The Lancet
Jul 10, 2010  Volume 376  Number 9735  Pages 69 – 140
http://www.thelancet.com/journals/lancet/issue/current

Viewpoint
Malaria in Africa: progress and prospects in the decade since the Abuja Declaration
Robert W Snow, Kevin Marsh

Preview
Malaria is a global health problem but more than 70% of the total morbidity is in Africa.1 10 years ago, heads of state from across Africa signed a declaration in Abuja, Nigeria, to “halve the malaria mortality for Africa’s people by 2010”.2 This Viewpoint discusses how far we have come in this effort, what we can expect for the future, and what our priorities should be.

Science
9 July 2010  Vol 329, Issue 5988, Pages 109-244
http://www.sciencemag.org/current.dtl

Special Report: HIV/AIDS
HIV/AIDS: Eastern Europe

Editorial:
AIDS Response at a Crossroads
Jessica Justman and Wafaa M. El-Sadr

Policy Forum
Gender Inequities Must Be Addressed in HIV Prevention
Rachel Jewkes

Building gender equity and reducing gender-based violence are vital in the fight against AIDS.
Universal Access in the Fight Against HIV/AIDS
Françoise Girard, Nathan Ford, Julio Montaner, Pedro Cahn, and Elly Katabira.

Vaccine
Volume 28, Issue 30, Pages 4687-4858 (5 July 2010)
http://www.sciencedirect.com/science/journal/0264410X

Meeting Reports
Cholera vaccines: WHO position paper—Recommendations
WHO Publication

Abstract
This article presents the WHO recommendations on the use of cholera vaccines excerpted from the recently published Cholera vaccines: WHO position paper. This document replaces the WHO position paper on Cholera vaccines published in the Weekly Epidemiological Record in April 2001. Footnotes to this paper provide a limited number of core references; their abstracts as well as a more comprehensive list of references may be found at http://www.who.int/immunization/documents/positionpapers/en/index.html.

Grading tables which assess the quality of scientific evidence for key conclusions are also available through this link and are referenced in the position paper. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO’s current position on the use of vaccines in the global context. This updated paper reflects the recent recommendations of WHO’s Strategic Advisory Group of Experts on immunization (SAGE).

Vaccine
Volume 28, Issue 30, Pages 4687-4858 (5 July 2010)
http://www.sciencedirect.com/science/journal/0264410X

MALVAC 2009: Progress and Challenges in Development of Whole Organism Malaria Vaccines for Endemic Countries, 3–4 June 2009, Dakar, Senegal
M. Pinder, V.S. Moorthy, B.D. Akanmori, B. Genton, G.V. Brown

Abstract
Research and development into whole organism malaria vaccines is progressing rapidly thanks to the major investments over recent years from several funders, and the commitment and interest of many leading researchers. Progress includes the discovery of potential new candidate vaccines and the start of the first phase 1/2a clinical trial of the radiation attenuated sporozoite approach for Plasmodium falciparum, under US Food and Drug Administration regulatory oversight. A group of leading scientists, clinical trialists and stakeholders, together with representatives of regulatory authorities including some from African countries, met recently to document the issues that will require detailed consideration to assess this promising approach. Questions related to scale-up, quality, purity and consistency of a manufacturing process using mosquitoes to generate a commercial product, and demonstration of the stability of attenuated sporozoites will need further work. Should a high level of efficacy be demonstrated in clinical challenge studies, it will become a priority to agree in which populations and age groups questions about strain-transcendence and duration of efficacy should be answered, and how clinical development can progress with an approach based on cryopreservation in liquid nitrogen.

Vaccine
Volume 28, Issue 30, Pages 4687-4858 (5 July 2010)
http://www.sciencedirect.com/science/journal/0264410X

Short Communications
Global production of seasonal and pandemic (H1N1) influenza vaccines in 2009–2010 and comparison with previous estimates and global action plan targets
Jeffrey Partridge, Marie Paule Kieny and the World Health Organization H1N1 influenza vaccine Task Force

Abstract
Immunization against influenza is considered among the most important interventions in reducing the public health impact of seasonal epidemic and pandemic influenza infections. However, there are marked differences across countries with regards to production, supply and access to influenza vaccines. A global action plan (GAP) to increase supply of pandemic influenza vaccine was developed by the World Health Organization in May 2006 to reduce the anticipated gap between potential vaccine demand and supply during an influenza pandemic. To quantify the increase in global influenza vaccine production capacity and actual production in response to the influenza A(H1N1) 2009 pandemic, 3 years after the development of the GAP, the WHO conducted a survey of vaccine producers from December 2009 through February 2010, and compared the results of this survey with results from surveys conducted in 2006–2007 and May 2009.

Vaccine
Volume 28, Issue 30, Pages 4687-4858 (5 July 2010)
http://www.sciencedirect.com/science/journal/0264410X

Reviews
A summary of the post-licensure surveillance initiatives for GARDASIL/SILGARD
Paolo Bonanni, Catherine Cohet, Susanne K. Kjaer, Nina B. Latham, Paul-Henri Lambert, Keith Reisinger, Richard M. Haupt

Abstract
GARDASIL has been shown to reduce the incidence of pre-cancerous cervical, vulvar, and vaginal lesions, and external genital warts causally related to HPV6/11/16/18. Because of its expected public health benefit on reduction of cervical cancer and other HPV-related diseases, this vaccine has been rapidly implemented in the routine vaccination programs of several countries. It is therefore essential to assess its impact and safety through post-licensure surveillance programs. Here, we present a summary of 16 post-licensure safety and impact studies across 20 countries. These studies address general safety, including autoimmune disorders, long-term effectiveness, and type replacement. A summary of the surveillance efforts of the Unites States Centers for Disease Control and Prevention can be found in the accompanying article by Markowitz et al.

Vaccine
Volume 28, Issue 30, Pages 4687-4858 (5 July 2010)
http://www.sciencedirect.com/science/journal/0264410X

Post-licensure monitoring of HPV vaccine in the United States
Lauri E. Markowitz, Susan Hariri, Elizabeth R. Unger, Mona Saraiya, S. Deblina Datta, Eileen F. Dunne

Abstract
Post-licensure evaluation of vaccines plays an important role in monitoring the progress of immunization programs, demonstrating population impact of vaccines, and providing data for ongoing policy decisions. Two human papillomovirus (HPV) vaccines are licensed and recommended for use in females in the United States, a quadrivalent human HPV vaccine, licensed in 2006 and a bivalent vaccine HPV vaccine licensed in 2009. HPV vaccination is recommended for females 11 or 12 years of age with catch-up vaccination through age 26 years. Post-licensure monitoring of the HPV vaccine program has included some of the same systems established for other vaccines, such as those for vaccine safety and coverage monitoring. However, monitoring HPV vaccine impact on infection and disease outcomes has required new efforts. While there are well established cancer registries in the United States, it will take decades before the impact of vaccine on cervical cancer is observed. More proximal measures of vaccine impact include outcomes such as prevalence of HPV vaccine types, incidence of cervical precancers and genital warts. We review systems in place or being established for post-licensure monitoring of HPV vaccine in the United States.

Vaccine
Volume 28, Issue 30, Pages 4687-4858 (5 July 2010)
http://www.sciencedirect.com/science/journal/0264410X

Regular Papers
Seasonal and Pandemic A (H1N1) 2009 influenza vaccination coverage and attitudes among health-care workers in a Spanish University Hospital
Silvia Vírseda, María Alejandra Restrepo, Elena Arranz, Purificación Magán-Tapia, Mario Fernández-Ruiz, Agustín Gómez de la Cámara, José María Aguado, Francisco López-Medrano

Abstract
Influenza vaccination coverage among health-care workers (HCWs) remains the lowest compared with other priority groups for immunization. Little is known about the acceptability and compliance with the pandemic (H1N1) 2009 influenza vaccine among HCWs during the current campaign. Between 23 December 2009 and 13 January 2010, once the workplace vaccination program was over, we conducted a cross-sectional, questionnaire-based survey at the University Hospital 12 de Octubre (Madrid, Spain). Five hundred twenty-seven HCWs were asked about their influenza immunization history during the 2009–2010 season, as well as the reasons for accepting or declining either the seasonal or pandemic vaccines. Multiple logistic-regression analysis was preformed to identify variables associated with immunization acceptance. A total of 262 HCWs (49.7%) reported having received the seasonal vaccine, while only 87 (16.5%) affirmed having received the pandemic influenza (H1N1) 2009 vaccine. “Self-protection” and “protection of the patient” were the most frequently adduced reasons for acceptance of the pandemic vaccination, whereas the existence of “doubts about vaccine efficacy” and “fear of adverse reactions” were the main arguments for refusal. Simultaneous receipt of the seasonal vaccine (odds ratio [OR]: 0.27; 95% confidence interval [95% CI]: 0.14–0.52) and being a staff (OR: 0.08; 95% CI: 0.04–0.19) or a resident physician (OR: 0.16; 95% CI: 0.05–0.50) emerged as independent predictors for pandemic vaccine acceptance, whereas self-reported membership of a priority group was associated with refusal (OR: 5.98; 95% CI: 1.35–26.5). The pandemic (H1N1) 2009 influenza vaccination coverage among the HCWs in our institution was very low (16.5%), suggesting the role of specific attitudinal barriers and misconceptions about immunization in a global pandemic scenario.

Vaccine
Volume 28, Issue 30, Pages 4687-4858 (5 July 2010)
http://www.sciencedirect.com/science/journal/0264410X

The potential global market size and public health value of an HIV-1 vaccine in a complex global market
Carol A. Marzetta, Stephen S. Lee, Sandra J. Wrobel, Kanwarjit J. Singh, Nina Russell, José Esparza

Abstract
An effective HIV vaccine will be essential for the control of the HIV pandemic. This study evaluated the potential global market size and value of a hypothetical HIV vaccine and considered clade diversity, disease burden, partial prevention of acquisition, impact of a reduction in viral load resulting in a decrease in transmission and delay to treatment, health care system differences regarding access, and HIV screening and vaccination, across all public and private markets. Vaccine product profiles varied from a vaccine that would have no effect on preventing infection to a vaccine that would effectively prevent infection and reduce viral load. High disease burden countries (HDBC; HIV prevalence ≥1%) were assumed to routinely vaccinate pre-sexually active adolescents (10 years old), whereas low disease burden countries (LDBC; HIV prevalence rate <1%) were assumed to routinely vaccinate higher risk populations only. At steady state, routine vaccination demand for vaccines that would prevent infection only was 22–61 million annual doses with a potential market value of $210 million to $2.7 billion, depending on the vaccine product profile. If one-time catch-up campaigns were included (11–14 years old for HDBC and higher risk groups for LDBC), the additional cumulative 70–237 million doses were needed over a 10-year period with a potential market value of $695 million to $13.4 billion, depending on the vaccine product profile. Market size and value varied across market segments with the majority of the value in high income countries and the majority of the demand in low income countries. However, the value of the potential market in low income countries is still significant with up to $550 million annually for routine vaccination only and up to $1.7 billion for a one-time only catch-up campaign in 11–14 years old. In the most detail to date, this study evaluated market size and value of a potential multi-clade HIV vaccine, accounting for differences in disease burden, product profile and health care complexities. These findings provide donors and suppliers highly credible new data to consider in their continued efforts to develop an HIV-1 vaccine to address the worldwide disease burden.

The International AIDS Vaccine Initiative (IAVI) announced that the Government of Japan pledged US$10 million to support AIDS vaccine research and development over the next five years. The grant will be managed through a newly-established World Bank trust fund. Seth Berkley, President and CEO of IAVI, said, “We are extremely grateful to Japan for its generous contribution to AIDS vaccine research and development, and also to the World Bank for its untiring support to IAVI and the fight against HIV/AIDS. Japan has been a leader in the fight against infectious diseases and has the scientific capacity to help advance research for one of the toughest public health challenges we face today, the control and ultimate elimination of HIV/AIDS.”

IAVI said that with funds from Japan, and in collaboration with its Japanese partners, it “will continue to advance an AIDS vaccine candidate that is constructed using a paramyxovirus known as the Sendai virus. Viral vectors based on the Sendai family have the potential to elicit a durable and highly-targeted immune response in mucosal tissues, where HIV often establishes infection before it amplifies and spreads.”

http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20100628005160&newsLang=en

[Editor’s Note: We will occasionally including opinion pieces from major media sources relevant of our focus on vaccines ethic and policy]

Pandemic lessons
Financial Times
Published: July 2 2010 22:26

As last year’s fear of a flu pandemic fades, the search for culprits is intensifying. Several post-mortems are under way, but the feverish search for scapegoats for the many billions of dollars spent by governments in preparations is misguided.

The UK’s evaluation, chaired by Dame Deirdre Hine and published last Thursday, offers a balanced judgment. It argues that the British response – which cost more than £1.2bn – was largely “proportionate and effective”.

Given the shortages of supply, the lengthy period required to make and test flu vaccines, and the uncertainties around the dangers of the virus at the time, ministers were understandably tempted to risk over-spending for a mild virus rather than under-spending and causing unnecessary deaths.

That is a better assessment than a recent hysterical report from the Council of Europe, which – relying on hindsight – claims a conspiracy of drug companies and health agencies exaggerated the threat of the pandemic. Its unsubstantiated critique risks undermining health agencies far more than they weakened themselves by what it claims amounted to “crying wolf.”

Seasonal flu kills hundreds of thousands of people each year. The current pandemic has claimed many more lives than the officially confirmed toll, including a disproportionate number of children and adults of working age.

The virus is still circulating and will return to the northern hemisphere this winter to cause more illness and death. It may yet mutate into a more serious form. Investments already made will help mitigate the effect.

Yet there are lessons to be drawn from the international response of the past few months. The World Health Organisation should introduce more subtlety to its flu pandemic assessment, adding a measure of severity to its simple definition of a new and fast-spreading virus.

Individual countries, including the UK, should modify their plans to make them more flexible. Many decisions were based on assumptions of a far more lethal virus than the current H1N1, and not adapted accordingly.

Greater efforts should also be made to include a broader range of experts in early risk assessments, such as carrying out more extensive blood tests across the UK. Such studies last year suggested early on that H1N1 was likely to be milder than initially feared.

Internationally, the slow pace of donations of flu vaccines to poorer countries has also highlighted excessive red tape that caused unnecessary infection and death.

A relatively benign virus more than any human intervention lay behind the current pandemic’s light burden. Next time, the threat may be greater and the response will need to be better.

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 107
Weekly update
2 July 2010
As of 27 June, worldwide more than 214 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 18239 deaths…

Situation update:
Summary: Worldwide, overall pandemic and seasonal influenza activity remains low. In the temperate regions of the Southern Hemisphere, Chile, and Argentina report low activity and only sporadic detections of both pandemic and seasonal influenza viruses during the early part of winter. South Africa, New Zealand, and Australia have all recently noted slight increases in the rate of respiratory disease. South Africa recently reported their first case of confirmed H1N1; however, the predominant influenza virus there currently is seasonal influenza A(H3N2). The H3N2 virus detected in South Africa is similar to the Perth-like strain, which is currently a component of the trivalent seasonal influenza vaccine. Active transmission of pandemic influenza virus still persists in localized areas of the tropics, particularly in South and Southeast Asia, the Caribbean and West Africa. During the last 2 to 3 weeks, seasonal influenza H3N2 viruses have also been detected at increasing levels in Nicaragua, and low levels or sporadically in Australia, Central America, South Africa and East Africa. Global circulation of seasonal influenza virus type B viruses persists at low levels in parts of East Asia, Central Africa, and Central America…

More at: http://www.who.int/csr/don/2010_07_02/en/index.html

Global Immunization News (GIN) for 30 June 2010 includes: Progress H1N1 Vaccination in the Americas” and is available at: http://www.who.int/immunization/GIN_June_2010.pdf

The WHO released a new podcast and transcript: “Polio: the fight till eradication.” The announcement noted that “polio eradication is at a critical juncture. While the world is close to stamping out polio, this will require renewed commitment. Specifically it will entail renewed political, financial and scientific commitment.”

Transcript at: http://www.who.int/mediacentre/multimedia/podcasts/2010/polio_20100702/en/index.html

Podcast at: http://terrance.who.int/mediacentre/podcasts/WHO_podcast_099.mp3

The MMWR weekly for July 2, 2010 / Vol. 59 / No. 25 includes:
– West Nile Virus Activity — United States, 2009

– Vaccinia Virus Infection After Sexual Contact with a Military Smallpox Vaccinee – — Washington, 2010

– Hepatitis A Vaccination Coverage Among U.S. Children Aged 12–23 Months — – Immunization Information System Sentinel Sites, 2006–2009

– Announcements: Immunization Update 2010 Webcast

http://www.cdc.gov/mmwr/PDF/wk/mm5925.pdf

Clinical Infectious Diseases
1 August 2010   Volume 51, Number 3
http://www.journals.uchicago.edu/toc/cid/current

Invited Articles
Emerging Infections: The Two Faces of Hepatitis E Virus
Eyasu H. Teshale, Dale J. Hu, and Scott D. Holmberg

Abstract
Hepatitis E virus (HEV) has at least 2 distinct epidemiological profiles: (1) large outbreaks and epidemics in developing countries, usually caused by HEV genotype 1, resulting in high morbidity and mortality among pregnant women and young children, and (2) very few symptomatic cases of HEV genotype 3, most cases without symptoms or clear source(s) of infection, but frequent seroreactivity in 5%–21% of asymptomatic persons in developed countries. We urge more epidemiological studies and public health interventions, including the promotion and development of existing and future vaccine candidates and the availability of US Food and Drug Administration–approved serological assays for this underappreciated and poorly understood virus, a major cause of disease throughout the world.

Human Vaccines
Volume 6, Issue 7 July 2010
http://www.landesbioscience.com/journals/vaccines/toc/volume/6/issue/6/

Reviews
Performance of rotavirus vaccines in developed and developing countries
Victoria Jiang, Baoming Jiang, Jacqueline Tate, Umesh D. Parashar and Manish M. Patel

Abstract
The World Health Organization estimates that rotavirus diarrhea results in approximately half a million deaths and approximately 2.4 million hospitalizations in developing countries each year. Two live oral rotavirus vaccines, RotaTeq (RV5; Merck) and Rotarix (RV1; GlaxoSmithKline) with good efficacy against severe rotavirus disease and a reassuring safety profile could substantially impact the burden of rotavirus disease. In April 2009, WHO provided a recommendation for global introduction of these vaccines in national immunization programs of developing countries worldwide. In this article, we review published data on previous candidate rotavirus vaccines and vaccines in current use, with emphasis on their performance in developed versus developing countries. In developed countries, both first and second generation rotavirus vaccines have demonstrated high efficacy against severe rotavirus disease (pooled efficacy = 73% and 85%, respectively). In developing countries, small early trials for the first generation vaccines failed to provide protection against rotavirus disease (pooled efficacy = 20%), however, trials of the second generation vaccines yielded substantial improvements in efficacy in developing countries (pooled efficacy of 51%), leading to a global recommendation for rotavirus vaccine introduction by WHO. Future efforts for these vaccines should focus on optimizing the efficacy and delivery of these vaccines in challenging target populations of Asia and Africa with the greatest burden of severe rotavirus disease.

Human Vaccines
Volume 6, Issue 7 July 2010
http://www.landesbioscience.com/journals/vaccines/toc/volume/6/issue/6/

Commentaries

China’s emerging vaccine industry
Jan Hendriks, Yan Liang and Bing Zeng

Abstract
The Chinese vaccine industry is developing rapidly due to an emerging and large market for current and new vaccines, a large potential for local vaccine manufacturing both in the public and private domain, and a governmental orientation towards national vaccine self-sufficiency. There are currently over 40 companies and institutions manufacturing a large variety of traditional (EPI) and some new vaccines. The innovative development capacity of state vaccine institutions is stimulated by significant government investments. Various Chinese influenza manufacturers were in 2009 among the first worldwide to obtain national license for their pandemic H1N1 flu vaccines. It is of interest to note that private but also governmental entities are committed to raise manufacturing quality standards to reach WHO prequalification. It is expected that WHO prequalification for at least one product from a Chinese manufacturer will have been obtained by 2011. This will open the door to the global market for Chinese vaccines.

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.