Brucellosis: Highly Neglected Zoonotic Disease

Brucellosis is one of the most prevalent bacterial zoonotic diseases causing significant economic losses due to livestock abortion, and also it is possibly life-threatening multisystem disease.

Authors: Dr. Muhammad Ali Tahir Rana, Dr. Muneeb Aslam Chaudhry, Dr. Muhammad Akram

History

In 1886, Brucella melitensis was first isolated by David Bruce from the spleen of a British soldier who had died of a febrile illness, which was known as Malta fever and it was common among military personnel stationed on the island of Malta. The bacterium was named Micrococcus melitensis, with ‘melitensis’ derived from the Roman name for Malta, ‘Melita’. In 1897, Bacillus abortus was identified as the cause of contagious abortion in cattle by Bernhard Bang. Later, in 1917, it was found that the causes of the two diseases were identical, and renamed Brucella in honor of Bruce.

Introduction

Brucellosis is a zoonotic infection transmitted from animals to humans by the ingestion of infected food products, direct contact with an infected animal, or inhalation of aerosols. Brucella is a facultative intracellular pathogen that can survive and multiply in the phagocytes and cause abortion in cattle and undulant fever in humans. Brucella species particularly B. melitensis, B. abortus, and B. suis represent a significant public health concern. At present, B. melitensis is the principal cause of human brucellosis in India. Molecular studies have demonstrated the phylogenetic affiliation of Brucella to Agrobacterium, Ochrobactrum, and Rhizobium. Human brucellosis still presents scientists and clinicians with several challenges, concerning the understanding of its pathogenic mechanism, severity, progression, and development of improved treatment regimens. It is a bacterial disease caused by several genus Brucella, which is an important zoonosis and a significant cause of reproductive losses in animals Brucellosis is usually caused by Brucella abortus and n cattle, B. melitensis or B. bovis in small ruminants, B. suis in pigs, and B. canis in dogs. Abortion, placentitis, epididymitis, and orchitis are the most common consequences, although another syndrome is also reported. The main impact is economic, death is rare except in the fetus and neonate some Brucella species are also maintained in the wildlife population. Brucellosis is a zoonosis primarily of domestic animals, causing a chronic debilitating septicemic disease leading to abortion. The disease is prevalent worldwide and is particularly common in the Mediterranean and Middle Eastern countries, and in parts of Africa and South America, there are also other names of this disease like Malta fever, Undulant fever, Mediterranean fever, and Gastric fever. It is Gram-negative, intracellular coccobacilli, non-motile, non-capsulated, and non – spore-forming

Brucellosis

Figure 1 Brucella spp. are gram-negative in their staining morphology. Brucella spp. are poorly staining, small gram-negative coccobacilli (0.5-0.7 x 0.6-1.5 µm), and are seen mostly as single cells and appearing like “fine sand”. 

Geo-graphic Distribution

It is found worldwide but it is well controlled in most developed countries. Clinical disease is still common in the Middle East, Asia, Africa, South, and Central America. Brucella species vary in their geographic distribution. Brucella abortus is found worldwide in cattle raising region to expect in Japan, Canada some European countries, Australia New Zealand, and Israel where it has been eradicated

Zoonotic importance around the world

Brucellosis causes more than 500,000 human infections per year worldwide. The disease has a limited geographic distribution, but it remains a major public health problem in the Mediterranean region, western Asia, parts of Africa, and Latin America. Brucellosis in animals causes tremendous economic losses due to abortion, premature birth, decreased milk production, and reduced reproduction rate. Despite the advances made in surveillance and control, the prevalence of brucellosis is increasing in many developing countries due to various sanitary, socioeconomic, and political factors. Brucellosis in cattle seems to be associated primarily with poor farm hygiene, unrestricted trade and movement of animals, use of local cattle yards and fairs for trading, the practice of returning non-lactating animals to villages for seasonal maintenance, and the use of semen from infected bulls of unknown health status for artificial insemination. WHO delivers instructions to member states to establish the standards and information regarding brucellosis management in humans and animals with the alliance of the Food and Agriculture Organization (FAO) and World Organization for Animal Health (OIE), WHO is currently working to deliver its assistance to countries for the proper management against brucellosis. Recently in 2020, the capital city of Gansu province, confirmed that 3,245 people had contracted the disease brucellosis, which is often caused by contact with livestock carrying the bacteria brucella.

Transmission of Disease;

  1. abortus, B. melitensis, B. suis, and B. canis are usually transmitted between animals by contact with the placenta, fetus, fetal fluids, and vaginal discharge from an infected animal. Animals are infectious after either an abortion or full-term parturition. Although ruminants are asymptomatic after their first abortion, they can become chronic carriers and continue to shed off Brucella in milk and uterine discharge during subsequent pregnancies. Mostly Brucella species can be found in semen too.

Pathogenesis

Their pathogenesis includes following steps such as ingestion, inhalation, inoculation, and person to person transmission is very rare. In the first step ingestion, maybe by raw milk and unpasteurized dairy products and rarely undercooked meat, while in the step of inhalation and inoculation, involve of placental or uterine discharge, blood, and urine Animal tissues and products such as placenta uterus and milk that are rich in erythritol (growth factor for Brucella) can be heavily contaminated and highly infectious. It is spread in the body via lymphatic system replication with lymph nodes and then wide hematogenous spread to organ and tissues. Intracellular parasitism: brucella have a particular tendency to persist intracellularly, notably in the reticuloendothelial system

Clinical signs:

In humans

In humans, brucellosis comprises dysfunction of different organs with multiple complications and different clinical symptoms including acute to chronic cases. That is the reason for misleading of brucellosis to the other diseases.

The first one is acute brucellosis, which is characterized by weakness, undulant fever, headaches, myalgia, fine red rash, splenomegaly, hepatomegaly, and gastrointestinal problems. It can lead to severe conditions and the result is death.

Second is sub-acute brucellosis, which is characterized by almost the same symptoms typical of the acute course but in somewhat milder type.

Chronic brucellosis is characterized by sweats, fatigue, undulant fever, arthritis, endocarditis and spondylitis, personality changes. It is often misdiagnosed with other diseases like malaria and typhoid fever, resulting in false treatment and leads to death.

In animals

The transmission mode in animals includes absorption it can be through inhalation of the infected aerosol route, conjunctival inoculation, skin abruption, and udder infection, or milking equipment. The other source of infection is Aborted fetuses and fetal membranes. The uterine secretions come out after abortion provides the source of infection.

This disease is known as bang disease in animals. In large animals, the symptoms include the loss of productivity, reduction in animal fertility, and a decrease in milk production. It is a sub-acute or chronic disease that can affect a wide range of domestic and wild animals.

The other symptoms include late-term abortions, reduction in body weight of calves, stillbirths, infertility. Placentitis, epididymitis, and orchitis are also characterized by brucellosis. Infected bulls may develop systemic signs of infection including fever, anorexia, and depression.

Treatment:

According to WHO recommendation, doxycycline with a dose rate of 100 mg can be given twice a day for up to 6 weeks. Rifampicin with a dose rate of 600 to 900 mg in a day up to 6 and streptomycin intramuscularly up to 3 weeks is sufficient for the treatment of brucellosis. Another treatment regimen consists of streptomycin u to 3 weeks with addition to doxycycline for 8 weeks or gentamicin for 5-7 days in addition to doxycycline for 8 weeks. For the second line of defense, quinolones or trimethoprim-sulfamethoxazole can be given for patients in case of treatment failure or repeated relapses. In complicated disease cases, treatment intervention needs a careful prescription of the patient and a thorough therapeutic regimen. Patients with spondylitis should be administered a quinolone as a preliminary treatment, for a protracted-time period.

Diagnostic tools:

The diagnosis of brucellosis should be based on medical history, which involves clinical evaluation and daily base laboratory and radiologic tests also with culture, serological tests, or polymerase chain reaction (PCR) assay. The standard and most specific test for diagnosis of Brucella spp. in bacterial isolation but it has a dark side that it is time-consuming. It also requires biosafety and expert personnel. The most commonly used serological screening tests are the serum agglutination test (SAT), Rose Bengal test, complement fixation test, and enzyme-linked immunosorbent assay. All tests have limitations concerning specificity and sensitivity, especially when testing individual animals. The SAT appears less sensitive and less specific than any other standardized test for all animal species compared. Thus, the SAT is no longer recommended as an official screening test for brucellosis within the EU

Prevention

  • Do not consume undercooked meat
  • Do not consume unpasteurized dairy products, including:
    • Milk
    • Cheese
    • Ice cream

People who handle animal tissues (such as veterinarians, hunters, and animal herdsman) should protect themselves by using the:

  • Rubber gloves
  • Goggles
  • Gowns or aprons
Authors: Dr. Muhammad Ali Tahir Rana, Dr. Muneeb Aslam Chaudhry, Dr. Muhammad Akram

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