Last data update: May 06, 2024. (Total: 46732 publications since 2009)
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Query Trace: Farrar J[original query] |
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ACIP Updates: Recommendations for Use of 20-Valent Pneumococcal Conjugate Vaccine in Children - United States, 2023
Centers for Disease Control and Prevention , Farrar J , Gierke R , Andrejko K , Ayabina D , Zielinski L , Cohen A , Kobayashi M . MMWR Morb Mortal Wkly Rep 2023 72 (39) 1072 On June 22, 2023, the Advisory Committee on Immunization Practices (ACIP) convened and approved recommendations for the use of 20-valent pneumococcal conjugate vaccine (PCV20 [Prevnar 20; Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer, Inc.]) in U.S. children. The ACIP recommendations were adopted by the CDC Director on June 27, 2023, and are official. The recommendations, underlying evidence and rationale, and clinical guidance are available (Supplementary Report, https://stacks.cdc.gov/view/cdc/133252). |
Pneumococcal vaccine for adults aged 19 years: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023
Kobayashi M , Pilishvili T , Farrar JL , Leidner AJ , Gierke R , Prasad N , Moro P , Campos-Outcalt D , Morgan RL , Long SS , Poehling KA , Cohen AL . MMWR Recomm Rep 2023 72 (3) 1-39 This report compiles and summarizes all published recommendations from CDC’s Advisory Committee on Immunization Practices (ACIP) for use of pneumococcal vaccines in adults aged ≥19 years in the United States. This report also includes updated and new clinical guidance for implementation from CDC. | | Before 2021, ACIP recommended 23-valent pneumococcal polysaccharide vaccine (PPSV23) alone (up to 2 doses), or both a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) in combination with 1–3 doses of PPSV23 in series (PCV13 followed by PPSV23), for use in U.S. adults depending on age and underlying risk for pneumococcal disease. In 2021, two new pneumococcal conjugate vaccines (PCVs), a 15-valent and a 20-valent PCV (PCV15 and PCV20), were licensed for use in U.S. adults aged ≥18 years by the Food and Drug Administration. | | ACIP recommendations specify the use of either PCV20 alone or PCV15 in series with PPSV23 for all adults aged ≥65 years and for adults aged 19–64 years with certain underlying medical conditions or other risk factors who have not received a PCV or whose vaccination history is unknown. In addition, ACIP recommends use of either a single dose of PCV20 or ≥1 dose of PPSV23 for adults who have started their pneumococcal vaccine series with PCV13 but have not received all recommended PPSV23 doses. Shared clinical decision-making is recommended regarding use of a supplemental PCV20 dose for adults aged ≥65 years who have completed their recommended vaccine series with both PCV13 and PPSV23. | | Updated and new clinical guidance for implementation from CDC includes the recommendation for use of PCV15 or PCV20 for adults who have received PPSV23 but have not received any PCV dose. The report also includes clinical guidance for adults who have received 7-valent PCV (PCV7) only and adults who are hematopoietic stem cell transplant recipients. |
Systematic Review and Meta-Analysis of the Efficacy and Effectiveness of Pneumococcal Vaccines in Adults (preprint)
Farrar JL , Childs L , Ouattara M , Akhter F , Britton A , Pilishvili T , Kobayashi M . medRxiv 2022 07 The 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) were previously recommended for adults in the United States. To help inform discussions on recently licensed 15- and 20-valent pneumococcal vaccine use among adults, we conducted a systematic review of PCV13 and PPSV23 efficacy or effectiveness. We conducted a search on PCV13 and PPSV23 efficacy or effectiveness (VE) studies against vaccine type (VT) invasive pneumococcal disease (IPD) and VT-pneumococcal pneumonia in adults. Nineteen studies were included: 13 on VT-IPD (four on PCV13, nine on PPSV23) and eight on VT- pneumococcal pneumonia (three on PCV13, four on PPSV23, one on PCV13 and PPSV23). One randomized-controlled trial (RCT) evaluated PCV13 and observed an efficacy of 75% and 45% against VT-IPD and VT-pneumococcal pneumonia, respectively. No RCTs reported PPSV23 efficacy. PCV13 effectiveness estimates against VTIPD ranged from 47% to 68%. Pooled PPSV23 effectiveness against VT-IPD was 45% (95% CI: 37%, 51%; I2=0%). PCV13 VE estimates against VT-pneumonia ranged from -2 to 46%. Pooled PPSV23 VE against VT-pneumococcal pneumonia was 18% (95% CI: -4%, 35%; I2=0%). Evidence suggests PCV13 and PPSV23 are effective against VT-IPD and VT-pneumococcal pneumonia in adults; this was used to inform PCV15 and PCV20 policy decisions. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Presence of Symptoms 6 Weeks After COVID-19 Among Vaccinated and Unvaccinated U.S. Healthcare Personnel (preprint)
Mohr NM , Plumb ID , Harland KK , Pilishvili T , Fleming-Dutra KE , Krishnadasan A , Hoth KF , Saydah SH , Mankoff Z , Haran JP , Leon ES , Talan DA , Smithline HA , Hou PC , Lee LC , Lim SC , Moran GJ , Steele MT , Beiser DG , Faine B , Nandi U , Schrading WA , Chinnock B , Chipman A , Fuentes M , LoVecchio F , Clinansmith B , Landers S , Horcher A , Wallace K , Uribe L , Pathmarajah K , Poronsky KE , Hashimoto DM , Bahamon M , Romain MSt , Kean E , Krebs E , Stubbs A , Roy S , Volturo G , Higgins A , Galbraith J , Crosby JC , Mulrow M , Gonzalez E , Gierke R , Farrar JL , Xing W , Chung Y , Yousaf A , Okaro JO , Briggs-Hagen M , Abedi GR , Nyanseor S , Watts CK . medRxiv 2022 25 Importance: Although COVID-19 vaccines protect against infection and severe disease, the role of vaccination in preventing prolonged symptoms in those with subsequent infection is unclear. Objective(s): To determine differences in symptoms stratified by prior vaccination reported by healthcare personnel (HCP) 6 weeks after onset of COVID-19, and whether there were differences in timing of return to work. Design(s): Nested cohort study within a multicenter vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. Setting(s): Health systems in 12 U.S. states. Participant(s): HCP participating in a vaccine effectiveness study were eligible for inclusion if they had confirmed COVID-19 with either verified mRNA vaccination (symptom onset =14 days after two doses) or no prior COVID-19 vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey approximately 6 weeks after illness onset. Exposures: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. Main Outcomes and Measures: Presence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work after COVID-19 illness. Result(s): Among 419 HCP with confirmed COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants (60.6%) compared with unvaccinated participants (60.6% vs. 79.1%; aRR 0.70, 95% CI 0.58-0.84). Vaccinated HCP returned to work a median 2.0 days (95% CI 1.0-3.0) sooner than unvaccinated HCP (aHR 1.37; 95% CI, 1.04-1.79). Conclusion(s): A history of two doses of COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased risk of COVID-like symptoms at 6 weeks and earlier to return to work. Vaccination is associated with improved recovery from COVID-19, in addition to preventing symptomatic infection. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Systematic review and meta-analysis of the efficacy and effectiveness of pneumococcal vaccines in adults
Farrar JL , Childs L , Ouattara M , Akhter F , Britton A , Pilishvili T , Kobayashi M . Pathogens 2023 12 (5) New pneumococcal conjugate vaccines (PCVs), 15- and 20-valent (PCV15 and PCV20), have been licensed for use among U.S. adults based on safety and immunogenicity data compared with the previously recommended 13-valent PCV (PCV13) and 23-valent pneumococcal polysaccharide vaccines (PPSV23). We conducted a systematic review of the literature on PCV13 and PPSV23 efficacy (randomized controlled trials [RCTs]) or effectiveness (observational studies) against vaccine type (PCV13 type or PPSV23 type, respectively), invasive pneumococcal disease (IPD), and pneumococcal pneumonia (PP) in adults. We utilized the search strategy from a previous systematic review of the literature published during the period from January 2016 to April 2019, and updated the search through March 2022. The certainty of evidence was assessed using the Cochrane risk-of-bias 2.0 tool and the Newcastle-Ottawa scale. When feasible, meta-analyses were conducted. Of the 5085 titles identified, 19 studies were included. One RCT reported PCV13 efficacy of 75% (PCV13-type IPD) and 45% (PCV13-type PP). Three studies each reported PCV13 effectiveness against PCV13-type IPD (range 47% to 68%) and against PCV13-type PP (range 38% to 68%). The pooled PPSV23 effectiveness was 45% (95% CI: 37%, 51%) against PPSV23-type IPD (nine studies) and 18% (95% CI: -4%, 35%) against PPSV23-type PP (five studies). Despite the heterogeneity across studies, our findings suggest that PCV13 and PPSV23 protect against VT-IPD and VT-PP in adults. |
Demographic and clinical characteristics of mpox in persons who had previously received 1 dose of JYNNEOS vaccine and in unvaccinated persons - 29 U.S. Jurisdictions, May 22-September 3, 2022
Farrar JL , Lewis NM , Houck K , Canning M , Fothergill A , Payne AB , Cohen AL , Vance J , Brassil B , Youngkin E , Glenn B , Mangla A , Kupferman N , Saunders K , Meza C , Nims D , Soliva S , Blouse B , Henderson T , Banerjee E , White B , Birn R , Stadelman AM , Abrego M , McLafferty M , Eberhart MG , Pietrowski M , DeLen SM , Creegan E , Diedhiou A , Wiedeman C , Murray-Thompson J , McCarty E , Marcinkevage J , Kocharian A , Torrone EA , Ray LC , Payne DC . MMWR Morb Mortal Wkly Rep 2022 71 (5152) 1610-1615 As of November 14, 2022, monkeypox (mpox) cases had been reported from more than 110 countries, including 29,133 cases in the United States.* Among U.S. cases to date, 95% have occurred among males (1). After the first confirmed U.S. mpox case on May 17, 2022, limited supplies of JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) were made available to jurisdictions for persons exposed to mpox. JYNNEOS vaccine was approved by the Food and Drug Administration (FDA) in 2019 as a 2-dose series (0.5 mL per dose, administered subcutaneously) to prevent smallpox and mpox disease.() On August 9, 2022, FDA issued an emergency use authorization to allow administration of JYNNEOS vaccine by intradermal injection (0.1 mL per dose) (2). A previous report on U.S. mpox cases during July 31-September 3, 2022, suggested that 1 dose of vaccine offers some protection against mpox (3). This report describes demographic and clinical characteristics of cases occurring 14 days after receipt of 1 dose of JYNNEOS vaccine and compares them with characteristics of cases among unvaccinated persons with mpox and with the vaccine-eligible vaccinated population in participating jurisdictions. During May 22-September 3, 2022, among 14,504 mpox cases reported from 29 participating U.S. jurisdictions,() 6,605 (45.5%) had available vaccination information and were included in the analysis. Among included cases, 276 (4.2%) were among persons who had received 1 dose of vaccine 14 days before illness onset. Mpox cases that occurred in these vaccinated persons were associated with lower percentage of hospitalization (2.1% versus 7.5%), fever, headache, malaise, myalgia, and chills, compared with cases in unvaccinated persons. Although 1 dose of JYNNEOS vaccine offers some protection from disease, mpox infection can occur after receipt of 1 dose, and the duration of protection conferred by 1 dose is unknown. Providers and public health officials should therefore encourage persons at risk for acquiring mpox to complete the 2-dose vaccination series and provide guidance and education regarding nonvaccine-related prevention strategies (4). |
Reduced risk for Mpox after receipt of 1 or 2 doses of JYNNEOS vaccine compared with risk among unvaccinated persons - 43 U.S. Jurisdictions, July 31-October 1, 2022
Payne AB , Ray LC , Cole MM , Canning M , Houck K , Shah HJ , Farrar JL , Lewis NM , Fothergill A , White EB , Feldstein LR , Roper LE , Lee F , Kriss JL , Sims E , Spicknall IH , Nakazawa Y , Gundlapalli AV , Shimabukuro T , Cohen AL , Honein MA , Mermin J , Payne DC . MMWR Morb Mortal Wkly Rep 2022 71 (49) 1560-1564 As of October 28, 2022, a total of 28,244* monkeypox (mpox) cases have been reported in the United States during an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series (with doses administered 4 weeks apart), was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and mpox disease (2); an FDA Emergency Use Authorization issued on August 9, 2022, authorized intradermal administration of 0.1 mL per dose, increasing the number of persons who could be vaccinated with the available vaccine supply(†) (3). A previous comparison of mpox incidence during July 31-September 3, 2022, among unvaccinated, but vaccine-eligible men aged 18-49 years and those who had received ≥1 JYNNEOS vaccine dose in 32 U.S. jurisdictions, found that incidence among unvaccinated persons was 14 times that among vaccinated persons (95% CI = 5.0-41.0) (4). During September 4-October 1, 2022, a total of 205,504 persons received JYNNEOS vaccine dose 2 in the United States.(§) To further examine mpox incidence among persons who were unvaccinated and those who had received either 1 or 2 JYNNEOS doses, investigators analyzed data on 9,544 reported mpox cases among men(¶) aged 18-49 years during July 31-October 1, 2022, from 43 U.S. jurisdictions,** by vaccination status. During this study period, mpox incidence (cases per 100,000 population at risk) among unvaccinated persons was 7.4 (95% CI = 6.0-9.1) times that among persons who received only 1 dose of JYNNEOS vaccine ≥14 days earlier and 9.6 (95% CI = 6.9-13.2) times that among persons who received dose 2 ≥14 days earlier. The observed distribution of subcutaneous and intradermal routes of administration of dose 1 among vaccinated persons with mpox was not different from the expected distribution. This report provides additional data suggesting JYNNEOS vaccine provides protection against mpox, irrespective of whether the vaccine is administered intradermally or subcutaneously. The degree and durability of such protection remains unclear. Persons eligible for mpox vaccination should receive the complete 2-dose series to optimize strength of protection(††) (5). |
Incidence of monkeypox among unvaccinated persons compared with persons receiving 1 JYNNEOS vaccine vose - 32 U.S. jurisdictions, July 31-September 3, 2022
Payne AB , Ray LC , Kugeler KJ , Fothergill A , White EB , Canning M , Farrar JL , Feldstein LR , Gundlapalli AV , Houck K , Kriss JL , Lewis NM , Sims E , Smith DK , Spicknall IH , Nakazawa Y , Damon IK , Cohn AC , Payne DC . MMWR Morb Mortal Wkly Rep 2022 71 (40) 1278-1282 Human monkeypox is caused by Monkeypox virus (MPXV), an Orthopoxvirus, previously rare in the United States (1). The first U.S. case of monkeypox during the current outbreak was identified on May 17, 2022 (2). As of September 28, 2022, a total of 25,341 monkeypox cases have been reported in the United States.* The outbreak has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (3). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series with doses administered 4 weeks apart, was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and monkeypox infection (4). U.S. distribution of JYNNEOS vaccine as postexposure prophylaxis (PEP) for persons with known exposures to MPXV began in May 2022. A U.S. national vaccination strategy(†) for expanded PEP, announced on June 28, 2022, recommended subcutaneous vaccination of persons with known or presumed exposure to MPXV, broadening vaccination eligibility. FDA emergency use authorization (EUA) of intradermal administration of 0.1 mL of JYNNEOS on August 9, 2022, increased vaccine supply (5). As of September 28, 2022, most vaccine has been administered as PEP or expanded PEP. Because of the limited amount of time that has elapsed since administration of initial vaccine doses, as of September 28, 2022, relatively few persons in the current outbreak have completed the recommended 2-dose series.(§) To examine the incidence of monkeypox among persons who were unvaccinated and those who had received ≥1 JYNNEOS vaccine dose, 5,402 reported monkeypox cases occurring among males(¶) aged 18-49 years during July 31-September 3, 2022, were analyzed by vaccination status across 32 U.S. jurisdictions.** Average monkeypox incidence (cases per 100,000) among unvaccinated persons was 14.3 (95% CI = 5.0-41.0) times that among persons who received 1 dose of JYNNEOS vaccine ≥14 days earlier. Monitoring monkeypox incidence by vaccination status in timely surveillance data might provide early indications of vaccine-related protection that can be confirmed through other well-controlled vaccine effectiveness studies. This early finding suggests that a single dose of JYNNEOS vaccine provides some protection against monkeypox infection. The degree and durability of such protection is unknown, and it is recommended that people who are eligible for monkeypox vaccination receive the complete 2-dose series. |
Use of 15-valent pneumococcal conjugate vaccine among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022
Kobayashi M , Farrar JL , Gierke R , Leidner AJ , Campos-Outcalt D , Morgan RL , Long SS , Poehling KA , Cohen AL . MMWR Morb Mortal Wkly Rep 2022 71 (37) 1174-1181 The 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc, a subsidiary of Pfizer, Inc]) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Merck Sharp & Dohme LLC]) have been recommended for U.S. children, and the recommendations vary by age group and risk group (1,2). In 2021, 15-valent pneumococcal conjugate vaccine (PCV15 [Vaxneuvance, Merck Sharp & Dohme LLC]) was licensed for use in adults aged ≥18 years (3). On June 17, 2022, the Food and Drug Administration (FDA) approved an expanded usage for PCV15 to include persons aged 6 weeks-17 years, based on studies that compared antibody responses to PCV15 with those to PCV13 (4). PCV15 contains serotypes 22F and 33F (in addition to the PCV13 serotypes) conjugated to CRM197 (genetically detoxified diphtheria toxin). On June 22, 2022, CDC's Advisory Committee on Immunization Practices (ACIP) recommended use of PCV15 as an option for pneumococcal conjugate vaccination of persons aged <19 years according to currently recommended PCV13 dosing and schedules (1,2). ACIP employed the Evidence to Recommendation (EtR) Framework,* using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)(†) approach to guide its deliberations regarding use of these vaccines. Risk-based recommendations on use of PPSV23 for persons aged 2-18 years with certain underlying medical conditions(§) that increase the risk for pneumococcal disease have not changed. |
Use of 15-valent pneumococcal conjugate vaccine and 20-valent pneumococcal conjugate vaccine among U.S. Adults: Updated recommendations of the Advisory Committee on Immunization Practices - United States, 2022
Kobayashi M , Farrar JL , Gierke R , Britton A , Childs L , Leidner AJ , Campos-Outcalt D , Morgan RL , Long SS , Talbot HK , Poehling KA , Pilishvili T . MMWR Morb Mortal Wkly Rep 2022 71 (4) 109-117 In 2021, 20-valent pneumococcal conjugate vaccine (PCV) (PCV20) (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.) and 15-valent PCV (PCV15) (Merck Sharp & Dohme Corp.) were licensed by the Food and Drug Administration for adults aged ≥18 years, based on studies that compared antibody responses to PCV20 and PCV15 with those to 13-valent PCV (PCV13) (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.). Antibody responses to two additional serotypes included in PCV15 were compared to corresponding responses after PCV13 vaccination, and antibody responses to seven additional serotypes included in PCV20 were compared with those to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) (Merck Sharp & Dohme Corp.). On October 20, 2021, the Advisory Committee on Immunization Practices (ACIP) recommended use of either PCV20 alone or PCV15 in series with PPSV23 for all adults aged ≥65 years, and for adults aged 19-64 years with certain underlying medical conditions or other risk factors* who have not previously received a PCV or whose previous vaccination history is unknown. ACIP employed the Evidence to Recommendation (EtR) framework,(†) using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)(§) approach to guide its deliberations regarding use of these vaccines. Before this, PCV13 and PPSV23 were recommended for use for U.S. adults and the recommendations varied by age and risk groups. This was simplified in the new recommendations. |
Effectiveness of mRNA Covid-19 Vaccine among U.S. Health Care Personnel.
Pilishvili T , Gierke R , Fleming-Dutra KE , Farrar JL , Mohr NM , Talan DA , Krishnadasan A , Harland KK , Smithline HA , Hou PC , Lee LC , Lim SC , Moran GJ , Krebs E , Steele MT , Beiser DG , Faine B , Haran JP , Nandi U , Schrading WA , Chinnock B , Henning DJ , Lovecchio F , Lee J , Barter D , Brackney M , Fridkin SK , Marceaux-Galli K , Lim S , Phipps EC , Dumyati G , Pierce R , Markus TM , Anderson DJ , Debes AK , Lin MY , Mayer J , Kwon JH , Safdar N , Fischer M , Singleton R , Chea N , Magill SS , Verani JR , Schrag SJ . N Engl J Med 2021 385 (25) e90 BACKGROUND: The prioritization of U.S. health care personnel for early receipt of messenger RNA (mRNA) vaccines against severe acute respiratory disease coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), allowed for the evaluation of the effectiveness of these new vaccines in a real-world setting. METHODS: We conducted a test-negative case-control study involving health care personnel across 25 U.S. states. Cases were defined on the basis of a positive polymerase-chain-reaction (PCR) or antigen-based test for SARS-CoV-2 and at least one Covid-19-like symptom. Controls were defined on the basis of a negative PCR test for SARS-CoV-2, regardless of symptoms, and were matched to cases according to the week of the test date and site. Using conditional logistic regression with adjustment for age, race and ethnic group, underlying conditions, and exposures to persons with Covid-19, we estimated vaccine effectiveness for partial vaccination (assessed 14 days after receipt of the first dose through 6 days after receipt of the second dose) and complete vaccination (assessed ≥7 days after receipt of the second dose). RESULTS: The study included 1482 case participants and 3449 control participants. Vaccine effectiveness for partial vaccination was 77.6% (95% confidence interval [CI], 70.9 to 82.7) with the BNT162b2 vaccine (Pfizer-BioNTech) and 88.9% (95% CI, 78.7 to 94.2) with the mRNA-1273 vaccine (Moderna); for complete vaccination, vaccine effectiveness was 88.8% (95% CI, 84.6 to 91.8) and 96.3% (95% CI, 91.3 to 98.4), respectively. Vaccine effectiveness was similar in subgroups defined according to age (<50 years or ≥50 years), race and ethnic group, presence of underlying conditions, and level of patient contact. Estimates of vaccine effectiveness were lower during weeks 9 through 14 than during weeks 3 through 8 after receipt of the second dose, but confidence intervals overlapped widely. CONCLUSIONS: The BNT162b2 and mRNA-1273 vaccines were highly effective under real-world conditions in preventing symptomatic Covid-19 in health care personnel, including those at risk for severe Covid-19 and those in racial and ethnic groups that have been disproportionately affected by the pandemic. (Funded by the Centers for Disease Control and Prevention.). |
Interim Estimates of Vaccine Effectiveness of Pfizer-BioNTech and Moderna COVID-19 Vaccines Among Health Care Personnel - 33 U.S. Sites, January-March 2021.
Pilishvili T , Fleming-Dutra KE , Farrar JL , Gierke R , Mohr NM , Talan DA , Krishnadasan A , Harland KK , Smithline HA , Hou PC , Lee LC , Lim SC , Moran GJ , Krebs E , Steele M , Beiser DG , Faine B , Haran JP , Nandi U , Schrading WA , Chinnock B , Henning DJ , LoVecchio F , Nadle J , Barter D , Brackney M , Britton A , Marceaux-Galli K , Lim S , Phipps EC , Dumyati G , Pierce R , Markus TM , Anderson DJ , Debes AK , Lin M , Mayer J , Babcock HM , Safdar N , Fischer M , Singleton R , Chea N , Magill SS , Verani J , Schrag S . MMWR Morb Mortal Wkly Rep 2021 70 (20) 753-758 Throughout the COVID-19 pandemic, health care personnel (HCP) have been at high risk for exposure to SARS-CoV-2, the virus that causes COVID-19, through patient interactions and community exposure (1). The Advisory Committee on Immunization Practices recommended prioritization of HCP for COVID-19 vaccination to maintain provision of critical services and reduce spread of infection in health care settings (2). Early distribution of two mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) to HCP allowed assessment of the effectiveness of these vaccines in a real-world setting. A test-negative case-control study is underway to evaluate mRNA COVID-19 vaccine effectiveness (VE) against symptomatic illness among HCP at 33 U.S. sites across 25 U.S. states. Interim analyses indicated that the VE of a single dose (measured 14 days after the first dose through 6 days after the second dose) was 82% (95% confidence interval [CI] = 74%-87%), adjusted for age, race/ethnicity, and underlying medical conditions. The adjusted VE of 2 doses (measured ≥7 days after the second dose) was 94% (95% CI = 87%-97%). VE of partial (1-dose) and complete (2-dose) vaccination in this population is comparable to that reported from clinical trials and recent observational studies, supporting the effectiveness of mRNA COVID-19 vaccines against symptomatic disease in adults, with strong 2-dose protection. |
Use of Real-Time PCR for Chlamydia psittaci Detection in Human Specimens During an Outbreak of Psittacosis - Georgia and Virginia, 2018.
McGovern OL , Kobayashi M , Shaw KA , Szablewski C , Gabel J , Holsinger C , Drenzek C , Brennan S , Milucky J , Farrar JL , Wolff BJ , Benitez AJ , Thurman KA , Diaz MH , Winchell JM , Schrag S . MMWR Morb Mortal Wkly Rep 2021 70 (14) 505-509 Psittacosis is typically a mild febrile respiratory illness caused by infection with the bacterium Chlamydia psittaci and usually transmitted to humans by infected birds (1). On average, 11 psittacosis cases per year were reported in the United States during 2000-2017. During August-October 2018, the largest U.S. psittacosis outbreak in 30 years (82 cases identified*) occurred in two poultry slaughter plants, one each in Virginia and Georgia, that shared source farms (2). CDC used C. psittaci real-time polymerase chain reaction (PCR) to test 54 human specimens from this outbreak. This was the largest number of human specimens from a single outbreak ever tested for C. psittaci using real-time PCR, which is faster and more sensitive than commercially available serologic tests. This represented a rare opportunity to assess the utility of multiple specimen types for real-time PCR detection of C. psittaci. C. psittaci was detected more frequently in lower respiratory specimens (59% [10 of 17]) and stool (four of five) than in upper respiratory specimens (7% [two of 28]). Among six patients with sputum and nasopharyngeal swabs tested, C. psittaci was detected only in sputum in five patients. Cycle threshold (Ct) values suggested bacterial load was higher in lower respiratory specimens than in nasopharyngeal swabs. These findings support prioritizing lower respiratory specimens for real-time PCR detection of C. psittaci. Stool specimens might also have utility for diagnosis of psittacosis. |
Limited added value of oropharyngeal swabs for detecting pneumococcal carriage in adults
Farrar JL , Odiembo H , Odoyo A , Bigogo G , Kim L , Lessa FC , Feikin DR , Breiman RF , Whitney CG , Carvalho MG , Pimenta FC . Open Forum Infect Dis 2020 7 (9) ofaa368 We compared pneumococcal isolation rates and evaluated the benefit of using oropharyngeal (OP) specimens in addition to nasopharyngeal (NP) specimens collected from adults in rural Kenya. Of 846 adults, 52.1% were colonized; pneumococci were detected from both NP and OP specimens in 23.5%, NP only in 22.9%, and OP only in 5.7%. Ten-valent pneumococcal conjugate vaccine strains were detected from both NP and OP in 3.4%, NP only in 4.1%, and OP only in 0.7%. Inclusion of OP swabs increased carriage detection by 5.7%; however, the added cost of collecting and processing OP specimens may justify exclusion from future carriage studies among adults. |
Characterization of pneumococcal meningitis before and after introduction of 13-valent pneumococcal conjugate vaccine in Niger, 2010-2018
Ousmane S , Kobayashi M , Seidou I , Issaka B , Sharpley S , Farrar JL , Whitney CG , Ouattara M . Vaccine 2020 38 (23) 3922-3929 Pneumococcal meningitis in the African meningitis belt is primarily caused by Streptococcus pneumoniae serotype 1, a serotype contained in the 13-valent pneumococcal conjugate vaccine (PCV13). In 2014, Niger introduced PCV13 with doses given at 6, 10, and 14 weeks of age. We leveraged existing meningitis surveillance data to describe pneumococcal meningitis trends in Niger. As a national reference laboratory for meningitis, Centre de Recherche Medicale et Sanitaire (CERMES) receives cerebrospinal fluid specimens from suspected bacterial meningitis cases and performs confirmatory testing for an etiology by culture or polymerase chain reaction (PCR). Specimens with S. pneumoniae detection during 2010-2018 were sent to the Centers for Disease Control and Prevention for serotyping by sequential triplex real-time PCR. Specimens that were non-typeable by real-time PCR underwent serotyping by conventional multiplex PCR. We tested differences in the distribution of pneumococcal serotypes before (2010-2012) and after (2016-2018) PCV13 introduction. During January 2010 to December 2018, CERMES received 16,155 specimens; 5,651 (35%) had bacterial etiology confirmed. S. pneumoniae accounted for 13.2% (744/5,651); 53.1% (395/744) were serotyped. During 2010-12, PCV13-associated serotypes (VT) constituted three-fourths of serotyped pneumococcus-positive specimens; this proportion declined in all age groups in 2016-18, most substantially in children aged < 5 years (74.0% to 28.1%; P < 0.05). Among persons aged >/= 5 years, VT constituted > 50% of pneumococcal meningitis after PCV13 introduction; serotype 1 remained the most common VT among persons aged >/= 5 years, but not among those < 5 years. VT as a group caused a smaller proportion of reported pneumococcal meningitis cases after PCV13 introduction in Niger. Serotype 1, however, remains the major cause of pneumococcal meningitis in older children and adults. Different vaccination strategies, such as changing the infant vaccination schedule or extending vaccine coverage to older children and adults, are needed, in addition to stronger surveillance. |
Impact of 10-valent pneumococcal conjugate vaccine introduction on pneumococcal carriage and antibiotic susceptibility patterns among children aged <5 years and adults with human immunodeficiency virus infection: Kenya, 2009-2013
Kobayashi M , Bigogo G , Kim L , Mogeni OD , Conklin LM , Odoyo A , Odiembo H , Pimenta F , Ouma D , Harris AM , Odero K , Milucky JL , Ouma A , Aol G , Audi A , Onyango C , Cosmas L , Jagero G , Farrar JL , da Gloria Carvalho M , Whitney CG , Breiman RF , Lessa FC . Clin Infect Dis 2020 70 (5) 814-826 BACKGROUND: Kenya introduced 10-valent pneumococcal conjugate vaccine (PCV10) among children <1 year in 2011 with catch-up vaccination among children 1-4 years in some areas. We assessed changes in pneumococcal carriage and antibiotic susceptibility patterns in children <5 years and adults. METHODS: During 2009-2013, we performed annual cross-sectional pneumococcal carriage surveys in 2 sites: Kibera (children <5 years) and Lwak (children <5 years, adults). Only Lwak had catch-up vaccination. Nasopharyngeal and oropharyngeal (adults only) swabs underwent culture for pneumococci; isolates were serotyped. Antibiotic susceptibility testing was performed on isolates from 2009 and 2013; penicillin nonsusceptible pneumococci (PNSP) was defined as penicillin-intermediate or -resistant. Changes in pneumococcal carriage by age (<1 year, 1-4 years, adults), site, and human immunodeficiency virus (HIV) status (adults only) were calculated using modified Poisson regression, with 2009-2010 as baseline. RESULTS: We enrolled 2962 children (2073 in Kibera, 889 in Lwak) and 2590 adults (2028 HIV+, 562 HIV-). In 2013, PCV10-type carriage was 10.3% (Lwak) to 14.6% (Kibera) in children <1 year and 13.8% (Lwak) to 18.7% (Kibera) in children 1-4 years. This represents reductions of 60% and 63% among children <1 year and 52% and 60% among children 1-4 years in Kibera and Lwak, respectively. In adults, PCV10-type carriage decreased from 12.9% to 2.8% (HIV+) and from 11.8% to 0.7% (HIV-). Approximately 80% of isolates were PNSP, both in 2009 and 2013. CONCLUSIONS: PCV10-type carriage declined in children <5 years and adults post-PCV10 introduction. However, PCV10-type and PNSP carriage persisted in children regardless of catch-up vaccination. |
A financial model for team-based opioid use disorder treatment
Farrar M , White Z , Hulkower S , Fagan EB , Wilson CG . J Am Board Fam Med 2020 33 (1) 124-128 INTRODUCTION: Opioid use disorder (OUD) affects 2 million Americans, yet many patients do not receive treatment. Lack of team-based care is a common barrier for office-based opioid treatment (OBOT). In 2015, we started OBOT in a family medicine practice. Based on our experiences, we developed a financial model for hiring a team member to provide nonbillable OBOT services through revenue from increased patient volume. METHODS: We completed a retrospective chart review from July 2015 to December 2016 to determine the average difference in medical visits per patient per month pre-OBOT versus post-OBOT. Secondary outcomes were the percentage of visits coded as a Level 3, Level 4, and Level 5, and the percentage of patients with Medicaid, private insurance, or self pay. With this information, we extrapolated to build a financial model to hire a team member to support OBOT. RESULTS: Twenty-three patients received OBOT during the study period. There was a net increase of 1.93 visits per patient per month (P < .001). Fourteen patients were insured by Medicaid, 7 had private insurance, and 2 were self pay. Twenty-three percent of OBOT visits were Level 3, 69% were Level 4, and 8% were Level 5. Assuming all visits were reimbursed by Medicaid and accounting for 20% cost of business, treating 1 existing patient for 1 year would generate $1,439. Treating 1 new patient would generate $1,677. CONCLUSIONS: In a fee-for-service model, the revenue generated from increased medical visits can offset the cost of hiring a team member to support nonbillable OBOT services. |
Impact of 13-valent pneumococcal conjugate vaccine on meningitis and pneumonia hospitalizations in children aged <5 years in Senegal, 2010-2016
Faye PM , Sonko MA , Diop A , Thiongane A , Ba ID , Spiller M , Ndiaye O , Dieye B , Mwenda JM , Sow AI , Diop B , Diallo A , Farrar JL . Clin Infect Dis 2019 69 S66-s71 BACKGROUND: Senegal introduced a 13-valent pneumococcal conjugate vaccine (PCV13) in October 2013, given at 6, 10, and 14 weeks of age. We document trends of meningitis and pneumonia after the PCV13 introduction. METHODS: From October 2010-October 2016, hospitalization data for clinical meningitis and pneumonia in children aged <5 years were collected from logbooks at a large, tertiary, pediatric hospital in Dakar. We used a set of predetermined keywords to define hospitalizations for extraction from hospital registers. We conducted a time-series analysis and compared hospitalizations before and after the PCV13 introduction, accounting for seasonality. The initial PCV13 uptake period (October 2013-September 2014) was considered to be transitional and was excluded. RESULTS: Over the 7-year period, 1836 and 889 hospitalizations with a discharge diagnosis of pneumonia and meningitis, respectively, occurred in children aged <5 years. In children aged <12 months, a small, significant reduction in pneumonia was observed post-PCV13 (-3.8%, 95% confidence interval [CI] -1.5 to -5.9%). No decline was observed among children aged 12-59 months (-0.7%, 95% CI -0.8 to 2.2%). Meningitis hospitalizations remained stable for children aged <12 months (1.8%, 95% CI -0.9 to 4.4%) and 12-59 months (-0.5%, 95% CI -3.6 to 2.6%). CONCLUSIONS: We used data from 1 hospital to detect a small, significant reduction in all-cause pneumonia hospitalizations 2 years post-PCV13 introduction in infants; the same trend was not measurable in children aged 12-59 months or in meningitis cases. There is a need for continued surveillance to assess the long-term impact of sustained PCV13 use and to monitor how pneumococcus is causing disease in the meningitis belt. |
Meningitis outbreak caused by vaccine-preventable bacterial pathogens - northern Ghana, 2016
Aku FY , Lessa FC , Asiedu-Bekoe F , Balagumyetime P , Ofosu W , Farrar J , Ouattara M , Vuong JT , Issah K , Opare J , Ohene SA , Okot C , Kenu E , Ameme DK , Opare D , Abdul-Karim A . MMWR Morb Mortal Wkly Rep 2017 66 (30) 806-810 Bacterial meningitis is a severe, acute infection of the fluid surrounding the brain and spinal cord that can rapidly lead to death. Even with recommended antibiotic treatment, up to 25% of infected persons in Africa might experience neurologic sequelae.. Three regions in northern Ghana (Upper East, Northern, and Upper West), located in the sub-Saharan "meningitis belt" that extends from Senegal to Ethiopia, experienced periodic outbreaks of meningitis before introduction of serogroup A meningococcal conjugate vaccine (MenAfriVac) in 2012 . During December 9, 2015-February 16, 2016, a total of 432 suspected meningitis cases were reported to health authorities in these three regions. The Ghana Ministry of Health, with assistance from CDC and other partners, tested cerebrospinal fluid (CSF) specimens from 286 patients. In the first 4 weeks of the outbreak, a high percentage of cases were caused by Streptococcus pneumoniae; followed by an increase in cases caused by Neisseria meningitidis, predominantly serogroup W. These data facilitated Ghana's request to the International Coordinating Group* for meningococcal polysaccharide ACW vaccine, which was delivered to persons in the most affected districts. Rapid identification of the etiologic agent causing meningitis outbreaks is critical to inform targeted public health and clinical interventions, including vaccination, clinical management, and contact precautions. |
Case-control vaccine effectiveness studies: Data collection, analysis and reporting results
Verani JR , Baqui AH , Broome CV , Cherian T , Cohen C , Farrar JL , Feikin DR , Groome MJ , Hajjeh RA , Johnson HL , Madhi SA , Mulholland K , O'Brien KL , Parashar UD , Patel MM , Rodrigues LC , Santosham M , Scott JA , Smith PG , Sommerfelt H , Tate JE , Victor JC , Whitney CG , Zaidi AK , Zell ER . Vaccine 2017 35 (25) 3303-3308 The case-control methodology is frequently used to evaluate vaccine effectiveness post-licensure. The results of such studies provide important insight into the level of protection afforded by vaccines in a 'real world' context, and are commonly used to guide vaccine policy decisions. However, the potential for bias and confounding are important limitations to this method, and the results of a poorly conducted or incorrectly interpreted case-control study can mislead policies. In 2012, a group of experts met to review recent experience with case-control studies evaluating vaccine effectiveness; we summarize the recommendations of that group regarding best practices for data collection, analysis, and presentation of the results of case-control vaccine effectiveness studies. Vaccination status is the primary exposure of interest, but can be challenging to assess accurately and with minimal bias. Investigators should understand factors associated with vaccination as well as the availability of documented vaccination status in the study context; case-control studies may not be a valid method for evaluating vaccine effectiveness in settings where many children lack a documented immunization history. To avoid bias, it is essential to use the same methods and effort gathering vaccination data from cases and controls. Variables that may confound the association between illness and vaccination are also important to capture as completely as possible, and where relevant, adjust for in the analysis according to the analytic plan. In presenting results from case-control vaccine effectiveness studies, investigators should describe enrollment among eligible cases and controls as well as the proportion with no documented vaccine history. Emphasis should be placed on confidence intervals, rather than point estimates, of vaccine effectiveness. Case-control studies are a useful approach for evaluating vaccine effectiveness; however careful attention must be paid to the collection, analysis and presentation of the data in order to best inform evidence-based vaccine policies. |
Case-control vaccine effectiveness studies: Preparation, design, and enrollment of cases and controls
Verani JR , Baqui AH , Broome CV , Cherian T , Cohen C , Farrar JL , Feikin DR , Groome MJ , Hajjeh RA , Johnson HL , Madhi SA , Mulholland K , O'Brien KL , Parashar UD , Patel MM , Rodrigues LC , Santosham M , Scott JA , Smith PG , Sommerfelt H , Tate JE , Victor JC , Whitney CG , Zaidi AK , Zell ER . Vaccine 2017 35 (25) 3295-3302 Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide policy-relevant data on vaccine performance under 'real world' conditions, contributing to the evidence base to support and sustain introduction of new vaccines. However, case-control studies do not measure the impact of vaccine introduction on disease at a population level, and are subject to bias and confounding, which may lead to inaccurate results that can misinform policy decisions. In 2012, a group of experts met to review recent experience with case-control studies evaluating the effectiveness of several vaccines; here we summarize the recommendations of that group regarding best practices for planning, design and enrollment of cases and controls. Rigorous planning and preparation should focus on understanding the study context including healthcare-seeking and vaccination practices. Case-control vaccine effectiveness studies are best carried out soon after vaccine introduction because high coverage creates strong potential for confounding. Endpoints specific to the vaccine target are preferable to non-specific clinical syndromes since the proportion of non-specific outcomes preventable through vaccination may vary over time and place, leading to potentially confusing results. Controls should be representative of the source population from which cases arise, and are generally recruited from the community or health facilities where cases are enrolled. Matching of controls to cases for potential confounding factors is commonly used, although should be reserved for a limited number of key variables believed to be linked to both vaccination and disease. Case-control vaccine effectiveness studies can provide information useful to guide policy decisions and vaccine development, however rigorous preparation and design is essential. |
Multistate outbreak of Escherichia coli O157:H7 infections associated with consumption of fresh spinach: United States, 2006
Sharapov UM , Wendel AM , Davis JP , Keene WE , Farrar J , Sodha S , Hyytia-Trees E , Leeper M , Gerner-Smidt P , Griffin PM , Braden C . J Food Prot 2016 79 (12) 2024-2030 During September to October, 2006, state and local health departments and the Centers for Disease Control and Prevention investigated a large, multistate outbreak of Escherichia coli O157:H7 infections. Case patients were interviewed regarding specific foods consumed and other possible exposures. E. coli O157:H7 strains isolated from human and food specimens were subtyped using pulsed-field gel electrophoresis and multiple-locus variable-number tandem repeat analyses (MLVA). Two hundred twenty-five cases (191 confirmed and 34 probable) were identified in 27 states; 116 (56%) case patients were hospitalized, 39 (19%) developed hemolytic uremic syndrome, and 5 (2%) died. Among 176 case patients from whom E. coli O157:H7 with the outbreak genotype (MLVA outbreak strain) was isolated and who provided details regarding spinach exposure, 161 (91%) reported fresh spinach consumption during the 10 days before illness began. Among 116 patients who provided spinach brand information, 106 (91%) consumed bagged brand A. E. coli O157:H7 strains were isolated from 13 bags of brand A spinach collected from patients' homes; isolates from 12 bags had the same MLVA pattern. Comprehensive epidemiologic and laboratory investigations associated this large multistate outbreak of E. coli O157:H7 infections with consumption of fresh bagged spinach. MLVA, as a supplement to pulsed-field gel electrophoresis genotyping of case patient isolates, was important to discern outbreak-related cases. This outbreak resulted in enhanced federal and industry guidance to improve the safety of leafy green vegetables and launched an independent collaborative approach to produce safety research in 2007. |
Assessment of traditional and improved stove use on household air pollution and personal exposures in rural western Kenya
Yip F , Christensen B , Sircar K , Naeher L , Bruce N , Pennise D , Lozier M , Pilishvili T , Loo Farrar J , Stanistreet D , Nyagol R , Muoki J , de Beer L , Sage M , Kapil V . Environ Int 2016 99 185-191 BACKGROUND: Over 40% of the world's population relies on solid fuels for heating and cooking. Use of improved biomass cookstoves (ICS) has the potential to reduce household air pollution (HAP). OBJECTIVES: As part of an evaluation to identify ICS for use in Kenya, we collected indoor air and personal air samples to assess differences between traditional cookstoves (TCS) and ICS. METHODS: We conducted a cross-over study in 2012 in two Kenyan villages; up to six different ICS were installed in 45 households during six two-week periods. Forty-eight hour kitchen measurements of fine particulate matter (PM2.5) and carbon monoxide (CO) were collected for the TCS and ICS. Concurrent personal CO measurements were conducted on the mother and one child in each household. We performed descriptive analysis and compared paired measurements between baseline (TCS only) and each ICS. RESULTS: The geometric mean of 48-hour baseline PM2.5 and CO concentrations in the kitchen was 586mug/m3 (95% CI: 460, 747) and 4.9ppm (95% CI: 4.3, 5.5), respectively. For each ICS, the geometric mean kitchen air pollutant concentration was lower than the TCS: median reductions were 38.8% (95% CI: 29.5, 45.2) for PM2.5 and 27.1% (95% CI: 17.4, 40.3) for CO, with statistically significant relationships for four ICS. We also observed a reduction in personal exposures to CO with ICS use. CONCLUSIONS: We observed a reduction in mean 48-hour PM2.5 and CO concentrations compared to the TCS; however, concentrations for both pollutants were still consistently higher than WHO air quality guidelines. Our findings illustrate that ICS tested in real-world settings can reduce exposures to HAP, but implementation of cleaner fuels and related stove technologies may also be necessary to optimize public health benefits. |
Epidemiology and risk factors for pneumonia severity and mortality in Bangladeshi children <5 years of age before 10-valent pneumococcal conjugate vaccine introduction
Saha S , Hasan M , Kim L , Farrar JL , Hossain B , Islam M , Ahmed AN , Amin MR , Hanif M , Hussain M , El-Arifeen S , Whitney CG , Saha SK . BMC Public Health 2016 16 (1) 1233 BACKGROUND: Pneumonia is the leading infectious cause of morbidity and mortality in young children in Bangladesh. We present the epidemiology of pneumonia in Bangladeshi children <5 years before 10-valent pneumococcal conjugate vaccine introduction and investigate factors associated with disease severity and mortality. METHODS: Children aged 2-59 months admitted to three Bangladeshi hospitals with pneumonia (i.e., cough or difficulty breathing and age-specific tachypnea without danger signs) or severe pneumonia (i.e., cough or difficulty breathing and ≥1 danger signs) were included. Demographic, clinical, laboratory, and vaccine history data were collected. We assessed associations between characteristics and pneumonia severity and mortality using multivariable logistic regression. RESULTS: Among 3639 Bangladeshi children with pneumonia, 61% had severe disease, and 2% died. Factors independently associated with severe pneumonia included ages 2-5 months (adjusted odds ratio [aOR] 1.60 [95% CI: 1.26-2.01]) and 6-11 months (aOR 1.31 [1.10-1.56]) relative to 12-59 months, low weight for age (aOR 1.22 [1.04-1.42]), unsafe drinking water source (aOR 2.00 [1.50-2.69]), higher paternal education (aOR 1.34 [1.15-1.57]), higher maternal education (aOR 0.74 [0.64-0.87]), and being fully vaccinated for age with pentavalent vaccination (aOR 0.64 [0.51-0.82]). Increased risk of pneumonia mortality was associated with age <12 months, low weight for age, unsafe drinking water source, lower paternal education, disease severity, and having ≥1 co-morbid condition. CONCLUSIONS: Modifiable factors for severe pneumonia and mortality included low weight for age and access to safe drinking water. Improving vaccination status could decrease disease severity. |
Use of temperature sensors to determine exclusivity of improved stove use and associated household air pollution reductions in Kenya
Lozier MJ , Sircar K , Christensen B , Pillarisetti A , Pennise D , Bruce N , Stanistreet D , Naeher L , Pilishvili T , Farrar JL , Sage M , Nyagol R , Muoki J , Wofchuck T , Yip F . Environ Sci Technol 2016 50 (8) 4564-71 Household air pollution (HAP) contributes to 3.5-4 million annual deaths globally. Recent interventions using improved cookstoves (ICS) to reduce HAP have incorporated temperature sensors as stove use monitors (SUMs) to assess stove use. We deployed SUMs in an effectiveness study of 6 ICSs in 45 Kenyan rural homes. Stove were installed sequentially for 2 weeks and kitchen air monitoring was conducted for 48 h during each 2-week period. We placed SUMs on the ICSs and traditional cookstoves (TCS), and the continuous temperature data were analyzed using an algorithm to examine the number of cooking events, days of exclusive use of ICS, and how stove use patterns affect HAP. Stacking, defined as using both a TCS and an ICS in the same day, occurred on 40% of the study days, and exclusive use of the ICS occurred on 25% of study days. When researchers were not present, ICS use declined, which can have implications for long-term stove adoption in these communities. Continued use of TCSs was also associated with higher HAP levels. SUMs are a valuable tool for characterizing stove use and provide additional information to interpret HAP levels measured during ICS intervention studies. |
Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.
Wong VK , Baker S , Pickard DJ , Parkhill J , Page AJ , Feasey NA , Kingsley RA , Thomson NR , Keane JA , Weill FX , Edwards DJ , Hawkey J , Harris SR , Mather AE , Cain AK , Hadfield J , Hart PJ , Thieu NT , Klemm EJ , Glinos DA , Breiman RF , Watson CH , Kariuki S , Gordon MA , Heyderman RS , Okoro C , Jacobs J , Lunguya O , Edmunds WJ , Msefula C , Chabalgoity JA , Kama M , Jenkins K , Dutta S , Marks F , Campos J , Thompson C , Obaro S , MacLennan CA , Dolecek C , Keddy KH , Smith AM , Parry CM , Karkey A , Mulholland EK , Campbell JI , Dongol S , Basnyat B , Dufour M , Bandaranayake D , Naseri TT , Singh SP , Hatta M , Newton P , Onsare RS , Isaia L , Dance D , Davong V , Thwaites G , Wijedoru L , Crump JA , De Pinna E , Nair S , Nilles EJ , Thanh DP , Turner P , Soeng S , Valcanis M , Powling J , Dimovski K , Hogg G , Farrar J , Holt KE , Dougan G . Nat Genet 2015 47 (6) 632-9 The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species. |
Comparison of patients hospitalized with influenza A subtypes H7N9, H5N1, and 2009 pandemic H1N1
Wang C , Yu H , Horby PW , Cao B , Wu P , Yang S , Gao H , Li H , Tsang TK , Liao Q , Gao Z , Ip DK , Jia H , Jiang H , Liu B , Ni MY , Dai X , Liu F , Van Kinh N , Liem NT , Hien TT , Li Y , Yang J , Wu JT , Zheng Y , Leung GM , Farrar JJ , Cowling BJ , Uyeki TM , Li L . Clin Infect Dis 2014 58 (8) 1095-103 BACKGROUND: Influenza A(H7N9) viruses isolated from humans show features suggesting partial adaptation to mammals. To provide insights into the pathogenesis of H7N9 virus infection, we compared risk factors, clinical presentation, and progression of patients hospitalized with H7N9, H5N1, and 2009 pandemic H1N1 (pH1N1) virus infections. METHODS: We compared individual-level data from patients hospitalized with infection by H7N9 (n = 123), H5N1 (n = 119; 43 China, 76 Vietnam), and pH1N1 (n = 3486) viruses. We assessed risk factors for hospitalization after adjustment for age- and sex-specific prevalence of risk factors in the general Chinese population. RESULTS: The median age of patients with H7N9 virus infection was older than other patient groups (63 years; P < .001) and a higher proportion was male (71%; P < .02). After adjustment for age and sex, chronic heart disease was associated with an increased risk of hospitalization with H7N9 (relative risk, 9.68; 95% confidence interval, 5.24-17.9). H7N9 patients had similar patterns of leukopenia, thrombocytopenia, and elevated alanine aminotransferase, creatinine kinase, C-reactive protein, and lactate dehydrogenase to those seen in H5N1 patients, which were all significantly different from pH1N1 patients (P < .005). H7N9 patients had a longer duration of hospitalization than either H5N1 or pH1N1 patients (P < .001), and the median time from onset to death was 18 days for H7N9 (P = .002) vs 11 days for H5N1 and 15 days for pH1N1 (P = .154). CONCLUSIONS: The identification of known risk factors for severe seasonal influenza and the more protracted clinical course compared with that of H5N1 suggests that host factors are an important contributor to H7N9 severity. |
Dogma in classifying dengue disease
Farrar JJ , Hien TT , Horstick O , Hung NT , Jaenisch T , Junghanns T , Kroeger A , Laksono IS , Lum L , Martinez E , Simmons CP , Tami A , Tomashek KM , Wills BA . Am J Trop Med Hyg 2013 89 (2) 198-201 In his recent perspective entitled Dengue: the Syndromic Basis to Pathogenesis Research, Inutility of the 2009 WHO Case Definition, Halstead expresses concern that adoption of the 2009 World Health Organization (WHO) classification scheme will compromise the “analytic clarity needed to understand mechanisms underlying dengue pathophysiology, pathogenesis, treatment, and therapeutics.”1 Leaving aside the important issue of how best to resolve the long running and convoluted debate on dengue case definitions and classification, two important misconceptions need to be addressed. | First, rather than being a research tool, the 2009 WHO dengue classification scheme is primarily intended to be used by clinicians and public health specialists engaged in dealing with the ever-expanding global pandemic of dengue disease.2,3 The main objectives of the classification scheme are to improve case management by timely identification of severe or potentially severe cases, and to ensure that scarce resources are directed towards those most in need. The simplicity and sensitivity of the classification scheme should enable the complete clinical spectrum of dengue to be captured by surveillance systems and enhance the comparability of epidemiologic data gathered over time from different countries and regions. If, in addition, the new system provides a valid framework for scientific research on dengue pathogenesis, this feature should be regarded as a bonus. |
Long-term safety assessment of live attenuated tetravalent dengue vaccines: deliberations from a WHO technical consultation
Bentsi-Enchill AD , Schmitz J , Edelman R , Durbin A , Roehrig JT , Smith PG , Hombach J , Farrar J . Vaccine 2013 31 (23) 2603-9 Dengue is a rapidly growing public health threat with approximately 2.5 billion people estimated to be at risk. Several vaccine candidates are at various stages of pre-clinical and clinical development. Thus far, live dengue vaccine candidates have been administered to several thousands of volunteers and were well-tolerated, with minimal short-term safety effects reported in Phase I and Phase II clinical trials. Based on the natural history of dengue, a theoretical possibility of an increased risk of severe dengue as a consequence of vaccination has been hypothesized but not yet observed. In October 2011, the World Health Organization (WHO) convened a consultation of experts in dengue, vaccine regulation and vaccine safety to review the current scientific evidence regarding safety concerns associated with live attenuated dengue vaccines and, in particular, to consider methodological approaches for their long-term evaluation. In this paper we summarize the scientific background and methodological considerations relevant to the safety assessment of these vaccines. Careful planning and a coordinated approach to safety assessment are recommended to ensure adequate long-term evaluation of dengue vaccines that will support their introduction and continued use. |
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