WHO reported on the meningococcal disease situation in the African Meningitis Belt. During the first 11 weeks of 2009 (January 1- March 15), a total of 24,868 suspected cases, including 1,513 deaths, have been reported to WHO by countries of the meningitis belt. More than 85% of the cases have occurred in one epidemic foci, encompassing Northern Nigeria and Niger and are characterized by the predominance of Neisseria meningitidis (Nm) serogroup A. WHO said it is supporting the Nigerian Federal and National Ministry of Health to strengthen disease surveillance, laboratory diagnosis, case management and in defining adapted vaccination strategies. Technical experts from WHO have been supporting the Federal Ministry of Health in Nigeria since mid February 2009.

The International Coordinating Group on Vaccine Provision for Epidemic Meningitis Control (ICG) have released 2.3 million doses of polysaccharide vaccines to Nigeria and 1.9 million doses of vaccine to Niger. ICG partners include WHO, International Federation of Red Cross and Red Crescent Societies, United Nations Children Fund, Médecins sans Frontières). The stockpile of the ICG for this epidemic season was set at 12.97 million doses. The emergency stockpile has been established with the support of Global Alliance for Vaccines and Immunization (GAVI) and EU Humanitarian Aid Office (ECHO).

http://www.who.int/csr/don/2009_03_25/en/index.html 25 March 2009

WHO released a new report noting that HIV-related TB deaths are higher than in past estimates with 1.37 million new TB cases in 2007 among HIV-infected people and 456,000 deaths. The total number of new tuberculosis (TB) cases remained stable in 2007, and the percentage of the world’s population becoming ill with TB has continued the slow decline that was first observed in 2004, according to the report. However, the new 2009 global TB control report “also reveals that one out of four TB deaths is HIV-related, twice as many as previously recognized.” The new figures “reflect an improvement in the quality of the country data, which are now more representative and available from more countries than in previous years.”

Dr Margaret Chan, Director-General of WHO, said, “These findings point to an urgent need to find, prevent and treat tuberculosis in people living with HIV and to test for HIV in all patients with TB in order to provide prevention, treatment and care. Countries can only do that through stronger collaborative programmes and stronger health systems that address both diseases.” The report also notes a sharp increase in HIV testing among people being treated for TB, especially in Africa. In 2004, just 4% of TB patients in the region were tested for HIV; in 2007 that number rose to 37%, with several countries testing more than 75% of TB patients for their HIV status.

Because of increased testing for HIV among TB patients, more people are getting appropriate treatment though the numbers still remain a small fraction of those in need.

TB/HIV co-infection and drug-resistant forms of tuberculosis present the greatest challenges, the report says. In 2007 an estimated 500,000 people had multidrug-resistant TB (MDR-TB), but less than 1% of them were receiving treatments that was known to be based on WHO’s recommended standards.

Dr Michel Kazatchkine, Executive Director of the Global Fund to Fight AIDS, Tuberculosis and Malaria, commented, “We have made remarkable progress against both TB and HIV in the last few years. But, TB still kills more people with HIV than any other disease. The financial crisis must not derail the implementation of the Global Plan to Stop TB. Now is the time to scale-up financing for effective interventions for the prevention, treatment and care of TB worldwide.” To meet the 2009 milestones in the Stop TB Partnership’s Global Plan to Stop TB, the funding shortfall for the core 94 countries has risen to about US$1.5 billion. Full funding of the Global Plan will achieve its aim of halving TB prevalence and deaths compared with 1990 levels by 2015, the report said.

http://www.who.int/mediacentre/news/releases/2009/tuberculosis_report_20090324/en/index.html

Global tuberculosis control – epidemiology, strategy, financing

WHO Report 2009
WHO/HTM/TB/2009.411

WHO’s report on Global TB Control compiles data from over 200 countries and territories each year, monitoring the scale and direction of TB epidemics, implementation and impact of the Stop TB Strategy, and progress towards the Millennium Development Goals.

http://www.who.int/tb/publications/global_report/2009/en/index.html

GAVI Alliance CEO Dr Julian Lob-Levyt thanked the United States government for a US$75 million contribution – its highest ever – “to support the Alliance’s work to immunise children and strengthen health systems in the world’s poorest countries.” The contribution was part of an omnibus appropriations bill passed by the US Congress that includes the contribution to support the work of the GAVI Alliance for fiscal year 2009. The new contribution will be administered through the US Agency for International Development, a GAVI partner and Board member. U.S. support to GAVI in FY 2008 amounted to $71.9 million. Dr Lob-Levyt commented, “As the deepening financial crisis forces donors to make tough choices, the priority must be to improve the health of the world’s poor, particularly children. We greatly appreciate the commitment of the US Congress and President Obama to increase support to GAVI.”

http://www.gavialliance.org/media_centre/statements/25_03_09__75_million_contribution_from_the_US.php

GAVI released an update on Immunisation Services Support (ISS) after a review by an independent task team around “the quality of data and the resulting estimates of coverage that this performance-based programme relies upon.”

GAVI said team members included academics and technical experts from a range of institutions, including the University of Aberdeen and the Harvard School of Public Health, the World Bank, and UNAIDS, among others. From December to March, the team “assessed the metrics that are currently used to measure ISS delivery and performance, reviewed relevant data collection sources and systems and compared these with alternative processes. Upon completion of its final meeting in February, the team produced a series of recommendations for GAVI.

The experts “agreed that there exists no single ‘gold standard’ for measuring the effectiveness of aid programme results and performance. The team recommended that GAVI continue to use the annual estimates compiled by WHO and UNICEF that relies on multiple data sources to monitor progress of immunisation programmes and calculate reward payments.” The experts also advised GAVI “to support the strengthening of the WHO/UNICEF estimation process to ensure systematic and transparent use of all data sources and made a number of specific recommendations to strengthen that process.

In order to provide an incentive to countries to increase immunisation coverage, as opposed to just the number of children immunised, the experts also recommended that future reward calculations be based in part on the number of children immunised and in part on the proportion of children immunised.”

The task team also recommended that GAVI “consider the reinstatement of ISS payments as soon as possible, whilst continuing to work with countries GAVI has identified as having data discrepancies.” At a meeting in early March, GAVI agreed to lift the suspension of ISS payments to all countries except for seven, which require further analysis. (GAVI originally identified 12 countries with discrepancies but removed five from the list after assessing their data collection processes and recognising that significant upgrades and improvements have been made which should prevent major discrepancies in the future.) The GAVI Alliance, in particular through the Health Metrics Network, WHO and UNICEF, is working with these remaining countries to address the data issues identified.

Further details on the review and recommendations at: http://www.gavialliance.org/media_centre/statements/25_03_09_UpdateonImmunisationServicesSupport_March.php

JAMA
Vol. 301 No. 12, pp. 1201-1304, March 25, 2009
http://jama.ama-assn.org/current.dtl

News and Analysis
Pneumonia Hospitalizations Among Young Children Before and After Introduction of Pneumococcal Conjugate Vaccine -United States, 1997-2006
JAMA. 2009;301(12):1220-1222.
[Extract: first 75 words]
Streptococcus pneumoniae is the leading bacterial cause of community-acquired pneumonia hospitalizations and an important cause of bacteremia and meningitis, especially among young children and older adults.^1-2 A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed and the Advisory Committee on Immunization Practices formulated recommendations for its use in infants and children in February 2000.² Vaccination coverage rapidly increased during the second half of 2000, in part through funding by CDC’s Vaccines for Children program. Subsequently, active population- and laboratory-based surveillance demonstrated substantial reductions in invasive pneumococcal disease (IPD) among children and adults.³ In addition, decreases in hospitalizations and ambulatory-care visits for all-cause pneumonia also were reported.^4-5 To gauge whether the effects of PCV7 on reducing pneumonia continue, CDC is monitoring pneumonia hospitalizations by using data from the Nationwide Inpatient Sample. This report provides an update for 2005 and 2006, the most recent years for . . .

The Lancet Infectious Disease
Apr 2009   Volume 9  Number 4   Pages 203 – 264
http://www.thelancet.com/journals/laninf/issue/current

Review
The prevalence of hypoxaemia among ill children in developing countries: a systematic review
Rami Subhi, Matthew Adamson, Harry Campbell, Martin Weber, Katherine Smith, Trevor Duke, for the Hypoxaemia in Developing Countries Study Group
Hypoxaemia is a common complication of childhood infections, particularly acute lower respiratory tract infections. In pneumonia-a disease that disproportionately impacts developing countries, and accounts for more than two million deaths of children worldwide-hypoxaemia is a recognised risk factor for death, and correlates with disease severity. Hypoxaemia also occurs in severe sepsis, meningitis, common neonatal problems, and other conditions that impair ventilation and gas exchange or increase oxygen demands.

The Lancet Infectious Disease
Apr 2009   Volume 9  Number 4   Pages 203 – 264
http://www.thelancet.com/journals/laninf/issue/current

Newsdesk
Vaccine investments raise millions to save children’s lives
Kathryn Senior
In March, HSBC, a leading UK bank, offered innovative vaccine-themed investments to individuals and institutional investors in the UK, to provide additional funding to the Global Alliance for Vaccines and Immunization (GAVI) for its childhood immunisation programme. Heike Reichelt from the treasury of the World Bank (Washington DC, USA) confirms that “the investments, issued by the International Finance Facility for Immunisation (IFFIm) and rated triple-A, are expected to raise at least UK£50 million.

The Lancet Infectious Disease
Apr 2009   Volume 9  Number 4   Pages 203 – 264
http://www.thelancet.com/journals/laninf/issue/current

Newsdesk
Infectious disease surveillance update
Onisillos Sekkides
In a recent report from, the UN Special Envoy for Malaria, Ray Chambers (New York, NY, USA), notes that the goal of reducing malaria deaths to near zero by the end of 2015 appears achievable. Currently the death rate is 1 million people per year, mostly children younger than 5 years. Of the 109 counties endemic for malaria, declines in malaria deaths have occurred in Ethiopia, Eritrea, Ghana, Kenya, Rwanda, and São Tomé and Príncipe. Zanzibar has reduced deaths to near zero, and Zambia has reduced the number of children carrying the malaria parasite by 50%

PLoS Medicine
[Accessed 30 March 2009)
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000048

Research Article
A World Malaria Map: Plasmodium falciparum Endemicity in 2007

Simon I. Hay1,2*, Carlos A. Guerra1,2, Peter W. Gething2,3, Anand P. Patil2, Andrew J. Tatem1,2,4,5, Abdisalan M. Noor1,6, Caroline W. Kabaria1, Bui H. Manh7, Iqbal R. F. Elyazar8, Simon Brooker1,9, David L. Smith5,10, Rana A. Moyeed11, Robert W. Snow1,6

Introduction
Maps are essential for all aspects of the coordination of malaria control [1]. In an international policy environment where the malaria control community has been challenged to rethink the plausibility of malaria elimination [2–4], malaria cartography will become an increasingly important tool for planning, implementing, and measuring the impact of malaria interventions worldwide. The last global map of P. falciparum endemicity was published in 1968 [5]. In common with all previous maps of the global distribution of malaria [6–10], and to a large extent those that followed [11–16], the map (i) suffered from an incomplete description of the input data used; (ii) defined contours of “risk” using subjective and poorly explained expert-opinion rules; and (iii) provided no quantification of the uncertainty around predictions. Here we describe the generation of a new global map of malaria endemicity that overcomes these major deficiencies….

Discussion
We have to our knowledge, for the first time in 40 y(ears) provided a contemporary map of P. falciparum malaria endemicity at the global scale. The map addresses the key deficiencies of older maps of the global distribution of malaria risk outlined previously and therefore is unique in the following ways. First, it is based on a heavily documented and geographically extensive malariometric survey database (Protocol S1) [58] that will be released in the public domain (where permission has been granted for individual surveys) for all to use and evaluate in 2009 [1]. Second, the MBG methods (Protocol S3) and validation procedures (Protocol S4) have also been documented in exhaustive detail and the relevant code been made available in the public domain. The entire mapping process should therefore be reproducible by those with access to the requisite computing resources. Third, a rigorous assessment of the uncertainty associated with the mapped outputs has been undertaken so that the confidence in the results can be evaluated objectively (Figure 5).

The World Malaria Situation in 2007
The world is substantially less malarious than would be predicted from the inspection of historical maps [5,14], both through a shrinking of the spatial limits and through a reduction in endemicity within this range. There is a striking global transition to a lower risk malaria ecology that will be explored in more detail in future work.

1 Malaria Public Health and Epidemiology Group, Centre for Geographic Medicine, Kenya Medical Research Institute (KEMRI)-University of Oxford-Wellcome Trust Collaborative Programme, Nairobi, Kenya, 2 Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, United Kingdom, 3 Centre for Geographical Health Research, School of Geography, University of Southampton, Highfield, Southampton, United Kingdom, 4 Department of Geography, University of Florida, Gainesville, Florida, United States of America, 5 Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America, 6 Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford, United Kingdom, 7 Oxford University Clinical Research Unit, Bach Mai Hospital, National Institute of Infectious and Tropical Diseases, Ha Noi, Vietnam, 8 Eijkman-Oxford Clinical Research Unit, Jakarta, Indonesia, 9 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, United Kingdom, 10 Department of Zoology, University of Florida, Gainesville, Florida, United States of America, 11 School of Mathematics and Statistics, University of Plymouth, Plymouth, Devon, United Kingdom

Science
27 March 2009  Vol 323, Issue 5922, Pages 1635-1762
http://www.sciencemag.org/current.dtl

News of the Week
BIOMEDICAL RESEARCH: Hughes Backs Institute at Epicenter of HIV and Resistant TB
Robert Koenig
Science 27 March 2009: 1659.
Summary: Last week, the Howard Hughes Medical Institute announced the KwaZulu-Natal Research Institute for Tuberculosis and HIV, a $60 million project on the campus of the Nelson R. Mandela School of Medicine at the University of KwaZulu-Natal in Durban.

Vaccine
Volume 27, Issue 18, Pages 2403-2528 (21 April 2009)
http://www.sciencedirect.com/science/journal/0264410X

Predictors of interest in HPV vaccination: A study of British adolescents
Pages 2483-2488
Laura A.V. Marlow, Jo Waller, Ruth E.C. Evans, Jane Wardle
Abstract
Human papillomavirus (HPV) vaccination is now offered to adolescent girls in the UK. Adolescents over 16 years old are likely to make their own decision about the vaccination. The purpose of this cross-sectional study was to assess acceptability of HPV vaccination among female adolescents (16-19 years) and investigate socio-cultural variation in intended acceptance. Participants were recruited through two further-education colleges in England. They read information about HPV before responding to questions assessing acceptability, demographics and attitudes based on the Health Belief Model. There were 367 cases included in analyses. Most participants said they would be likely to accept HPV vaccination (89%). Ethnicity, religion and English as a first language were associated with acceptability (pseudo-R2 = 0.11). In multivariate analysis only religion remained significant, with girls from Muslim (OR = 0.20, CI: 0.05-0.90) or Hindu/Sikh (OR = 0.09, CI: 0.01-0.56) backgrounds less likely to accept vaccination. Perceived susceptibility, benefits and barriers were also associated with acceptability (pseudo-R2 = 0.25), but did not mediate the effect of the ethnicity-related variables. Interventions based on the health belief model may help encourage HPV vaccine acceptance among adolescents. Future research to understand the issues associated with HPV vaccination in different religious groups is needed.

Director-General of the World Health Organization Dr Margaret Chan, addressed the 23rd Forum on Global Issues in Berlin, Germany on 18 March 2009 in a speech titled
“The impact of global crises on health: money, weather and microbes.” We excerpt extended portions of the speech; the full text is available at the link below.

“…The financial crisis and climate change are not the only markers of bad policies and failed systems of governance. The gaps in health outcomes, seen within and between countries, are greater now than at any time in recent history. The difference in life expectancy between the richest and poorest countries now exceeds 40 years. Globally, annual government expenditure on health varies from as little as US$ 20 per person to well over US$ 6000.

Medicine has never before possessed such a sophisticated arsenal of tools and interventions for curing disease and prolonging life. Yet each year, nearly 10 million young children and pregnant women have their lives cut short by largely preventable causes.

Something has gone wrong.

Collectively, we have failed to give the systems that govern international relations a moral dimension. The values and concerns of society rarely shape the way these international systems operate. If businesses, like the pharmaceutical industry, are driven by the need to make a profit, how can we expect them to invest in R&D for diseases of the poor, who have no purchasing power?

In far too many cases, economic growth has been pursued, with single-minded purpose, as the be-all, end-all, cure-for-all. Economic growth, as many believed, would cure poverty and improve health. This did not happen.

Globalization was embraced as the rising tide that would lift all boats. This did not happen. Instead, wealth has come in waves that lift the big boats, but swamp or sink many smaller ones.

Greater market efficiency, it was thought, would work to achieve greater equity in health. This did not happen.

Trade liberalization was put forward as a sure route to prosperity for developing countries. But trade liberalization slashed tariff revenues and brought no alternative source of finances for public services, including health care. This has meant a disaster for health and social protection in the many countries where most labour is concentrated in the informal sector and the tax base is small.

User fees for health care were put forward as a way to recover costs and discourage the excessive use of health services and the over-consumption of care. This did not happen. Instead, user fees punished the poor.

WHO estimates that, each year, the costs of health care push around 100 million people below the poverty line. This is a bitter irony at a time when the international community is committed to poverty reduction. It is all the more bitter at a time of financial crisis…”

“…Let me turn to a third issue: global crises that arise from the constantly changing microbial world. This issue is different from the financial crisis and climate change.

It is different because the health sector is in the lead. The health sector makes the policy, and implements governance through the International Health Regulations. We do not have to compete against economic interests. In fact, the tables are turned.

Emerging and epidemic-prone diseases are considered threats to international security precisely because of the tremendous economic and social disruption they can cause.

Public health has very few estimates that come even close to the multi-billion dollar financial bailouts we seem to hear about every week. But according to the latest World Bank estimate, the next influenza pandemic could easily cost the global economy US$ 3 trillion.

World leaders tell us that the financial crisis is so severe and unpredictable because it is the first such event under the unique conditions of the 21st century.

SARS, which emerged in 2003, was the first severe new disease of the 21st century. Like the financial crisis, it emerged at a time of radically increased interdependence.

SARS was the first disease to move rapidly around the world along the routes of international air travel. It put every city with an international airport at risk. It closed airports, businesses, schools, and some borders. It paralysed economies, and paralysed the public with fear.

But never forget: the response to SARS was a deliberate effort to prevent this new disease from becoming permanently established in this world, to keep it from joining the league of killer diseases like AIDS, TB, and malaria.

This was one severe global contagion that was quickly ended. WHO and its partners stopped SARS, dead in its tracks, within four months.

The health sector was prepared. Surveillance, alert, and response mechanisms were in place. We managed the risks. And this crisis did not spiral out of control.

From the beginning of the outbreak, the world’s top scientists set aside competition and worked together, in a virtual laboratory, around the clock. They identified the virus within a month.

This is the brighter side of globalization. This is an example of collaboration and solidarity before a shared threat.

We see this same international solidarity in support for the drive to eradicate polio, including humanitarian support from Rotary International, and support from several enlightened governments, including Germany.

Concern for health can also motivate ethical behaviour in industry, as when pharmaceutical companies dramatically cut prices for AIDS medicines. Concern for health can persuade the international community to agree on the control of harmful, yet profitable products, like tobacco.

There is hope….”

http://www.who.int/dg/speeches/2009/financial_crisis_20090318/en/index.html

Journal of Infectious Diseases
15 April 2009   Volume 199, Number 8
http://www.journals.uchicago.edu/toc/jid/current

EDITORIAL COMMENTARY
Prevention of Invasive Pneumococcal Disease in HIV-Infected Children: Expanding the Toolbox
Mark J. Abzug (1) and Stephen I. Pelton (2)
1University of Colorado Denver School of Medicine and The Children’s Hospital, Aurora; 2Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts

MAJOR ARTICLE
Quantitative and Qualitative Anamnestic Immune Responses to Pneumococcal Conjugate Vaccine in HIV-Infected and HIV–Uninfected Children 5 Years after Vaccination
Shabir A. Madhi,1,2; Keith P. Klugman,1,3; Locadiah Kuwanda,1,2; Clare Cutland,1,2; Helena Käyhty,3 and Peter Adrian1,2
Background.
Administration of pneumococcal conjugate vaccine (PCV) to HIV-infected children during infancy confers limited long-term protection in the absence of antiretroviral therapy. The objective of the present study was to determine the immune responses to PCV at 5 years of age in HIV-infected and HIV-uninfected children who had been primed with vaccine during infancy (i.e., previous vaccinees) and in those receiving their first dose of vaccine (i.e., control subjects).
Methods.
Serotype-specific antibodies were quantified by enzyme immunoassay, and antibody functionality to serotypes 6B, 9V, and 19F were evaluated using an opsonophagocytic killing assay 1 month after vaccination.
Results.
Of the HIV-infected children, 19.7% were receiving antiretroviral therapy, and 40.5% had a CD4+ cell percentage <15%. Geometric mean concentrations of antibody and the proportion with a concentration 0.35 μg/mL after vaccination were greater among HIV‐uninfected children than among HIV-infected children for both previous vaccinees and control subjects. Antibody concentrations after vaccination were lower for 3 of 7 serotypes among HIV-infected previous vaccinees than among control subjects. Detectable opsonophagocytic activity to all studied serotypes was lower among HIV-infected than among HIV‐uninfected previous vaccinees and control subjects. Postvaccination antibody‐mediated killing activity as determined by the opsonophagocytic killing assay was enhanced in control subjects compared with previous vaccinees among HIV‐uninfected children.
Conclusion.
HIV-infected vaccinees experience a partial loss of anamnestic responses to PCV. The optimal timing and frequency of booster vaccination as well as the responses to them among HIV-infected children need to be determined.

1Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand/Medical Research Council, and 2Vaccine Preventable Diseases, Department of Science and Technology/National Research Foundation, University of the Witwatersrand, Johannesburg, South Africa; 3Hubert Department of Global Health, Rollins School of Public Health and Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, Georgia; 4National Public Health Institute, Helsinki, Finland

The Lancet
Mar 21, 2009  Volume 373  Number 9668  Pages 979 – 1052
http://www.thelancet.com/journals/lancet/issue/current

Editorial
Dear Gordon: can we discuss the G20?
Preview
On April 2, world leaders from the G20-a group of 19 industrialised and emerging markets, plus the EU, which represents 85% of the global economic output-will meet in London at a summit hosted by the UK Prime Minister, Gordon Brown. The top item on their agenda is the financial crisis. A key, but neglected, dimension of this crisis is the effect of the global economic downturn on the health of the most vulnerable members of our society. What should the health professions expect-and ask for-from our political leaders?

The Lancet
Mar 21, 2009  Volume 373  Number 9668  Pages 979 – 1052
http://www.thelancet.com/journals/lancet/issue/current

Measles mortality reduction in Africa
Robin J Biellik, David WG Brown
Preview
Population-based measles serology is a well-established measure of the performance of vaccination programmes. This composite measure of immunity after vaccination and natural infection has been used extensively to inform programme strategies.1 Furthermore, WHO recommends the use of measles IgM serology for case confirmation in measles surveillance in countries that adopt measles mortality reduction or elimination goals.2 However, collection of serum specimens is invasive and creates a risk of exposure to blood-borne infections, and might be resisted in certain communities in developing countries.

The Lancet
Mar 21, 2009  Volume 373  Number 9668  Pages 979 – 1052
http://www.thelancet.com/journals/lancet/issue/current

Population immunity to measles virus and the effect of HIV-1 infection after a mass measles vaccination campaign in Lusaka, Zambia: a cross-sectional survey
Sara A Lowther, Frank C Curriero, Brian T Kalish, Timothy M Shields, Mwaka Monze, William J Moss
Summary
Background:
Measles control efforts are hindered by challenges in sustaining high vaccination coverage, waning immunity in HIV-1-infected children, and clustering of susceptible individuals. Our aim was to assess population immunity to measles virus after a mass vaccination campaign in a region with high HIV prevalence.
Methods:
3 years after a measles supplemental immunisation activity (SIA), we undertook a cross-sectional survey in Lusaka, Zambia. Households were randomly selected from a satellite image. Children aged 9 months to 5 years from selected households were eligible for enrollment. A questionnaire was administered to the children’s caregivers to obtain information about measles vaccination history and history of measles. Oral fluid samples were obtained from children and tested for antibodies to measles virus and HIV-1 by EIA.
Findings:
1015 children from 668 residences provided adequate specimens. 853 (84%) children had a history of measles vaccination according to either caregiver report or immunisation card. 679 children (67%) had antibodies to measles virus, and 64 (6%) children had antibodies to HIV-1. Children with antibodies to HIV-1 were as likely to have no history of measles vaccination as those without antibodies to HIV-1 (odds ratio [OR] 1·17, 95% CI 0·57-2·41). Children without measles antibodies were more likely to have never received measles vaccine than those with antibodies (adjusted OR 2·50, 1·69-3·71). In vaccinated children, 33 (61%) of 54 children with antibodies to HIV-1 also had antibodies to measles virus, compared with 568 (71%) of 796 children without antibodies to HIV-1 (p=0·1).
Interpretation:
3 years after an SIA, population immunity to measles was insufficient to interrupt measles virus transmission. The use of oral fluid and satellite images for sampling are potential methods to assess population immunity and the timing of SIAs.
Funding:
Thrasher Research Fund.

New England Journal of Medicine
Volume 360 – March 19, 2009 – Number 12
http://content.nejm.org/current.shtml

Editorial
One Step Closer to a CMV Vaccine
C. L. Dekker and A. M. Arvin
“In this issue of the Journal, Pass and colleagues describe the results of a phase 2 trial of a vaccine containing recombinant cytomegalovirus (CMV) glycoprotein B subunit antigen combined with MF59 adjuvant for the prevention of CMV infection in seronegative women of childbearing age.1 The primary end point was the time to CMV infection in the women. Their report of 50% vaccine efficacy (95% confidence interval, 7 to 73) is a promising development in the long search for an effective vaccine to protect against congenital CMV infection…”

Vaccine Prevention of Maternal Cytomegalovirus Infection
Robert F. Pass, M.D., Changpin Zhang, M.D., Ashley Evans, M.D., Tina Simpson, M.D., William Andrews, M.D., Meei-Li Huang, Ph.D., Lawrence Corey, M.D., Janie Hill, R.N., Elizabeth Davis, R.N., M.P.H., Cynthia Flanigan, B.S., and Gretchen Cloud, M.S.
ABSTRACT
Background: Congenital infection with cytomegalovirus (CMV) is an important cause of hearing, cognitive, and motor impairments in newborns.

Methods: In this phase 2, placebo-controlled, randomized, double-blind trial, we evaluated a vaccine consisting of recombinant CMV envelope glycoprotein B with MF59 adjuvant, as compared with placebo. Three doses of the CMV vaccine or placebo were given at 0, 1, and 6 months to CMV-seronegative women within 1 year after they had given birth. We tested for CMV infection in the women in quarterly tests during a 42-month period, using an assay for IgG antibodies against CMV proteins other than glycoprotein B. Infection was confirmed by virus culture or immunoblotting. The primary end point was the time until the detection of CMV infection.

Results: We randomly assigned 234 subjects to receive the CMV vaccine and 230 subjects to receive placebo. A scheduled interim analysis led to a stopping recommendation because of vaccine efficacy. After a minimum of 1 year of follow-up, there were 49 confirmed infections, 18 in the vaccine group and 31 in the placebo group. Kaplan-Meier analysis showed that the vaccine group was more likely to remain uninfected during a 42-month period than the placebo group (P=0.02). Vaccine efficacy was 50% (95% confidence interval, 7 to 73) on the basis of infection rates per 100 person-years. One congenital infection among infants of the subjects occurred in the vaccine group, and three infections occurred in the placebo group. There were more local reactions (pain, erythema, induration, and warmth) and systemic reactions (chills, arthralgias, and myalgias) in the vaccine group than in the placebo group.

Conclusions: CMV glycoprotein B vaccine has the potential to decrease incident cases of maternal and congenital CMV infection. (ClinicalTrials.gov number, NCT00125502 [ClinicalTrials.gov] .)

Vaccine
Volume 27, Issue 17, Pages 2299-2402 (14 April 2009)
http://www.sciencedirect.com/science/journal/0264410X

Influenza vaccination coverage among adult solid organ transplant recipients at three health maintenance organizations, 1995-2005
Pages 2335-2341
KaLynne Harris, James Baggs, Robert L. Davis, Steven Black, Lisa A. Jackson, John P. Mullooly, Louisa E. Chapman
Abstract
Annual immunization against influenza is recommended for solid organ transplant (SOT) recipients. We used Vaccine Safety Datalink data from 1995 to 2005 to assess influenza vaccination during the first full vaccination season (September-February) following transplant among 1800 kidney, liver, and heart transplant recipients at three health maintenance organizations. Overall, 52% of recipients were vaccinated. Older age at transplant (age 50-64 years, OR 1.81, 95% CI 1.43-2.30; age ≥65 years, OR 1.94, 95% CI 1.39-2.69), receiving vaccination in the full season pre-transplant (OR 4.54, 95% CI 3.67-5.60), and year of transplantation were significant predictors of post-transplant vaccination. Although vaccine coverage increased during study years, SOT recipients are under-immunized against influenza. Efforts to understand barriers to vaccination and increase education of physicians managing patients while awaiting and after receipt of transplant are needed.

Vaccine
Volume 27, Issue 17, Pages 2299-2402 (14 April 2009)
http://www.sciencedirect.com/science/journal/0264410X

Influenza vaccination rates in Ontario children: Implications for universal childhood vaccination policy
Pages 2350-2355
Kathy Moran, Sarah Maaten, Astrid Guttmann, David Northrup, Jeffrey C. Kwong
Abstract
The aims of this study were to estimate influenza vaccination coverage for children during the 2006-2007 influenza season in Ontario, Canada, where universal vaccination is available, and to compare the rate among children aged 6-23 months with corresponding rates from other Canadian provinces that specifically target this high-risk group. We conducted a telephone survey of caregivers of children aged 6 months-11 years that included 4854 children from 3029 households. Ontario’s vaccination rate (complete and partial coverage combined) for children aged 2-11 years was 28.3% (95% CI 26.3-30.5%) for healthy children and 36.8% (95% CI 31.4-42.5%) for those with chronic conditions. Immunization coverage of children aged 6-23 months was 24.0% (95% CI 20.6-27.7%) in Ontario, similar to Manitoba’s rate of 24.1% but lower than rates in other provinces: Nova Scotia (35.5%), Quebec (41.8% for 1 year olds and 37.7% for 2 year olds during the 2005-2006 season), Saskatchewan (32.5%) and Alberta (52.2%). Universal vaccination in Ontario has achieved modest coverage in children aged 2-11 years, but has been less successful than targeted programs in vaccinating infants aged 6-23 months.

The University of Florida (UF) announced that it has received a US$1.5 million grant from the Bill & Melinda Gates Foundation “to develop modeling tools for malaria elimination.” This is the first time a UF researcher has been awarded a direct grant from the foundation. David L. Smith, associate director of disease ecology at UF’s Emerging Pathogens Institute and an associate professor in the zoology department, will lead work on the new project. Dr. Smith commented, “To plan, we need to understand how malaria parasites move around in humans, and we also need to understand the interplay between economic and ecological aspects of malaria elimination. These are difficult questions to answer, but we hope to provide some quantitative advice to help guide countries as they make strategic decisions about malaria elimination.”

The Emerging Pathogens Institute of UF “brings together researchers from diverse fields to develop control, diagnostic and treatment plans including vaccines and other antimicrobials for new and emerging diseases. The Institute’s focus is to develop the research capabilities to prevent and contain outbreaks of new diseases that threaten Florida, the rest of the country and ultimately the world.” This research is also part of efforts by the Malaria Atlas Project (MAP) to develop evidence-based high spatial resolution maps of malaria endemicity. The modeling tools will help to fill gaps in malaria theory so these maps can be used for malaria elimination planning. The new research will increase the general understanding of disease transmission.

http://www.uff.ufl.edu/News/PressRelease.asp?Story=110

The U.S. Food and Drug Administration (FDA) approved “the first DNA test that identifies the two types of human papillomavirus (HPV) that cause the majority of cervical cancers among women in the United States.” The test, called Cervista HPV 16/18, detects the DNA sequences for HPV type 16 and HPV type 18 in cervical cells. A positive Cervista 16/18 test result indicates whether HPV type 16, 18 or both types are present in the cervical sample. Differentiating these HPV types “gives health care professionals more information on a patient’s risk of subsequently developing cervical cancer.” The FDA also approved yesterday the Cervista HPV HR test, which is the second DNA test that detects essentially all of the high-risk HPV types in cervical cell samples. The Cervista HPV HR test uses a method similar to the Cervista HPV 16/18 test to detect the DNA sequences of these HPV types. Daniel G. Schultz, M.D., director of the FDA’s Center for Devices and Radiological Health, said, “Results from these two tests, when considered with a physician’s assessment of the patient’s history, other risk factors, and professional guidelines, can help physicians better determine risk and could lead to better patient management.”
http://www.fda.gov/bbs/topics/NEWS/2009/NEW01974.html

JAMA
Vol. 301 No. 10, pp. 997-1086, March 11, 2009
http://jama.ama-assn.org/current.dtl

The Evolution of Influenza Resistance and Treatment
David M. Weinstock, MD; Gianna Zuccotti, MD
JAMA. 2009;301(10):1066-1069. Published online March 2, 2009 (doi:10.1001/jama.2009.324).

[Concluding paragraph]
“… The understanding of influenza biology and epidemiology has advanced markedly; however, the global dissemination of oseltamivir-resistant influenza came as a great surprise. Undoubtedly, new surprises await in the perpetual struggle with influenza as one thing is certain-the organism will continue to evolve. Anticipating the rapid and endless changes in influenza biology and dynamics will require faster diagnostics to molecularly characterize specimens, extensive surveillance among humans and animals, and more rapid and malleable systems for translating basic and epidemiological discoveries into clinically applicable interventions. For now, the best tools to mitigate influenza infection are tried-and-true-vaccination, social distancing, hand washing, and common sense.”

Journal of Infectious Diseases
1 April 2009   Volume 199, Number 7
http://www.journals.uchicago.edu/toc/jid/current

EDITORIAL COMMENTARY
Human Papillomavirus (HPV) Vaccines: Limited Cross-Protection against Additional HPV Types
Rolando Herrero Epidemiológico Guanacaste, Fundación INCIENSA, San José, Costa Rica Proyecto
[No abstract available]

Viruses
The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus–Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Generally HPV–Naive Women Aged 16-26 Years
Darron R. Brown, Susanne K. Kjaer, Kristján Sigurdsson, Ole‐Erik Iversen, Mauricio Hernandez‐Avila, Cosette M. Wheeler, Gonzalo Perez, Laura A. Koutsky, Eng Hseon Tay, Patricía Garcia, Kevin A. Ault, Suzanne M. Garland, Sepp Leodolter, Sven‐Eric Olsson, Grace W. K. Tang, Daron G. Ferris, Jorma Paavonen, Marc Steben, F. Xavier Bosch, Joakim Dillner, Elmar A. Joura, Robert J. Kurman, Slawomir Majewski, Nubia Muñoz, Evan R. Myers, Luisa L. Villa, Frank J. Taddeo, Christine Roberts, Amha Tadesse, Janine Bryan, Lisa C. Lupinacci, Katherine E. D. Giacoletti, Heather L. Sings, Margaret James, Teresa M. Hesley, and Eliav Barr

The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus–Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Sexually Active Women Aged 16-26 Years
Cosette M. Wheeler, Susanne K. Kjaer, Kristján Sigurdsson, Ole‐Erik Iversen, Mauricio Hernandez-Avila, Gonzalo Perez, Darron R. Brown, Laura A. Koutsky, Eng Hseon Tay, Patricia García, Kevin A. Ault, Suzanne M. Garland, Sepp Leodolter, Sven‐Eric Olsson, Grace W. K. Tang, Daron G. Ferris, Jorma Paavonen, Marc Steben, F. Xavier Bosch, Joakim Dillner, Elmar A. Joura, Robert J. Kurman, Slawomir Majewski, Nubia Muñoz, Evan R. Myers, Luisa L. Villa, Frank J. Taddeo, Christine Roberts, Amha Tadesse, Janine Bryan, Lisa C. Lupinacci, Katherine E. D. Giacoletti, Margaret James, Scott Vuocolo, Teresa M. Hesley, and Eliav Barr

New England Journal of Medicine
Volume 360 – March 12, 2009 – Number 11
http://content.nejm.org/current.shtml

Perspectives
Global Health: Rotavirus Vaccines – Early Success, Remaining Questions
U. D. Parashar and R. I. Glass

[Final paragraphs]
“…Despite the promising early data from the United States, a key unanswered question is whether rotavirus vaccines will work equally well in the developing world, where they offer the greatest potential lifesaving benefits. Experience with previous candidate rotavirus vaccines, as well as vaccines against polio, cholera, and typhoid fever, has shown that the efficacy of live, oral vaccines can be impaired in developing countries. Several host and environmental factors – such as interference by maternal antibodies, concurrent administration of oral polio vaccine, prevalent viral and bacterial infections of the gut, and malnutrition – could affect the processing of vaccine in the infant gut and impair an infant’s ability to generate an effective immune response. For these reasons, the World Health Organization (WHO) has recommended evaluation of the efficacy of rotavirus vaccines in developing countries of Asia and Africa before issuing a recommendation for global vaccine use. Both RotaTeq and Rotarix are being tested in these regions, and the results of these trials are eagerly anticipated.

“If rotavirus vaccines demonstrate acceptable efficacy in developing countries and the WHO issues a global recommendation for their use, mechanisms for financing the introduction of the vaccines and securing a sustainable and affordable supply will be key to ensuring that they reach children in the poorest countries, where the vast majority of deaths from rotavirus occur. The Global Alliance for Vaccines and Immunization (GAVI) has already approved financial support for the purchase of rotavirus vaccines for eligible countries (those with a gross national income of less than $1,000 per capita) in Latin America and Europe, where vaccine efficacy has been proven, with a copayment for countries of 15 to 30 cents for a full vaccine series for each child. GAVI will decide whether to provide financial support for the purchase of rotavirus vaccine for countries in Asia and Africa after data from trials in these areas become available.

“With financial support and recommendations from the WHO and other international health organizations, the long wait for safe and effective vaccines to prevent deaths and severe disease from rotavirus diarrhea among children in the developing world may soon be over. In countries where these vaccines are currently being used as part of childhood immunization programs, their benefits are becoming readily apparent. In the United States, with increasing uptake of vaccine, we anticipate significant respite for children, parents, physicians, and health care facilities from the large burden of rotavirus disease in the current rotavirus season.”

Vaccine
Volume 27, Issue 16, Pages 2195-2298 (6 April 2009)
http://www.sciencedirect.com/science/journal/0264410X

Guidelines for collection, analysis and presentation of vaccine safety data in pre- and post-licensure clinical studies
Pages 2282-2288
[No abstract available]

Guidelines for collection, analysis and presentation of vaccine safety data in surveillance systems
Pages 2289-2297
Jan Bonhoeffer, Adwoa Bentsi-Enchill, Robert T. Chen, Margaret C. Fisher, Michael S. Gold, Katharina Hartman, Ulrich Heininger, Bernard Hoet, Thomas Jefferson, Najwa Khuri-Bulos, Katrin Kohl, S. Michael Marcy, David Nalin, Robert Pless, Hernan Sanabria-Rojas, Karen Sleeman, Robert Wise and The Brighton Collaboration Methods Working Group
[No abstract available]

Vaccine
Volume 27, Issue 16, Pages 2195-2298 (6 April 2009)
http://www.sciencedirect.com/science/journal/0264410X

A predictive model of the economic effects of an influenza vaccine adjuvant for the older adult (age 65 and over) population
Pages 2251-2257
Bruce Y. Lee, Anna K. Ercius, Kenneth J. Smith
Abstract
Immunosenescence decreases influenza vaccine efficacy in older adults (age 65 and over). Strategies such as vaccine adjuvants are being developed to overcome immunosenescence. Our computer simulation model represented the decision to give an older adult either standard influenza vaccine or adjuvanted influenza vaccine and found the adjuvanted vaccine to be dominant in many scenarios, resulting in lowered cost and greater effectiveness. An adjuvanted vaccine that is 100% effective in overcoming immunosenescence remained dominant until its cost exceeded the standard vaccine cost by $65. In a single influenza season, the adjuvant would prevent 496,533 influenza cases, 171,981 hospitalizations, and 70,429 deaths.

Vaccine
Volume 27, Issue 16, Pages 2195-2298 (6 April 2009)
http://www.sciencedirect.com/science/journal/0264410X

Vaccination against the Human Papillomavirus: The lessons we have not learned
Pages 2195-2198
Brianna Hoffner
Abstract
Recent conversations regarding the vaccine against the Human Papillomavirus have focused on scientific concerns of effectiveness and scope of prevention as well as social, political and economic concerns including who should be eligible to receive the vaccine and why. However, discussions to date have not reflected on comparable historical perspectives including lessons learned in the development and marketing of the Hepatitis B vaccine. These two vaccines have remarkably similar public health implications in the prevention of specific cancers as well as generating alike social, political and financial concerns. The present paper examines these similarities with the intention of providing perspective on the current Human Papillomavirus vaccine debate and advocating for more expedient and expansive vaccine availability.

The GAVI Alliance said it “has started implementing a proactive gender policy into its work to ensure equal access to immunisation for boys and girls.” GAVI’s Gender Policy “commits the Alliance to use a gender perspective in the design, planning, and delivery of vaccinations and other health services. One of the largest providers of life-saving vaccines to children in the developing world, the Alliance believes that access to vaccines and better health should be an equal right for all.”

GAVI Policy Director Nina Schwalbe commented, “Immunisation has often been perceived as gender neutral, however initial studies indicate that there may be differences both in coverage and burden of disease that need to be considered. By implementing a gender policy, GAVI promotes the principles enshrined in international commitments. It also aligns the Alliance with the Paris Declaration on Aid Effectiveness, with its cross-cutting issues of human rights and gender equality. As an Alliance we are in an ideal position to raise awareness and promote efforts towards gender equality in immunisation and related services on the country-level and globally.”

GAVI said that as part of its implementation plan, “from this year on, the Alliance will generate new data on the gender aspects of vaccination coverage and related health services. The Alliance will also assess the gender impact of all new vaccines it introduces, including the vaccine against cervical cancer. GAVI has already started applying the policy in its Health Systems Strengthening programmes.”

http://www.gavialliance.org/media_centre/press_releases/GAVI_Alliance_promotes_gender_equality.php

WHO summarized presentations made at the 4th Global Immunization Meeting, held in New York, 17-19 February 2009, focused on funding shortfalls in WHO’s current annual budget for immunization. The budget is about US$140 million, and main contributors to the 2008-09 budget include the Bill & Melinda Gates Foundation; the GAVI Alliance; the governments and aid agencies of Canada and the United States of America; Johns Hopkins University; the Measles Partnership; PATH; and UNICEF.

During recent years, direct financial support for WHO’s immunization work has decreased, with “increasing specificity of funds.” The projected budget required for 2010-11 is US$210 million. Of this amount, there is a funding gap of US$109 million, or 52%. Since 2002, on average only 80% of WHO’s immunization budget has been met each year. This has “led to challenges in fulfilling core functions in the area of immunization.”

In 2007-2008, “various critical activities were not implemented due to the persistence of funding gaps. Updated recommendations for the production, control and evaluation of a number of existing vaccines could not be developed, resulting in a subsequent delay in their prequalification and a potential shortage in their availability. Funding gaps also impacted the evaluation of pneumococcal vaccines as well as the provision of technical support to countries, particularly in the WHO African Region.”

The structure of WHO’s immunization budget “has become such that today donors providing direct support are committed, but few in number, with the funds that they provide highly specified, leaving little flexibility. These factors do not allow WHO to allocate resources for immunization optimally and are impacting upon WHO’s ability to deliver on its global immunization mandate. Increased direct, flexible funding from a greater number of donors would improve WHO’s ability to deliver on core immunization functions.”

http://www.who.int/immunization/funding/en/index.html

Presentations

Global immunization efforts. Successes, gaps and challenges [pdf 3.30Mb]
Update of GIVS Financing and Current Gaps/Needs since 2005 [pdf 954kb]

The Weekly Epidemiological Record (WER) 6 March 2009, vol. 84, 10 includes “Progress towards poliomyelitis eradication in Afghanistan and Pakistan, 2008” and “Poliomyelitis in Sudan: heightened risk of international spread.”
http://www.who.int/wer/2009/wer8410.pdf

Poliomyelitis in Sudan: heightened risk of international spread

The recent expansion of a prolonged outbreak of wild poliovirus type 1 (WPV1) in Sudan poses a very high risk of further international spread, requiring urgent and immediate outbreak response activities in the affected areas and heightened surveillance in countries at risk. Previously restricted to southern Sudan and western Ethiopia, the outbreak has now spread to Kenya, northern Sudan (in Khartoum and Port Sudan) andUganda.

Of particular concern is the confirmation of WPV1 in Port Sudan. It is from this area that, in 2004-2006, WPV1 spread to reinfect several countries, including Indonesia, Saudi Arabia, Somalia and Yemen, causing outbreaks that generated >1200 cases and >US$ 150 million in international emergency outbreak response costs. Given the historical international spread of polioviruses from Port Sudan, the new international spread from southern Sudan to Kenya and Uganda, and the suboptimal quality of outbreak response activities in southern Sudan and western Ethiopia (monitoring data indicate that >30% of children remain unimmunized or under-immunized with ≤3 doses of oral poliovirus vaccine, or OPV3), WHO assesses the risk of further international spread from the Sudan as being very high. Stopping this outbreak requires full implementation of international polio outbreak response standards, adopted by the World Health Assembly in May 2006, until transmission has been confirmed to be interrupted.

In northern Sudan, large-scale supplementary immunization activities (SIAs) began on 15 February, with additional campaigns planned for 23 March and again in late April. In southern Sudan, SIAs were held on 13 January and 23 February, with further activities planned for 23 March and late April, following which the onset of the rainy season in May could complicate the logistics of reaching all populations in this already difficult-to-access terrain. Consequently, particular attention is being given to closing the persistent gaps in drug coverage with OPV during the upcoming SIAs.

In coordination with the polio campaigns in the Sudan, plans for rapid outbreak response campaigns are being finalized for late March, late April and possibly again in late May in the affected areas of Kenya and Uganda. Genetic sequencing data suggest that the importations into these countries have been rapidly detected, improving the prospects for interrupting transmission in the near term if the campaigns are of sufficiently high quality to reach >90% of children in the affected areas.

It is important that countries across central Africa, the Horn of Africa and the Gulf strengthen surveillance for cases of acute flaccid paralysis, in order to promptly detect any new poliovirus importations and facilitate a rapid response. Countries should also analyse routine immunization coverage data to identify any subnational gaps in population immunity to guide catch-up immunization activities and thereby minimize the consequences of any new virus introduction. Priority should be given to areas at high risk of importations and to where routine coverage of OPV3/DTP31 is <80%.

Also reported as an MMWR summary at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5808a4.htm

The Pneumococcal Awareness Council of Experts (PACE) reported on two new studies which highlight the increased risk for children in Africa of contracting pneumococcal disease. The studies were presented at the Sabin Vaccine Institute’s 4th Regional Pneumococcal Symposium in Johannesburg, South Africa. According to PACE, the results “reinforce the urgent need for improving access to life-saving vaccines and treatments throughout the continent.” The South African Ministry of Health was honored at the meeting “for its leadership in making South Africa the first country in Africa to introduce pneumococcal vaccine.”

The PACE studies show that “sickle cell disease, which is common in many parts of Africa, increases the risk of pneumococcal disease by 37 times, and together with HIV infection, malnutrition and indoor air pollution, puts African children at high risk.

Even when treated with antibiotics in a hospital, up to one-half of all children in Africa who get pneumococcal meningitis will either die or be disabled as a consequence of the disease.” Dr. Jean Marie Okwo-Bele, director of the WHO Department of Immunization, Vaccines and Biologicals, commented, “Millions of lives can be saved through the routine introduction of the pneumococcal vaccine in developing countries. The World Health Organization recommends that countries at all income levels introduce this vaccine, with the highest priority given to countries with high child mortality rates.”

The media release noted that “as a result of collaborative efforts by WHO, UNICEF, the GAVI Alliance, academia, foundations, industry and developing country governments, estimates indicate that developing countries are now able to introduce affordable pneumococcal vaccines at least 10 years faster than historical precedents.”

The Pneumococcal Awareness Council of Experts (PACE), a project of the Sabin Vaccine Institute, “is comprised of leading global experts in infectious diseases and vaccines. The Council raises awareness among policy-makers and aims to secure global commitments to prevent pneumococcal disease, a leading infectious killer of children and adults worldwide. The Council works through collaboration and partnership with countries, NGOs, academia and industry to achieve its goals.”

(BUSINESS WIRE, 3 March 2009)

Department of Ethics
Moving from research ethics review to research ethics systems in low-income and middle-income countries
Adnan A Hyder, Liza Dawson, Abdulgafoor M Bachani, James V Lavery
Abstract
The challenges associated with research ethics in low-income and middle-income countries are complex. The development of effective programmes for reviewing research and protecting participants in these countries engages wider issues surrounding the general stage of development and democratisation of developing-world societies, and cannot be addressed by regulatory processes alone. Despite sustained attention to the challenges of research-capacity building by developing countries, there have been few attempts to describe how a country’s stage of development relates to the two challenges central to research ethics—protection of research participants and promotion of ethical conduct in research.

The Lancet
Mar 07, 2009 Volume 373 Number 9666 Pages 781 – 866
http://www.thelancet.com/journals/lancet/issue/current

Common attitudes about concomitant vaccine injections for infants and adolescents in Flanders, Belgium
Heidi Theeten, Niel Hens, Marc Aerts, Corinne Vandermeulen, Mathieu Roelants, Karel Hoppenbrouwers, Pierre Van Damme, Philippe Beutels
Abstract
Quantitative information on parents’ preferences regarding multiple vaccine injections and on work-loss due to vaccination is important to guide decision making on the use of combination vaccines for universal vaccination. Our survey in families of 1347 toddlers (18–24 months) and 1315 adolescents residing in Flanders, Belgium, revealed common attitudes in both age groups. The majority of parents would allow maximum two injections in one visit. 39% were not willing to pay anything to avoid a concomitant injection, whereas the remainder mentioned amounts around a median of €20. The responses were hardly influenced by the socioeconomic determinants studied and the concordance between the number of concomitant injections parents would allow and their willingness-to-pay assessed by an open-ended question was limited, which suggests that more sensitive quantification using other methods would be useful. Work-loss due to vaccination was assessed for infants only and was rare (4.5%).

Vaccine
Volume 27, Issue 13, Pages 1881-1984 (18 March 2009)
http://www.sciencedirect.com/science/journal/0264410X

Designing phase III or IV trials for vaccines: Choosing between individual or cluster randomised trial designs
Paul Vaucher
Abstract
The choice of design between individual randomisation, cluster or pseudo-cluster randomisation is often made difficult. Clear methodological guidelines have been given for trials in general practice, but not for vaccine trials. This article proposes a decisional flow-chart to choose the most adapted design for evaluating the effectiveness of a vaccine in large-scale studies. Six criteria have been identified: importance of herd immunity or herd protection, ability to delimit epidemiological units, homogeneity of transmission probability across sub-populations, population’s acceptability of randomisation, availability of logistical resources, and estimated sample size. This easy to use decisional method could help sponsors, trial steering committees and ethical committees adopt the most suitable design.

Vaccine Volume 27, Issue 13, Pages 1881-1984 (18 March 2009) http://www.sciencedirect.com/science/journal/0264410X

“Vaccine manufacturers have substantially increased their capacity to produce pandemic influenza vaccines during the past two years…(and) while capacity is increasing, it would not be sufficient to meet the global need for emergency production of pandemic influenza vaccines at the time of a pandemic,” according to a new study by Oliver Wyman, an international strategy consulting firm.

The study was conducted in collaboration with the World Health Organization (WHO) and The International Federation of Pharmaceutical Manufacturers Associations (IFPMA) and funded by the Bill & Melinda Gates Foundation.

IFPMA Director General Alicia D. Greenidge said, “This study advances our understanding of the world’s ability to address pandemic influenza, and demonstrates the progress made by our member companies in developing new vaccine technologies and expanding production facilities. Our member companies are committed to working with the WHO and countries to ensure that we make the best use of the surplus capacity to prepare for a pandemic. The findings suggest that the early use of stockpiled H5N1-based vaccines, followed by pandemic vaccines as soon as these become available, offers a realistic strategy to address this significant threat.”

The study reported that:
– Pandemic influenza vaccine production capacity has increased by 300 percent over the last two years, largely driven by improvements in production yields and dosage-sparing technologies.
– With current technology, doses of vaccine tailored to the actual pandemic influenza strain will not be available until four months after identification of that strain by the WHO due to the technical lead time required to adapt the strain for vaccine production, manufacture vaccine, and distribute product.
– In the base (most likely) case, manufacturers could produce 2.5 billion doses of pandemic vaccine in the 12 months following receipt of the production strain, requiring 4 years to satisfy global demand. In the best case, 7.7 billion doses could be produced in the first 12 months, requiring 1.5 years to satisfy global demand.
– This capacity is expected to rise to 5 – 14.5 billion doses over the next five years. The resulting time to meet global demand would be reduced to between 2.5 years (in the base case) and 1 year (in the best case).
– Surplus capacity (above current seasonal influenza and stockpile demand) currently exists to produce 2.5 billion annual doses of H5N1 vaccine prior to a pandemic. This surplus capacity is expected to rise to between 2.6 and 5.4 billion doses per year over the next 5 years.

http://www.ifpma.org/News/NewsReleaseDetail.aspx?nID=11559

Cincinnati Children’s Hospital Medical Center (Ohio, USA) said it received a US$6.7 million grant from the Bill & Melinda Gates Foundation “to help prevent flu in pregnant women and their infants in rural areas around the world.” Researchers led by the Cincinnati Children’s Division of Global Health “will expand on a recent study (also supported by a Gates Foundation grant) showing that influenza vaccine not only prevents pregnant women from getting the flu, but also protects their infants. The new study, to be conducted in Asia, will evaluate the safety and effectiveness of maternal flu vaccination in areas with limited medical resources.” Cincinnati Children’s Hospital, with researchers from Johns Hopkins and the University of Washington, will carry out the study in rural areas of Bangladesh or Nepal. The study of 1,500 women will take five years to complete.

http://www.cincinnatichildrens.org/about/news/release/2009/gates-foundation-gives-grant-02-23-09.htm

The WHO said that “the emergence of parasites resistant to artemisinin at the Thai-Cambodia border could seriously undermine the success of the global malaria control efforts.” WHO noted that surveillance systems and research studies it supports to monitor antimalarial drug efficacy “are providing new evidence that parasites resistant to artemisinin have emerged along the border between Cambodia and Thailand.”

Strong malaria control programmes have helped to lower infection rates in several countries, WHO said, and the recent shift from failing drugs to the highly effective artemisinin-based combination therapies (ACTs) has been a breakthrough. Appropriate treatment with ACTs succeeds in more than 90% of cases. But malaria drug resistance now emerging along the Thai-Cambodia border threatens these gains.    Resistance along the Thai-Cambodia border started with chloroquine, followed by resistance to sulfadoxine-pyrimethamine and mefloquine, drugs used in malaria control several years ago.

With a US$ 22.5 million grant from the Bill & Melinda Gates Foundation, WHO said it “will endeavour to contain artemisinin-resistant malaria parasites before they spread.” WHO will work in collaboration with several key partners including the National Center for Parasitology, Entomology and Malaria Control of the Cambodian Ministry of Health, Bureau of Vector-Borne Disease of the Thai Ministry of Public Health, Faculty of Tropical Medicine of Mahidol University Bangkok, Institut Pasteur Cambodia, Mahidol Oxford Tropical Medicine Research Unit, Bangkok and the Malaria Consortium.

http://www.who.int/mediacentre/news/releases/2009/malaria_drug_resistance_20090225/en/index.html

The Weekly Epidemiological Record (WER) 27 February 2009, vol. 84, 9 (pp 65-76) includes: Recommended composition of influenza virus vaccines for use in the 2009-2010 influenza season (northern hemisphere winter);and Antigenic and genetic characteristics of H5N1 viruses and candidate vaccine viruses developed for potential use in human vaccines, February 2009

http://www.who.int/wer/2009/wer8409.pdf

The Lancet
Feb 28, 2009   Volume 373  Number 9665  Pages 693 – 780
http://www.thelancet.com/journals/lancet/issue/current

Editorial: The Lancet
Pharmaceuticals, patents, publicity…and philanthropy?

Tensions between provision of and payment for health care are familiar. Though doctors assume principal responsibility for patients’ health, those who work for pharmaceutical companies view the patented medicines they design as key components of health care. Creative ways are continually found to make such drugs available to as many patients in high-income countries as possible, the profits contributing to future investment in development and leaving national drug budgets affordable, just. Yet, a few hours’ flying away, patients in developing countries usually have no access to these very same patented drugs.

GlaxoSmithKline (GSK) has grown in size and influence by successful drug development, timely takeovers, and shrewd management. Andrew Witty, who ascended to the vertiginous position of chief executive at GSK in the past year, has attracted attention by a surprising presentation at Harvard Medical School on Feb 13. He promises that GSK will now not only make its medicines available much more cheaply to patients in low-income countries, but also make a bolder commitment to research into neglected diseases. As one blogger puts it, “arise Sir Andrew Witty (or is it Saint Andrew?)”.

Does this announcement mark a sea change in pharma’s attitude to the provision of drugs in poor countries, or could it be more reminiscent of the zany hybrid vehicles that distract attention from car manufacturers’ shamelessly polluting stock in trade? Witty’s words were carefully weighed to cast a rosy glow around GSK’s existing efforts. He name checked the company’s Spanish centre focused on research into “diseases of the developing world”, including tuberculosis, and the company’s malaria vaccine programme (a vaccine that will in any event need to find its main markets in low-income and middle-income regions). But a statement of intent was made, and some clear ideas put forward. In the 50 poorest countries, patented medicines are to be sold at no more than a quarter of their price in developed countries, and a commitment has been made to reinvest 20% of GSK’s developing-country profits back into local health-care infrastructure. Most intriguingly, the idea of a patent pool has been floated, by which holders of intellectual property rights would share them with others to invigorate research into neglected diseases.

GSK has made philanthropic gestures in the past-witness its ancestor SmithKlineBeecham’s donation of albendazole for treatment of lymphatic filariasis-and positive publicity might help to lift some of the dark clouds that have been gathering on pharma’s horizon, including depleted development pipelines and increased regulatory oversight. To be sure, Witty is not intending to alarm shareholders. GSK (2007 annual revenue £22·7 billion, profit after tax £5·5 billion) currently earns annual revenues of just US$43 million in the poorest countries, suggesting that the money to be reinvested locally will be less than 0·1% of overall profits. Flaws have been spotted in Witty’s new way too. Médecins Sans Frontière’s campaign for access to essential medicines notes that, despite a need for new paediatric and combination antiretroviral drugs to combat HIV, GSK does not plan to share its HIV patents with other researchers. Voluntary price reductions seem unlikely to match the dramatic falls in price, and consequent transformational increase in poor-country access, wrought by generic competition on antiretrovirals in the past decade.

Those committed to the forbidding task of improving health care in developing countries should commend Witty’s stance, but continue to press for more, and broader, action. GSK is not offering to give away its drugs and vaccines-someone will need to pay for patented medicines that can now be made available to patients in poor countries more cheaply, and likewise development of patent-pooled orphan drugs is yet to be planned, pursued, and paid for. And who will pay, amid a financial ice age of unknown extent? To convert a promising soundbite into improved health for people in developing countries, GSK must work openly with funding bodies, governments, and other stakeholders to identify clinical and public health problems that offer the greatest potential benefit to human health. These efforts will need close scrutiny to ensure that they register measurable achievements and, given the substantial obstacles of unstable health systems and uncertain funding, gather momentum.

Now that Andrew Witty has chosen this particular agenda, as a test of GSK’s resolve he can be presented with one straightforward preventive challenge-to make GSK’s licensed human papillomavirus vaccine affordable for girls and young women in low-income countries, and work proactively with funding agencies to deliver the vaccine in countries with suitable health systems.

Nature
Volume 457    Number 7232 pp935-1046   19 February 2009
http://www.nature.com/nature/journal/v457/n7232/
News
Drug patent plan gets mixed reviews
GlaxoSmithKline’s bid to tackle neglected diseases receives a muted response from the rest of the industry.
[This article summaries reactions to GSK’s patent pool idea announced in a speech earlier in February at Harvard Medical School by CEO Andrew Witty. The article presents a sidebar snapshot of programs and actions by other firms]:
A selection of other drug firms’ efforts on neglected tropical diseases.
Natasha Gilbert

Pfizer
– Donates medicines through individual deals with governments and non-governmental organizations.
– Mobilize Against Malaria initiative in Ghana, Kenya and Senegal to improve access to malaria treatment.
– International Trachoma Initiative has donated 54 million antibiotic treatments to patients in 13 countries

Hoffmann-La Roche
– Expert assistance given to the Medicines for Malaria Venture, a non-profit organization aimed at discovering malaria drugs.
– Donated to the Brazilian government all rights and technology to manufacture benznidazole for the treatment of Chagas’ disease.
– Technology-transfer initiative helps developing countries produce their own generic HIV medicines.

Novartis
– Provides not-for-profit treatments for dengue fever, tuberculosis and malaria in countries where endemic.
– Novartis Institute for Tropical Diseases in Singapore established in 2002 as a public-private partnership with the Singapore Economic Development Board.
– Novartis Vaccines Institute for Global Health in Siena, Italy, established in 2007 to develop vaccines for neglected diseases.

Sanofi-aventis
– Sells key medicines at cost to governments and aid agencies.
– In 2007 spent €14 million (US$18 million) on improving access to medicines in developing countries; €4 million on neglected tropical diseases; and more than €20 million on R&D for malaria, leishmaniasis and tuberculosis.

Bayer
– Donates drugs for sleeping sickness and Chagas’ disease to the World Health Organization.
– Donates antibiotics for tuberculosis to the Global Alliance for TB Drug Development.
– Bayer CropScience donates mosquito nets and insecticides in key countries.

Pediatrics
March 2009 / VOLUME 123 / ISSUE 3
http://pediatrics.aappublications.org/current.shtml

Article
Burden of Acute Gastroenteritis Hospitalizations and Emergency Department Visits in US Children That Is Potentially Preventable by Rotavirus Vaccination: A Probe Study Using the Now-Withdrawn RotaShield Vaccine
Jacqueline E. Tate, PhDa, Aaron T. Curns, MPHa, Margaret M. Cortese, MDa, Eric S. Weintraub, MPHb, Simon Hambidge, MD, PhDc, Kenneth M. Zangwill, MDd, Manish M. Patel, MD, MSca, James M. Baggs, PhDb and Umesh D. Parashar, MBBS, MPHa
BACKGROUND. With the implementation of a new rotavirus immunization program in the United States in 2006, determining the potential health benefits of rotavirus vaccination is important. We estimated the burden of acute gastroenteritis hospitalizations and emergency department visits in US children that are potentially preventable by rotavirus vaccination.
METHODS. We conducted a retrospective cohort analysis of children who in 1998-1999 were eligible to receive a now-withdrawn rotavirus vaccine (RotaShield) and were continuously enrolled in 1 of 6 managed care organizations in the Vaccine Safety Datalink. Estimates of vaccine effectiveness against all-cause gastroenteritis hospitalizations and emergency department visits adjusted according to month of birth, gender, and managed care organizations were calculated as 1 minus the risk ratio of outcomes among children in different dose groups. The burden of acute gastroenteritis prevented by vaccination was compared with the rotavirus burden estimated by 2 previously used indirect methods.
RESULTS. The effectiveness of a full 3-dose RotaShield series over a 1-year follow-up period was 83% against all-cause gastroenteritis hospitalizations and 43% against all-cause gastroenteritis emergency department visits. An increasing number of doses improved the effectiveness in preventing gastroenteritis hospitalizations, but no clear trend was observed between number of doses and effectiveness in prevention of gastroenteritis emergency department visits. The proportion of gastroenteritis hospitalizations and emergency department visits prevented by vaccination was substantially greater than the 48% to 53% of year-round hospitalizations and 33% of emergency department visits estimated to result from rotavirus by indirect methods.
CONCLUSIONS. The withdrawn rotavirus vaccine was highly effective in preventing hospitalizations and emergency department visits for all-cause acute gastroenteritis and the health benefits of vaccination against rotavirus may be greater than previously estimated.

a Division of Viral Disease
b Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, Georgia
c Kaiser Permanente Colorado, Denver, Colorado
d UCLA Center for Vaccine Research, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, California

Vaccine
Volume 27, Issue 11, Pages 1667-1776 (10 March 2009)
http://www.sciencedirect.com/science/journal/0264410X

Literature review of human papillomavirus vaccine acceptability among women over 26 years
Pages 1668-1673
Lora L. Black, Gregory D. Zimet, Mary B. Short, Lynne Sturm, Susan L. Rosenthal
Abstract
Vaccines for the human papillomavirus (HPV) are currently licensed for females, ages 9 through 26 years old in the U.S., and for adult women up to 45 years in some countries such as Australia. As licensure for adult women, over 26 years, is sought in other countries, it will be important to determine the acceptability to them. We reviewed the available articles on adult opinions and acceptability of vaccinating women against HPV. Predictors of acceptability included barriers, knowledge, risk, age, and marital status. Overall, acceptability rates were high, if adequate information was given and the cost was affordable.

Vaccine
Volume 27, Issue 11, Pages 1667-1776 (10 March 2009)
http://www.sciencedirect.com/science/journal/0264410X

Leadership in Immunization: The relevance to Japan of the U.S.A. experience of the Centers for Disease Control and Prevention (CDC) and the Advisory Committee on Immunization Practices (ACIP)
Pages 1724-1728
Hajime Kamiya, Nobuhiko Okabe
Abstract
Immunization is one of the most effective public health interventions available. However, the difference of how recommendations are established influence the utilization of the vaccine and the number of patients with vaccine preventable diseases (VPDs). In this paper, we compared and highlighted the difference of the situation of the immunization program in Japan and the United States in terms of structure of policy setting system. Since the disease epidemiology clearly indicates that the US has better control of VPDs over Japan, we considered the advantage of development of a comparable vaccine policy setting system of the US in Japan.