Primecuts – This Week In The Journals

January 12, 2015

By Jessica Yee, MD

Peer Reviewed

Welcome to the first PrimeCuts of 2015!

Welcome to the first PrimeCuts of 2015! The year started with a shout-out from 200 years ago in the form of a time capsule buried by Paul Revere and Samuel Adams in 1797 (1)! While the general public will be able to visit treasured items such as newspapers from the period, colony records and preserved coins for some time, the city plans to eventually rebury the time capsule at the Massachusetts State House for a future generation. More locally, New York City is seeing unusually few arrests and ticketing as we enter week two of silent police protest against Mayor de Blasio following the recent killing of two NYPD officers (2). While some New Yorkers rejoice in the police’s more lax attitude towards illegal parking, others are concerned about public safety with reduced patrol. Internationally, the world is now reacting to the tragedy of last week’s Charlie Hebdo massacre, where 12 people, including prominent cartoonists and staffers of the satirical magazine, were gunned down by terrorists, presumably for their provocative and controversial work (3).

While the battle against extremism and terrorism continues, the world of medicine forges on with our own war against microbes and diseases. This week’s PrimeCuts focuses on the strides made in the field of infectious disease:

A New Antibiotic Kills Pathogens without Detectable Resistance (4)

This week, Ling et al published in Nature their exciting discovery of a new antibiotic called teixobactin, made by a bacterium Eleftheria terrae not cultured previously. Teixobactin inhibits cell wall synthesis via multiple targets and, even at very low MIC, has demonstrated excellent activity against drug-resistant Gram-positive pathogens, including MRSA and VRE, M. tuberculosis, C. difficile and B. anthracis. Prolonged exposure to sub-MIC levels of teixobactin failed to develop any resistance in S. aureus. In mice, teixobactin successfully treated S. aureus and S. pneumoniae infections without noted toxicity. However, perhaps even more exciting is that the study introduced a new technology called iChip, a device that allows for simultaneous isolation and growth of bacteria in a laboratory setting by using a diluted sample of soil from the bacteria’s original growth environment. This technology allows scientists to expedite screening of bacterial isolates for antimicrobial activity and may just blow the field of antibiotic development wide open after decades of stagnation.

Effect of Ebola Progression on Transmission and Control in Liberia (5)

This month marks a-year-long fight against the current Ebola epidemic that claimed its first victim on December 28, 2013. Liberia is arguably the most effected country, with 8000 cases and 3500 mortalities to date (6). In order to improve containment and eliminate disease, Yamin et al developed a stochastic model of transmission to characterize spread and identify patients for more effective isolation. They obtained incidence and case fatality of Ebola as reported by the Liberian Ministry of Health from July to September 2014, and calculated a viral reproductive ratio (R), defined as the average number of secondary cases generated throughout the infectious period of a single case, to be 1.73 (95% CI, 1.66 to 1.83). They stratified cohorts into survivors and nonsurvivors, identified with late-phase symptoms of diarrhea, vomiting, hemorrhagic diathesis and high viral loads. The study estimates that nonsurvivors are responsible for 86% of transmission, with the highest risk 4 days after symptom onset. By timely isolation of 75% of those nonsurvivors within 4 days of symptoms, they calculated at least 74% probability of disease elimination. While very promising, the study is limited by likely underreporting of cases and fatality assessment. Even so, it highlights the need for timely isolation of symptomatic patients.

Flu is now widespread in 46 US states, CDC reports (7)

The CDC published its latest weekly update of influenza activity now reporting in at least 46 states, with the Midwest seeing a recent increase in cases, and warned that most of the northeast and west has yet to experience the full brunt of the flu season. In the past three months alone, at least 211,000 specimens were tested for flu, and 18% have tested positive. Influenza A virus (H3N2) has so far accounted for 95% of influenza cases and has been associated with more severe illness and higher mortality, especially in older people and young children, relative to H1N1 or B predominant seasons. On average, 29,000 people died from flu during H3N2 seasons, compared with 10,600 in years of non-H3N2 predominance. To compound an already severe season, most of this year’s H3N2 virus has undergone genetic drift from the H3N2 vaccine virus. Previous studies based on the 2007-08 season show that genetic drift reduces vaccine efficacy from 60% to 45%. Nonetheless, the CDC still recommends vaccination as it reduces risk of infection and complications, and confers protection against strains of viruses that may circulate later in the season. So if you haven’t done so already, get your vaccine on!

Influence of the Timing of Antiretroviral Therapy on the Potential for Normalization of Immune Status in HIV 1–Infected Individuals (8)

In this retrospective, observational cohort study, Okulicz at el investigated whether initiating early antiretroviral therapy (ART) within 12 months of estimated date of seroconversion (EDS) of HIV-1 infection increases normalization of CD4 counts (defined as greater than 900 cells/muL, the immunologic level in an HIV-negative person). They utilized the US Military HIV Natural History Study (NHS) cohort of 1119 patients to assess four primary outcomes: CD4 normalization, progression to AIDS, suppression of T-cell activation, and in vivo functional immune responses by HBV vaccine responses. The results affirmed that early ART initiation was associated with greater chance of CD4 normalization > 900 (38.4% vs 28.3%; P=.001; ARR 10%), decreased AIDS developments (hazard ratio 0.41), decreased T cell activation during ART (median percentage of CD4+HLA-DR+ EM T cells, 12.0% vs 15.6%) and increased positive seroresponses to HBV vaccine (57.1% vs 36.1%). Subgroup analysis showed that patients with lower pre-ART CD4 levels have increased chance of CD4 normalization and decreased AIDS progression with early use of ART. Although the study was not blinded and looked only at HIV-1 subtype B infection in young participants, there is a strong take-home message to consider: start ART early in HIV-positive patients.

Quadrivalent HPV Vaccination and Risk of Multiple Sclerosis and Other Demyelinating Diseases of the Central Nervous System (9)

Amidst many vaccine-related scares, concern that human papillomavirus (HPV) vaccine is associated with risk of developing multiple sclerosis (MS) and other demyelinating diseases persists despite no link seen multiple large cohort studies in Europe and USA. Scheller et al designed this observational cohort study using the Swedish and Danish nationwide registers of nearly 4 million females who received quadrivalent HPV (qHPV) vaccines from 2006 to 2013. After excluding those with a family history, they identified 322 MS cases and 3,300 cases of other demyelinating diseases, of which 73 and 90, respectively, occurred within the risk period of 2 years after vaccination. The researchers also included a self-controlled case-series within the cohort to control for time-independent factors of socioeconomic status and general health within the cases. There was no increased risk of MS (adjusted rate ratio, 0.90 [95% CI, 0.70-1.15]) or other demyelinating diseases (adjusted rate ratio, 1.00 [95% CI, 0.80-1.26]) associated with qHPV vaccination. Although the study is powered adequately, it utilizes date of disease diagnosis to classify cases, rather than symptom onset, which could lead to misclassification favoring no association, although likely insignificant. Thus, this study should lend another helpful voice to quell fears of vaccination among the general population.

In other news…

JAMA Internal Medicine published a study that suggests diabetic veterans with dual benefits from the VA and from Medicare who receive glucose tests strips from both sources receive the most tests strips (10). They are more likely to potentially overuse strips, leading to possible waste and redundancy between the two governmental systems.

In Chest, Barker et al quantified pathogenic microorganisms found in sputum samples of 120 COPD subjects via PCR, and found that bacterial load of H influenzae is associated with increased airway inflammation in stable state, while M. catarrhalis is noted to increase during exacerbations, leading to further speculation of the relationship between bacterial load changes of specific pathogens and airway inflammation at exacerbation and recovery (11).

Using negative d-dimers as a means to gauge appropriateness to withdraw anticoagulation in patients with a first unprovoked venous thromboembolism, Kearon et al argued that serial negative d-dimers justify stopping anticoagulation in women (12). Men, however, have higher rates of recurrence and d-dimer did not prove a reliable marker on which to discontinue treatment.

Finally, looking for some interesting reviews to brush up on an unfamiliar topic? Check out the review article from BMJ on heparin-induced thrombocytopenia (13), or the latest updated USPSTF guideline on thyroid dysfunction and screening (14)!

Dr. Jessica Yee is a 3rd year resident at NYU Langone Medical Center

Peer reviewed by Jessica Taff, MD, Associate Editor, Clinical Correlations, Resident Chief, NYU Langone Medical Center


1. Shoichert, C. 1795 time capsule opened, centuries after Revere and Adams buried it. CNN News Online.  Accessed Jan 6 2014

2. Goodman JD and Baker AL. For Second Week, Arrests Plunge in New York City. New York Times online.  Accessed Jan 7, 2015.

3. Erlanger S. and Bilefsky D. Police Hunt for Suspects in Paris Attack as Nation Mourns. New York Times. Online. Accessed Jan 9, 2015.

4. Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A, Schaberle TF, Hughes DE, Epstein S, Jones M, Lazarides L, Steadman VA, Cohen DR, Felix CR, Fetterman KA, Millett WP, Nitti AG, Zullo AM, Chen C and Lewis K. A new antibiotic kills pathogens without detectable resistance. Nature. Advanced online publication Jan 7, 2015.

5. Yamin D, Gertler S, Ndeffo-Mbah ML, Skrip LA, Fallah M, Nyenswah TG, et al. Effect of Ebola Progression on Transmission and Control in Liberia. Annals of Internal Medicine.162:11-17. Jan 2015.

6. CDC. 2014 Ebola Outbreaks in West Africa – Case Counts. Updated Jan 7,2015.  Accessed Jan 8, 2015.

7. CDC. FluView: A Weekly Influenza Surveillance Report.  Accessed Jan 9, 2015.

8. Okulicz JF, Le TD, Agan BK, et al. Influence of the Timing of Antiretroviral Therapy on the Potential for Normalization of Immune Status in Human Immunodeficiency Virus 1–Infected Individuals. JAMA Internal Medicine. 175(1):88-99. Jan 2015.

9.Scheller N, Svanström H, Pasternak B, et al. Quadrivalent HPV Vaccination and Risk of Multiple Sclerosis and Other Demyelinating Diseases of the Central Nervous System. JAMA. 313(1):54-61. Jan 2015.

10. Gellad WF, Zhao X, Thorpe CT, Mor MK, Good CB, Fine MJ. Dual Use of Department of Veterans Affairs and Medicare Benefits and Use of Test Strips in Veterans With Type 2 Diabetes Mellitus. JAMA Internal Medicine. 175(1):26-34. Jan 2015.

11. Barker BL, Haldar K, Patel H, et al. Association Between Pathogens Detected Using Quantitative Polymerase Chain Reaction With Airway Inflammation In Copd At Stable State And Exacerbations. Chest. 147(1):46-55. Jan 2015.

12. Kearon C, Spencer FA, O’Keeffe D, Parpia S, Schulman S, Baglin T, et al. d-Dimer Testing to Select Patients With a First Unprovoked Venous Thromboembolism Who Can Stop Anticoagulant Therapy: A Cohort Study. Annals of Internal Medicine. 162:27-34. Jan 2015.

13. Linkins LA. Clinical Review: Heparin Induced Thrombocytopenia. BMJ. Online publication. 2015; 350 doi:

14. Rugge JB, Bougatsos C, Chou R. Screening and Treatment of Thyroid Dysfunction: An Evidence Review for the U.S. Preventive Services Task Force. Annals of Internal Medicine. 162:35-45. Jan 2015.