Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
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Rate and durability of clearance of hepatitis B surface antigen in Alaska Native persons with long-term hepatitis B virus infection: 1982-2019
Bruden D , McMahon BJ , Snowball M , Towshend-Bulson L , Homan C , Johnston JM , Simons BC , Bruce MG , Cooley L , Spradling PR , Harris AM . Hepatology 2024 79 (6) 1412-1420 BACKGROUND AND AIMS: A functional cure and therapeutic end point of chronic HBV infection is defined as the clearance of HBsAg from serum. Little is known about the long-term durability of HBsAg loss in the Alaskan Native population. APPROACH AND RESULTS: We performed a retrospective cohort study of Alaska Native patients with chronic HBV-monoinfection from January 1982 through December 2019. The original group in this cohort was identified during a 1982 to 1987 population-based screening for 3 HBV serologic markers in 53,000 Alaska Native persons. With close to 32,000 years of follow-up, we assessed the frequency and duration of HBsAg seroclearance (HBsAg-negative for > 6 mo). We examined factors associated with HBsAg clearance and followed persons for a median of 13.1 years afterward to assess the durability of HBsAg clearance. Among 1079 persons with an average length of follow-up of 33 years, 260 (24%) cleared HBsAg at a constant rate of 0.82% per person/per year. Of the 260 persons who cleared, 249 (96%) remained HBsAg-negative, while 11 persons had ≥ 2 transient HBsAg-positive results in subsequent follow-up. CONCLUSIONS: Of the patients with chronic HBV monoinfection, 0.82% of people per year achieved a functional cure. HBsAg seroclearance was durable for treated and nontreated patients and lasted, on average, over 13 years without seroreversion. |
Factors associated with hepatitis A seropositivity at 23 years after childhood vaccination
Scobie HM , Negus S , Stevenson T , Bressler S , Bruden D , Simons BC , Snowball M , Hofmeister MG , Bruce M , Townshend-Bulson L , Fischer M , McMahon B . Open Forum Infect Dis 2024 11 (7) ofae417 We evaluated factors associated with the presence of hepatitis A virus antibodies 23 years after initiating vaccination at ages 6-15 months. Among 67 participants, 86% (42/49) of those vaccinated at ages 12-15 months and 61% (11/18) of those vaccinated at 6 months remained seropositive at 23 years. Lack of maternal antibodies at enrollment and higher initial vaccine response were independently associated with higher antibody concentrations at 23 years. Further research is needed to assess the duration of hepatitis A vaccine protection and possible need for a booster dose. |
Immunogenicity of quadrivalent human papillomavirus vaccine among Alaska Native children aged 9-14 years at 5 years after vaccination
Davis BM , Blake I , Panicker G , Meites E , Thompson G , Geis J , Bruden D , Fischer M , Singleton R , Unger ER , Markowitz LE , Bruce MG . Vaccine 2024 BACKGROUND: Persistent human papillomavirus (HPV) infection can cause anogenital and oropharyngeal cancers. Many HPV infections and HPV-associated cancers are vaccine-preventable. Studies suggest long-term persistence of vaccine-induced antibodies. However, data are limited among Alaska Native people. METHODS: During 2011-2014, we enrolled Alaska Native children aged 9-14 years who received a 3-dose series of quadrivalent HPV vaccine (4vHPV). We collected sera at 1 month and 1, 2, 3, and 5 years post-vaccination to evaluate trends in type-specific immunoglobulin G antibody concentrations for the 4vHPV types (HPV 6/11/16/18). RESULTS: All participants (N = 469) had detectable antibodies against all 4vHPV types at all timepoints post-vaccination. For all 4vHPV types, antibody levels peaked by 1 month post-vaccination and gradually declined in subsequent years. At 5 years post-vaccination, antibody levels were higher among children who received 4vHPV at a younger age. CONCLUSIONS: Alaska Native children maintained antibodies against all 4vHPV types at 5 years post-vaccination. |
Trends in otitis media ambulatory visits in American Indian and Alaska native children during the pneumococcal conjugate vaccine period and the COVID-19 Pandemic
Bressler SS , Bruden D , Hammitt LL , Chukwuma U , Fischer M , Singleton R . Pediatr Infect Dis J 2024 Otitis media-associated outpatient visits among American Indians/Alaska Natives children aged <5 years decreased by 52% (100 to 48 per 100 children per year) from 2003 to 2019. Otitis media visits decreased by another 50% from 2019 to 2020, but rebounded between 2020 and 2021 back to a rate similar to 2019. |
Invasive pneumococcal disease and potential impact of pneumococcal conjugate vaccines among adults, including persons experiencing homelessness - Alaska, 2011-2020
Steinberg J , Bressler SS , Orell L , Thompson GC , Kretz A , Reasonover AL , Bruden D , Bruce MG , Fischer M . Clin Infect Dis 2023 BACKGROUND: Adults aged ≥65 years, adults with certain underlying medical conditions, and persons experiencing homelessness are at increased risk for invasive pneumococcal disease (IPD). Two new pneumococcal conjugate vaccines, 15-valent pneumococcal conjugate vaccine (PCV15) and 20-valent pneumococcal conjugate vaccine (PCV20), were recently approved for use in U.S. adults. We described the epidemiology of IPD among Alaska adults and estimated the proportion of IPD cases potentially preventable by new vaccines. METHODS: We used statewide, laboratory-based surveillance data to calculate and compare IPD incidence rates and 95% confidence intervals (CI) among Alaska adults aged ≥18 years during 2011-2020 and estimate the proportion of IPD cases that were caused by serotypes in PCV15 and PCV20. RESULTS: During 2011-2020, 1,164 IPD cases were reported among Alaska adults for an average annual incidence of 21.3 cases per 100,000 adults per year (95% CI: 20.1-22.5). Incidence increased significantly during the study period (p<0.01). IPD incidence among Alaska Native adults was 4.7 times higher than among non-Alaska Native adults (95% CI: 4.2-5.2). Among adults experiencing homelessness in Anchorage, IPD incidence was 72 times higher than the general adult population (95% CI: 59-89). Overall, 1,032 (89%) Alaska adults with IPD had an indication for pneumococcal vaccine according to updated vaccination guidelines; 456 (39%) and 700 (60%) cases were caused by serotypes in PCV15 and PCV20, respectively. CONCLUSIONS: Use of PCV15 and PCV20 could substantially reduce IPD among adults in Alaska, including Alaska Native adults and adults experiencing homelessness. |
The Alaska Native/American Indian experience of hepatitis C treatment with sofosbuvir-based direct-acting antivirals (preprint)
Townshend-Bulson L , Roik E , Barbour Y , Bruden DJT , Homan CE , Espera HGF , Stevenson TJ , Hewitt AM , Rhodes W , Gove JE , Plotnik JN , Snowball MM , McGilvray J , Simons BC , McMahon BJ . medRxiv 2021 2021.09.03.21263089 Background Direct-acting antiviral (DAA) drugs have been effective in the treatment of chronic hepatitis C virus (HCV) infection. Limited data are available on safety, tolerability, and efficacy in American Indian or Alaska Native people. We aim to evaluate the treatment outcomes of sofosbuvir-based regimens for treatment of HCV in a real life setting in Alaska Native/American Indian (AN/AI) people.Methods AN/AI patients within the Alaska Tribal Health System with confirmed positive anti-HCV and HCV RNA, who were 18 years of age and older were included in the study. Pretreatment baseline patient characteristics, treatment efficacy based on sustained virologic response (SVR) 12 weeks after treatment completion, and adverse effects were assessed. The following treatments were given according to the American Association for the Study of Liver Diseases/Infectious Disease Society of America (AASLD/IDSA) HCV Guidance: ledipasvir/sofosbuvir, sofosbuvir plus weight-based ribavirin, and sofosbuvir/velpatasvir.Results We included 501 patients with a mean age of 54.3 (range 21.3 -78.3) in the study. Overall SVR was achieved in 95.2% of patients who received one of the three DAA regimens. For those with cirrhosis, overall SVR was 92.8% and for those with genotype 3 91.1% achieved SVR. The most common symptom experienced during treatment was headache. Joint pain was found to decrease during treatment. One person discontinued sofosbuvir plus ribavirin due to myocardial infarction and one discontinued sofosbuvir/velpatasvir due to urticaria.Conclusions In the real-world setting, sofosbuvir-based treatment is safe, effective, and well tolerated in AN/AI patients. Sustained virologic response was high regardless of HCV genotype or cirrhosis status.Competing Interest StatementPartial funding from Gilead Sciences.Funding StatementPartial funding from Gilead Sciences.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Alaska Area Institutional Review Board (IHS IRB #2) Dr. Shanda Lohse, Chair, Alaska Area IRB Terry Powell, Administrator, Alaska Area IRB 4315 Diplomacy Drive - RMCC Anchorage, AK 99508 Phone: 907-729-3924 or 907-729-3917 Email: akaalaskaareaIRB{at}anthc.orgAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAccess to data for this study is subject to tribal review. Requests for data should be directed to the Alaska Native Tribal Health Consortium Privacy Officer c/o Ethics and Compliance Services, 4315 Diplomacy Drive, Anchorage, AK 99508. |
RSV among American Indian and Alaska Native children: 2019 to 2020
Atwell JE , Hartman RM , Parker D , Taylor K , Brown LB , Sandoval M , Ritchie N , Desnoyers C , Wilson AS , Hammes M , Tiesinga J , Halasa N , Langley G , Prill MM , Bruden D , Close R , Moses J , Karron RA , Santosham M , Singleton RJ , Hammitt LL . Pediatrics 2023 152 (2) Respiratory syncytial virus (RSV) is the leading viral cause of acute lower respiratory tract infections, including bronchiolitis and pneumonia, in children under 5 years of age globally.1 Historically, RSV-associated hospitalization rates among American Indian and Alaska Native (AI/AN) children have been among the highest in the world.2,–7 Contemporary estimates of RSV-acute respiratory infection (ARI) are needed to inform RSV prevention strategies for AI/AN children. |
Effectiveness of the COVID-19 vaccines on preventing symptomatic SARS-CoV-2 infections and hospitalizations in Southwestern Alaska, January-December 2021
Lefferts B , Bruden D , Plumb ID , Hodges E , Bates E , January G , Bruce MG . Vaccine 2023 The population in rural southwest Alaska has been disproportionately affected by COVID-19. To assess the benefit of COVID-19 vaccines, we analyzed data from the regional health system. We estimated vaccine effectiveness (VE) during January 16-December 3, 2021, against symptomatic SARS-CoV-2 infection after a primary series or booster dose, and overall VE against hospitalization. VE of a primary series against symptomatic infection among adult residents was 91.3% (95% CI: 85.7, 95.2) during January 16-May 7, 2021, 50.3% (95% CI, 41.1%-58.8%) during July 17-September 24, and 37.0% (95% CI, 27.8-45.0) during September 25-December 3, 2021; VE of a booster dose during September 25-December 3, 2021, was 92.1% (95% CI: 87.2-95.2). During the overall study period, VE against hospitalization was 91.9% (95% CI: 85.4-95.5). COVID-19 vaccination offered strong protection against hospitalization and a booster dose restored protection against symptomatic infection. |
Risk factors for Ebola virus disease among household care providers, Sierra Leone, 2015
Duffy N , Bruden D , Thomas H , Nichols E , Knust B , Hennessy T , Reichler MR . Int J Epidemiol 2022 51 (5) 1457-1468 BACKGROUND: Household contacts who provide care to an Ebola virus disease (EVD) case have a 3-fold higher risk of EVD compared with contacts who do not provide care. METHODS: We enrolled persons with confirmed EVD from December 2014 to April 2015 in Freetown, Sierra Leone, and their household contacts. Index cases and contacts were interviewed, and contacts were followed for 21 days to identify secondary cases. Epidemiological data were analysed to describe household care and to identify risk factors for developing EVD. RESULTS: Of 838 contacts in 147 households, 156 (17%) self-reported providing care to the index case; 56 households had no care provider, 52 a single care provider and 39 multiple care providers. The median care provider age was 29 years, 68% were female and 32% were the index case's spouse. Care providers were more likely to report physical contact, contact with body fluids or sharing clothing, bed linens or utensils with an index case, compared with non-care providers (P <0.01). EVD risk among non-care providers was greater when the number of care providers in the household increased (odds ratio: 1.61; 95% confidence interval: 1.1, 2.4). In multivariable analysis, factors associated with care provider EVD risk included no piped water access and absence of index case fever, and protective factors included age <20 years and avoiding the index case. CONCLUSIONS: Limiting the number of care providers in a household could reduce the risk of EVD transmission to both care providers and non-care providers. Strategies to protect care providers from EVD exposure are needed. |
Protection and antibody levels 35 years after primary series with hepatitis B vaccine and response to a booster dose
Bruce MG , Bruden D , Hurlburt D , Morris J , Bressler S , Thompson G , Lecy D , Rudolph K , Bulkow L , Hennessy T , Simons BC , Weng MK , Nelson N , McMahon BJ . Hepatology 2022 76 (4) 1180-1189 BACKGROUND: The duration of protection from hepatitis B vaccination in children and adults is not known. In 1981, we used three doses of plasma-derived hepatitis B vaccine to immunize a cohort of 1578 Alaska Native adults and children from 15 Alaska communities who were 6 months or older. METHODS: We tested persons for anti-HBs levels 35 years after receiving the primary series. Those with levels <10 mIU/ml received 1 booster dose of recombinant hepatitis B vaccine 2-4 weeks later and were then evaluated on the basis of anti-HBs measurements 30 days post-booster. RESULTS: Among the 320 recruited, 112 persons had not participated in the 22 nor 30-year follow-up study (Group 1) and 208 persons had participated but were not given an HBV booster dose (Group 2). Among the 112 persons in Group 1 who responded to the original primary series, 53 (47.3%) had an anti-HBs level ≥10 mIU/ml. Among group 1, 73.7% (28/38) of persons available for a booster dose responded to it with an anti-HBs level ≥10 mIU/ml at 30 days. Initial anti-HBs level after the primary series was correlated with higher anti-HBs levels at 35 years. Among 8 persons who tested positive for anti-HBc, none tested positive for HBsAg nor HBV DNA. CONCLUSIONS: Based on anti-HBs level ≥10 mIU/ml at 35 years and a 73.7% booster dose response, we estimate 86% of participants had evidence of protection 35 years later. Booster doses are not needed in the general population at this time. |
Antigen Test Positivity After COVID-19 Isolation - Yukon-Kuskokwim Delta Region, Alaska, January-February 2022.
Lefferts B , Blake I , Bruden D , Hagen MB , Hodges E , Kirking HL , Bates E , Hoeldt A , Lamont B , Saydah S , MacNeil A , Bruce MG , Plumb ID . MMWR Morb Mortal Wkly Rep 2022 71 (8) 293-298 Isolation is recommended during acute infection with SARS-CoV-2, the virus that causes COVID-19, but the duration of infectiousness varies among individual persons. Rapid antigen test results have been correlated with detection of viable virus (1-3) and might inform isolation guidance, but data are limited for the recently emerged SARS-CoV-2 B.1.1.529 (Omicron) variant. On January 5, 2022, the Yukon-Kuskokwim Health Corporation (YKHC) recommended that persons with SARS-CoV-2 infection isolate for 10 days after symptom onset (or, for asymptomatic persons, 10 days after a positive nucleic acid amplification or antigen test result). However, isolation could end after 5-9 days if symptoms were resolving or absent, fever was absent for 24 hours without fever-reducing medications, and an Abbott BinaxNOW COVID-19 Ag (BinaxNOW) rapid antigen test result was negative. Antigen test results and associated individual characteristics were analyzed among 3,502 infections reported to YKHC during January 1-February 9, 2022. After 5-9 days, 396 of 729 persons evaluated (54.3%) had a positive antigen test result, with a declining percentage positive over time. In a multivariable model, a positive antigen test result was more likely after 5 days compared with 9 days (adjusted odds ratio [aOR]=6.39) or after symptomatic infection (aOR=9.63), and less likely after previous infection (aOR=0.30), receipt of a primary COVID-19 vaccination series (aOR=0.60), or after both previous infection and receipt of a primary COVID-19 vaccination series (aOR=0.17). Antigen tests might be a useful tool to guide recommendations for isolation after SARS-CoV-2 infection. During the 10 days after infection, persons might be infectious to others and are recommended to wear a well-fitting mask when around others, even if ending isolation after 5 days. |
Mortality among Alaska Native adults with confirmed hepatitis C virus infection compared with the general population in Alaska, 1995-2016
Bressler SS , Bruden D , Nolen LD , Bruce MG , Towshend-Bulson L , Spradling P , McMahon BJ . Can J Gastroenterol Hepatol 2022 2022 2573545 BACKGROUND: Hepatitis C virus (HCV) infection incidence rates in the United States have increased since 2010 as a byproduct of the opioid crisis despite the introduction of direct-acting antiviral agents in 2013. HCV infection is associated with higher rates of liver-related and nonhepatic causes of death. METHODS: This study compared demographic characteristics and age-adjusted death rates from 1995 to 2016 among Alaska Native (AN) adults infected with HCV (AK-HepC) to rates among the AN and non-AN adult populations living in Alaska. Liver-related disease (LRD) and other disease-specific age-adjusted death rates were compared between the populations. RESULTS: The all-cause death rate among the AK-HepC cohort was 2.2- and 3.4-fold higher than AN and non-AN adults, respectively, and remained stable over time in all populations. The LRD death rate among the AK-HepC cohort was 18- and 11-fold higher than the non-AN and AN, respectively. The liver cancer rate among the AK-HepC cohort was 26-fold higher compared to the Alaska statewide population. The AK-HepC cohort had elevated rates of death associated with nonhepatic diseases with circulatory disease having the highest rate in all populations. Among liver cancer deaths in the AK-HepC cohort, 32% had HCV listed as a contributing cause of death on the death certificate. CONCLUSIONS: Death rates in the AK-HepC cohort remained stable since 1995 and higher compared to the general population. People with HCV infection had an elevated risk for all-cause, liver-related, and nonhepatic causes of death. Hepatitis C infection may be underrepresented as a cause of mortality in the United States. |
The Alaska Native/American Indian experience of hepatitis C treatment with sofosbuvir-based direct-acting antivirals
Townshend-Bulson L , Roik E , Barbour Y , Bruden DJT , Homan CE , Espera HGF , Stevenson TJ , Hewitt AM , Rhodes W , Gove JE , Plotnik JN , Snowball MM , McGilvray J , Simons BC , Johnston JM , McMahon BJ . PLoS One 2021 16 (12) e0260970 BACKGROUND: Direct-acting antiviral (DAA) drugs have been effective in the treatment of chronic hepatitis C virus (HCV) infection. Limited data are available on safety, tolerability, and efficacy in American Indian or Alaska Native people. We aim to evaluate the treatment outcomes of sofosbuvir- based regimens for treatment of HCV in a real life setting in Alaska Native/American Indian (AN/AI) people. METHODS: AN/AI patients within the Alaska Tribal Health System with confirmed positive anti-HCV and HCV RNA, who were 18 years of age and older were included in the study. Pretreatment baseline patient characteristics, treatment efficacy based on sustained virologic response (SVR) 12 weeks after treatment completion, and adverse effects were assessed. The following treatments were given according to the American Association for the Study of Liver Diseases/Infectious Disease Society of America (AASLD/IDSA) HCV Guidance: ledipasvir/sofosbuvir, sofosbuvir plus weight-based ribavirin, and sofosbuvir/velpatasvir. RESULTS: We included 501 patients with a mean age of 54.3 (range 21.3-78.3) in the study. Overall SVR was achieved in 95.2% of patients who received one of the three DAA regimens. For those with cirrhosis, overall SVR was 92.8% and for those with genotype 3 91.1% achieved SVR. The most common symptom experienced during treatment was headache. Joint pain was found to decrease during treatment. One person discontinued sofosbuvir plus ribavirin due to myocardial infarction and one discontinued sofosbuvir/velpatasvir due to urticaria. CONCLUSIONS: In the real-world setting, sofosbuvir-based treatment is safe, effective, and well tolerated in AN/AI patients. Sustained virologic response was high regardless of HCV genotype or cirrhosis status. |
Hepatitis A vaccine immunogenicity 25 years after vaccination in Alaska
Ramaswamy M , Bruden D , Nolen LD , Mosites E , Snowball M , Nelson NP , Bruce M , McMahon BJ . J Med Virol 2021 93 (6) 3991-3994 The hepatitis A vaccine is recommended for all children greater than or equal to 1 year of age, however, the duration of vaccine protection is unknown and protection through adulthood is crucial to prevent symptomatic hepatitis later in life. We report on 25 years of follow-up of a cohort of Alaska Native individuals who were vaccinated in early childhood. We assessed the duration of vaccine protection by calculating the geometric mean concentration and proportion of participants with protective levels of IgG antibody to hepatitis A virus (anti-HAV) (≥20 mIU/mL) every 2 to 3 years. We estimated the amount of time until the anti-HAV dropped below protective levels using survival analyses. At 25 years, 43 of the original 144 participants were available, mean anti-HAV levels were 91.5 mIU/mL, and 35 (81.4%) had protective levels of anti-HAV. Using data from all persons and all time points, a survival analysis estimated 78.7% of participants had protective levels of anti-HAV at 25 years. The high level of protective antibodies in this cohort indicate that supplemental doses of hepatitis A vaccine are not needed 25 years after completion of the vaccine series. |
Use of Rapid Antigen Testing for SARS-CoV-2 in Remote Communities - Yukon-Kuskokwim Delta Region, Alaska, September 15, 2020-March 1, 2021.
Bruden D , Bruce M . MMWR Morb Mortal Wkly Rep 2021 70 (33) 1120-1123 Controlling the spread of SARS-CoV-2, the virus that causes COVID-19, in Alaska is challenging. Alaska includes many remote and isolated villages with small populations (ranging from 15 to >1,000 persons) that are accessible only by air from larger communities. Until rapid point-of-care testing became widely available, a primary challenge in the diagnosis of COVID-19 in rural Alaska was slow turnaround times for SARS-CoV-2 test results, attributable to the need to transport specimens to testing facilities. To provide more timely test results and isolation of cases, the Yukon Kuskokwim Health Corporation (YKHC) introduced Abbott BinaxNOW COVID-19 Ag rapid antigen test (BinaxNOW) on November 9, 2020, in the rural Yukon-Kuskokwim Delta region in southwestern Alaska. To evaluate the impact of implementing antigen testing, YKHC reviewed the results of 54,981 antigen and molecular tests for SARS-CoV-2 performed in the Yukon-Kuskokwim Delta during September 15, 2020-March 1, 2021. Introduction of rapid, point-of-care testing was followed by a more than threefold reduction in daily SARS-CoV-2 case rates during approximately 1 month before the introduction of COVID-19 vaccination. The median turnaround time for SARS-CoV-2 test results decreased by >30%, from 6.4 days during September 15-November 8, 2020, to 4.4 days during November 9, 2020-March 1, 2021 (p<0.001). Daily incidence decreased 65% after the introduction of BinaxNOW, from 342 cases per 100,000 population during the week of November 9 to 119 during the week of December 13 (p<0.001). These findings indicate that point-of-care rapid antigen testing can be a valuable tool in reducing turnaround times in rural communities where local access to laboratory-based nucleic acid amplification testing (NAAT) is not readily available and could thereby reduce transmission by facilitating rapid isolation of infected persons, contact tracing, and implementation of local mitigation strategies. |
Hepatitis B Virus (HBV) Genotype: A Significant Risk Factor in Determining which Patients with Chronic HBV Infection should Undergo Surveillance for Hepatocellular Carcinoma: The Hepatitis B Alaska (HEP-B-AK) Study.
McMahon BJ , Nolen S , Snowball M , Homan C , Negus S , Roik E , Spradling PR , Bruden D . Hepatology 2021 74 (6) 2965-2973 BACKGROUND AND AIMS: Information is limited regarding hepatitis B virus (HBV) genotype and the outcome of chronic HBV (CHB) infection. We examined HBV genotype on hepatocellular carcinoma (HCC) occurrence in Alaska Native (AN) persons with CHB where five HBV genotypes are found, A2, B6, C2, D and F1. APPROACH AND RESULTS: We calculated HCC incidence per 1000 person-years of follow-up to determine which groups by age, sex, and genotype met current American Association for the Study of Liver Diseases HCC surveillance criteria. We used Poisson regression to compare HCC risk by genotype, age, sex, and Alaska region. Incidence of HCC was calculated using the sex specific AASLD cutoff recommended for the Asian population of 50 years for women and 40 years for men. HCC screening was conducted semiannually using alpha-fetoprotein levels and abdominal ultrasound. Among 1185 AN persons, median follow up was 35.1 years; 667 (63%) were male. The HBV genotype distribution was: 49% D, 18% F, 13% A, 6% C, 3% B, 0.1% H, and 12% undetermined. Sixty-three cases of HCC occurred. HCC incidence for genotype F was 5.73 per 1000 person-years of follow-up, followed by 4.77 for C, 1.28 for A, 0.47 for D and 0.00 for B. The HCC risk was higher for genotypes F (Relative rate [RR] : 12.7, 95% confidence interval [CI]: 6.1-26.4) , C (RR: 10.6, 95% CI: 4.3-26.0) and A (RR: 2.9, 95% CI: 1.0-8.0) compared to genotypes B or D. Among males < 40 years of age and females < 50 years of age, genotype F had the highest incidence (4.79/1000 person-years). CONCLUSIONS: HBV genotype was strongly associated with HCC HBV genotype should be considered in risk factor stratification. |
Changes in invasive pneumococcal disease caused by streptococcus pneumoniae serotype 1 following introduction of pcv10 and pcv13: Findings from the PSERENADE project
Bennett JC , Hetrich MK , Quesada MG , Sinkevitch JN , Knoll MD , Feikin DR , Zeger SL , Kagucia EW , Cohen AL , Ampofo K , Brandileone MCC , Bruden D , Camilli R , Castilla J , Chan G , Cook H , Cornick JE , Dagan R , Dalby T , Danis K , de Miguel S , De Wals P , Desmet S , Georgakopoulou T , Gilkison C , Grgic‐vitek M , Hammitt LL , Hilty M , Ho PL , Jayasinghe S , Kellner JD , Kleynhans J , Knol MJ , Kozakova J , Kristinsson KG , Ladhani SN , Macdonald L , Mackenzie GA , Mad’arová L , McGeer A , Mereckiene J , Morfeldt E , Mungun T , Muñoz‐almagro C , Nuorti JP , Paragi M , Pilishvili T , Puentes R , Saha SK , Khan AS , Savrasova L , Scott JA , Skoczyńska A , Suga S , Linden M , Verani JR , von Gottberg A , Winje BA , Yildirim I , Zerouali K , Hayford K , Pserenade Team . Microorganisms 2021 9 (4) Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococ-cal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) con-taining ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERE‐ NADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) compar-ing the pre‐PCV10/13 period to each post‐PCV10/13 year by site using a Bayesian multi‐level, mixed-effects Poisson regression and all‐site IRRs using a linear mixed‐effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all‐site IRR was 0.05 (95% credibility interval 0.04–0.06) for all ages, 0.05 (0.04–0.05) for <5 years of age, 0.08 (0.06–0.09) for 5–17 years, 0.06 (0.05–0.08) for 18–49 years, 0.06 (0.05–0.07) for 50–64 years, and 0.05 (0.04–0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3+0 schedule constrains generalizability and data from these settings are needed. |
Using electronic dental records to establish a surveillance system for dental decay in rural Western Alaska
Thomas TK , Lenaker D , Day GM , Wilson JC , Holck P , Newman J , Bruden D , Hennessy TW . J Public Health Dent 2020 81 (3) 224-231 OBJECTIVES: Previous surveys have demonstrated high rates of early childhood caries (ECC) in the Alaska Native (AN) population of western Alaska. There are many challenges to providing dental care in this road-less Yukon-Kuskokwim Delta region. The regional Tribal Health Organization implemented an electronic dental record (EDR) system in the late 1990s. We explored use of the EDR to establish an oral health surveillance system in children. METHODS: We contracted with EDR software developers to implement calculation of a summary count of decayed (d), missing (m) or filled (f) primary (dmft) score for each individual. We calculated the yearly average dmft scores for 2011-2019 for children aged 3 and 5 years with a comprehensive exam in a given year. We also assessed the number of children undergoing full mouth dental rehabilitation (FMDR). We used US census data population estimates for these age groups to calculate rates. RESULTS: Over the 9-year period, 2,427 3-year-old children (47 percent of all 3-year olds over this period), received a comprehensive exam; increasing from 24 percent in 2011 to 62 percent in 2019. Their average dmft score over the 9-years was 6.4 with a significant annual decline over this period. Seventy percent of AN children who turned 6 between 2015 and 2019 had received at least one FMDR. CONCLUSIONS: An oral health surveillance system has been established in western Alaska using the Electronic Dental Record. High rates of ECC and FMDR were observed. This surveillance system will allow assessments of ECC prevalence and impact of dental interventions. |
Impact of Social Distancing and Travel Restrictions on non-COVID-19 Respiratory Hospital Admissions in Young Children in Rural Alaska.
Nolen LD , Seeman S , Bruden D , Klejka J , Desnoyers C , Tiesinga J , Singleton R . Clin Infect Dis 2020 72 (12) 2196-2198 Hospitalizations due to non-COVID-19 respiratory illnesses decreased dramatically after social distancing was implemented in a high-risk population in rural Alaska. Our data from the past ten respiratory seasons show that this decline is unprecedented. This demonstrates the potential secondary benefits of implementing social distancing and travel restrictions on respiratory illnesses. |
Upper airways colonisation of Streptococcus pneumoniae in adults aged 60 years and older: A systematic review of prevalence and individual participant data meta-analysis of risk factors
Smith EL , Wheeler I , Adler H , Ferreira DM , Sá-Leão R , Abdullahi O , Adetifa I , Becker-Dreps S , Esposito S , Farida H , Kandasamy R , Mackenzie GA , Nuorti JP , Nzenze S , Madhi SA , Ortega O , Roca A , Safari D , Schaumburg F , Usuf E , Sanders EAM , Grant LR , Hammitt LL , O'Brien KL , Gounder P , Bruden DJT , Stanton MC , Rylance J . J Infect 2020 81 (4) 540-548 BACKGROUND: Colonisation with Streptococcus pneumoniae can lead to invasive pneumococcal disease and pneumonia. Pneumococcal acquisition and prevalence of colonisation are high in children. In older adults, a population susceptible to pneumococcal disease, colonisation prevalence is reported to be lower, but studies are heterogeneous. METHODS: This is a systematic review and meta-analysis of prevalence of, and risk factors for, pneumococcal colonisation in adults ≥ 60 years of age (PROSPERO #42016036891). We identified peer-reviewed studies reporting the prevalence of S. pneumoniae colonisation using MEDLINE and EMBASE (until April 2016), excluding studies of acute disease. Participant-level data on risk factors were sought from each study. FINDINGS: Of 2202 studies screened, 29 were analysable: 18 provided participant-level data (representing 6290 participants). Prevalence of detected pneumococcal colonisation was 0-39% by conventional culture methods and 3-23% by molecular methods. In a multivariate analysis, colonisation was higher in persons from nursing facilities compared with the community (odds ratio (OR) 2•30, 95% CI 1•26-4•21 and OR 7•72, 95% CI 1•15-51•85, respectively), in those who were currently smoking (OR 1•69, 95% CI 1•12-2•53) or those who had regular contact with children (OR 1•93, 95%CI 1•27-2•93). Persons living in urban areas had significantly lower carriage prevalence (OR 0•43, 95%CI 0•27-0•70). INTERPRETATION: Overall prevalence of pneumococcal colonisation in older adults was higher than expected but varied by risk factors. Future studies should further explore risk factors for colonisation, to highlight targets for focussed intervention such as pneumococcal vaccination of high-risk groups. FUNDING: No funding was required. |
Presence of antibodies against Haemophilus influenzae serotype a in Alaska prior to and after the emergence of invasive infections
McClure M , Miernyk K , Bruden D , Rudolph K , Hennessy TW , Bruce MG , Nolen LD . J Infect Dis 2020 223 (2) 326-332 BACKGROUND: Haemophilus influenzae bacteria can cause asymptomatic carriage and invasive disease. H. influenzae serotype a (Hia) is an emerging cause of invasive disease in Alaska, with greatest burden occurring among rural Alaska Native (AN) children. The first case of invasive Hia (iHia) in Alaska was reported in 2002; however, it is unclear how long the pathogen has been in Alaska. METHODS: We quantified IgG antibodies against Hia (anti-Hia) in 839 banked serum samples from Alaska residents, comparing antibody concentrations in samples drawn in the decades prior to (1980s and 1990s) and after (2000s) the emergence of iHia. We also assessed serum antibody concentration by age group, region of residence, and race. RESULTS: Anti-Hia was >0.1 microg/mL in 88.1% (348/395) and 91.0% (404/444) of samples from the decades prior and after the emergence of Hia, respectively (p=0.17). No significant differences in antibody levels were detected between people from rural and urban regions (1.55 microg/mL vs. 2.08 microg/mL, p=0.91 for age >/=5) or between AN and non-AN people (2.50 microg/mL vs 2.60 microg/mL, p=0.26). CONCLUSIONS: Our results are consistent with widespread Hia exposure in Alaska predating the first iHia case. No difference in Hia antibody prevalence was detected between populations with differing levels of invasive disease. |
Haemophilus influenzae serotype a (Hia) carriage in a small Alaska community after a cluster of invasive Hia disease, 2018
Nolen LD , Tiffany A , DeByle C , Bruden D , Thompson G , Reasonover A , Hurlburt D , Mosites E , Simons BC , Klejka J , Castrodale L , McLaughlin J , Bruce MG . Clin Infect Dis 2020 73 (2) e280-e286 BACKGROUND: Between May and July 2018, four invasive Haemophilus influenzae serotype a (iHia) infections occurred in a remote Alaska community. We performed a public health response to prevent further illness and understand Hia carriage in the community. METHODS: We collected oropharyngeal (OP) samples community-wide from untreated individuals to evaluate baseline carriage. Risk factor data was collected by interview. To prevent additional illness, we offered prophylactic rifampin to individuals in contact with iHia patients (contacts) and to all children aged <10 years. OP samples were collected again eight weeks post-rifampin distribution. Samples were tested using real-time PCR and culture. RESULTS: At baseline, Hia was carried by 4/27 (14.8%) contacts and 7/364 (1.9%) non-contacts (p<0.01). Contacts aged <10 years were more likely to carry Hia at any timepoint (11/18, 61%) than contacts aged >/=10 years (3/34, 8.8%) or non-contacts aged <10 years (2/139, 1.4%) and >/=10 years (6/276, 2.2%)(p<0.001 for all). Hia carriers were clustered in nine households (7% of total households). At the household level, carriage was associated with households with >/=1 contact (PR=5.6, CI:1.3-21.6), crowding (PR=7.7, CI:1.1-199.5) and >/=3 tobacco users (PR=5.0, CI:1.2-19.6). Sixty-six percent (40/61) of contacts and 90% (111/124) of non-contacts aged <10 years received rifampin. Elevated carriage prevalence persisted in contacts when retested eight weeks after rifampin distribution (contacts 6/25 (24%), non-contacts 2/114 (1.8%), p<0.001). CONCLUSIONS: Hia carriage prevalence was significantly higher among people who had contact with iHia patients than the general community. Rifampin prophylaxis did not result in a reduction of Hia carriage prevalence in this community. |
Increasing non-susceptibility to antibiotics within carried pneumococcal serotypes - Alaska, 2008-2015
Plumb ID , Gounder PP , Bruden DJT , Bulkow LR , Rudolph KM , Singleton RJ , Hennessy TW , Bruce MG . Vaccine 2020 38 (27) 4273-4280 BACKGROUND: In Alaska, while introduction of 13-valent pneumococcal conjugate vaccine led to declines in invasive pneumococcal disease, carriage prevalence remained stable because of replacement with non-vaccine serotypes. We assessed antibiotic non-susceptibility of carried pneumococci during serotype redistribution, determined the contributions of within-serotype shifts, and assessed factors that could explain changes in non-susceptibility. METHODS: Each year from 2008 to 2015, at multiple sites in Alaska, we collected nasopharyngeal swabs and completed surveys for a convenience sample of participants. Pneumococcal serotyping and antimicrobial susceptibility testing for penicillin and erythromycin were performed. We described changes in non-susceptibility of isolates from 2008-2011 to 2012-2015, and assessed the contributions of serotype redistribution and within-serotype changes in non-susceptibility by comparing observed data to modeled data removing either factor. We used weighted logistic regression to assess whether reported risk factors could explain changes over time in non-susceptibility within serotypes. RESULTS: From 2008-2011 to 2012-2015, the overall proportion of isolates non-susceptible to penicillin or erythromycin increased by 3%, from 23% (n = 1,183) to 26% (n = 1,589; P < 0.05). However, a decrease of 3% would be expected if serotype redistribution occurred without within-serotype changes in non-susceptibility. Standardization by either factor produced hypothetical data significantly different to observed data. Within serotypes, the average annual increase in odds of non-susceptibility to penicillin or erythromycin was 1.08 (95% CI 1.05-1.11). Recent antibiotic exposure, urban residence and increased household size of participants predicted isolate non-susceptibility but did not explain the increase over time. DISCUSSION: An overall increase in non-susceptibility of carried pneumococcal isolates to penicillin or erythromycin resulted from increases in non-susceptibility within serotypes, which outweighed a protective effect of serotype redistribution. Characterization of emerging resistant clones within carried non-vaccine serotypes, including risk factors for colonization and disease, would support disease prevention efforts and inform vaccine strategies. |
Respiratory syncytial virus and influenza hospitalizations in Alaska native adults
Nolen LD , Seeman S , Desnoyers C , DeByle C , Klejka J , Bruden D , Rudolph K , Gerber SI , Kim L , Langley G , Patel M , Englund J , Chu HY , Tiesinga J , Singleton R . J Clin Virol 2020 127 104347 BACKGROUND: Alaska Native (AN) infants from Yukon Kuskokwim Delta (YKD) have the highest U.S. infant hospitalization rate for respiratory syncytial virus (RSV). RSV can cause significant morbidity and mortality in adult populations, although the RSV burden in AN adults is unknown. Here we investigate RSV, influenza, and human metapneumovirus (hMPV) in hospitalized rural AN adults. METHODS: YKD AN adults, hospitalized with acute respiratory illness between November 2016 and October 2018 were enrolled prospectively. Nasopharyngeal (NP) swabs were tested for RSV, influenza and hMPV using polymerase chain reaction. Hospitalization rates were calculated. RESULTS: Of 251 patients who had an NP swab, RSV was detected in 8 (3.2 %), influenza in 31 (12.4 %), and hMPV in no patients. Weighted annual rates of lower respiratory tract infection (LRTI), RSV and influenza hospitalization were 192.0 (95 % CI: 176.5-208.4), 9.1 (6.0-13.3), and 42.2 (35.1-50.2) per 10,000. The most common discharge diagnosis was pneumonia (57.0 %), followed by chronic obstructive pulmonary disease (51.4 %). Ninety-eight percent (246/251) had a medical co-morbidity and 49.8 % (125/251) lived in a house with a smoker. Overall, 6.4 % (16/251) required mechanical ventilation, and 3.6 % (9/251) died during hospitalization. Only 35.7 % (66/185) of patients admitted during influenza season had received the annual influenza vaccine. DISCUSSION: We examined adult LRTI, influenza, and RSV hospitalization rates in an AN population with high infant RSV hospitalization rates. While we confirmed a high rate of hospitalization from LRTIs and influenza, we did not find a high rate due to RSV or hMPV. Improving influenza vaccination rates, and addressing co-morbidities could reduce respiratory hospitalizations. |
Presence of cagPAI genes and characterization of vacA s, i and m regions in Helicobacter pylori isolated from Alaskans and their association with clinical pathologies.
Miernyk KM , Bruden D , Rudolph KM , Hurlburt DA , Sacco F , McMahon BJ , Bruce MG . J Med Microbiol 2020 69 (2) 218-227 Introduction. Gastric cancer is a health disparity in the Alaska Native people. The incidence of Helicobacter pylori infection, a risk factor for non-cardia gastric adenocarcinoma, is also high. Gastric cancer is partially associated with the virulence of the infecting strain.Aim. To genotype the vacA s, m and i and cag pathogenicity island (cagPAI) genes in H. pylori from Alaskans and investigate associations with gastropathy.Methodology. We enrolled patients with gastritis, peptic ulcer disease (PUD) and intestinal metaplasia (IM) in 1998-2005 and patients with gastric cancer in 2011-2013. Gastric biopsies were collected and cultured and PCR was performed to detect the presence of the right and left ends of the cagPAI, the cagA, cagE, cagT and virD4 genes and to genotype the vacA s, m and i regions.Results. We recruited 263 people; 22 (8 %) had no/mild gastritis, 121 (46 %) had moderate gastritis, 40 (15%) had severe gastritis, 38 (14 %) had PUD, 30 (11 %) had IM and 12 (5 %) had gastric cancer. H. pylori isolates from 150 (57%) people had an intact cagPAI; those were associated with a more severe gastropathy (P</=0.02 for all comparisons). H. pylori isolates from 77 % of people had either the vacA s1/i1/m1 (40 %; 94/234) or s2/i2/m2 (37 %; 86/234) genotype. vacA s1/i1/m1 was associated with a more severe gastropathy (P</=0.03 for all comparisons).Conclusions. In this population with high rates of gastric cancer, we found that just over half of the H. pylori contained an intact cagPAI and 40 % had the vacA s1/i1/m1 genotype. Infection with these strains was associated with a more severe gastropathy. |
Combating gastric cancer in Alaska Native people: An expert and community symposium: Alaska Native Gastric Cancer Symposium
Nolen LD , Vindigni SM , Parsonnet J , Bruce MG , Martinson HA , Thomas TK , Sacco F , Nash S , Olnes MJ , Miernyk K , Bruden D , Ramaswamy M , McMahon B , Goodman KJ , Bass AJ , Hur C , Inoue M , Camargo MC , Cho SJ , Parnell K , Allen E , Woods T , Melkonian S . Gastroenterology 2019 158 (5) 1197-1201 Alaska Native (AN) people experience higher incidence of, and mortality from, gastric cancer compared to other U.S. populations(1, 2). Compared to the general U.S. population, gastric cancer in AN people occurs at a younger age, is diagnosed at later stages, is more evenly distributed between the sexes, and is more frequently signet-ring or diffuse histology(3). It is known that the prevalence of Helicobacter pylori (Hp) infection, a risk factor for gastric cancer, is high in AN people(4); however, high antimicrobial resistance combined with high reinfection rates in Alaska make treatment at the population level complex(5). In addition, health issues in AN people are uniquely challenging due to the extremely remote locations of many residents. A multiagency workgroup hosted a symposium in Anchorage that brought internationally-recognized experts and local leaders together to evaluate issues around gastric cancer in the AN population. The overall goal of this symposium was to identify the best strategies to combat gastric cancer in the AN population through prevention and early diagnosis. |
Ebola patient virus cycle threshold and risk of household transmission of Ebola virus
Reichler MR , Bruden D , Thomas H , Erickson BR , Knust B , Duffy N , Klena J , Hennessy T . J Infect Dis 2019 221 (5) 707-714 BACKGROUND: Identifying risk factors for household transmission of Ebola virus (EBOV) is important to guide preventive measures during Ebola outbreaks. METHODS: We enrolled all confirmed persons with EBOV disease who were the first case patient in a household from December 2014 to April 2015 in Freetown, Sierra Leone, and their household contacts. Index patients and contacts were interviewed, and contacts were followed up for 21 days to identify secondary cases. Epidemiologic data were linked to EBOV real-time reverse-transcription polymerase chain reaction cycle threshold (Ct) data from initial diagnostic specimens obtained from enrolled index case patients. RESULTS: Ct data were available for 106 (71%) of 150 enrolled index patients. Of the Ct results, 85 (80%) were from blood specimens from live patients and 21 (20%) from oral swab specimens from deceased patients. The median Ct values for blood and swab specimens were 21.0 and 24.0, respectively (P = .007). In multivariable analysis, a Ct value from blood specimens in the lowest quintile was an independent predictor of both increased risk of household transmission (P = .009) and higher secondary attack rate among household contacts (P = .03), after adjustment for epidemiologic factors. CONCLUSIONS: Our findings suggest the potential to use Ct values from acute EBOV diagnostic specimens for index patients as an early predictor of high-risk households and high-risk groups of contacts to help prioritize EBOV disease investigation and control efforts. |
Risk for invasive streptococcal infections among adults experiencing homelessness, Anchorage, Alaska, USA, 2002-2015
Mosites E , Zulz T , Bruden D , Nolen L , Frick A , Castrodale L , McLaughlin J , Van Beneden C , Hennessy TW , Bruce MG . Emerg Infect Dis 2019 25 (10) 1911-8 The risk for invasive streptococcal infection has not been clearly quantified among persons experiencing homelessness (PEH). We compared the incidence of detected cases of invasive group A Streptococcus infection, group B Streptococcus infection, and Streptococcus pneumoniae (pneumococcal) infection among PEH with that among the general population in Anchorage, Alaska, USA, during 2002-2015. We used data from the Centers for Disease Control and Prevention's Arctic Investigations Program surveillance system, the US Census, and the Anchorage Point-in-Time count (a yearly census of PEH). We detected a disproportionately high incidence of invasive streptococcal disease in Anchorage among PEH. Compared with the general population, PEH were 53.3 times as likely to have invasive group A Streptococcus infection, 6.9 times as likely to have invasive group B Streptococcus infection, and 36.3 times as likely to have invasive pneumococcal infection. Infection control in shelters, pneumococcal vaccination, and infection monitoring could help protect the health of this vulnerable group. |
Cascade of care for Alaska Native people with chronic hepatitis C virus infection: Statewide program with high linkage to care
McMahon BJ , Townshend-Bulson L , Homan C , Gounder P , Barbour Y , Hewitt A , Bruden D , Espera H , Plotnik J , Gove J , Stevenson TJ , Luna SV , Simons BC . Clin Infect Dis 2019 70 (9) 2005-2007 Most persons with chronic HCV infection in the United States are undiagnosed or linked to care. We describe a program for the management of Alaska Native patients with HCV infection utilizing a computerized registry and statewide liver clinics resulting in higher linkage to care (86%) compared to national estimates (approximately 25%). |
The relationship between previous antimicrobial use, antimicrobial resistance and treatment outcome among Alaskans treated for Helicobacter pylori infection
Bruce MG , Bruden D , Newbrough D , Hurlburt DA , Hennessy TW , Morris JM , Reasonover AL , Sacco F , McMahon BJ . GastroHep 2019 1 (4) 172-179 Background: Helicobacter pylori isolates from Alaska have demonstrated a high prevalence of antimicrobial resistance. Objective(s): To determine treatment failure in three groups, and analyse the relationship between treatment failure and antimicrobial resistance. Method(s): Antimicrobial susceptibility was determined using agar dilution and Etest. Treatment success was determined using the urea breath test 2 months after antimicrobial therapy. Result(s): Among 303 treated adult patients, 103 (34%) failed initial treatment despite a 91% compliance with medication. About 222 (73%) patients were treated with a clarithromycin-based regimen, 55 (18%) with a metronidazole-based regimen, 15 (5%) with a regimen that contained clarithromycin and metronidazole and 11 (4%) with other antimicrobials. Among 260 culture-positive patients, 156 (60%) were infected with metronidazole-resistant isolates, 74 (28%) clarithromycin-resistant, 52 (20%) clarithromycin/metronidazole-resistant, 40 (15%) levofloxacin-resistant, 11 (4%) clarithromycin/metronidazole/levofloxacin-resistant and nine (3%) amoxicillin-resistant. Overall, 34% of patients were treated with at least one antibiotic to which their infecting organism was resistant. Among patients treated with clarithromycin-based regimens, treatment failed in 72% of patients carrying clarithromycin-resistant H pylori vs 20% with clarithromycin-sensitive strains (RR = 3.7, P < 0.001). Among patients treated with metronidazole-based regimens, treatment failed in 19% of patients carrying metronidazole-resistant H pylori vs 24% with metronidazole-sensitive strains (P = 0.72). Conclusion(s): A high proportion of H pylori isolates demonstrate resistance to clarithromycin, metronidazole or levofloxacin. Over one third of H pylori-infected patients were treated with an antibiotic to which their infecting organism demonstrated resistance. Clarithromycin resistance is associated with a greater risk for failure with clarithromycin-based multidrug regimens compared to clarithromycin-sensitive; resistance to metronidazole did not affect treatment failure. |
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