Updates

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.

New Ehrlichia species discovered

Source: Pritt BS, et al. Emergence of a new pathogenic Ehrlichia species, Wisconsin and Minnesota, 2009. N Engl J Med 2011;365:422-429.

The increasing sophistication of molecular tools is allowing for the discovery of all kinds of novel strains of bacteria; witness the multiple new strains of Rickettsia discovered around the world. Ehrlichia and Anaplasma are obligate intracellular parasites, which infect various white blood cells, and are transmitted by tick species. While strains of some Ehrlichia (E. muris and E. canis) have been implicated in human infection in other parts of the world, Ehrlichia chaffeensis and Ehrlichia ewingii are believed to cause human disease limited to the United States.

These authors describe a novel species of Ehrlichia closely related to E. muris, which resulted in symptomatic infection in 4 people from Minnesota and Wisconsin. In the process of conducting a large epidemiological study for these organisms in the United States, whole blood specimens from 4247 patients suspected of having Ehrlichia or Anaplasma infection were collected from 45 states from June through December 2009. Real-time PCR targeting a conserved region of GroEL heat-shock protein operon was used. Specimens with an atypical result (not consistent with recognized species of Ehrlichia) were tested using broad range 16S ribosomal primers and Anaplasmataceae rrs assay.

Of 1,518 specimens submitted from Minnesota and Wisconsin residents, 163 (10.7%) were positive for A. phagocytophilum and none were positive for E. chaffeensis or E. ewingii. However, 4 of the specimens had an atypical GroEL PCR reaction; all 4 also tested positive by the Anaplasmataceae PCR assay. Nucleotide sequencing suggested that all 4 specimens were identical and shared 98% homology with E. muris. Cultures of whole blood did yield an organism when inoculated on live cell culture, and produced morulae visible by light microscopy at 5 weeks.

All 4 patients were suspected of having some kind of ehrlichial-like infection but their initial tests were negative or inconclusive. All 4 presented with fever, headache, and lymphocytopenia, three had thrombocytopenia, and 2 had abnormal liver function tests. One patient had a lung transplant and another had a kidney transplant; both were receiving immunosuppressive therapy. One required hospitalization. All 4 recovered with administration of doxycycline. The authors indicate that all 4 had "peri-domestic" activities that put them at risk for tick exposure (such as mowing the lawn or hiking).

Peripheral blood specimens from the 4 patients failed to demonstrate parasites or morulae. Serum from one patient was positive for E. chaffeensis IgG antibodies at days 5 and 54 of illness by immunofluorescence, but another patient had negative studies at days 2 and 15 of illness. At least one serum and plasma specimen from each patient submitted to the CDC tested positive for IgM or IgG by IFA for E. chaffeensis but not A. phagocytophilum.

DNA consistent with this new species was identified in 16 of 534 Ixodes scapularis ticks and 1 of 15 nymph groups submitted from Minnesota, but was not found in 9 I. scapularis or 88 dermocentor ticks from Wisconsin.

Commercial assays currently available may not detect this new species of Ehrlichia, although specific PCR and IFA studies are available through the CDC, if needed. The molecular similarity to E. muris raises an interesting point — E. muris is an Old World parasite, present in Eastern Europe, Russia, and Japan, where it infects mice and deer, and their ticks. Serological studies have found that 1.1% of residents in Tokyo test positive for E. muris. Perhaps these organisms are distantly related.

Chinese herbal remedy for H1N1

Source: Wang C, et al. Oseltamivir compared with the Chinese Traditional Therapy Maxingshigan-Yinqiaosan in the treatment of H1N1 Influenza. Ann Intern Med 2011;15:217-225.

Thousands of Chinese used a compound called maxingshigan-yinqiaosan (MY) for treatment of flu symptoms during the 2009 H1N1 epidemic. MY is a concoction of 12 different herbs, including toasted Herba ephedra, as well as qinghao, gypsum fibrosum, and rhizoma.

To test the efficacy of this herbal remedy for influenza, the authors conducted an unblinded, randomized study of 410 adults (ages 15-59; average age, 19 years) with laboratory-confirmed influenza H1N1. Patients were randomly assigned in a 1:1 fashion to receive 5 days of either oseltamivir (OS), OS plus MY, MY alone, or nothing. Patients were excluded from study if they had pneumonia or abnormal chest radiographs, other significant underlying illness or HIV infection, or had received influenza vaccination in the past year. All of the participants were hospitalized for quarantine and close monitoring. Serial real-time PCR for viral RNA titers were conducted daily in a subset of 148 randomly selected patients.

The MY compound met Chinese safety standards and was tested for heavy metals, bacterial contamination, and pesticides, and was centrally distributed to the study sites. Antibiotics could be used at the discretion of the treating physician.

The median time from onset of illness to randomization was 35 hours (range, 18-48 hours), and was similar between the three active treatment groups and controls. The use of concomitant antibacterials was similar in the 4 groups prior to randomization. Following randomization, the control group received significantly more antibiotics than the three active treatment groups (34% vs. 15.7% for OS, 9.7% for MY, and 7.8% for OS + MY; P < 0.001). Time to resolution of fever was significantly less for all three treatment groups compared with the control group (median time, 15 hours for OS + MY, 16 hours for MY, 20 hours for OS, and 26 hours for the control group; P < 0.001). A borderline statistically significant difference in favor of the combined treatment group compared with the OS group was observed for time to resolution of fever. No difference in the reduction of other symptoms (cough, headache, fatigue) between the groups was observed. Only two patients developed nausea and vomiting to MY, and none reported side effects to OS.

Throat swabs demonstrated a rapid reduction in H1N1 viral shedding between baseline and day 5, although no significant difference between the treatment groups and controls was detected. By day 5 of illness, viral shedding was still detectable by PCR in 40% of the control group, 30% of the MY group, and 16-18% of the groups receiving OS. Further analysis revealed that this subgroup of patients had a lower symptom score compared with the other study patients.

The combination of this Chinese herbal remedy plus oseltamivir for influenza H1N1 appeared more effective than OS alone in the reduction of fever, and was well-tolerated.

UTIs increased after PAP testing

Source: Tiemstra JD, et al. Genitourinary infections after a routine pelvic exam. J Am Board Fam Med 2011;24:296-303.

Anecdotal data suggest that women may be at increased risk for UTI following routine PAP and pelvic examination. To examine the risk of UTI following PAP smear, these authors conducted a historical cohort study to assess the frequency of UTI in women attending a family medicine clinic who had undergone a PAP in the previous 52 weeks. The frequency of UTI was compared in women who had undergone PAP smear within the previous 1-7 weeks vs. the remaining women, who served as a control group, who had had PAP smears 8-52 weeks earlier.

A total of 1,582 women were included in the analysis, 30% of whom had student health insurance. Variables such as vaginitis, sexually transmitted disease, and the frequency of visits for UTI before and after the PAP smear were examined. The women were examined by 22 different clinicians, one-fourth of whom were students or residents. Although the frequency of bimanual pelvic examination was not specifically assessed, the authors commented that a bimanual exam was generally performed with the PAP smear. Specific information on sexual activity was not available.

UTIs were significantly more frequent in women who had undergone PAP smear in the previous 7 weeks compared with controls (12.7% vs. 6.51% per 100 person-years; P < 0.01). An increased frequency of Candida and bacterial vaginitis in the 7 weeks following PAP compared to weeks 8-52 also was observed. The frequency of STDs remained uniform throughout the 52-week follow-up period. There was no significant difference in the frequency of UTI within 2 weeks of PAP compared with weeks 3-7, suggesting that occult infection at the time of the PAP was not responsible for the increased incidence of UTI observed (0.3% risk of asymptomatic colonization).

Based on these data, the risk of UTI per individual following a PAP smear was approximately 0.83%. Although seemingly small, this figure translates into 415,000 extra UTIs in the United States when factoring in the number of women who have an annual PAP smear. This figure represents approximately 11% of all observed UTIs in the United States. The authors suggest that the increased risk of UTI following routine PAP smear lends further weight to the argument that routine annual PAP smears may not be necessary in all women, especially those with no risk factors or a history of abnormal PAPs. In addition, no good data exist to support the use of the bimanual pelvic examination as a screening tool in asymptomatic women. Since the bimanual exam may further add to the risk of UTI beyond just the simple speculum exam, perhaps it should not be routine in otherwise healthy, asymptomatic young women.