In conclusion the genetic diversity of P jirovecii appears l

In conclusion, the genetic order RVX-208 of P. jirovecii appears limited, suggesting a constant exchange between human individuals and the simultaneous presence of several genotypes in a given individual. On this constant exchange background, some temporal and geographical evolutions of genotypes were observed in independent centres suggesting recent acquisition of new genotypes and more rapidly circulating genotypes between immunocompromised patients. This reinforces the supposed dynamic transmission of P. jirovecii between non-immunocompromised and immunocompromised hosts, the first being reservoir from which new genotypes can be contracted by immunocompromised patients and subsequently transmitted to other patients (Alanio and Bretagne, 2017). The following are the supplementary data related to this article.
Acknowledgments
Introduction Shigella infections are endemic throughout the world, but the main disease burden is in developing countries, especially in children younger than 5years of age (Kotloff et al., 1999). The recently published Global Burden of Disease Study 2015 estimates that 12.5% (i.e., 164,410) of the 1.3 million deaths due to diarrheal diseases were caused by Shigella (GBD 2015 Mortality and Causes of Death Collaborators, 2016). In that study, 98.5% of Shigella deaths occurred in low and middle income countries and 33% in children younger than 5years old. These data agree with data from more geographically limited studies: the estimated incidence of disease in Asia alone is approximately 125 million cases per year (Bardhan et al., 2010), with approximately 122,000 annual deaths (Lozano et al., 2012). These estimates are supplemented with incidence data from specific sites of the Global Enteric Multicentre Study (GEMS) in sub-Saharan Africa and South Asia (Kotloff et al., 2013) that found that shigellosis is one of the top causes of moderate and severe diarrhoea (MSD) in under 5year olds. Shigella was the fourth, second and first cause of medium or severe diarrhoea (MSD), in children aged 0–11months, 12–23months and 24–59months, respectively (Kotloff et al., 2013). Of 1124 Shigella cases in the GEMS study 23.9% were caused by S. sonnei (single serotype), 5.5% by S. boydii (multiple serotypes), 4.9% by S. dysenteriae (multiple serotypes, but no cases of S. dysenteriae I) and 65.7% by S. flexneri (mostly by serotypes 1b, 2a, 3a, and 6) (Livio et al., 2014). A subsequent re-analysis of GEMS data with more sensitive molecular diagnostic techniques (Lindsay et al., 2013; Liu et al., 2014) showed an even higher incidence of Shigella as a cause of MSD. These data from developing countries and evidence of increasing levels of antibiotic resistance (Gu et al., 2012; Klontz and Singh, 2015) support the need for a broadly protective vaccine for efficient prevention of the disease (Livio et al., 2014). S. sonnei alone causes significant disease in industrialized countries and travellers, and in these populations is responsible for 60–70% of all cases of shigellosis (Ekdahl and Andersson, 2005). Antibiotic resistant strains of S. sonnei also cause disease and local outbreaks in people who have not travelled to endemic countries (Bowen et al., 2015). Thus, a S. sonnei monovalent vaccine may also have public health value. No vaccine is widely available to prevent shigellosis (Mani et al., 2016). So far, vaccine candidates based on O Antigen (OAg) conjugates and live attenuated strains have shown protection against homologous strains in Phase 3 clinical studies (Cohen et al., 1997; Levine et al., 2007; Kaminski and Oaks, 2009; Camacho et al., 2013; Passwell et al., 2010). Vaccines using inactivated bacteria and vaccine candidates based on sub-cellular components are currently under development. Most of these also contain OAg (Levine et al., 2007; Kaminski and Oaks, 2009; Camacho et al., 2013). The central role of the serotype specific OAg repeating unit of Shigella LPS in clinical protection has been demonstrated in various settings. More specifically, i) subjects naturally exposed to Shigella develop a serotype-specific immunity, but remain susceptible to disease caused by heterologous serotypes (Ferreccio et al., 1991); ii) subjects previously infected/challenged with either S. sonnei or S. flexneri develop protection only against the challenge strain as shown with re-challenge experiments (Kotloff et al., 1995; Herrington et al., 1990); iii) subjects lacking homologous anti-LPS antibodies have a significantly higher risk of contracting shigellosis of the same serovar type (Cohen et al., 1991); iv) subjects with a high level of anti-LPS serum antibodies show significantly reduced disease severity (Wahid et al., 2013); and v) subjects vaccinated IM with a conjugate vaccine containing Shigella sonnei O polysaccharide bound to Pseudomonas aeruginosa recombinant exoprotein A develop a serotype specific 71–74% efficacy in older children and adults and show a significant association between anti-S. sonnei LPS serum antibody and clinical protection (Cohen et al., 1997; Passwell et al., 2010). These findings demonstrate that natural immunity against Shigella is primarily serotype-specific; the OAg of the Shigella LPS is the dominant protective antigen and anti-S. sonnei LPS antibody is a strong marker of acquired immunity.