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; is Associate Editor for Infectious Disease Alert.

Serologies for Congenital Toxoplasmosis

Source: Olariu TR, et al. Severe congenital toxoplasmosis in the United States: Clinical and serological findings in untreated infants. Pediatr Infect Dis J 2011;30:1-6.

Congenital toxoplasmosis occurs exclusively in infants born to mothers who acquire primary infection during their pregnancy. Unfortunately, many of these infections occur without clinical signs or symptoms, and the mothers go untreated. It is estimated that approximately 500-5,000 infants are born annually in the United States with congenital toxoplasmosis, some of which are never recognized as such; and the diagnosis, especially in later months or years of life, can be difficult to confirm.

The Palo Alto Medical Foundation Toxoplasma Serology Laboratory has been doing research on toxoplasma serologic studies for more than 20 years. They examined clinical and serological findings for 164 infants (0-180 days old) diagnosed with congenital toxoplasmosis in the United States between 1991 and 2005, whose mothers had not received treatment during pregnancy. The utility of IgM and IgA toxoplasma-specific antibody in infants with suspected or confirmed congenital toxo was examined. All infants in this study had confirmed congenital toxoplasmosis, defined as a positive Sabin Feldman IgG antibody test, plus at least one other laboratory finding (presence of IgM or IgA antibody, persistence of IgG through 12 months of life, presence of IgM in CSF, and a positive PCR on amniotic fluid, blood, CSF, or urine).

More than half (56%) of the children were diagnosed within the first month of birth. One or more severe clinical findings were identified in 116 (84%) of the infants, including eye disease (92%), cerebral calcifications (80%), and hydrocephalus (68%). All three of these findings were observed in 61% of the infants. Other clinical findings included hepatosplenomegaly (29%), jaundice (19.5%), rash or purpurea (10%), microcephaly (6%), and cerebral atrophy (4%). Thrombocytopenia, CSF pleocytosis, and elevated CSF protein were common.

IgM antibodies were found in 87% of the infants, whereas IgA antibodies were identified in 77%, including 11 infants in whom IgM antibody was not present. Both IgM and IgA antibodies were more commonly found in neonates (< 90 days old) than in older infants (91-180 days old; P = 0.036), and decreased with increasing age. Eleven (7%) of the infants did not have detectable IgM nor IgA antibody (and were diagnosed by other means, including persistent of IgG antibody > 12 months or a positive PCR). PCR results were positive in 27/58 (46%) CSF specimens, 5/10 (50%) urine specimens, and 2/7 (29%) whole blood specimens.

These results lend support to the use of both IgM and IgA toxoplasma-specific antibodies in the diagnosis of congenital toxoplasmosis, especially if done within the first 3 months of life. Nearly 11% of infants in this study were IgM-negative but had detectable IgA antibody.

Overuse of Antibiotics: Still a Problem

Source: Centers for Disease Control and Prevention. Office-related antibiotic prescribing for persons aged ≤ 14 years — United States, 1993-1994 to 2007-2008. MMWR Morb Mortal Wkly Rep 2011;60:1157-1163.

Data derived from the National Ambulatory Medical Care Survey, which is a survey of ~3000 ambulatory care physicians conducted annually by the CDC, were examined for changes in office visits and antibiotic use from 1993-1994 to 1997-1998. Antibiotic prescriptions written for five common acute respiratory infections (ARIs) for children ≤ 14 years of age were compared during this period (including otitis, pharyngitis, bronchitis, sinusitis, and nonspecific upper respiratory infection, e.g., the common cold).

Overall, office visits increased 18% for this age group during the period of study, up from 2,180 visits per 1,000 children in 1993-1994 to 2,581 visits per 1,000 children in 2007-2008. During the same period, office visits for ARIs decreased by 14%. Antibiotic prescriptions for ARIs also decreased 24% during this period (from 300/1,000 visits to 229/1,000 visits). This was largely due to a decrease in antibiotic prescriptions for pharyngitis (-26%) and the common cold (-19%). There was no apparent change in the frequency of prescriptions written for sinusitis, bronchitis, or otitis.

Despite the modest decrease observed in antibiotic prescriptions written for ARIs in 2007-2008, 58% of office visits during that period for children ≤ 14 years of age in which an antibiotic was prescribed were for one of the five ARIs — most of which do not require antibacterial treatment. Arguably, the reduction in treatment for pharyngitis may be due to the introduction of the rapid strep antigen test during this period, and not improvement in prescribing habits. The use of antibiotics for ARIs in the ambulatory care setting remains inappropriately high, despite an ongoing public health campaign against such prescribing habits and an active conversation in the lay press about increasing antibiotic resistance.

Use of Newer Assays for Syphilis

Source: Park IU, et al. Screening for syphilis with the treponemal immunoassay: Analysis of discordant serology results and implications for clinical management. J Infect Dis 2011;204:1297-1304.

Clinical laboratories in North America are increasingly switching to the newer treponemal-specific assays, such as the enzyme immunoassay (EIA) or chemiluminescence immunoassay (CIA) for syphilis testing. Because these assays are automated, they are cost-effective for clinical laboratories compared with the traditional RPR/VDRL testing. But whether they are cost-effective for clinical purposes is uncertain. While the EIA/CIA assays are highly sensitive (95%-99%) and specific (98%-99%), they may result in a larger number of false-positive or discordant results in a low prevalence population, which arguably increases the cost for treatment and follow-up, as well as potential over-treatment. Furthermore, data are lacking on the management of patients with discordant test results (CIA-positive/RPR-negative). The CDC presently recommends the use of a second treponemal test (e.g., FTA or TP-PA) for discordant specimens. Data suggest that, in a low-prevalence population, approximately 40% of these discordant specimens will be negative by a second treponemal-specific test; treatment may not be necessary for these individuals. For those who test positive by a second-treponemal-specific assay, physical findings and clinical risk factors should be assessed, and patients with risk factors should be offered antibiotic therapy, if not previously treated.

Researchers at Kaiser Permanente in San Francisco and Oakland, CA, examined the clinical characteristics of patients with discordant serology, who would not be identified by standard screening methods (i.e., CIA-positive, RPR-negative). A total of 21,623 assays were performed between August 2007 and October 2007, 439 (2%) of which were CIA-positive. Of these, 255/439 (58%) were RPR-negative. Of these 255 CIA-positive/RPR-negative discordant specimens, 184 (72%) were TP-PA-positive and 71 (28%) were TP-PA-negative. The CIA-positive/RPR-negative/TP-PA-positive group was significantly more likely to be male, men having sex with men (MSM), and HIV-positive compared with the TP-PA-negative group (all P < 0.001). They were also more likely to be African-American, and to have received previous treatment for syphilis (57% vs. 9%). However, even after excluding patients with history of syphilis, discordant TP-PA-positive patients were still more likely to be male, MSM, HIV-positive, and African American compared to those who were TP-PA-negative.

In addition, the median CIA test quantitative index was significantly higher in the CIA-positive/RPR-negative/TP-PA-positive group compared with the TP-PA-negative group (9.8 vs. 1.6), suggesting that the CIA index may be potentially useful in treatment decisions. Two-thirds of the TP-PA-negative patients had CIA index values ≤ 2, whereas only 9% of the TP-PA-positive patients had a result ≤ 2.

Several additional interesting observations were made from these data. One individual was initially CIA-positive/RPR-negative/TP-PA-negative but subsequently TP-PA-positive on follow-up testing, suggesting that he may have been in the "window period" and seroconverted the CIA test earlier than the TP-PA. On the other hand, 6 of 31 (23%) patients with discordant results who were initially TP-PA-negative, and who were followed with repeat testing, "seroreverted" their CIA result, suggesting their initial CIA test was falsely positive. Of the 28 pregnant woman identified with discordant serology, 12 (43%) were CIA-positive/RPR-negative/FTA-positive; 5 of these had a history of syphilis. Of the remaining 16 women who were CIA-positive/RPR-negative/TP-PA-negative, none had a prior history of syphilis.

Of the 255 patients with discordant serology, 100 (39%) were HIV-positive; most (86%) of these were CIA-positive/RPR-negative/TP-PA-positive. The use of the tests and interpretation of discordant test results in HIV-positive individuals presents a difficult challenge. Current guidelines recommend a lumbar puncture (LP) for HIV+ patients with latent syphilis of uncertain duration or late latent disease (although neurosyphilis is less likely in patients with an RPR titer ≤ 1:16). Because the CIA quantitative results are often masked, it is uncertain whether all of these patients require an LP. Further study is required to examine the utility of the CIA as a quantitative index.