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To date, vaccination is the most cost-effective strategy to combat infectious diseases. Recently, a productivity gap affects the pharmaceutical industry. The productivity gap describes the situation whereby the invested resources within an industry do not match the expected product turn-over. While risk profiles (combining research and development timelines and transition rates) have been published for new chemical entities (NCE), little is documented on vaccine development. The objective is to calculate risk profiles for vaccines targeting human infectious diseases. A database was actively compiled to include all vaccine projects in development from 1998 to 2009 in the pre-clinical development phase, clinical trials phase I, II and III up to Market Registration. The average vaccine, taken from the preclinical phase, requires a development timeline of 10.71 years and has a market entry probability of 6%. Stratification by disease area reveals pandemic influenza vaccine targets as lucrative. Furthermore, vaccines targeting acute infectious diseases and prophylactic vaccines have shown to have a lower risk profile when compared to vaccines targeting chronic infections and therapeutic applications. In conclusion; these statistics apply to vaccines targeting human infectious diseases. Vaccines targeting cancer, allergy and autoimmune diseases require further analysis. Additionally, this paper does not address orphan vaccines targeting unmet medical needs, whether projects are in-licensed or self-originated and firm size and experience. Therefore, it remains to be investigated how these - and other - variables influence the vaccine risk profile. Although we find huge differences between the risk profiles for vaccine and NCE; vaccines outperform NCE when it comes to development timelines. [ABSTRACT FROM AUTHOR]

Measurement of malaria burden is fraught with complexity, due to the natural history of the disease, delays in seeking treatment or failure of case management. Attempts to establish an appropriate case definition for a malaria episode has often resulted in ambiguities and challenges because of poor information about treatment seeking, patterns of infection, recurrence of fever and asymptomatic infection. While the primary reason for treating malaria is to reduce disease burden, the effects of treatment are generally ignored in estimates of the burden of malaria morbidity, which are usually presented in terms of numbers of clinical cases or episodes, with the main data sources being reports from health facilities and parasite prevalence surveys. The use of burden estimates that do not consider effects of treatment, leads to under-estimation of the impact of improvements in case management. Official estimates of burden very likely massively underestimate the impact of the roll-out of ACT as first-line therapy across Africa. This paper proposes a novel approach for estimating burden of disease based on the point prevalence of malaria attributable disease, or equivalently, the days with malaria fever in unit time. The technique makes use of data available from standard community surveys, analyses of fever patterns in malaria therapy patients, and data on recall bias. Application of this approach to data from Zambia for 2009–2010 gave an estimate of 2.6 (95% credible interval: 1.5–3.7) malaria attributable fever days per child-year. The estimates of recall bias, and of the numbers of days with illness contributing to single illness recalls, could be applied more generally. To obtain valid estimates of the overall malaria burden using these methods, there remains a need for surveys to include the whole range of ages of hosts in the population and for data on seasonality patterns in confirmed case series. [ABSTRACT FROM AUTHOR]

Background: Infectious diseases after solid organ transplantation (SOT) are one of the major complications in transplantation medicine. Vaccination-based prevention is desirable, but data on the response to active vaccination after SOT are conflicting. Methods: In this systematic review, we identify the serologic response rate of SOT recipients to post-transplantation vaccination against tetanus, diphtheria, polio, hepatitis A and B, influenza, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitides, tick-borne encephalitis, rabies, varicella, mumps, measles, and rubella. Results: Of the 2478 papers initially identified, 72 were included in the final review. The most important findings are that (1) most clinical trials conducted and published over more than 30 years have all been small and highly heterogeneous regarding trial design, patient cohorts selected, patient inclusion criteria, dosing and vaccination schemes, follow up periods and outcomes assessed, (2) the individual vaccines investigated have been studied predominately only in one group of SOT recipients, i.e. tetanus, diphtheria and polio in RTX recipients, hepatitis A exclusively in adult LTX recipients and mumps, measles and rubella in paediatric LTX recipients, (3) SOT recipients mount an immune response which is for most vaccines lower than in healthy controls. The degree to which this response is impaired varies with the type of vaccine, age and organ transplanted and (4) for some vaccines antibodies decline rapidly. Conclusion: Vaccine-based prevention of infectious diseases is far from satisfactory in SOT recipients. Despite the large number of vaccination studies preformed over the past decades, knowledge on vaccination response is still limited. Even though the protection, which can be achieved in SOT recipients through vaccination, appears encouraging on the basis of available data, current vaccination guidelines and recommendations for post-SOT recipients remain poorly supported by evidence. There is an urgent need to conduct appropriately powered vaccination trials in well-defined SOT recipient cohorts. [ABSTRACT FROM AUTHOR]

Background: A large proportion of patients receiving antiretroviral therapy (ART) in low and middle income countries (LMICs) have unknown treatment outcomes and are classified as lost to follow-up (LTFU). Physical tracing of patients classified as LTFU is common; however, effects of tracing on outcomes remains unclear. The objective of this systematic review is to compare estimates of LTFU, mortality and retention in LMIC in cohorts of patients with and without physical tracing. Methods and Findings: We systematically identified studies in LMIC programmatic settings using MEDLINE (2003–2011) and HIV conference abstracts (2009–2011). Studies reporting the proportion LTFU 12-months after ART initiation were included. Tracing activities were determined from manuscripts or by contacting study authors. Studies were classified as “tracing studies” if physical tracing was available for the majority of patients. Summary estimates from the 2 groups of studies (tracing and non-tracing) for LTFU, mortality, stop of ART, transfers out, and retention on ART were determined. 261 papers and 616 abstracts were identified of which 39 studies comprising 54 separate cohorts (n = 187,666) met inclusion criteria. Of those, physical tracing was available for 46% of cohorts. Treatment programs with physical tracing activities had lower estimated LTFU (7.6% vs. 15.1%; p<.001), higher estimated mortality (10.5% vs. 6.6%; p = .006), higher retention on ART (80.0 vs. 75.8%; p = .04) and higher retention at the original site (80.0% vs. 72.9%; p = .02). Conclusions: Knowledge of patient tracing is critical when interpreting program outcomes of LTFU, mortality and retention. The reduction of the proportion LTFU in tracing studies was only partially explained by re-classification of unknown outcomes. These data suggest that tracing may lead to increased re-engagement of patients in care, rather than just improved classification of unknown outcomes. [ABSTRACT FROM AUTHOR]