The Lancet Global Health – Jul 2014

The Lancet Global Health
Jul 2014 Volume 2 Number 7 e364 – 430

Herd protection induced by pneumococcal conjugate vaccine
Keith P Klugman
Why is herd protection from pneumococcal disease important? The pneumococcus is the leading cause of death in children worldwide,1 and children who die are likely to be those who are unable to access lifesaving antibiotics and pneumococcal conjugate vaccine (PCV). However, if vaccination of other children in the community stops transmission of the serotypes in the vaccine, then protection is provided to those most at risk of mortality, even if they are not given the vaccine themselves. The immunisation of infants with PCV in developed countries extends protection beyond direct protection of the immunised infants, to include children too young to be immunised,2 adults with substantial risk of pneumococcal disease such as those infected by HIV,3 and older people.

HPV vaccinations—possibly necessary but not sufficient
Gary M Ginsberg
Using country specific epidemiological-economic modelling, Mark Jit and colleagues1 show how the adoption of safe, well tolerated,2 immunogenic, and effective vaccination3 of 12-year-old girls against the cancer-causing human papillomaviruses (HPV)4 will prevent hundreds of thousands of cases of, and deaths from, cervical cancer worldwide.

Population effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and non-typeable Haemophilus influenzae in Kilifi, Kenya: findings from cross-sectional carriage studies
Dr Laura L Hammitt MD a b, Donald O Akech BSc a, Susan C Morpeth FRACP a c, Angela Karani BSc a, Norbert Kihuha BSc a, Sammy Nyongesa MSc a, Tahreni Bwanaali MBA a c, Edward Mumbo BSc d, Tatu Kamau MPH e, Shahnaaz K Sharif MD e, Prof J Anthony G Scott FRCP a c f
The effect of 7-valent pneumococcal conjugate vaccine (PCV) in developed countries was enhanced by indirect protection of unvaccinated individuals, mediated by reduced nasopharyngeal carriage of vaccine-serotype pneumococci. The potential indirect protection of 10-valent PCV (PCV10) in a developing country setting is unknown. We sought to estimate the effectiveness of introduction of PCV10 in Kenya against carriage of vaccine serotypes and its effect on other bacteria.
PCV10 was introduced into the infant vaccination programme in Kenya in January, 2011, accompanied by a catch-up campaign in Kilifi County for children aged younger than 5 years. We did annual cross-sectional carriage studies among an age-stratified, random population sample in the 2 years before and 2 years after PCV10 introduction. A nasopharyngeal rayon swab specimen was collected from each participant and was processed in accordance with WHO recommendations. Prevalence ratios of carriage before and after introduction of PCV10 were calculated by log-binomial regression.
About 500 individuals were enrolled each year (total n=2031). Among children younger than 5 years, the baseline (2009—10) carriage prevalence was 34% for vaccine-serotype Streptococcus pneumoniae, 41% for non-vaccine-serotype Streptococcus pneumoniae, and 54% for non-typeable Haemophilus influenzae. After PCV10 introduction (2011—12), these percentages were 13%, 57%, and 40%, respectively. Adjusted prevalence ratios were 0•36 (95% CI 0•26—0•51), 1•37 (1•13—1•65), and 0•62 (0•52—0•75), respectively. Among individuals aged 5 years or older, the adjusted prevalence ratios for vaccine-serotype and non-vaccine-serotype S pneumoniae carriage were 0•34 (95% CI 0•18—0•62) and 1•13 (0•92—1•38), respectively. There was no change in prevalence ratio for Staphylococcus aureus (adjusted prevalence ratio for those <5 years old 1•02, 95% CI 0•52—1•99, and for those ≥5 years old 0•90, 0•60—1•35).
After programmatic use of PCV10 in Kilifi, carriage of vaccine serotypes was reduced by two-thirds both in children younger than 5 years and in older individuals. These findings suggest that PCV10 introduction in Africa will have substantial indirect effects on invasive pneumococcal disease.
GAVI Alliance and Wellcome Trust.

Cost-effectiveness of female human papillomavirus vaccination in 179 countries: a PRIME modelling study
Mark Jit PhD a b, Marc Brisson PhD c d e †, Allison Portnoy MSPH f Dr Raymond Hutubessy PhD g
Introduction of human papillomavirus (HPV) vaccination in settings with the highest burden of HPV is not universal, partly because of the absence of quantitative estimates of country-specific effects on health and economic costs. We aimed to develop and validate a simple generic model of such effects that could be used and understood in a range of settings with little external support.
We developed the Papillomavirus Rapid Interface for Modelling and Economics (PRIME) model to assess cost-effectiveness and health effects of vaccination of girls against HPV before sexual debut in terms of burden of cervical cancer and mortality. PRIME models incidence according to proposed vaccine efficacy against HPV 16/18, vaccine coverage, cervical cancer incidence and mortality, and HPV type distribution. It assumes lifelong vaccine protection and no changes to other screening programmes or vaccine uptake. We validated PRIME against existing reports of HPV vaccination cost-effectiveness, projected outcomes for 179 countries (assuming full vaccination of 12-year-old girls), and outcomes for 71 phase 2 GAVI-eligible countries (using vaccine uptake data from the GAVI Alliance). We assessed differences between countries in terms of cost-effectiveness and health effects.
In validation, PRIME reproduced cost-effectiveness conclusions for 24 of 26 countries from 17 published studies, and for all 72 countries in a published study of GAVI-eligible countries. Vaccination of a cohort of 58 million 12-year-old girls in 179 countries prevented 690 000 cases of cervical cancer and 420 000 deaths during their lifetime (mostly in low-income or middle-income countries), at a net cost of US$4 billion. HPV vaccination was very cost effective (with every disability-adjusted life-year averted costing less than the gross domestic product per head) in 156 (87%) of 179 countries. Introduction of the vaccine in countries without national HPV vaccination at present would prevent substantially more cases of cervical cancer than in countries with such programmes, although the disparity has narrowed since 2012. If 71 phase 2 GAVI-eligible countries adopt vaccination according to forecasts, then in 2070 GAVI Alliance-funded vaccination could prevent 200 000 cases of cervical cancer and 100 000 deaths in some of the highest-burden countries.
Large between-country disparities exist for HPV vaccination, with countries with the most to gain yet to introduce national HPV vaccination. Support from the GAVI Alliance could help to reduce such disparities, but a substantial burden will remain even after presently projected vaccine introductions.

Polio eradication in Syria

The Lancet Infectious Diseases
Jul 2014 Volume 14 Number 7 p533 – 656

Polio eradication in Syria
Balsam Ahmad a, Sanjoy Bhattacharya b

The negative public health effects of the Syrian conflict were dramatically underlined by confirmation of a polio cluster in the northeastern rebel-held city of Deir al-Zour in October, 2013. The re-emergence of polio, 14 years after a WHO Eastern Mediterranean Regional Certification Commission certified the country to be rid of naturally occurring poliovirus, has caused vigorous discussion. Accusations and counter-accusations have flowed, with the Syrian health authorities and WHO’s networks coming under scrutiny. Several commentators queried the effectiveness of the so-called Early Warning Alert and Response System that was established in September, 2012, by the Syrian Ministry of Health with technical support from WHO.1 Others argue that the early warning system has succeeded in tackling the consequences of local polio outbreaks.2 Parallel systems of reporting and immunisation have been created in opposition-held governorates, and are reportedly supported, financially and technically, by the US Centers for Disease Control and Prevention.3

Questions have been raised about the transparency and impartiality of WHO and its ability to ensure the vaccination of all children, irrespective of their location inside Syria.1, 3 WHO’s representatives have not remained silent through these interactions. They have provided explanations as to why the Syrian polio outbreak was confirmed as late as October, 2013, when a case was identified as early as July of that year.4 WHO sources acknowledged that the current polio outbreak in Syria had been one of the biggest challenges facing the global eradication initiative.4 The organisation, unsurprisingly, has associated itself with efforts to counter the issue, such as initiation of vaccination campaigns in Syria and across the borders. WHO has also engaged itself with recent negotiations intended to strengthen cross-party cooperation for tackling of the polio outbreak. This approach is most notable in relation to the recent declaration made by the First Global Islamic Advisory Group Meeting on Polio Eradication, held in Jeddah, Saudi Arabia, on Feb 26—27, 2014. The gathering issued an appeal that every community, government, civil society, and religious organisation should ensure that all children benefit from access to the polio vaccine.5 The collaborations underpinning the event are noteworthy; it was organized by Al Azhar Sharif, the International Islamic Fiqh Academy, the Organization of Islamic Cooperation, the Islamic Development Bank, WHO, and UNICEF.

However, there are further issues to consider. For instance, the polio outbreak in Syria might be attributable to trends that predate the civil war. In a letter published in The Lancet, Sahloul and colleagues1 assessed WHO figures about routine polio immunisations and noted that vaccination coverage in rebel areas had been below accepted standards in the past. In a media report, WHO has acknowledged that Deir al-Zour had been excluded from a mass vaccination campaign associated with the Global Polio Eradication Initiative in 2012 because of the relocation of most of its residents to other areas.6 These trends raise deeper questions about the collection, analysis, dissemination, and use of data relating to the presence and transmission of polio in Syria (and elsewhere) by the Global Polio Eradication Initiative and WHO. How has the search for poliovirus been done? Have researchers relied too long on intermittent and incomplete data collection, with relatively uninformed projections made about the regression of polio incidence and the scale of the dangers from the disease? The definition of the basis for the certification of polio eradication has not remained stable since the Global Polio Eradication Initiative was launched in 1988. Even the choice of polio as an eradicable disease has been questioned.7 Robust data collection and attendant certification processes are of utmost importance. These measures, necessarily, require impartiality and transparency, the lack of any conflicts of interest, and the absence of interference from governments or funders. The case of Syria seems to suggest that such high standards have generally been rare. The dream of global polio eradication will remain a chimera until reliable frameworks for immunisation and evaluation are put in place.
We declare no competing interests.
1 Sahloul Z, Coutts A, Fouad FM, et al. Health response system for Syria: beyond official narrative. Lancet 2014; 383: 407. Full Text | PDF(91KB) | PubMed
2 Muhjazi G, Bashour H, Abourshaid N, Laham H. An early warning and response system for Syria. Lancet 2013; 382: 2066. Full Text | PDF(50KB) | PubMed
3 Coutts A, Fouad MF. Response to Syria’s health crisis—poor and uncoordinated. Lancet 2013; 381: 2242-2243. Full Text | PDF(1493KB) | PubMed
4 Aylward RB, Alwan A. Polio in Syria. Lancet 2014; 383: 489-491. Full Text | PDF(364KB) | PubMed
5 First Global Islamic Advisory Group Meeting on Polio Eradication. Final communiqué. (accessed June 3, 2014).
6 WHO Regional Office for the Eastern Mediterranean. Measles and polio vaccination campaign targets 2.5 million children in the Syrian Arab Republic, 6 December 2012. (accessed March 26, 2014).
7 Muraskin W. Polio eradication was an ideological project. BMJ 2012; 345: e8545. PubMed
Dengue outlook for the World Cup in Brazil: an early warning model framework driven by real-time seasonal climate forecasts
Rachel Lowe, Christovam Barcellos, Caio A S Coelho, Trevor C Bailey, Giovanini Evelim Coelho, Richard Graham, Tim Jupp, Walter Massa Ramalho, Marilia Sá Carvalho, David B Stephenson, Xavier Rodó
This timely dengue early warning permits the Ministry of Health and local authorities to implement appropriate, city-specific mitigation and control actions ahead of the World Cup.

Brief Report: Evidence for Camel-to-Human Transmission of MERS Coronavirus

New England Journal of Medicine
June 26, 2014 Vol. 370 No. 26

Brief Report: Evidence for Camel-to-Human Transmission of MERS Coronavirus
E.I. Azhar and Others
Free Full Text
We describe the isolation and sequencing of Middle East respiratory syndrome coronavirus (MERS-CoV) obtained from a dromedary camel and from a patient who died of laboratory-confirmed MERS-CoV infection after close contact with camels that had rhinorrhea. Nasal swabs collected from the patient and from one of his nine camels were positive for MERS-CoV RNA. In addition, MERS-CoV was isolated from the patient and the camel. The full genome sequences of the two isolates were identical. Serologic data indicated that MERS-CoV was circulating in the camels but not in the patient before the human infection occurred. These data suggest that this fatal case of human MERS-CoV infection was transmitted through close contact with an infected camel.

Costs of Introducing and Delivering HPV Vaccines in Low and Lower Middle Income Countries: Inputs for GAVI Policy on Introduction Grant Support to Countries

PLoS One
[Accessed 28 June 2014]

Research Article
Costs of Introducing and Delivering HPV Vaccines in Low and Lower Middle Income Countries: Inputs for GAVI Policy on Introduction Grant Support to Countries
Ann Levin, Susan A. Wang, Carol Levin, Vivien Tsu, Raymond Hutubessy mail
Published: June 26, 2014
DOI: 10.1371/journal.pone.0101114
In November 2011, the GAVI Alliance made the decision to add HPV vaccine as one of the new vaccines for which countries eligible for its funding (less than $1520 per capita income) could apply to receive support for national HPV vaccination, provided they could demonstrate the ability to deliver HPV vaccines. This paper describes the data and analysis shared with GAVI policymakers for this decision regarding GAVI HPV vaccine support. The paper reviews why strategies and costs for HPV vaccine delivery are different from other vaccines and what is known about the cost components from available data that originated primarily from HPV vaccine delivery costing studies in low and middle income-countries.
Financial costs of HPV vaccine delivery were compared across three sources of data: 1) vaccine delivery costing of pilot projects in five low and lower-middle income countries; 2) cost estimates of national HPV vaccination in two low income countries; and 3) actual expenditure data from national HPV vaccine introduction in a low income country. Both costs of resources required to introduce the vaccine (or initial one-time investment, such as cold chain equipment purchases) and recurrent (ongoing costs that repeat every year) costs, such as transport and health personnel time, were analyzed. The cost per dose, cost per fully immunized girl (FIG) and cost per eligible girl were compared across studies.
Costs varied among pilot projects and estimates of national programs due to differences in scale and service delivery strategy. The average introduction costs per fully immunized girl ranged from $1.49 to $18.94 while recurrent costs per girl ranged from $1.00 to $15.69, with both types of costs varying by delivery strategy and country. Evaluating delivery costs along programme characteristics as well as country characteristics (population density, income/cost level, existing service delivery infrastructure) are likely the most informative and useful for anticipating costs for HPV vaccine delivery.
This paper demonstrates the importance of country level cost data to inform global donor policies for vaccine introduction support. Such data are also valuable for informing national decisions on HPV vaccine introduction.

Evidence for the Selective Reporting of Analyses and Discrepancies in Clinical Trials: A Systematic Review of Cohort Studies of Clinical Trials

PLoS Medicine
(Accessed 28 June 2014)

Research Article
Evidence for the Selective Reporting of Analyses and Discrepancies in Clinical Trials: A Systematic Review of Cohort Studies of Clinical Trials
Kerry Dwan mail, Douglas G. Altman, Mike Clarke, Carrol Gamble, Julian P. T. Higgins, Jonathan A. C. Sterne, Paula R. Williamson, Jamie J. Kirkham
Published: June 24, 2014
DOI: 10.1371/journal.pmed.1001666
Most publications about selective reporting in clinical trials have focussed on outcomes. However, selective reporting of analyses for a given outcome may also affect the validity of findings. If analyses are selected on the basis of the results, reporting bias may occur. The aims of this study were to review and summarise the evidence from empirical cohort studies that assessed discrepant or selective reporting of analyses in randomised controlled trials (RCTs).
Methods and Findings
A systematic review was conducted and included cohort studies that assessed any aspect of the reporting of analyses of RCTs by comparing different trial documents, e.g., protocol compared to trial report, or different sections within a trial publication. The Cochrane Methodology Register, Medline (Ovid), PsycInfo (Ovid), and PubMed were searched on 5 February 2014. Two authors independently selected studies, performed data extraction, and assessed the methodological quality of the eligible studies. Twenty-two studies (containing 3,140 RCTs) published between 2000 and 2013 were included. Twenty-two studies reported on discrepancies between information given in different sources. Discrepancies were found in statistical analyses (eight studies), composite outcomes (one study), the handling of missing data (three studies), unadjusted versus adjusted analyses (three studies), handling of continuous data (three studies), and subgroup analyses (12 studies). Discrepancy rates varied, ranging from 7% (3/42) to 88% (7/8) in statistical analyses, 46% (36/79) to 82% (23/28) in adjusted versus unadjusted analyses, and 61% (11/18) to 100% (25/25) in subgroup analyses. This review is limited in that none of the included studies investigated the evidence for bias resulting from selective reporting of analyses. It was not possible to combine studies to provide overall summary estimates, and so the results of studies are discussed narratively.
Discrepancies in analyses between publications and other study documentation were common, but reasons for these discrepancies were not discussed in the trial reports. To ensure transparency, protocols and statistical analysis plans need to be published, and investigators should adhere to these or explain discrepancies.
Editors’ Summary
In the past, clinicians relied on their own experience when choosing the best treatment for their patients. Nowadays, they turn to evidence-based medicine—the systematic review and appraisal of trials, studies that investigate the benefits and harms of medical treatments in patients. However, evidence-based medicine can guide clinicians only if all the results from clinical trials are published in an unbiased and timely manner. Unfortunately, the results of trials in which a new drug performs better than existing drugs are more likely to be published than those in which the new drug performs badly or has unwanted side effects (publication bias). Moreover, trial outcomes that support the use of a new treatment are more likely to be published than those that do not support its use (outcome reporting bias). Recent initiatives—such as making registration of clinical trials in a trial registry (for example, a prerequisite for publication in medical journals—aim to prevent these biases, which pose a threat to informed medical decision-making.
Why Was This Study Done?
Selective reporting of analyses of outcomes may also affect the validity of clinical trial findings. Sometimes, for example, a trial publication will include a per protocol analysis (which considers only the outcomes of patients who received their assigned treatment) rather than a pre-planned intention-to-treat analysis (which considers the outcomes of all the patients regardless of whether they received their assigned treatment). If the decision to publish the per protocol analysis is based on the results of this analysis being more favorable than those of the intention-to-treat analysis (which more closely resembles “real” life), then “analysis reporting bias” has occurred. In this systematic review, the researchers investigate the selective reporting of analyses and discrepancies in randomized controlled trials (RCTs) by reviewing published studies that assessed selective reporting of analyses in groups (cohorts) of RCTs and discrepancies in analyses of RCTs between different sources (for example, between the protocol in a trial registry and the journal publication) or different sections of a source. A systematic review uses predefined criteria to identify all the research on a given topic.
What Did the Researchers Do and Find?
The researchers identified 22 cohort studies (containing 3,140 RCTs) that were eligible for inclusion in their systematic review. All of these studies reported on discrepancies between the information provided by the RCTs in different places, but none investigated the evidence for analysis reporting bias. Several of the cohort studies reported, for example, that there were discrepancies in the statistical analyses included in the different documents associated with the RCTs included in their analysis. Other types of discrepancies reported by the cohort studies included discrepancies in the reporting of composite outcomes (an outcome in which multiple end points are combined) and in the reporting of subgroup analyses (investigations of outcomes in subgroups of patients that should be predefined in the trial protocol to avoid bias). Discrepancy rates varied among the RCTs according to the types of analyses and cohort studies considered. Thus, whereas in one cohort study discrepancies were present in the statistical test used for the analysis of the primary outcome in only 7% of the included studies, they were present in the subgroup analyses of all the included studies.
What Do These Findings Mean?
These findings indicate that discrepancies in analyses between publications and other study documents such as protocols in trial registries are common. The reasons for these discrepancies in analyses were not discussed in trial reports but may be the result of reporting bias, errors, or legitimate departures from a pre-specified protocol. For example, a statistical analysis that is not specified in the trial protocol may sometimes appear in a publication because the journal requested its inclusion as a condition of publication. The researchers suggest that it may be impossible for systematic reviewers to distinguish between these possibilities simply by looking at the source documentation. Instead, they suggest, it may be necessary for reviewers to contact the trial authors. However, to make selective reporting of analyses more easily detectable, they suggest that protocols and analysis plans should be published and that investigators should be required to stick to these plans or explain any discrepancies when they publish their trial results. Together with other initiatives, this approach should help improve the quality of evidence-based medicine and, as a result, the treatment of patients.

PLoS Neglected Tropical Diseases – June 2014

PLoS Neglected Tropical Diseases
June 2014

Open Access
“Vaccine Diplomacy”: Historical Perspectives and Future Directions
Peter J. Hotez mail
Published: June 26, 2014
DOI: 10.1371/journal.pntd.0002808
Vaccine diplomacy is the branch of global health diplomacy that relies on the use or delivery of vaccines, while vaccine science diplomacy is a unique hybrid of global health and science diplomacy. Both offer innovative opportunities to promote United States (US) foreign policy and diplomatic relations between adversarial nations. Vaccine science diplomacy could also lead to the development and testing of some highly innovative neglected disease vaccines.

Social Sciences Research on Infectious Diseases of Poverty: Too Little and Too Late?
José Azoh Barry mail
Published: June 12, 2014
DOI: 10.1371/journal.pntd.0002803
Infectious diseases of poverty, also labeled tropical diseases or neglected tropical diseases (NTDs) and caused by pathogenic agents (viruses, bacteria, fungi, and other parasites), are viciously more prevalent among poor people. Though being preventable for the most part in a cost-effective way, they are devastating. These are, to name a few, Chagas disease, schistosomiasis, malaria, leprosy, visceral leishmaniasis, lymphatic filariasis, Buruli ulcer, and onchocerciasis. Besides the vicious circle these diseases maintain with dire conditions of poverty, an increased microbial resistance to some therapeutic drugs adds to the complexity of health disparities and human suffering among the socially disadvantaged, marginalized, and prejudiced against. Fostering virtuous circles (as opposed to vicious circles) against infections of poverty and putting the disenfranchised first are primary concerns for social scientists engaged with research into infectious diseases of poverty. The historical role of social science research into these diseases, its current impacts, substantial contributions, and opportunities and interests for future endeavors are the focus of this article. Persistent disruptions and their propensity to wholly hamper productivity, derail economic and social progress, and deny child development are part of the complex reality to look into. In forcing the displacement of populations and creating chaos, they increase the risk for the spread of infections and maintain the infected poor in a downward spiral of poverty through their capacity of securing the vicious relationship with NTDs. Rather than compassion for inequalities, vulnerabilities, deprivations and misery, or bad fate, foci such as social justice, preparedness, and empowerment are of utmost importance. The case for bridging the divide among scientific disciplines has been strongly made over the years by scholars and outside of academic institutions. Acknowledging the importance of interdisciplinary science and contemplating the need for funded multidisciplinary research is hopeful for broadening the expertise needed to tackle these multidimensional afflictions. However, it should also call for a cautious enthusiasm…

Polio vaccines: WHO position paper, January 2014 – Recommendations

Volume 32, Issue 33, Pages 4111-4242 (16 July 2014)

Polio vaccines: WHO position paper, January 2014 – Recommendations
Pages 4117-4118
This article presents the World Health Organizations (WHO) evidence and recommendations for the use of polio vaccination from the WHO position paper on polio vaccines – January 2014 recently published in the Weekly Epidemiological Record . This position paper summarizes the WHO position on the introduction of at least one dose of inactivated polio vaccine (IPV) into routine immunization schedules as a strategy to mitigate the potential risk of re-emergence of type 2 polio following the withdrawal of Sabin type 2 strains from oral polio vaccine (OPV). The current document replaces the position paper on the use of polio vaccines published in 2010 .
Footnotes to this paper provide a number of core references. 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 paper reflects the recommendations of WHO’s Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its November 2013 meeting.