Human Brucellosis

Background: Brucellosis caused by Brucella species is a zoonotic disease prevalent in Nigeria. Data on this disease in humans and its risk factors in Lafia, Nasarawa State, are lacking.

Materials and Methods: This study was conducted on high-risk individuals in the area using the Rose Bengal test (RBT) and questionnaire.

Results: Out of the 160 respondents tested for seropositivity to brucellosis, 10% (16/160) prevalence was recorded with the RBT. None of the factors evaluated was found to be significantly associated with the seroprevalence of brucellosis in the area. On the other hand, final logistic regression analysis found the knowledge of brucellosis to be significantly associated with the profession (OR=11.52; 95% CI=1.47-90.46; p=0.02) and age (OR=2.6; 95% CI=1.11-4.19; p=0.023). Furthermore, practices that expose to Brucella infection were found to be significantly associated with the site (OR=4.02; 95% CI=5.29- 333.33; p=0.000) and marital status (OR=2.44; 95% CI=1.03-5.75; p=0.042).

Conclusion: Brucellosis is prevalent among occupationally exposed individuals in Lafia. There should be continued surveillance for the disease and education of high-risk individuals in the area.

Brucellosis is a serious infectious disease that continues to be a significant cause of morbidity worldwide and across all ages. Despite early diagnosis and treatment, 10–30% of patients develop chronic brucellosis. Although there have been recent advances in our knowledge of Brucella virulence factors and hosts' immune response to the infection, there is a lack of clear data regarding how the infection bypasses the immune system and becomes chronic. The present study investigated immunological factors and their roles in the transition of brucellosis from an acute to a chronic infection in CD4+ T cells. CD4+ T cells sorted from peripheral blood samples of patients with acute or chronic brucellosis and healthy controls using flow cytometry as well as more than 2000 miRNAs were screened using the GeneSpring GX (Agilent) 13.0 miRNA microarray software and were validated using reverse transcription polymerase chain reaction (RT-qPCR). Compared to acute cases, the expression levels of 28 miRNAs were significantly altered in chronic cases. Apart from one miRNA (miR-4649-3p), 27 miRNAs were not expressed in the acute cases (p <0.05, fold change> 2). According to KEGG pathway analysis, these miRNAs are involved in the regulation of target genes that were previously involved in the MAPK signalling pathway, regulation of the actin cytoskeleton, endocytosis, and protein processing in the endoplasmic reticulum. This indicates the potential role of these miRNAs in the development of chronic brucellosis. We suggest that these miRNAs can be used as markers to determine the transition of the disease into chronicity. This is the first study of miRNA expression that analyses human CD4+ T cells to clarify the mechanism of chronicity in brucellosis.

A seroprevalence study of brucellosis in humans was undertaken among high risk population of north Karnataka. A total of 201 serum samples were collected from various high risk group individuals and subjected to three different tests i.e., Rose Bengal plate test (RBPT), standard tube agglutination test (STAT) and 2 mercaptoethanol test (2-MET). On the analysis of 201 serum samples, 30 (14.92%) were positive to RBPT, 33 (16.41%) to STAT and 8 (3.98%) to 2-MET. The prevalence of brucellosis was found to be highest among individuals in the age group of >50 yrs and lowest in age group of <20 yrs. Sex wise prevalence of brucellosis was more prevalent among males compared to females.

Introduction: Pulmonary involvement is a rare, focal complication of human brucellosis. The aim of this review is to describe clinical and radiologic features, treatment administered and clinical course of these patients.

Areas covered: We conducted a systematic search of scientific reports of brucellosis with pulmonary involvement published from January 1985 to July 2016. Four main patterns of disease were observed: pneumonia, pleural effusion, nodules and interstitial pattern. Cough and fever were the most common symptoms. Brucella spp. culture was obtained from blood (50%) or pleural fluid. Treatment is based on the same antibiotics and combinations of antibiotics as for patients with acute no complicated brucellosis. The most frequent antimicrobial combination was doxycycline and rifampin for six weeks. The clinical course was favorable in most reports, and mortality was remarkably low (<1%).

Expert Commentary: Non-specific clinical and radiological manifestations were the main reason for the delay in proper treatment. Difficulty in distinguishing Brucellosis from other pulmonary infections, such as tuberculosis, sometimes posed an added diagnostic challenge.

Biología. La brucelosis es una de las zoonosis más frecuentes de distribución universal, ligada a la prevalencia de la enfermedad en animales domésticos (ganado ovino y bovino). Existen 9 especies distintas de Brucella, las más virulentas
son B. mellitensis, B. abortus y B. suis.
Epidemiología. Se transmite al hombre desde el animal infectado a través del contacto directo o del consumo de productos lácteos sin higienizar. Es un bacilo intracelular facultativo que puede sobrevivir en el interior de las células fagocíticas,
producir manifestaciones clínicas agudas, formas focalizadas y con tendencia a la recidiva de la enfermedad.
Clínica. El cuadro clínico es característico, en presencia de antecedente epidemiológico adecuado, con fiebre, sudoración, astenia, cefalea y artromialgias. La forma focalizada osteoarticular es la más frecuente. La focalización neurológica o cardiaca es la más grave.
Diagnóstico. El método diagnóstico definitivo es el aislamiento del germen en el hemocultivo, médula ósea u otros especímenes. Es un germen de crecimiento lento, por lo que es necesario mantener en proceso la muestra hasta 6 semanas. El diagnóstico serológico se basa en la demostración de anticuerpos específicos frente a la cadena O del LPS mediante técnicas clásicas (seroaglutinación, Rosa de Bengala y prueba de Coombs anti-brucela) o las pruebas de ELISA, inmunocaptura o fluoroinmunoensayo.
Tratamiento. Los objetivos primarios del tratamiento de la brucelosis son mejorar los
síntomas, reducir complicaciones y prevenir recidivas. El régimen preferido es una terapia combinada con doxiciclina (100 mg cada 12 horas durante 45 días) y estreptomicina (1g al día intramuscular durante 2-3 semanas) o gentamicina en dosis de 5 mg/kg al día durante 7- 14 días en una sola dosis intramuscular. La
combinación de doxiciclina 100 mg al día más rifampicina 900 mg al día durante 45 días es una alternativa razonable. En los pacientes que presenten enfermedad focal la duración del tratamiento debe ser individualizada.

Vertebral osteomyelitis (VO) is an infrequent disease that requires early antibiotic treatment to prevent serious disabling sequels. The aim of our study was to identify clinical variables capable to guide the initial treatment. Patients and methods. Our retrospective study involved 103 patients seen during a 13 years period, mostly (94%) diagnosed by magnetic resonance imaging. Patients were classified as having brucellar (50 patients), pyogenic (29 patients), tuberculous (20 patients), and other  (4 patients) spondylitis. Clinical and laboratory variables entered into a multivariate analysis to identify those independently associated with each etiologic subgroup. Results. Brucellar spondylitis was associated with epidemiological exposure (LR+: 14,9; LR­: 0,02), and with a blood neutrofil percentage ≤ 65% (LR+: 6,6; LR­: 0,12). The presence of an underlying chronic disease (LR+: 29,5; LR­: 0,01), an erythrocyte sedimentation rate ≥ 60 mm/h (LR+: 11,3; LR­: 0,07), and the absence of constitutional symptoms (LR+: 5,2; LR­: 0,18), were independent predictors of a pyogenic spondylitis. Finally, previous exposure or tuberculous disease (LR+: 11,2; LR­: 0,06), and a delay of ≥ 8 weeks in first consulting (LR+: 10,6; LR­: 0,07) were associated with tuberculous spondylitis. Conclusion. The combination of a few clinical and laboratory variables facilitates the differential diagnosis between pyogenic, brucelar and tuberculous vertebral osteomyelitis, allowing the choice of the initial antibiotic treatment.

Unresolved issues remain surrounding the treatment of human brucellosis. The present work aims to provide useful information to help clinicians make decisions when treating brucellosis patients. Information based on scientific evidence from clin‐ ical trials published over the past 30 years has been compiled and presented in an up‐ dated form, covering both focal and non-focal, or uncomplicated, human brucellosis. This chapter shows that, despite the studies published in recent years, areas such as the role of monotherapy or treatment in cases of focal disease, have not been ade‐ quately addressed in clinical trials, and demonstrates the need for further research.

The use of enzyme-linked immunosorbent assay (ELISA) for the detection of IgG and IgM antibodies antibrucella has become widespread in the diagnosis of human brucellosis. IgM anti-Brucella antibodies are indicative of acute infection. Between 2009–2013, 5307 patients were evaluated for serologic diagnosis at the Microbiology Laboratory of the Albacete General Hospital. A ELISA IgM-positive, IgG-negative anti-Brucella antibody serology pattern was detected in 17 of those patients. Epidemiology data, symptoms, laboratory data, treatment and outcome from these patients were reviewed. Sixteen patients presented with musculoskeletal pain, fatigue and/or fever and 1 was asymptomatic. Five patients received treatment with doxycycline combined with rifampin, gentamycin or streptomycin during 6–12 weeks, with no improvement. None of the 17 patients were finally diagnosed with brucellosis. Our results indicate that anti-Brucella IgM positive serology, per se, is not enough to diagnose acute brucellosis and other methods should be used for confirmation. Brucella serology data should be interpreted taking into account the patient's clinical history and epidemiological context.

Infectious diseases have been a major health problem to humans, since humans emerged as a species. Until the 20th century, the only source of information for diagnosing and estimating the virulence and prevalence of diseases in antiquity was literary sources. PCR identification, however, added another source of evidence to make such analyses. While this advance in biology has aided the study of paleopathology, another biotechnology is now available. Even though Next-Generation Sequencing (NGS) has been available since the mid-1990, its use in paleopathology has been limited because of its high-cost. Over the course of the last decade, however, refinements in the technology have made it cheaper and therefore, more available. As a result of that decrease in cost, the amount of literature for paleopathology has grown significantly over the last ten years. This paper reviews the literature for three infectious diseases—brucellosis, tuberculosis and Yersinia pestis¬—and demonstrates how NGS has revolutionized the study of these diseases in antiquity. Furthermore, it outlines future questions that scholars should consider when applying NGS techniques to ancient samples. One question that scholars should consider in future research is how these diseases have affected humans at the genome-level. The coevolutionary relationship between humans and diseases has been understood poorly up to this time. NGS research on ancient remains of both humans and diseases could change this understanding.

This is the second chapter of my honors thesis.

Brucellosis is an infectious disease that has infected humans for thousands of years. Little is known about the origin of the disease and how its virulence has evolved over the centuries. NGS on more ancient strains of brucellosis may provide information about the history of its virulence and in turn its prevalence. This chapter investigates the co-evolutionary relationship shared between this disease and man.

Background: Brucellosis is a worldwide zoonotic disease that remains an important public health problem especially in rural Turkey. The aim of this study is to identify Brucella species and investigate the in-vitro susceptibilities of clinical isolates against various antibiotics.

Diffuse involvement of liver and spleen is frequently seen in brucellosis, suppurative abscesses caused by Brucella are less common but well described. With the increased availability of cross-sectional imaging techniques, reports have become more frequent. Four patients with hepatosplenic abscesses caused by Brucella spp. are described and included in a review of 115 previously published cases. Clinical characteristics and patterns on ultrasound (US) and computer tomography imaging were analyzed. Furthermore, the proportion of patients with brucellosis affected by suppurative hepatosplenic lesions was estimated. Hepatosplenic abscesses were seen in 1.2% of patients with brucellosis, which were mostly caused by Brucella melitensis. Imaging analysis revealed two main distinct patterns. Solitary abscesses involving liver more frequently than spleen, and showing characteristic central calcifications, characterize the first pattern. Multiple smaller abscesses, frequent spleen involvement, and absence of calcifications characterize the second pattern. Blood and aspirate cultures were frequently negative, however, the positivity rate increased over the past years. Indirect Coombs test was positive in 96%. Half of the patients were cured by antibiotic treatment; case fatality in this series was 1.9%. Hepatosplenic abscesses due to Brucella infections have characteristic imaging findings. Clinicians should be aware of these and the proactive use of cross-sectional imaging, particularly US, should be encouraged in endemic regions.

The seroprevalence of three bacterial re-emerging diseases namely brucellosis, leptospirosis and melioidosis was investigated in farmers and technical staff of Selangor and Negeri Sembilan. The study found that the highest seroprevalence for both Selangor and Negeri Sembilan was among the farmers with seroprevalence of 5.05% ± 2.15 and 5.88% ± 3.7 respectively. Among the technical staff, the highest seroprevalence for the disease was observed among the staff in Negeri Sembilan. Antibodies against Leptospira spp was the most commonly detected among the three pathogens. Knowledge of the mode of transmission of zoonotic infections may have been an advantage for the technical staff in preventing exposure to these pathogens.