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.

Non-gonococcal urethritis

Source: Yokoi S, et al. The role of Mycoplasma genitalium and Ureaplasma urealyticum biovar 2 in postgonococcal urethritis. Clin Infect Dis. 2007;45:866-871.

The possible causative infectious agents of non-gonococcal urethritis (NGU) in men remain somewhat controversial. Studies point to a role for genital mycoplasmas and genital ureaplasmas, although some men with evidence of colonization or infection with these organisms remain asymptomatic, while others without evidence of infection have persisting symptoms.

Yokoi and colleagues examined the prevalence of infection due to genital mycoplasmas and ureaplasmas in men diagnosed with acute gonococcal urethritis and their association with persistent inflammation and clinical symptoms. A total of 390 men were treated for acute GU with cefixime, ceftriaxone, or spectinomycin. They were told to refrain from sex and return to the clinic 7 days later; at which time, cultures for GC were obtained and urethral smears were examined for the presence of PMNs. Using molecular techniques, first voided urines at both the initial and second visit were tested for non-GC organisms. NGU was defined as the presence of PMNs 7-14 days post-treatment for GC in the absence of a positive gram stain or culture for GC.

At the initial visit, chlamydia trachomatis, genital mycoplasma, and/or ureaplasmas were detected in 34%. Twenty-two percent had positive specimens for C. trachomatis, and 3.8% had both C. trachomatis and one or two species of genital mycoplasmas and ureaplasmas. Twelve percent had one or more species of genital Mycoplasma and/or ureaplasmas without chlamydia co-infection.

A total of 327 (84%) men returned to the clinic for a second visit, of which 11% were still positive for GC. Of the remaining patients, 36% had detection of urethral PMNs detected, nearly two-thirds of whom were symptomatic, and one-third were asymptomatic. NGU (as defined by the presence of urethral PMNs) was found in 51 of 66 men with positive C. trachomatis specimens (or co-infection with Chlamydia and one or more of the other species); 15 of 30 men without C. trachomatis but with positive specimens for one or more species of genital mycoplasmas and ureaplasmas; and 38 of 195 men who had negative urine studies. In other words, no bacterial etiology was identified in 38/104 (36%) of men with evidence of persisting inflammation 7-14 days post-treatment for GC.

Multivariate logistic regression analysis demonstrated that several species were associated with an increased risk of NGU, including Chlamydia (an 11-fold increase), M. genitalium (a 14-fold increase), and U. urealyticum biovar 2 (a 3.6-fold increase). M. hominis and U. parvum did not appear to be causative factors in this study.

In conclusion, one-third of the men receiving treatment for GC had evidence of one or more NGU species, data which support the current PHS guidelines recommending concurrent empiric treatment for NGC organisms in men being treated for GC. Treatment with a 7-day course of doxycycline is effective in > 90% of cases due to C. trachomatis, although there is controversy how best to treat M. genitalium. However, at least one-third of men with NGU post-treatment for GC have no bacterial etiology found in this study. It would have been interesting to see if any of those men were symptomatically improved or had resolution of urethral inflammation with empiric treatment.

Abnormalities Common on Routine Brain MRI

Source: Vernooij MW, et al. Incidental findings on brain MRI in the general population. N Engl J Med. 2007;357;1821-1828.

As part of a broader population-based survey, Vernooij and colleagues determined the prevalence of incidental asymptomatic brain findings (infarcts, tumors, white matter lesions) in 2000 people undergoing non-contract brain MRI. Volumetric techniques were used to quantify white matter lesions. The films were initially reviewed by a resident in radiology and a resident in neurology. Two experienced neuroradiologists, blinded to clinical history, reviewed any film with abnormalities and reached a consensus reading.

The mean age was 63 years (range, 46 -97 years), and 52% were woman. Asymptomatic brain infarcts were the most common findings, present in 145 persons (7.2%), more-than two-thirds of which were lacunar infarcts. The next most common finding was asymptomatic aneurysms in 1.8% of people, all but 2 of which were located in the anterior circulation, and all but 3 of which were 7 mm in diameter or smaller. (Other data found the risk of rupture of aneurysms of this size present in the anterior circulation was 0% over 4 years of observation). Benign tumors were detected in 31 (1.6%) people, more than half of which appeared to be benign meningiomas (overall prevalence, 0.9%), but also included a few vestibular (0.2%) and trigeminal schwannomas (< 0.1%), pituitary adenomas (0.3%), and intracranial lipomas (0.1%).

White matter lesions proved to be the norm in almost every patient scanned, and increased in volume and distribution with older age. Only 5% of persons 45 to 59 years of age had no evidence of white matter lesions, and this figure dropped to 2% in persons 75 years or older. The prevalence of meningiomas also increased with increasing age.

Only 3 patients had findings of urgent clinical significance, including one person each with multiple metastatic lesions (he confirmed an earlier history of lung cancer); a probable primary brain tumor; and a large chronic subdural hematoma (with a recent history of minor head trauma 4 weeks earlier). A weakness to this study is the lack of confirmatory histological data, since none of these findings required surgical intervention. However, the prevalence of asymptomatic findings on brain MRI is fairly common, and higher than reported in earlier studies. While the identification of some of these findings may result in an increase in unnecessary referrals to specialists and follow-up scans, some, such as meningiomas actually probably do require long-term follow-up.

The Immune System's Response to M. Leprae

Source: De Messias-Reason IJ, et al. The association between mannin-binding lectin gene polymorphism and clinical leprosy: new insight into an old paradigm. J Infect Dis. 2007;196:1379-1385.

Only a minority of people infected or exposed to M. leprae develop clinical disease, probably as the result of host genetic factors and immunity. At the same, those same host factors play a significant role in the progression of disease and spectrum of disease manifestations. For instance, we know that M. leprae-specific Th1 activation leads to a vigorous immune system response, with limited numbers of lesions and few organisms (tuberculoid leprosy), whereas the lack of Th1 responsiveness leads to proliferation of bacteria, extensive clinical lesions, and a resulting strong humoral response (Lepromatous leprosy).

Other factors may also play a role in the immune system response to M. leprae. Mannin-binding lectin (MBL) is a soluble protein which binds to organisms, such as mycobacteria, and facilitates their attachment to, and enhanced opsonization by, macrophages. MBL deficiency is known to protect against leishmania, and it is theorized that similar deficiency may protect against lepromatous leprosy.

De Messias and colleagues examined 264 patients with leprosy in southern Brazil, comparing them with 214 unrelated healthy adults, matched by ethnic background. The frequency of MBL genotypes and haplotypes were assessed and divided into those with low or high expression of MBL. Haplotypes associated with low production of MBL were significantly less frequent in patients with lepromatous leprosy than those with tuberculoid leprosy. For example, the LYPB/LYQC haplotypes were more frequent in patients with multibacillary disease, although their presence was nonetheless found to increase the risk of tuberculoid leprosy as well. The LYPA haplotype, which is also associated with a low expression of MBL, also conferred a 2-fold increase in susceptibility to leprosy, as well as to progression to the lepromatous and borderline forms of the disease.

In other words, the inability to express MBL not only failed to protect against infection with M. leprae, but actually increased the risk of infection, although it protected against the most severe multibacillary form of disease. De Messias et al theorize that the selective pressure of leprosy has actually shaped and defined MBL genotypes and haplotypes in populations at higher risk for leprosy. MBL2 haplotypes/genotypes associated with low expression of MBL are more common in places such as Africa and South American and, on the other hand, older (more ancient) haplotypes associated with a high amount of MBL are commonly found in populations with little selective pressure. Australian aboriginal population, which had no exposure to leprosy until the 19th century, is currently experiencing a significant problem with leprosy infection, as well as tuberculosis.