Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 32 Records) |
Query Trace: Gleason ME[original query] |
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Descriptive analysis of targeted carbapenemase genes and antibiotic susceptibility profiles among carbapenem-resistant Acinetobacter baumannii tested in the Antimicrobial Resistance Laboratory Network-United States, 2017-2020
Sabour S , Bantle K , Bhatnagar A , Huang JY , Biggs A , Bodnar J , Dale JL , Gleason R , Klein L , Lasure M , Lee R , Nazarian E , Schneider E , Smith L , Snippes Vagnone P , Therrien M , Tran M , Valley A , Wang C , Young EL , Lutgring JD , Brown AC . Microbiol Spectr 2024 e0282823 The Centers for Disease Control and Prevention has classified CRAB as an urgent public health threat. In this paper, we used a collection of >6,000 contemporary clinical isolates to evaluate the phenotypic and genotypic properties of CRAB detected in the United States. We describe the frequency of specific carbapenemase genes detected, antimicrobial susceptibility profiles, and the distribution of CRAB isolates categorized as multidrug resistant, extensively drug-resistant, or difficult to treat. We further discuss the proportion of isolates showing susceptibility to Food and Drug Administration-approved agents. Of note, 84% of CRAB tested harbored at least one class A, B, or D carbapenemase genes targeted for detection and 83% of these carbapenemase gene-positive CRAB were categorized as extensively drug resistant. Fifty-four percent of CRAB isolates without any of these carbapenemase genes detected were still extensively drug-resistant, indicating that infections caused by CRAB are highly resistant and pose a significant risk to patient safety regardless of the presence of one of these carbapenemase genes. |
Childcare and School Acute Gastroenteritis Outbreaks: 2009-2020.
Mattison CP , Calderwood LE , Marsh ZA , Wikswo ME , Balachandran N , Kambhampati AK , Gleason ME , Lawinger H , Mirza SA . Pediatrics 2022 150 (5) OBJECTIVES: Acute gastroenteritis (AGE) outbreaks commonly occur in congregate settings, including schools and childcare facilities. These outbreaks disrupt institutions, causing absences and temporary facility closures. This study analyzed the epidemiology of school and childcare AGE outbreaks in the United States. METHODS: We analyzed AGE outbreaks occurring in kindergarten to grade 12 schools and childcare facilities reported via the National Outbreak Reporting System in the United States from 2009 to 2019 and compared this information to 2020 data. Outbreak and case characteristics were compared using the Kruskal-Wallis rank sum test, 2 goodness-of-fit test, and Fisher exact test. RESULTS: From 2009 to 2019, there were 2623 school, 1972 childcare, and 38 school and childcare outbreaks. School outbreaks were larger (median, 29 cases) than childcare outbreaks (median, 10 cases). Childcare outbreaks were longer (median, 15 days) than school outbreaks (median, 9 days). Norovirus (2383 outbreaks; 110190 illnesses) and Shigella spp. (756 outbreaks; 9123 illnesses) were the most reported etiologies. Norovirus was the leading etiology in schools; norovirus and Shigella spp. were dominant etiologies in childcare centers. Most (85.7%) outbreaks were spread via person-to-person contact. In 2020, 123 outbreaks were reported, 85% in the first quarter. CONCLUSIONS: Schools and childcare centers are common AGE outbreak settings in the United States. Most outbreaks were caused by norovirus and Shigella spp. and spread via person-to-person transmission. Fewer outbreaks were reported in 2020 from the COVID-19 pandemic. Prevention and control efforts should focus on interrupting transmission, including environmental disinfection, proper handwashing, safe diapering, and exclusion of ill persons. |
Outbreaks of acute gastrointestinal illness associated with a splash pad in a Wildlife Park - Kansas, June 2021
Aluko SK , Ishrati SS , Walker DC , Mattioli MC , Kahler AM , Vanden Esschert KL , Hervey K , Rokisky JJr , Wikswo ME , Laco JP , Kurlekar S , Byrne A , Molinari NA , Gleason ME , Steward C , Hlavsa MC , Neises D . MMWR Morb Mortal Wkly Rep 2022 71 (31) 981-987 In June 2021, Kansas state and county public health officials identified and investigated three cases of shigellosis (a bacterial diarrheal illness caused by Shigella spp.) associated with visiting a wildlife park. The park has animal exhibits and a splash pad. Two affected persons visited animal exhibits, and all three entered the splash pad. Nonhuman primates are the only known animal reservoir of Shigella. The splash pad, which sprays water on users and is designed so that water does not collect in the user area, was closed on June 19. The state and county public health codes do not include regulations for splash pads. Thus, these venues are not typically inspected, and environmental health expertise is limited. A case-control study identified two distinct outbreaks associated with the park (a shigellosis outbreak involving 21 cases and a subsequent norovirus infection outbreak involving six cases). Shigella and norovirus can be transmitted by contaminated water; in both outbreaks, illness was associated with getting splash pad water in the mouth (multiply imputed adjusted odds ratio [aOR(MI)] = 6.4, p = 0.036; and 28.6, p = 0.006, respectively). Maintaining adequate water disinfection and environmental health expertise and targeting prevention efforts to caregivers of splash pad users help prevent splash pad-associated outbreaks. Outbreak incidence might be further reduced when U.S. jurisdicitons voluntarily adopt CDC's Model Aquatic Health Code (MAHC) recommendations and through the prevention messages: "Don't get in the water if sick with diarrhea," "Don't stand or sit above the jets," and "Don't swallow the water."(†). |
Pediatric HIV Case Identification Across 22 PEPFAR-Supported Countries During the COVID-19 Pandemic, October 2019-September 2020.
Traub AM , Medley A , Gross J , Sloan M , Amzel A , Gleason MM , Fernando NB , Wong V , Grillo MP , Wolf HT , Al-Samarrai T , Frawley A , Segwabe M , Motswere C , Baramperanye E , Nzima V , Mange Mayer M , Balachandra S , N'Siesi F X , Longuma HO , Nyembo P , Mazibuko S , Tilahun T , Teferi W , Desinor O , Reginald JL , Simiyu T , Nyabiage L , Mirembe J , Ts'oeu M , Zomba G , Nyangulu M , Wate A , Greenberg Cowan J , Mali D , Pietersen I , Ogundehin D , Onotu D , Ikpeazu A , Niyonsaba E , Bamwesigye J , Mabasa H , Kindra G , Bunga S , Rwegerera F , Machage E , King'ori G , Calnan J , Nazziwa E , Lingenda G , Musokotwane K , Bulaya-Tembo R , Maphosa T , Srivastava M . MMWR Morb Mortal Wkly Rep 2022 71 (28) 894-898 During 2020, an estimated 150,000 persons aged 0-14 years acquired HIV globally (1). Case identification is the first step to ensure children living with HIV are linked to life-saving treatment, achieve viral suppression, and live long, healthy lives. Successful interventions to optimize pediatric HIV testing during the COVID-19 pandemic are needed to sustain progress toward achieving Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets.* Changes in HIV testing and diagnoses among persons aged 1-14 years (children) were assessed in 22 U.S. President's Emergency Plan for AIDS Relief (PEPFAR)-supported countries during October 1, 2019-September 30, 2020. This period corresponds to the two fiscal quarters before the COVID-19 pandemic (i.e., Q1 and Q2) and the two quarters after the pandemic began (i.e., Q3 and Q4). Testing was disaggregated by age group, testing strategy, and fiscal year quarter. During October 2019-September 2020, PEPFAR supported 4,312,343 HIV tests and identified 74,658 children living with HIV (CLHIV). The number of HIV tests performed was similar during Q1 and Q2, decreased 40.1% from Q2 to Q3, and increased 19.7% from Q3 to Q4. The number of HIV cases identified among children aged 1-14 years (cases identified) increased 7.4% from Q1 to Q2, decreased 29.4% from Q2 to Q3, and increased 3.3% from Q3 to Q4. Although testing in outpatient departments decreased 21% from Q1 to Q4, testing from other strategies increased during the same period, including mobile testing by 38%, facility-based index testing (offering an HIV test to partners and biological children of persons living with HIV) by 8%, and testing children with signs or symptoms of malnutrition within health facilities by 7%. In addition, most tests (61.3%) and cases identified (60.9%) were among children aged 5-14 years (school-aged children), highlighting the need to continue offering HIV testing to older children. These findings provide important information on the most effective strategies for identifying CLHIV during the COVID-19 pandemic. HIV testing programs should continue to use programmatic, surveillance, and financial data at both national and subnational levels to determine the optimal mix of testing strategies to minimize disruptions in pediatric case identification during the COVID-19 pandemic. |
Foodborne outbreak rates associated with restaurant inspection grading and posting at the point of service: Evaluation using national foodborne outbreak surveillance data
Kim TN , Wildey L , Gleason B , Bleser J , Firestone MJ , Bare G , Bliss J , Dewey-Mattia D , Stueven H , Brown L , Dyjack D , Hedberg CW . J Food Prot 2022 85 (7) 1000-1007 A previously conducted national survey of restaurant inspection programs associated the practice of disclosing inspection results to consumers at the restaurant point-of-service (POS) with fewer foodborne outbreaks. We used data from the national Foodborne Disease Outbreak Surveillance System (FDOSS) to assess the reproducibility of the survey results. Programs that participated in the survey accounted for approximately 23% of the single state, foodborne illness outbreaks in restaurant settings reported to FDOSS during 2016 - 2018. Agencies that disclosed inspection results at the POS reported fewer outbreaks (mean = 0.29 outbreaks per 1,000 establishments) than those that disclosed results online (0.7) or not at all (1.0). Having any grading method for inspections was associated with fewer reported outbreaks than having no grading method. Agencies that used letter grades had the lowest numbers of outbreaks per 1,000 establishments. There was a positive association (correlation coefficient, r= 0.54) between the mean number of foodborne illness complaints per 1,000 establishments, per the survey, and the mean number of restaurant outbreaks reported to FDOSS (R2= 0.29). This association was stronger for bacterial toxin-mediated outbreaks (R2= 0.35) than for norovirus (R2= 0.10) or Salmonella (R2= 0.01) outbreaks. Our cross-sectional study findings are consistent with previous observations that linked the practice of posting graded inspection results at the POS with reduced occurrence of foodborne illnesses and outbreaks associated with restaurants. Support for foodborne illness surveillance programs and food regulatory activities at local health agencies is foundational for food safety systems coordinated at state and federal levels. |
Novel outbreak-associated food vehicles, United States
Whitham HK , Sundararaman P , Dewey-Mattia D , Manikonda K , Marshall KE , Griffin PM , Gleason BL , Subramhanya S , Crowe SJ . Emerg Infect Dis 2021 27 (10) 2554-2559 Novel outbreak-associated food vehicles (i.e., foods not implicated in past outbreaks) can emerge as a result of evolving pathogens and changing consumption trends. To identify these foods, we examined data from the Centers for Disease Control and Prevention Foodborne Disease Outbreak Surveillance System and found 14,216 reported outbreaks with information on implicated foods. We compared foods implicated in outbreaks during 2007-2016 with those implicated in outbreaks during 1973-2006. We identified 28 novel food vehicles, of which the most common types were fish, nuts, fruits, and vegetables; one third were imported. Compared with other outbreaks, those associated with novel food vehicles were more likely to involve illnesses in multiple states and food recalls and were larger in terms of cases, hospitalizations, and deaths. Two thirds of novel foods did not require cooking after purchase. Prevention efforts targeting novel foods cannot rely solely on consumer education but require industry preventive measures. |
Enteric illness outbreaks reported through the National Outbreak Reporting System, United States, 2009-19
Wikswo ME , Roberts V , Marsh Z , Manikonda K , Gleason B , Kambhampati A , Mattison C , Calderwood L , Balachandran N , Cardemil C , Hall AJ . Clin Infect Dis 2021 74 (11) 1906-1913 BACKGROUND: The National Outbreak Reporting System (NORS) captures data on foodborne, waterborne, and enteric illness outbreaks in the United States. The aim of this study is to describe enteric illness outbreaks reported during 11 years of surveillance. METHODS: We extracted finalized reports from NORS for outbreaks occurring during 2009-2019. Outbreaks were included if they were caused by an enteric etiology or if any patients reported diarrhea, vomiting, bloody stools, or unspecified acute gastroenteritis. RESULTS: A total of 38,395 outbreaks met inclusion criteria, increasing from 1,932 in 2009 to 3,889 in 2019. Outbreaks were most commonly transmitted through person-to-person contact (n=23,812, 62%) and contaminated food (n=9,234, 24%). Norovirus was the most commonly reported etiology, reported in 22,820 (59%) outbreaks, followed by Salmonella (n=2,449, 6%) and Shigella (n=1,171, 3%). Norovirus outbreaks were significantly larger, with a median of 22 illnesses per outbreak, than outbreaks caused by the other most common outbreak etiologies (p<0.0001, all comparisons). Hospitalization rates were higher in outbreaks caused by Salmonella and E. coli outbreaks (20.9% and 22.8%, respectively) than those caused by norovirus (2%). The case fatality rate was highest in E. coli outbreaks (0.5%) and lowest in Shigella and Campylobacter outbreaks (0.02%). CONCLUSIONS: Norovirus caused the most outbreaks and outbreak-associated illness, hospitalizations, and deaths. However, persons in E. coli and Salmonella outbreaks were more likely to be hospitalized or die. Outbreak surveillance through NORS provides the relative contributions of each mode of transmission and etiology for reported enteric illness outbreaks, which can guide targeted interventions. |
Shiga toxin-producing Escherichia coli outbreaks in the United States, 20102017
Tack DM , Kisselburgh HM , Richardson LC , Geissler A , Griffin PM , Payne DC , Gleason BL . Microorganisms 2021 9 (7) Shiga toxin-producing Escherichia coli (STEC) cause illnesses ranging from mild diarrhea to ischemic colitis and hemolytic uremic syndrome (HUS); serogroup O157 is the most common cause. We describe the epidemiology and transmission routes for U.S. STEC outbreaks during 2010– 2017. Health departments reported 466 STEC outbreaks affecting 4769 persons; 459 outbreaks had a serogroup identified (330 O157, 124 non-O157, 5 both). Among these, 361 (77%) had a known transmission route: 200 foodborne (44% of O157 outbreaks, 41% of non-O157 outbreaks), 87 person-toperson (16%, 24%), 49 animal contact (11%, 9%), 20 water (4%, 5%), and 5 environmental contamination (2%, 0%). The most common food category implicated was vegetable row crops. The distribution of O157 and non-O157 outbreaks varied by age, sex, and severity. A significantly higher percentage of STEC O157 than non-O157 outbreaks were transmitted by beef (p = 0.02). STEC O157 outbreaks also had significantly higher rates of hospitalization and HUS (p < 0.001). © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
Evaluation of health system readiness and coverage of intermittent preventive treatment of malaria in infants (IPTi) in Kambia district to inform national scale-up in Sierra Leone.
Lahuerta M , Sutton R , Mansaray A , Eleeza O , Gleason B , Akinjeji A , Jalloh MF , Toure M , Kassa G , Meshnick SR , Deutsch-Feldman M , Parmley L , Friedman M , Smith SJ , Rabkin M , Steinhardt L . Malar J 2021 20 (1) 74 BACKGROUND: Intermittent preventive treatment of malaria in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a proven strategy to protect infants against malaria. Sierra Leone is the first country to implement IPTi nationwide. IPTi implementation was evaluated in Kambia, one of two initial pilot districts, to assess quality and coverage of IPTi services. METHODS: This mixed-methods evaluation had two phases, conducted 3 (phase 1) and 15-17 months (phase 2) after IPTi implementation. Methods included: assessments of 18 health facilities (HF), including register data abstraction (phases 1 and 2); a knowledge, attitudes and practices survey with 20 health workers (HWs) in phase 1; second-generation sequencing of SP resistance markers (pre-IPTi and phase 2); and a cluster-sample household survey among caregivers of children aged 3-15 months (phase 2). IPTi and vaccination coverage from the household survey were calculated from child health cards and maternal recall and weighted for the complex sampling design. Interrupted time series analysis using a Poisson regression model was used to assess changes in malaria cases at HF before and after IPTi implementation. RESULTS: Most HWs (19/20) interviewed had been trained on IPTi; 16/19 reported feeling well prepared to administer it. Nearly all HFs (17/18 in phase 1; 18/18 in phase 2) had SP for IPTi in stock. The proportion of parasite alleles with dhps K540E mutations increased but remained below the 50% WHO-recommended threshold for IPTi (4.1% pre-IPTi [95%CI 2-7%]; 11% post-IPTi [95%CI 8-15%], p < 0.01). From the household survey, 299/459 (67.4%) children ≥ 10 weeks old received the first dose of IPTi (versus 80.4% for second pentavalent vaccine, given simultaneously); 274/444 (62.5%) children ≥ 14 weeks old received the second IPTi dose (versus 65.4% for third pentavalent vaccine); and 83/217 (36.4%) children ≥ 9 months old received the third IPTi dose (versus 52.2% for first measles vaccine dose). HF register data indicated no change in confirmed malaria cases among infants after IPTi implementation. CONCLUSIONS: Kambia district was able to scale up IPTi swiftly and provide necessary health systems support. The gaps between IPTi and childhood vaccine coverage need to be further investigated and addressed to optimize the success of the national IPTi programme. |
Integrated TB and HIV care for Mozambican children: temporal trends, site-level determinants of performance, and recommendations for improved TB preventive treatment
Buck WC , Nguyen H , Siapka M , Basu L , Greenberg Cowan J , De Deus MI , Gleason M , Ferreira F , Xavier C , Jose B , Muthemba C , Simione B , Kerndt P . AIDS Res Ther 2021 18 (1) 3 BACKGROUND: Pediatric tuberculosis (TB), human immunodeficiency virus (HIV), and TB-HIV co-infection are health problems with evidence-based diagnostic and treatment algorithms that can reduce morbidity and mortality. Implementation and operational barriers affect adherence to guidelines in many resource-constrained settings, negatively affecting patient outcomes. This study aimed to assess performance in the pediatric HIV and TB care cascades in Mozambique. METHODS: A retrospective analysis of routine PEPFAR site-level HIV and TB data from 2012 to 2016 was performed. Patients 0-14 years of age were included. Descriptive statistics were used to report trends in TB and HIV indicators. Linear regression was done to assess associations of site-level variables with performance in the pediatric TB and HIV care cascades using 2016 data. RESULTS: Routine HIV testing and cotrimoxazole initiation for co-infected children in the TB program were nearly optimal at 99% and 96% in 2016, respectively. Antiretroviral therapy (ART) initiation was lower at 87%, but steadily improved from 2012 to 2016. From the HIV program, TB screening at the last consultation rose steadily over the study period, reaching 82% in 2016. The percentage of newly enrolled children who received either TB treatment or isoniazid preventive treatment (IPT) also steadily improved in all provinces, but in 2016 was only at 42% nationally. Larger volume sites were significantly more likely to complete the pediatric HIV and TB care cascades in 2016 (p value range 0.05 to < 0.001). CONCLUSIONS: Mozambique has made significant strides in improving the pediatric care cascades for children with TB and HIV, but there were missed opportunities for TB diagnosis and prevention, with IPT utilization being particularly problematic. Strengthened TB/HIV programming that continues to focus on pediatric ART scale-up while improving delivery of TB preventive therapy, either with IPT or newer rifapentine-based regimens for age-eligible children, is needed. |
Geographic range of recreational water-associated primary amebic meningoencephalitis, United States, 1978-2018
Gharpure R , Gleason M , Salah Z , Blackstock AJ , Hess-Homeier D , Yoder JS , Ali IKM , Collier SA , Cope JR . Emerg Infect Dis 2021 27 (1) 271-274 Naegleria fowleri is a free-living ameba that causes primary amebic meningoencephalitis (PAM), a rare but usually fatal disease. We analyzed trends in recreational water exposures associated with PAM cases reported during 1978-2018 in the United States. Although PAM incidence remained stable, the geographic range of exposure locations expanded northward. |
Trends in the use of active surveillance and treatments in Medicare beneficiaries diagnosed with localized prostate cancer
Liu Y , Hall IJ , Filson C , Howard DH . Urol Oncol 2020 39 (7) 432 e1-432 e10 BACKGROUND: The treatment for men diagnosed with localized prostate cancer has changed over time given the increased attention to the harms associated with over-diagnosis and the development of protocols for active surveillance. METHODS: We examined trends in the treatment of men diagnosed with localized prostate cancer between 2004 and 2015, using the most recently available data from Surveillance, Epidemiology, and End Results Program (SEER)-Medicare. Patients were stratified by Gleason score, age, and race groups. RESULTS: The use of active surveillance increased from 22% in 2004-2005 to 50% in 2014-2015 for patients with a Gleason score of 6 or below and increased from 9% in 2004-2005 to 13% in 2014-2015 for patients with a Gleason score of 7 or above. Patients with a Gleason score of 7 or above had increased use of intensity-modulated radiation therapy and prostatectomy, especially among patients aged 75 years and older. Among patients with a Gleason score of 6 or below non-Hispanic black men were less likely to undergo active surveillance than non-Hispanic white men. CONCLUSIONS: There has been a large increase in the use of active surveillance among men with a Gleason score of 6 or below. However, non-Hispanic black men with a Gleason score of 6 or below are less likely to receive active surveillance. |
Adapting HIV services for pregnant and breastfeeding women, infants, children, adolescents and families in resource-constrained settings during the COVID-19 pandemic.
Vrazo AC , Golin R , Fernando NB , Killam WP , Sharifi S , Phelps BR , Gleason MM , Wolf HT , Siberry GK , Srivastava M . J Int AIDS Soc 2020 23 (9) e25622 INTRODUCTION: The COVID-19 pandemic has impacted global health service delivery, including provision of HIV services. Countries with high HIV burden are balancing the need to minimize interactions with health facilities to reduce the risk of COVID-19 transmission, while delivering uninterrupted essential HIV prevention, testing and treatment services. Many of these adaptations in resource-constrained settings have not adequately accounted for the needs of pregnant and breastfeeding women, infants, children and adolescents. We propose whole-family, tailored programme adaptations along the HIV clinical continuum to protect the programmatic gains made in services. DISCUSSION: Essential HIV case-finding services for pregnant and breastfeeding women and children should be maintained and include maternal testing, diagnostic testing for infants exposed to HIV, index testing for children whose biological parents or siblings are living with HIV, as well as for children/adolescents presenting with symptoms concerning for HIV and comorbidities. HIV self-testing for children two years of age and older should be supported with caregiver and provider education. Adaptations include bundling services in the same visit and providing testing outside of facilities to the extent possible to reduce exposure risk to COVID-19. Virtual platforms can be used to identify vulnerable children at risk of HIV infection, abuse, harm or violence, and link them to necessary clinical and psychosocial support services. HIV treatment service adaptations for families should focus on family based differentiated service delivery models, including community-based ART initiation and multi-month ART dispensing. Viral load monitoring should not be a barrier to transitioning children and adolescents experiencing treatment failure to more effective ART regimens, and viral load monitoring for pregnant and breastfeeding women and children should be prioritized and bundled with other essential services. CONCLUSIONS: Protecting pregnant and breastfeeding women, infants, children and adolescents from acquiring SARS-CoV-2 while sustaining essential HIV services is an immense global health challenge. Tailored, family friendly programme adaptations for case-finding, ART delivery and viral load monitoring for these populations have the potential to limit SARS-CoV-2 transmission while ensuring the continuity of life-saving HIV case identification and treatment efforts. |
Data on the implementation of VaxTrac electronic immunization registry in Sierra Leone
Namageyo-Funa A , Jalloh MF , Gleason B , Wallace AS , Friedman M , Sesay T , Ocansey D , Jalloh MS , Feldstein LR , Conklin L , Hersey S , Singh T , Kaiser R . Data Brief 2020 32 106167 Following the piloting of VaxTrac, an electronic immunization registry (EIR), we conducted a rapid assessment in November-December 2017 to evaluate the use of the EIR in 10 health facilities in Western Area Urban district in Sierra Leone [1]. In this data-in-brief report, we provide additional descriptive data from the assessment of the VaxTrac EIR in Sierra Leone. The assessment comprised aggregate data on vaccine doses administered that were abstracted from VaxTrac and three paper-based sources (daily tally sheets, register of children under the age of 2 years, and a summary form of doses administered). Data were abstracted for the following six vaccine doses in the immunization schedule in Sierra Leone: 1) Bacillus Calmette-Guérin vaccine, 2) first dose of pentavalent vaccine, 3) second dose of pentavalent vaccine, 4) third dose of pentavalent vaccine, 5) first dose of measles-containing vaccine, and 6) second dose of measles-containing vaccine. We descriptively analysed the abstracted data to examine the congruity between VaxTrac records and the three paper-based sources. Bar graphs were generated to visually depict the variations in number of administered vaccine doses by data source for each health facility. We provide the aggregated data for each vaccine dose abstracted by data source from each health facility as supplemental material (Excel file). The supplementary data reveal patterns in the congruity of vaccine doses captured that have implications for policy and programmatic decisions regarding the use of VaxTrac and other similar EIRs in low resource urban settings. |
Assessment of VaxTrac electronic immunization registry in an urban district in Sierra Leone: Implications for data quality, defaulter tracking, and policy
Jalloh MF , Namageyo-Funa A , Gleason B , Wallace AS , Friedman M , Sesay T , Ocansey D , Jalloh MS , Feldstein LR , Conklin L , Hersey S , Singh T , Kaiser R . Vaccine 2020 38 (39) 6103-6111 BACKGROUND: In 2016, the Sierra Leone Ministry of Health and Sanitation (MoHS) piloted VaxTrac, an electronic immunization registry (EIR), in an urban district to improve management of vaccination records and tracking of children who missed scheduled doses. We aimed to document lessons learned to inform decision-making on VaxTrac and similar EIRs' future use. METHODS: Ten out of 50 urban health facilities that implemented VaxTrac were purposively selected for inclusion in a rapid mixed-method assessment from November to December 2017. For a one-month period, records of six scheduled vaccine doses among children < 2 years old in VaxTrac were abstracted and compared to three paper-based records (register of under-two children, daily tally sheet, and monthly summary form). We used the under-two register as the reference gold standard for comparison purposes. We interviewed and observed 10 heath workers, one from each selected facility, who were using VaxTrac. RESULTS: Overall, VaxTrac captured < 65% of the vaccine doses reported in the paper-based sources, but in the largest health facility VaxTrac captured the highest number of doses. Two additional notable patterns emerged: 1) the aggregated data sources reported higher doses administered compared to the under-two register and VaxTrac; 2) data sources that need real-time data capture during the vaccination session reported fewer doses administered compared to the monthly HF2 summary form. Health workers expressed that the EIR helped them to shorten the time to manage, summarize, and report vaccination records. Workflows for data entry in VaxTrac were inconsistent among facilities and rarely integrated into existing processes. Data sharing restrictions contributed to duplicate records. CONCLUSION: Although VaxTrac helped to shorten the time to manage, summarize, and report vaccination records, data sharing restrictions coupled with inconsistent and inefficient workflows were major implementation challenges. Readiness-to-introduce and sustainability should be carefully considered before implementing an EIR. |
Improving inpatient provider-initiated HIV testing and counseling in Sierra Leone
Kassa G , Dougherty G , Madevu-Matson C , Egesimba G , Sartie K , Akinjeji A , Tamba F , Gleason B , Toure M , Rabkin M . PLoS One 2020 15 (7) e0236358 BACKGROUND/SETTING: Only 47% of HIV-positive Sierra Leoneans knew their status in 2017, making expanded HIV testing a priority. National guidelines endorse provider-initiated HIV testing and counselling (PITC) to increase testing coverage, but PITC is rarely provided in Sierra Leone. In response, a Quality Improvement Collaborative (QIC) was implemented to improve PITC coverage amongst adult inpatients. METHODS: Ten hospitals received the intervention between October 2017 and August 2018; there were no control facilites. Each hospital aimed to improve PITC coverage to ≥ 95% of eligible patients. Staff received training on PITC and QIC methods and a package of PITC best practices and tools. They then worked to identify additional contextually-appropriate interventions, conducted rapid tests of change, and tracked performance using shared indicators and time-series data. Supportive supervision bolstered QI skills, and quarterly meetings enabled diffusion of innovations while spurring friendly competition. RESULTS: Baseline PITC coverage was 4%. The hospital teams tested diverse interventions using QI methods, including staff training; data review meetings; enhanced workflow processes and supervision; and patient education and sensitization activities Nine hospitals reached and sustained the 95% target, and all saw rapid and durable improvement, which was sustained for a median of six months. Of the 5,238 patients tested for HIV, 311 (6%) were found to be HIV-positive and were referred for treatment. HIV rapid test kit stockouts occurred during the project period, limiting PITC services in some cases. CONCLUSIONS: The intervention led to swift and sustained improvement in inpatient PITC coverage and to the diagnosis of hundreds of people living with HIV. Sierra Leone's Ministry of Health and Sanitation plans to take the initiative to national scale, with close attention to the issue of test kit stockouts. |
An innovative quality improvement approach for rapid improvement of infection prevention and control at health facilities in Sierra Leone
Rondinelli I , Dougherty G , Madevu-Matson CA , Toure M , Akinjeji A , Ogongo I , Kolwaite A , Weiss J , Gleason B , Lyman MM , Benya H , Rabkin M . Int J Qual Health Care 2020 32 (2) 85-92 QUALITY CHALLENGE: The Sierra Leone (SL) Ministry of Health and Sanitation's National Infection Prevention and Control Unit (NIPCU) launched National Infection and Prevention Control (IPC) Policy and Guidelines in 2015, but a 2017 assessment found suboptimal compliance with standards on environmental cleanliness (EC), waste disposal (WD) and personal protective equipment (PPE) use. METHODS: ICAP at Columbia University (ICAP), NIPCU and the Centers for Disease Control and Prevention (CDC) designed and implemented a Rapid Improvement Model (RIM) quality improvement (QI) initiative with a compressed timeframe of 6 months to improve EC, WD and PPE at eight purposively selected health facilities (HFs). Targets were collaboratively developed, and a 37-item checklist was designed to monitor performance. HF teams received QI training and weekly coaching and convened monthly to review progress and exchange best practices. At the final learning session, a "harvest package" of the most effective ideas and tools was developed for use at additional HFs. RESULTS: The RIM resulted in marked improvement in WD and EC performance and modest improvement in PPE. Aggregate compliance for the 37 indicators increased from 67 to 96% over the course of 4 months, with all HFs showing improvement. Average PPE compliance improved from 85 to 89%, WD from 63 to 99% and EC from 51 to 99%. LESSONS LEARNED: The RIM QIC approach is feasible and effective in SL's austere health system and led to marked improvement in IPC performance. The best practices are being scaled up and the RIM QIC methodology is being applied to other domains. |
Cost analysis of health facility electronic integrated disease surveillance and response in one district in Sierra Leone
Sloan ML , Gleason BL , Squire JS , Koroma FF , Sogbeh SA , Park MJ . Health Secur 2020 18 S64-s71 Global health security depends on effective surveillance systems to prevent, detect, and respond to disease threats. Real-time surveillance initiatives aim to develop electronic systems to improve reporting and analysis of disease data. Sierra Leone, with the support of Global Health Security Agenda partners, developed an electronic Integrated Disease Surveillance and Response (eIDSR) system capable of mobile reporting from health facilities. We estimated the economic costs associated with rollout of health facility eIDSR in the Western Area Rural district in Sierra Leone and projected annual direct operational costs. Cost scenarios with increased transport costs, decreased use of partner personnel, and altered cellular data costs were modeled. Cost data associated with activities were retrospectively collected and were assessed across rollout phases. Costs were organized into cost categories: personnel, office operating, transport, and capital. We estimated costs by category and phase and calculated per health facility and per capita costs. The total economic cost to roll out eIDSR to the Western Area Rural district over the 14-week period was US$64,342, a per health facility cost of $1,021. Equipment for eIDSR was the primary cost driver (45.5%), followed by personnel (35.2%). Direct rollout costs were $38,059, or 59.2% of total economic costs. The projected annual direct operational costs were $14,091, or $224 per health facility. Although eIDSR equipment costs are a large portion of total costs, annual direct operational costs are projected to be minimal once the system is implemented. Our findings can be used to make decisions about establishing and maintaining electronic, real-time surveillance in Sierra Leone and other low-resource settings. |
Evolving epidemiology of reported giardiasis cases in the United States, 1995-2016
Coffey CM , Collier SA , Gleason ME , Yoder JS , Kirk MD , Richardson AM , Fullerton KE , Benedict KM . Clin Infect Dis 2020 72 (5) 764-770 BACKGROUND: Giardiasis is the most common intestinal parasitic disease of humans identified in the United States and an important waterborne disease. In the United States, giardiasis has been variably reportable since 1992 and was made a nationally notifiable disease in 2002. Our objective was to describe the epidemiology of US giardiasis cases from 1995-2016 using National Notifiable Disease Surveillance System data. METHODS: Negative binomial regression models were used to compare incidence rates by age groups (0-4, 5-9, 10-19, 20-29, 30-39, 40-49, 50-64 and >/=65 years) during three time periods (1995-2001, 2002-2010 and 2011-2016). RESULTS: From 1995-2016, the average number of reported cases were 19 781 per year (range 14 623-27 778 cases). The annual incidence of reported giardiasis in the US decreased across all age groups. This decrease differs by age group and sex and may reflect either changes in surveillance methods (for example changes to case definitions or reporting practices) or changes in exposure. Incidence rates in males and older age groups did not decrease to the same extent as rates in females and children. CONCLUSIONS: Trends suggest that differences in exposures by sex and age group are important to the epidemiology of giardiasis. Further investigation into the risk factors of populations with higher rates of giardiasis will support prevention and control efforts. |
Implementing nationwide facility-based electronic disease surveillance in Sierra Leone: Lessons learned
Martin DW , Sloan ML , Gleason BL , de Wit L , Vandi MA , Kargbo DK , Clemens N , Kamara A , Njuguna C , Sesay S , Singh T . Health Secur 2020 18 S72-s80 The Global Health Security Agenda aims to improve countries' ability to prevent, detect, and respond to infectious disease threats by building or strengthening core capacities required by the International Health Regulations (2005). One of those capacities is the development of surveillance systems to rapidly detect and respond to occurrences of diseases with epidemic potential. Since 2015, the US Centers for Disease Control and Prevention (CDC) has worked with partners in Sierra Leone to assist the Ministry of Health and Sanitation in developing an Integrated Disease Surveillance and Response (IDSR) system. Beginning in 2016, CDC, in collaboration with the World Health Organization and eHealth Africa, has supported the ministry in the development of Android device mobile data entry at the health facility for electronic IDSR (eIDSR), also known as health facility-based eIDSR. Health facility-based eIDSR was introduced via a pilot program in 1 district, and national rollout began in 2018. With more than 1,100 health facilities now reporting, the Sierra Leone eIDSR system is substantially larger than most mobile-device health (mHealth) projects found in the literature. Several technical innovations contributed to the success of health facility-based eIDSR in Sierra Leone. Among them were data compression and dual-mode (internet and text) message transmission to mitigate connectivity issues, user interface design tailored to local needs, and a continuous-feedback process to iteratively detect user or system issues and remediate challenges identified. The resultant system achieved high user acceptance and demonstrated the feasibility of an mHealth-based surveillance system implemented on a national scale. |
REDCap for biocontainment worker symptom monitoring
O'Keefe AL , Buss BF , Koirala S , Gleason MX , Mudgapalli A , Schwedhelm S . Health Secur 2019 17 (1) 3-10 The Ebola epidemic of 2014 demonstrated that outbreaks of high-consequence infectious diseases, even in remote parts of the world, can affect communities anywhere in the developed world and that every healthcare facility must be prepared to identify, isolate, and provide care for infected patients. The Nebraska Biocontainment Unit (NBU), located at Nebraska Medicine in Omaha, Nebraska, cared for 3 American citizens exposed in West Africa and confirmed with Ebola virus disease (EVD). Symptom monitoring of healthcare workers caring for these patients was implemented, which included twice daily contact to document the absence or presence of signs of fever or illness. This article describes the symptom monitoring experience of the NBU and local and state public health agencies. Based on lessons learned from that experience, we sought a more efficient solution to meet the needs of both the healthcare facility and public health authorities. REDCap, an open-source application used commonly by academic health centers, was used to develop an inexpensive symptom monitoring application that could reduce the burden of managing these activities, thus freeing up valuable time. Our pilot activities demonstrated that this novel use of REDCap holds promise for minimizing costs and resource demands associated with symptom monitoring while offering a more user-friendly experience for people being monitored and the officials managing the response. |
The contribution of parent-to-offspring transmission of telomeres to the heritability of telomere length in humans.
Delgado DA , Zhang C , Gleason K , Demanelis K , Chen LS , Gao J , Roy S , Shinkle J , Sabarinathan M , Argos M , Tong L , Ahmed A , Islam T , Rakibuz-Zaman M , Sarwar G , Shahriar H , Rahman M , Yunus M , Doherty JA , Jasmine F , Kibriya MG , Ahsan H , Pierce BL . Hum Genet 2018 138 (1) 49-60 Leukocyte telomere length (LTL) is a heritable trait with two potential sources of heritability (h(2)): inherited variation in non-telomeric regions (e.g., SNPs that influence telomere maintenance) and variability in the lengths of telomeres in gametes that produce offspring zygotes (i.e., "direct" inheritance). Prior studies of LTL h(2) have not attempted to disentangle these two sources. Here, we use a novel approach for detecting the direct inheritance of telomeres by studying the association between identity-by-descent (IBD) sharing at chromosome ends and phenotypic similarity in LTL. We measured genome-wide SNPs and LTL for a sample of 5069 Bangladeshi adults with substantial relatedness. For each of the 6318 relative pairs identified, we used SNPs near the telomeres to estimate the number of chromosome ends shared IBD, a proxy for the number of telomeres shared IBD (Tshared). We then estimated the association between Tshared and the squared pairwise difference in LTL ((DeltaLTL)(2)) within various classes of relatives (siblings, avuncular, cousins, and distant), adjusting for overall genetic relatedness (varphi). The association between Tshared and (DeltaLTL)(2) was inverse among all relative pair types. In a meta-analysis including all relative pairs (varphi > 0.05), the association between Tshared and (DeltaLTL)(2) (P = 0.01) was stronger than the association between varphi and (DeltaLTL)(2) (P = 0.43). Our results provide strong evidence that telomere length (TL) in parental germ cells impacts TL in offspring cells and contributes to LTL h(2) despite telomere "reprogramming" during embryonic development. Applying our method to larger studies will enable robust estimation of LTL h(2) attributable to direct transmission of telomeres. |
Annual Report to the Nation on the Status of Cancer, part II: Recent changes in prostate cancer trends and disease characteristics
Negoita S , Feuer EJ , Mariotto A , Cronin KA , Petkov VI , Hussey SK , Benard V , Henley SJ , Anderson RN , Fedewa S , Sherman RL , Kohler BA , Dearmon BJ , Lake AJ , Ma J , Richardson LC , Jemal A , Penberthy L . Cancer 2018 124 (13) 2801-2814 BACKGROUND: Temporal trends in prostate cancer incidence and death rates have been attributed to changing patterns of screening and improved treatment (mortality only), among other factors. This study evaluated contemporary national-level trends and their relations with prostate-specific antigen (PSA) testing prevalence and explored trends in incidence according to disease characteristics with stage-specific, delay-adjusted rates. METHODS: Joinpoint regression was used to examine changes in delay-adjusted prostate cancer incidence rates from population-based US cancer registries from 2000 to 2014 by age categories, race, and disease characteristics, including stage, PSA, Gleason score, and clinical extension. In addition, the analysis included trends for prostate cancer mortality between 1975 and 2015 by race and the estimation of PSA testing prevalence between 1987 and 2005. The annual percent change was calculated for periods defined by significant trend change points. RESULTS: For all age groups, overall prostate cancer incidence rates declined approximately 6.5% per year from 2007. However, the incidence of distant-stage disease increased from 2010 to 2014. The incidence of disease according to higher PSA levels or Gleason scores at diagnosis did not increase. After years of significant decline (from 1993 to 2013), the overall prostate cancer mortality trend stabilized from 2013 to 2015. CONCLUSIONS: After a decline in PSA test usage, there has been an increased burden of late-stage disease, and the decline in prostate cancer mortality has leveled off. Cancer 2018. (c) 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. |
Geospatial analysis of household spread of Ebola virus in a quarantined village - Sierra Leone, 2014
Gleason BL , Foster S , Wilt GE , Miles B , Lewis B , Cauthen K , King M , Bayor F , Conteh S , Sesay T , Kamara SI , Lambert G , Finley P , Beyeler W , Moore T , Gaudioso J , Kilmarx PH , Redd JT . Epidemiol Infect 2017 145 (14) 1-9 We performed a spatial-temporal analysis to assess household risk factors for Ebola virus disease (Ebola) in a remote, severely-affected village. We defined a household as a family's shared living space and a case-household as a household with at least one resident who became a suspect, probable, or confirmed Ebola case from 1 August 2014 to 10 October 2014. We used Geographic Information System (GIS) software to calculate inter-household distances, performed space-time cluster analyses, and developed Generalized Estimating Equations (GEE). Village X consisted of 64 households; 42% of households became case-households over the observation period. Two significant space-time clusters occurred among households in the village; temporal effects outweighed spatial effects. GEE demonstrated that the odds of becoming a case-household increased by 4.0% for each additional person per household (P < 0.02) and 2.6% per day (P < 0.07). An increasing number of persons per household, and to a lesser extent, the passage of time after onset of the outbreak were risk factors for household Ebola acquisition, emphasizing the importance of prompt public health interventions that prioritize the most populated households. Using GIS with GEE can reveal complex spatial-temporal risk factors, which can inform prioritization of response activities in future outbreaks. |
A national profile of attention-deficit hyperactivity disorder diagnosis and treatment among US children aged 2 to 5 years
Danielson ML , Visser SN , Gleason MM , Peacock G , Claussen AH , Blumberg SJ . J Dev Behav Pediatr 2017 38 (7) 455-464 OBJECTIVE: Clinical guidelines provide recommendations for diagnosis and treatment of attention-deficit hyperactivity disorder (ADHD), with specific guidance on caring for children younger than 6 years. This exploratory study describes ADHD diagnosis and treatment patterns among young children in the United States using 2 nationally representative parent surveys. METHODS: The National Survey of Children's Health (2007-2008, 2011-2012) was used to produce weighted prevalence estimates of current ADHD and ADHD medication treatment among US children aged 2 to 5 years. The National Survey of Children with Special Health Care Needs (2009-2010) provided additional estimates on types of medication treatment and receipt of behavioral treatment among young children with special health care needs (CSHCN) with ADHD. RESULTS: In 2011 to 2012, 1.5% of young children (approximately 237,000) had current ADHD compared to 1.0% in 2007 to 2008. In 2011 to 2012, 43.7% of young children with current ADHD were taking medication for ADHD (approximately 104,000). In young CSHCN with ADHD, central nervous system stimulants were the most common medication type used to treat ADHD, and 52.8% of young CSHCN with current ADHD had received behavioral treatment for ADHD in the past year. CONCLUSION: Nearly a quarter million In young CSHCN have current ADHD, with a prevalence that has increased by 57% from 2007 to 2008 to 2011 to 2012. The demographic patterns of diagnosis and treatment described in this study can serve as a benchmark to monitor service use patterns of young children diagnosed with ADHD over time. |
Collaborative public health investigation of clenbuterol-adulterated heroin outbreak - Richmond, Virginia, March-April 2015
Gleason B , West A , Avula D , Utah O , Vogt M , Cumpston K , Kelly M , Brasler P , Wyatt S , Forlano L . J Public Health Manag Pract 2017 23 (2) e8-e11 CONTEXT: In March 2015, the Virginia Department of Health (VDH) was alerted by the Virginia Poison Center of a 6-patient cluster treated for severe clinical presentations after using heroin. Patients' symptoms were atypical for heroin use, and concern existed that patients were exposed to heroin that had been adulterated with or replaced by another substance. OBJECTIVE: To understand the extent and characterization of the outbreak and implement response measures to prevent further cases. The purpose of this report is to highlight the collaborative nature of a public health investigation among a diverse group of stakeholders. DESIGN: Active surveillance and retrospective case finding. SETTING: Richmond metro area community and hospitals. PARTICIPANTS: Regional poison centers, the Division of Consolidated Laboratory Services, the Department of Behavioral Health and Developmental Services, community partners, local law enforcement, and multiple VDH divisions. INTERVENTION: Outbreak investigation, communication to public health professionals, clinicians, and the community, and liaising with the local law enforcement. MAIN OUTCOME MEASURES: Outbreak control. RESULTS: Laboratory confirmation of clenbuterol in clinical specimens implicated it as the heroin adulterant. Thirteen patients met clinical and epidemiologic criteria for exposure to clenbuterol-adulterated heroin. All patients were associated with a localized area within Richmond, and patient interviews elucidated heroin supplier information. VDH collaborated with local law enforcement agents who investigated and arrested the supplier, leading to cessation of the outbreak. CONCLUSION: This outbreak highlights the value of policies and practices that support an integrated outbreak response among public health practitioners, poison center staff, laboratorians, clinicians, law enforcement agents, community groups, and other agencies. Collaboration enabled implementation of effective control measures-including those outside the purview of the health department-and should be standard practice in future outbreaks involving illicit substances. |
Establishment of an Ebola treatment unit and laboratory - Bombali District, Sierra Leone, July 2014-January 2015
Gleason B , Redd J , Kilmarx P , Sesay T , Bayor F , Mozalevskis A , Connolly A , Akpablie J , Prybylski D , Moffett D , King M , Bass M , Joseph K , Jones J , Ocen F . MMWR Morb Mortal Wkly Rep 2015 64 (39) 1108-1111 The first confirmed case of Ebola virus disease (Ebola) in Sierra Leone related to the ongoing epidemic in West Africa occurred in May 2014, and the outbreak quickly spread. To date, 8,704 Ebola cases and 3,955 Ebola deaths have been confirmed in Sierra Leone. The first Ebola treatment units (ETUs) in Sierra Leone were established in the eastern districts of Kenema and Kailahun, where the first Ebola cases were detected, and these districts were also the first to control the epidemic. By September and October 2014, districts in the western and northern provinces, including Bombali, had the highest case counts, but additional ETUs outside of the eastern province were not operational for weeks to months. Bombali became one of the most heavily affected districts in Sierra Leone, with 873 confirmed patients with Ebola during July-November 2014. The first ETU and laboratory in Bombali District were established in late November and early December 2014, respectively. T- evaluate the impact of the first ETU and laboratory becoming operational in Bombali on outbreak control, the Bombali Ebola surveillance team assessed epidemiologic indicators before and after the establishment of the first ETU and laboratory in Bombali. After the establishment of the ETU and laboratory, the interval from symptom onset to laboratory result and from specimen collection to laboratory result decreased. By providing treatment to Ebola patients and isolating contagious persons to halt ongoing community transmission, ETUs play a critical role in breaking chains of transmission and preventing uncontrolled spread of Ebola (4). Prioritizing and expediting the establishment of an ETU and laboratory by pre-positioning resources needed to provide capacity for isolation, testing, and treatment of Ebola are essential aspects of pre-outbreak planning. |
Type and dose of radiotherapy used for initial treatment of non-metastatic prostate cancer
Wang D , Ho A , Hamilton AS , Wu XC , Lo M , Fleming S , Goodman M , Thompson T , Owen J . Radiat Oncol 2014 9 (1) 47 BACKGROUND: We sought to describe patterns of initial radiotherapy among non-metastatic prostate cancer (PC) patients by recurrence risk groups. METHODS: Medical records were abstracted for a sample of 9017 PC cases diagnosed in 2004 as a part of the Center for Disease Control and Prevention's Prostate and Breast Patterns of Care Study in seven states. Non-metastatic PC cases are categorized as low-risk (LR), intermediate-risk (IR) or high-risk (HR) groups based on pretreatment PSA, tumor stage, and Gleason score per 2002 NCCN guidelines. Univariate and multivariate analyses were employed to determine factors associated with the type and dose of radiotherapy by the risk groups. RESULTS: Of the 9,017 patients, 3153 who received definitive radiotherapy either alone or in combination with hormone therapy (HT) were selected for in-depth analysis. Multivariate models showed that LR patients were more likely to receive seed implant brachytherapy (BT) than those in higher risk groups. Those in the IR group were most likely to receive external beam radiotherapy (EBRT) combined with BT or high-dose radiotherapy. Use of HT in combination with radiotherapy was more common in the IR and HR groups than for LR patients. Intensity modulated radiation treatment (IMRT) was used to treat 32.6% of PC patients treated with EBRT, with the majority (60.6%) treated with high-dose radiotherapy. CONCLUSIONS: Radiotherapy types and dosage utilization varied by PC risk groups. Patients in IR were more likely than those in LR or HR to receive high-dose radiotherapy. IMRT was used in about one third of patients to deliver high-dose radiotherapy. |
Developmental genetics of secretory vesicle acidification during Caenorhabditis elegans spermatogenesis.
Gleason EJ , Hartley PD , Henderson M , Hill-Harfe KL , Price PW , Weimer RM , Kroft TL , Zhu GD , Cordovado S , L'Hernault S W . Genetics 2012 191 (2) 477-91 Secretory vesicles are used during spermatogenesis to deliver proteins to the cell surface. In Caenorhabditis elegans, secretory membranous organelles (MO) fuse with the plasma membrane to transform spermatids into fertilization-competent spermatozoa. We show that, like the acrosomal vesicle of mammalian sperm, MOs undergo acidification during development. Treatment of spermatids with the V-ATPase inhibitor bafilomycin blocks both MO acidification and formation of functional spermatozoa. There are several spermatogenesis-defective mutants that cause defects in MO morphogenesis, including spe-5. We determined that spe-5, which is on chromosome I, encodes one of two V-ATPase B paralogous subunits. The spe-5 null mutant is viable but sterile because it forms arrested, multi-nucleate spermatocytes. Immunofluorescence with a SPE-5-specific monoclonal antibody shows that SPE-5 expression begins in spermatocytes and is found in all subsequent stages of spermatogenesis. Most SPE-5 is discarded into the residual body during spermatid budding, but a small amount remains in budded spermatids where it localizes to MOs as a discrete dot. The other V-ATPase B subunit is encoded by vha-12, which is located on the X chromosome. Usually, spe-5 mutants are self-sterile in a wild-type vha-12 background. However, an extrachromosomal transgene containing wild-type vha-12 driven by its own promoter allows spe-5 mutant hermaphrodites to produce progeny, indicating that VHA-12 can at least partially substitute for SPE-5. Others have shown that the X chromosome is transcriptionally silent in the male germline, so expression of the autosomally located spe-5 gene ensures that a V-ATPase B subunit is present during spermatogenesis. |
No association of xenotropic murine leukemia virus-related viruses with prostate cancer.
Switzer WM , Jia H , Zheng H , Tang S , Heneine W . PLoS One 2011 6 (5) e19065 BACKGROUND: The association of the xenotropic murine leukemia virus-related virus (XMRV) with prostate cancer continues to receive heightened attention as studies report discrepant XMRV prevalences ranging from zero up to 23%. It is unclear if differences in the diagnostic testing, disease severity, geography, or other factors account for the discordant results. We report here the prevalence of XMRV in a population with well-defined prostate cancers and RNase L polymorphism. We used broadly reactive PCR and Western blot (WB) assays to detect infection with XMRV and related murine leukemia viruses (MLV). METHODOLOGY/PRINCIPAL FINDINGS: We studied specimens from 162 US patients diagnosed with prostate cancer with a intermediate to advanced stage (Gleason Scores of 5-10; moderate (46%) poorly differentiated tumors (54%)). Prostate tissue DNA was tested by PCR assays that detect XMRV and MLV variants. To exclude contamination with mouse DNA, we also designed and used a mouse-specific DNA PCR test. Detailed phylogenetic analysis was used to infer evolutionary relationships. RNase L typing showed that 9.3% were homozygous (QQ) for the R462Q RNase L mutation, while 45.6% and 45.1% were homozygous or heterozygous, respectively. Serologic testing was performed by a WB test. Three of 162 (1.9%) prostate tissue DNA were PCR-positive for XMRV and had undetectable mouse DNA. None was homozygous for the QQ mutation. Plasma from all three persons was negative for viral RNA by RT-PCR. All 162 patients were WB negative. Phylogenetic analysis inferred a distinct XMRV. CONCLUSIONS AND THEIR SIGNIFICANCE: We found a very low prevalence of XMRV in prostate cancer patients. Infection was confirmed by phylogenetic analysis and absence of contaminating mouse DNA. The finding of undetectable antibodies and viremia in all three patients may reflect latent infection. Our results do not support an association of XMRV or MLV variants with prostate cancer. |
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