fever in Brazil.

Amblyomma ovale (Ixodida: Ixodidae) Koch, 1844 is widely-reported in the neotropical region and is the main vector in the epidemic cycle of Rickettsia parkeri strain Atlantic rainforest, a bioagent of a milder variety of spotted fever (SF). Because species with wide geographical distributions are known to exhibit variations that influence their vectorial capacity, the present study aimed to analyze genetic diversity and rickettsia infection of A. ovale collected during the investigation and surveillance of SF cases in the Cerrado and Atlantic rainforest (ARF) Brazilian biomes. Samples had their DNA extracted, amplified and sequenced for 16S rDNA, 12S rDNA, cytochrome oxidase subunit II and D-loop markers for tick analyses, as well as the gltA, htrA, ompA and ompB genes for rickettsia detection. Between 11 and 33 A. ovale haplotypes were identified, all of them exclusive to areas within individual analyzed biome areas. The A. ovale populations appeared to be structured, with Cluster I restricted to Cerrado + ARF isolated in Caatinga and Cluster II to ARF continuous area. Rickettsia bellii, R. parkeri strain Atlantic rainforest (first report for Goiás state, Cerrado), Rickettsia asemboensis (first record in A. ovale for Brazil) and Rickettsia felis (first detection in this ixodid) were identified. A. ovale clusters were not associated with rickettsia types.

Trend of epidemics and variation of pathogens of hand, foot and mouth disease in China: a dynamic series analysis, 2008-2017

Objective: To understand the trend of epidemics and variation of pathogens on hand, foot and mouth diseases (HFMD) in China for setting up appropriate intervention measures. Methods: Data related to reported cases and outbreaks of HFMD from the National Notifiable Disease Surveillance Reporting System of China, 2008 to 2017, was collected and analyzed. Based on the geographical location and types of climate, the total 31 provinces, autonomous regions and municipalities in the mainland of China, were divided into seven regions: north-west, north, mid-north, east, mid-south, south, and south-west regions, with epidemic trends and variation of pathogens analyzed. The average speed of growth on the dynamic series from 2008 to 2017 was calculated, using the Geometric Average method. Results: The overall reported incidence rate of HFMD during 2008-2017 was 134.59 per 100 000 population with an average increase of 15.92%. The proportion of severe cases was 0.84%, with 9.56% increase. The reported mortality rate of HFMD was 0.03/100 000, with an average decrease of 3.49%. The case fatality rate was 0.02% and with a decrease of 16.86%. A total of 6 000 outbreaks were reported during the decade. Except for 1.09% decrease on the incidence rate in the north region, all the other regions showed an increase on the morbidity rates, with the highest as25.20% in the south region. Mortality rates showed 27.53% and 0.60% increases in both the south-west and mid-north regions, respectively. Mortality rates in the other regions all showed a decreasing trend. In terms of case fatality rate, it increased 4.15% in the south-west region while all decreased in the other regions. Two higher age-special morbidity rates appeared in the 1 year olds as 3 184.19/100 000 and in the 2 year olds as 2 547.47/100 000, with the most increase seen in both 0 year (26.08%) and 1 year age groups (23.35%). High age-specific mortality rates were noticed in both the 1-year group as 0.86/100 000 and the 2-year group as 0.54/100 000, however with reductions as 1.21% and 10.70% respectively. As for the case fatalities, the 0 year olds and 1 year olds accounted for 0.039% and 0.027% but both of them had decreased by 19.12% and 19.91%, respectively. Case fatality rates decreased by 16.93% and 16.75%, in males and females. Proportions of EV71 and Cox A16 decreased by 4.28% and 3.07%, but the proportion of other entero-viruses increased by 16.07%. EV71 was responsible for the high frequency of epidemics in both mid-north and the mid-south regions. However, in other five regions, other strains of EV's were responsible for the epidemics. Conclusions: The characteristics of HFMD in China showed that the morbidity of HFMD and proportion of severe cases were both in increasing trends but both the mortality and case fatality of HFMD were decreasing. Children younger than 3 years old showed both high infection and death rates for HFMD. Epidemics caused by other enteroviruses of non-EV71 and non-Cox A16 were seen more. Variance and pathogens related to the epidemic cycles appeared different in the seven regions.

Multi stability and global bifurcations in epidemic model with distributed delay SIRnS-model

Many diseases, such as influenza and the common cold, cause recurrent epidemics. The classical SIRS model fails to obtain recurrent epidemics as it predicts a globally stable endemic fixed point. This endemic fixed point is, however, linearly unstable for most parameters, if one assumes that the time spent in the recovered state is deterministic rather than exponentially distributed. In that case all trajectories converge to a stable epidemic limit cycle. It has been shown that a similar region of instability exists for systems with intermediate immune time distributions. Furthermore, it has been suggested that a bistable region could exist. Here, we first characterize this bistable region using a combination of direct simulation and bifurcation theory. We find that it has a bound where the stable epidemic limit cycle annihilates with an unstable limit cycle in a non-local bifurcation. Secondly, we extend the bifurcation-analysis to narrower immune time distributions than previous studies. Here, we find new levels of complexity in the bifurcation diagram, including the possibility for at least two different epidemic limit cycles at the same disease parameters. Overall our study highlights that a given disease may have multiple epidemic signatures, dependent on how it is introduced.

Pertussis in Low and Medium Income Countries: A Pragmatic Approach.

Pertussis is a vaccine preventable disease since late 1940s. However, it is still endemic in all countries and occurs in epidemic cycles. The number of cases/deaths has decreased during the last decade but a high number of deaths persists in Low and Medium Income Countries (LMIC). The epidemiological situation in LMIC is not precisely known due to lack of surveillance and specific diagnostic tools. A pragmatic approach in these countries should be to establish; (i) a hospital-based surveillance in the largest cities of the country with clinicians and nurses trained to detect clinical symptoms, to obtain biological samples for specific analysis and diagnosis; (ii) a reference laboratory as part of an international network of reference laboratories, under quality assurance, and able to perform at least PCR diagnosis and if possible detection of antibiotic resistance. This surveillance network would allow specific diagnosis of pertussis and facilitate the reporting of cases at national level, thereby improving awareness of the disease at clinician, population and decision maker levels. This network could allow a better evaluation of vaccine coverage, timely vaccination and impacts of modification of national vaccine strategy or type of pertussis vaccine used. Collaboration between this network and basic scientists should be strengthened through translational research projects in order to improve fundamental knowledge on pertussis in LMIC and help clinicians' access to specific diagnostic tools.

Differences in the Impact of Pneumococcal Serotype Replacement in Individuals With and Without Underlying Medical Conditions.

Pneumococcal conjugate vaccines (PCVs) have had a well-documented impact on the incidence of invasive pneumococcal disease (IPD). However, declines in IPD due to vaccine-targeted serotypes have been partially offset by increases in IPD due to nonvaccine serotypes (NVTs). The goal of this study was to quantify serotype-specific changes in the incidence of IPD that occurred in different age groups, with or without certain comorbidities, following the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) in the childhood vaccination program in Denmark. We used nationwide surveillance data for IPD and a hierarchical Bayesian regression framework to estimate changes in the incidence of IPD associated with the introduction of PCV7 (2007) and PCV13 (2010) while controlling for serotype-specific epidemic cycles and unrelated secular trends. Following the introduction of PCV7 and PCV13 in children, the net impact of serotype replacement varied considerably by age group and comorbidities. Differences in the magnitude of serotype replacement were due to variations in the incidence of NVTs in the different risk groups before the introduction of PCVs. The relative increases in the incidence of IPD caused by specific NVTs did not differ appreciably between risk groups in the postvaccination period. Serotype replacement offset a greater proportion of the benefit of PCVs in strata in which the NVTs comprised a larger proportion of cases prior to the introduction of the vaccines. These findings could help to predict the impact of next-generation PCVs in specific risk groups.

Long-term monitoring of virus antibody titers in human intravenous immunoglobulin lots derived from donors in Japan.

Intravenous immunoglobulin (IVIG) contains immunoglobulin G against various viruses, except those that have been screened, such as human immunodeficiency and hepatitis C viruses. Antivirus titers reflect the serostatus of the blood donor population in the collection region and are of clinical interest. During the past 10 years, measles, mumps, rubella, varicella-zoster, hepatitis A and B, Epstein-Barr, and human respiratory syncytial viruses; human parainfluenza viruses 1, 2, and 3; human herpes simplex viruses 1 and 2; human herpesvirus 6; cytomegalovirus (CMV); human adenoviruses (HAdVs) 1, 2, 3, 7, and 11; human parvovirus B19; and human echovirus 9 and 11 titers in IVIG lots have been measured by a commercial testing facility. A viral neutralizing assay for CMV has been used at our facility. Herein, we summarize the measurements and results of a regression analysis of the trends in virus antibody titers. IVIG lots contained significant titers against all of the above viruses, except for HAdV 7. Three patterns-stable, increasing, and decreasing-were observed, without any drastic changes. Although these trends reflect the seroprevalence in Japan, the titers were not obviously affected by the cycle of epidemics. On the other hand, the prevalence data suggest that titers against hepatitis A virus and other viruses will decrease in the near future, although they are currently stable. Monitoring the titer of IVIG lots and seroprevalence of donor populations is important for anticipating future changes in virus antibody titers of IVIG lots and can provide useful information of clinical interest.

Epidemic cycles and environmental pressure in colonial Quebec.

Research on historical populations in Europe finds that infectious disease epidemics appear to induce predictable cycles in age-specific mortality. We know little, however, about whether such cycles also occurred in less dense founder populations of North America. We used high-quality data on the Quebecois population from 1680 to 1798 to examine the extent to which age-specific mortality showed predictable epidemic cycles. We further examined whether environmental pressures-temperature, lack of precipitation, or crop failure-may have set the stage for the emergence of epidemics. We applied autoregressive, integrated, moving average time series methods to annual counts of period mortality for the following age groups: < 1 year, 1 to < 5 years, 5 to < 15 years, 15 to < 50 years, and 50 years and above. These methods controlled for other patterns (e.g., trend) before empirically identifying cycles. Results indicate a strong seven-year cycle in mortality among infants and children under seven years of age. Warm temperatures (across Quebec overall) and relatively dry years (in Eastern Quebec) also predicted an increased risk of mortality in infancy and childhood, although these environmental variables appear to act independently of the epidemic cycle pattern. Findings indicate a strong seven-year epidemic cycle in historical Quebec which afflicted naïve birth cohorts not previously exposed to the prior epidemic. We contend that smallpox epidemics likely contributed to this cycle. The seven-year cycle occurred only in the latter half of the test period (post 1740) with increasing size of the colony and population concentration in urban areas.

Effectiveness and impact of a single-dose vaccine against chickenpox in the community of Madrid between 2001 and 2015

ABSTRACTBackground: Chickenpox is a contagious airborne disease. Immunization by varicella vaccine is an effective preventive measure. The objective of this study is to evaluate the impact and effectiveness of a single-dose vaccination against chickenpox at 15 months of age.Methods: Observational study based on data from the Epidemiological Surveillance System of the Autonomous Community of Madrid from 2001 to 2015. The years were grouped into 4 periods according to epidemic cycles and vaccination schedule: 2001–06, 2007–10, 2011–13 and 2014–15. The impact was calculated as Relative Risk (RR) between the incidence of chickenpox in children between 15 months and 13 years of age between 2011–13 and 2001–06 through Poisson regression using notifications made to the Diseases of Compulsory Declaration (DCD) system, the Sentinel Physicians Network (SPN) and hospital discharge records noted as Minimum Basic Data Set (MBDS). The vaccine effectiveness (VE) was calculated using the screening method and a 1:2 case-control study paired by age and paediatrician in population from 15 months to 13 years and between 2007 and 2015 using SPN source data.Results: The RR2011–13/2001–06 using data from the DCD was 0.14 (95% CI: 0.14 to 0.15), 0.07 (95% CI: 0.06 to 0.08) from SPN and 0.17 (95% CI: 0.15 to 0.20) from MBDS. A total of 338 cases were included in the VE screening obtaining an overall of 93.1 (90.9 to 94.8). For a case-control study, 120 cases and 247 controls were recruited obtaining a VE of 92.4% (IC 95%: 80.8 to 97.0%).Conclusions: The single-dose vaccination against chickenpox at 15 months of age has high impact and effectiveness.

Bordetella pertussis (Pertussis).

1. Heather L. Daniels, DO* 2. Camille Sabella, MD* 1. *Center for Pediatric Infectious Diseases, Cleveland Clinic Children’s, Cleveland, OH * Abbreviations: CDC: : Centers for Disease Control and Prevention DTaP: : diphtheria, tetanus, and acellular pertussis vaccine DTwP: : diphtheria, tetanus, and whole cell pertussis vaccine IHPS: : infantile hypertrophic pyloric stenosis PCR: : polymerase chain reaction Tdap: : tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine Th: : T-helper After completing this article, readers should be able to: Bordetella pertussis is a fastidious gram-negative coccobacillus responsible for the respiratory infection commonly known as “whooping cough.” The organism is spread by respiratory droplets and is highly contagious among close contacts. The typical incubation period is 7 to 10 days, but it may be as long as 21 days. Neither natural infection nor pertussis vaccination results in long-lasting immunity, contributing to endemic infection and 3- to 5-year cycles of pertussis epidemics. Several active components, which play a role in immunity and are responsible for the organism’s ability to cause disease, are produced by B pertussis . (1) Pertussis toxin, filamentous hemagglutinin, pertactin, and agglutinogen allow the organism to adhere to ciliated epithelium of the respiratory tract, where it exerts its effects. Pertussis toxin also induces cell cytoxicity, inhibits neutrophilic and monocytic responses, and delays induction of specific immune responses. Pertussis toxin is postulated to be responsible for the systemic manifestations of pertussis, …

Joint coevolutionary–epidemiological models dampen Red Queen cycles and alter conditions for epidemics

Host–parasite interactions in the form of infectious diseases are a topic of interest in both evolutionary biology and public health. Both fields have relied on mathematical models to predict and understand the dynamics and consequences of these interactions. Yet few models explicitly incorporate both epidemiological and coevolutionary dynamics, allowing for genetic variation in both hosts and parasites. By comparing a matching-alleles model of coevolution, a susceptible–infected–recovered–susceptible compartmental model from epidemiology, and a combined coevolutionary–epidemiology model we assess the effect of the coevolutionary feedback on the epidemiological dynamics and vice versa. We find that Red-Queen cycles are not robust in an epidemiological framework and that coevolutionary interactions can alter the conditions under which epidemic cycles arise. Incorporating both explicit epidemiology and genetic diversity may have important implications for the maintenance of sexual reproduction as well as disease management.

Epidemiological and genetic characteristics of EV71 in hand, foot, and mouth disease in Guangxi, southern China, from 2010 to 2015.

Hand, foot, and mouth disease (HFMD) is a significant public health challenge in China. Human enterovirus 71 (EV71) is regarded as the predominant causative pathogen of HFMD. Since 2015, two inactivated EV71 vaccines have been approved in mainland China, and because their use could change the HFMD pathogen spectrum, this should now be monitored. However, the epidemiological and genetic trends of EV71 with respect to HFMD in Guangxi, southern China, are still not clear. In this study, we describe the epidemiological and genetic characterization of this virus in clinically-diagnosed HFMD reported from 2010 to 2015 in Guangxi. Data showed that a two-year epidemic cycle, with a predominance of EV71 infections, contributed to HFMD outbreaks in Guangxi. Furthermore, this virus is a major causative agent of severe and fatal HFMD. Interestingly, in Guangxi, EV71-positive rates tended to decrease over time. In particular, EV71-positive rates were found in Fangchenggang city, which reported very few severe and fatal cases over the six-year period. Phylogenetic analysis of the VP1 gene revealed that the major circulating strains belonged exclusively to genotype C, subtype 4a (C4a), and most clustered with strains circulating in southern China. The most interesting finding was that a strain isolated in 2012 clustered with Vietnamese strains isolated from 2011–2012. The data highlight the importance of pathogen surveillance for HFMD in China, especially Guangxi, which is located on the border of China and the Association of Southeast Asian Nations.

Seasonal pattern of influenza activity in a subtropical city, China, 2010\u20132015

Influenza seasonality study is critical for policy-makers to choose an optimal time for influenza vaccination campaign, especially for subtropical regions where influenza seasonality and periodicity are unclear. In this study, we explored the seasonality and periodicity of influenza in Hefei, China during 2010 to 2015 using five proxies originated from three data sources of clinical surveillance of influenza-like illness (ILI), laboratory surveillance of influenza and death registration of pneumonia and influenza. We combined both wavelets analysis and de-linear-trend regression with Fourier harmonic terms to estimate seasonal characteristics of epidemic phase, peak time, amplitude, ratio of dominant seasonality. We found both annual cycle of influenza epidemics peaking in December-February and semi-annual cycle peaking in December-February and June-July in subtropical city Hefei, China. Compared to proxies developed by ILI and death registration data separately, influenza proxies incorporated laboratory surveillance data performed better seasonality and periodicity, especially in semi-annual periodicity in Hefei. Proxy of ILI consultation rate showed more timeliness peak than other proxies, and could be useful in developing the early warning model for influenza epidemics. Our study suggests to integrate clinical and laboratory surveillance of influenza for future influenza seasonality studies in subtropical regions.

Definitive tests for dengue fever: when and which should I use?

Dengue is a mosquito-borne viral disease that has established itself globally in both endemic and epidemic transmission cycles. While diagnostic decision-making for dengue is often guided by clinical judgement, definitive laboratory tests, including rapid point-of-care tests, have many advantages in the primary care setting. These include providing epidemiological data and diagnostic clarity for atypical cases, as well as contributing to patient education and compliance. This article discussed the types of diagnostic methods for dengue, when to use them and the appropriateness of each test. Viral detection diagnostic methods such as NS1 antigen assays are generally used within the first week of illness onset, whereas dengue serology testing is most appropriate after that time frame. Locally available rapid point-of-care tests, which include both assays in one convenient test kit, can enhance dengue diagnosis in an endemic setting.

The effects of heterogeneity on stochastic cycles in epidemics

Models of biological processes are often subject to different sources of noise. Developing an understanding of the combined effects of different types of uncertainty is an open challenge. In this paper, we study a variant of the susceptible-infective-recovered model of epidemic spread, which combines both agent-to-agent heterogeneity and intrinsic noise. We focus on epidemic cycles, driven by the stochasticity of infection and recovery events, and study in detail how heterogeneity in susceptibilities and propensities to pass on the disease affects these quasi-cycles. While the system can only be described by a large hierarchical set of equations in the transient regime, we derive a reduced closed set of equations for population-level quantities in the stationary regime. We analytically obtain the spectra of quasi-cycles in the linear-noise approximation. We find that the characteristic frequency of these cycles is typically determined by population averages of susceptibilities and infectivities, but that their amplitude depends on higher-order moments of the heterogeneity. We also investigate the synchronisation properties and phase lag between different groups of susceptible and infected individuals.

Human Brucellosis - New Public Health Problem in Bulgaria

The aim of this study was to describe trends over time of human brucellosis (HB) based on national surveillance data from 1992 to 2016 in Bulgaria and to assess the factors of its re-emergence after 50 years elimination. Retrospective analytical study was applied and performed descriptive, spatial and time series analyses using national aggregated data for HB incidence from National Center of Infectious and Parasitic Diseases (NCIPD)-Sofia. During the 25-year period, 190 confirmed cases were reported, resulting in annual incidence of 0.10 cases per 100,000 populations. Dynamic model of the epidemic process and risk factor were analyzed. The fitted Autoregressive integrated moving average (ARIMA) model of HB incidence also was selected. There were differentiated two cycles of infection spreading out lasting 12-13 years with two epidemic waves (1996 and 2002). Greater incidence of HB was recorded during the peaks of epidemic waves in the second epidemic cycle – 0.52-0.76/100,000 population. Re-emergence of brucellosis in Bulgaria started from areas bordering endemic countries and gradually extended inland. The geographic location of Bulgaria as external border of European Union (EU) and transit crossroad among Asia, Africa and Europe increases the risk of HB re-emergence to the country. Involvement of all responsible institutions for public healthcare is required.