Brucella melitensis is the causative agent of brucellosis disease in humans. Understanding brucellosis symptoms help treat Brucellosis to avoid further risk.

Brucellosis

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Iqra Mazhar

Overview

Brucellosis is caused by a group of bacteria that belong to the genus Brucella, which can infect both animals and humans. It is spread through contaminated food, for example, raw meat and unpasteurized milk. Moreover, the bacteria are also airborne and can also spread by contact with an open wound.

Brucellosis is an infectious disease that is caused by Brucella bacteria. The bacteria can spread from animals to humans.

Brucella bacteria has several different strains and some of the types are seen in cows, while others occur in sheep, dogs, and camels. Moreover, new strains have been seen in the red fox and some marine animals, for example, seals. However, brucellosis in animals is incurable.

It is very rare in the United States because of programs that effectively control animal diseases. It is mostly seen either during the spring or summer in Texas, Virginia, Florida, and California.

Furthermore, brucellosis is a threat to public health in other parts of the world, and according to the WHO, it has been reported in more than half a million people every year in hundred countries<a href="#accordion">[1]</a>. It is more common in males compared to females. The reason behind gender vulnerability is occupational exposure to animals<a href="#accordion">[2]</a>.

Brucellosis is a zoonotic infection meaning that the bacteria spread from animals to humans through contaminated food products, direct contact with Brucella-infected animals, and/or by inhaling the aerosols. It is an old disease, referred to by multiple names - Mediterranean fever, gastric remittent fever, Malta fever, and undulant fever. Although humans are accidental hosts, brucellosis is a major threat to public health across the globe, and it is the most common zoonotic infection<a href="#accordion">[3]</a>. 
&nbsp;

Brucella organisms are aerobic intercellular coccobacilli that are present in the host animal&rsquo;s reproductive organs, which causes sterility and natural abortions. They shed in the urine, milk, and placental fluid of the animals in large numbers. Researchers have identified twelve species that are the primary source of the infection. However, only four of them have moderate or significant human pathogenicity. 
&nbsp;

<ul>
	<li>Brucella melitensis (from sheep; highest pathogenicity)</li>
	<li>Brucella suis (from pigs; high pathogenicity)</li>
	<li>Brucella abortus (from cattle; moderate pathogenicity)</li>
	<li>Brucella canis (from dogs; moderate pathogenicity) 
	&nbsp;</li>
</ul>

Domesticated animals are of more importance, but brucellosis is also found in animals that travel in herds (wild animals). Humans are at very low risk of wild animals, because of low frequency and low probability of contact. However, there have been some concerns about wild animals transferring the bacteria to domesticated animals. This can cause the infection to spread in agricultural herds, but the evidence to back this is quite low.

Brucellosis has a tremendous global burden with more than 50,000 infections across the world per year<a href="#accordion">[4]</a>. The cases have dropped in the US because of animal vaccination programs and the pasteurization of milk. However, it is possible due to the consumption of imported dairy products.&nbsp;

&nbsp;

It is important to be familiar with how brucellosis presents, and equally important is to recognize zoonosis. B melitensis, B suis, and B abortus are sequenced completely, which can help in improving the data and understanding the pathogenies of the disease or its complexity. Moreover, brucellosis is diagnosed based on serologic techniques and culture. Therapy is initiated based on the clinical identification of the genus. However, the type of Brucella does not change the therapeutic agents. Though, speciation is necessary for epidemiologic surveillance. 
&nbsp;

Signs And Symptoms

The symptoms of brucellosis are mostly vague. They are like the flu and may include the following:

<ul>
	<li>The most common symptom is fever with high spikes, and it mostly occurs in the afternoon</li>
	<li>Aches and pain in the whole body</li>
	<li>Back pain</li>
	<li>Weight loss and poor appetite</li>
	<li>Headache&nbsp;</li>
	<li>Night sweats</li>
	<li>Weakness</li>
	<li><a href="https://merisehat.pk/disease/cold-flu">Cough</a></li>
	<li>Abdominal pain 
	&nbsp;</li>
</ul>

The symptoms appear around five to thirty days after a person encounters the bacteria. Moreover, the severity of the symptoms is dependent on the type of Brucella that the person has contracted.&nbsp; 
&nbsp;

<ul>
	<li>B. Abortus</li>
</ul>

It causes mild to moderate symptoms. However, they become chronic.

<ul>
	<li>B. Canis</li>
</ul>

The symptoms occur intermittently and are similar to ones due to B. abortus infection. However, people with B. canis often suffer from vomiting and diarrhea.

<ul>
	<li>B. Suis</li>
</ul>

It may cause abscesses in different organs.

<ul>
	<li>B. Melitensis</li>
</ul>

The symptoms of B.&nbsp;melitensis&nbsp;may be sudden and severe, which can also lead to disability. 
&nbsp;

<h5>Long-Term Symptoms Of Brucellosis</h5>

The symptoms disappear after a few weeks or months. However, they may return and some people with chronic brucellosis experience them for years, despite treatment. The long-term signs and symptoms are: 
&nbsp;

<ul>
	<li>Fatigue</li>
	<li>Recurrent fevers</li>
	<li>Endocarditis</li>
	<li><a href="https://merisehat.pk/disease/arthritis">Arthritis</a></li>
	<li>Spondylitis (spinal bones arthritis)</li>
	<li>Sacroiliitis (arthritis in joints where the spine connects with the pelvis) 
	&nbsp;</li>
</ul>

Causes

Brucellosis can affect wild and domestic animals. The most common ways the bacteria transfer from animals to people are: 
&nbsp;

<ul>
	<li>Raw Dairy Products</li>
</ul>

Unpasteurized milk, butter, cheese, and ice cream infected with Brucella bacteria can spread the infection to humans. It can also be transferred through infected animals and uncooked meat.

<ul>
	<li>Inhaling Contaminated Air</li>
</ul>

The bacteria can spread through the air. It is common among farmers, hunters, slaughterhouse workers, and lab technicians who may inhale it.

<ul>
	<li>Body Fluids And Blood Of Infected Animals</li>
</ul>

The bacteria in the blood, semen, or placenta of infected animals can enter the bloodstream through either cuts or wounds. Normal contact doesn&rsquo;t transfer the bacteria and people don&rsquo;t get brucellosis from their pets. However, those who are immunocompromised should avoid handling dogs with the disease. 
&nbsp;

<h5>Does It Spread From Person to Person?</h5>

Brucellosis doesn&rsquo;t spread from one person to another, but in some cases, it has passed from pregnant women to their children during birth. In addition, it has also passed from their breast milk while feeding their babies. It rarely spreads sexually, through marrow transplants, or contaminated blood. 
&nbsp;

Bacterial isolation and serologic tests can be performed for brucellosis. It is known as the Brucella microagglutination test (BMAT), which is a modified version of SAT (serum agglutination test). It detects the antibodies to Brucella species. For example, suis, abortus, or melitensis. However, no serological test is available for the detection of canis.

The diagnosis of brucellosis is made through two serum samples, using serology. The first sample is taken when the patient is ill, and the second is taken two to four weeks after to check whether there is a rise in the antibodies. If the antibodies have risen, it means the patient is positive for brucellosis.

If paired sera is not possible, healthcare providers can diagnose the patient based on a single serum sample. Moreover, currently, serology is not available for the monitoring of RB51 vaccine exposure or exposure to Brucella canis. 
&nbsp;

<h5>Monitoring After Lab Exposure</h5>

Lab serology is drawn at 0, 6, 12, 18, and 24 weeks after exposure. The immune response is characterized by the production of IgM antibodies initially, which is followed by the production of IgG antibodies. The agents that are used in the diagnosis are smooth lipopolysaccharide (S-LPS) of the internal proteins and outer membrane.

SAT (serum agglutination test) detects antibodies to the smooth lipopolysaccharide. Other tests, for example, ELISA and Coombs Test, can also detect the antibodies that react against S-LPS. Furthermore, the Coombs test remains positive for longer, compared to other agglutination tests. 
&nbsp;

Diagnosis

Brucellosis is life-threatening and a multisystem disease in which IgM antibodies appear in the serum against LPS antigens. It is followed by IgG antibodies in the second week. Both IgM and IgG peak during the fourth week and antibiotics are used.&nbsp;

Healthcare providers diagnose brucellosis based on the medical history of the patients and Brucella species isolation. Blood culture is the standard method, and the definitive diagnosis is done based on blood culture, tissue samples, or bone marrow samples.&nbsp;

&nbsp;

Laboratory practices have an impact on the sensitivity of the blood culture, which can change between 15% to 70%. Bone marrow is the gold standard diagnostic test for brucellosis due to the high concentration of Brucella in the reticuloendothelial system.&nbsp;

SAT is used for serologic confirmation and ELISA (enzyme immunoassay) measures the specific IgG, IgA, and IgM antibodies. ELISA also overcomes the false negative and positive that is possible with serum agglutination test<a href="#accordion">[5]</a>.

&nbsp;

<h5>Diagnosis Confirmation</h5>

The diagnosis of brucellosis is usually confirmed through blood tests and bone marrow cultures. These tests, test the blood for antibodies. Additional tests help in detecting the complications, which include:

<h5>X-rays&nbsp;</h5>

They reveal the changes in the bones and joints.

<h5>CT Scan Or MRI</h5>

Computerized tomography or magnetic resonance imaging can identify the presence of any inflammation or abscesses in the brain or other tissues.

<h5>CSF Culture</h5>

A small sample of the cerebrospinal fluid is taken to check for meningitis and encephalitis.

<h5>ECG</h5>

Sound waves are used for creating images of the heart to check for infection and damage.

<h5>Bone Marrow Culture</h5>

It is the gold standard method to check for diagnosis of brucellosis. The high concentration of Brucella in the reticuloendothelial system allows the detection of the bacteria. 
&nbsp;

<h5 dir="ltr">Diagnosis Of Brucellosis In Pakistan&nbsp;</h5>

Serology is the preferred testing method in Pakistan for brucellosis. The most common tests used are RBPT, MRT, SAT, and indirect-ELISA. PCR or Brucella isolation is used less frequently. Moreover, since RBPT is less expensive, it is used more often for the screening of Sera.

The complementary test that is performed for RBPT-positive sera is ELISA. Though, it is used as a single test for screening at some standard labs only. The standard SAT and its modified tests are used in Punjab and KPK. All these tests have high sensitivity and lower specificity<a href="#accordion">[6]</a>. 
&nbsp;

Treatment

It may be difficult to treat brucellosis. Healthcare providers prescribe antibiotics, which are: 
&nbsp;

<ul>
	<li>Doxycycline</li>
	<li>Streptomycin</li>
	<li>Rifampin</li>
	<li>Ciprofloxacin or Ofloxacin&nbsp;</li>
	<li>Tetracycline</li>
	<li>Sulfamethoxazole/Trimethropin 
	&nbsp;</li>
</ul>

Doxycycline and rifampin are given as a combination for six to eight weeks. The antibiotics must be taken for several weeks to prevent relapse of the disease. The rate of relapse is five to fifteen percent and usually occurs six months after the treatment.

The recovery period can be weeks or months. However, patients who get treatment within a month of the disease symptoms can be cured completely. 
&nbsp;

Brucellosis affects any part of the body, which also includes the reproductive system, heart, liver, and nervous system. Chronic brucellosis complications can either be in the whole body or just one organ. They include: 
&nbsp;

<h5>Endocarditis</h5>

Endocarditis is one of the most serious complications of brucellosis. Left untreated, it can destroy the valves of the heart, leading to death.

<h5>Arthritis</h5>

The inflammation in the joints is marked by pain, swelling, and stiffness of the ankles, knees, hips, wrists, and spine. Spondylitis (inflammation in the spine) or sarcoidosis (inflammation in the lower spine and pelvis) can cause lasting damage and is difficult to treat.

<h5>Epididymo-orchitis&nbsp;</h5>

Brucellosis-causing bacteria can infect the epididymis (the coiled tube that connects the testicles and vas deferens). From there, the infection spreads to the testicles, which can cause severe pain and swelling.

<h5>Infection And Inflammation Of The Liver And Spleen&nbsp;</h5>

Brucellosis can cause splenomegaly and hepatomegaly (spleen and liver enlarge respectively).

<h5>CNS Infection</h5>

The infections of the central nervous system include <a href="https://merisehat.pk/disease/bacterial-meningitis">meningitis</a> and <a href="https://merisehat.pk/disease/encephalitis">encephalitis</a>, which are potentially life-threatening. 
&nbsp;

Brucellosis is not common in the United States. However, it is common in other parts of the world, which are:

<ul>
	<li>Southern Europe</li>
	<li>Eastern Europe</li>
	<li>South America and Central America</li>
	<li>Mexico</li>
	<li>Asia</li>
	<li>Africa</li>
	<li>The Middle East</li>
	<li>The Caribbean 
	&nbsp;</li>
</ul>

<h5>Which Occupations Are At A Higher Risk?</h5>

People who work in close contact with animals are at a high risk of brucellosis. They include:

<ul>
	<li>Veterinarians</li>
	<li>Hunters</li>
	<li>Ranchers</li>
	<li>Dairy farmers</li>
	<li>Slaughterhouse workers</li>
	<li>Microbiologists 
	&nbsp;</li>
</ul>

The following precautions can reduce the risk of brucellosis: 
&nbsp;

<h5>Unpasteurized&nbsp;Dairy Foods</h5>

A lot of the cases of brucellosis are linked to unpasteurized dairy products. Therefore, it is best to avoid milk, ice cream, and cheese that is unpasteurized no matter what the origin is. Travelers should avoid it altogether.

<h5>Cooked Meat</h5>

Meat should be cooked thoroughly till it reaches 63&deg;C temperature. Ground meat should be cooked at 71&deg;C and well done. Moreover, poultry should be cooked to 74&deg;C. Undercooked meats should be completely avoided.

<h5>Gloves</h5>

Farmers, people who work in slaughterhouses, and veterinarians should wear latex gloves while handling meat, dead animals, and animal tissues, and when they assist animals in giving birth.

<h5>Safety Precautions For High-Risk Workers</h5>

People who work in laboratories, and handle specimens should do it under appropriate biosafety conditions. Protective measures should be followed by slaughterhouses as well, which include wearing protective clothing and separating the area of slaughter from the processing area.

<h5>Vaccination Of Domestic Animals</h5>

Vaccination programs in the US have eliminated the incidence of brucellosis in livestock herds. However, since the vaccine is live attenuated, it can cause diseases in people if anyone gets pricked while vaccinating the animals. In such cases, they should be treated immediately. 
&nbsp;

Key Points

<ul>
	<li>Brucellosis is a notification priority disease in Pakistan, and respective authorities need to be informed immediately upon presentation of any cases.</li>
	<li>Brucellosis is acquired from direct contact with the secretion and excretions of infected animals. It is also acquired by the ingestion of contaminated dairy products or food.</li>
	<li>The infection causes fever, and constitutional symptoms of specific organs are rare.</li>
	<li>Most of the patients recover in two to three weeks even if they don&rsquo;t seek treatment. However, some people develop subacute, intermittent, and chronic diseases.</li>
	<li>The diagnosis is made through blood cultures, bone marrow, or CSF cultures. Acute and serologic testing are also used.</li>
	<li>The treatment is through antibiotics, and the patients are monitored for at least one year to avoid relapse. 
	&nbsp;</li>
</ul>

[1] Franc, K.A., Krecek, R.C., Häsler, B.N. and Arenas-Gamboa, A.M., 2018. Brucellosis remains a neglected disease in the developing world: a call for interdisciplinary action. BMC public health, 18(1), pp.1-9.

[2] Corbel, M.J., 1997. Brucellosis: an overview. Emerging infectious diseases, 3(2), p.213.

[3] Pappas, G., Papadimitriou, P., Akritidis, N., Christou, L. and Tsianos, E.V., 2006. The new global map of human brucellosis. The Lancet infectious diseases, 6(2), pp.91-99.

[4] Hull, N.C. and Schumaker, B.A., 2018. Comparisons of brucellosis between human and veterinary medicine. Infection ecology & epidemiology, 8(1), p.1500846.

[5] Alişkan, H., 2008. The value of culture and serological methods in the diagnosis of human brucellosis. Mikrobiyoloji bulteni, 42(1), pp.185-195.

[6] Jamil, T., Khan, A.U., Saqib, M., Hussain, M.H., Melzer, F., Rehman, A., Shabbir, M.Z., Khan, M.A., Ali, S., Shahzad, A. and Khan, I., 2021. Animal and Human Brucellosis in Pakistan. Frontiers in public health, 9.