Natural history of chronic hepatitis B
McMahon BJ . Clin Liver Dis 2010 14 (3) 381-96 In this article, the 4 phases of chronic HBV infection are reviewed and the factors that are associated with disease progression and the development of hepatocellular carcinoma (HCC) and cirrhosis are discussed. Also discussed is what is known to date about how to identify persons at the highest risk of developing HCC and/or cirrhosis. Finally, ways in which the natural history can be altered by hepatitis B vaccination and identification, close monitoring, and appropriate treatment of chronically infected individuals are reviewed. |
No associations between serum concentrations of 25-hydroxyvitamin D and parathyroid hormone and depression among US adults
Zhao G , Ford ES , Li C , Balluz LS . Br J Nutr 2010 104 (11) 1-7 Although there is evidence that vitamin D deficiency may play a role in depression, studies done on the associations have yielded mixed results. The present study aimed to examine the associations between serum concentrations of 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) and the presence of depression among US adults. A cross-sectional, population-based sample (including 3916 participants aged ≥ 20 years) from the 2005-6 National Health and Nutrition Examination Survey was used. Participants' depressive symptoms were assessed using the Patient Health Questionnaire-9 diagnostic algorithm. The associations of 25(OH)D and PTH with depression were explored using multivariate logistic regression models. For all the participants, the age-adjusted prevalence was 5.3 (95 % CI 4.3, 6.5) % for having moderate-to-severe depression, 2.3 (95 % CI 1.7, 3.1) % for having major depression and 3.8 (95 % CI 3.0, 4.6) % for having minor depression. Although the age-adjusted prevalence and the unadjusted OR of having moderate-to-severe depression or major depression decreased linearly with increasing quartiles of 25(OH)D (P < 0.05 for trends), no significant associations remained after adjusting for multiple potential confounders such as demographic variables, lifestyle factors and coexistence of a number of chronic conditions. Neither the age-adjusted prevalence nor the OR (unadjusted or adjusted) of having depression differed significantly by the quartiles of PTH. Thus, in contrast to some of the previous findings, the present results did not show significant associations between serum concentrations of 25(OH)D and PTH and the presence of moderate-to-severe depression, major depression or minor depression among US adults. However, these findings need to be further confirmed in future studies. |
Prevalence of coronary heart disease risk factors and screening for high cholesterol levels among young adults, United States, 1999-2006
Kuklina EV , Yoon PW , Keenan NL . Ann Fam Med 2010 8 (4) 327-33 PURPOSE: Previous studies have reported low rates of screening for high cholesterol levels among young adults in the United States. Although recommendations for screening young adults without risk factors for coronary heart disease (CHD) differ, all guidelines recommend screening adults with CHD, CHD equivalents, or 1 or more CHD risk factors. This study examined national prevalence of CHD risk factors and compliance with the cholesterol screening guidelines among young adults. METHODS: National estimates were obtained using results for 2,587 young adults (men aged 20 to 35 years; women aged 20 to 45 years) from the 1999-2006 National Health and Nutrition Examination Surveys. We defined high low-density lipoprotein cholesterol (LDL-C) as levels higher than the goal specific for each CHD risk category outlined in the National Cholesterol Education Program Adult Treatment Panel III guidelines. RESULTS: About 59% of young adults had CHD or CHD equivalents, or 1 or more of the following CHD risk factors: family history of early CHD, smoking, hypertension, or obesity. In our study, the overall screening rate in this population was less than 50%. Moreover, no significant difference in screening rates between young adults with no risk factors and their counterparts with 1 or more risk factors was found even after adjustment for sociodemographic and health care factors. Approximately 65% of young adults with CHD or CHD equivalents, 26% of young adults with 2 or more risk factors, 12% of young adults with 1 risk factor, and 7% with no risk factor had a high level of LDL-C. CONCLUSIONS: CHD risk factors are common in young adults but do not appear to alter screening rates. Improvement of risk assessment and management for cardiovascular disease among young adults is warranted. |
Hazard of incident and progressive knee and hip radiographic osteoarthritis and chronic joint symptoms in individuals with and without limb length inequality
Golightly YM , Allen KD , Helmick CG , Schwartz TA , Renner JB , Jordan JM . J Rheumatol 2010 37 (10) 2133-40 OBJECTIVE: To examine the hazard of incident and progressive radiographic osteoarthritis (rOA) and chronic joint symptoms at the hip and knee by limb length inequality (LLI) in a large, community-based sample. METHODS: A longitudinal cohort completed baseline (1991-97) clinical evaluation and identical followup assessment (1999-2003) (median followup time 5.9 yrs, range 3.0-13.1 yrs). LLI was defined at baseline as a measured difference between limbs ≥ 2 cm. The study groups with LLI data comprised 1583 participants with paired (baseline and followup) knee radiographs and 1453 participants with paired hip radiographs. Multivariable Cox regression models were used to examine the hazard of incident and progressive knee and hip rOA and chronic joint symptoms, with adjustment for demographic and clinical factors. RESULTS: The hazard of developing incident knee or hip rOA was 20%-30% higher and of developing progressive knee or hip rOA was 35%-83% higher among participants with LLI, but results were only statistically significant for progressive knee rOA (adjusted hazard ratio = 1.83, 95% CI 1.10-3.05). The hazards of progressive chronic knee symptoms and incident and progressive chronic hip symptoms were 13%-59% higher among participants with LLI, but were not statistically significant. CONCLUSION: LLI was associated with progressive knee rOA and was nonsignificantly associated with incident knee or hip rOA and progressive hip rOA, progressive chronic knee symptoms, and incident and progressive chronic hip symptoms. Longer studies may strengthen these associations and help determine whether LLI is a risk factor or marker of these outcomes. |
Comparison of characteristics from White- and Black-Americans with venous thromboembolism: a cross-sectional study
Heit JA , Beckman MG , Bockenstedt PL , Grant AM , Key NS , Kulkarni R , Manco-Johnson MJ , Moll S , Ortel TL , Philipp CS . Am J Hematol 2010 85 (7) 467-71 When compared with Whites, Black-Americans may have a 40% higher incidence venous thromboembolism (VTE) incidence. However, whether other VTE characteristics and risk factors vary by race is uncertain. To compare demographic and baseline characteristics among White- and Black-Americans with VTE, we used data prospectively collected from consecutive consenting adults enrolled in seven Centers for Disease Control (CDC) Thrombosis and Hemostasis Centers from August 2003 to March 2009. These characteristics were compared among Whites (n = 2002) and Blacks (n = 395) with objectively diagnosed VTE, both overall, and by age and gender. When compared with Whites, Blacks had a significantly higher proportion with pulmonary embolism (PE), including idiopathic PE among Black women, and a significantly higher proportion of Blacks were women. Blacks had a significantly higher mean BMI and a significantly lower proportion with recent surgery, trauma or infection, family history of VTE, and documented thrombophilia (solely from reduced factor V Leiden and prothrombin G20210A prevalence). Conversely, Blacks had a significantly higher proportion with hypertension, diabetes mellitus, chronic renal disease and dialysis, HIV, and sickle cell disease. When compared with White women, Black women had a significantly lower proportion with recent oral contraceptive use or hormone therapy. We conclude that Whites and Blacks differ significantly regarding demographic and baseline characteristics that may be risk factors for VTE. The prevalence of transient VTE risk factors and idiopathic VTE among Blacks appears to be lower and higher, respectively, suggesting that heritability may be important in the etiology of VTE among Black-Americans. |
Measles outbreak in Tanzania, 2006-2007
Goodson JL , Perry RT , Mach O , Manyanga D , Luman ET , Kitambi M , Kibona M , Wiesen E , Cairns KL . Vaccine 2010 28 (37) 5979-85 We conducted a measles outbreak investigation in Dar es Salaam, Tanzania. Surveillance data were analyzed; a susceptibility profile developed, and case-control study conducted. The age distribution of cases peaked among those <2, 5-7, and ≥18 years, corresponding to the age distribution of susceptibles. Risk factors included being unvaccinated (aOR=5.7, p<0.01) or having received one dose of vaccine compared to two (aOR=2.4, p=0.01), being younger, and having a less-educated caretaker. Vaccine effectiveness was 88% (one dose) and 96% (two doses). Results highlight the importance of receiving one dose of measles vaccine, and the added benefit of two doses. |
Epidemiology of tuberculosis among US- and foreign-born children and adolescents in the United States, 1994-2007
Menzies HJ , Winston CA , Holtz TH , Cain KP , MacKenzie WR . Am J Public Health 2010 100 (9) 1724-9 OBJECTIVES: We examined trends in tuberculosis (TB) cases and case rates among US- and foreign-born children and adolescents and analyzed the potential effect of changes to overseas screening of applicants for immigration to theUnited States. METHODS: We analyzed TB case data from the National Tuberculosis Surveillance System for 1994 to 2007. RESULTS: Foreign-born children and adolescents accounted for 31% of 18659 reported TB cases in persons younger than age 18 years from 1994 to 2007. TB rates declined 44% among foreign-born children and adolescents (20.3 per 10000 to 11.4 per 100000 population) and 48% (2.1 per 100000 to 1.1 per 100000) among those who were born in the United States. Rates were nearly 20 times as high among foreign-born as among US-born adolescents. Among foreign-born children and adolescents with known month of US entry (88%), more than 20% were diagnosed with TB within 3 months of entry. CONCLUSIONS: Marked disparities in TB morbidity persist between foreign- and US-born children and adolescents. These disparities and the high proportion of TB cases diagnosed shortly after US entry suggest a need for enhanced pre- and postimmigration screening. |
Estimated future HIV prevalence, incidence, and potential infections averted in the United States: a multiple scenario analysis
Hall HI , Green TA , Wolitski RJ , Holtgrave DR , Rhodes P , Lehman JS , Durden T , Fenton KA , Mermin JH . J Acquir Immune Defic Syndr 2010 55 (2) 271-6 OBJECTIVES: To estimate the potential future burden of HIV in the United States under different intervention scenarios. METHODS: We modeled future HIV incidence, prevalence, and infections averted using 2006 estimates of HIV incidence (55,400 new infections per year), prevalence (1,107,000 persons living with HIV), and transmission rate (5.0 per 100 persons living with HIV). We modeled 10-year trends for 3 base-case scenarios (steady incidence, steady transmission rate, declining transmission rate based on the 2000-2006 trend) and 2 intensified HIV intervention scenarios (50% reduction in transmission rate within 10 and 5 years). RESULTS: Base-case scenarios predicted HIV prevalence increases of 24%-38% in 10 years. Reducing the transmission rate by 50% within 10 years reduces incidence by 40%; prevalence increases 20% to an estimated 1,329,000 persons living with HIV. Halving the transmission rate within 5 years reduces incidence by 46%; prevalence increases 13%, to 1,247,000. Although in year 10 incidence is similar regardless of the intervention time frame, more infections are averted when halving the transmission rate within 5 years. CONCLUSIONS: HIV prevalence will likely increase creating additional demands for health care services. These analyses are instructive for setting HIV prevention goals for the nation and assessing potential cost savings of intensified HIV prevention efforts. |
HIV testing and HIV/AIDS treatment services in rural counties in 10 southern states: service provider perspectives
Sutton M , Anthony MN , Vila C , McLellan-Lemal E , Weidle PJ . J Rural Health 2010 26 (3) 240-7 CONTEXT: Forty percent of AIDS cases are reported in the southern United States, the region with the largest proportion of HIV/AIDS cases from rural areas. Data are limited regarding provider perspectives of the accessibility and availability of HIV testing and treatment services in southern rural counties. PURPOSE: We surveyed providers in the rural south to better understand: (1) the accessibility and availability, and (2) the facilitators and barriers of HIV testing and treatment services. METHODS: All county health departments (N = 326) serving populations of <50,000 persons, within 10 southern states, were mailed surveys. Responding health departments identified up to 3 HIV testing sites and up to 3 HIV treatment sites to which they refer clients. FINDINGS: Overall, 243 of 326 (75%) health departments, 133 of 250 (53%) HIV testing sites, and 73 of 152 (48%) HIV treatment sites responded to the surveys. The number of testing sites per county ranged from 0 to 20; the number of treatment sites ranged from 0 to 4. An average distance of 50 miles for clients to travel for HIV treatment was reported by health department respondents as a barrier. Facilitators of HIV testing were (1) integrating HIV testing into other health services; (2) using rapid HIV testing; and (3) establishing easily accessible HIV testing locations and free testing services. CONCLUSION: Providers perceive that distance from local health departments to HIV treatment sites presents a barrier to HIV care for their clients. Future studies should ascertain clients' perspectives to ensure appropriate service provisions. |
Impact of a statewide childhood vaccine program in controlling hepatitis A virus infections in Alaska
Singleton RJ , Hess S , Bulkow LR , Castrodale L , Provo G , McMahon BJ . Vaccine 2010 28 (38) 6298-304 Historically, Alaska experienced cyclic hepatitis A virus (HAV) epidemics, and the HAV rate among Alaska Native people was significantly higher than among other racial/ethnic groups. We evaluated the impact of universal childhood vaccination, initiated in 1996, on HAV epidemiology in Alaska by analyzing HAV cases reported to the State of Alaska. HAV incidence in all age groups declined 98.6% from 60.0/100,000 in 1972-1995 to 0.9/100,000 in 2002-2007. The largest decrease (99.9%) was in Alaska Native people, whose incidence (0.3) in 2002-2007 was lower than the overall US 2007 rate (1.0). Among age groups, the decrease (99.8%) among children aged 0-14 years was the largest. Routine childhood vaccination has nearly eliminated HAV infection in Alaska. |
Seasonality and time of host-seeking activity of Culex tarsalis and floodwater Aedes in Northern Colorado, 2006-2007
Godsey MS Jr , Burkhalter K , Delorey M , Savage HM . J Am Mosq Control Assoc 2010 26 (2) 148-159 Effective and economical control of adult vector and pest mosquitoes requires knowledge of their seasonal abundance and host-seeking activity patterns. We conducted research in 2006-2007 to study these variables for Culex tarsalis, Aedes vexans, Ae. melanimon, and Ae. dorsalis in Larimer County, CO. Mosquitoes were collected with traps that segregated catches in 7 consecutive 2-h intervals initiating at 1730 h at 4 sites. Seasonal abundance varied for all species by site and year. Time of host-seeking activity was consistent for all species by site and year. Culex tarsalis counts were significantly higher 1.2-4.5 h after sunset than during the preceding time intervals. Maximum host-seeking activity of the 3 Aedes species occurred from 0.8 h before sunset to 6.5 h after. Host seeking by all species continued throughout the night. For optimal control of Cx. tarsalis adulticide application should start approximately 1 h after sunset, and control of Aedes species should begin soon after sunset, and for all species applications can continue throughout most of the night. |
Blood pressure and hypertension in relation to levels of serum polychlorinated biphenyls in residents of Anniston, Alabama
Goncharov A , Bloom M , Pavuk M , Birman I , Carpenter DO . J Hypertens 2010 28 (10) 2053-60 OBJECTIVE: To determine risk factors for elevated blood pressure and hypertension in residents of Anniston, Alabama who live near a plant that manufactured polychlorinated biphenyls (PCBs). METHODS: A total of 758 Anniston residents had multiple measurements of blood pressure, provided information on demographic factors, medications, smoking, and exercise, and provided blood samples for determination of PCBs and total serum lipid. RESULTS: Rates of hypertension increased significantly (P < 0.05) with age and concentration of serum PCBs and were higher in African-Americans (n = 351) than in whites (n = 407). Hypertension also increased with BMI, but was not related to total serum lipid, sex, smoking, or exercise. Among 394 persons not on antihypertensive medication, linear regression analysis demonstrated a significant positive relation between serum PCB level and both systolic and diastolic blood pressure. After adjustment for potentially confounding variables, logistic regression gave odds ratios for the highest to lowest tertiles of total serum PCBs that exceeded 3.5 for both systolic and diastolic hypertension. When analyzed by quintiles of PCBs, the highest odds ratio was in the third quintile, suggesting a low dose effect. CONCLUSION: In individuals not on antihypertensive medication, serum PCB levels were significantly associated with prevalence of hypertension. Significant positive associations were also observed between PCB concentrations and systolic and diastolic blood pressure even in normotensive ranges. The strength of the relationships between PCB exposure and both hypertension and blood pressure suggests that PCB exposure may be an important contributing factor in regulation of blood pressure. |
Clostridium difficile in food and domestic animals: a new foodborne pathogen?
Gould LH , Limbago B . Clin Infect Dis 2010 51 (5) 577-82 Clostridium difficile infection is increasingly recognized as a cause of diarrhea in outpatients and persons with no apparent health care facility contacts. In contrast to C. difficile infection acquired in health care settings, few risk factors for development of community-associated C. difficile infection are known. Foodborne transmission of C. difficile has been hypothesized as a possible source for community-associated infections; however, the evidence to confirm or refute this hypothesis is incomplete. Recent studies have demonstrated isolation of C. difficile from foods in the United States, Canada, and Europe and from meat products intended for consumption by pets. This raises questions about foodborne transmission of this pathogen to humans through consumption of contaminated products. This review summarizes the available data on C. difficile in animals and food and discusses the potential for foodborne transmission of this pathogen. |
Score-based adjustment for confounding by population stratification in genetic association studies
Allen A , Epstein MP , Satten GA . Genet Epidemiol 2010 34 (5) 383-5 We read with some interest the paper by Zhao, Rebbeck and Mitra “A propensity score approach to correction for bias due to population stratification using genetic and non-genetic factors.” We feel there are a number of issues raised by this paper that are not adequately addressed, which motivates this letter. Further, we take this opportunity to make some general comments that contrast stratification-based and direct (model-based) control of confounding by population stratification. | Zhao, Rebbeck and Mitra (ZRM) give as their stated goal the development of a propensity score-based method for correcting for confounding by population stratification in population-based association studies. We note that ZRM demonstrate their genomic propensity score (GPS) approach using simulation studies of case-control data. However, the propensity score can only be properly used to adjust for confounding in a cohort or case-cohort study [Joffe and Rosenbaum, 1999]. The artificial ratio of case to control participants in a case-control study yields a biased estimate of the propensity score; stratification on a biased estimate of the propensity score can lead to residual bias [Månsson et al., 2007]. With no theoretical basis for believing that adjustment using the propensity score can control bias, the GPS approach applied to case-control data under a general association model is suspect even given the favorable simulation results in ZRM. The suggestion of Månsson et al. [2007] that the propensity score can be estimated using data from control-participants only and then making the rare disease approximation should be viewed with caution, as this scoring function corresponds to one of Miettinen’s confounder scores [Miettinen, 1976]. Estimated odds ratios after stratification using Miettinen’s confounder scores are known to have biased variance estimates due to collinearity [Pike, 1977]. |
Characterization of novel Brucella strains originating from wild native rodent species in North Queensland, Australia
Tiller RV , Gee JE , Frace MA , Taylor TK , Setubal JC , Hoffmaster AR , De BK . Appl Environ Microbiol 2010 76 (17) 5837-45 We report on the characterization of a group of seven novel Brucella strains isolated in 1964 from three native rodent species in North Queensland, Australia during a survey of wild animals. The strains were initially reported as Brucella suis biovar 3 based on microbiological tests. Our results indicated that the rodent strains had distinct microbiological traits compared to B. suis biovar 3 and all other Brucella spp. To reinvestigate these rodent strains, we sequenced the 16S rRNA gene, recA, rpoB, and nine house-keeping genes, and also performed multiple-locus variable-number tandem-repeat analysis (MLVA). The rodent strains have a unique 16S rRNA gene sequence compared to that of the classical Brucella spp. Sequence analysis of recA, rpoB and nine house-keeping genes reveals that the rodent strains are genetically identical to each other at these loci and divergent from any of the currently described Brucella sequence types. However, all seven of the rodent strains do exhibit distinctive allelic MLVA profiles; though none demonstrated an amplicon for VNTR 7 in comparison to other Brucella spp. Phylogenetic analysis of MLVA data reveals the rodent strains form a distinct clade separate from the classical Brucella spp. Furthermore, whole genome sequence comparison using the maximal unique exact matches index (MUMi), demonstrated a high degree of relatedness of one (NF 2653) of the seven rodent Brucella strains with another Australian rodent Brucella strain 83-13. Our findings strongly suggest that this group of Brucella strains isolated from wild Australian rodents define a new species in the Brucella genus. |
Reframing HIV prevention in sub-Saharan Africa using couple-centered approaches
Grabbe KL , Bunnell R . JAMA 2010 304 (3) 346-7 Despite modest prevention successes, 2.7 million new human immunodeficiency virus (HIV) infections occurred worldwide in 2008 and there were at least 2 million HIV-associated deaths.1 Nearly 3 million persons in sub-Saharan Africa are now taking antiretroviral therapy (ART)1—an impressive accomplishment. The urgency of sustaining treatment for these patients, and reaching more than 15 million persons with unmet care and treatment needs,1 underscores the need to reduce HIV incidence. HIV testing and counseling among serodiscordant couples has been associated with reduced transmission, increased condom use, and reduction in sex acts with outside partners2,3 as well as increased ART uptake among pregnant women in antenatal clinics.4 Reframing HIV prevention using a couple-centered approach could help enhance current prevention efforts. | Sexual HIV transmission occurs within couples. Couple types vary widely and may be polygamous or monogamous; casual or formal; between cohabiting or noncohabiting partners; among heterosexual, same-sex, or transgender persons; and among low-risk or higher-risk individuals such as injecting drug users and sex workers. Yet, to best identify viable HIV prevention options, all couple members should know the answers to 2 questions: what is my HIV status and what is my partner's HIV status? | Fundamental as these questions are for HIV prevention, few individuals can answer them. Among responding countries in sub-Saharan Africa, only 22% of adults aged 15 to 49 years know their HIV status.5 Cohabitation ranges from 56% in South Africa to more than 70% of adults in East Africa, and condom use within regular partnerships is very low.6 In East Africa, nearly half of cohabiting HIV-infected individuals are in an HIV-discordant relationship,7 and modeling suggests that 55% to 93% of new HIV infections occur within cohabiting relationships.3,8 Most transmissions occur within couples unaware of their HIV status. |
Seroconversion following incomplete human rabies postexposure prophylaxis
Robertson K , Recuenco S , Niezgoda M , Garcia ER , Rupprecht CE . Vaccine 2010 28 (39) 6523-6 In August 2008, CDC and the Puerto Rico Department of Health conducted a serosurvey of patients who had discontinued rabies postexposure prophylaxis (PEP) prior to completing a schedule of five vaccine doses. The objective was to determine whether further vaccination of these patients was needed based on serum rabies neutralizing antibody levels. Eighteen patients consented to serology using the rapid fluorescent focus inhibition test. The World Health Organization's cutoff value of 0.5IU/mL was used as the basis for recommending PEP continuance, while complete virus neutralization at the 1:5 dilution indicated seroconversion per current Advisory Committee for Immunization Practices recommendations. Serum samples were collected a median of 147 days (range 24-215) after receipt of the last vaccine dose. Ten patients were recommended for PEP continuance for titers below 0.5IU/mL; however, of 11 patients, 33% of 2-dose, 100% of 3-dose, and 100% of 4-dose patients exhibited seroconversion. These findings corroborate previous studies that suggest a less than five dose rabies vaccine regimen elicits adequate immunogenicity against rabies. |
Sustained protection from pentavalent rotavirus vaccination during the second year of life at a large, urban US pediatric hospital
Boom JA , Tate JE , Sahni LC , Rench MA , Quaye O , Mijatovic-Rustempasic S , Patel MM , Baker CJ , Parashar UD . Pediatr Infect Dis J 2010 29 (12) 1133-5 Fecal specimens from children presenting to Texas Children's Hospital with acute gastroenteritis were tested for the presence of rotavirus. Children were grouped according to vaccination status, and pentavalent rotavirus vaccine effectiveness was calculated. Pentavalent rotavirus vaccine effectiveness against severe rotavirus gastroenteritis was sustained during the first 2 years of the vaccination program. Overall 3-dose effectiveness was 83% to 86%; it was 92% to 93% among children 6 to 11 months of age and 78% to 84% among children ≥12 months of age. |
Fractional doses of inactivated poliovirus vaccine in Oman
Mohammed AJ , AlAwaidy S , Bawikar S , Kurup PJ , Elamir E , Shaban MM , Sharif SM , van der Avoort HG , Pallansch MA , Malankar P , Burton A , Sreevatsava M , Sutter RW . N Engl J Med 2010 362 (25) 2351-9 BACKGROUND: We conducted a clinical trial of fractional doses of inactivated poliovirus vaccine administered to infants in Oman, in order to evaluate strategies for making the vaccine affordable for use in developing countries. METHODS: We compared fractional doses of inactivated poliovirus vaccine (0.1 ml, representing one fifth of a full dose) given intradermally with the use of a needle-free jet injector device, with full doses of vaccine given intramuscularly, with respect to immunogenicity and reactogenicity. Infants were randomly assigned at birth to receive either a fractional dose or a full dose of inactivated poliovirus vaccine at 2, 4, and 6 months. We also administered a challenge dose of monovalent type 1 oral poliovirus vaccine at 7 months and collected stool samples before and 7 days after administration of the challenge dose. RESULTS: A total of 400 infants were randomized, of whom 373 (93.2%) fulfilled the study requirements. No significant baseline differences between the groups were detected. Thirty days after completion of the three-dose schedule, the rates of seroconversion to types 1, 2, and 3 poliovirus were 97.3%, 95.7%, and 97.9%, respectively, in the fractional-dose group, as compared with 100% seroconversion to all serotypes in the full-dose group (P=0.01 for the comparison with respect to type 2 poliovirus; results with respect to types 1 and 3 poliovirus were not significant). The median titers were significantly lower in the fractional-dose group than in the full-dose group (P<0.001 for all three poliovirus serotypes). At 7 months, 74.8% of the infants in the fractional-dose group and 63.1% of those in full-dose group excreted type 1 poliovirus (P=0.03). Between birth and 7 months, 42 hospitalizations were reported, all related to infectious causes, anemia, or falls, with no significant difference between vaccination groups. CONCLUSIONS: These data show that fractional doses of inactivated poliovirus vaccine administered intradermally at 2, 4, and 6 months, as compared with full doses of inactivated poliovirus vaccine given intramuscularly on the same schedule, induce similar levels of seroconversion but significantly lower titers. (Current Controlled Trials number, ISRCTN17418767.) |
Generation of Trypanosoma cruzi-specific CD8+ T-cell immunity is unaffected by the absence of type I interferon signaling
Martin DL , Murali-Krishna K , Tarleton RL . Infect Immun 2010 78 (7) 3154-9 Trypanosoma cruzi is a protozoan parasite that causes human Chagas' disease, a leading source of congestive heart failure in Central and South America. CD8+ T cells are critical for control of T. cruzi infection, and CD8+ T cells recognizing the immunodominant trans-sialidase gene-encoded peptide TSKB20 (ANYKFTLV) account for approximately 30% of the total CD8+ T-cell population at the peak of infection in C57BL/6 mice. Type I interferons (IFN-I) are pleiotropic cytokines that play a critical role in both innate and adaptive immunity against a variety of infections, but their induction and their role in infection are dictated by the infectious agent. Because type I IFNs and IFN-responsive genes are evident early after T. cruzi infection of host cells, we examined the influence of IFN-I on the development of CD8+ T-cell responses during this infection. Mice lacking the receptor for IFN-I (IFNARKO) and their wild-type counterparts both developed chronic infections and generated similar frequencies of immunodominant TSKB20- and subdominant TSKB18-specific CD8+ T cells following T. cruzi infection. In contrast, peak TSKB20-specific CD8+ T-cell responses generated during infection with vaccinia virus engineered to express TSKB20 were approximately 2.5-fold lower in IFNARKO mice than B6 mice, although after viral clearance, the frequencies of TSKB20-specific CD8+ T cells stabilized at similar levels. Together, these data suggest that IFN-I induction and biology are dependent upon the microbial context and emphasize the need to investigate various infection models for a full understanding of CD8+ T-cell development. |
Newspaper reports: a source of surveillance for burns among women in Pakistan
Nasrullah M , Muazzam S . J Public Health (Oxf) 2010 32 (2) 245-9 BACKGROUND: Our study attempts to describe the demographics, characteristics of victims and perpetrators, and circumstances leading to burn events among females in Pakistan. METHODS: Human Rights Commission of Pakistan (HRCP) systematically collected data on burns among women using newspaper reports from January 2004 till December 2005. We analyzed the aggregated data and estimated burn rates. RESULTS: A total of 222 burn events were reported from 2004 to 2005; complete data were not available for all variables. Adults (>or=18 years) constituted 74% (91/123) of cases with 95% (121/127) being married. Most burns were caused by bursting of stoves (34%; 64/189) or victims set-on fire (33%; n = 63/189). Burns using acids accounted for 13% (25/189). Husbands (52%; 51/98) and in-laws (23%; 23/98) were the perpetrators in known burn events. Burns were classified as accidental in half of cases (51%; 97/189) and related to domestic issues in a quarter (25%; 47/189). There were 49% of (92/189) burns that were reported as intentional. The mean annual rate of burns among women (15-64 years of age) was found to be 33 per 100,000. CONCLUSION: Newspaper reports are good source of surveillance when information is otherwise limited. Majority of burns (51%) were classified as accidental while 49% were reported as intentional, though there is a limitation in the accuracy of reported accidental events. There is a dire need for systematic data collection and devising preventive strategies for this important public health problem that remains largely neglected in Pakistan. |
Physical dating violence norms and behavior among sixth-grade students from four U.S. sites
Simon TR , Miller S , Gorman-Smith D , Orpinas P , Sullivan T . J Early Adolesc 2010 30 (3) 395-409 Relatively little is known about the prevalence of physical dating violence behaviors and perceived norms about dating violence among early adolescents. A sample of 5,404 sixth-grade students was recruited from four diverse U.S. sites. Over half of the respondents reported that girls hitting their boyfriends was acceptable under certain circumstances (e.g., if made mad or jealous) and more than one in four reported acceptance of boys hitting their girlfriends. Among those reporting that they had a recent boy/girlfriend, nearly one third of girls (31.5%) and more than one fourth of boys (26.4%) reported being physically aggressive toward this person (e.g., punching, slapping). These data support the need to address the problem of violence within students' perceived dating relationships in sixth grade or earlier and suggest that preventive interventions should focus on changing norms that support violence between males and females. |
Blast injuries from bombings: what craniofacial and maxillofacial surgeons need to know
Armstrong JH , Sullivent EE , Sasser SM . J Craniofac Surg 2010 21 (4) 954-9 Why should specialists in craniofacial and maxillofacial surgery care about blast injury from bombings, and what is important to know about blast injuries? The recently revised bombings curriculum Bombings: Injury Patterns and Care, Version 2.0, released through the Centers for Disease Control and Prevention National Center for Injury Prevention and Control, provides answers by addressing the global context of bombings, reviewing the 4 mechanisms of blast injury, and describing the management and care of blast casualties. |
A practical biomechanical model of the index finger simulating the kinematics of the muscle/tendon excursions
Wu JZ , An KN , Cutlip RG , Dong RG . Biomed Mater Eng 2010 20 (2) 89-97 Biomechanical models of the hand and fingers are useful tools for hand surgeons to improve surgical procedures and for biomedical researchers to explore the mechanical loading in the musculoskeletal system that cannot be easily measured in vivo. The purpose of the present study was to develop a realistic index finger model for solving practical problems. The model includes the meshes of four bony sections (distal, middle, proximal and metacarpal bones) obtained via micro-CT scans. The tendon attachment sites are adopted from the normative finger model. A total of seven tendon/muscles are included in the model. The predicted tendon excursions and moment arms were compared with published experimental data. One of the advantages of the current approach over previous studies is that the current model has been developed on a platform of a commercial software package, such that researchers can apply it as a universal tool for practical problems. |
Changes and variability in high levels of low-density lipoprotein cholesterol among children
Freedman DS , Wang YC , Dietz WH , Xu JH , Srinivasan SR , Berenson GS . Pediatrics 2010 126 (2) 266-73 OBJECTIVE: A 2008 report from the American Academy of Pediatrics recommended both population and individual approaches (including pharmacologic interventions) for adolescents who had low-density lipoprotein (LDL) cholesterol levels above various cutoff points (130, 160, and 190 mg/dL). However, the tracking and variability of these very high levels have not been investigated. METHODS: A total of 6827 subjects underwent multiple LDL cholesterol determinations in childhood and adulthood in the Bogalusa Heart Study. The total number of determinations was 26748, and the median interval between examinations was 3 years. RESULTS: Correlations between initial and subsequent LDL cholesterol levels ranged from r approximately 0.8 for measurements made within the same year to r approximately 0.5 for periods of ≥20 years. Most children who had very high LDL cholesterol levels, however, had substantially lower levels at the next examination. LDL cholesterol levels between 160 and 189 mg/dL (n = 201) decreased, on average, by 21 mg/dL at the next examination, whereas levels of ≥190 mg/dL (n = 44) decreased by 34 mg/dL. In contrast, the mean increase for LDL cholesterol levels of <70 mg/dL was 13 mg/dL. These changes were equal to those expected on the basis of regression to the mean. CONCLUSIONS: There can be large changes in extreme levels of LDL cholesterol because of regression to the mean, and practitioners should be aware that very high levels may decrease substantially in the absence of any intervention. |
Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV
Hyde TB , Schmid DS , Cannon MJ . Rev Med Virol 2010 20 (5) 311-26 Congenital CMV infection is caused by in utero mother-to-fetus transmission and is a leading cause of birth defects and developmental disabilities. The highest risk of disability is to children born to women who have a primary infection during pregnancy, which can be detected by measuring seroconversion. We reviewed studies that reported rates of CMV seroconversion in different populations. Among pregnant women, annual seroconversion rates typically ranged from 1 to 7% (summary annual rate = 2.3%, 95% CI = 2.1-2.4%). Healthcare workers, including those caring for infants and children, had seroconversion rates similar to pregnant women (summary annual rate = 2.3%, 95% CI = 1.9-2.9%). Among day-care providers, seroconversion rates ranged from 0 to 12.5% (summary annual rate = 8.5%, 95% CI = 6.1-11.6%). Parents whose child was not shedding CMV were much less likely to seroconvert (summary annual rate = 2.1%, 95% CI = 0.3-6.8%) than were parents who had a child shedding CMV (summary annual rate = 24%, 95% CI = 18-30%). Nevertheless, over the course of a year, most parents exposed to a CMV-shedding child do not become infected. Other groups with elevated risk included families with a CMV-shedding member, female minority adolescents and women attending sexually transmitted disease clinics. The relatively low rate of CMV seroconversion in most populations is encouraging for behavioural interventions and for vaccine strategies attempting to prevent infection during pregnancy. |
Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice
Zeidler-Erdely PC , Kashon ML , Li S , Antonini JM . Respir Res 2010 11 (1) 70 BACKGROUND: Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant) or non-carcinogenic (iron abundant) metal-containing welding fumes at the transcriptome level. METHODS: Mice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done. RESULTS: Overall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as CCL3, CCL4, CXCL2, and MMP12 in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as S100A8, S100A9 and MMP9. CONCLUSIONS: Collectively, our results demonstrate that lung tumor susceptibility may predispose the A/J strain to a prolonged dysregulation of immunomodulatory genes, thereby delaying the recovery from welding fume-induced lung inflammation. Additionally, our results provide unique insight into strain- and welding fume-dependent genetic factors involved in the lung response to welding fume. |
Reservoir diagnosis of longwall gobs through drawdown tests and decline curve analyses of gob gas venthole productions
Dougherty HN , Karacan CO , Goodman GVR . Int J Rock Mech Min Sci 2010 47 (5) 851-857 During longwall mining, fracturing and relaxation in the gob creates new and highly permeable flow paths. Methane inflow from the gob into the mining environment is influenced by the magnitude of fracturing and the extent to which the fractures stay open during mining. Singh and Kendorski [1] evaluated the disturbance of rock strata resulting from mining and described a caved zone that extends from the mining level to 3–6 times the seam thickness, a fractured zone that extends from the mining level to 30–58 times the seam thickness, and a bending zone where there is no change in permeability that extends from 30 times the seam thickness to 50 ft below ground surface. The characteristics of fracturing and the subsidence of overburden were revealed through predictive techniques and field studies [2], [3], [4], [5], [6]. It was concluded that rock failure leading to increased hydraulic conductivity in the gob was initiated by high compressive stresses ahead of the face with the fractures subsequently opened by tensile stresses behind the face [7]. | Gas, particularly methane that is contained within the gob, will be released over time as mining progresses and is a big contributor to ventilation emissions if not controlled. Relaxation of the roof rocks, ventilation pressure and the associated fracture connectivity allow gas to flow from all surrounding gas sources toward the mine workings, which eventually may create an unsafe condition for the underground workforce. |
Modeling the national pediatric vaccine stockpile: supply shortages, health impacts and cost consequences
Shrestha SS , Wallace GS , Meltzer MI . Vaccine 2010 28 (38) 6318-32 Pediatric vaccine stockpiles have been in place in the U.S. since 1983 to address the potential disruption in supply of routine pediatric vaccines. Increases in the number of vaccines recommended for pediatric and adolescent patients have increased the cost of stocking and maintaining the stockpile. Based on a spreadsheet-based model (VacStockpile) we developed, we estimated potential supply shortages of 14 stockpiled vaccines as of August 1, 2008 and its health and financial impacts under various shortage and stockpile scenarios. To illustrate the implications of policy options, we compared "high" to "low" stockpile scenarios. The high stockpile scenario ensures a 6-month vaccine supply to vaccinate all children according to recommended schedules. The low scenario comprised of 50% of the high scenario or existing stocks, whichever is smaller. For each vaccine, we used a weighted average of five shortage scenarios ranging from 0% to 100%, in 25% increments. Demand for each vaccine was based on current distribution or birth cohort size. The probabilities of shortages were based on number of manufacturers, market stability, history of manufacturing problems, and production complexity. CDC contract prices were used to estimate costs. Expert opinion and literature provided estimates of health impacts due to shortages. Applying the probabilities of shortages to all vaccines in a single year, the "low" scenario could cost $600 million, with 376,000 vaccine-preventable cases occurring and 1774 deaths. The "high" scenario could cost $2 billion, with an additional $1.6 billion initial stocking, and result in 7100 vaccine-preventable cases occurring and 508 deaths. Based on the assumptions in the model, there is the potential for large differences in outcomes between the scenarios although some outcomes could potentially be averted with measures such as catch-up campaigns after shortages. Using the VacStockpile policy makers can readily evaluate the implications of assumptions and decide which set of assumptions they wish to use in planning. |
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