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By Carol A. Kemper, MD, FACP, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, Section Editor, Updates; Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
Arizona Battles Coccidioidomycosis
Source: ProMED-mail posts January 14 and 16, 2007; www.promedmail.org.
Cases of coccidioidomycosis in the desert states have increased substantially in the past few years, but Arizona has been the hardest hit, with a record number of 5493 cases in 2006. This is a 56% jump in the number of cases compared with 2005, and nearly a 10-fold increase compared with 1995. Pre-1995, there were an average of 460 cases per year. Arguably the population has increased, but data show the rate of infection per 100,000 persons is also increasing. Coccidioidomycosis is now the 4th most common infectious disease in Arizona, after gonorrhea, chlamydia and chronic hepatitis C infection. In Tucson, 29% of adults diagnosed with community acquired pneumonia are later found to have coccidioidomycosis.
Nearly half the cocci cases in Arizona reside in Mariposa County, around Tucson. While the basis for the increased number of cases is not known, it is likely due to a confluence of factors. Arizona experienced an unusually wet winter in 2005, promoting the growth of the organism in topsoil, following by a long hot summer and fall, resulting in dry, dusty conditions. In addition, an increasing number of people are settling in Arizona, pushing the population farther out into the desert, especially around Tucson, where their risk of infection is higher. The resulting construction boom in the suburbs and surrounding areas of Tucson has also no doubt contributed to the increased risk. And, many of the people moving to the area are older, retired folk, with an increased incidence of diabetes, pulmonary disease and immune suppression, all of which increase. The risk of symptomatic infection and dissemination.
And, as reported here in IDA in 2003, the increasing popularity of all terrain vehicles (ATVs) may be another important factor. ATVs are literally tearing up the desert, where the dust can hang in the air for hours, exposing both drivers and nearby residents to airborne arthroconidia.
Ocular Findings In Syphilis
After a 40 year decline in cases, an explosion of syphilis is occurring in the Bay Area and other urban centers over the past 5-6 years. Men having sex with men (MSM) are most commonly affected. This increase is, in large part, fueled by the internet, anonymous sex clubs, and an increase in unprotected sex, making contact tracing of cases difficult.
Emergency room and primary care physicians (as well as ID physicians) should revisit the ocular complications of syphilis, as they will no doubt come across this finding. While primary syphilis can occasionally occur as a primary chancre involving the conjunctiva, ocular complications of secondary syphilis are far more common, occurring in up to 10%. Secondary syphilis, which often presents with fever and rash, occurs within 2 to 12 months of a primary infection. The spirochetemia of secondary syphilis can result in inflammation of any of the structures of the eye, including an episcleritis, scleritis, conjunctivitis, iritis, and vitritis. Neuroretinitis and chorioretinitis may also occur. Patients may complain of red, painful eyes, blurry vision, light sensitivity or loss of vision. A lesser known complication might be retinal detachment from the retinal inflammation. A key point: about one-fourth of those with ocular symptoms of secondary syphilis will have no other physical findings to suggest the diagnosis.
Newer TB Blood Tests
Source: Richeldi L. An Update on the diagnosis of tuberculosis infection. Am J Respir Crit Care Med, 2006: 174:736-742.
Newer blood tests for the detection of latent tuberculosis infection (LTBI) may offer advantages over the tuberculin skin test (TST), especially in those vaccinated with BCG. Two blood tests have been developed, the first of which, QuantiFERON-TB Gold, has been approved for use in the United States. The second, T-SPOT.TB, has been approved in Europe and is being evaluated by the U.S. Food and Drug Administration. Both tests eliminate the need for a follow-up visit, and can provide results the same day or overnight. This is especially helpful in screening employees in the health care setting.
While the 2 blood assays offer some distinct advantages over PPD, there are some important differences between the assays, they perform differently in vitro and they provide somewhat differing results, especially in patients with cellular immune suppression. Both assays are based on the release of gamma-interferon from activated T cells previously exposed to mycobacterial antigens. The assays are based on the use of a protein from a stretch of DNA not found in strains of M. bovis, and therefore no antigenic cross-reactivity occurs in patients previously vaccinated with M. bovis-derived BCG. In contrast, PPD shares about 200 antigens with BCG, resulting in a lower specificity for LTBI in BCG-vaccinated persons.
The QuantiFERON-TB Gold assay uses tubes prefilled with antigen, making it more useful in the field or in smaller community laboratories. The T-SPOT.TB test is based on an ex-vivo overnight enzyme linked immunospot (ELISpot) assay developed by Prof. Lalvani and colleagues in Oxford in the late 1990s (sometimes referred to as the Lalvani ELISpot assay). Both assays make use of an internal positive control with a sample well containing a potent nonspecific stimulator of interferon-gamma production. Thus the failure of the positive control provides important information about the test subject's T cell function.
The QuantiFERON-TB Gold assay uses whole blood, with an unknown number of white blood cells, and provides quantitation of the total amount of interferon-gamma produced in the supernatent. The T-Spot.TB tests utilizes peripheral blood mononuclear cells, and provides quantitation of the level of interferon-gamma produced per cell. Both assays can be processed within one day, although the first assay is somewhat less complicated to perform in the lab. There is no potential for boosting with either assay.
Both the ELISpot and QuantiFERON-TB Gold assays demonstrate improved specificity in unexposed BCG vaccinated persons (100% and 96-98%, respectively) in clinical trials, and are more sensitive than TST in immune competent persons with active TB. In a series of 5 blinded contact investigations comparing ELISpot with TST, the ELISpot appeared significantly more specific than TST in detecting LTBI infection in BCG-vaccinated persons, and the ELISpot assay results appeared to correlate with the level of exposure. It is theorized that the ELISpot may provide a letter measure of degree of T cell antigenic exposure.
In the largest contact investigation study involving 535 students exposed to a highly contagious person, the ELISpot was significantly associated with the proximity and duration of exposure. In contrast, in separate investigations, the Quantiferon-TB Gold assay results appeared similar to TST. In one study of mostly BCG-vaccinated subjects in which subjects were grouped into high and low risk depending on their level of exposure, there were more TST-positive results than TB-Gold positives, even when taking into consideration the estimated risk of exposure.
Both assays also appear to be more sensitive and specific in immunosuppressed persons compared with TST, although both depend on functional T cells. In a series of clinical trials in immunosuppressed persons with LTBI infection, the QuantiFERON-TB Gold appears to provide more indeterminate test results compared with the ELISpot. The ELISpot has been shown to correlate with risk factors for immune suppression. In one study of 293 African children with suspected TB, the ELISpot was significantly more sensitive than TST, even in children less than 3 years of age, those with malnutrition, and in those with co-infection with HIV. In adults co-infected with TB and HIV, the ELISpot was positive in 92% (although TST was not performed in this study, the estimated TST positive rate in this population is about 50%). Another study in HIV+ persons found that blood test results correlate with the degree of immune suppression, as measured by CD4 cell count. In various studies, both blood tests gave higher rates of indeterminate responses in children less than 5 years of age (up to 17%).
In summary, both assays are highly specific in detecting LTBI in BCG-vaccinated persons; are more sensitive than TST in immunocompetent persons with LTBI and in patients with active TB. The ELISpot may correlate better with the degree of exposure. The 2 tests perform differently in patients with cellular immune suppression, and various studies suggest that ELISpot test may be more sensitive. Additional data comparing the two assays with TST are needed, especially in populations with LTBi and immune system dysfunction who are at greatest risk for progression to active disease.
New Bartonella Species Identified
Source: Eremeeva ME, et al. the N Engl J Med 2007; 356:2381-2387.
A new species of bartonella, Bartonella rochalimae, has been identified in the bloodstream of a 43-year old American woman returning from Peru, making this the 19th Bartonella species to have been identified since the identification of B. henselae in 1992. The patient had traveled to Lima, and then traveled on to Cuzco and Machu Picchu, where she spent the night. She presented with a one week history of fever, myalgias, headache, mild cough and a macular rash. Blood tests were obtained and she appeared to respond to a 5 day course of empiric ciprofloxacin.
Blood cultures (obtained in BACTEC Standard/10 aerobic/F bottles) flagged on the 15th day of incubation, and samples were subcultured on to heart infusion agar containing chocolate agar and rabbit blood. Acridine orange staining revealed clusters of organisms, which later on electron microscope appeared indistinguishable from B. bacilliformis, the causative agent of Oroyo Fever and verruga peruana. Further studies showed that the isolate was a novel Bartonella species, most closely related to B. clarridgeiae and similar to an uncultured Bartonella organism found in a human flea in Cuzco.
Humans are the sole reservoir host for 2 species of Bartonella, including both B. bacilliformis and B. quintana, whereas cats are considered to be the reservoir for B. clarridgeiae. B. clarridgeiae has never been cultured from a human. This finding raises the possibility that not all cases of Oroyo fever in Peru, most of which are never cultured, may be due to this new Bartonella species. Although the insect vector is not known, it is interesting to speculate that human fleas could be the vector, similar to B. quintana.