The medical literature is flooded with numerous studies from different parts of the world, especially those endemic with brucellosis, addressing the clinical and complication aspects of this most widespread zoonotic disease. Among a considerable number of papers published on this topic, there is a shortlist that we can consider as landmark in this field [8, 10–15, 25–28, 30, 37, 40]. On a more specific aspect dealing with neurobrucellosis, a couple of studies on this critical complication have been well noted in the literature [18, 35].

Though the clinical and complication aspects have not changed, brucellosis remains a significant zoonotic disease that is emerging or reemerging in many parts of the world. In addition, the inclusion of Brucella spp. in the potential biological weapon lists of most authorities has renewed interest in this these pathogens [17]. However, the improved knowledge and awareness, as well as the introduction of newer technology and tests, have helped detect and reveal more of such episodes in a short time [1, 3].

Whatever is presented in this chapter essentially refers to the above noted studies.

Brucellosis has been known with many synonyms mainly pertaining to the geographic locations where the disease occurred, e.g., Malta fever, Gibraltar fever, Mediterranean fever, and Cyprus fever [21].

Brucella spp. are common zoonoses among domestic animals and wildlife and have been recovered from marine mammals. Though over 10 Brucella spp. have been recognized, only four have been well recognized to cause human infections, and, together with their preferred/predominant host, they are B. melitensis (mostly in goats, sheep, and camels), B. abortus (mostly in cattle), B. suis (mostly in swine), and B. canis (in dogs). Brucella spp. recovered from marine animals were reported to cause human infections [21].

The incubation period may be long but the symptoms can appear in a short time (within 1–4 weeks). Once the organisms enter the body by various routes, they are encountered by the polymorphonuclear and mononuclear phagocytes. The intracellular location contributes to their virulence and pathogenesis, as they preferentially replicate within phagocytic cells. Brucella uses several mechanisms to avoid being killed and establish a survival niche within macrophages. To help evade the immune system and facilitate propagation, and persistence within macrophages and other cells, the pathogen forms Brucella-containing vacuoles (BCV) and inhibits the phagosome-lysosome. Subsequently, they are transported through regional lymph nodes into the circulatory system to seed and involve a wide range of body organs or systems, with tropism for the reticuloendothelial system, resulting in different clinical phases of disease [22].

Though receiving close attention, the exact nature of the immune response and protective antigens/factors involved in this disease are still being investigated, and the pathogenic mechanisms of reinfection remain unknown. Recently, the production of cytokines, chemokines, and matrix metalloproteinases has been associated with induced osteoclastogenesis in Brucella arthritis and osteomyelitis, and the outer membrane protein 19 lipoprotein, together with tumor necrosis factor-alpha, was reported to be associated with astrocyte apoptosis in neurobrucellosis [9].

Since Brucella can infect and survive without inducing a massive inflammatory response, this bacteria was labeled as “stealth pathogen” [22, 29].

Though present worldwide, Brucella spp. endemicity is well noted in many regions such as the Arabian Peninsula, Middle East, eastern Mediterranean basin, Latin America, Southern Europe, Central Asia, and the Indian subcontinent [16].

Globally, around 500,000 cases are reported annually. Because of nonspecific presentation of its signs and symptom features, it is estimated that for each reported case, 25 cases are not reported [41].

In many countries, brucellosis remains continuing or reemerging causing significant economic losses, not only from cost associated with clinical treatment and lost productivity in human infections but also by economic costs associated with reproductive losses in livestock [31].

Animals are generally asymptomatic carriers of these bacteria, and the major symptoms appear during infectious abortion of the animal fetus and placenta. In humans, its epidemiology differs between areas of endemicity and nonendemicity in terms of age, sex, season, and risk factors. In regions of endemicity, the disease occurs among the general population, with the levels of infection being almost equal among adults and children of both sexes and mostly due to ingestion of unpasteurized dairy products (e.g., soft cheese, ice cream) from goat, sheep, cow, and camel [26, 34].

In nonendemic areas, infection is seen predominantly among adult males, acquired occupationally by handling or manipulating infected animals or cultures of the pathogen and by transmission through direct skin contact (e.g., accidental inoculation through skin cuts and abrasions) and through inhalation of infected aerosols or aerosols inoculated into the eye, mouth, and nose. These infections occur mostly among dairy industry professionals, veterinarians, abattoir workers, and clinical and research microbiology staff. Most cases of laboratory-acquired disease result from mishandling and misidentification of the organism [38].

Infection of humans with Brucella spp. ranges from asymptomatic to full-blown clinical features. Among the latter, different criteria has been suggested to define clinical categories of human brucellosis. For example, in 1956, Spink [37] based them on the duration of symptoms: acute (presentation ≤2 months), subacute (2–12 months), and chronic (≥12 months). Subsequently, others based them primarily on extent of clinical manifestations (e.g., subclinical, localized, chronic, and active, with or without localized disease, including bacteremic and serological classifications) [13, 27, 41]. It is interesting to note that the variation in the incident rates of clinical presentation and complications reported among different published studies can be attributed to the lack of consensus/uniform categorization definition used.

Brucella has a very low infectious dose (≤10² organisms) and a variable incubation period. The disease onset is insidious and can present with a diverse range of over 30 nonspecific clinical signs and symptoms mainly fever, weakness, malaise, headache, sweats, joint manifestations, myalgia,, fatigue, cough, loss of appetite, weight loss, hepatomegaly, and splenomegaly. All these can be present but at variable rates in the acute, subacute, or chronic clinical categories [11, 26].

Brucellosis complications can involve different body sites with common localization. The routine hematology and biochemical profiles are usually within normal limits. Some elevation in liver function tests and erythrocyte sedimentation rate can be noted [11, 15, 19, 26, 28, 32, 40].

Complications of human brucellosis remains medically problematic and challenging [11, 26, 32]. They present in diverse features and can occur at variable rates in the acute, subacute, or chronic clinical categories [26]. The variability in the reported rates among different studies could be attributed to the variable delay in the diagnosis of brucellosis [3, 26].