Stability of a stochastic brucellosis model with semi-Markovian switching and diffusion.

To explore the influence of state changes on brucellosis, a stochastic brucellosis model with semi-Markovian switchings and diffusion is proposed in this paper. When there is no switching, we introduce a critical value R s and obtain the exponential stability in mean square when R s < 1 by using the stochastic Lyapunov function method. Sudden climate changes can drive changes in transmission rate of brucellosis, which can be modelled by a semi-Markov process. We study the influence of stationary distribution of semi-Markov process on extinction of brucellosis in switching environment including both stable states, during which brucellosis dies out, and unstable states, during which brucellosis persists. The results show that increasing the frequencies and average dwell times in stable states to certain extent can ensure the extinction of brucellosis. Finally, numerical simulations are given to illustrate the analytical results. We also suggest that herdsmen should reduce the densities of animal habitation to decrease the contact rate, increase slaughter rate of animals and apply disinfection measures to kill brucella.

Brucellosis screening and follow-up of seropositive asymptomatic subjects among household members of shepherds in China.

To measure the seroprevalence of high-exposure populations in brucellosis endemic areas and report the outcome and duration of seropositive asymptomatic subjects, we screened 595 family members of shepherds in Jilin Province, China and then followed up 15 seropositive asymptomatic subjects for 18 months. We found that the seropositive rate of 15.5%. Nearly half of seropositive asymptomatic subjects (7/15) developed into brucellosis in the short term; others were still seropositive asymptomatic or had decreased SAT titer in a longer time.

Opposite outcomes of coinfection at individual and population scales.

Coinfecting parasites and pathogens remain a leading challenge for global public health due to their consequences for individual-level infection risk and disease progression. However, a clear understanding of the population-level consequences of coinfection is lacking. Here, we constructed a model that includes three individual-level effects of coinfection: mortality, fecundity, and transmission. We used the model to investigate how these individual-level consequences of coinfection scale up to produce population-level infection patterns. To parameterize this model, we conducted a 4-y cohort study in African buffalo to estimate the individual-level effects of coinfection with two bacterial pathogens, bovine tuberculosis (bTB) and brucellosis, across a range of demographic and environmental contexts. At the individual level, our empirical results identified bTB as a risk factor for acquiring brucellosis, but we found no association between brucellosis and the risk of acquiring bTB. Both infections were associated with reductions in survival and neither infection was associated with reductions in fecundity. The model reproduced coinfection patterns in the data and predicted opposite impacts of coinfection at individual and population scales: Whereas bTB facilitated brucellosis infection at the individual level, our model predicted the presence of brucellosis to have a strong negative impact on bTB at the population level. In modeled populations where brucellosis was present, the endemic prevalence and basic reproduction number ([Formula: see text]) of bTB were lower than in populations without brucellosis. Therefore, these results provide a data-driven example of competition between coinfecting pathogens that occurs when one pathogen facilitates secondary infections at the individual level.

A case report on mother-to-child transmission of Brucella in human, China.

BACKGROUND: Human brucellosis is endemic in China and commonly occurs through contact with infected animals from working with livestock or consumption of unpasteurized dairy products. Although rare, human-to-human, and possible sexual transmission, of Brucella has been reported. In this report, we describe a case of likely mother-to-child transmission of Brucella in Hunan Province, China. CASE PRESENTATION: Between June and October 2016, a 28-year old man sought care for testicular swelling and pain at several health facilities. His 26-year old wife developed intermittent fever along with right thigh and hip pain between November 2016 and February 2017 respectively. On April 5, 2017, the female patient delivered a male neonate at 34 weeks of gestation through natural labor. The child's venal blood sample was cultured on April 5, 2017. Brucella was isolated and identified on April 12, 2017. On the same date, serum antibodies of the father and mother were above 1:100 (based on the serum agglutination test [SAT]). The strains isolated from the mother and neonate were identified as Brucella melitensis biotype 1. CONCLUSIONS: This report highlights a family cluster of brucellosis. Culture results strongly support mother-to-child transmission, and a high probability of sexual transmission from husband to wife.

Associated factors in distinguishing patients with brucellosis from suspected cases.

BACKGROUND: To investigate the risk factors for brucellosis in suspected cases of the disease. METHODS: A self-designed questionnaire was developed to collect data from 3557 people whose initial visit site was the Songyuan Center for Disease Control and Prevention (CDC) from January 1st, 2009 to December 31st, 2012. After collecting blood samples, a plate agglutination test (PAT) and serum agglutination test (SAT) were used to distinguish the patients with brucellosis from the suspected cases. RESULTS: Sex, occupation (farmers and herdsmen), contact with abortion products, and contact with feces were the main risk factors for brucellosis in the suspected cases (all P < 0.05). No difference existed between the confirmed cases and suspected cases in the demographic characteristics, contact with animals (except swine), contact with substances, or clinical symptoms (except fever). However, the confirmed cases showed significant differences from people without brucellosis in demographic characteristics, contact with animals (except cattle and swine), contact with substances, and clinical symptoms. Suspected cases exhibited significant differences from people without brucellosis in the demographic characteristics (except education), contact with animals (except swine), contact with substances (except dust), and clinical symptoms (except chills and acratia). Brucella was cultured from the blood samples of three of 30 suspected cases with fever. Using AMOS-PCR and agarose electrophoresis, the detailed species of Brucella strain was identified as Brucella melitensis. CONCLUSIONS: Abortion products and feces are the main risk factors for brucellosis in suspected cases of the disease. Pyrexia in suspected cases with a history of contact with abortion products or feces should raise suspicion for the disease.

Successful Endovascular Aneurysm Repair for Brucella Mycotic Aneurysm Acquired from Ingestion of Sheep Placenta.

An aortic aneurysm infected by Brucella is rarely seen. In this case report, we describe a Brucella mycotic abdominal aortic aneurysm acquired from ingestion of sheep placenta. Clinical symptoms included fever, fatigue, and abdominal pain. Diagnosis was confirmed by blood culture and computed tomography (CT) angiography. The patient had increased abdominal pain during hospitalization, and repeated CT showed a rapidly enlarging mycotic aneurysm. Emergent endovascular repair was successfully performed using a bifurcated stent graft, and combined intravenous and oral antibiotics were administrated. The patient was asymptomatic after operation, and follow-up CT showed thrombosis in the aneurysmal sac and significant decrease of aneurysmal size.

Zoonosis and veterinary waste disposal in rural practice.

The objectives of this study were to estimate: (a) the frequency of zoonoses in large animal veterinarians from rural areas of the province of Buenos Aires, Argentina, and (b) to describe the use and disposal of personal protective equipment (PPE) and selective veterinary clinical waste. A cross-sectional study was carried out on large animal veterinary practitioners in the Province of Buenos Aires (n=106). One third (29.2%) of them had been diagnosed with a zoonosis by laboratory-methods, being brucellosis the most frequent (22.6%). The more years passed since their graduation, the greater the chances of becoming ill (p<0.001). Gloves were the most adopted PPE; however, other elements had little or no use at all. Older and experienced professionals used PPE less frequently than young inexperienced practitioners. Some PPE was frequently reused and the final disposal of veterinary waste was often inappropriate. A change in behavior is an urgent need to preserve not only the veterinarians' health but also their families' wellbeing and to ensure proper disposal of potentially hazardous waste.

Brucellosis in Dogs and Public Health Risk.

Brucella canis infects dogs and humans. In dogs, it can cause reproductive failure; in humans, it can cause fever, chills, malaise, peripheral lymphadenomegaly, and splenomegaly. B. canis infection in dogs is underrecognized. After evaluating serologic data, transmission patterns, and regulations in the context of brucellosis in dogs as an underrecognized zoonosis, we concluded that brucellosis in dogs remains endemic to many parts of the world and will probably remain a threat to human health and animal welfare unless stronger intervention measures are implemented. A first step for limiting disease spread would be implementation of mandatory testing of dogs before interstate or international movement.

Brucellosis: Improved Diagnostics and Vaccine Insights from Synthetic Glycans.

Brucellosis is a serious zoonotic bacterial disease that is ranked by the World Health Organization among the top seven "neglected zoonoses" that threaten human health and cause poverty. It is a costly, highly contagious disease that affects ruminants, cattle, sheep, goats, and other productive animals such as pigs. Symptoms include abortions, infertility, decreased milk production, weight loss, and lameness. Brucellosis is also the most common bacterial disease that is transmitted from animals to humans, with approximately 500 000 new human cases each year. Detection and slaughter of infected animals is required to eradicate the disease, as vaccination alone is currently insufficient. However, as the most protective vaccines compromise serodiagnosis, this creates policy dilemmas, and these often result in the failure of eradication and control programs. Detection of antibodies to the Brucella bacterial cell wall O-polysaccharide (OPS) component of smooth lipopolysaccharide is used in diagnosis of this disease, and the same molecule contributes important protective efficacy to currently deployed veterinary whole-cell vaccines. This has set up a long-standing paradox that while Brucella OPS confers protective efficacy to vaccines, its presence results in similar antibody profiles in infected and vaccinated animals. Consequently, differentiation of infected from vaccinated animals (DIVA) is not possible, and this limits efforts to combat the disease. Recent clarification of the chemical structure of Brucella OPS as a block copolymer of two oligosaccharide sequences has provided an opportunity to utilize unique oligosaccharides only available via chemical synthesis in serodiagnostic tests for the disease. These oligosaccharides show excellent sensitivity and specificity compared with the native polymer used in current commercial tests and have the added advantage of assisting discrimination between brucellosis and infections caused by several bacteria with OPS that share some structural features with those of Brucella. During synthesis and immunochemical evaluation of these synthetic antigens, it became apparent that an opportunity existed to create a polysaccharide-protein conjugate vaccine that would not create antibodies that give false positive results in diagnostic tests for infection. This objective was reduced to practice, and immunization of mice showed that antibodies to the Brucella A antigen could be developed without reacting in a diagnostic test based on the M antigen. A conjugate vaccine of this type could readily be developed for use in humans and animals. However, as chemical methods advance and modern methods of bacterial engineering mature, it is expected that the principles elucidated by these studies could be applied to the development of an inexpensive and cost-effective vaccine to combat endemic brucellosis in animals.

A study to identify the practices of the buffalo keepers which inadvertently lead to the spread of brucellosis in Delhi.

BACKGROUND: India has the largest Buffalo population in the world, with every household in rural India owning buffaloes depending upon daily milk requirement - dairy farmers can own between 10 to 70 buffaloes. The health of Indian buffaloes is of economic importance since India is one of the largest buffalo meat exporters in the world, and Indian Buffalo semen is sold in the USA for breeding purposes. However, National Control Program on brucellosis is only active in South India and in Panjab (a North Indian state with high human brucellosis incidence). Our aim was to assess the knowledge and practices of the buffalo keepers of Delhi that make them susceptible to brucellosis. RESULTS: Amongst all the 11 districts of Delhi, there was 0% awareness about brucellosis and also about the S19 vaccine as the buffalo keepers had never heard of S19 vaccine which is available at minimal cost from Indian Veterinary Research Institute, Bareilly, India. Majority of the respondents drink raw milk, sleep in cattle sheds, do not isolate sick cattle, do not test buffaloes blood for any disease before purchasing them, apply intrauterine medication with bare hands to buffalo after abortion of foetus, never clean their cattle sheds with a disinfectant and believe that they can only acquire skin infections from cattle. All of these habits make them prone to brucellosis. While about 20 to 27% of respondents reported a history of abortions and retained placenta, disposed of the placenta with bare hands, and applied raw milk on cracked lips. It was surprising to note that majority of them never reared small ruminants like sheep and goat with buffaloes or Bos species as they were aware of the rapid spread of disease from small to big ruminants. CONCLUSIONS: We found that buffalo keepers were ignorant of brucellosis, its causative agent, relevant vaccines and that they also involved in high-risk activities. As such, our findings highlight a need for buffalo keepers to be better educated via several awareness camps to minimize human exposure to Brucella in Delhi.

Identification of Brucella genus and eight Brucella species by Luminex bead-based suspension array.

Globally, unpasteurized milk products are vehicles for the transmission of brucellosis, a zoonosis responsible for cases of foodborne illness in the United States and elsewhere. Existing PCR assays to detect Brucella species are restricted by the resolution of band sizes on a gel or the number of fluorescent channels in a single real-time system. The Luminex bead-based suspension array is performed in a 96-well plate allowing for high throughput screening of up to 100 targets in one sample with easily discernible results. We have developed an array using the Bio-Plex 200 to differentiate the most common Brucella species: B. abortus, B. melitensis, B. suis, B. suis bv5, B. canis, B. ovis, B. pinnipedia, and B. neotomae, as well as Brucella genus. All probes showed high specificity, with no cross-reaction with non-Brucella strains. We could detect pure DNA from B. abortus, B. melitensis, and genus-level Brucella at concentrations of ≤5 fg/µL. Pure DNA from all other species tested positive at concentrations well below 500 fg/µL and we positively identified B. neotomae in six artificially contaminated cheese and milk products. An intra-laboratory verification further demonstrated the assay's accuracy and robustness in the rapid screening (3-4 h including PCR) of DNA.

Changing Epidemiology of Human Brucellosis, China, 1955-2014.

Brucellosis, a zoonotic disease, was made statutorily notifiable in China in 1955. We analyzed the incidence and spatial-temporal distribution of human brucellosis during 1955-2014 in China using notifiable surveillance data: aggregated data for 1955-2003 and individual case data for 2004-2014. A total of 513,034 brucellosis cases were recorded, of which 99.3% were reported in northern China during 1955-2014, and 69.1% (258, 462/374, 141) occurred during February-July in 1990-2014. Incidence remained high during 1955-1978 (interquartile range 0.42-1.0 cases/100,000 residents), then decreased dramatically in 1979-1994. However, brucellosis has reemerged since 1995 (interquartile range 0.11-0.23 in 1995-2003 and 1.48-2.89 in 2004-2014); the historical high occurred in 2014, and the affected area expanded from northern pastureland provinces to the adjacent grassland and agricultural areas, then to southern coastal and southwestern areas. Control strategies in China should be adjusted to account for these changes by adopting a One Health approach.

Human-to-human transmission of Brucella - a systematic review.

OBJECTIVE: The most common form of transmitting human brucellosis is through contaminated food or direct contact with infected animals. Human-to-human transmission (HHT) has been described as isolated case reports. The aim of this systematic review was to describe all cases of HHT of human brucellosis reported in the medical literature. METHODS: A literature search was conducted using PubMed, Scopus and Scielo databases using specific search terms published until March 2016. Two investigators independently determined study eligibility. All clinical data were evaluated to construct a table comprising the most important clinical aspects, age, gender, confirmed infection and detection method, transmission method and HHT confirmation and potential source of infection for human transmission. No statistical method was employed in this study. RESULTS: The initial search resulted in 615 publications, but only 35 were included. 45 brucellosis HHT cases were identified. 61% of patients who acquired brucellosis from another human were <1 year old (newborn and breastfeeding). Other cases include sexual transmission, blood transfusion, bone marrow transplantation and aerosol from an infected patient. Most patients (40/45) presented symptoms upon diagnosis. Diagnostic tests included culture, molecular methods and serum testing. CONCLUSION: Human brucellosis is a disease liable to transmission between humans by placental barrier, lactation, sexual and tissues such as blood and bone marrow. The indication for screening in tissue banks, transplants, blood and pregnancy is not yet established.

Brucellosis and thrombosis of the inferior vena cava.

We describe the case of a 23-year old woman with a newly diagnosed thrombosis of the inferior vena cava associated with a Brucella melitensis infection. We suggest possible mechanisms leading to brucellosis-associated venous thrombosis and review 14 previously reported cases.
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[Serological detection of Brucella suis, influenza virus and Aujeszky's disease virus in backyard and small swine holders in Argentina]. / Detección serológica de Brucella suis, virus de influenza y virus de la enfermedad de Aujeszky en criaderos porcinos familiares de menos de 100 madres en Argentina.

Farmers raising less than 100 sows represent more than 99% of swine producers in Argentina, although little is known about their sanitary status and productive characteristics in the country. Sanitary and productive information was obtained. Furthermore, samples for serological studies were taken to detect antibodies against Brucella suis (Bs), Aujeszky's disease virus (AV) and influenza virus (IV) in 68 backyard and small producers with less than 100 sows located in the north, central and south regions of Argentina. Antibodies against H1 pandemic were detected in 80% of the farms while 11%, 11.7% and 6.0% of the producers were positive to influenza H3 cluster 2, AV and Bs, respectively. None of the producers was aware of the risk factors concerning the transmission of diseases from pigs to humans. A percentage of 47% of them buy pigs for breeding from other farmers and markets. With regard to biosecurity measures, only 16% of the farms had perimeter fences. The results of this study demonstrate that productive characterization and disease surveys are important to improve productivity and to reduce the risk of disease transmission among animals and humans. The study of sanitary status and risk factors is necessary for better control and eradication of diseases in backyard or small producers. More representative studies at country level should be carried out to detect the pathogensthat circulate and, with this knowledge, to implement prevention and control measures.

Interactions of the human pathogenic Brucella species with their hosts.

Brucellosis is a zoonotic infection caused primarily by the bacterial pathogens Brucella melitensis and B. abortus. It is acquired by consumption of unpasteurized dairy products or by contact with infected animals. Globally, it is one of the most widespread zoonoses, with 500,000 new cases reported each year. In endemic areas, Brucella infections represent a serious public health problem that results in significant morbidity and economic losses. An important feature of the disease is persistent bacterial colonization of the reticuloendothelial system. In this review we discuss recent insights into mechanisms of intracellular survival and immune evasion that contribute to systemic persistence by the pathogenic Brucella species.

Integrating serological and genetic data to quantify cross-species transmission: brucellosis as a case study.

Epidemiological data are often fragmented, partial, and/or ambiguous and unable to yield the desired level of understanding of infectious disease dynamics to adequately inform control measures. Here, we show how the information contained in widely available serology data can be enhanced by integration with less common type-specific data, to improve the understanding of the transmission dynamics of complex multi-species pathogens and host communities. Using brucellosis in northern Tanzania as a case study, we developed a latent process model based on serology data obtained from the field, to reconstruct Brucella transmission dynamics. We were able to identify sheep and goats as a more likely source of human and animal infection than cattle; however, the highly cross-reactive nature of Brucella spp. meant that it was not possible to determine which Brucella species (B. abortus or B. melitensis) is responsible for human infection. We extended our model to integrate simulated serology and typing data, and show that although serology alone can identify the host source of human infection under certain restrictive conditions, the integration of even small amounts (5%) of typing data can improve understanding of complex epidemiological dynamics. We show that data integration will often be essential when more than one pathogen is present and when the distinction between exposed and infectious individuals is not clear from serology data. With increasing epidemiological complexity, serology data become less informative. However, we show how this weakness can be mitigated by integrating such data with typing data, thereby enhancing the inference from these data and improving understanding of the underlying dynamics.

Outbreak of Occupational Brucellosis in a Laboratory Technician at Her Royal Highness Princess Sirindhorn Medical Center, Srinakharinwirot University, Thailand.

Objective: To document laboratory transmission of brucellosis and identify the likely mechanism of transmission of brucellosis at Her Royal Highness (HRH) Princess Sirindhorn Medical Center, Thailand. Material and Method: Using small subunit ribosomal RNA (rRNA) sequencing technique to analyze Brucella melitensis cultured from the first 2 patients of the hospital and an infected laboratory technician, and using brucellosis serologic test to rule out infections in all other involved technicians. Results: We had encountered the first 2 cases of brucellosis. Both had infected from community exposure with goat. The first case had pancreatic abscess and spinal bone involvement with a positive blood culture. The second case presented with fever of unknown origin and had a positive blood culture. A few weeks later, 1 of our laboratory technicians presented with fever, myalgia and fatigue. Blood culture grew B. melitensis. He never had any associated community-acquired risk factors for brucellosis. The presumed mechanism of transmission was an inhalation while taking photographs of the bacterial plate of the first patient. B. melitensis identified from our laboratory technician and both patients were analyzed based on 16S-23S rRNA intergenic transcribed spacer (ITS) region. Results of 16S-23S rRNA ITS sequence testing confirmed a match from all patients and laboratory technician's isolate. All other 10 potentially exposed laboratory technicians were asymptomatic. A brucellosis serologic test was negative in all non-infected technicians but was only positive in the 1 infected technician. Conclusion: This is the first report in Thailand of occupational brucellosis transmitted in microbiologic laboratory. The most likely mechanism is air-borne inhalation of bacterial organisms on culture media in the absence of adequate precautions. Laboratory technicians should handle Brucella cultivation with caution utilizing appropriate measures to prevent inhalation.

The milk delivery chain and presence of Brucella spp. antibodies in bulk milk in Uganda.

This study examined the influence of informal milk delivery chains on the risk of human exposure to Brucella spp. through milk consumption in two regions of Uganda (Gulu and Soroti Districts). The work involved describing milk delivery chains, investigating brucellosis awareness amongst milk deliverers and determining the presence of Brucella spp. antibodies in cattle milk on delivery to primary collection points (boiling points and dairies). Milk samples (n = 331) were collected from deliverers at primary collection points and from street vendors at point of sale and analysed using indirect enzyme-linked immunosorbent assay (I-ELISA). A written questionnaire was used to collect data from deliverers (n = 279) on their milk delivery chains and their brucellosis awareness. The most common delivery points in Gulu District were small dairies and in Soroti District boiling points. The presence of Brucella spp. antibodies in milk samples was higher in Soroti (40 %) than in Gulu (11 %) (P < 0.0001). There are possible public health risk consequences of this finding as 42 % of deliverers in Soroti District reported drinking raw milk, compared with 15 % in Gulu District (P < 0.0001). Awareness of brucellosis was low, with 70 % of all milk deliverers reporting not having heard of the disease or the bacterium. Application of quality controls for milk (colour and odour) along the delivery chain varied depending upon supply and demand. This study provides evidence of the diversity of informal milk markets in low-income countries and of the potential public health risks of consuming unpasteurised milk. These results can be useful to those planning interventions to reduce brucellosis.

Quantitative analysis of risk factors associated with brucellosis in livestock in the Katavi-Rukwa ecosystem, Tanzania.

Brucellosis is a neglected contagious bacterial disease of public health and economic importance. Nevertheless, its spread is not well known to many livestock farmers. Unmatched case control study was carried out to identify risk factors associated with brucellosis in cattle and goats at the herd level in Mpanda, Mlele and Nsimbo districts of Katavi region, in Tanzania between September 2012 and July 2013. A total of 138 adult respondents were selected randomly for the interview using a structured questionnaire. The criterion for inclusion was to have at least one Brucella-positive animal in the herd while the control was chosen from among the herds which these animals tested negative. The presence of seropositive herds were statistically linked (P < 0.1) by univariate analysis with such variables as lack of formal education among the herders; slaughtering of cattle or goats in the household; the history of occurrence of abortion in the herd; and the history of occurrence of retained foetal membranes in the herd following parturition. However, in the multivariate analysis, lack of formal education among the herders and the previous history of occurrence of retained foetal membrane in the herd following parturition were significantly associated with Brucella seropositive (P < 0.05). This study suggests the need for raising community awareness on the risk factors associated with the transmission of brucellosis between animals and humans and the implementation of disease prevention and control programmes.