Brucellosis

Brucellosis also known as Malta fever, Undulant fever, Brucella infection is an infectious disease caused by infection with the bacteria of the genus Brucella. These bacteria are primarily passed among animals. Humans become infected by coming in contact with animals or animal products that are contaminated with these bacteria. Brucellosis initially results in flu-like symptoms but more severe symptoms may also occur. According to the CDC, there are fewer than 200 cases annually in the US.

Symptoms of Brucellosis
In humans brucellosis can cause a range of symptoms that are similar to the flu and may include fever, sweats, headaches, back pains, and physical weakness. Severe infections of the central nervous system or lining of the heart may occur. Brucellosis can also cause long-lasting or chronic symptoms that include recurrent fevers, joint pain, and fatigue. Brucellosis causes a non specific illness, meaning that it does not have any features that are unique to Brucellosis. It also does not cause the same illness in every patient. Brucellosis tends to cause fevers, which can be of long duration. These are often the reason for patients to seek medical advice since there may be no obvious cause. Other symptoms include night sweats, poor diet, joint aches, tiredness, weight loss, and low mood. Brucellosis may start suddenly or it may develop over several days to weeks. Often people with brucellosis have many complaints but a normal physical exam when seen by a doctor, with the exception of a persistent fever. Although the disease is commonly non-specific, suggesting a generalized infection, in about one third of patients, the infection shows signs of "localizing". This means that the infection becomes confined to a specific site of the body. The most common sites for localization are the joints, the genitals, the brain, the heart and the liver. Other sites may also become involved but these are less common. On occasion, brucellosis occurs on foreign material in the body such as artificial joints or pacemakers and their leads. Brucellosis may also relapse, with recurrence of global or localized symptoms, and this is more difficult to treat.

Causes
Brucellosis is caused by the bacteria in the genus Brucella, including Brucella melitensis, Brucella abortus, Brucella suis, and Brucella canis. As one might guess from the species names, these various species infect sheep, goats, cattle, deer, elk, pigs, dogs, and several other animals. Brucella are small, Gram-negative, non-motile, non-spore-forming rods. They grow slowly on most laboratory culture media.

Although brucellosis can be found worldwide, it is more common in countries that do not have good standardized and effective public health and domestic animal health programs. Areas currently listed as high risk are the Mediterranean Basin (Portugal, Spain, Southern France, Italy, Greece, Turkey, North Africa), South and Central America, Eastern Europe, Asia, Africa, the Caribbean, and the Middle East. Unpasteurized cheeses, sometimes called "village cheeses," from these areas may represent a particular risk for tourists.

Diagnosis
Brucellosis is diagnosed in a laboratory by finding Brucella organisms in samples of blood or bone marrow. Also, blood tests can be done to detect antibodies against the bacteria. If this method is used, two blood samples need to be collected 2 weeks apart.

Treatment
Brucellosis can be treated with antibiotics, but treatment can be difficult. Usually, doxycycline and rifampin are used in combination for 6 weeks to prevent re-occuring infection. Depending on the timing of treatment and severity of illness, recovery may take a few weeks to several months. Mortality is low (~2%), and is usually associated with endocarditis (infection of the inner lining of the heart).

Prevention
There is no Brucellosis vaccine available for humans. The following can help in preventing the infection:
 * Not consuming unpasteurized milk, cheese, or ice cream while traveling.
 * If it is unclear whether a dairy product is pasteurized, the best idea is not to eat it. * It is a good idea for hunters and animal herdsman to use rubber gloves when handling viscera of animals.

Chances of Developing Brucellosis
Brucellosis is not very common in the United States, where 100 to 200 cases occur each year. Brucellosis can be very common in countries where animal disease control programs have not reduced the amount of disease among animals.

How Brucellosis is Spread
Humans are generally infected in one of three ways: The most common way to be infected is by eating or drinking contaminated milk products. When sheep, goats, cows, or camels are infected, their milk is contaminated with the bacteria. If the milk is not pasteurized, these bacteria can be transmitted to persons who drink the milk or eat cheeses made from it. Inhalation of Brucella organisms is not a common route of infection, but it can be a significant hazard for people in certain occupations, such as those working in laboratories where the organism is cultured. Inhalation is often responsible for a significant percentage of cases among slaughterhouse employees. Contamination of skin wounds may be a problem for persons working in slaughterhouses or meat packing plants or for veterinarians. Hunters may be infected through skin wounds or by accidentally ingesting the bacteria after cleaning deer, elk, moose, or wild pigs that they have killed.
 * Eating or drinking something that is contaminated with Brucella
 * Breathing in the organism (inhalation)
 * Having the bacteria enter the body through skin wounds.

Direct person-to-person spread of brucellosis is extremely rare. Mothers who are breast-feeding may transmit the infection to their infants. Sexual transmission has also been reported. For both sexual and breast-feeding transmission, if the infant or person at risk is treated for brucellosis, their risk of becoming infected will probably be eliminated within three days. Although uncommon, transmission may also occur via contaminated tissue transplantation. B. canis is the species of Brucella that can infect dogs. This species has occasionally been transmitted to humans, but the vast majority of dog infections do not result in human illness. Although veterinarians exposed to blood of infected animals are at risk, pet owners are not considered to be at risk for infection. This is partly because it is unlikely that they will come in contact with the blood, semen, or placenta of the dog. The bacteria may be cleared from the animal within a few days of treatment. However re-infection is common and some animal body fluids may be infectious for weeks. Immunocompromised people (cancer patients, HIV-infected individuals, or transplantation patients) should not handle dogs known to be infected with B. canis.

Veterinarian transmission
The animal vaccines (RB-51 or strain 19, or REV-1) for brucellosis are live vaccines, and strain 19 is known to cause disease in humans. Accidental innoculation of humans (such as a veterinarian) can cause disease in humans. A baseline blood sample usually needs to be collected for testing for antibodies. Doctors usually recommend taking antibiotics (doxycycline and rifampin for strain 19 and REV-1, or doxycycline alone for RB-51) for 3 weeks. At the end of that time a person needs to be rechecked and a second blood sample collected. (The sample can also be collected at 2 weeks.) The same recommendations hold true if the vaccine is sprayed in the eyes or spraying onto open wounds on the skin, both of which require 6 weeks of treatment.

Laboratory transmission
According to the CDC, brucellosis is among the most commonly reported laboratory-acquired bacterial infections. In a review of laboratory-associated infections during 1979--1999, Brucella spp. accounted for approximately 8% of all laboratory infections, 16% of bacterial infections, and 4% of deaths. Infections have occurred from sniffing culture plates, spilling blood-culture bottles, mucous membrane or skin exposure to sprays of organism-containing suspensions, aerosol generation from ruptured centrifuge tubes, or routine laboratory work with Brucella cultures outside of biological safety cabinets. Once Brucella has been identified (or is highly suspect), clinical laboratories need to notify the state health department and send the isolate to the state public health laboratory or nearest Laboratory Reference Network laboratory for confirmation and species identification. When Brucella is confirmed, the state public health laboratory needs to notify all other laboratories that handled the specimen. Exposure to workers needs to be assessed at the submitting laboratory and other laboratories involved.

Specifically implicated procedures or events related to pathogenic Brucella species include sniffing bacteriological cultures, direct skin contact, mouth pipetting, innoculations, and sprays into eyes, nose, and mouth. Manipulation of Brucella organisms on an open bench without use of the recommended practices has led to infections. Anyone who practiced a specifically implicated procedure (above), anyone who was within five feet of any manipulation of Brucella on an open bench, or anyone present in a laboratory during a Brucella aerosol-generating event is at risk for acquiring brucellosis. High-risk exposure: Individuals who performed a specifically implicated practice (see above), individuals who were near (within five feet) of work with Brucella on an open bench, or individuals present in the laboratory during a Brucella aerosol-generating event need to be considered as having a high risk exposure. Low-risk exposure: Others in the lab at the time of manipulation on an open bench, but who do not have high-risk exposures as defined above, have a low-risk exposure.

After a potential laboratory exposure, all individuals classified as high-risk should begin PEP. PEP should be discussed with, and offered to, laboratory workers with low-risk exposures. For women who are pregnant, PEP should be considered in consultation with an obstetrician. Both those with high and low risk exposures should be monitored for the development of symptoms of brucellosis. Routine serologic tests for brucellosis are not effective in monitoring for infection. From the last exposure, temperature needs to be actively monitored for fever for four weeks. Broader symptoms of brucellosis need to be passively monitored for six months from the last exposure. Persons potentially exposed to RB51 who develop symptoms should consult with a health care provider.

Bioterrorism
Brucella spp. are dangerous infectious bacteria listed among CDC's category B bioterrorism agents. CDC and the Animal and Plant Health Inspection Service (APHIS) regulate the transfer, possession, or use of such agents in the United States. New isolations, laboratory exposures, and other incidents associated with the intentional or unintentional release of B. abortus(excluding RB51), B. melitensis, or B. suis must be reported as soon as possible to either CDC or APHIS.