Moving forward: Using the experience of the CDCs' Colorectal Cancer Screening Demonstration Program to guide future colorectal cancer programming efforts
Seeff LC , Degroff A , Joseph DA , Royalty J , Tangka FK , Nadel MR , Plescia M . Cancer 2013 119 Suppl 15 2940-6 BACKGROUND: The Centers for Disease Control and Prevention (CDC) established and supported a 4-year Colorectal Cancer Screening Demonstration Program (CRCSDP) from 2005 to 2009 for low-income, under- or uninsured men and women aged 50-64 at 5 sites in the United States. METHODS: A multiple methods evaluation was conducted including 1) a longitudinal, comparative case study of program implementation, 2) the collection and analysis of client-level screening and diagnostic services outcome data, and 3) the collection and analysis of program- and patient-level cost data. RESULTS: Several themes emerged from the results reported in the series of articles in this Supplement. These included the benefit of building on an existing infrastructure, strengths and weakness of both the 2 most frequently used screening tests (colonoscopy and fecal occult blood tests), variability in costs of maintaining this screening program, and the importance of measuring the quality of screening tests. Population-level evaluation questions could not be answered because of the small size of the participating population and the limited time frame of the evaluation. The comprehensive evaluation of the program determined overall feasibility of this effort. CONCLUSIONS: Critical lessons learned through the implementation and evaluation of the CDC's CRCSDP led to the development of a larger population-based program, the CDC's Colorectal Cancer Control Program (CRCCP). Cancer 2013;119(15 suppl):2940-6. (c) 2013 American Cancer Society. |
Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes
Wing RR , Bolin P , Brancati FL , Bray GA , Clark JM , Coday M , Crow RS , Curtis JM , Egan CM , Espeland MA , Evans M , Foreyt JP , Ghazarian S , Gregg EW , Harrison B , Hazuda HP , Hill JO , Horton ES , Hubbard VS , Jakicic JM , Jeffery RW , Johnson KC , Kahn SE , Kitabchi AE , Knowler WC , Lewis CE , Maschak-Carey BJ , Montez MG , Murillo A , Nathan DM , Patricio J , Peters A , Pi-Sunyer X , Pownall H , Reboussin D , Regensteiner JG , Rickman AD , Ryan DH , Safford M , Wadden TA , Wagenknecht LE , West DS , Williamson DF , Yanovski SZ . N Engl J Med 2013 369 (2) 145-54 BACKGROUND: Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients. METHODS: In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years. RESULTS: The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51). CONCLUSIONS: An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes. (Funded by the National Institutes of Health and others; Look AHEAD ClinicalTrials.gov number, NCT00017953.). |
COPD surveillance-United States, 1999-2011
Ford ES , Croft JB , Mannino DM , Wheaton AG , Zhang X , Giles WH . Chest 2013 144 (1) 284-305 This report updates surveillance results for COPD in the United States. For 1999 to 2011, data from national data systems for adults aged ≥ 25 years were analyzed. In 2011, 6.5% of adults (approximately 13.7 million) reported having been diagnosed with COPD. From 1999 to 2011, the overall age-adjusted prevalence of having been diagnosed with COPD declined (P = .019). In 2010, there were 10.3 million (494.8 per 10,000) physician office visits, 1.5 million (72.0 per 10,000) ED visits, and 699,000 (32.2 per 10,000) hospital discharges for COPD. From 1999 to 2010, no significant overall trends were noted for physician office visits and ED visits; however, the age-adjusted hospital discharge rate for COPD declined significantly (P = .001). In 2010 there were 312,654 (11.2 per 1,000) Medicare hospital discharge claims submitted for COPD. Medicare claims (1999-2010) declined overall (P = .045), among men (P = .022) and among enrollees aged 65 to 74 years (P = .033). There were 133,575 deaths (63.1 per 100,000) from COPD in 2010. The overall age-adjusted death rate for COPD did not change during 1999 to 2010 (P = .163). Death rates (1999-2010) increased among adults aged 45 to 54 years (P < .001) and among American Indian/Alaska Natives (P = .008) but declined among those aged 55 to 64 years (P = .002) and 65 to 74 years (P < .001), Hispanics (P = .038), Asian/Pacific Islanders (P < .001), and men (P = .001). Geographic clustering of prevalence, Medicare hospitalizations, and deaths were observed. Declines in the age-adjusted prevalence, death rate in men, and hospitalizations for COPD since 1999 suggest progress in the prevention of COPD in the United States. |
Unusual Enterocytozoon bieneusi genotypes and Cryptosporidium hominis subtypes in HIV-infected patients on highly active antiretroviral therapy.
Akinbo FO , Okaka CE , Omoregie R , Adamu H , Xiao L . Am J Trop Med Hyg 2013 89 (1) 157-61 Abstract. Human immunodeficiency virus (HIV)-infected persons are commonly infected with Cryptosporidium species and Enterocytozoon bieneusi in both developed and developing countries, particularly patients with CD4+ cell counts below 200 cells/muL; 285 HIV-infected patients on highly active antiretroviral therapy (HAART) were enrolled in this study, and both stool and blood specimens were collected from participants. The stool specimens were analyzed and typed for E. bieneusi and Cryptosporidium spp. by polymerase chain reaction (PCR) and DNA sequencing. CD4 count was analyzed using flow cytometry. E. bieneusi and Cryptosporidium were detected in 18 (6.3%) and 4 (1.4%) patients, respectively. The E. bieneusi detected mostly belonged to a new genotype group that, thus far, has only been found in a few humans: genotype Nig4 in 2 patients and two new genotypes related to Nig4 in 12 patients. The Cryptosporidium detected included C. hominis (two patients), C. parvum (one patient), and C. felis (one patient), with the two C. hominis infections belonging to an unusual subtype family. Additional studies are required to determine whether some E. bieneusi genotypes and C. hominis subtypes are more prevalent in HIV patients on HAART. |
Rapid advances in understanding viral gastroenteritis from domestic surveillance
Payne DC , Parashar UD . Emerg Infect Dis 2013 19 (8) 1189 Winter vomiting disease was the clinical moniker for viral acute gastroenteritis (AGE), including illnesses caused by norovirus and rotavirus, nearly 100 years ago (1). This nonspecific diagnosis represented a frequently observed illness, with the symptoms of vomiting and diarrhea that occurred particularly in the colder months. One hundred years later, diagnosing specific AGE pathogens in clinical settings continues to be an elusive task. Clinical treatment options are nonspecific as well—primarily rehydration and supportive therapies—and the identification of the viral pathogens is considered relatively time-consuming and costly. | In truth, viral AGE has likely caused misery, illness, and death among human populations for thousands of years, since people first facilitated disease transmission by congregating in groups. But, it has been only during the lifetime of many current readers (and during the long career spans of several), beginning in the early 1970s, that norovirus, rotavirus, and an expanding collection of other viral AGE pathogens have been discovered. The advent of sensitive laboratory tools to detect and study the genetic evolution of these viruses has uncovered their critical role in the etiology of AGE. The flow of information is now so great that in each year since 2008, >800 scientific papers have been published on this topic as determined by a search of PubMed using the term acute gastroenteritis. |
Recognizing Laboratory Cross-Contamination: Two False-Positive Cultures of Mycobacterium tuberculosis-Oklahoma, 2011
Johnson MG , Lindsey PH , Harvey CF , Bradley KK . Chest 2013 144 (1) 319-22 Mycobacterium tuberculosis (MTB) isolation from clinical specimens is the standard for TB diagnosis. Positive MTB cultures are rarely questioned, but false-positive culture rates range from 2% to 4%. In December 2011, two smear-negative, culture-positive TB cases were reported to the Oklahoma State Department of Health (OSDH) in people without TB signs or symptoms. OSDH TB control officers interviewed physicians and laboratory personnel, reviewed patient charts, traced epidemiologic links, and performed microbiologic studies to determine if these were true TB cases. Both specimens were found to have been processed on the same day, at the same laboratory, under the same hood, and by the same technician sequentially after a strongly smear-positive TB specimen. No epidemiologic links were identified among the three patients. Spoligotyping and 24-locus mycobacterial interspersed repetitive unit typing of the three specimens were identical. Only liquid media grew MTB in the two questionable specimens. A laboratory splash incident was suspected, whereby all three liquid media sample lids were open during inoculation rather than being opened one at a time, causing cross-contamination. Also, the two specimens were incubated for 2-3 weeks longer than standard protocol before MTB growth was observed. Patient 1 was not treated for TB because her physician doubted the culture result. Patient 2, an organ transplant recipient, began four-drug anti-TB therapy, and an investigation was initiated for transplant-associated TB. Adherence to strict laboratory techniques and recognizing the possibility of false-positive MTB cultures, especially when inconsistent with clinical data, are essential in preventing erroneous TB diagnoses. |
Rotavirus G9P[4] in 3 countries in Latin America, 2009-2010
Quaye O , McDonald S , Esona MD , Lyde FC , Mijatovic-Rustempasic S , Roy S , Banegas DJ , Quinonez YM , Chinchilla BL , Santiago FG , Lozano HG , Rey-Benito G , de Oliveira LH , Gentsch JR , Bowen MD . Emerg Infect Dis 2013 19 (8) 1332-3 Group A rotaviruses are the most common viral cause of acute gastroenteritis in young children. The most frequently detected group A rotavirus genotype combinations include G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8]. The G9 genotype has been associated with multiple P types, including P[8], P[6], and P[4], although genotype G9P[8] is predominant (1). | In Latin America, a large number of unusual G-P combinations have been reported, and among these is the rare G9P[4] genotype, which was identified in Brazil in the 1990s (2), and later reported infrequently elsewhere in Latin America (3). In 2010, cases of group A rotavirus gastroenteritis associated with genotype G9P[4] were reported in Mexico (4). Increases in the incidence of group A rotavirus gastroenteritis were reported in 2010 in Mexico and Guatemala and in 2009 in Honduras (http://new.paho.org/hq/dmdocuments/2010/Epi_Alerts_2010_mar_5_rotavirus.pdf). | In response to these reports of increased group A rotavirus disease, fecal samples collected in Chiapas State, Mexico (in 2010, 30% of the cases in Mexico were from Chiapas), Guatemala, and Honduras in 2009–2010 that were positive by enzyme immunoassay were sent to the US Centers for Disease Control and Prevention (Atlanta, GA, USA) for characterization. Viral protein 4 (VP4) (P) and VP7 (G) genotyping, nucleotide sequencing, and genotype identification were performed by using consensus and genotype-specific oligonucleotide primers (5), and sequences were subjected to phylogenetic analyses. VP6 and nonstructural protein 4 (NSP4) genes of selected samples were also sequenced. |
Screening for sexually transmitted diseases in short-term correctional institutions: summary of evidence reviewed for the 2010 Centers for Disease Control and Prevention sexually transmitted diseases treatment guidelines
Spaulding AC , Miller J , Trigg BG , Braverman P , Lincoln T , Reams PN , Staples-Horne M , Sumbry A , Rice D , Satterwhite CL . Sex Transm Dis 2013 40 (9) 679-684 Young persons entering US jails and youth detention facilities have high rates of sexually transmitted diseases (STDs). The Centers for Disease Control and Prevention added STD screening guidelines specific to correctional settings to the 2010 STD Treatment Guidelines. This article summarizes published evidence from 1990 to 2009 used to develop the recommendations. The literature supports routine screening of adolescents and young women (aged ≤35 years, or on the basis of local institutional prevalence data) for chlamydia and gonorrhea because of high prevalence and the subsequent risk of adverse reproductive outcomes. Chlamydia positivity among young women (aged <20 years) in juvenile detention facilities and adult facilities is more than 14%. Men in correctional settings are also at high risk for chlamydia and gonorrhea. Among boys in juvenile detention facilities, chlamydia positivity is estimated at 6.6%; among young men in adult facilities, positivity is 16.6%. Screening men (to reduce sequelae among women) should be considered based on local epidemiology and resource availability. Syphilis screening is not strongly supported in published literature because of low prevalence and is not routinely recommended; however, some screening may be warranted based on local prevalence. Although there is a great diversity in the organization of correctional facilities, implementation of screening recommendations is possible owing to improvements in test technology (urine specimens) and through integration of a standard screening protocol. Based on the high burden of disease and substantial opportunities to reach a high-risk population, correctional facilities are important venues to target efforts to control STDs. |
Sensitive assessment of the virologic outcomes of stopping and restarting non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy
Geretti AM , Fox Z , Johnson JA , Booth C , Lipscomb J , Stuyver LJ , Tachedjian G , Baxter J , Touloumi G , Lehmann C , Owen A , Phillips A . PLoS One 2013 8 (7) e69266 BACKGROUND: Non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutants have been shown to emerge after interruption of suppressive NNRTI-based antiretroviral therapy (ART) using routine testing. The aim of this study was to quantify the risk of resistance by sensitive testing and correlate the detection of resistance with NNRTI concentrations after treatment interruption and virologic responses after treatment resumption. METHODS: Resistance-associated mutations (RAMs) and NNRTI concentrations were studied in plasma from 132 patients who interrupted suppressive ART within SMART. RAMs were detected by Sanger sequencing, allele-specific PCR, and ultra-deep sequencing. NNRTI concentrations were measured by sensitive high-performance liquid chromatography. RESULTS: Four weeks after NNRTI interruption, 19/31 (61.3%) and 34/39 (87.2%) patients showed measurable nevirapine (>0.25 ng/ml) or efavirenz (>5 ng/ml) concentrations, respectively. Median eight weeks after interruption, 22/131 (16.8%) patients showed ≥1 NNRTI-RAM, including eight patients with NNRTI-RAMs detected only by sensitive testing. The adjusted odds ratio (OR) of NNRTI-RAM detection was 7.62 (95% confidence interval [CI] 1.52, 38.30; p = 0.01) with nevirapine or efavirenz concentrations above vs. below the median measured in the study population. Staggered interruption, whereby nucleos(t)ide reverse transcriptase inhibitors (NRTIs) were continued for median nine days after NNRTI interruption, did not prevent NNRTI-RAMs, but increased detection of NRTI-RAMs (OR 4.25; 95% CI 1.02, 17.77; p = 0.03). After restarting NNRTI-based ART (n = 90), virologic suppression rates <400 copies/ml were 8/13 (61.5%) with NNRTI-RAMs, 7/11 (63.6%) with NRTI-RAMs only, and 51/59 (86.4%) without RAMs. The ORs of re-suppression were 0.18 (95% CI 0.03, 0.89) and 0.17 (95% CI 0.03, 1.15) for patients with NNRTI-RAMs or NRTI-RAMs only respectively vs. those without RAMs (p = 0.04). CONCLUSIONS: Detection of resistant mutants in the rebound viremia after interruption of efavirenz- or nevirapine-based ART affects outcomes once these drugs are restarted. Further studies are needed to determine RAM persistence in untreated patients and impact on newer NNRTIs. |
A single early introduction of HIV-1 subtype B into Central America accounts for most current cases
Murillo W , Veras N , Prosperi M , de Rivera IL , Paz-Bailey G , Morales-Miranda S , Juarez SI , Yang C , DeVos J , Marin JP , Mild M , Albert J , Salemi M . J Virol 2013 87 (13) 7463-70 Human immunodeficiency virus type 1 (HIV-1) variants show considerable geographical separation across the world, but there is limited information from Central America. We provide the first detailed investigation of the genetic diversity and molecular epidemiology of HIV-1 in six Central American countries. Phylogenetic analysis was performed on 625 HIV-1 pol gene sequences collected between 2002 and 2010 in Honduras, El Salvador, Nicaragua, Costa Rica, Panama, and Belize. Published sequences from neighboring countries (n = 57) and the rest of the world (n = 740) were included as controls. Maximum likelihood methods were used to explore phylogenetic relationships. Bayesian coalescence-based methods were used to time HIV-1 introductions. Nearly all (98.9%) Central American sequences were of subtype B. Phylogenetic analysis revealed that 437 (70%) sequences clustered within five significantly supported monophyletic clades formed essentially by Central American sequences. One clade contained 386 (62%) sequences from all six countries; the other four clades were smaller and more country specific, suggesting discrete subepidemics. The existence of one large well-supported Central American clade provides evidence that a single introduction of HIV-1 subtype B in Central America accounts for most current cases. An introduction during the early phase of the HIV-1 pandemic may explain its epidemiological success. Moreover, the smaller clades suggest a subsequent regional spread related to specific transmission networks within each country. |
Norovirus disease in the United States
Hall AJ , Lopman BA , Payne DC , Patel MM , Gastanaduy PA , Vinje J , Parashar UD . Emerg Infect Dis 2013 19 (8) 1198-205 Although recognized as the leading cause of epidemic acute gastroenteritis across all age groups, norovirus has remained poorly characterized with respect to its endemic disease incidence. Use of different methods, including attributable proportion extrapolation, population-based surveillance, and indirect modeling, in several recent studies has considerably improved norovirus disease incidence estimates for the United States. Norovirus causes an average of 570-800 deaths, 56,000-71,000 hospitalizations, 400,000 emergency department visits, 1.7-1.9 million outpatient visits, and 19-21 million total illnesses per year. Persons >65 years of age are at greatest risk for norovirus-associated death, and children <5 years of age have the highest rates of norovirus-associated medical care visits. Endemic norovirus disease occurs year round but exhibits a pronounced winter peak and increases by ≤50% during years in which pandemic strains emerge. These findings support continued development and targeting of appropriate interventions, including vaccines, for norovirus disease. |
The proportions of people living with HIV in low and middle-income countries who test tuberculin skin test positive using either a greater or equal to 5 mm or a greater or equal to 10 mm cut-off: a systematic review
Kerkhoff AD , Gupta A , Samandari T , Lawn SD . BMC Infect Dis 2013 13 (1) 307 BACKGROUND: A positive tuberculin skin test (TST) is often defined by skin induration of >=10 mm in people who are HIV-seronegative. However, to increase sensitivity for detection of Mycobacterium tuberculosis infection in the context of impaired immune function, a revised cut-off of >=5 mm is used for people living with HIV infection. The incremental proportion of patients who are included by this revised definition and the association between this proportion and CD4+ cell count are unknown. METHODS: The literature was systematically reviewed to determine the proportion of people living with HIV (PLWH) without evidence of active tuberculosis in low and middle-income countries who tested TST-positive using cut-offs of >=5 mm and >=10 mm of induration. The difference in the proportion testing TST-positive using the two cut-off sizes was calculated for all eligible studies and was stratified by geographical region and CD4+ cell count. RESULTS: A total of 32 studies identified meeting criteria were identified, providing data on 10,971 PLWH from sub-Saharan Africa, Asia and the Americas. The median proportion of PLWH testing TST-positive using a cut-off of >=5 mm was 26.8% (IQR, 19.8-46.1%; range, 2.5-81.0%). Using a cut-off of >=10 mm, the median proportion of PLWH testing TST-positive was 19.6% (IQR, 13.7-36.8%; range 0--52.1%). The median difference in the proportion of PLWH testing TST-positive using the two cut-offs was 6.0% (IQR, 3.4-10.1%; range, 0--37.6%). Among those with CD4+ cell counts of <200, 200--499 and >=500 cells/muL, the proportion of positive tests defined by the >=5 mm cut-off that were between 5.0 and 9.9 mm in diameter was similar (12.5%, 12.9% and 10.5%, respectively). CONCLUSIONS: There is a small incremental yield in the proportion of PLWH who test TST-positive when using an induration cut-off size of >=5 mm compared to >=10 mm. This proportion was similar across the range of CD4+ cell strata, supporting the current standardization of this cut-off at all levels of immunodeficiency. |
Gonorrhea infections diagnosed among persons living with HIV/AIDS: identifying opportunities for integrated prevention services in New York City, Washington, DC, Miami/Dade County, and Arizona
Taylor MM , Schillinger JA , Furness BW , Brewer T , Newman DR , Pathela P , Skinner J , Braunstein S , Shepard C , Ahmed T , Griffin A , Blank S , Peterman TA . J Acquir Immune Defic Syndr 2013 64 (1) 115-20 Persons living with HIV/AIDS who acquire new sexually transmitted diseases (STDs) pose a risk for enhanced transmission of both HIV and STDs. To describe the frequency of HIV coinfection among gonorrhea cases (GC), HIV and GC surveillance databases (2000-2008) were cross-matched in New York City (NYC), Washington, DC (DC), Miami/Dade County (MDC), and Arizona (AZ). During 2000-2008, 4.6% (9471/205,689) of reported GCs occurred among persons with previously diagnosed HIV: NYC (5.5%), DC (7.3%), MDC (4%), and AZ (2%). The overall HIV-GC coinfection rates increased over the study period in all 4 sites. Real-time data integration could allow for enhanced prevention among persons with HIV infection and acute STDs. |
Hepatitis E virus infection in a liver transplant recipient: delayed diagnosis due to variable performance of serologic assays
Yoo N , Bernstein J , Caldwell C , Dong C , Drobeniuc J , Kamili S , Landry ML . Transpl Infect Dis 2013 15 (4) E166-8 Hepatitis E virus (HEV) infection within the United States has traditionally been associated with travel to hyperendemic regions. Recent reports have shown that autochthonous HEV occurs in developed countries and is caused by HEV genotype 3, which commonly infects swine 1. In Europe, clusters of HEV genotype 3 infections have been reported in immunocompromised hosts, especially solid organ transplant recipients in whom risk factors include eating game meat, pork products, and mussels 1, 2. Chronic HEV infection is common in transplant patients and early ribavirin treatment may be lifesaving 3, 4. Unfortunately, serologic assays for diagnostic testing for HEV infection have variable performance characteristics 5, 6, which can delay accurate diagnosis and thus affect the decision to initiate therapy as illustrated in the case presented below. | Five years after liver transplantation, a 58-year-old man presented with 1 week of dark urine and fatigue, with elevated total and direct bilirubin (3.16 mg/dL, 1.26 mg/dL), elevated transaminase levels (aspartate aminotransferase 260 U/L, alanine aminotransferase [ALT] 532 U/L), and a normal alkaline phosphatase (114 U/L). Liver biopsy was read as moderate acute cellular rejection (ACR). The patient was given intravenous methylprednisolone, his tacrolimus dose was doubled, and he was started on mycophenolate mofetil. Three weeks later, repeat testing revealed ALT of 668 U/L, and a second liver biopsy suggested mild ACR. He was given increased immunosuppression and his transaminase levels slowly decreased, but never returned to normal. |
High impact prevention and management strategies for improving outcomes in an HIV/AIDS population
Branson BM . J Manag Care Med 2013 16 (2) 63-65 The health care community continues to battle the HIV epidemic. The keys to preventing the spread of this infection are to screen those at risk and get them into treatment. All patients infected with HIV should receive antiretroviral therapy (AR T) to achieve viral suppression. Getting patients to adhere with therapy and stay in care should be major goals for managed care plans. |
Household environmental conditions are associated with enteropathy and impaired growth in rural Bangladesh
Lin A , Arnold BF , Afreen S , Goto R , Huda TM , Haque R , Raqib R , Unicomb L , Ahmed T , Colford JM Jr , Luby SP . Am J Trop Med Hyg 2013 89 (1) 130-137 Abstract. We assessed the relationship of fecal environmental contamination and environmental enteropathy. We compared markers of environmental enteropathy, parasite burden, and growth in 119 Bangladeshi children (≤ 48 months of age) across rural Bangladesh living in different levels of household environmental cleanliness defined by objective indicators of water quality and sanitary and hand-washing infrastructure. Adjusted for potential confounding characteristics, children from clean households had 0.54 SDs (95% confidence interval [CI] = 0.06, 1.01) higher height-for-age z scores (HAZs), 0.32 SDs (95% CI = -0.72, 0.08) lower lactulose:mannitol (L:M) ratios in urine, and 0.24 SDs (95% CI = -0.63, 0.16) lower immunoglobulin G endotoxin core antibody (IgG EndoCAb) titers than children from contaminated households. After adjusting for age and sex, a 1-unit increase in the ln L:M was associated with a 0.33 SDs decrease in HAZ (95% CI = -0.62, -0.05). These results are consistent with the hypothesis that environmental contamination causes growth faltering mediated through environmental enteropathy. |
Influenza-associated excess mortality in southern Brazil, 1980-2008
Freitas FTM , Souza LRO , Azziz-Baumgartner E , Cheng PY , Zhou H , Widdowson MA , Shay DK , Oliveira WK , Araujo WN . Epidemiol Infect 2013 141 (8) 1731-1740 In order to estimate influenza-associated excess mortality in southern Brazil, we applied Serfling regression models to monthly mortality data from 1980 to 2008 for pneumonia/influenza- and respiratory/circulatory-coded deaths for all ages and for those aged >=60 years. According to viral data, 735% of influenza viruses were detected between April and August in southern Brazil. There was no clear influenza season for northern Brazil. In southern Brazil, influenza-associated excess mortality was 14/100 000 for all ages and 92/100 000 person-years for persons aged >=60 years using underlying pneumonia/influenza-coded deaths and 100/100 000 for all ages and 866/100 000 person-years for persons aged >=60 years using underlying respiratory/circulatory-coded deaths. Influenza-associated excess mortality rates for southern Brazil are similar to those published for other countries. Our data support the need for continued influenza surveillance to guide vaccination campaigns to age groups most affected by this virus in Brazil. Cambridge University Press 2012. |
Interleukin-21 is a critical cytokine for the generation of virus-specific long-lived plasma cells
Rasheed MA , Latner DR , Aubert RD , Gourley T , Spolski R , Davis CW , Langley WA , Ha SJ , Ye L , Sarkar S , Kalia V , Konieczny BT , Leonard WJ , Ahmed R . J Virol 2013 87 (13) 7737-46 Long-lived plasma cells that reside in the bone marrow constitutively produce antibody in the absence of antigen and are the cellular basis of durable humoral immunity. The generation of these long-lived plasma cells depends upon a series of highly orchestrated interactions between antigen-specific CD4 T cells and B cells and the formation of germinal centers (GCs). In this study, we have examined the role of the cytokine interleukin-21 (IL-21) in regulating humoral immunity during acute viral infections. Using IL-21 receptor-deficient (IL-21R(-/-)) mice, we found that virus-specific CD4 T cells were generated after infection with lymphocytic choriomeningitis virus (LCMV) and that these CD4 T cells differentiated into T follicular helper (TFH)-like cells in the absence of IL-21 signaling. There was also no defect in the formation of GCs, although after day 15 these GCs disappeared faster in IL-21R(-/-) mice than in wild-type mice. Isotype switching and the initial LCMV-specific IgG response were normal in IL-21R(-/-) mice. However, these mice exhibited a profound defect in generating long-lived plasma cells and in sustaining antibody levels over time. Similar results were seen after infection of IL-21R(-/-) mice with vesicular stomatitis virus and influenza virus. Using chimeric mice containing wild-type or IL-21R(-/-) CD4 T cells and B cells, we showed that both B and CD4 T cells need IL-21 signaling for generating long-term humoral immunity. Taken together, our results highlight the importance of IL-21 in humoral immunity to viruses. |
Afriflu2-Second international workshop on influenza vaccination in the African continent-8 November 2012, Cape Town (South Africa)
Schoub BD , Gessner BD , Ampofo W , Cohen AL , Steffen CA . Vaccine 2013 31 (35) 3461-6 The second meeting of the Afriflu conferences took place in Cape Town, South Africa, with over 60 participants from 15 countries in Africa and also outside the continent. Significant progress in surveillance has been made in better understanding the illness burden of influenza on the continent, which limited evidence suggests is greater than that in the developed world. In southern Africa HIV and TB coinfections play a major role in increasing hospitalisation and mortality, while elsewhere in Africa other cofactors still need to be determined. There is currently no indigenous vaccine production in sub-Saharan Africa and only one facility, based in South Africa, capable of filling imported bulk. Innovative vaccine strategies will need to be explored, such as maternal immunisation, and also the possibility of other influenza vaccine options, such as live attenuated influenza vaccine for young children. Sustained indigenous vaccine production is essential for the continent to have vaccine security in the event of a pandemic even though establishing local production faces considerable challenges especially ensuring adequate markets on the continent. There is an urgent need to develop effective communication messages for decision makers as well as healthcare workers addressing the importance of influenza even in the face of the major competing health burdens of the continent. |
Association between CD4+ T-lymphocyte counts and fecal excretion of schistosoma mansoni eggs in patients coinfected with S. mansoni and human immunodeficiency virus before and after initiation of antiretroviral therapy
Muok EM , Simiyu EW , Ochola EA , Ng'ang'a ZW , Secor WE , Karanja DM , Mwinzi PN . Am J Trop Med Hyg 2013 89 (1) 42-5 Previously, we have shown that persons with human immunodeficiency virus 1 (HIV-1) infection and reduced CD4(+) T-lymphocyte counts excrete significantly fewer Schistosoma mansoni eggs than HIV-1-negative persons with similar intensities of schistosome infections. To determine how antiretroviral therapy (ART) might affect egg excretion, we conducted a study of HIV+ adults living in an area highly endemic for S. mansoni as they began an ART program. Fecal egg excretion and CD4(+) T-lymphocyte counts were evaluated at enrollment as well as 2 and 4 weeks after initiation of ART. Fourteen individuals who were Kato-Katz-negative at enrollment subsequently started excreting S. mansoni eggs accompanied by a significant increase in CD4(+) T lymphocytes (P = 0.004). Study participants who were S. mansoni egg-positive at enrollment and received both praziquantel and ART also showed significantly increased CD4(+) T-lymphocyte counts compared with baseline (P < 0.0001). Our data support a role for CD4(+) T lymphocytes in S. mansoni egg excretion. |
Differences in human immunodeficiency virus care and treatment among subpopulations in the United States
Hall HI , Frazier EL , Rhodes P , Holtgrave DR , Furlow-Parmley C , Tang T , Gray KM , Cohen SM , Mermin J , Skarbinski J . JAMA Intern Med 2013 173 (14) 1337-44 IMPORTANCE Early diagnosis of human immunodeficiency virus (HIV) infection, prompt linkage to and sustained care, and antiretroviral therapy are associated with reduced individual morbidity, mortality, and transmission of the virus. However, levels of these indicators may differ among population groups with HIV. Disparities in care and treatment may contribute to the higher incidence rates among groups with higher prevalence of HIV. OBJECTIVE To examine differences between groups of persons living with HIV by sex, age, race/ethnicity, and transmission category at essential steps in the continuum of care. DESIGN AND SETTING We obtained data from the National HIV Surveillance System of the Centers for Disease Control and Prevention to determine the number of persons living with HIV who are aware and unaware of their infection using back-calculation models. We calculated the percentage of persons linked to care within 3 months of diagnosis on the basis of CD4 level and viral load test results. We estimated the percentages of persons retained in care, prescribed antiretroviral therapy, and with viral suppression using data from the Medical Monitoring Project, a surveillance system of persons receiving HIV care in select areas representative of all such persons in the United States. PARTICIPANTS All HIV-infected persons in the United States. MAIN OUTCOMES AND MEASURES Percentage of persons living with HIV who are aware of their infection, linked to care, retained in care, receiving antiretroviral therapy, and achieving viral suppression. RESULTS Of the estimated 1 148 200 persons living with HIV in 2009 in the United States, 81.9% had been diagnosed, 65.8% were linked to care, 36.7% were retained in care, 32.7% were prescribed antiretroviral therapy, and 25.3% had a suppressed viral load (≤200 copies/mL). Overall, 857 276 persons with HIV had not achieved viral suppression, including 74.8% of male, 79.0% of black, 73.9% of Hispanic/Latino, and 70.3% of white persons. The percentage of blacks in each step of the continuum was lower than that for whites, but these differences were not statistically significant. Among persons with HIV who were 13 to 24 years of age, only 40.5% had received a diagnosis and 30.6% were linked to care. Persons aged 25 to 34, 35 to 44, and 45 to 54 years were all significantly less likely to achieve viral suppression than were persons aged 55 to 64 years. CONCLUSIONS AND RELEVANCE Significant age disparities exist at each step of the continuum of care. Additional efforts are needed to ensure that all persons with HIV receive a diagnosis and optimal care to reduce morbidity, mortality, disparities in care and treatment, and ultimately HIV transmission. Ensuring that people stay in care and receive treatment will increase the proportion of HIV-infected individuals who achieve and maintain a suppressed viral load. |
Disparities in HIV transmission risk among HIV-infected black and white MSM, Medical Monitoring Project, 2009
Beer L , Oster AM , Mattson CL , Skarbinski J . AIDS 2013 28 (1) 105-14 OBJECTIVE: To better understand why HIV incidence is substantially higher among black than white MSM, we present the first nationally representative estimates of factors that contribute to transmission - sexual behavior, antiretroviral therapy (ART) use, and viral suppression - among HIV-infected black and white MSM in the United States. DESIGN: The Medical Monitoring Project (MMP) is a complex sample survey of HIV-infected adults receiving medical care in the United States. METHODS: We used weighted interview and medical record data collected during June 2009 to May 2010 to estimate the prevalence of sexual behaviors, ART use, and viral suppression among sexually active HIV-infected black and white MSM. We used chi tests to assess significant differences between races and logistic regression models to identify factors that mediated the racial differences. RESULTS: Sexual risk behaviors among black and white MSM were similar. Black MSM were significantly less likely than white MSM to take ART (80 vs. 91%) and be durably virally suppressed (48 vs. 69%). Accounting for mediators (e.g., age, insurance, poverty, education, time since diagnosis, and disease stage) reduced, but did not eliminate, disparities in ART use and rendered differences in viral suppression among those on ART insignificant. CONCLUSION: Lower levels of ART use and viral suppression among HIV-infected black MSM may increase the likelihood of HIV transmission. Addressing the patient-level factors and structural inequalities that contribute to lower levels of ART use and viral suppression among this group will improve clinical outcomes and might reduce racial disparities in HIV incidence. |
Dracunculiasis eradication: and now, South Sudan
Hopkins DR , Ruiz-Tiben E , Weiss A , Withers PC Jr , Eberhard ML , Roy SL . Am J Trop Med Hyg 2013 89 (1) 5-10 Abstract. This report summarizes the status of the global Dracunculiasis Eradication Program as of the end of 2012. Dracunculiasis (Guinea worm disease) has been eliminated from 17 of 21 countries where it was endemic in 1986, when an estimated 3.5 million cases occurred worldwide. Only 542 cases were reported from four countries in 2012, and 103 villages still had indigenous transmission. Most remaining cases were reported from the new Republic of South Sudan, whereas Chad, Ethiopia, and Mali each reported 10 cases or less. Political instability and insecurity in Mali may become the main obstacles to interrupting dracunculiasis transmission forever. |
The impact of succimer chelation on blood cadmium in children with background exposures: a randomized trial
Cao Y , Chen A , Bottai M , Caldwell KL , Rogan WJ . J Pediatr 2013 163 (2) 598-600 Succimer lowers blood lead concentrations in children, and the structure of succimer chelates of lead and cadmium are similar. Using blood samples from a randomized trial of succimer for lead poisoning, however, we found that succimer did not lower blood cadmium in children with background exposure. |
Epidemiology of community-associated clostridium difficile infection, 2009 Through 2011
Chitnis AS , Holzbauer SM , Belflower RM , Winston LG , Bamberg WM , Lyons C , Farley MM , Dumyati GK , Wilson LE , Beldavs ZG , Dunn JR , Gould LH , Maccannell DR , Gerding DN , McDonald LC , Lessa FC . JAMA Intern Med 2013 173 (14) 1359-67 IMPORTANCE Clostridium difficile infection (CDI) has been increasingly reported among healthy individuals in the community. Recent data suggest that community-associated CDI represents one-third of all C difficile cases. The epidemiology and potential sources of C difficile in the community are not fully understood. OBJECTIVES To determine epidemiological and clinical characteristics of community-associated CDI and to explore potential sources of C difficile acquisition in the community. DESIGN AND SETTING Active population-based and laboratory-based CDI surveillance in 8 US states. PARTICIPANTS Medical records were reviewed and interviews performed to assess outpatient, household, and food exposures among patients with community-associated CDI (ie, toxin or molecular assay positive for C difficile and no overnight stay in a health care facility within 12 weeks). Molecular characterization of C difficile isolates was performed. Outpatient health care exposure in the prior 12 weeks among patients with community-associated CDI was a priori categorized into the following 3 levels: no exposure, low-level exposure (ie, outpatient visit with physician or dentist), or high-level exposure (ie, surgery, dialysis, emergency or urgent care visit, inpatient care with no overnight stay, or health care personnel with direct patient care). MAIN OUTCOMES AND MEASURES Prevalence of outpatient health care exposure among patients with community-associated CDI and identification of potential sources of C difficile by level of outpatient health care exposure. RESULTS Of 984 patients with community-associated CDI, 353 (35.9%) did not receive antibiotics, 177 (18.0%) had no outpatient health care exposure, and 400 (40.7%) had low-level outpatient health care exposure. Thirty-one percent of patients without antibiotic exposure received proton pump inhibitors. Patients having CDI with no or low-level outpatient health care exposure were more likely to be exposed to infants younger than 1 year (P = .04) and to household members with active CDI (P = .05) compared with those having high-level outpatient health care exposure. No association between food exposure or animal exposure and level of outpatient health care exposure was observed. North American pulsed-field gel electrophoresis (NAP) 1 was the most common (21.7%) strain isolated; NAP7 and NAP8 were uncommon (6.7%). CONCLUSIONS AND RELEVANCE Most patients with community-associated CDI had recent outpatient health care exposure, and up to 36% would not be prevented by reduction of antibiotic use only. Our data support evaluation of additional strategies, including further examination of C difficile transmission in outpatient and household settings and reduction of proton pump inhibitor use. |
Clinical, epidemiologic, and laboratory features of an outbreak of campylobacter-associated guillain-barre syndrome along the United States/Mexico Border
Sejvar JJ , Zegarra JA , Jackson BR , Lopez-Gatell H , Philen R , Fonseco-Ford M , Mahon B , Arzate F , Lopez B , Weiss J , Kamatsu K , Muley S , Lahda S , Talkington D , Waterman S . J Peripher Nerv Syst 2013 18 S104 Outbreaks of Guillain-Barre syndrome (GBS) are rare. In June 2011, a cluster of cases of acute flaccid paralysis with features consistent with GBS was identified along the international border in the town of San Luis Rio Colorado (SLRC) in Sonora, Mexico, and in Yuma County, Arizona. A binational investigation involving United States and Mexican state and federal officials identified additional cases, and epidemiologic information suggested an association of GBS cases with a concomitant outbreak of Campylobacter jejuni .We describe the clinical, laboratory, and epidemiologic features of this outbreak. We identified cases of AFP in Mexico from national reporting data, and suspected GBS cases in Arizona through active casefinding and physician outreach at local hospitals. We categorized cases using standardized diagnostic criteria (Brighton International Criteria) for GBS through physical and neurological examination, medical record review, laboratory testing, and electrodiagnostic studies. Of 31 identified AFP cases, we classified 26 (18 from Sonora, 8 from Arizona) as GBS. All cases had weakness onset between May 4-July 21, 2011; 21 (81%) cases were male. One GBS case (4%) reached Brighton Level 1 (most diagnostically certain), 14 (54%) Level 2, and 11 (42%) Level 3. Estimated incidence was 26/100,000 persons/year, over 26 times the typical expected rate in this area. Clinical phenotype suggested acute motor axonal neuropathy (AMAN) or Fisher syndrome in all; electrodiagnostic studies in 14 of 16 cases tested also suggested AMAN. Twenty-one cases (81%) reported antecedent diarrhea a median of 11 days before weakness 11/18 cases tested (61%) had C. jejuni -specific serum IgM antibodies and 16/18 (89%) were seropositive for one or more antiganglioside antibodies. Although the exact source of exposure to C. jejuni in the cluster could not be determined with certainty, epidemiologic evidence suggested contaminated ground water in SLRC. In conclusion, in addition to epidemiologic evidence, the clinical and laboratory features of this unprecedented outbreak of GBS clustered in geographical location and time suggested C. jejuni infection as the precipitant. The reason for this outbreak is unknown, but may be related to specific host, pathogen, or environmental factors. |
Phenotypic, genomic, and transcriptional characterization of Streptococcus pneumoniae interacting with human pharyngeal cells.
Kimaro Mlacha SZ , Romero-Steiner S , Hotopp JC , Kumar N , Ishmael N , Riley DR , Farooq U , Creasy TH , Tallon LJ , Liu X , Goldsmith CS , Sampson J , Carlone GM , Hollingshead SK , Scott JA , Tettelin H . BMC Genomics 2013 14 383 BACKGROUND: Streptococcus pneumoniae is a leading cause of childhood morbidity and mortality worldwide, despite the availability of effective pneumococcal vaccines. Understanding the molecular interactions between the bacterium and the host will contribute to the control and prevention of pneumococcal disease. RESULTS: We used a combination of adherence assays, mutagenesis and functional genomics to identify novel factors involved in adherence. By contrasting these processes in two pneumococcal strains, TIGR4 and G54, we showed that adherence and invasion capacities vary markedly by strain. Electron microscopy showed more adherent bacteria in association with membranous pseudopodia in the TIGR4 strain. Operons for cell wall phosphorylcholine incorporation (lic), manganese transport (psa) and phosphate utilization (phn) were up-regulated in both strains on exposure to epithelial cells. Pneumolysin, pili, stress protection genes (adhC-czcD) and genes of the type II fatty acid synthesis pathway were highly expressed in the naturally more invasive strain, TIGR4. Deletion mutagenesis of five gene regions identified as regulated in this study revealed attenuation in adherence. Most strikingly, SP_1922 which was predicted to contain a B-cell epitope and revealed significant attenuation in adherence, appeared to be expressed as a part of an operon that includes the gene encoding the cytoplasmic pore-forming toxin and vaccine candidate, pneumolysin. CONCLUSION: This work identifies a list of novel potential pneumococcal adherence determinants. |
Roadmap for the international collaborative epidemiologic monitoring of safety and effectiveness of new high priority vaccines
Izurieta HS , Zuber P , Bonhoeffer J , Chen RT , Sankohg O , Laserson KF , Sturkenboom M , Loucq C , Weibel D , Dodd C , Black S . Vaccine 2013 31 (35) 3623-7 With the advent of new vaccines targeted to highly endemic diseases in low- and middle-income countries (LMIC) and with the expansion of vaccine manufacturing globally, there is an urgent need to establish an infrastructure to evaluate the benefit-risk profiles of vaccines in LMIC. Fortunately the usual decade(s)-long time gap between introduction of new vaccines in high and low income countries is being significantly reduced or eliminated due to initiatives such as the Global Alliance for Vaccines and Immunizations (GAVI) and the Decade of Vaccines for the implementation of the Global Vaccine Action Plan. While hoping for more rapid disease control, this time shift may potentially add risk, unless appropriate capacity for reliable and timely evaluation of vaccine benefit-risk profiles in some LMIC's are developed with external assistance from regional or global level. An ideal vaccine safety and effectiveness monitoring system should be flexible and sustainable, able to quickly detect possible vaccine-associated events, distinguish them from programmatic errors, reliably and quickly evaluate the suspected event and its association with vaccination and, if associated, determine the benefit-risk of vaccines to inform appropriate action. Based upon the demonstrated feasibility of active surveillance in LMIC as shown by the Burkina Faso assessment of meningococcal A conjugate vaccine or that of rotavirus vaccine in Mexico and Brazil, and upon the proof of concept international GBS study, we suggest a sustainable, flexible, affordable and timely international collaborative vaccine safety monitoring approach for vaccines being newly introduced. While this paper discusses only the vaccine component, the same system could also be eventually used for monitoring drug effectiveness (including the use of substandard drugs) and drug safety. |
Measles vaccination using a microneedle patch
Edens C , Collins ML , Ayers J , Rota PA , Prausnitz MR . Vaccine 2013 31 (34) 3403-9 Measles vaccination programs would benefit from delivery methods that decrease cost, simplify logistics, and increase safety. Conventional subcutaneous injection is limited by the need for skilled healthcare professionals to reconstitute and administer injections, and by the need for safe needle handling and disposal to reduce the risk of disease transmission through needle re-use and needlestick injury. Microneedles are micron-scale, solid needles coated with a dry formulation of vaccine that dissolves in the skin within minutes after patch application. By avoiding the use of hypodermic needles, vaccination using a microneedle patch could be carried out by minimally trained personnel with reduced risk of blood-borne disease transmission. The goal of this study was to evaluate measles vaccination using a microneedle patch to address some of the limitations of subcutaneous injection. Viability of vaccine virus dried onto a microneedle patch was stabilized by incorporation of the sugar, trehalose, and loss of viral titer was less than 1log10(TCID50) after storage for at least 30 days at room temperature. Microneedle patches were then used to immunize cotton rats with the Edmonston-Zagreb measles vaccine strain. Vaccination using microneedles at doses equaling the standard human dose or one-fifth the human dose generated neutralizing antibody levels equivalent to those of a subcutaneous immunization at the same dose. These results show that measles vaccine can be stabilized on microneedles and that vaccine efficiently reconstitutes in vivo to generate a neutralizing antibody response equivalent to that generated by subcutaneous injection. |
Exposure to carbon nanotubes leads to changes in the cellular biomechanics
Dong C , Kashon ML , Lowry D , Dordick JS , Reynolds SH , Rojanasakul Y , Sargent LM , Dinu CZ . Adv Healthc Mater 2013 2 (7) 945-51 Exposure to carbon nanotubes induces significant changes in cellular biomechanics. Using nanoindentation, it is observed that the exposed cells have significantly higher stiffness when compared to controls, especially at the nuclear region, and significant increases in surface area. |
HPLC-ESI-MS/MS analysis of hemoglobin peptides in tryptic digests of dried-blood spot extracts detects HbS, HbC, HbD, HbE, HbO-Arab, and HbG-Philadelphia mutations
Haynes CA , Guerra SL , Fontana JC , Dejesus VR . Clin Chim Acta 2013 424C 191-200 BACKGROUND: Hemoglobinopathies are mutations resulting in abnormal globin chain structure; some have clinically significant outcomes such as anemia or reduced lifespan. Five beta-globin mutations are (c.20A>T, p.E6V), (c.19G>A, p. E6K), (c.79G>A, p.E26K), (c.364G>C, p.E121Q), and (c.364G>A, p.E121K), resulting in HbS (sickle-cell hemoglobin), HbC, HbE, HbD-Los Angeles, and HbO-Arab, respectively. One alpha-globin mutation is (c.[207C>G or 207C>A], p.N68K), resulting in HbG-Philadelphia. METHODS: HPLC-ESI-MS/MS analysis of dried-blood spot (DBS) punches from newborns extracted with a trypsin-containing solution provides greater than 90% coverage of alpha-, beta-, and gamma-globin amino acid sequences. Because the (c.20A>T, p.E6V), (c.19G>A, p. E6K), (c.79G>A, p.E26K), (c.364G>C, p.E121Q), (c.364G>A, p.E121K), and (c.[207C>G or 207C>A], p.N68K) mutations generate globin peptides with novel amino acid sequences, detecting one of these peptides in DBS extracts is indicative of the presence of a hemoglobinopathy in the newborn. RESULTS: The method described here can distinguish normal beta-globin peptides from the mutant HbS, HbC, HbE, HbD-Los Angeles and HbO-Arab peptides, as well as normal alpha-globin peptide from the mutant HbG-Philadelphia peptide, allowing the identification of unaffected heterozygotes such as HbAS, and of compound heterozygotes such as HbASG-Philadelphia. CONCLUSIONS: This HPLC-ESI-MS/MS analytical approach provides information that is not available from traditional hemoglobin analyses such as isoelectric focusing and HPLC-UV. It is also capable of determining the amino acid sequence of hemoglobin peptides, potentially allowing the detection of numerous hemoglobinopathies resulting from point mutations. |
Distribution and fibrotic response following inhalation exposure to multi-walled carbon nanotubes
Mercer RR , Scabilloni JF , Hubbs AF , Battelli LA , McKinney W , Friend S , Wolfarth MG , Andrew M , Castranova V , Porter DW . Part Fibre Toxicol 2013 10 (1) 33 BACKGROUND: Prior studies have demonstrated a rapid an progressive acute phase response to bolus aspiration of multi-walled carbon nanotubes (MWCNTs). In this study we sought to test the hypothesis that inhalation exposure to MWCNT produces a fibrotic response and that the response is chronically persistent. To address the hypothesis that inhaled MWCNTs cause persistent morphologic changes, male C57BL/6 J mice were exposed in a whole-body inhalation system to a MWCNT aerosol and the fibrotic response in the alveolar region examined at up to 336 days after termination of exposure. METHODS: Inhalation exposure was to a 5 mcg/m3 MWCNT aerosol for 5 hours/day for 12 days (4 times/week for 3 weeks). At the end of inhalation exposures, lungs were either lavaged for analysis of bronchoalveolar lavage (BAL) or preserved by vascular perfusion of fixative while inflated with air at 1, 14, 84, 168 and 336 days post inhalation exposure. Separate, clean-air control groups were also studied. Light microscopy, enhanced darkfield microscopy and field emission electron microscopy (FESEM) of tissue sections were used to analyze the distribution of lung burden following inhalation exposure. Morphometric measurements of Sirius Red staining for fibrillar collagen were used to assess the connective tissue response. Serial section analysis of enhanced darkfield microscope images was used to examine the redistribution of MWCNT fibers within the lungs during the post-exposure period. RESULTS: At day 1 post-exposure 84 +/- 3 and 16 +/- 2 percent of the lung burden (Mean +/- S.E., N = 5) were in the alveolar and airway regions, respectively. Initial distribution within the alveolar region was 56 +/- 5, 7 +/- 4 and 20 +/- 3 percent of lung burden in alveolar macrophages, alveolar airspaces and alveolar tissue, respectively. Clearance reduced the alveolar macrophage burden of MWCNTs by 35 percent between 1 and 168 days post-exposure, while the content of MWCNTs in the alveolar tissue increased by 63 percent. Large MWCNT structures containing greater than 4 fibers were 53.6 percent of the initial lung burden and accounted for the majority of the decline with clearance, while lung burden of singlet MWCNT was essentially unchanged. The mean linear intercept of alveolar airspace, a measure of the expansion of the lungs, was not significantly different between groups. Pulmonary inflammation and damage, measured as the number of polymorphnuclear leukocytes (PMNs) or lactate dehydrogenase activity (LDH) and albumin in BAL, increased rapidly (1 day post) after inhalation of MWCNTs and declined slowly with time post-exposure. The fibrillar collagen in the alveolar region of MWCNT-exposed mice demonstrated a progressive increase in thickness over time (0.17 +/- 0.02, 0.22 +/-0.02, 0.26 +/- 0.03, 0.25 +/- 0.02 and 0.29 +/- 0.01 microns for 1, 14, 84, 168 and 336 days post-exposure) and was significantly different from clean-air controls (0.16 +/- 0.02) at 84 and (0.15 +/- 0.02) at 336 days post-exposure. CONCLUSIONS: Despite the relatively low fraction of the lung burden being delivered to the alveolar tissue, the average thickness of connective tissue in the alveolar region increased by 70% in the 336 days after inhalation exposure. These results demonstrate that inhaled MWCNTs deposit and are retained within the alveolar tissue where they produce a progressive and persistent fibrotic response up to 336 days post-exposure. |
Maternal periconceptional occupational exposure to pesticides and selected musculoskeletal birth defects
Kielb C , Lin S , Herdt-Losavio M , Bell E , Chapman B , Rocheleau CM , Lawson C , Waters M , Stewart P , Olney RS , Romitti PA , Cao Y , Druschel C . Int J Hyg Environ Health 2013 217 248-54 This population-based U.S. study investigated the association between major musculoskeletal malformations and periconceptional maternal occupational pesticide exposure for a wide range of occupations. We conducted a multi-site case-control analysis using data from the National Birth Defects Prevention Study among employed women with due dates from October 1, 1997 through December 31, 2002. Cases included 871 live-born, stillborn, or electively terminated fetuses with isolated craniosynostosis, gastroschisis, diaphragmatic hernia, or transverse limb deficiencies. Controls included 2857 live-born infants without major malformations. Using self-reported maternal occupational information, an industrial hygienist used a job-exposure matrix and expert opinion to evaluate the potential for exposure to insecticides, herbicides or fungicides for each job held during one month pre-conception through three months post-conception. Exposures analyzed included any exposure (yes/no) to pesticides, to insecticides only, to both insecticides and herbicides (I+H) and to insecticides, herbicides and fungicides (I+H+F). We used logistic regression to evaluate the association between exposures and defects, controlling for infant and maternal risk factors. Occupational exposure to I+H+F was associated with gastroschisis among infants of women aged 20 years or older (adjusted odds ratio [aOR]=1.88; 95% confidence interval [CI]: 1.16-3.05), but not for women under age 20 (aOR=0.48; 95% CI: 0.20-1.16). We found no significant associations for the other defects. Additional research is needed to validate these findings in a separate population. |
Pulmonary and cardiovascular responses of rats to inhalation of silver nanoparticles
Roberts JR , McKinney W , Kan H , Krajnak K , Frazer DG , Thomas TA , Waugh S , Kenyon A , Maccuspie RI , Hackley VA , Castranova V . J Toxicol Environ Health A 2013 76 (11) 651-68 Exposure to wet aerosols generated during use of spray products containing silver (Ag) has not been evaluated. The goal was to assess the potential for cardiopulmonary toxicity following an acute inhalation of wet silver colloid. Rats were exposed by inhalation to a low concentration (100 mug/m(3) ) using an undiluted commercial antimicrobial product (20 mg/L total silver; approximately 33 nm mean aerodynamic diameter [MAD]) or to a higher concentration (1000 mug/m(3)) using a suspension (200 mg/L total silver; approximately 39 nm MAD) synthesized to possess a similar size distribution of Ag nanoparticles for 5 h. Estimated lung burdens from deposition models were 0, 1.4, or 14 mug Ag/rat after exposure to control aerosol, low, and high doses, respectively. At 1 and 7 d postexposure, the following parameters were monitored: pulmonary inflammation, lung cell toxicity, alveolar air/blood barrier damage, alveolar macrophage activity, blood cell differentials, responsiveness of tail artery to vasoconstrictor or vasodilatory agents, and heart rate and blood pressure in response to isoproterenol or norepinephrine, respectively. Changes in pulmonary or cardiovascular parameters were absent or nonsignificant at 1 or 7 d postexposure with the exceptions of increased blood monocytes 1 d after high-dose Ag exposure and decreased dilation of tail artery after stimulation, as well as elevated heart rate in response to isoproterenol 1 d after low-dose Ag exposure, possibly due to bioavailable ionic Ag in the commercial product. In summary, short-term inhalation of nano-Ag did not produce apparent marked acute toxicity in this animal model. |
Communicating risks after exposure has ended: former workers' perspectives on PCBs
Fujishiro K , Mobley A , Lehman E . New Solut 2013 23 (2) 347-367 While the importance of worker notification has been widely recognized, little attention has been paid to social and psychological contexts in which worker notification occurs, especially after the exposure has ended. This study explores workers' perspectives on exposure to polychlorinated biphenyls (PCBs), a toxic material whose manufacture in the United States ended in 1977. Four focus groups were conducted with former workers ( n = 29) who were exposed to PCBs. Verbatim transcriptions were analyzed. Participants considered living in the PCB-contaminated community more dangerous than handling PCBs on the job. While they firmly believed that PCBs in the environment caused serious health problems, participants expressed doubts about the toxicity of PCBs in the workplace. Both beliefs undermined the value of worker notification about occupational exposure to PCBs. A long-term relationship between workers and researchers would provide opportunities to cultivate better understanding of the hazard and facilitate the process of worker notification. |
Diagnostic approach in cases with suspected work-related asthma
Aasen TB , Burge PS , Henneberger PK , Schlunssen V , Baur X . J Occup Med Toxicol 2013 8 (1) 17 BACKGROUND: Work-related asthma (WRA) is a major cause of respiratory disease in modern societies. The diagnosis and consequently an opportunity for prevention are often missed in practice. METHODS: Based on recent studies and systematic reviews of the literature methods for detection of WRA and identification of specific causes of allergic WRA are discussed. RESULTS AND CONCLUSIONS: All workers should be asked whether symptoms improve on days away from work or on holidays. Positive answers should lead to further investigation. Spirometry and non-specific bronchial responsiveness should be measured, but carefully performed and validly analysed serial peak expiratory flow or forced expiratory volume in one second (FEV1) measurements are more specific and confirm occupational asthma in about 82% of those still exposed to the causative agent. Skin prick testing or specific immunoglobulin E assays are useful to document allergy to high molecular weight allergens. Specific inhalational challenge tests come closest to a gold standard test, but lack standardisation, availability and sensitivity. Supervised workplace challenges can be used when specific challenges are unavailable or the results non-diagnostic, but methodology lacks standardisation. Finally, if the diagnosis remains unclear a follow-up with serial measurements of FEV1 and non-specific bronchial hyperresponsiveness should detect those likely to develop permanent impairment from their occupational exposures. |
A National action plan for promoting preconception health and health care in the United States (2012-2014)
Floyd RL , Johnson KA , Owens JR , Verbiest S , Moore CA , Boyle C . J Womens Health (Larchmt) 2013 22 (10) 797-802 Abstract Preconception health and health care (PCHHC) has gained increasing popularity as a key prevention strategy for improving outcomes for women and infants, both domestically and internationally. The Action Plan for the National Initiative on Preconception Health and Health Care: A Report of the PCHHC Steering Committee (2012-2014) provides a model that states, communities, public, and private organizations can use to help guide strategic planning for promoting preconception care projects. Since 2005, a national public-private PCHHC initiative has worked to create and implement recommendations on this topic. Leadership and funding from the Centers for Disease Control and Prevention combined with the commitment of maternal and child health leaders across the country brought together key partners from the public and private sector to provide expertise and technical assistance to develop an updated national action plan for the PCHHC Initiative. Key activities for this process included the identification of goals, objectives, strategies, actions, and anticipated timelines for the five workgroups that were established as part of the original PCHHC Initiative. These are further described in the action plan. To assist other groups doing similar work, this article discusses the approach members of the PCHHC Initiative took to convene local, state, and national leaders to enhance the implementation of preconception care nationally through accomplishments, lessons learned, and projections for future directions. |
Determinants of urinary bisphenol A concentrations in Mexican/Mexican-American pregnant women
Quiros-Alcala L , Eskenazi B , Bradman A , Ye X , Calafat AM , Harley K . Environ Int 2013 59C 152-160 Prenatal exposure to bisphenol A (BPA) may be associated with adverse health effects in the developing fetus; however, little is known about predictors of BPA exposure during pregnancy. We examined BPA exposure in 491 pregnant women from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort and explored the role of living in the United States on significant dietary predictors of BPA exposure. Women provided urine samples up to two times during pregnancy (n=866 total samples). We computed the intraclass correlation coefficient (ICC) to evaluate variability in concentrations between collections and used generalized estimating equation (GEE) models to assess predictors of exposure. Geometric mean (GSD) BPA concentrations were 0.9 (2.8)mug/L and 1.0 (2.6)mug/L at the first and second prenatal visits, respectively. We observed greater within- than between-woman variability in urinary BPA concentrations (ICC=0.22). GEE models suggest that women who lived in the United States their entire life had 38% (CI: -0.1, 89.3) higher urinary BPA concentrations compared with other immigrant women. Additionally, women who consumed ≥3 sodas per day or hamburgers three times a week or more had 58% (CI: 18.0, 112.1) and 20% (CI: -0.2, 45.2) higher urinary BPA concentrations, respectively, compared with women who consumed no sodas or hamburgers. A higher percentage of women who lived their entire life in the United States reported increased consumption of sodas and hamburgers compared with other immigrant women. Independent of other factors, BPA urinary concentrations were slightly higher when the sample was collected later in the day. As in previous studies, high within-woman variability in urinary BPA concentrations confirms that several samples are needed to properly characterize exposure during pregnancy. Results also suggest that some factors could be modified to minimize exposures during pregnancy in our study participants (e.g., reducing soda and hamburger intake) and that factors associated with acculturation might increase BPA concentrations. |
The effect of ultrafast laser wavelength on ablation properties and implications on sample introduction in inductively coupled plasma mass spectrometry
LaHaye NL , Harilal SS , Diwakar PK , Hassanein A , Kulkarni P . J Appl Phys 2013 114 (2) 023103 (10 pp.) We investigated the role of femtosecond (fs) laser wavelength on laser ablation (LA) and its relation to laser generated aerosol counts and particle distribution, inductively coupled plasma-mass spectrometry (ICP-MS) signal intensity, detection limits, and elemental fractionation. Four different NIST standard reference materials (610, 613, 615, and 616) were ablated using 400 nm and 800 nm fs laser pulses to study the effect of wavelength on laser ablation rate, accuracy, precision, and fractionation. Our results show that the detection limits are lower for 400 nm laser excitation than 800 nm laser excitation at lower laser energies but approximately equal at higher energies. Ablation threshold was also found to be lower for 400 nm than 800 nm laser excitation. Particle size distributions are very similar for 400 nm and 800 nm wavelengths; however, they differ significantly in counts at similar laser fluence levels. This study concludes that 400 nm LA is more beneficial for sample introduction in ICP-MS, particularly when lower laser energies are to be used for ablation. |
Tobacco use in 3 billion individuals from 16 countries: an analysis of nationally representative cross-sectional household surveys
Giovino GA , Mirza SA , Samet JM , Gupta PC , Jarvis MJ , Bhala N , Peto R , Zatonski W , Hsia J , Morton J , Palipudi KM , Asma S . Lancet 2012 380 (9842) 668-79 BACKGROUND: Despite the high global burden of diseases caused by tobacco, valid and comparable prevalence data for patterns of adult tobacco use and factors influencing use are absent for many low-income and middle-income countries. We assess these patterns through analysis of data from the Global Adult Tobacco Survey (GATS). METHODS: Between Oct 1, 2008, and March 15, 2010, GATS used nationally representative household surveys with comparable methods to obtain relevant information from individuals aged 15 years or older in 14 low-income and middle-income countries (Bangladesh, Brazil, China, Egypt, India, Mexico, Philippines, Poland, Russia, Thailand, Turkey, Ukraine, Uruguay, and Vietnam). We compared weighted point estimates and 95% CIs of tobacco use between these 14 countries and with data from the 2008 UK General Lifestyle Survey and the 2006-07 US Tobacco Use Supplement to the Current Population Survey. All these surveys had cross-sectional study designs. FINDINGS: In countries participating in GATS, 48.6% (95% CI 47.6-49.6) of men and 11.3% (10.7-12.0) of women were tobacco users. 40.7% of men (ranging from 21.6% in Brazil to 60.2% in Russia) and 5.0% of women (0.5% in Egypt to 24.4% in Poland) in GATS countries smoked a tobacco product. Manufactured cigarettes were favoured by most smokers (82%) overall, but smokeless tobacco and bidis were commonly used in India and Bangladesh. For individuals who had ever smoked daily, women aged 55-64 years at the time of the survey began smoking at an older age than did equivalently aged men in most GATS countries. However, those individuals who had ever smoked daily and were aged 25-34-years when surveyed started to do so at much the same age in both sexes. Quit ratios were very low (<20% overall) in China, India, Russia, Egypt, and Bangladesh. INTERPRETATION: The first wave of GATS showed high rates of smoking in men, early initiation of smoking in women, and low quit ratios, reinforcing the view that efforts to prevent initiation and promote cessation of tobacco use are needed to reduce associated morbidity and mortality. FUNDING: Bloomberg Philanthropies' Initiative to Reduce Tobacco Use, Bill and Melinda Gates Foundation, Brazilian and Indian Governments. |
Content Index (Achived Edition)
About
CDC Science Clips is an online, continuously updated, searchable database of scientific literature published by CDC authors. Each article features an Altmetric Attention Score to track social and mainstream media mentions. If you are aware of a CDC-authored publication that does not appear in this database, please let us know.
- Page last reviewed:Feb 1, 2024
- Page last updated:Sep 03, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure