Brucellosis: Infectious Disease

Abstract

Brucellosis is a zoonotic disease caused by Brucella species, a small, Gram-negative coccobacilli group, with four species (B. melitensis, B. abortus, B. canis, and B. suis), causing illness in humans. These bacteria have a different type of outer membrane containing lipopolysaccharides (LPS) compared to similar bacteria like those in the Enterobacteriaceae family. Symptoms typically begin with a sudden fever, and as the illness progresses, it can enter into chronic stage characterized by recurring episodes of fever, along with symptoms such as weakness, sweating, and general discomfort. Human brucellosis is caused by various strains of Brucella bacteria, including B. abortus (from cattle), B. melitensis (from sheep and goats), and B. suis (from hogs). While infections from B. canis (from dogs) are infrequent, they have been reported. Among these, B. melitensis and B. suis tend to be more potent in terms of their pathogenicity. Farm animals, raw dairy products, and wild animals such as deer, bison, horses, moose, caribou, hares, chickens, and desert rats can carry brucellosis, which can also infect humans. In this chapter, we will discuss how brucellosis is contracted and the diseases it can cause. We will focus on Iraq, where brucellosis is a common disease.

1. Introduction

Brucellosis is a prevalent zoonotic illness caused by parthenogenetic intracellular parasites known as Brucella. Its discovery dates to 1860 when British physician JA Marston identified it as a distinct infectious disease on the Mediterranean island of Malta, naming it “Mediterranean flaccid fever” and “Maltese fever.” In 1887, British army doctor David Bruce successfully isolated the causative agent, “Micrococcus Maltese,” from the spleen of a deceased soldier in Malta. As a tribute to Bruce’s contribution, the disease was subsequently named brucellosis [1, 2]. The authors in Ref. [3] referred to the bacterial infection humans can acquire from infected animals’ meat, urine, body fluids, aborted materials, unpasteurized milk, and milk products or contaminated environment. Brucellosis is a disease caused by several species of bacteria collectively called Brucella. The disease is one of the highest priority animal diseases in different regions of the world. Brucellosis infects many species including livestock, wildlife, and humans. Most human infections are acquired through direct contact with infectious livestock or via indirect transmission by ingesting unpasteurized milk and milk products or by engaging in occupational activities.

The disease has a wide range of impacts that include losses due to abortion, culling of infected animals, lost milk production, animal replacement costs, veterinary fees, and human illness—causing reduced work capacity [1]. The history of brucellosis goes beyond the 1887 isolation and identification of Brucella melitensis and extends back to people’s initial contact with animals [1, 3, 4]. The disease has been known by various names including Malta fever, Crimean fever, Bang’s disease, Rock fever, Maltese fever, Gibraltar fever, Undulant fever, Mediterranean fever, or Gastric remittent [5, 6]. It remains the most common and continually reemerging zoonosis worldwide since 1884, and it is accountable for more than 500,000 new human cases annually [7]. Additionally, low infectious doses (10–100 bacterial cells), rapid transmission through different pathways, persistence in the environment, and treatment difficulties with antibiotics make Brucella a possible bioterrorism agent [6]. The most harmful species of Brucella, which can infect a wide range of hosts, are the ones that are most likely to infect pets (Figure 1) [8]. Brucellosis is a zoonotic disease, which means it can be transmitted from animals to humans and each Brucella species can be transmitted from animals to humans. The Brucella bacteria that cause this disease are very similar to each other, with about 97% of their genes being identical.

Figure 1.

The Brucella species shown in blue are known to cause disease in humans. The thickness of the solid arrows shows how often these animals are the source of human infection. The dashed arrows show that Brucella strains have been isolated from human disease, but there is no evidence that they were transmitted directly from the corresponding natural host to humans. The question mark indicates that the natural host for B. inopinata is unknown.

2. Infectious

2.1 Brucellosis, a zoonosis

Brucellosis, a Zoonosis Humans, is accidental hosts for Brucella. Humans are not the natural hosts for Brucella bacteria, but they can become infected through contact with infected animals, inhalation of airborne agents, or ingestion of contaminated dairy products [9]. Human-to-human transmission is rare, but it can occur through organ transplantation, blood transfusion, or breastfeeding [10, 11]. The symptoms of brucellosis can be mild or severe, and they often mimic other diseases. Common symptoms include fever, fatigue, malaise, and anorexia. If left untreated, brucellosis can progress to a chronic phase, leading to serious complications such as endocarditis, orchitis, spondylitis, osteomyelitis, arthritis, meningoencephalitis, and recurring fevers [12, 13].

Brucellosis can have serious consequences for domestic animals, such as cattle, sheep, goats, and swine. It can cause abortion and metritis in females, and orchiepididymitis and infertility in males. These infections can lead to reduced fertility and a significant decline in milk production [14].

Animal brucellosis is a highly contagious disease that can spread between animals and humans (cross-species transmission of certain Brucella spp. exists) [15]. It is mostly transmitted through direct contact with infected animals or their secretions, [16] such as aborted fetuses and fetal membranes; the bacteria can be found in large amounts in it [17].

2.2 Infection and dissemination

Brucella bacteria enter the host through the linings of the respiratory and digestive tracts [18]. Once inside their host, specialized immune cells called phagocytes, such as macrophages and dendritic cells, engulf and destroy the Brucella bacteria. After engulfing the bacteria, phagocytes transport them to the nearest lymph nodes, where they are sampled by the immune system. This leads to subsequent dissemination to the different organs of the reticuloendothelial system, including lungs, spleen, liver, and bone marrow [19]. In pregnant animals, the bacterium Brucella has a strong affinity for the placenta and mammary glands [20]. It replicates extensively in these tissues, causing inflammation of the placenta (placentitis) and abortion in the last trimester of pregnancy in ruminants [19].

In humans, brucellosis can affect any organ in the body, but it is most likely to affect the joints and liver. It can also affect the brain and heart, but to a lesser extent [20]. This is because the brain and heart are protected by the blood-brain and heart-blood barriers, respectively. These barriers make it more difficult for bacteria to enter these organs. The endoplasmic reticulum is the preferred intracellular niche for Brucella [21]; the data in Figure 2 provide evidence for this claim that Brucella bacteria have a variety of places in the body where they can live and multiply. This includes the ER, which is a preferred intracellular niche for Brucella bacteria. It also includes certain organs, such as the placenta, epididymis, mammary glands, lymph nodes, spleen, liver, lungs, and bone marrow. These organs are all important for reproduction, immunity, and metabolism, which makes them ideal for Brucella bacteria to hide.

Figure 2.

Summary of Brucella’s cellular niches and reservoirs Brucella bacteria can replicate rapidly in certain organs, such as the placenta, epididymis, mammary glands, lymph nodes, spleen, liver, lungs, and bone marrow. These organs are also where the most severe symptoms of brucellosis are seen. Once the immune system responds to the infection or granulomas form, Brucella bacteria can persist in the body at low levels. These bacteria can then start new infection cycles in other hosts. Brucella bacteria have also been found in wild animals, such as sheep, goats, frogs, foxes, bats, and rodents. The zoonotic potential of these wildlife reservoirs is still unknown, but they represent an important risk of transmission to livestock or humans. Created with BioRender.com (accessed on 15 December 2020).

3. Diseases

As mentioned above brucellosis is a major public health problem in many countries. Despite the fact that brucellosis is a serious illness with 500,000 new cases annually and the potential to have a major negative impact on both health and the economy [22]. The World Health Organization (WHO) classifies it as a “neglected logical disease” [23]. Brucellosis is a common disease in many parts of the world, including the Middle East, Asia, Africa, South and Central America, the Mediterranean, and the Caribbean. More than 170 countries and territories have reported cases of brucellosis, and outbreaks have been particularly severe in Syria, Mexico, Peru, Argentina, and Africa [24].

Humans are usually infected incidentally in one of three ways:

• Direct contact with infected animals: Humans can become infected with brucellosis through direct contact with the tissues of infected animals. This can happen through skin abrasions, cuts, or conjunctival exposure. Occupational exposures that put people at risk include veterinarians, shepherds, ranchers, and slaughterhouse workers [24].

• Ingestion of contaminated food or water: The most common way to get brucellosis is by ingesting contaminated food or water. This can happen through contaminated milk products, such as cheese, yogurt, and ice cream. Pasteurization of dairy products prevents transmission and has drastically reduced the incidence of brucellosis in the developed world. Meat products are rarely the source of infection because they are not usually eaten raw, and the number of organisms in muscle tissue is low.

• Inhalation of infectious aerosols: The inhalational route is another way that humans can get brucellosis. This is most likely to happen in occupational settings, such as slaughterhouses, where people are exposed to Brucella bacteria in the air. Laboratory workers who culture Brucella bacteria may also be at risk of inhalational exposure [25, 26].

Due to its high contagiousness among animals and the potential for disease transmission through aerosol inhalation, Brucella species are frequently listed as potential bioterrorism agents. Despite not forming spores and being less adept at surviving in extreme environments compared to B. anthracis, Brucella can remain viable for several weeks in moist soil and farm slurry at ambient temperature [27]. Clinically, brucellosis often presents with non-specific symptoms including fever, excessive sweating, fatigue, muscle and joint pain, decreased appetite, weight loss, and enlargement of the liver, spleen, and lymph nodes. The disease has a prolonged and recurrent course, affecting multiple systems and organs. Osteoarticular involvement is the most common complication, with a prevalence ranging from 2 to 77%, typically leading to conditions such as spondylitis, sacroiliac arthritis, and peripheral arthritis.

Around 50% of brucellosis patients experience hepatosplenomegaly, and gastrointestinal disturbances such as abdominal pain, nausea, and vomiting are common. Although respiratory involvement is less frequent, cases of pneumonia, pleurisy, pleural effusion, and pulmonary nodules have been reported. Additionally, 2–20% of cases involve infections of the male genitourinary system, primarily resulting in unilateral epididymal-orchitis and orchitis. Cardiovascular involvement poses the most serious complication, with brucellosis endocarditis accounting for more than 80% of deaths despite the overall mortality rate of brucellosis being approximately 1%. Hematologic complications are also observed, with anemia occurring in around 20–53% of children during the acute phase. Neurological manifestations, mainly in the form of meningitis, are reported in approximately 0.5–25% of brucellosis cases [24]. Brucellosis is a significant public health issue in developing countries, posing a major threat to human health and the entire social and economic development. Because its clinical symptoms are not specific, it is easy to be misdiagnosed and that leads to a chronic phase. What is more, if treatment is not taken in the acute phase, various complications will occur, resulting in disability, skeletal deformity, and even death. Besides, brucellosis may accumulate complications of the locomotor-osteoarticular system, digestive system, respiratory system, genitourinary system, cardiovascular system, nervous system, and blood, posing a major threat to human health and the entire social and economic development [24].

Brucella bacteria can be found in different parts of the body, including adipose tissue. The role of adipose tissue in brucellosis is still not fully understood.

We can prevent brucellosis by:

• Do not consume unpasteurized dairy products while traveling.

• Be careful when handling wild pig meat and bury the remains deeply.

• Hunters, herdsmen, and animal processors should wear gloves when handling animal tissue.

• Dispose of afterbirths, discharges, and fetuses safely.

• People with weakened immune systems should not handle dogs that are known to be infected with Brucella canis [28].

4. Conclusions

Furthermore, the prolonged viability of concealed Brucella bacteria emphasizes the ability of the pathogen to establish a chronic state, a characteristic that adds complexity to the treatment, control, and eradication efforts of brucellosis. A better understanding of where Brucella bacteria hide in the body could lead to new treatments that can reach these bacteria and kill them. Current treatments are not effective against Brucella in certain cells and organs, such as the bone marrow. Brucella bacteria can hide in different parts of the host, including adipose tissue. The role of adipose tissue in brucellosis is not yet fully understood. This presents opportunities for further research that will undoubtedly enhance our understanding of brucellosis and, more broadly, the mechanisms behind chronicity in intracellular pathogens. It will aid in the development of strategies to control and manage the disease, which is experiencing a global increase in prevalence over time.