The dynamics of measles in sub-Saharan Africa.

Although vaccination has almost eliminated measles in parts of the world, the disease remains a major killer in some high birth rate countries of the Sahel. On the basis of measles dynamics for industrialized countries, high birth rate regions should experience regular annual epidemics. Here, however, we show that measles epidemics in Niger are highly episodic, particularly in the capital Niamey. Models demonstrate that this variability arises from powerful seasonality in transmission-generating high amplitude epidemics-within the chaotic domain of deterministic dynamics. In practice, this leads to frequent stochastic fadeouts, interspersed with irregular, large epidemics. A metapopulation model illustrates how increased vaccine coverage, but still below the local elimination threshold, could lead to increasingly variable major outbreaks in highly seasonally forced contexts. Such erratic dynamics emphasize the importance both of control strategies that address build-up of susceptible individuals and efforts to mitigate the impact of large outbreaks when they occur

Fate and transformation of silver nanoparticles in different biological conditions

The exploitation of silver nanoparticles (AgNPs) in biomedicine represents more than one third of their overall application. Despite their wide use and significant amount of scientific data on their effects on biological systems, detailed insight into their in vivo fate is still lacking. This study aimed to elucidate the biotransformation patterns of AgNPs following oral administration. Colloidal stability, biochemical transformation, dissolution, and degradation behaviour of different types of AgNPs were evaluated in systems modelled to represent biological environments relevant for oral administration, as well as in cell culture media and tissue compartments obtained from animal models. A multimethod approach was employed by implementing light scattering (dynamic and electrophoretic) techniques, spectroscopy (UV-vis, atomic absorption, nuclear magnetic resonance) and transmission electron microscopy. The obtained results demonstrated that AgNPs may transform very quickly during their journey through different biological conditions. They are able to degrade to an ionic form and again reconstruct to a nanoparticulate form, depending on the biological environment determined by specific body compartments. As suggested for other inorganic nanoparticles by other research groups, AgNPs fail to preserve their specific integrity in in vivo settings

From regional pulse vaccination to global disease eradication: insights from a mathematical model of Poliomyelitis

Mass-vaccination campaigns are an important strategy in the global fight against poliomyelitis and measles. The large-scale logistics required for these mass immunisation campaigns magnifies the need for research into the effectiveness and optimal deployment of pulse vaccination. In order to better understand this control strategy, we propose a mathematical model accounting for the disease dynamics in connected regions, incorporating seasonality, environmental reservoirs and independent periodic pulse vaccination schedules in each region. The effective reproduction number, $R_e$, is defined and proved to be a global threshold for persistence of the disease. Analytical and numerical calculations show the importance of synchronising the pulse vaccinations in connected regions and the timing of the pulses with respect to the pathogen circulation seasonality. Our results indicate that it may be crucial for mass-vaccination programs, such as national immunisation days, to be synchronised across different regions. In addition, simulations show that a migration imbalance can increase $R_e$ and alter how pulse vaccination should be optimally distributed among the patches, similar to results found with constant-rate vaccination. Furthermore, contrary to the case of constant-rate vaccination, the fraction of environmental transmission affects the value of $R_e$ when pulse vaccination is present.Comment: Added section 6.1, made other revisions, changed titl

Mixing patterns and the spread of close-contact infectious diseases

Surprisingly little is known regarding the human mixing patterns relevant to the spread of close-contact infections, such as measles, influenza and meningococcal disease. This study aims to estimate the number of partnerships that individuals make, their stability and the degree to which mixing is assortative with respect to age. We defined four levels of putative at-risk events from casual (physical contact without conversation) to intimate (contact of a sexual nature), and asked university student volunteers to record details on those they contacted at these levels on three separate days. We found that intimate contacts are stable over short time periods whereas there was no evidence of repeat casual contacts with the same individuals. The contacts were increasingly assortative as intimacy increased. Such information will aid the development and parameterisation of models of close contact diseases, and may have direct use in outbreak investigations

Natural variation in immune responses to neonatal mycobacterium bovis bacillus calmette-guerin (BCG) vaccination in a cohort of Gambian infants

Background There is a need for new vaccines for tuberculosis (TB) that protect against adult pulmonary disease in regions where BCG is not effective. However, BCG could remain integral to TB control programmes because neonatal BCG protects against disseminated forms of childhood TB and many new vaccines rely on BCG to prime immunity or are recombinant strains of BCG. Interferon-gamma (IFN-) is required for immunity to mycobacteria and used as a marker of immunity when new vaccines are tested. Although BCG is widely given to neonates IFN- responses to BCG in this age group are poorly described. Characterisation of IFN- responses to BCG is required for interpretation of vaccine immunogenicity study data where BCG is part of the vaccination strategy. Methodology/Principal Findings 236 healthy Gambian babies were vaccinated with M. bovis BCG at birth. IFN-, interleukin (IL)-5 and IL-13 responses to purified protein derivative (PPD), killed Mycobacterium tuberculosis (KMTB), M. tuberculosis short term culture filtrate (STCF) and M. bovis BCG antigen 85 complex (Ag85) were measured in a whole blood assay two months after vaccination. Cytokine responses varied up to 10 log-fold within this population. The majority of infants (89-98% depending on the antigen) made IFN- responses and there was significant correlation between IFN- responses to the different mycobacterial antigens (Spearman’s coefficient ranged from 0.340 to 0.675, p=10-6-10-22). IL-13 and IL-5 responses were generally low and there were more non-responders (33-75%) for these cytokines. Nonetheless, significant correlations were observed for IL-13 and IL-5 responses to different mycobacterial antigens Conclusions/Significance Cytokine responses to mycobacterial antigens in BCG-vaccinated infants are heterogeneous and there is significant inter-individual variation. Further studies in large populations of infants are required to identify the factors that determine variation in IFN- responses

Results from evaluations of models and cost-effectiveness tools to support introduction decisions for new vaccines need critical appraisal

The World Health Organization (WHO) recommends that the cost-effectiveness (CE) of introducing new vaccines be considered before such a programme is implemented. However, in low- and middle-income countries (LMICs), it is often challenging to perform and interpret the results of model-based economic appraisals of vaccines that benefit from locally relevant data. As a result, WHO embarked on a series of consultations to assess economic analytical tools to support vaccine introduction decisions for pneumococcal, rotavirus and human papillomavirus vaccines. The objectives of these assessments are to provide decision makers with a menu of existing CE tools for vaccines and their characteristics rather than to endorse the use of a single tool. The outcome will provide policy makers in LMICs with information about the feasibility of applying these models to inform their own decision making. We argue that if models and CE analyses are used to inform decisions, they ought to be critically appraised beforehand, including a transparent evaluation of their structure, assumptions and data sources (in isolation or in comparison to similar tools), so that decision makers can use them while being fully aware of their robustness and limitations

Knowledge, perceived stigma, and care-seeking experiences for sexually transmitted infections: a qualitative study from the perspective of public clinic attendees in Rio de Janeiro, Brazil

BACKGROUND: An estimated 12 million sexually transmitted infections (STIs) are documented in Brazil per year. Given the scope of this public health challenge and the importance of prompt treatment and follow-up counseling to reduce future STI/HIV-related risk behavior, we sought to qualitatively explore STI clinic experiences among individuals diagnosed with STIs via public clinics in Rio de Janeiro, Brazil. The study focused on eliciting the perspective of clinic users with regard to those factors influencing their STI care-seeking decisions and the health education and counseling which they received during their clinic visit. METHODS: Thirty semi-structured interviews were conducted with heterosexual men and women and men who have sex with men presenting with STIs at two public clinics. Content analysis was conducted by coding transcripts of audio-taped interviews for key domains of interest and comparing and synthesizing code output across participants and sub-groups. Thematic narratives were then developed per each of the study sub-groups. RESULTS: Salient themes that emerged from participant narratives included the importance of low STI-related knowledge and high perceived stigma, both STI-related and other types of social stigma, on STI care-seeking delays. However, there are indications in the data that the level of STI-related knowledge and the amount and types of stigma experienced vary across the study sub-groups suggesting the need for further research on the significance and program relevance of these potential differences. Interview findings also suggest that such barriers to care seeking are not adequately addressed through ongoing health education and counseling efforts at public STI clinics and in turn critical opportunities for STI/HIV prevention are currently being missed. CONCLUSION: Information, communication and education regarding early recognition and prompt care-seeking for STIs should be developed, with consideration given to the possibility of tailoring messages tailored to specific sub-groups. To promote prompt treatment-seeking, interventions must also address both STI-specific and other forms of social stigma which may limit access to care. Efforts to further assess and respond to barriers related to the delivery of quality health education and counseling within the context of public STI clinics are also needed

Prospecting environmental mycobacteria: combined molecular approaches reveal unprecedented diversity

Background: Environmental mycobacteria (EM) include species commonly found in various terrestrial and aquatic environments, encompassing animal and human pathogens in addition to saprophytes. Approximately 150 EM species can be separated into fast and slow growers based on sequence and copy number differences of their 16S rRNA genes. Cultivation methods are not appropriate for diversity studies; few studies have investigated EM diversity in soil despite their importance as potential reservoirs of pathogens and their hypothesized role in masking or blocking M. bovis BCG vaccine. Methods: We report here the development, optimization and validation of molecular assays targeting the 16S rRNA gene to assess diversity and prevalence of fast and slow growing EM in representative soils from semi tropical and temperate areas. New primer sets were designed also to target uniquely slow growing mycobacteria and used with PCR-DGGE, tag-encoded Titanium amplicon pyrosequencing and quantitative PCR. Results: PCR-DGGE and pyrosequencing provided a consensus of EM diversity; for example, a high abundance of pyrosequencing reads and DGGE bands corresponded to M. moriokaense, M. colombiense and M. riyadhense. As expected pyrosequencing provided more comprehensive information; additional prevalent species included M. chlorophenolicum, M. neglectum, M. gordonae, M. aemonae. Prevalence of the total Mycobacterium genus in the soil samples ranged from 2.3×107 to 2.7×108 gene targets g−1; slow growers prevalence from 2.9×105 to 1.2×107 cells g−1. Conclusions: This combined molecular approach enabled an unprecedented qualitative and quantitative assessment of EM across soil samples. Good concordance was found between methods and the bioinformatics analysis was validated by random resampling. Sequences from most pathogenic groups associated with slow growth were identified in extenso in all soils tested with a specific assay, allowing to unmask them from the Mycobacterium whole genus, in which, as minority members, they would have remained undetected