Medical Blogs

May 7, 2007

Tuberculosis Bacillus Hides From The Immune System In Its Host's Fat Cells

A team from the Institut Pasteur has recently shown that the tuberculosis bacillus hides from the immune system in its host's fat cells. This formidable pathogen is protected against even the most powerful antibiotics in these cells, in which it may remain dormant for years. This discovery, published in PLoS ONE, sheds new light on possible strategies for fighting tuberculosis. Attempts to eradicate the bacillus entirely from infected individuals should take these newly identified reservoir cells into account.

Mycobacterium tuberculosis, the bacillus responsible for tuberculosis can hide, in a dormant state, in adipose cells throughout the body. The bacterium is protected in this cellular environment, to which the natural immune defences have little access, and is inaccessible to isoniazid, one of the main antibiotics used to treat tuberculosis worldwide. These results were obtained by Olivier Neyrolles* and his colleagues from the Mycobacterial Genetics Unit directed by Brigitte Gicquel at the Institut Pasteur, in collaboration with Paul Fornès, a pathologist from Hôpital Européen Georges Pompidou. They raise questions of considerable importance in the fight against tuberculosis.

Tuberculosis kills almost two million people worldwide every year and is considered by the World Health Organisation to represent a global health emergency. However, the bacillus is much more prevalent in the world's population than the statistics would lead us to believe, because only 5 to 10% of those infected actually develop tuberculosis. The bacillus may be present in a significant proportion of the population, remaining in a "dormant" state in the body, sometimes for years, and may be "reactivated" at any time. The risk of rea ctivation is particularly high in immunocompromised individuals, such as those infected with AIDS: the HIV virus and the tuberculosis bacillus make a formidable team, with each infectious agent facilitating the progression of the other.

Neyrolles' team first demonstrated, in cell and tissue cultures, that adipose cells served as a reservoir for Mycobacterium tuberculosis, and that this protected the bacillus against isoniazid. They then investigated whether the pathogen was present in adipose cells in humans. They did this by testing for traces of the genetic structure of the bacillus in samples from people considered not to be infected. Analyses were carried out on samples from deceased subjects from Mexico, where tuberculosis is endemic, and from Parisian districts reporting very few cases of tuberculosis.

The bacterium was detected in the adipose tissue of about a quarter of these people, all of whom were unaware they were infected, in both Mexico and France. These results suggest that the bacillus responsible for tuberculosis can remain protected in the adipose tissue of the body in the absence of any sign of disease.

This work has important implications for the prevention of this disease. It helps to explain how, many years after first testing positive for tuberculosis, people with no trace of the microbe in the lungs may develop some form of tuberculosis attacking the lungs, bones or genitals. It also suggests that isoniazid treatment, prescribed to the close friends and family of patients as a preventative measure, may in some cases not provide sufficient protection against the disease. This is particularly important for immunocompromised patients and for people with AIDS, for whom a secondary infection with tuberculosis bacillus may have very serious consequences.

This work highlights the importance of the search for new targeted therapeutic weapons, such as new antibiotics, which must be able to reach the dormant bacillus that has been hiding in adipose cells without our knowing it.



The following press releases refer to a selection of the upcoming articles in PLoS ONE. They are contributed by the article authors and/or their institutions. The opinions expressed do not necessarily reflect the views of the staff or the editors of PLoS ONE.

* Olivier Neyrolles belongs to URA 2172, CNRS,

Citation: Neyrolles O, Hernández-Pando R, Pietri-Rouxel F, Fornès P, Tailleux L, et al. (2006) Is Adipose Tissue a Place for Mycobacterium tuberculosis Persistence? PLoS ONE 1(1): e43. doi:10.1371/journal.pone.0000043


Contact: Bruno Baron
Public Library of Science

Faropenem Phase III Clinical Trial Stopped To Consider Exclusion Of Ketek Comparator

Replidyne, Inc. (Nasdaq: RDYN), reported today that the current phase III clinical trial comparing faropenem medoxomil (faropenem) to placebo and Ketek (telithromycin) in patients being treated for acute exacerbation of chronic bronchitis (AECB) is being temporarily stopped to consider the exclusion of the Ketek arm in the study. This decision has been made in response to the findings from the December 14 and 15, 2006 joint Advisory Committee meeting of the FDA's Anti-Infective Drug and Drug Safety and Risk Management committees that considered the benefit risk of Ketek for the indication of AECB. The Advisory Committee recommended to the FDA that the risks of Ketek outweigh the benefits of using the drug for the treatment of patients with AECB in a 17 to 2 vote.

"We believe that stopping enrollment in this trial to consider the inclusion of Ketek in the study is the appropriate and responsible action at this time to consider the new scientific evidence presented at the recent FDA Advisory Committee meeting," said Kenneth J. Collins, President and Chief Executive Officer of Replidyne. "While this action will cause a delay in obtaining the results from this AECB study we do not expect that it will impact the total time to complete the clinical program required to support the overall submission for the adult respiratory indications of Acute Bacterial Sinusitis (ABS), Community Acquired Pneumonia (CAP) and AECB. This action today will not impact the development of our pediatric clinical program for faropenem."

The phase III clinical trial for AECB is designed to compare faropenem to placebo and Ketek, an approved ketolide antibiotic. The primary objective of the study is to demonstrate superiority of faropenem to placebo. The additional comparison to Ketek represented a secondary analysis and was initially included primarily for commercial competitive reasons.

About Faropenem Medoxomil

Replidyne's lead product candidate, faropenem medoxomil (faropenem), is a novel oral community antibiotic under development for the treatment of respiratory and other community infections. Faropenem is a member of the penem sub-class within the beta-lactam class of antibiotics. Beta-lactams are generally characterized by their favorable safety and tolerability profiles, as well as their broad spectrum of activity, and as a result are typically first-line therapy in many respiratory and skin infections in adult and pediatric patients.

About Replidyne, Inc.

Replidyne is a biopharmaceutical company focused on discovering, developing, in-licensing and commercializing innovative anti-infective products. In February 2006, Replidyne entered into a partnership agreement with Forest Laboratories to develop and commercialize faropenem medoxomil in the US. An IND for Replidyne's second drug candidate, REP8839, was submitted to the FDA in May 2006. REP8839 is a topical anti-infective product under development for the treatment of skin and wound infections, and the prevention of S. aureus infections, including multiple antibiotic-resistant S. aureus (MRSA) infections, in hospital settings. Replidyne is also pursuing the development of other novel anti-infective products based on its in-house discovery research.

Safe Harbor

This press release contains plans, intentions, objectives, estimates and expectations that constitute forward-looking statements about Replidyne, Inc. that involve significant risks and uncertainties. Actual results could differ materially from those discussed due to a number of factors including, the success and timing of pre-clinical studies and clinical trials; the Company's ability to obtain and maintain regulatory approval of product candidates and the labeling under any approval that may be obtained; plans to develop and commercialize product candidates; the loss of key scientific or management personnel; the size and growth of the potential markets for the Company's product candidates and the Company's ability to serve those markets; regulatory developments in the U.S. and foreign countries; the rate and degree of market acceptance of any future products; the accuracy of Company estimates regarding expenses, future revenues and capital requirements; the Company's ability to obtain and maintain intellectual property protection for our product candidates; the successful development of the Company's sales and marketing capabilities; the success of competing drugs that are or become available; and the performance of third party manufacturers. These and additional risks and uncertainties are described more fully in the Company's Form S-1 and most recent periodic report filed with the SEC under the Securities Exchange Act of 1934. Copies of filings made with the SEC are available through the SEC's electronic data gather analysis and retrieval system (EDGAR) at All forward-looking statements made in the press release are made as of the date hereof and the Company assumes no obligation to update the forward-looking statements in the document.

Replidyne, Inc.

Adams Respiratory Therapeutics Seeks Approval For New Prescription Cough Suppressant

Adams Respiratory Therapeutics, Inc. (Nasdaq: ARxT) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for 600 mg and 1200 mg oral solid extended-release guaifenesin combination products for the treatment of cough. This new drug represents the first prescription product in Adams' current portfolio of respiratory products.

"This NDA filing is an important milestone for Adams," said president and CEO Michael J. Valentino. "Upon FDA approval of the NDA, this new drug will be our first prescription product offering and will move us closer to our vision of becoming a pre-eminent specialty pharmaceutical company, with leading products in both the over-the-counter and prescription respiratory drug markets. Secondly, it exemplifies our core strategy to build upon our successful guaifenesin business, utilizing our patented extended-release technology platform. Finally, it demonstrates our internal capabilities and technical know-how as a company to develop our own brand name prescription products." Adams has two other guaifenesin-based combination products currently under development in addition to the ongoing clinical program for erdosteine, a mucoregulator product, currently in Phase IIb.

At this time, Adams is not disclosing the name of the second active ingredient in the combination product for competitive reasons. However, the prescription market for products that treat cough is significant. Approximately 24 million prescriptions are written by physicians in the United States every year for the treatment of cough caused by the common cold, chronic bronchitis and other respiratory disorders, according to IMS Health. In addition, cough is among the most common reasons for a doctor visit, as reported by Dr. Peter Dicpinigaitis, a leading physician in the field of cough, and Fellow of the American College of Chest Physicians.

About Adams Respiratory Therapeutics, Inc.

Adams is a specialty pharmaceutical company focused on the late-stage development, commercialization and marketing of over-the-counter and prescription pharmaceuticals for the treatment of respiratory disorders.

Forward-Looking Statements

This press release contains certain "forward-looking" statements, including the Company's belief and anticipation that the FDA will approve the NDA. Such forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those in the forward-looking statements. Factors that could cause actual results to differ materially include, among others, the FDA's denial of the NDA and other risk factors set forth Item 1A. Risk Factors in the Company's Annual Report on Form 10-K for the fiscal year ended June 30, 2006. Except to the extent required by applicable securities laws, Adams is not under any obligation to (and expressly disclaims any such obligation to) update its forward-looking statements, whether as a result of new information, future events, or otherwise. All statements contained in this press release are made only as of the date of this presentation.

Adams Respiratory Therapeutics, Inc.

HHS Pandemic Influenza Implementation Plan, USA


When the U.S. Department of Health & Human Services released the Pandemic Influenza Strategic Plan Part I, a year ago, I noted: “We are better prepared today than we were yesterday, and we will be better prepared tomorrow than we are today.” Indeed, we are better prepared this year than we were one year ago - and, by continuing to implement the plans we have outlined, we will continue to improve our readiness into the future.

Since the release of our report last November, Congress has allotted $5.5 billion to support our preparation efforts, and our progress has been unprecedented. HHS, for example, has conducted pandemic flu summits in every state and territory, engaging state, local and tribal leaders and community representatives in preparation for an effective response to a pandemic. We are building our vaccine production capacity by investing in new technology, while continuing to grow our stockpile of medical interventions and supplies needed for response. We launched, a cross-governmental internet resource used by millions of Americans seeking planning and guidance tools to increase their personal and community preparedness. In addition, we facilitated and subsidized state purchase of antiviral drugs and provided millions of dollars to states to enhance their efforts to develop an exercise preparedness plan.

This substantial commitment and investment has taken us a long way down the path of preparedness - but this should not make us complacent. Though it has not yet achieved sustained transmission between humans, the H5N1 strain of avian influenza has reached dozens of countries and claimed more than one hundred-fifty lives. A pandemic remains a serious local and global threat, and there is more work to be done to prepare for it.

Preparation is a continuum. We remain fortunate that we have not yet been faced with a pandemic and can use this time to prepare. If we continue to be vigilant in our commitment to preparedness, we will be better prepared to limit the severity and duration of a pandemic. We have an opportunity to be the first generation in history to be prepared for a pandemic and to save millions of lives in this country and around the world as a result. We must renew our commitment to seize this opportunity.


Michael O. Leavitt


An influenza pandemic has the capacity to affect individuals and disrupt society on multiple levels. Pandemic influenza preparedness is a public health priority and a shared responsibility of the U.S. Department of Health and Human Services (HHS), the World Health Organization (WHO), and other Federal and non-Federal stakeholders across the country and abroad. The global nature of an influenza pandemic compels Federal, State, local, and tribal governments, communities, corporations, institutions, families, and individuals to learn about, prepare for, and collaborate in efforts to slow, mitigate, and recover from a pandemic. The development, refinement, integration, exercise, and communication of pandemic influenza plans by all stakeholders are critical components of preparedness. To this end, the Federal Government has developed the following documents to guide the Nation's pandemic influenza preparedness planning and response activities:

-- National Strategy for Pandemic Influenza: On November 1, 2005, the President released the National Strategy for Pandemic Influenza, which provides a framework for the U.S. Government's pandemic influenza preparedness and response efforts. (click here.)
-- The National Strategy for Pandemic Influenza Implementation Plan: The White House Homeland Security Council (HSC) released the National Strategy for Pandemic Influenza Implementation Plan in May 2006. This Implementation Plan provides a common frame of reference for understanding the pandemic threat and summarizes key planning assumptions to set a framework for effective action. It also proposes that Federal Departments and Agencies take specific coordinated steps to achieve the goals of the National Strategy, and outlines expectations for Federal and non-Federal stakeholders in the U.S. and abroad. This plan directs all Federal Departments to develop a pandemic influenza plan. (click here.)

-- HHS Pandemic Influenza Plan: On November 2, 2005, HHS released Parts 1 and 2 of the HHS Pandemic Influenza Plan, which serves as a strategic blueprint for all HHS pandemic influenza preparedness planning and response activities. (click here) The Plan builds on the actions and expectations set out in the National Strategy and its Implementation Plan, and updates the August 2004 draft HHS Pandemic Influenza Preparedness and Response Plan. The Plan integrates the changes made in the 2005 WHO classification of pandemic phases and its concomitant expansion of international guidance. It also is consistent with the National Response Plan (NRP) published in December 2004. It includes:

- The HHS Strategic Plan (Part 1): Part 1 outlines Federal plans and preparation for public health and medical support in the event of a pandemic. It identifies the key roles of HHS and its agencies during a pandemic, and provides planning assumptions for Federal, State, and local health and public health operations plans.

- Public Health Guidance for State and Local Partners (Part 2): Part 2 provides detailed guidance to State and local health departments in 11 key areas. Parts 1 and 2 will be regularly updated and refined, and will serve as tools for continued engagement with all stakeholders, including State and local partners.

- HHS Implementation Plan (Part 3): This document implements the strategy laid out in Parts 1 and 2 and itemizes the specific roles and responsibilities of each of HHS' operational and staff divisions in planning for and responding to a pandemic. This document identifies specific steps that operationalize and implement the actions and expectations outlined for HHS in the HSC National Strategy for Pandemic Influenza Implementation Plan. In addition, it identifies additional actions that are required for successfully accomplishing the activities laid out in both the National Strategy and the HHS Strategic Plan. This plan itemizes the specific roles and responsibilities of each HHS operational and staff division in preparing for a pandemic, not necessarily responding to one. The HHS Implementation Plan is divided into two parts as follows:

1. Part I discusses Department-wide issues such as international activities, international and domestic surveillance, public health interventions, the medical response, vaccines, antiviral drugs, diagnostic devices and personal protective equipment (PPE), communications, and State and local preparedness, all of which require coordination of efforts across HHS operational divisions. It details the specific steps needed to meet the challenges of a pandemic response and the critical capabilities as identified in both the National Strategy Implementation Plan and the HHS Strategic Plan.

2. Part II includes detailed continuity of operations plans that ensure that the essential functions of each HHS operating division are identified and maintained in the presence of an expected decrease in staffing levels during a pandemic event.

The HHS Implementation Plan is a dynamic document that will be reviewed and revised as needed as HHS efforts in pandemic preparedness mature. The plan will be tested to identify preparedness weaknesses and to promote effective implementation. Throughout this process, the pandemic influenza response will be optimized by effectively engaging partners and stakeholders during all phases of pandemic planning and response.


An influenza pandemic has the potential to cause more death and illness than any other public health threat. Although the timing, nature, and severity of the next pandemic cannot be predicted with any certainty, preparedness planning is imperative to lessen the impact of a pandemic. The unique characteristics and events of a pandemic will strain local, State, and Federal resources. For example, it is unlikely that there will be sufficient personnel, equipment, and supplies to simultaneously respond adequately in multiple areas of the country for a sustained period of time. Therefore, the minimization of social and economic disruption will require a coordinated response by the whole country. All governments, communities, and public- and private-sector stakeholders will need to anticipate and prepare for a pandemic by defining their roles and responsibilities, and developing continuity-of-operations plans. To this end, the President directed the Secretary of HHS to initiate a State and local preparedness process. HHS is actively working to help States, tribes, cities, schools, businesses, churches, individuals, and families across the country plan for a pandemic. HHS is collaborating with Governors' offices in every State to hold pandemic summits and exercises. HHS/Centers for Disease Control and Prevention (CDC) have developed checklists to aid in pandemic influenza preparations. These checklists provide specific guidance for State and local planning, businesses, health care providers, community organizations, individuals, and families. (

During a pandemic, and consistent with the National Response Plan (NRP), as head of Emergency Support Function (ESF) #8, Public Health and Medical Services, the Secretary of HHS will lead the Federal public health and medical response efforts. The HHS Pandemic Influenza Plan serves as a blueprint for all HHS pandemic influenza preparedness and response planning. Part 1, the Strategic Plan, describes a coordinated public health and medical care strategy to prepare for, and begin responding to, an influenza pandemic. Part 2, Public Health Guidance for State, Local, and Tribal Partners, provides guidance on specific aspects of pandemic influenza planning and response for the development of State, local, and tribal preparedness plans.

This document, Part 3, the HHS Implementation Plan, operationalizes the strategy described in the White House Homeland Security Council (HSC) National Strategy for Pandemic Implementation Plan by detailing Department-wide HHS pandemic preparedness actions and steps (Part I) and by outlining Agencies' continuity-of-business plans (Part II).

Part 1 - Pandemic Influenza Implementation Plan (PDF - 271 pages, 1.8MB)

Part I of the HHS Implementation Plan identifies eight cross-cutting issues that encompass many of the themes noted in the HHS Strategic Plan and Guidance for State and Local Partners. These themes include infection control, laboratory diagnostics, surveillance, health care planning, and workforce support. Each chapter outlines actions and specific steps the Department will undertake to fulfill the directives of the HSC and accomplish pandemic preparedness. The eight cross-cutting issue chapters are:

-- International Activities

-- Domestic Surveillance

-- Public Health Interventions

-- Federal Medical Response

-- Vaccines

-- Antiviral Drugs

-- Communications

-- State, Local, and Tribal Preparedness

The action steps in these eight chapters are organized by the three pillars identified in the National Strategy for Pandemic Influenza: preparedness and communication; surveillance and detection; and response and containment. The implementation of the HHS action steps is contingent upon the availability of resources.

International Activities

While a novel influenza virus could emerge anywhere in the world at any time, current concern focuses on the continued spread of avian influenza A/(H5N1), which is highly pathogenic in poultry and has caused sporadic cases of severe disease in humans.1,2,3 The emergence and intercontinental spread of avian influenza A/(H5N1) in birds underscores the interrelatedness of all countries and communities with respect to public health emergencies. Chapter 1 emphasizes the need to work in partnership with countries and provide technical assistance to enhance surveillance and response activities in low-resourced countries. International disease-surveillance efforts could permit the identification of the earliest stages of an evolution of avian or animal influenza virus into a human pathogen that is capable of human-to-human spread. The early detection of a pandemic virus will facilitate a rapid and well-orchestrated global public health containment response whose goal is the slowing or limiting of the spread of influenza. Slowing the spread of a pandemic overseas may also allow the United States to implement public health measures that might mitigate the impact of the disease when it arrives on U.S. shores. Continued surveillance, once a pandemic is underway, is important for monitoring and documenting changes in viral characteristics and pathogenesis. The HHS plan focuses on strengthening global surveillance and timely response capacity. It also emphasizes education of, and risk communication to, all stakeholders and partners.

Domestic Surveillance

Continuous surveillance, both domestic and abroad, will provide data on trends in disease activity and virus subtype circulation, and will inform policy and public health decisionmaking in the pre-pandemic and pandemic periods. Initially, domestic surveillance efforts are designed to detect influenza virus types and subtypes, including pandemic strains, circulating in the United States, and will focus on detecting initial cases and clusters of human illness. Early detection of initial cases ensures timely investigation and implementation of public health interventions to limit further spread of disease. Detection of early cases and appropriate laboratory investigation will facilitate the prompt identification of viral characteristics (antiviral susceptibility, antigenicity, transmissibility, and virulence) that can affect medical case management as well as public health response measures. It will also facilitate the development of both pre-pandemic and pandemic vaccines. Early delineation of viral characteristics will increase the likelihood that a vaccine could be available in a timely manner. Early identification of cases will also maximize the chances of delaying the spread of the pandemic across the country.

Surveillance requires that laboratory systems are in place to characterize viral subtypes, enable detection and investigation of suspected cases in a community, and detect sentinel increases in disease activity. Surveillance data will direct decisions on vaccine development, antiviral drug use, and the implementation and continuation of public health interventions, including diagnostic devices and personal protection equipment (PPE) use, to limit the spread of disease. Ongoing surveillance and the generation of real-time data can also help monitor the progression of a pandemic and the effectiveness of various interventions. Surveillance data may be used by researchers to model and project the trajectory of a pandemic.

HHS activities concentrate initially on continuing to build laboratory and epidemiologic capacity for surveillance and response; and on establishing comprehensive, integrated, timely, and sensitive surveillance systems; by building on existing systems and by initiating new systems where gaps currently exist. In addition, current HHS activities will support the faster development and deployment of new virus detection products. These rapid diagnostics may cut the time needed to confirm a human infection. If used at the point of care, rapid diagnostics could allow early recognition of infected individuals and promote the timely institution of appropriate medical care and public health measures.

Public Health Interventions

At the start of a pandemic, a vaccine may not be widely available, and the supply of antiviral drugs may be limited. Public health interventions, such as containment strategies (isolation of infected individuals and social distancing measures), could delay the introduction and/or spread of a novel, pandemic influenza virus in the United States. In the absence of available drugs, and before a pandemic vaccine is produced, public health interventions are the main defense mechanism against viral infection. The specific interventions implemented will depend on the pandemic phase. For example, early in a pandemic that emerges overseas-before the virus is detected in the United States-local containment strategies and travel-related actions (travel advisories and precautions, including entry and exit screening of persons arriving from infected countries or regions) could impede the establishment of the pandemic virus in this country. Later, after the virus is widespread in the United States, public health interventions such as closing schools, restricting public gatherings, quarantining exposed persons, isolating infected persons, and telecommuting or working from home could reduce the number of people infected with the virus. During this time, public health interventions that retard the spread of infection could mitigate the disruptive impact of a pandemic until such medical interventions became available. The HHS Plan outlines steps to develop recommendation protocols to implement and evaluate public health interventions throughout a pandemic cycle.

Federal Medical Response

An influenza pandemic will place extraordinary demands on the U.S. health care system. Efficient use of existing medical resources and expedient deployment of Federal medical assets, including personnel, are crucial in addressing the medical surge requirements imposed by a pandemic. Because the provision of health care is almost entirely a local responsibility, planning at the State and local level is essential for pandemic preparedness. Integration of the medical response across the local, State, and Federal levels becomes critical to optimize the use of scarce medical resources. HHS is working with its State, local, and tribal partners to increase surge capacity of medical materiel and personnel.

For the most efficient use of medical resources, effective response plans must be developed and tested at all levels. Plans must include a functional command structure consistent with the National Incident Management System (NIMS), a regional approach to the stockpiling and distribution of medical materiel, and a schedule of exercises for evaluating the effectiveness of the plans. Guidelines must be developed and disseminated to all partners. These guidelines should offer approaches for the allocation of scarce resources and the altering of medical care such that scarce resources are applied to benefit the greatest number of those in need. The success of the medical response to an influenza pandemic will be determined by how medical providers and facilities can implement interventions that enable them to meet the increased medical demands that result from a pandemic.

The HHS Implementation Plan describes specific steps to develop deployment strategies for Federal medical resources, including personnel, and steps to develop guidelines for the health care system to augment surge capacity, distribute medical resources, institute appropriate infection control measures, and review/modify standards of care without compromising clinical outcome.

Chapter 4, Federal Medical Response, primarily addresses the Federal medical response, and also addresses integrated planning across all jurisdictions. For additional preparedness guidance for State and local partners, see Part 2 of the HHS Pandemic Influenza Plan (Public Health Guidance for State and Local Partners) and Chapter 8, State, Local, and Tribal Preparedness, of this plan.


Historically, vaccination has been the most effective measure for minimizing the morbidity and mortality associated with influenza. Vaccines may also limit virus spread, and thus, the course of a pandemic. Since a pandemic vaccine can only be made once a pandemic virus is identified and isolated, it cannot be available during the early phases of a pandemic. Therefore, a pre-pandemic vaccine based on novel influenza viruses with pandemic potential that are known to be in circulation, and for which a vaccine has already been developed and stockpiled, may provide partial protection or immunologic priming of persons at high risk during the early phases of a pandemic.

When a pandemic is declared and a specific vaccine against the pandemic virus becomes available, its distribution and delivery will be a major focus of the pandemic response. Vaccines produced for a pandemic virus must be safe, produced in large quantities, delivered quickly, and be effective for the largest number of individuals possible to minimize mortality and morbidity. Thus, the rapid production and clinical evaluation of a pandemic vaccine and the tracking of its use and distribution, particularly if two or more doses are required, is an urgent priority of HHS pandemic planning and response preparations. HHS is currently working with private industry to increase the U.S. vaccine production capacity. The HHS Plan describes specific action steps HHS will take to facilitate vaccine development, production, and distribution. The Plan also identifies steps HHS will take to track vaccine efficacy and adverse events. Antiviral Drugs.

If used appropriately, antiviral drugs may limit the spread of influenza, reduce its morbidity and mortality, and thereby diminish the demands placed on the U.S. health care system during a pandemic. However, the susceptibility of the pandemic influenza virus strain to antiviral agents cannot be determined until the pandemic virus strain emerges. Assuming susceptibility, antivirals may also be used in attempts to contain small disease clusters and potentially slow the introduction and spread of the infection in and between communities. Indiscriminate use of antiviral drugs in a pandemic could deplete national and local supplies. Therefore, a comprehensive approach for the appropriate distribution and use of antiviral stocks is an essential component of HHS pandemic preparedness. The HHS Implementation Plan outlines the steps to facilitate the development, licensure/approval, production, and availability of pandemic influenza countermeasures. It also provides guidance for evaluating antiviral efficacy and developing prioritization, allocation, and distribution strategies for antiviral stockpiles.


Another critical component of HHS preparedness for an influenza pandemic is a clear communications strategy and campaign that informs the public and other stakeholders about this potential threat and provides a solid foundation of information upon which future actions can be based. To be effective, this strategy should be based on scientifically derived risk-communications principles that are developed before, during, and after an influenza pandemic. The HHS Plan outlines a communications strategy and campaign that effectively provides reliable information and guides the public-including individuals and families, the news media, health care providers, and other groups-in responding to outbreak situations appropriately by adhering to public health measures and undertaking actions that protect individuals and family members.

HHS is currently developing communications and outreach materials, messages, and procedures for implementing communications plans. In addition, HHS is developing strategies for health care providers and the public to address any psychosocial concerns. During a pandemic, HHS will provide accurate and timely information on the pandemic to the public. It will also monitor and evaluate its interventions, and will communicate lessons learned to health care providers and public health agencies on the effectiveness of clinical and public health responses.

State, Local, and Tribal Preparedness

An effective pandemic response requires planning and coordination among all levels of Government and all stakeholders. The country's success in responding to and recovering from a pandemic necessarily depends on preparedness by the State, local and tribal jurisdictions. State, local and tribal leaders will be responsible for conducting surveillance, epidemiologic investigation, disseminating information, implementing containment measures, and distributing countermeasures (vaccine and antiviral drugs). In addition, the provision of health care is almost entirely a local responsibility that is shared by both private and public sector entities. Planning for the preservation of societal functioning is also a critical local function.

Moreover, for pandemic influenza preparedness to be effective, it must be a multidisciplinary effort, engaging all stakeholders, including traditional public health and health care partners, as well as other sector partners, such as the business community, public safety and law enforcement, emergency management, education, transportation, social services, mental health and substance abuse services, public utilities, and community- and faith-based organizations. The duration, scope, and scale of the event will challenge infrastructure across most, if not all, sectors. Multi-sectored mutual aid agreements among local jurisdictions may aid in addressing the duration, scope, and scale of the pandemic.

In FY06, the U.S. Congress appropriated $350 million as part of an emergency supplemental appropriation to fund local and State preparedness. HHS is currently working with its State, local, and tribal partners to increase the health care surge capacity of medical materiel and personnel. With State Governors, HHS is co-hosting pandemic summits and exercises in every State. In addition, HHS has developed checklists to aid in community-level pandemic influenza preparations. These checklists provide specific guidance for State and local planning authorities, businesses, health care providers, community organizations, and individuals and families.

The HHS Implementation Plan addresses cross-cutting preparedness issues for which the Department will provide further assistance for State, local and tribal pandemic preparedness. This assistance includes the development of guidelines and operational plans for the distribution of available supplies of pandemic vaccine and antiviral drugs.

Part II

HHS provides and operates many essential services and programs for individuals across the United States. Disruption of business and community operations by a pandemic can seriously jeopardize the health and well-being of many Americans. Part II provides detailed continuity of operations plans for the Office of the Secretary (OS) and HHS agencies, including:

-- The Administration for Children and Families (ACF)
-- The Agency for Health care Research and Quality (AHRQ)
-- The Agency for Toxic Substances and Disease Registry (ATSDR)
-- The Administration on Aging (AOA)
-- The Centers for Disease Control and Prevention (CDC)
-- The Centers for Medicare and Medicaid Services (CMS)
-- The Food and Drug Administration (FDA)
-- The Health Resources and Services Administration (HRSA)
-- The Indian Health Service (IHS)
-- The National Institutes of Health (NIH)
-- The Substance Abuse and Mental Health Services Administration (SAMHSA)

In Part II, each HHS agency and the OS identify essential activities, programs, and personnel, and provide strategies to continue departmental operations in the face of significant absenteeism during a pandemic. Agencies' plans also include leadership succession, plans for the delegation of authority, and options and procedures for alternate worksites. In addition, each plan includes steps to protect the workforce (and the agency's customers) during a pandemic. Finally, each agency outlines its role and responsibilities in a coordinated inter-agency/departmental response to a pandemic.

Given its critical mission, HHS will occupy a central position in any Federal pandemic influenza response. However, a robust, comprehensive response consistent with the National Response Plan requires coordination across Federal Departments and with international partners of the United States. Moreover, an effective pandemic response that preserves human lives and societal infrastructure requires collaboration with all State, local, and tribal partners. This HHS Implementation Plan provides definitive guidance and action steps to maximize our collective efforts in preparing for and responding to pandemic influenza.


1 Chotpitayasunondh T, Ungchusak K, Hanshaoworakul W, Chunsuthiwat S, Sawanpanyalert P, Kijphati R, Lochindarat S, Srisan P, Suwan P, Osotthanakorn Y, Anantasetagoon T, Kanjanawasri S, Tanupattarachai S, Weerakul J, Chaiwirattana R, Maneerattanaporn M, Poolsavathitikool R, Chokephaibulkit K, Apisarnthanarak A, Dowell SF. Human disease from influenza A (H5N1), Thailand, 2004. Emerg Infect Dis. 2005 Feb;11(2):201-9.

2 Beigel JH, Farrar J, Han AM, Hayden FG, Hyer R, de Jong MD, Lochindarat S, Nguyen TK, Nguyen TH, Tran TH, Nicoll A, Touch S, Yuen KY; Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5. Avian influenza A (H5N1) infection in humans. N Engl J Med. 2005 Sep 29;353(13):1374-85. Review.

3 Hien TT, de Jong M, Farrar J. Avian influenza-a challenge to global health care structures. N Engl J Med. 2004 Dec 2;351(23):2363-5.

Part 1 - Pandemic Influenza Implementation Plan (PDF - 271 pages, 1.8MB)

Part 1 - Overview (PDF - 11 pages, 178KB)

Asthma Medicine Halts Pancreatic Cancer Cell Growth

A common asthma drug reduced pancreatic cancer cell growth in laboratory experiments and animal tests, a new study reports.

A protein called S100P is found in excess amounts in some cancers and is important for pancreatic cancer cell growth and survival. This protein also activates a cell surface protein receptor called RAGE that plays a role in Alzheimer disease, diabetes, and cancer.

A drug called cromolyn, an allergy and asthma treatment, has been shown to bind to proteins similar to S100P. To test cromolyn’s effects on S100P in pancreatic cancer cells, Thiruvengadam Arumugam, Ph.D., Vijaya Ramachandran, Ph.D., and Craig D. Logsdon, Ph.D., of the University of Texas M. D. Anderson Cancer Center in Houston, conducted experiments with the drug in tissue cultures and in mice with implanted pancreatic cancer.

They found that cromolyn bound to S100P, halted the activation of RAGE, and slowed cancer cell growth and survival in cell lines. In mice, the drug slowed pancreatic tumor growth and improved the effectiveness of gemcitabine, a chemotherapy drug used to treat pancreatic cancer.

"Together, these data support the further investigation of cromolyn as a possible treatment for pancreatic cancer," the authors write.

Contact: Scott Merville, M. D. Anderson Cancer Center External Communications


Other highlights in the December 20 JNCI

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at

Contact: Andrea Widener
Journal of the National Cancer Institute

April 16, 2007

WFP Resumes Programs Providing Food To People With TB, HIV In Cambodia After Receiving Aid From Spain, U.S.

The World Food Program has resumed its programs providing people living with HIV and tuberculosis in Cambodia with access to food after receiving aid from Spain and the U.S., the agency said on Thursday, the AP/International Herald Tribune reports (AP/International Herald Tribune, 2/8). Thomas Keusters, country director for WFP's Cambodia office, said recently that WFP had been "forced to suspend" the programs because of funding shortages. The programs distribute food rations to 18,000 people with TB and 70,000 people with HIV. They also ensure that HIV-positive people and people with TB needing medicine are connected with food distribution points. "The sick need food first before taking medicines," Haidy Ear-Dupuy -- advocacy manager at the Phnom Penh, Cambodia, office of World Vision -- said, adding, "You cannot take medication on an empty stomach. You must maintain a balance" (Macan-Markar, Inter Press Service, 2/6). WFP in a statement on Thursday said that Spain has provided about $650,000 and that the U.S. has provided 6,100 tons of legumes, as well as 2,370 tons of vegetable oil, for a period of three years. WFP three weeks ago announced that it needed at least $10 million to run its programs in Cambodia through July (AP/International Herald Tribune, 2/8). Keusters said WFP welcomed the donations but added that more "urgent donations" are needed (Agence France-Presse, 2/8). HIV prevalence in Cambodia is 1.6%, the highest in Southeast Asia, according to Inter Press Service (Inter Press Service, 2/6).

"Reprinted with permission from You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at The Kaiser Daily Health Policy Report is published for, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Slow-Release Morphine Reduces Level Of Intractable Cough

Slow-release morphine helped a group of patients with long-term, treatment-resistant chronic cough reduce their daily cough score levels by 40 percent.

The research results appear in the second issue for February 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Alyn H. Morice, M.D., of the Department of Academic Medicine at the University of Hull and Castle Hill Hospital in East Yorkshire, United Kingdom, and six associates enrolled 27 patients with intractable cough in an eight-week, randomized, double-blind, placebo-controlled study to test the use of slow-release morphine sulfate versus a placebo on their cough. Each phase lasted four weeks.

Morphine, derived from opium, is used in medicine as an analgesic, light anesthetic or a sedative. Although opiates have been long advocated for the suppression of cough, there are few trial data to support this recommendation. In fact, prior to this research, the use of opiates in intractable chronic cough had never been studied.

"Although acute cough is benign and self-limiting, chronic persistent cough can have a devastating effect on the quality of life of sufferers," said Dr. Morice. "This research provides evidence for the use of opiates in chronic cough."

The investigators found a "rapid and highly significant reduction by 40 percent in daily cough scores was noted by patients on slow-release morphine sulfate."

Patients responded quickly to treatment starting at five milligrams twice daily. The researchers found patients benefited the most by day five of treatment, and that this response was sustained through the remainder of the four-week period. The authors noted that the rapid response to morphine was in contrast to the absence of any effect of placebo.

The 27 participants, 18 of whom were female, were recruited from a hospital cough clinic. All had endured a chronic, persistent cough for more than three months. Their average age was 55.

During each four-week interval, patients made three visits to a clinical trial center, where they filled out a quality-of-life questionnaire on the impact of chronic cough on activities of daily living. A spirometric lung test was performed at the first visit, and lung function was measured on each subsequent visit.

In addition, each participant assessed their cough severity daily, rating it from 0 to 9 on a record card. Participants could not use other cough remedies, including over-the-counter products, during the eight-week study period.

According to the authors, one-third of the participants increased their dose of morphine sulfate from 5 mg to 10 mg twice daily during the first month; 11 percent did so in the second month; and a further 22 percent joined them in the third month. By the end of the study, two-thirds of the patients had increased their dose to 10 milligrams.

"The optimum dose in the suppression of chronic cough lies between 5 and 10 mg twice daily," said Dr. Morice, who added that the most common side effects were constipation (40 percent) and drowsiness (25 percent).

The investigators believe that the risk-benefit ratio makes low-dose morphine sulfate a credible therapeutic option for patients with chronic cough who fail other specific treatments.

Founded in 1905, the American Thoracic Society is the world's leading medical association dedicated to advancing pulmonary, critical care and sleep medicine. The Society has more than 18,000 members who prevent and fight respiratory disease around the globe, through research, education, patient care and advocacy.

American Thoracic Society
61 Broadway, 4th Floor
New York, NY 10006-2755
See you at ATS 2007-the 103rd International Conference, May 18-23 San Francisco, CA

Drug Reduces Unscheduled Trips To Doctor For Childhood Asthma Attacks

Young children with attacks of sporadic, recurring asthma who were treated with the prescription drug montelukast by their parents had fewer unscheduled trips to the doctor, missed less days from school or childcare, and caused their parents to take fewer days off work for their care.

Results from this multi-center, randomized, double-blind and placebo-controlled trial appear in the second issue for February 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Colin F. Robertson, M.D., of the Department of Respiratory Medicine at Royal Children's Hospital in Melbourne, Australia, and eight associates studied 202 children, ages 2 to 14, who were given either montelukast or placebo by their parents when needed for one year. All of the children had intermittent, doctor-diagnosed asthma.

By the end of the year-long study, the patients treated with montelukast had 163 unscheduled health resource visits for their illness, as compared with 228 in the placebo group.

"Symptoms were reduced by 14 percent, nights awakened by 8.6 percent, days off from school or childcare by 37 percent and parent time off from work by 33 percent," said Dr. Robertson.

In asthma, children's airways become chronically inflamed, with various stimuli causing episodes of airway obstruction and breathing difficulties. The disease is the most common chronic disorder of childhood and affects an estimated 6.2 million children under age 18 in the U.S.

Intermittent asthma is the most common pattern of the disease in children, accounting for attacks in 75 percent of affected youngsters.

Montelukast sodium, a specific leukotriene receptor antagonist that has been shown to be effective in children, is used to prevent mild, persistent asthma. It reduces the swelling and inflammation that tend to close airways, and relaxes the walls of the bronchial tubes, allowing more air to pass through to the lungs.

"Acute episodes of asthma in young children place a significant burden on healthcare resources," said Dr. Robertson. "Admission to the hospital for asthma in children aged 0 to 4 years is five times more common, and for those aged 5 to 14 years, twice as common as for adults who have asthma."

The study was designed to evaluate parent-initiated therapy with montelukast at the onset of each upper respiratory infection or asthma symptom. Treatment continued for a minimum of seven days or until symptoms had resolved for 24 hours.

"A key component of the study was the impact of asthma on the family, as measured by days absent from school or childcare, nights of disturbed sleep, and the number of parent days lost from work," said Dr. Robertson. "Furthermore, the strategy of parent-initiated therapy required children on average to take the study drug only 30 days per year, rather than 365, providing a further cost-benefit for the family."

The authors noted that there was no significant reduction in specialist care, hospitalizations, duration of episodes, or use of beta-agonists and prednisolone as a result of montelukast study.

An analysis of cost showed that the use of montelukast resulted in a savings of $124 Australian dollars - about $96 U.S. dollars - or 29 percent less per treated episode than the placebo controlled arm of the trial.

Founded in 1905, the American Thoracic Society is the world's leading medical association dedicated to advancing pulmonary, critical care and sleep medicine. The Society has more than 18,000 members who prevent and fight respiratory disease around the globe, through research, education, patient care and advocacy.

American Thoracic Society
61 Broadway, 4th Floor
New York, NY 10006-2755
See you at ATS 2007-the 103rd International Conference, May 18-23 San Francisco, CA

Animal Testing Reduced By Soft-Cell Approach

The new in-vitro technique pioneered by Dr Amanda Hayes and her UNSW colleagues, Shahnaz Bakand and Chris Winder, directly exposes human cells to airborne toxicants and measures cytotoxic effects. The cells are grown on a porous polyester membrane inside a small diffusion chamber and then exposed to selected toxic air pollutants. After as little as one hour's exposure, they can study cell growth and metabolism, and a range of routine toxicological endpoints.

Importantly, the toxic measurements obtained by the in vitro method, such as the amount of a contaminant needed to inhibit cell growth, mirror well-established lethal values obtained from animal studies - a long-established method in toxicological studies. "In-vitro toxicity tests can improve the scientific, economic, and ethical value of research and play a significant role in the screening of toxic chemicals and the replacement of animals," Dr Hayes says.

This research earned Hayes and her colleagues the 2006 Australian Museum Voiceless Eureka Prize for Research. This prize rewards scientists for work that has reduced the use of animals or animal products in laboratory-based research, education and testing.

Many industrial and environmental air pollutants are already known to have adverse health effects on the respiratory system of workers. Increasingly, new formulations are using tiny nanoparticles and ultrafine particulates in cosmetics, pharmaceuticals and petrochemical products. Little is known about their toxicity and safety to human health but this new category of pollutants poses possible dangers, both medically and environmentally, especially if they get airborne.

Most nanoparticles have a high surface area-to-mass ratio that can make the particles very reactive or catalytic. Being so small, they may also be able to pass through cell walls in organisms, and their reactions inside the body are relatively unknown.

"These tiny new substances are the tip of a huge chemical iceberg," says Hayes, Manager of the Chemical Safety and Applied Toxicology Laboratories at the University of New South Wales.

"Worldwide, there are millions of known chemicals, of which more than 100,000 chemical compounds are in commercial use in an unknown but extremely large number of chemical mixtures.

"Continued conventional animal toxicity testing of this large number of chemicals is simply unachievable from a scientific and economic standpoint," says Dr Hayes. "It's also unethical, given that in Australia alone, more than a million dogs, cats, rabbits, sheep, cattle, pigs and mice are used each year for toxicological testing and research." This is a drop in the ocean, compared with the animal death toll in the rest of the world.

In many inhalation studies, the toxicity of airborne chemicals is tested on laboratory animals by placing them in enclosed chambers and subjecting them to increasing concentrations of the test compounds for specified times until half of the test animals are killed. One type of test commonly used where this occurs is the LD50 test, where LD stands for lethal dose.

This heavy reliance on animal data in toxicology has long been a concern of the scientific community. Predicting the biological activities of toxic chemicals in humans by using animal data always poses uncertainty due to differences between animals and humans.

In a series of published experiments, the UNSW team has demonstrated the feasibility of their in vitro technique for:

* formaldehyde, an industrial contaminant linked to human cancer;

* nitrogen dioxide, a lung irritant that causes inflammation, pulmonary oedema, and pneumonia;

* fire combustion products, including cyanide, hydrogen sulphide, and ammonia; and,

* the volatile organic compounds (VOCs) xylene and toluene, found in solvents used by the printing, painting, and petrochemical industries.

The in vitro method "opens new possibilities for toxicity testing of industrial chemicals, environmental contaminants, workplace airborne contaminants, and fire combustion products", says Dr Hayes.

The technique has several advantages over conventional tests:

* The use of human cells (as opposed to animal cells) generates data representative of direct human chemical exposure.

* A number of human cell types such as lung, skin and liver can be used to represent target organs that are more likely to be significantly exposed or affected by air pollutants. As the respiratory system is both a site of toxicity for pulmonary toxicants, and a pathway for inhaled chemicals to reach other organs, relevant airway cells and lung cells are a major focus for inhalation studies.

* The advantage of using human cell lines and cultures is that the researcher can study toxicity mechanisms at the molecular/cellular level at an earlier stage specifically for individual chemicals, depending on their site of action within the human body without using animals. For example, when assessing the toxicity of formaldehyde, which is known to have a toxic effect on the liver, liver type cells such as hepatocytes can be chosen.

* The in vitro technique is cheap and portable, so scientists can measure immediate toxicity events, rather than waiting for toxicity to be expressed as organ or organism failure many months or even years down the track from initial exposure.

* The application of in vitro methods could open new possibilities for toxicity testing of industrial chemicals, occupational and environmental contaminants, combustion products and respiratory therapeutics and lead to a better understanding of the interactions between chemical exposure and toxic effects of single chemicals and chemical mixtures.


Contact: Dr Amanda Hayes
University of New South Wales

Medicsight Plc Receives Canadian Medical Device Licenses For ColonCAD API And LungCAD API

MGT Capital Investments, Inc. (Amex: MGT), an investment company focused on the health care information technology sector, announced today that its subsidiary, Medicsight plc, was granted medical device licenses from the Therapeutic Products Directorate (TPD) of Health Canada to begin marketing and selling Medicsight ColonCAD API and Medicsight LungCAD API.

David Sumner, chief executive officer of Medicsight plc, commented, "We are extremely pleased to receive Canadian medical device licenses for our colon and lung CAD products. These approvals build on Medicsight's recent ColonCAR(TM) market release in the United States and Europe and expands the addressable market of our CAD products for the Company and its distribution partners."

Mr. Sumner continued, "Medicsight's ColonCAD addresses many of the difficulties faced by radiologists and has been designed to help unlock the full potential of virtual colonoscopy. Our LungCAD is designed to allow radiologists to detect and segment lung nodules at early stage, enhancing treatment options and disease management. For these reasons we believe that our products will be well received by the Canadian market and we will continue to work diligently to bring this important software to radiologists around the globe."

Medicsight's CAD products are designed to be seamlessly integrated into either 3D workstations or Picture Archiving Systems (PACS) and assist radiologists in the identification of potentially fatal lesions found in the lung and polyps found in the colon. Medicsight's CAD products are designed to improve radiologist workflow and productivity.

Medicsight ColonCAD API is an image-analysis software tool designed to be used with CT (computed tomography) colonography (virtual colonoscopy) to assist radiologists in detecting and measuring potential colorectal polyps. ColonCAD has been developed using one of the world's largest CT scan databases of verified CT colonography data.

Medicsight LungCAD API is a medical imaging software tool designed to assist radiologists in the evaluation of pulmonary nodules on CT scans of the lung. Developed using one of the world's largest and most population-diverse CT scan databases, the product aims to assist radiologists in detecting lesions in the lung, such as nodules, while providing valuable information to the radiologist to assess patient images more effectively.

About MGT Capital Investments, Inc.

MGT Capital Investments is an investment company with two direct subsidiaries that focus solely on the dynamic and consolidating HCIT sector. The first subsidiary, Medicsight plc, is a leading developer of computer-aided detection (CAD) and computer assisted reader (CAR) software solutions that are validated using one of the world's largest databases of verified CT scan data. Medicsight's CAD and CAR products help clinicians identify, measure, and analyze suspicious pathology, such as colorectal polyps and lung lesions. MGT Capital Investments has invested in and controls a second subsidiary, Medicexchange plc, which operates, an online multi-vendor sales channel for diagnostic, treatment and surgery planning solutions for cardiac, thoracic, breast imaging, orthopedic, and gastro intestinal imaging. provides these solutions in a low-cost, on-demand and downloadable format, enhancing access to information and products for medical imaging professionals. Additional information can be found at

All forward-looking statements are made pursuant to the 'safe harbor' provisions of the Private Securities Litigation Reform Act of 1995. Forward- looking statements are based on current management expectations that involve risks and uncertainties that may result in such expectations not being realized. Potential risks and uncertainties include, but are not limited to, the risks described in company filings with the Securities and Exchange Commission.

MGT Capital Investments, Inc.