several months after exposure may occur with P. falciparum if drug-resistant parasites are inadequately treated (Guerrant et al. 1999). That would be expected to occur weeks to months later, rather than years later. P. malariae may lead to chronic, low-level parasitemia that may be difficult to detect and may persist for many decades. The unusual cases of truly chronic malaria due to P. malariae may require immunodiagnostic techniques or repeated smears to detect the parasite because of low levels of parasitemia.
The committee concludes that there is sufficient evidence of a causal relationship between malaria infection and relapse of disease (Plasmodium vivax or Plasmodium ovale) or late presentation of disease (Plasmodium malariae) months to years after acute infection.
The committee concludes that there is sufficient evidence of an association between infection by Plasmodium falciparum and recrudescence weeks to months after the primary infection, but only in the case of inadequate therapy.
Coxiella burnetii is the etiologic agent of the zoonosis Q fever, which was first described in abattoir workers in Australia in 1935 (Derrick 1937). The organism has since been demonstrated to have a worldwide distribution and has been isolated in a wide variety of animal and arthropod species. Remarkable for its heterogeneity, it is a highly pleomorphic gram-negative coccobacillus that uses multiple routes of transmission.
In vertebrate hosts, C. burnetii targets the host macrophage, where it survives as an obligate intracellular pathogen in the harsh acidic environment of the phagolysosome. The bacteria exhibits phase variation on passage through cell culture; from the phase I virulent stage observed in natural and animal infections, it can shift to an avirulent phase II stage after repeated passage through cell culture. Under adverse conditions, C. burnetii undergoes sporulation, yielding an atypical spore-like form that can survive extreme environmental conditions. It is highly infectious, producing disease after infection with a single organism.
C. burnetii infection causes a wide array of acute and chronic presentations in humans, as described below. Nonetheless, only about 40% of people infected with it report clinical symptoms. About 7% of the general US population is seropositive for C. burnetii (McQuiston and Childs 2002).
Most human cases of Q fever result from the inhalation of aerosols contaminated with C. burnetii of animal origin (Raoult et al. 2005). Infected aerosols may be generated by domesticated farm animals—especially cattle, sheep, and goats—but can also arise from cats, dogs, and birds. Although the organism is not known to cause overt disease in animals, it is shed in milk, urine, feces, and especially amniotic fluid and products of conception. The placenta of an infected ewe may contain up to a billion infectious doses of C. burnetii per gram of tissue; thus, the parturition of livestock can generate highly infectious aerosols.
Most humans who become infected with C. burnetii are exposed through direct contact with farm animals, domesticated animals, or animals in abattoirs. However, several outbreaks of Q fever appear to have been caused by C. burnetii aerosols transported by wind (Tissot-Dupont