Recall accuracy of weekly automated surveys of health care utilization and infectious disease symptoms among infants over the first year of life.

Automated surveys, by interactive voice response (IVR) or email, are increasingly used for clinical research. Although convenient and inexpensive, they have uncertain validity. We sought to assess the accuracy of longitudinally-collected automated survey responses compared to medical records. Using data collected from a well-characterized, prospective birth cohort over the first year of life, we examined concordance between guardians' reports of their infants' health care visits ascertained by weekly automated survey (IVR or email) and those identified by medical chart review. Among 180 survey-visit pairs, concordance was 51%, with no change as number of visits per baby increased. Accuracy of recall was higher by email compared to IVR (61 vs. 43%; adjusted OR = 2.5 95% CI: 1.3-4.8), did not vary by health care encounter type (hospitalization: 50%, ER: 64%, urgent care: 44%, primary care: 52%; p = 0.75), but was higher for fever (77%, adjusted OR = 5.1 95%CI: 1.5-17.7) and respiratory illness (58%, adjusted OR = 2.9 95%CI: 1.5-5.8) than for other diagnoses. For the 75 mothers in these encounters, 69% recalled at least one visit; among 41 mothers with two or more visits, 85% recalled at least one visit. Predictors of accurate reporting by mothers after adjusting for illness in the baby included increased age and increased years of education (age per year, ß = 0.05, p = 0.03; education per year, ß = 0.08, p = 0.04). Additional strategies beyond use of automated surveys are needed to ascertain accurate health care utilization in longitudinal cohort studies, particularly in healthy populations with little motivation for accurate reporting.

Discovery of a novel polyomavirus in acute diarrheal samples from children.

Polyomaviruses are small circular DNA viruses associated with chronic infections and tumors in both human and animal hosts. Using an unbiased deep sequencing approach, we identified a novel, highly divergent polyomavirus, provisionally named MX polyomavirus (MXPyV), in stool samples from children. The ∼5.0 kB viral genome exhibits little overall homology (<46% amino acid identity) to known polyomaviruses, and, due to phylogenetic variation among its individual proteins, cannot be placed in any existing taxonomic group. PCR-based screening detected MXPyV in 28 of 834 (3.4%) fecal samples collected from California, Mexico, and Chile, and 1 of 136 (0.74%) of respiratory samples from Mexico, but not in blood or urine samples from immunocompromised patients. By quantitative PCR, the measured titers of MXPyV in human stool at 10% (weight/volume) were as high as 15,075 copies. No association was found between the presence of MXPyV and diarrhea, although girls were more likely to shed MXPyV in the stool than boys (p=0.012). In one child, viral shedding was observed in two stools obtained 91 days apart, raising the possibility of chronic infection by MXPyV. A multiple sequence alignment revealed that MXPyV is a closely related variant of the recently reported MWPyV and HPyV10 polyomaviruses. Further studies will be important to determine the association, if any, of MXPyV with disease in humans.

Infection with Helicobacter pylori is associated with protection against tuberculosis.

BACKGROUND: Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. METHODOLOGY/PRINCIPAL FINDINGS: We first examined M. tuberculosis-specific IFN-gamma and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-gamma responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36-0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63-2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12-0.80], p = 0.04). CONCLUSIONS/SIGNIFICANCE: H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for vaccine development and disease control.

Association between the proliferative rate of neoplastic B cells, their maturation stage, and underlying cytogenetic abnormalities in B-cell chronic lymphoproliferative disorders: analysis of a series of 432 patients.

Limited knowledge exists about the impact of specific genetic abnormalities on the proliferation of neoplastic B cells from chronic lymphoproliferative disorders (B-CLPDs). Here we analyze the impact of cytogenetic abnormalities on the proliferation of neoplastic B cells in 432 B-CLPD patients, grouped according to diagnosis and site of sampling, versus their normal counterparts. Overall, proliferation of neoplastic B cells highly varied among the different B-CLPD subtypes, the greatest numbers of proliferating cells being identified in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Compared with normal B cells, neoplastic B-CLPD cells showed significantly increased S + G(2)/M-phase values in mantle cell lymphoma (MCL), B-chronic lymphocytic leukemia (B-CLL), BL, and some DLBCL cases. Conversely, decreased proliferation was observed in follicular lymphoma, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), and some DLBCL patients; hairy cell leukemia, splenic marginal zone, and MALT-lymphoma patients showed S + G(2)/M phase values similar to normal mature B lymphocytes from LN. Interestingly, in B-CLL and MCL significantly higher percentages of S + G(2)/M cells were detected in BM versus PB and in LN versus BM and PB samples, respectively. In turn, presence of 14q32.3 gene rearrangements and DNA aneuploidy, was associated with a higher percentage of S + G(2)/M-phase cells among LPL/WM and B-CLL cases, respectively.

Gastroenteritis and transmission of Helicobacter pylori infection in households.

The mode of transmission of Helicobacter pylori infection is poorly characterized. In northern California, 2,752 household members were tested for H. pylori infection in serum or stool at a baseline visit and 3 months later. Among 1,752 person considered uninfected at baseline, 30 new infections (7 definite, 7 probable, and 16 possible) occurred, for an annual incidence of 7% overall and 21% in children <2 years of age. Exposure to an infected household member with gastroenteritis was associated with a 4.8-fold (95% confidence interval [CI] 1.4-17.1) increased risk for definite or probable new infection, with vomiting a greater risk factor (adjusted odds ratio [AOR] 6.3, CI 1.6-24.5) than diarrhea only (AOR 3.0, p = 0.65). Of probable or definite new infections, 75% were attributable to exposure to an infected person with gastroenteritis. Exposure to an H. pylori-infected person with gastroenteritis, particularly vomiting, markedly increased risk for new infection.

Household transmission of gastroenteritis.

Transmission of infectious gastroenteritis was studied in 936 predominately Hispanic households in northern California. Among 3,916 contacts of 1,099 primary case-patients, the secondary attack rate was 8.8% (95% confidence interval 7.9-9.7); children had a 2- to 8-fold greater risk than adults. Bed-sharing among children in crowded homes is a potentially modifiable risk.

Validation of Spanish language dyspepsia questionnaire.

No dyspepsia-specific questionnaire currently exists in Spanish. The Spanish Language Dyspepsia Questionnaire (SLDQ) was developed based on Rome dyspepsia criteria, other questionnaires, and common symptoms. Self-reported normal and dyspeptic volunteers (N = 63) in Chiapas, Mexico, participated in a validation study. We assessed intra- and interrater reliability by test-retest studies and established validity by both correlation to the Short Form-36 (SF-36) and comparison of scores between normals and dyspeptics. The total SLDQ score showed a wide distribution (range 0-78, mean 23.7 +/- 21.9). Internal reliability of the SLDQ was high (Cronbach's a = 0.93). Intra- and interrater reliability were excellent (scores from the first and second interviews not statistically different; P = 0.94; intraclass correlation coefficient = 0.96). SLDQ scales correlated appropriately with the SF-36. The SLDQ distinguished self-classified normals from dyspeptics (P < 0.001). The SLDQ fills the unmet need for a valid, reproducible, and multidimensional Spanish-language instrument to measure dyspepsia. Additionally, we have made suggestions for the development of symptom-quantifying questionnaires.