PATH said that MenAfriVac, a vaccine developed through the Meningitis Vaccine Project (MVP) to protect against life-threatening meningococcal meningitis, received prequalification from the World Health Organization. The action clears the way for phased introduction of the vaccine in Africa later this year, PATH said.  Dr. Christopher J. Elias, president and CEO of PATH, commented, “Prequalification is a major milestone for MenAfriVac and MVP. This partnership between PATH and WHO is a stellar example of our mission and strategy at work. Through nine years of collaboration with a range of partners, WHO and PATH have been able to bring this vaccine from idea to reality, and we’re poised now to deliver it to the people who need it most.” PATH described meningococcal meningitis as a bacterial infection of the fluid surrounding the brain and spinal cord which is highly contagious and kills about one in ten people who get it. Even with treatment, as many as a quarter of survivors suffer permanent damage—most commonly hearing loss, mental retardation, or epilepsy. The infection causes repeated epidemics during the annual dry season in sub-Saharan Africa—a region known as “the meningitis belt.”

Dr. F. Marc LaForce, director of the Meningitis Vaccine Project, said, “At 40 cents a dose, it is a moral imperative to introduce the vaccine in meningitis belt countries, most of which are among the poorest countries in the world. It is everybody’s wish that the global health community and funding agencies will come forward to help introduce the first affordable conjugate vaccine that offers the hope to end 100 years of group A meningitis epidemics in Africa.” MenAfriVac is produced by the Serum Institute of India Ltd. (SIIL), which received marketing authorization for export and use of MenAfriVac in Africa earlier this year.

http://www.path.org/news/an100623-menafrivac.php

The WHO continues to issue weekly updates and occasional briefing notes on the H1N1 pandemic at http://www.who.int/csr/disease/swineflu/en/index.html
Pandemic (H1N1) 2009 – update 106
Weekly update
25 June 2010 — As of 20 June, worldwide more than 214 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 18209 deaths.

Situation update:
Worldwide, overall pandemic and seasonal influenza activity remains low. Active transmission of pandemic influenza virus persists in parts of the tropics, particularly in the Caribbean, West Africa, and South and Southeast Asia. Pandemic and seasonal influenza viruses have been detected only sporadically during the early part of winter in the temperate regions of the southern hemisphere. Global circulation of seasonal influenza virus type B viruses has declined substantially and persists at low levels in parts of East Asia, Central Africa, and Central America. During the past month, seasonal influenza H3N2 viruses have been detected at low levels across parts of East Africa and South America. More at: http://www.who.int/csr/don/2010_06_25/en/index.html

The IFPMA released a statement on the overall response to the 2009-10 H1N1 influenza pandemic. IFPMA noted that “from the perspective of the vaccine manufacturers, several elements of the response were particularly effective:
– High level of preparedness. For many years prior to the H1N1 outbreak, public health authorities, regulatory agencies and vaccine producers worked together on pandemic preparedness. These efforts intensified following the spread of H5N1 ‘avian’ influenza. The resulting level of preparedness allowed authorities to respond robustly to the H1N1 pandemic, in a manner that was not previously possible.
– Global co-operation and flexibility. The rapid development and testing of H1N1 vaccines presented many technical challenges, particularly in the initial stages. WHO network and industry scientists worked together, to share technical information and resolve urgent key issues, such as improving vaccine virus production yields and vaccine standardization. Industry interaction with the WHO regarding the H1N1 pandemic was focused on the development of H1N1 pandemic vaccines and on improving vaccine availability, and did not extend to pandemic alert status decision-making.
– Robust vaccine monitoring. By implementing existing surveillance plans and sharing data publicly, authorities were able to confirm rapidly the safety of H1N1 vaccines.
IFPMA also noted that “improvements to several areas of the pandemic response could strengthen future preparedness.
– Technical improvements. Production yields from initial H1N1 vaccine viruses were 1/3 to 1/2 of those achieved with seasonal strains. Therefore, processes to rapidly evaluate multiple candidate vaccine strains and to select those with the best growth potential could improve yields and increase vaccine supply. Similarly, processes to speed up reagent production and broadening the range of techniques available for vaccine standardization would accelerate vaccine availability.
– Establishing advance supply agreements. Large numbers of countries initiated negotiations for vaccine supply after the emergence of H1N1 influenza. Establishing advance supply agreements beforehand could avoid the need for complex discussions under intense time pressure during a pandemic.
– Enhancing regulatory processes. International co-operation, mutual recognition of existing regulatory approvals and reduction of bureaucracy could all accelerate vaccine availability, while maintaining robust safety standards.
– Strengthening public communications. Throughout the pandemic, vaccination rates have remained low even in target risk groups (for instance, coverage among healthcare workers reached just 37.1% in the USA by mid-January 2010(1) while a study of healthcare workers in Greece showed an acceptance rate of only 17% for pandemic vaccination(2)). In some instances, views propagated by social media may have eroded public confidence in the safety of H1N1 vaccines. Authorities need to recognize the importance of new communication channels to motivate the public to seek vaccination. It is important to emphasize the public health value and safety of vaccination, as well as the comprehensive system that is in place to evaluate and monitor vaccine safety.
1) US Centers for Disease Control and Prevention. MMWR April 2, 2010;59(12):357-362. (http://www.cdc.gov/mmwr/pdf/wk/mm5912.pdf).
2) Rachiotis G, Mouchtouri VA, Kremastinou J, Gourgoulianis K, Hadjichristodoulou C. Low acceptance of vaccination against the 2009 pandemic influenza A(H1N1) among healthcare workers in Greece. Euro Surveill. 2010;15(6): pii=19486. Available online: (http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19486)

http://www.ifpma.org/News/NewsReleaseDetail.aspx?nID=13803

The PhRMA (Pharmaceutical Research and Manufacturers of America) issued a statement regarding clinical trials conducted abroad:

“America’s biopharmaceutical research companies are proud to be among the nation’s primary economic engines. Pharmaceutical research companies lead the world in the search for new life-saving and life-enhancing medications and, in 2009 alone, invested an estimated $65.3 billion to discover and develop new medicines.

“While the number of experimental medicines in clinical testing today – more than 2,900 medicines for nearly 4,600 different indications – represents an all-time high, America’s biopharmaceutical research companies develop drugs for a worldwide market and conduct clinical trials inside and outside the U.S.

“It’s important to remember that the Food and Drug Administration (FDA) has jurisdiction over clinical trials conducted in foreign countries for drugs approved in the U.S. or being studied for approval in the U.S. The same strict regulatory standards apply to foreign trials as trials conducted domestically. Sponsors are typically in communication with the FDA throughout clinical trials – no matter where they are conducted.

“Clinical trials occur globally because we have global companies that make medicines for use around the world. Our member companies make every effort to combat diseases that are common in the developed, as well as the developing world. That can, ultimately, deliver life-saving and life-enhancing medications to patients around the world more quickly.

“Is it ethical to conduct such studies outside of the U.S.? In a word: Yes. Consistent with PhRMA’s Principles on Conduct of Clinical Trials and Communication of Clinical Trial Results, our member companies are committed to adhering to Good Clinical Practice guidelines around the world.

“In fact, PhRMA has conducted educational seminars and symposiums – at times, in conjunction with the FDA – in other countries to educate potential clinical trial principal investigators about Good Clinical Practices, ethics oversight by outside review boards, and the need to maintain the highest standards for data quality.

“Regardless of the location, however, companies seeking U.S. approval must maintain the FDA’s high standards for conducting the trial. For instance, any related trials conducted outside the U.S. must comply with FDA requirements covering Good Clinical Practices, in addition to meeting the requirements mandated in these important emerging markets.

“Clinical research is a critical element in the development of revolutionary medicines that help patients live longer, healthier lives. Through carefully controlled clinical studies, researchers thoroughly assess the safety and efficacy of new drug candidates.

“America’s pharmaceutical research and biotechnology companies have a long-standing commitment to help ensure physicians and other healthcare providers receive meaningful information from these clinical trials.

“The PhRMA Clinical Trial Principles, created in 2002 and strengthened last year, have been an invaluable guide to member companies and underscore our commitment to the safety of clinical trial participants and communication of important medical findings from clinical trials.”

http://www.phrma.org/news/news/phrma_statement_foreign_clinical_trials

The MMWR for June 25, 2010 / Vol. 59 / No. SS–7 includes: Malaria Surveillance — United States, 2008
Abstract
The majority of malaria infections in the United States occur among persons who have traveled to areas with ongoing malaria transmission. CDC received reports of 1,298 cases of malaria with an onset of symptoms in 2008 among patients in the United States, a decrease of 13.8% from the 1,505 cases reported for 2007 (p<0.001). The first documented case of simian malaria, Plasmodium knowlesi, was reported in a U.S. traveler. The highest estimated relative case rates of malaria among travelers occurred among those returning from countries in West Africa. In the majority of reported cases, U.S. civilians who acquired malaria abroad had not adhered to a chemoprophylaxis regimen that was appropriate for the country in which they acquired the infection. Any person who has been to a malarious area and who subsequently develops a fever or influenza-like symptoms should seek medical care immediately and report their travel history to the clinician; investigation should always include blood-film tests for malaria with results available immediately. Malaria infections can be fatal if not diagnosed and treated promptly.

http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5907a1.htm?s_cid=ss5907a1_w

WHO’s Department of Immunization, Vaccines and Biologicals released a call for peer-reviewers for its publications in the vaccines and/or immunization field/s. http://www.who.int/immunization/documents/peer_review_publications/en/index.html

Nature
Volume 465 Number 7301 pp985-1110  24 June 2010
http://www.nature.com/nature/current_issue.html

Special Sponsored Section: Outlook: Chagas disease

Nature
Volume 465 Number 7301 pp985-1110  24 June 2010
http://www.nature.com/nature/current_issue.html
[free full-text]

Nature | Editorial
A pandemic of hindsight?

We must learn lessons from the handling of the flu pandemic to improve future research and public-health responses to emerging diseases, but retrospective hindsight and recriminations are not the answer.

Late this week, the Council of Europe’s parliamentary assembly, a 47-member-state body that promotes democracy and human rights in Strasbourg, France, is scheduled to vote on a resolution expressing alarm over the World Health Organization’s (WHO’s) handling of the H1N1 influenza pandemic.

The council should think twice. In conversations with more than a dozen flu researchers and public-health officials from Australia, the United States, the United Kingdom and several other countries, Nature heard many objections to the conclusions of the report on which the resolution is based. Angus Nicoll, a senior influenza expert at the European Centre for Disease Prevention and Control (ECDC) in Stockholm, says that in the ECDC’s opinion: “The conclusions of the report do not fit the facts as we see them, and as are backed up by science.”

Certainly, the council’s inquiry into the pandemic started off by taking a strong angle, with a December 2009 parliamentary motion entitled ‘Faked pandemics — a threat for health’. The motion asserted that “to promote their patented drugs and vaccines against flu, pharmaceutical companies have influenced scientists and official agencies, responsible for public health standards, to alarm governments worldwide”.

Similar ideas are reiterated in the inquiry’s draft final report, which was adopted on 4 June by the council’s health committee, and which also contains the resolution to be voted on this week (see http://go.nature.com/txThYG). “Drug firms ‘encouraged world health body to exaggerate swine flu threat’,” declared Britain’s Daily Mail newspaper that day, in a typical headline.

It is this kind of response that the WHO’s defenders find so potentially damaging — not least because it can only encourage the conspiracy theories that already swirl around the pandemic, and diminish public confidence in health authorities. It is indeed vital that health authorities are transparent in their dealings with industry. But the drug industry is a necessary partner in a pandemic response, as the producer of antivirals and vaccines. It would have been irresponsible to exclude top academic experts from the decision-making just because of industrial competing interests, which do not necessarily represent conflicts of interest. Critics also tend to forget that in spring 2009 the WHO and national officials were struggling with large scientific uncertainties, and the possibility that millions of people would die if the response was inadequate (a reality that the Council of Europe report does acknowledge).

Paul Flynn, a UK Labour Member of Parliament and rapporteur of the inquiry, says he could not fully address Nature’s queries as to the accuracy of the science of some statements in the report, given the short deadline, but says he feels that these are minor and do not significantly alter its conclusions. “I will, of course consider your comments, but our concerns remain unchallenged,” he says, adding that he would have any errors corrected in the final report. He questions the criticism of the report, saying that he believes industry lobbyists are working to undermine it.

The resolution states that the council is “alarmed” about the WHO’s, the European Union’s and national governments’ handling of the pandemic, arguing that some decisions taken led to “distortion of priorities of public health services across Europe, waste of large sums of public money, and also unjustified scares and fears about health risks faced by the European public at large”. It also affirms its concern over possible “undue influence” on decisions by the pharmaceutical industry. Some of its recommendations, such as calls for greater transparency, and creating a public fund for research and trials independent of industry, are sensible. But many researchers dispute its highly critical analysis of the pandemic response, which is expanded on in an accompanying 15-page explanatory memorandum.

That said, however, there are plenty of lessons to be learned from the WHO’s response to the pandemic. Fortunately, there is at least one independent review that seems to be looking for those lessons in the right way — slowly and impartially, and without indulging in 20/20 hindsight. The 29-member panel, chaired by Harvey Fineberg, the president of the US Institute of Medicine, is due to deliver its findings at next year’s World Health Assembly. Meanwhile, several national investigations are also under way — as the flu pandemic played out, it was largely national governments, at least in the rich countries, not the WHO, that led the pandemic responses. And they have plenty of their own lessons to learn.

http://www.nature.com/nature/journal/v465/n7301/full/465985a.html

New England Journal of Medicine
Volume 362 — June 24, 2010 — Number 25
http://content.nejm.org/current.shtml

Original Articles

Fractional Doses of Inactivated Poliovirus Vaccine in Oman
A. J. Mohammed and Others [Free full-text]

ABSTRACT
Background We conducted a clinical trial of fractional doses of inactivated poliovirus vaccine administered to infants in Oman, in order to evaluate strategies for making the vaccine affordable for use in developing countries.

Methods We compared fractional doses of inactivated poliovirus vaccine (0.1 ml, representing one fifth of a full dose) given intradermally with the use of a needle-free jet injector device, with full doses of vaccine given intramuscularly, with respect to immunogenicity and reactogenicity. Infants were randomly assigned at birth to receive either a fractional dose or a full dose of inactivated poliovirus vaccine at 2, 4, and 6 months. We also administered a challenge dose of monovalent type 1 oral poliovirus vaccine at 7 months and collected stool samples before and 7 days after administration of the challenge dose.

Results A total of 400 infants were randomized, of whom 373 (93.2%) fulfilled the study requirements. No significant baseline differences between the groups were detected. Thirty days after completion of the three-dose schedule, the rates of seroconversion to types 1, 2, and 3 poliovirus were 97.3%, 95.7%, and 97.9%, respectively, in the fractional-dose group, as compared with 100% seroconversion to all serotypes in the full-dose group (P=0.01 for the comparison with respect to type 2 poliovirus; results with respect to types 1 and 3 poliovirus were not significant). The median titers were significantly lower in the fractional-dose group than in the full-dose group (P<0.001 for all three poliovirus serotypes). At 7 months, 74.8% of the infants in the fractional-dose group and 63.1% of those in full-dose group excreted type 1 poliovirus (P=0.03). Between birth and 7 months, 42 hospitalizations were reported, all related to infectious causes, anemia, or falls, with no significant difference between vaccination groups.

Conclusions These data show that fractional doses of inactivated poliovirus vaccine administered intradermally at 2, 4, and 6 months, as compared with full doses of inactivated poliovirus vaccine given intramuscularly on the same schedule, induce similar levels of seroconversion but significantly lower titers. (Current Controlled Trials number, ISRCTN17418767 [controlled-trials.com] .)

New England Journal of Medicine
Volume 362 — June 24, 2010 — Number 25
http://content.nejm.org/current.shtml

Implications of a Circulating Vaccine-Derived Poliovirus in Nigeria
H. E. Jenkins and Others [Free full-text]

ABSTRACT

Background The largest recorded outbreak of a circulating vaccine-derived poliovirus (cVDPV), detected in Nigeria, provides a unique opportunity to analyze the pathogenicity of the virus, the clinical severity of the disease, and the effectiveness of control measures for cVDPVs as compared with wild-type poliovirus (WPV).

Methods We identified cases of acute flaccid paralysis associated with fecal excretion of type 2 cVDPV, type 1 WPV, or type 3 WPV reported in Nigeria through routine surveillance from January 1, 2005, through June 30, 2009. The clinical characteristics of these cases, the clinical attack rates for each virus, and the effectiveness of oral polio vaccines in preventing paralysis from each virus were compared.

Results No significant differences were found in the clinical severity of paralysis among the 278 cases of type 2 cVDPV, the 2323 cases of type 1 WPV, and the 1059 cases of type 3 WPV. The estimated average annual clinical attack rates of type 1 WPV, type 2 cVDPV, and type 3 WPV per 100,000 susceptible children under 5 years of age were 6.8 (95% confidence interval [CI], 5.9 to 7.7), 2.7 (95% CI, 1.9 to 3.6), and 4.0 (95% CI, 3.4 to 4.7), respectively. The estimated effectiveness of trivalent oral polio vaccine against paralysis from type 2 cVDPV was 38% (95% CI, 15 to 54%) per dose, which was substantially higher than that against paralysis from type 1 WPV (13%; 95% CI, 8 to 18%), or type 3 WPV (20%; 95% CI, 12 to 26%). The more frequent use of serotype 1 and serotype 3 monovalent oral polio vaccines has resulted in improvements in vaccine-induced population immunity against these serotypes and in declines in immunity to type 2 cVDPV.

Conclusions The attack rate and severity of disease associated with the recent cVDPV identified in Nigeria are similar to those associated with WPV. International planning for the management of the risk of WPV, both before and after eradication, must include scenarios in which equally virulent and pathogenic cVDPVs could emerge

GAVI’s confirmed that it will hold its first “replenishment meeting” on 6 October in New York as its Board agreed in principle to move forward with funding for applications from 15 developing countries and also agreed in principle to call for a new round of applications to support country immunization programs, and. Donors and potential donors “will be invited to come with firm financial commitments to support GAVI’s immunisation programmes.”  GAVI said its Board “heard that it (GAVI) needs US$4.3 billion between now and 2015 if it is to continue its current programmes and roll out new vaccines against pneumococcal disease and rotavirus to more than 40 countries. This figure includes an additional US$ 2.6 billion over and above current levels of funding.”

GAVI Board Chair Mary Robinson. “Children have a right to health and we have it in our power to set them on a path to healthy and productive lives. There comes a time to stop talking and start doing. I sincerely hope that we will see donors put their money on the table. Without this funding for immunisation, the world will not reach Millennium Development Goal 4 to reduce under-five mortality by two-thirds by 2015.”  http://www.gavialliance.org/media_centre/press_releases/2010_06_18_donors_increased_funding.php

In a Financial Times (15 June 2010) article, GAVI CEO Julian Lob-Levyt, commenting on the funding shortfall, said: “The board has been pretty responsible, but we will need to raise more funding if we are to roll out vaccines as fast as planned. Did anyone anticipate the international financial crisis? We have a prioritisation strategy that will focus on having the maximum impact.” The article notes that “…to help maintain its plans, the board may seek $500M-$700M in cost savings, including a $50M cut in support it provides to the World Health Organisation, more aggressive negotiations on vaccine prices with pharmaceutical companies, and demands that richer developing countries make larger contributions to the cost of the immunisation programmes.”

http://www.ft.com/cms/s/0/6b378748-7875-11df-942a-00144feabdc0.html

A range of stakeholders formally launched a new 2010-12 polio eradication strategic plan in Geneva. Last month, the World Health Assembly “welcomed the new plan while expressing deep concern about the US$ 1.3 billion funding shortfall (out of a budget of US$ 2.6 billion) over the next three years. This financing shortfall is a serious risk to the eradication of polio – activities are already being cut back or postponed due to a lack of funds.” The meting was co-hosted by WHO and UNICEF and attended by the Ministers of Health of Nigeria, Afghanistan, Angola and Senegal, among a number of other senior health ministry officials; existing and potential funders; vaccine manufacturers, and key partner organizations.  Tachi Yamada, president of global health at the Bill & Melinda Gates Foundation, commented, “Polio eradication remains an urgent priority for our foundation. We call on donor governments to also prioritize polio as we seek to eliminate these last, most difficult cases.”

The Global Polio Eradication Initiative (GPEI) is ‘spearheaded by national governments, WHO, Rotary International, the US Centers for Disease Control and Prevention (CDC) and UNICEF. Since 1988 (the year the GPEI was launched), the incidence of polio has been reduced by more than 99%. In 1988, more than 350 000 children were paralyzed each year in more than 125 endemic countries. In 2009, 1 595 children were paralyzed in 24 countries. Only four countries remain endemic: Afghanistan, India, Nigeria, and Pakistan.”

http://www.who.int/mediacentre/news/releases/2010/polio_eradication_20100616/en/index.html

The WHO continues to issue weekly updates and occasional briefing notes on the H1N1 pandemic at http://www.who.int/csr/disease/swineflu/en/index.html
Pandemic (H1N1) 2009 – update 105
Weekly update
18 June 2010 —
As of 13 June, worldwide more than 214 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 18172 deaths…

Situation update:
The situation remains largely unchanged since the last update. Overall pandemic influenza activity remains low worldwide with geographically limited circulation of pandemic influenza virus in parts of the tropics, particularly in parts of Central America and the Caribbean and in parts of South and Southeast Asia. Seasonal influenza type B viruses continue to circulate at low levels across Asia and to a lesser extent across parts of Africa and South America. Recently re-emerged seasonal influenza H3N2 viruses continue to circulate in East Africa. As countries of the temperate southern hemisphere enter winter, overall only sporadic influenza activity has been detected so far…

More at: http://www.who.int/csr/don/2010_06_18/en/index.html

Pandemic (H1N1) 2009 briefing note 21
10 June 2010
The international response to the influenza pandemic: WHO responds to the critics

Background
On Friday 4 June 2010, the BMJ, formerly British Medical Journal, and the Parliamentary Assembly of the Council of Europe (PACE) simultaneously released reports critical of the World Health Organization’s handling of the H1N1 pandemic. WHO provided a response organized around key questions as below:

– Did WHO remove severity from the definition of a pandemic?

– Did WHO exaggerate the threat?

– Were any WHO pandemic decisions made to increase industry profits?

– What safeguards are in place to guard against conflicts of interest?

– What is the function of the Emergency Committee and why have the names of its members not been disclosed?

– What evidence supports a role for antiviral drugs during an influenza pandemic?

– Was a WHO meeting held in 2002 on influenza vaccines and antiviral drugs influenced by industry?

The full response is available at:

http://www.who.int/csr/disease/swineflu/notes/briefing_20100610/en/index.html

The International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) said it delivered a formal statement to the United Nations General Assembly Hearings with NGOs, Civil Society and the Private Sector on the UN Millennium Development Goals. The IFPMA said it is the only industry body selected to make such a statement, which “outlined its members’ major contributions to the health-related UN MDGs, their observations on the lessons learnt from their wide range of programs to help improve health in developing countries, and recommendations for advancing progress in this area.”  IFPMA Director General Eduardo Pisani said: “The scale of the challenge posed by the UN MDGs is large. We can only hope to achieve them through global partnerships, with contributions from countries of all levels of economic development, and the active participation of governments, intergovernmental organizations, NGOs, philanthropic groups and the private sector. The R&D-based pharmaceutical industry contributes to global health through its normal business activity of developing new medicines, but it also makes additional contributions to improving developing country health, through an extensive range of not-for-profit and philanthropic partnership programs to improve access to health care, strengthen health care capacity and develop new medicines for diseases of the developing world.”
http://www.ifpma.org/News/NewsReleaseDetail.aspx?nID=13802

The U.S. Department of State, U.S. Agency for International Development and U.S. Department of Health and Human Services jointly announced the first round of “GHI Plus” countries under the U.S. Global Health Initiative (GHI). GHI is described as “a six-year, $63 billion initiative to help partner countries improve measurable health outcomes by strengthening health systems and building upon proven results. It places a particular focus on improving the health of women, newborns and children.” GHI includes programs addressing HIV/AIDS, malaria, tuberculosis, maternal and child health, nutrition, family planning and reproductive health, and neglected tropical diseases.

GHI activities are being implemented in the more than 80 countries where U.S. government global health dollars are already at work. Under GHI, the U.S. government “will coordinate with partner country governments to ensure that investments align with national priorities and build capacity. Eight countries have been selected as the first set of “GHI Plus” countries: Bangladesh, Ethiopia, Guatemala, Kenya, Malawi, Mali, Nepal, and Rwanda. These countries “will receive additional technical and management resources to quickly implement GHI’s approach, including integrated programs and investments across the spectrum of infectious diseases, maternal and child health, family planning, and health systems activities. GHI Plus countries will provide enhanced opportunities to build upon existing public health programs; improve program performance; and work in close collaboration with partner governments, across U.S. government agencies, and with global partners.”     Through GHI, the U.S. government said it is pursuing a comprehensive “whole-of-government” approach to global health and health assistance. More at: www.cdc.gov/globalhealth/.

http://www.cdc.gov/media/pressrel/2010/r100618.htm

The Weekly Epidemiological Record (WER) for 18 June 2010, vol. 85, 25 (pp 236–248) includes: Monitoring the coverage and impact of human papillomavirus vaccine – report of WHO meeting, November 2009; Performance of acute flaccid paralysis (AFP) surveillance and incidence of poliomyelitis, 2010; Monthly report on dracunculiasis cases, January– April 2010

http://www.who.int/wer/2010/wer8525.pdf

Journal of Infectious Diseases
15 July 2010   Volume 202, Number 2
http://www.journals.uchicago.edu/toc/jid/current

Major Articles and Brief Reports: Viruses
The Prevalence of Hepatitis B Virus Infection in the United States in the Era of Vaccination
Annemarie Wasley, Deanna Kruszon-Moran, Wendi Kuhnert, Edgar P. Simard, Lyn Finelli, Geraldine McQuillan, and Beth Bell

Background.Our objective was to assess trends in the prevalence of hepatitis B virus (HBV) infection in the United States after widespread hepatitis B vaccination.

Methods.The prevalence of HBV infection and immunity was determined in a representative sample of the US population for the periods 1999–2006 and 1988–1994. National Health and Nutrition Examination Surveys participants 6 years of age were tested for antibody to hepatitis B core antigen (anti-HBc), hepatitis B surface antigen (HBsAg), and antibody to hepatitis B surface antigen (anti-HBs). Prevalence estimates were weighted and age-adjusted.

Results.During the period 1999–2006, age‐adjusted prevalences of anti‐HBc (4.7%) and HBsAg (0.27%) were not statistically different from what they were during 1988–1994 (5.4% and 0.38%, respectively). The prevalence of anti-HBc decreased among persons 6–19 years of age (from 1.9% to 0.6%; ) and 20–49 years of age (from 5.9% to 4.6%; ) but not among persons 50 years of age (7.2% vs 7.7%). During 1999–2006, the prevalence of anti-HBc was higher among non-Hispanic blacks (12.2%) and persons of “Other” race (13.3%) than it was among non-Hispanic whites (2.8%) or Mexican Americans (2.9%), and it was higher among foreign-born participants (12.2%) than it was among US‐born participants (3.5%). Prevalence among US-born children 6–19 years of age (0.5%) did not differ by race or ethnicity. Disparities between US‐born and foreign‐born children were smaller during 1999–1996 (0.5% vs 2.0%) than during 1988–1994 (1.0% vs 12.8%). Among children 6–19 years of age, 56.7% had markers of vaccine-induced immunity.

Conclusions.HBV prevalence decreased among US children, which reflected the impact of global and domestic vaccination, but it changed little among adults, and 730,000 US residents (95% confidence interval, 550,000–940,000) are chronically infected.

The Lancet
Jun 19, 2010  Volume 375  Number 9732  Pages 2121 – 2192
http://www.thelancet.com/journals/lancet/issue/current

Series
Health-system strengthening and tuberculosis control
Rifat Atun, Diana EC Weil, Mao Tan Eang, David Mwakyusa

Weak health systems are hindering global efforts for tuberculosis care and control, but little evidence is available on effective interventions to address system bottlenecks. This report examines published evidence, programme reviews, and case studies to identify innovations in system design and tuberculosis control to resolve these bottlenecks. We outline system bottlenecks in relation to governance, financing, supply chain management, human resources, health-information systems, and service delivery; and adverse effects from rapid introduction of suboptimum system designs.

Scale-up of services and research priorities for diagnosis, management, and control of tuberculosis: a call to action
Ben J Marais, Mario C Raviglione, Peter R Donald, Anthony D Harries, Afranio L Kritski, Stephen M Graham, Wafaa M El-Sadr, Mark Harrington, Gavin Churchyard, Peter Mwaba, Ian Sanne, Stefan HE Kaufmann, Christopher JM Whitty, Rifat Atun, Alimuddin Zumla

The Millennium Development Goal target for tuberculosis control is to halt the spread of tuberculosis by 2015, and begin to reverse the worldwide incidence. After the introduction of standard control practices in 1995, 36 million people were cured and about 6 million deaths were averted. However, substantial scientific advances and innovative solutions are urgently needed together with creative new strategies. Strong international and national political commitment is essential. Urgent action is needed by national governments to fund their own programmes, and for the G8 countries and other donor governments and organisations to support governmental and non-governmental efforts.

The Lancet Infectious Disease
Jul 2010  Volume 10 Number 7  Pages 441 – 504
http://www.thelancet.com/journals/laninf/issue/current

Leading Edge
The deadly synergy of HIV and tuberculosis
The Lancet Infectious Diseases
To coincide with the International AIDS Conference being held this month in Vienna, Austria, we publish in this issue of the journal six Review and Personal View papers on a diversity of subjects related to HIV/AIDS. In addition, page 446 features a profile of Gottfried Hirnschall, the newly appointed Director of WHO’s HIV/AIDS Department.

Review
Effect of treating co-infections on HIV-1 viral load: a systematic review
Kayvon Modjarrad, Sten H Vermund

Co-infections contribute to HIV-related pathogenesis and often increase viral load in HIV-infected people. We did a systematic review to assess the effect of treating key co-infections on plasma HIV-1-RNA concentrations in low-income countries. We identified 18 eligible studies for review: two on tuberculosis, two on malaria, six on helminths, and eight on sexually transmitted infections, excluding untreatable or non-pathogenic infections. Standardised mean plasma viral load decreased after the treatment of co-infecting pathogens in all 18 studies.

Risk of resistance to highly active antiretroviral therapy among HIV-positive injecting drug users: a meta-analysis
Daniel Werb, Edward J Mills, Julio SG Montaner, Evan Wood

Although highly active antiretroviral therapy (HAART) is an effective treatment for HIV, many physicians withhold this treatment from HIV-positive injecting drug users (IDUs) because of fears of non-adherence and consequent development of antiretroviral resistance. Little is known, however, about whether the rates of resistance differ between IDUs and non-IDUs. We did a meta-analysis of studies that compared antiretroviral resistance rates in IDUs (current or previous) with those in HIV-positive patients infected by other routes and who had never injected drugs.

HIV-associated psoriasis: pathogenesis, clinical features, and management
Nilesh Morar, Saffron A Willis-Owen, Toby Maurer, Christopher B Bunker

Psoriasis is a chronic papulosquamous skin disease that is thought to be a T-cell-mediated autoimmune disorder of keratinocyte proliferation. The association between psoriasis and HIV infection seems paradoxical, but insights into the role of T-cell subsets, autoimmunity, genetic susceptibility, and infections associated with immune dysregulation might clarify our understanding of the pathogenesis of psoriasis with HIV in general. HIV-associated psoriasis can be clinically confusing because several comorbid skin disorders in patients with HIV can mimic psoriasis.

Central Asia: hotspot in the worldwide HIV epidemic
Claire Thorne, Nina Ferencic, Ruslan Malyuta, Jadranka Mimica, Tomasz Niemiec

The HIV epidemic in central Asia (Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan) has accelerated since 2000. This expansion in the epidemic is largely attributable to escalating injection drug use, reflecting central Asia’s geographic position along major drug trafficking routes. Although up to 75% of cumulative HIV cases have been among injection drug users (IDUs) so far, HIV infections are increasing in other population groups, including female sex workers and their clients, prisoners, and migrants.

New England Journal of Medicine
Volume 362 — June 17, 2010 — Number 24
http://content.nejm.org/current.shtml

Perspective
Enrolling Pregnant Women in Research — Lessons from the H1N1 Influenza Pandemic
S. F. Goldkind, L. Sahin, and B. Gallauresi

The global H1N1 influenza pandemic disproportionately affected pregnant women, drawing attention to the fact that although they need safe and effective medical treatment, they have always been a marginalized study population. Antiviral agents for treating influenza have been available in the United States for more than 10 years and are widely prescribed for pregnant women. Despite the understanding that physiological changes associated with pregnancy (e.g., changes in renal and hepatic function) can markedly alter pharmacokinetics, pharmacokinetic studies have not routinely been conducted in this population.

PLoS Medicine
(Accessed 21 June 2010)
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&document_count=1533&ct=1&SESSID=aac96924d41874935d8e1c2a2501181c#results

Estimating the Global Clinical Burden of Plasmodium falciparum Malaria in 2007
Simon I. Hay, Emelda A. Okiro, Peter W. Gething, Anand P. Patil, Andrew J. Tatem, Carlos A. Guerra, Robert W. Snow

Background
The epidemiology of malaria makes surveillance-based methods of estimating its disease burden problematic. Cartographic approaches have provided alternative malaria burden estimates, but there remains widespread misunderstanding about their derivation and fidelity. The aims of this study are to present a new cartographic technique and its application for deriving global clinical burden estimates of Plasmodium falciparum malaria for 2007, and to compare these estimates and their likely precision with those derived under existing surveillance-based approaches.

Methods and Findings
In seven of the 87 countries endemic for P. falciparum malaria, the health reporting infrastructure was deemed sufficiently rigorous for case reports to be used verbatim. In the remaining countries, the mapped extent of unstable and stable P. falciparum malaria transmission was first determined. Estimates of the plausible incidence range of clinical cases were then calculated within the spatial limits of unstable transmission. A modelled relationship between clinical incidence and prevalence was used, together with new maps of P. falciparum malaria endemicity, to estimate incidence in areas of stable transmission, and geostatistical joint simulation was used to quantify uncertainty in these estimates at national, regional, and global scales.

Combining these estimates for all areas of transmission risk resulted in 451 million (95% credible interval 349–552 million) clinical cases of P. falciparum malaria in 2007. Almost all of this burden of morbidity occurred in areas of stable transmission. More than half of all estimated P. falciparum clinical cases and associated uncertainty occurred in India, Nigeria, the Democratic Republic of the Congo (DRC), and Myanmar (Burma), where 1.405 billion people are at risk.

Recent surveillance-based methods of burden estimation were then reviewed and discrepancies in national estimates explored. When these cartographically derived national estimates were ranked according to their relative uncertainty and replaced by surveillance-based estimates in the least certain half, 98% of the global clinical burden continued to be estimated by cartographic techniques.

Conclusions and Significance
Cartographic approaches to burden estimation provide a globally consistent measure of malaria morbidity of known fidelity, and they represent the only plausible method in those malaria-endemic countries with nonfunctional national surveillance. Unacceptable uncertainty in the clinical burden of malaria in only four countries confounds our ability to evaluate needs and monitor progress toward international targets for malaria control at the global scale. National prevalence surveys in each nation would reduce this uncertainty profoundly. Opportunities for further reducing uncertainty in clinical burden estimates by hybridizing alternative burden estimation procedures are also evaluated.

Editor’s Note: Vaccines: The Week in Review adds a new feature beginning this week called “Information Resources,” intended to highlight important websites, repositories and sources of information covering global vaccines, immunization, public health and related ethical and policy issues.

Our first entry is the PATH Vaccine Resource Library which “seeks to gather the world’s best immunization resources in a single, easy-to-use website. The VRL offers high-quality, scientifically accurate documents and links on specific diseases and topics in immunization.” PATH is currently seeking feedback on this resource, available at  http://www.path.org/vaccineresources/details.php?i=1008

The WHO and the Health Department of South Africa developed a brochure – Health advice for travellers to the FIFA World Cup – which includes information about required immunizations and other health precautions. The full text section on vaccinations is below:

Vaccinations

Before travelling, you must be up-to-date on your routine travel vaccinations. These include diphtheria, tetanus, pertussis, polio, measles, and mumps. Making sure your measles and polio vaccinations are up-to-date is especially important – there have

been recent outbreaks of measles in South Africa, and polio has been eliminated from South Africa and must not be re-introduced.

If you are coming from a country where polio cases occurred recently, this vaccination is crucial (see www.polioeradication.org/casecount.asp ) for countries where polio cases occurred recently).

As well as the essential vaccines, your doctor might suggest you get others. What extra vaccines you need depends on where in South Africa you’re going, and what you’ll be doing when you get there. Other vaccines you might need include hepatitis A, hepatitis B and typhoid fever.

Yellow fever

If you are arriving in South Africa from an area at risk of yellow fever, you must have a valid certificate of yellow fever vaccination. This certificate must show you were vaccinated at least 10 days before travelling, and not more than 10 years before arriving in South Africa. Find out from your doctor what areas are at risk of yellow fever transmission: if you need the right papers and you don’t have them, you will be refused entry to South Africa. Please also note that if you are transiting through a yellow fever area, you’ll need the vaccine as well – no matter how short a time you spend in transit.

Flu: Seasonal Influenza and Pandemic A(H1N1) Influenza

It’s going to be winter in South Africa during the World Cup, and this means you’ll be more at risk from influenza, or flu. Vaccination is the best protection against flu. If you are coming to South Africa for the World Cup, you should get vaccinated against seasonal flu and Pandemic A(H1N1) Influenza. In most countries, routine flu

vaccinations already include protection against Pandemic A(H1N1) Influenza, but do check this with your doctor.

If you are at high risk of serious disease from flu viruses, it’s even more important that you receive the right flu vaccinations. You should make flu vaccinations a priority if you’re pregnant or elderly; if you have a chronic disease; or if your immune system is already compromised.

http://www.who.int/ith/updates/health_advice_2010_world_cup.pdf

The Bill & Melinda Gates Foundation announced a new initiative “…to help advance a comprehensive approach to women’s and children’s health” and said it will “invest $1.5 billion from 2010 through 2014 to support innovative projects addressing family planning; health care for pregnant women, newborns, and children; and nutrition.” This new pledge will add to the foundation’s spending in other areas that affect women’s and children’s health – such as developing and delivering children’s vaccines, and preventing pneumonia, diarrhea, malaria, and HIV/AIDS.  Gates said that a significant portion of the new funding will support programs in India, Ethiopia, and other countries that have relatively high rates of maternal and child mortality. http://www.gatesfoundation.org/press-releases/Pages/women-deliver-2010-100607.aspx

The WHO continues to issue weekly updates on the H1N1 pandemic at http://www.who.int/csr/disease/swineflu/en/index.html

Pandemic (H1N1) 2009 – update 104
Weekly update
11 June 2010

As of 6 June, worldwide more than 214 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 18156 deaths…

Situation update:
Active but declining transmission of pandemic influenza virus persists in limited areas of the tropics, particularly in Southeast Asia and the Caribbean. As countries of the temperate southern hemisphere enter winter, only sporadic influenza activity has been detected so far, except in Chile and Uruguay, both of which have recently reported small numbers of pandemic influenza virus detections. Although seasonal influenza B viruses have been the predominant type of influenza virus circulating worldwide since the end of February 2010, there have been increasing but low level detections of seasonal influenza H3N2 viruses, particularly in South America and in East Africa…

More at: http://www.who.int/csr/don/2010_06_11/en/index.html

The International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) approved a Joint Industry Position on the Publication of Clinical Trial Results in the Scientific Literature, previously approved by the European Federation of Pharmaceutical Industries and Associations (EFPIA), the Japanese Pharmaceutical Manufacturers Association (JPMA) and the Pharmaceutical Research and Manufacturers of America (PhRMA). Through the new industry position, “the associations and their member companies and associations commit, as a minimum, to submit for publication as a manuscript in a peer-reviewed journal, the results of all their industry-sponsored phase III clinical trials, as well as the results of other trials of significant medical importance.” The new Joint Position requires submission for publication of the results of all trials within its scope, regardless of whether the outcome was positive or negative.
Mr. Haruo Naito, President of the IFPMA and President and CEO of Eisai, said: “Our earlier Joint Position on Disclosure of Clinical Trials already requires members to disclose the trials they are undertaking and to publish summary results in online registries. This new Joint Position on publication is a logical extension of that approach, requiring members to seek scientific journal publication of the results of the specified trials.”
The position notes that submission of manuscripts should occur ideally within 12 months and no more than 18 months after approval of the product concerned or the decision to discontinue the trial. In the case of trials of a product which is already marketed, submission should ideally be within 12 months of the completion of the trial and not more than 18 months after that date.
The Position also “lays down guidelines which enhance transparency regarding the authorship of manuscripts. An authorship credit requires a substantial contribution to the design of the trial, data acquisition or interpretation, plus drafting or revision of the text, plus final approval. The roles of medical writers, statisticians and other who contribute to a manuscript but who do not meet the authorship criteria should be mentioned appropriately. Company involvement in both the research and publication should be disclosed, and sponsors should encourage authors to disclose all relevant interests. The primary publication for a particular trial should provide an accurate report of its findings, including adverse events, and there should be a discussion of the strengths and limitations of the study.”
http://www.ifpma.org/News/NewsReleaseDetail.aspx?nID=13801

The MMWR Weekly for June 11, 2010 / Vol. 59 / No. 22 includes:

– Deaths and Hospitalizations Related to 2009 Pandemic Influenza A (H1N1) — Greece, May 2009–February 2010

– Addition of Severe Combined Immunodeficiency as a Contraindication for Administration of Rotavirus Vaccine

http://www.cdc.gov/mmwr/PDF/wk/mm5922.pdf

The Lancet
Jun 12, 2010  Volume 375  Number 9731 Pages 2051 – 2120
http://www.thelancet.com/journals/lancet/issue/current

Series
New vaccines for tuberculosis
Stefan HE Kaufmann, Gregory Hussey, Paul-Henri Lambert

Summary
New vaccines are urgently needed if we want to reach the goal of substantially reducing the incidence of tuberculosis by 2050. Despite a steady increase in funding over the past decade, there is still a striking financial shortfall for vaccine research and development for tuberculosis. Yet, around ten vaccine candidates have left the laboratory stage and entered clinical trials. These vaccines are either aimed at replacing the present vaccine, BCG, or at enhancing immunity induced by BCG. However, these pre-exposure candidates are designed for prevention of disease and will therefore neither eradicate the pathogen, nor prevent stable infection. Long-term vaccination strategies need to target these more ambitious goals. Even though vaccine development will have a price, the return of investment will greatly exceed original costs.

New England Journal of Medicine
Volume 362 — June 10, 2010 — Number 23
http://content.nejm.org/current.shtml

Original Articles
Comparative Epidemiology of Pandemic and Seasonal Influenza A in Households
[free full text]
B. J. Cowling and Others

ABSTRACT
Background There are few data on the comparative epidemiology and virology of the pandemic 2009 influenza A (H1N1) virus and co-circulating seasonal influenza A viruses in community settings.

Methods We recruited 348 index patients with acute respiratory illness from 14 outpatient clinics in Hong Kong in July and August 2009. We then prospectively followed household members of 99 patients who tested positive for influenza A virus on rapid diagnostic testing. We collected nasal and throat swabs from all household members at three home visits within 7 days for testing by means of quantitative reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay and viral culture. Using hemagglutination-inhibition and viral-neutralization assays, we tested baseline and convalescent serum samples from a subgroup of patients for antibody responses to the pandemic and seasonal influenza A viruses.

Results Secondary attack rates (as confirmed on RT-PCR assay) among household contacts of index patients were similar for the pandemic influenza virus (8%; 95% confidence interval [CI], 3 to 14) and seasonal influenza viruses (9%; 95% CI, 5 to 15). The patterns of viral shedding and the course of illness among index patients were also similar for the pandemic and seasonal influenza viruses. In a subgroup of patients for whom baseline and convalescent serum samples were available, 36% of household contacts who had serologic evidence of pandemic influenza virus infection did not shed detectable virus or report illness.

Conclusions Pandemic 2009 H1N1 virus has characteristics that are broadly similar to those of seasonal influenza A viruses in terms of rates of viral shedding, clinical illness, and transmissibility in the household setting.

Science
11 June 2010  Vol 328, Issue 5984, Pages 1323-1419
http://www.sciencemag.org/current.dtl

Policy Forum: Public Health
Global HIV/AIDS Policy in Transition
John Bongaarts and Mead Over

Summary
In 2007, the United Nations Joint Programme on HIV/AIDS (UNAIDS) concluded that “Global HIV incidence likely peaked in the late 1990s” (1), due to “natural trends in the epidemic as well as the result of prevention programmes” (1). The slow decline in new infections together with a recent rise in antiretroviral therapies (ARTs) halted the rise in the estimated number of AIDS deaths at about 2.2 million per year—equivalent to 4% of all global deaths (2). Among adults 15 to 49, the proportion currently infected with HIV (HIV prevalence) plateaued at just under 1% before declining to 0.8% worldwide (1, 3). These trends raise the question of how global health funding should be rebalanced between AIDS treatment and HIV prevention, as well as other health-care investments.

Vaccine
Volume 28, Issue 29, Pages 4539-4686 (23 June 2010)
http://www.sciencedirect.com/science/journal/0264410X

Meeting Report
Utilization of serologic assays to support efficacy of vaccines in nonclinical and clinical trials: Meeting at the Crossroads
Dace V. Madore, Bruce D. Meade, Fran Rubin, Carolyn Deal, Freyja Lynn and the Meeting Contributors

Abstract
In May 2009 the National Institute of Allergy and Infectious Diseases hosted a workshop on serologic assays that support vaccine efficacy evaluations. The meeting promoted exchange of ideas among investigators from varying disciplines who are working on anti-infectious agent vaccines at different stages of development. The presentations and discussions at the workshop illustrated the challenges common across various pathogens with recurring themes: (1) A thorough understanding of the science regarding the pathogen and the host response to disease and immunization is fundamental to assay selection. (2) The intended use of the immunoassay data must be clearly defined to ensure appropriate specificity, accuracy, and precision; a laboratory must also commit resources to assure data quality and reliability. (3) During vaccine development, an immunoassay may evolve with respect to quality, purpose, and degree of standardization, and, in some cases, must be changed or replaced as data are accumulated. (4) Collaboration on standardized reagents and methods, harmonization efforts, and multidisciplinary teams facilitate consistent generation of quality data. This report provides guidance for effective development and utilization of immunoassays based on the lessons learned from currently licensed vaccines. Investigators are encouraged to create additional opportunities for scientific exchange, noting that the discussed themes are relevant for immunoassays used for other purposes such as therapeutics and diagnostics.

Vaccine
Volume 28, Issue 29, Pages 4539-4686 (23 June 2010)
http://www.sciencedirect.com/science/journal/0264410X

Regular Papers
Measles in the United Kingdom 1990–2008 and the effectiveness of measles vaccines
Hershel Jick, Katrina Wilcox Hagberg

Abstract
We identified all children in the UK General Practice Research Database diagnosed with measles from 1990 to 2008 and calculated annual incidence according to age and geographic region by dividing the number of cases per year by the number of children who were active in the population. We evaluated the effectiveness of the measles vaccines by comparing the vaccination histories of children who were diagnosed with measles (cases) to children who were not (controls). The annual incidence of measles fell after the introduction of the MMR vaccine in late 1988. However, a modest outbreak of measles occurred in 1994, leading to large nationwide programs to immunize children. Since 1996, the incidence of measles has fallen by more than 80%. Prior measles vaccination is highly effective and has substantially reduced the risk of measles.

Vaccine
Volume 28, Issue 29, Pages 4539-4686 (23 June 2010)
http://www.sciencedirect.com/science/journal/0264410X

A cost–effectiveness analysis of Japanese encephalitis vaccine in Cambodia
Sok Touch, Chutima Suraratdecha, Chham Samnang, Seng Heng, Lauren Gazley, Chea Huch, Ly Sovann, Chab Seak Chhay, Sann Chan Soeung

Abstract
This study aimed to evaluate the cost and effectiveness of introducing a live, attenuated vaccine (SA 14-14-2) against Japanese encephalitis (JE) into the immunization program. The study demonstrated that SA 14-14-2 immunization is cost–effective in controlling JE in Cambodia compared to no vaccination. Averting one disability-adjusted life year, from a societal perspective, through the introduction of SA 14-14-2 through routine immunization, or a combination of routine immunization plus a campaign targeting children 1–5 or 1–10 years of age, costs US$22, US$34 and US$53, respectively. Sensitivity analyses confirmed that there was a high probability of SA 14-14-2 immunization being cost–effective under conditions of uncertainty.

Vaccine
Volume 28, Issue 29, Pages 4539-4686 (23 June 2010)
http://www.sciencedirect.com/science/journal/0264410X

Influenza vaccination of future healthcare workers: A cross-sectional study of uptake, knowledge and attitudes
Debra L. Blank, David M.S. Bodansky, Anna Forbes, Emma Garde, Fleur Story, Andrea K. Roalfe, Lynda Tait

Abstract
Promotional campaigns recommend immunisation against influenza in healthcare workers (HCWs) but the uptake in this group remains low. We conducted a survey study during the 2008–2009 influenza vaccination period amongst future HCWs to quantify uptake and identify barriers to immunisation. Overall uptake was 8.0% (95% CI 5.9–10.8%), which is lower than the uptake amongst current HCWs (13.4%) and short of current government targets (75%). Knowledge about influenza was good but insufficient to encourage HCWs to get vaccinated. Promotional campaigns are needed that emphasise the role of vaccination in personal and patient protection.

WHO released its Pandemic (H1N1) 2009 vaccine deployment update – 31 May 2010. The update, reflecting activity in the WHO “stockpile”, notes that:

– 99 countries have requested vaccine donations

– 86 countries have signed agreements with WHO

– National Deployment Plans: 67 are complete and final; 7 plans are being refined

– Through 31 May 2010, 49 countries have received 32,393, 600 doses of pandemic (H1N1) vaccine. The overall stockpile has received pledges of some 200 million doses, and commitments of 118 million doses. The report notes that the apparent gap is “not applicable since sufficient vaccines have been pledged to meet at least 10% population coverage of all countries that have requested vaccine.”

This one-page update available at:

http://www.who.int/csr/disease/swineflu/action/h1n1_vaccine_deployment_update20100531.pdf

The WHO continues to issue weekly updates on the H1N1 pandemic at http://www.who.int/csr/disease/swineflu/en/index.html
Pandemic (H1N1) 2009 – update 103
Weekly update
4 June 2010

As of 30 May, worldwide more than 214 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 18138 deaths…

Situation update:
Active but declining transmission of pandemic influenza virus continued to be detected in parts of the Caribbean and Southeast Asia. In the countries of temperate southern hemisphere there is no evidence yet to suggest that the winter influenza season has begun, however there has been limited localized pandemic influenza virus transmission in Chile. In the rest of the world, overall pandemic influenza virus transmission remains low. Seasonal influenza B viruses are currently the predominant type of influenza virus circulating globally, although at low levels. Of note, during the later part of May 2010, low but significant levels of predominantly seasonal influenza H3N2 viruses have been detected in several countries of East Africa.

More at: http://www.who.int/csr/don/2010_05_21/en/index.html

The MMWR Weekly for June 4, 2010 / 59(21);657-661, includes:

Preliminary Results: Surveillance for Guillain-Barré Syndrome After Receipt of Influenza A (H1N1) 2009 Monovalent Vaccine — United States, 2009–2010

On June 2, this report was posted as an MMWR Early Release on the MMWR website (http://www.cdc.gov/mmwr).

Guillain-Barré syndrome (GBS) is an uncommon peripheral neuropathy causing paralysis and in severe cases respiratory failure and death. GBS often follows an antecedent gastrointestinal or upper respiratory illness but, in rare cases, can follow vaccination. In 1976, vaccination against a novel swine-origin influenza A (H1N1) virus was associated with a statistically significant increased risk for GBS in the 42 days after vaccination (approximately 10 excess cases per 1 million vaccinations), a consideration in halting the vaccination program in the context of limited influenza virus transmission (1). To monitor influenza A (H1N1) 2009 monovalent vaccine safety, several federal surveillance systems, including CDC’s Emerging Infections Program (EIP), are being used. In October 2009, EIP began active surveillance to assess the risk for GBS after 2009 H1N1 vaccination. Preliminary results from an analysis in EIP comparing GBS patients hospitalized through March 31, 2010, who did and did not receive 2009 H1N1 vaccination showed an estimated age-adjusted rate ratio of 1.77 (GBS incidence of 1.92 per 100,000 person-years among vaccinated persons and 1.21 per 100,000 person-years among unvaccinated persons). If end-of-surveillance analysis confirms this finding, this would correspond to 0.8 excess cases of GBS per 1 million vaccinations, similar to that found in seasonal influenza vaccines (2,3). No other federal system to date has detected a statistically significant association between GBS and 2009 H1N1 vaccination. Surveillance and further analyses are ongoing.

The 2009 H1N1 vaccine safety profile is similar to that for seasonal influenza vaccines, which have an excellent safety record. Vaccination remains the most effective method to prevent serious illness and death from 2009 H1N1 influenza infection; illness from the 2009 H1N1 influenza virus has been associated with a hospitalization rate of 222 per 1 million and a death rate of 9.7 per 1 million population.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5921a3.htm

The MMWR Weekly for May 28, 2010 / Vol. 59 / No. 20 / Pg. 613 – 648, includes:

– FDA Licensure of Bivalent Human Papillomavirus Vaccine (HPV2, Cervarix) for Use in Females and Updated HPV Vaccination Recommendations from the Advisory Committee on Immunization Practices (ACIP)

– FDA Licensure of Quadrivalent Human Papillomavirus Vaccine (HPV4, Gardasil) for Use in Males and Guidance from the Advisory Committee on Immunization Practices (ACIP)

http://www.cdc.gov/mmwr/mmwr_wk/wk_cvol.html

The Weekly Epidemiological Record (WER) for 4 June 2010, vol. 85, 23 (pp 213–228) includes: Polio vaccines and polio immunization in the pre-eradication era: WHO position paper. http://www.who.int/wer/2010/wer8523.pdf

In a posting, WHO noted:

“A new position paper covering routine polio immunization in the pre-eradication era, particularly in developing country settings, was published today in the WHO Weekly Epidemiological Record. The position paper includes information on the types of polio vaccine available, and their safety, immunogenicity, field efficacy and cost-effectiveness. It concludes with policy recommendations.

“Prior to polio eradication, national immunization schedules should include either oral polio vaccine, inactivated polio vaccine, or a combination of both. Vaccine decisions should be based on assessments of the potential for importation of wild poliovirus (WPV) and subsequent transmission. High immunization coverage is essential to ensure adequate population immunity. As long as WPV transmission has not been interrupted everywhere, all polio-free countries and areas remain at risk of re-importation, particularly from the remaining polio-endemic countries.

http://www.who.int/immunization/newsroom/news_routine_polio_immunization_position_paper_2010/en/index.html

iBio, Inc. and the Fraunhofer USA Center for Molecular Biotechnology (CMB) announced an agreement which provides a license of iBio’s proprietary technology to CMB for the development and manufacture of Global Health Vaccines for, and financed by, the Bill & Melinda Gates Foundation. The announcement noted that “…a principal focus of the Bill & Melinda Gates Foundation is to provide access to vaccines for the neediest people in the developing countries in the world (Global Alliance for Vaccines & Immunization (GAVI) Eligible Countries), representing vast numbers of people currently unable to afford preventive and therapeutic medical care (Global Access Objectives). Global Health Vaccines, subject to this agreement, are vaccines for human or veterinary use for the prevention of malaria, tuberculosis, rotavirus, trypanosomiasis, hookworm and rabies.”

The announcement continues: “Under the terms of the Agreement, CMB will use iBio’s technology under a non-exclusive, non-royalty bearing grant to develop and test new Global Health Vaccines funded by the Bill & Melinda Gates Foundation. The Agreement establishes iBio as the preferred manufacturer of Global Health Vaccines and provides a right of first refusal to iBio to provide technology transfer and vaccine manufacturing services to achieve Global Access Objectives on a commercially reasonable, competitive and sustainable cost basis. In accordance with prior agreements, iBio will own commercial rights to new technology and improvements arising during the course of the programs. Additional terms of the Agreement provide for mutual cooperation with respect to the sharing of clinical data and regulatory filings related to the program.”

Robert Kay, Chairman and CEO of iBio, said, “The attributes of our technology – including rapid response to pandemic disease threats, surge capacity, and scalable manufacturing facilities with much lower capital and operating costs – should enable the Foundation to achieve its objective to provide vaccines to vast populations that have been neglected until now. In this symbiotic relationship, as we help the Foundation achieve its Foundation-funded Global Access Objectives, iBio is helped to optimize and broaden its technology platform for commercial purposes and expand its commercial manufacturing and tech transfer programs.”

Dr. Vidadi Yusibov, Executive Director of CMB and Chief Scientific Officer of iBio, commented, “The Bill & Melinda Gates Foundation and iBio, along with the Defense Advanced Research Projects Agency (DARPA), are key stakeholders in the success of our technology development. Their support was critical for establishing this technology and demonstrating its potential for development of vaccines against viral, bacterial and parasitic diseases. I am confident this cooperation will provide great benefit for all parties.”

iBio describes itself as “a biopharmaceutical company commercializing its proprietary technology, the iBioLaunch™ platform, for the production of biologics including vaccines and therapeutic proteins. The iBioLaunch platform uses transient gene expression in green plants for superior efficiency in protein production. Advantages include significantly lower capital and process costs, and the technology is ideally suited to infectious disease applications where speed, scalability, and surge capacity are important. iBio’s strategy is to utilize its technology for development and manufacture of its own product candidates and work with both corporate and government clients to reduce their costs during product development and meet their needs for low cost, high quality biologics manufacturing systems. iBio owns technology developed at the Fraunhofer USA Center for Molecular Biotechnology, and continues to sponsor development and refinement of the technology for broad applications in human healthcare.”

http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20100603005415&newsLang=en

GAVI said the International Finance Facility for Immunisation (IFFIm), in collaboration with GAVI Alliance, the World Bank and HSBC Securities (Japan) Limited, would begin offering another in a series of vaccine investment bonds, also known as “vaccine bonds”, to Japanese retail investors starting 7 June 2010. The multi-tranche transaction includes the first IFFIm bond denominated in Brazilian real (BRL) and settled in JPY. The triple-A rated IFFIm is offering investors the three investment options. http://www.gavialliance.org/media_centre/press_releases/2010_06_04_iffim_japanese_bonds.php

WHO posted The Smallpox Eradication Programme – SEP (1966-1980), an archive and photo gallery marking the 30th anniversary of the eradication of smallpox. Smallpox was officially declared eradicated in 1980 and is the first disease to have been fought on a global scale. This extraordinary achievement was accomplished through the collaboration of countries around the world.

At the end of the 1960s, smallpox was still endemic in Africa and Asia. Vaccination campaigns, surveillance and prevention measures aimed to contain epidemic hotspots and to better inform affected populations. All these strategies were used to combat the disease.

The photographs presented in the galleries below illustrate the various activities carried out to eradicate smallpox around the world. They show how the same eradication methods and strategies were repeated in very different countries around the globe.

http://www.who.int/features/2010/smallpox/en/index.html

Clinical Infectious Diseases
1 July 2010  Volume 51, Number 1
http://www.journals.uchicago.edu/toc/cid/current

MAJOR ARTICLE
Treatment Outcomes among Patients with Extensively Drug-Resistant Tuberculosis: Systematic Review and Meta-Analysis
Karen R. Jacobson,1; Dylan B. Tierney,1; Christie Y. Jeon,2; Carole D. Mitnick,3,4, and Megan B. Murray1,2,4

1Division of Infectious Disease, Massachusetts General Hospital, 2Department of Epidemiology, Harvard School of Public Health, 3Department of Global Health and Social Medicine, Harvard Medical School, and 4Division of Global Health Equity, Brigham and Women’s Hospital, Boston, Massachusetts

Background.There is debate surrounding the effectiveness of the 23‐valent pneumococcal polysaccharide vaccine (PPV). We determined whether PPV was associated with reduced mortality or additional hospitalization for vaccine‐preventable infections in patients previously hospitalized for community‐acquired pneumonia (CAP).

Methods.From 2000 through 2002, adults with CAP admitted to the hospital in Edmonton, Alberta, Canada, were enrolled in a population‐based cohort. Postdischarge outcomes during 5 years were ascertained using administrative databases. The primary outcome was the composite of all‐cause mortality or additional hospitalization for vaccine-preventable infections. Proportional hazards analysis was used to determine the association between PPV use and outcomes.

Results.A total of 2950 patients were followed up for a median of 3.8 years. The mean patient age was 68 years; 52% were male. One-third (n=956) received PPV: 667 (70%) before and 289 (30%) during hospitalization. After discharge, 1404 patients (48%) died, 504 (17%) were admitted with vaccine-preventable infections, and 1626 (55%) reached the composite outcome of death or infection. PPV was not associated with reduced risk of the composite outcome (589 [62%] vs 1037 [52%] for those unvaccinated; adjusted hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.79–1.04). Results were not altered in sensitivity analyses using propensity scores (adjusted HR, 0.91; 95% CI, 0.79–1.04), restricting the sample to patients 65 years or older (adjusted HR, 0.90; 95% CI, 0.77–1.04), or considering only those who received PPV at discharge (adjusted HR, 0.84; 95% CI, 0.71–1.00).

Conclusions.One-half of patients discharged from the hospital after pneumonia die or are subsequently hospitalized with a vaccine-preventable infection within 5 years. PPV was not associated with a reduced risk of death or hospitalization. Better pneumococcal vaccination strategies are urgently needed.

Human Vaccines
Volume 6, Issue 6  June 2010
http://www.landesbioscience.com/journals/vaccines/toc/volume/6/issue/6/

News
Malaria Vectored Vaccines Consortium (MVVC)
Sharmila Bakshi and Egeruan Babatunde Imoukhuede

The European Vaccine Initiative (EVI) is coordinating the Malaria Vectored Vaccines Consortium (MVVC), a four year project set-up with the aim of integrating capacity-building and networking in the design and conduct of Phase I and II clinical trials of viral vectored candidate malaria vaccines in East and West African adults, children, and infants. The overall objective of the project is to develop a safe, non-reactogenic, effective, and affordable malaria vaccine for use by the malaria endemic populations of the world.

The MVVC Consortium consists of eight partners; European Vaccine Initiative (EVI); UniversitätsKlinikum Heidelberg, Germany; The University of Oxford (UOXF), United Kingdom (UK); Vienna School of Clinical Research (VSCR), Austria; Okairos s.r.l, Italy; Centre National de Recherche et Formation sur le Paludisme (CNRFP), Burkina Faso; Kenya Medical Research Institute (KEMRI ), Kenya; Medical Research Council Gambia (MRC Gambia), The Gambia; and Université Cheikh Anta Diop (UCAD), Senegal.

Human Vaccines
Volume 6, Issue 6  June 2010
http://www.landesbioscience.com/journals/vaccines/toc/volume/6/issue/6/

Research Paper
Knowledge and attitudes towards vaccines and immunization among adolescents in South Africa
Simona Zipursky, Charles Shey Wiysonge and Gregory Hussey

Despite evidence showing their benefits, routine adolescent immunization programmes are still lacking across Africa. In 2008 we conducted a qualitative study of adolescents’ knowledge and attitudes towards immunization in a peri-urban community in South Africa. Results show that while vaccination as a concept is acceptable amongst adolescents, low levels of knowledge about vaccines, the process of being vaccinated, as well as unfamiliarity with the concept of preventative medicine in general will likely hinder achieving high and equitable routine adolescent immunization coverage. Effective educational programs and integrated adolescent healthcare strategies will be critical to delivering successful immunization services to this group.

Human Vaccines
Volume 6, Issue 6  June 2010
http://www.landesbioscience.com/journals/vaccines/toc/volume/6/issue/6/

Research Paper
Acceptability of prophylactic human papillomavirus vaccination among adult men
Brenda Y Hernandez, Lynne Wilkens, Pamela Thompson, Yurii Shvetso, Marc Goodman, Lily Ning and Lana Kaopua

Objectives: HPV vaccine acceptability was examined as part of a cohort study of HPV infection among adult males.

Methods: Between July 2004 and June 2007, 445 adult males aged ≥18 years were enrolled primarily from a university-based population. A structured questionnaire addressed HPV vaccine awareness, attitudes, and intention to be vaccinated.

Results: Overall, 69% of men reported that they were likely or very likely to be vaccinated against HPV if a prophylactic vaccine were available. Men most frequently cited side effects (69%), efficacy (65%), and safety (63%) as the major factors that would influence their decision to be vaccinated against HPV. Issues of vaccine costs and efficacy were important considerations for men of vaccine-eligible ages (18-26 years). Men who cited cost as a major factor in their HPV vaccine decisions and those indicating cost as a potential barrier had greater intention to be vaccinated. Heterosexual men had less intention to be vaccinated compared to men who have sex with men.

Conclusion. Acceptability of HPV vaccination among males is generally high. Costs and sexual history may influence vaccine utilization.

The Lancet
http://www.thelancet.com/journals/lancet/issue/current
Jun 05, 2010  Volume 375 Number 9730 Pages 1939 – 2050

Review
Countdown to 2015 decade report (2000–10): taking stock of maternal, newborn, and child survival
Zulfiqar A Bhutta, Mickey Chopra, Henrik Axelson, Peter Berman, Ties Boerma, Jennifer Bryce, Flavia Bustreo, Eleonora Cavagnero, Giorgio Cometto, Bernadette Daelmans, Andres de Francisco, Helga Fogstad, Neeru Gupta, Laura Laski, Joy Lawn, Blerta Maliqi, Elizabeth Mason, Catherine Pitt, Jennifer Requejo, Ann Starrs, Cesar G Victora, Tessa Wardlaw

Summary
The Countdown to 2015 for Maternal, Newborn, and Child Survival monitors coverage of priority interventions to achieve the Millennium Development Goals (MDGs) for child mortality and maternal health. We reviewed progress between 1990 and 2010 in coverage of 26 key interventions in 68 Countdown priority countries accounting for more than 90% of maternal and child deaths worldwide. 19 countries studied were on track to meet MDG 4, in 47 we noted acceleration in the yearly rate of reduction in mortality of children younger than 5 years, and in 12 countries progress had decelerated since 2000. Progress towards reduction of neonatal deaths has been slow, and maternal mortality remains high in most Countdown countries, with little evidence of progress. Wide and persistent disparities exist in the coverage of interventions between and within countries, but some regions have successfully reduced longstanding inequities. Coverage of interventions delivered directly in the community on scheduled occasions was higher than for interventions relying on functional health systems. Although overseas development assistance for maternal, newborn, and child health has increased, funding for this sector accounted for only 31% of all development assistance for health in 2007. We provide evidence from several countries showing that rapid progress is possible and that focused and targeted interventions can reduce inequities related to socioeconomic status and sex. However, much more can and should be done to address maternal and newborn health and improve coverage of interventions related to family planning, care around childbirth, and case management of childhood illnesses.

The Lancet
http://www.thelancet.com/journals/lancet/issue/current
May 29, 2010  Volume 375 Number 9729 Pages 1845 – 1938

Series
The HIV-associated tuberculosis epidemic—when will we act?
Anthony D Harries, Rony Zachariah, Elizabeth L Corbett, Stephen D Lawn, Ezio T Santos-Filho, Rhehab Chimzizi, Mark Harrington, Dermot Maher, Brian G Williams, Kevin M De Cock

Preview
Despite policies, strategies, and guidelines, the epidemic of HIV-associated tuberculosis continues to rage, particularly in southern Africa. We focus our attention on the regions with the greatest burden of disease, especially sub-Saharan Africa, and concentrate on prevention of tuberculosis in people with HIV infection, a challenge that has been greatly neglected. We argue for a much more aggressive approach to early diagnosis and treatment of HIV infection in affected communities, and propose urgent assessment of frequent testing for HIV and early start of antiretroviral treatment (ART).

The Lancet Infectious Disease
Jun 2010  Volume 10 Number 6  Pages 367 – 440
http://www.thelancet.com/journals/laninf/issue/current

Leading Edge
Polio—a pathogen on a precipice
The Lancet Infectious Diseases

Original Text
30 years ago, on May 8, 1980, the World Health Assembly formally recognised the global eradication of smallpox. For thousands of years the disease had claimed many millions of lives (an estimated 300 million to 500 million in the 20th century alone). The culmination of 200 years of public health efforts from Edward Jenner’s discovery of the cowpox vaccine, the achievement was a milestone in global health and gave hope that other diseases might too be consigned to the history books. But despite efforts before and since the eradication of smallpox, no other infectious disease has been successfully eradicated, and to some people the demise of smallpox seems like a fluke.

Efforts to eradicate yellow fever, yaws, and malaria have all fallen by the wayside; or, if not completely forgotten, their realisation seems a long way off—in the 1950s and 1960s people talked of malaria eradication in decades, now we talk of it optimistically in terms of the next century. Programmes for perhaps the two most promising candidates, polio and dracunculiasis, have seen eradication come tantalisingly within reach, but both diseases cling on in a few endemic countries from which outbreaks in non-endemic countries emanate—such as the polio outbreak in Tajikistan this year.

Polio, like dracunculiasis and smallpox, has no non-human reservoir and has known preventive interventions, in this case highly effective vaccines, and therefore is an attractive target. And the prominence of the disease in high-income countries charged early control efforts. In the USA, for example, President Franklin D Roosevelt, who was paralysed by the disease, initiated the huge charitable fundraising efforts known as The March of Dimes, which was instrumental in funding the development of both Salk and Sabin polio vaccines. Resulting immunisation programmes in the USA and Europe staring in the 1950s saw rapid and early success. The incidence of polio in the USA and Europe declined rapidly, and in 1960 Czechoslovakia became the first country to declare polio eradicated. In 1985 the Pan American Health Organization launched an initiative to eradicate polio from the Americas, and in the same year, the Rotary Organisation pledged to raise US$120 million to immunise all children worldwide. With such positive initial gains WHO, UNICEF, the Rotary Organisation, and the US Centres for Disease Control and Prevention launched the Global Polio Eradication Initiative in 1988.

Within the first 5 years of the initiative, global incidence of the disease declined from an estimated 350 000 to 100 000. Since then, enormous gains have been made freeing much of the world from the crippling viral disease, which is now endemic in just a handful of regions in four countries: Afghanistan, India, Nigeria, and Pakistan.

Nonetheless, despite 22 years of gains, in the past 5 years the disease and its would-be eradicators have reached something of a stalemate. Each year 1000—2000 people have been affected by the disease, with outbreaks in both endemic and non-endemic countries. The impasse has led some to question the goal of eradication. Given the low incidence of the disease, are the benefits of achieving eradication worth the ongoing expense? But this question misses the point—the incidence is so low only because of eradication efforts; were surveillance to be relaxed and were mass immunisation campaigns to give way to routine vaccination alone, numbers of cases would surely rise again, and the disease spread to regions from which it has been eliminated.

Clearly, new approaches are needed to achieve eradication in the last strongholds. In a new strategic plan launched in April, the Global Polio Eradication Initiative highlights that, in addition to the old tools of government accountability, mass immunisation, and public engagement, new diplomacy, education, and accountability on ever more local levels are needed to reach the specific populations affected. In India, for example, the disease is not a national problem, but associated with populations in Uttar Pradesh and Bihar in the northwest, so targeting these regions and migrants from them will be essential in preventing the spread of disease.

The eradication of polio seems imminent, but with so few cases, there is a temptation to think an acceptable level of infection has been achieved. Not so. To stop short of eradication would not only be a snub to the hundreds of thousands of health workers and community members involved in the effort so far, but also would risk resurgence of a disease that for many is now a distant memory. The new levels of engagement in the last strongholds of polio will sever its grip from the precipice to which it clings. We look forward to 30 years or so from now, when we can reflect on the polio eradication programme and its legacy in global health.