Q fever

Q fever is a disease caused by infection with Coxiella burnetii,^[1] a bacterium that affects humans and other animals. This organism is uncommon, but may be found in cattle, sheep, goats and other domestic mammals, including cats and dogs. The infection results from inhalation of a spore-like small cell variant, and from contact with the milk, urine, feces, vaginal mucus, or semen of infected animals. Rarely, the disease is tick borne.^[2] The incubation period is 9–40 days. A human being can be infected by a single bacterium.^[3] The bacterium is an obligate intracellular pathogen.

History

Image A: A normal chest X-ray Image B: Q fever pneumonia

It was first described by Edward Holbrook Derrick^[4] in abattoir workers in Brisbane, Queensland, Australia. The "Q" stands for "query" and was applied at a time when the causative agent was unknown; it was chosen over suggestions of "abattoir fever" and "Queensland rickettsial fever", to avoid directing negative connotations at either the cattle industry or the state of Queensland.^[5]

The pathogen of Q fever was discovered in 1937, when Frank Macfarlane Burnet and Mavis Freeman isolated the bacterium from one of Derrick’s patients.^[6] It was originally identified as a species of Rickettsia. H.R. Cox and Gordon Davis isolated it from ticks in Montana, USA in 1938.^[7] It is a zoonotic disease whose most common animal reservoirs are cattle, sheep and goats. Coxiella burnetii is no longer regarded as closely related to Rickettsiae, but as similar to Legionella and Francisella, and is a proteobacterium.

Signs and symptoms

Incubation period is usually two to three weeks.^[8] The most common manifestation is mild flu-like symptoms with abrupt onset of fever, malaise, profuse perspiration, severe headache, myalgia (muscle pain), joint pain, loss of appetite, upper respiratory problems, dry cough, pleuritic pain, chills, confusion and gastrointestinal symptoms, such as nausea, vomiting and diarrhea. The fever lasts approximately seven to 14 days.^{[citation needed]}

Approximately half of infected individuals exhibit no symptoms.^[8]

During its course, the disease can progress to an atypical pneumonia, which can result in a life-threatening acute respiratory distress syndrome (ARDS), whereby such symptoms usually occur during the first four to five days of infection.^{[citation needed]}

Less often, Q fever causes (granulomatous) hepatitis, which may be asymptomatic or becomes symptomatic with malaise, fever, liver enlargement (hepatomegaly) and pain in the right upper quadrant of the abdomen. Whereas transaminase values are often elevated, jaundice is uncommon. Retinal vasculitis is a rare manifestation of Q fever.^[9]

The chronic form of Q fever is virtually identical to inflammation of the inner lining of the heart (endocarditis),^[10] which can occur months or decades following the infection. It is usually fatal if untreated. However, with appropriate treatment, the mortality falls to around 10%.

Clinical signs in animals

Cattle, goats and sheep are most commonly infected, and can serve as a reservoir for the bacteria. Q fever is a well recognized cause of abortions in ruminants and in pets. C. burnetii infection in dairy cattle has been well documented and its association with reproductive problems in these animals has been reported in Canada, USA, Cyprus, France, Hungary, Japan, Switzerland and West Germany.^[11] For instance, in a study published in 2008,^[12]a significant association has been shown between the herds’ seropositivity and typical clinical signs of Q Fever observed such as abortion, stillbirth, weak calves and repeat breeding. Moreover, experimental inoculation of C. burnetii in cattle induced not only respiratory disorders and cardiac failures (myocarditis) but also frequent abortions and irregular repeat breedings.^[13]

Appearance and incidence

C. burnetii, the Q fever-causing agent

The pathogenic agent is to be found everywhere except New Zealand.^[14] The bacterium is extremely sustainable and virulent: a single organism is able to cause an infection. The common way of infection is inhalation of contaminated dust, contact with contaminated milk, meat, wool and particularly birthing products. Ticks can transfer the pathogenic agent to other animals. Transfer between humans seems extremely rare and has so far been described in very few cases.

Some studies have shown more men to be affected than women,^[15][16] which may be attributed to different employment rates in typical professions.

"At risk" occupations include, but are not limited to:

• veterinary personnel
• stockyard workers
• farmers
• shearers
• animal transporters
• laboratory workers handling potentially infected veterinary samples or visiting abattoirs
• people who cull and process kangaroos
• hide (tannery) workers

Diagnosis

Q fever management algorithm from the CDC

Diagnosis is usually based on serology^[17][18] (looking for an antibody response) rather than looking for the organism itself. Serology allows to detect chronic infection as high antibody levels are found against the virulent form of the bacterium. Molecular detection of bacterial DNA is increasingly used. Culture is technically difficult and not routinely available in most microbiology laboratories.

Q fever can cause endocarditis (infection of the heart valves) which may require transoesophageal echocardiography to diagnose. Q fever hepatitis manifests as an elevation of ALT and AST, but a definitive diagnosis is only possible on liver biopsy, which shows the characteristic fibrin ring granulomas.^[19]

Treatment

Treatment of the acute Q fever with antibiotics is very effective^{[citation needed]} and should take place in consultation with an infectious diseases specialist.^{[citation needed]} Commonly used are doxycycline, tetracycline, chloramphenicol, ciprofloxacin, ofloxacin, and hydroxychloroquine. The chronic form is more difficult to treat and can require up to four years of treatment with doxycycline and quinolones or doxycycline with hydroxychloroquine.

Q fever in pregnancy is especially difficult to treat because doxycycline and ciprofloxacin are contraindicated in pregnancy. The preferred treatment is five weeks of co-trimoxazole.^[20]

Prevention

Protection is offered by Q-Vax, a whole-cell, inactivated vaccine developed by an Australian vaccine manufacturing company, CSL.^[21] The intradermal vaccination is composed of killed Coxiella burnetii organisms. Skin and blood tests should be done before vaccination to identify pre-existing immunity, because vaccinating subjects who already have an immunity can result in a severe local reaction. After a single dose of vaccine, protective immunity lasts for many years. Revaccination is not generally required. Annual screening is typically recommended.^[22]

In 2001, Australia introduced a national Q fever vaccination program for people working in "at risk" occupations.

The Soviet Union had earlier developed a killed vaccine, but its side effects prevented its licensing abroad.

Preliminary results suggest vaccination of animals may be a method of control. Published trials proved that use of a registered Phase I vaccine (Coxevac) in infected farms is a tool of major interest to manage or prevent early or late abortion, repeat breeding, anoestrus, silent oestrus, metritis and decreases in milk yield when C. burnetii is the major cause of these problems.^[23][24]

Biological warfare

Q fever has been described as a possible biological weapon.^[25] The United States investigated Q fever as a potential biological warfare agent in the 1950s, with eventual standardization as agent OU. At Fort Detrick and Dugway Proving Ground, human trials were conducted on Whitecoat volunteers to determine the median infective dose (18 MICLD₅₀/person i.h.) and course of infection. The Deseret Test Center dispensed biological Agent OU with ships and aircraft, during Project 112 and Project SHAD.^[26] As a standardized biological, it was manufactured in large quantities at Pine Bluff Arsenal, with 5,098 gallons in the arsenal in bulk at the time of demilitarization in 1970. Q fever is a category "B" agent.^[27] It can be contagious, and is very stable in aerosols in a wide range of temperatures. Q fever microorganisms may survive on surfaces up to 60 days. It is considered a good agent in part because its ID50 (number of bacilli needed to infect 50% of individuals) is considered to be 1, making it the lowest known to man.

In popular Culture

A mention of Q fever was important in one of the early Dr. Kildare films (1939, Calling Dr. Kildare). Kildare's mentor Dr. Gillespie (Lionel Barrymore) tires of his protege working fruitlessly on "exotic diagnoses" ("I think it's Q fever!") and sends him to work in a neighborhood clinic instead.^[28][29]

Q fever was also highlighted in an episode of the U.S. television medical drama House (The Dig, Season 7, Episode 18).

References

External links

• Q fever at the CDC
• Coxiella burnetii genomes and related information at PATRIC, a Bioinformatics Resource Center funded by NIAID