Slideset on: - Zika virus and fetal/neonatal microcephaly - Microbiota, infections and immune response to vaccines - Antibiotic use and weight gain in childhood

1. RECENT TOP PAPERS IN
PEDIATRIC INFECTIOUS
DISEASES: PEDIATRIC
INFECTIONS
Susanna Esposito
Pediatric Highly Intensive Care Unit,
University of Milan, Fondazione IRCCS Ca’
Granda Ospedale Maggiore Policlinico
Milan, Italy

2. AGENDA
• Zika virus and fetal/neonatal microcephaly
• Microbiota, infections and immune response
to vaccines
• Antibiotic use and weight gain in childhood

4. ZIKA EPIDEMIOLOGY (UP TO DECEMBER 2015)
(Fauci & Morens, N Engl J Med 2016)

6. CLINICAL FINDINGS IN PREGNANT WOMEN
(Brasil et al., N Engl J Med 2016)

7. WEEK OF GESTATION ATTHE TIME OF
INFECTION AND US FINDINGS
(Brasil et al., 2016)

8. NEONATAL CHARACTERISTICS AFTER ZIKA
INFECTION DURING PREGNANCY
(Brasil et al., 2016)

10. FINDINGS IN A FETUS WHOSE MOTHER
ACQUIRED ZIKA INFECTION DURING
PREGNANCY
(Mlakar et al., N Engl J Med 2016)

11. ELECTRONIC MICROSCOPY OF ZIKA VIRUS IN
FETAL BRAIN
(Mlakar et al., N Engl J Med 2016)

12. The candidate viral entry
receptor AXL is highly
expressed by human radial
glial cells, astrocytes,
endothelial cells, and microglia
in developing human cortex
and by progenitor cells in
developing retina.
CANDIDATE ZIKA VIRUS RECEPTOR IN
NEURAL STEM CELLS
(Nowakoski et al., Cell Stem Cell 2016)

14. SYMPTOMS AND CHARACTERISTICS IN A ZIKA-
INFECTED PREGNANT WOMEN
(Driggers et al., N Engl J Med 2016)

15. HISTOPATHOLOGICAL FINDINGS IN FETAL
BRAIN AFTER ZIKA INFECTION AQUIRED In
PREGNANCY
(Driggers et al., N Engl J Med 2016)

16. ZIKA VIRUS AND FETAL BRAIN
(Driggers et al., N Engl J Med 2016)

18. TAKE HOME MESSAGES
• In human-dominated crowded world, human
behaviors with human-caused microperturbations
in ecologic balance can cause infectious agent to
emerge
• Broad and integrated research is needed for the
understanding of the complex ecosystems in whic
agents of future pandemics are evolving

19. Dominguez-Bello MG et al. Gastroenterology 2011;140:1713–1719
Initial gut bacteria (founder
species) depends upon delivery
mode
Vaginal delivery:
-Lactobacillus,
Prevotella spp
-Vertical
inheritance
from mother
C-section:
Staphylococcus
Corynebaterium
Propionibacterium spp
-Higher susceptibility
to certain pathogens
-Higher risk of atopic
disease
New strains (less certain in
origin) outcompete old ones
-Rapid increase in diversity
-Early microbiota in
development=high instability
-Shifts in response to diet,
illness
-Highly distinct,
differentiate microbiota
-Microbial community
may continue to change,
but at a slower rate than
in childhood
Substantially different
gut communities than in
younger adults

20. Coreen L. Johnson and James Versalovic Pediatrics 2012;129:950–960
Antibiotic use, diet, host, and environmental
factors can affect the composition of the microbiota.
In this model, balanced microbial composition may
result in symbiosis among resident microbes,
production of immunomodulatory compounds, and
subsequent regulation of the immune response.
Disruption or alteration of the microbiota by
environmental factors such as diet and antibiotic
use could result in dysbiosis and dysregulation
of the immune response

24. Wei et al., BMC Infect Dis 2015

25. MICROBIOTA COLONIZATION IN
NASOPHARYNX IN HEALTHY CHILDREN
(Biesbroek et al., AMRCCM 2014)

27. MICROBIOLOGICAL COLONIZATION
PATTERN OVER TIME
(Pravaes et al., AJRCCM 2016)

28. NETWORK ANALYSIS OF THE MICROBIAL
COMMUNITY (Prevaes et al., AMRCCM 2016)

29. GUT-BRAIN AXIS
(De Angelis et al., Gut Microbes 2015)

31. IMMUNE
RESPONSE
TO
VACCINES
(Pulendran,
PNAS 2015)

32. TAKE HOME MESSAGES
• Microbiota plays a relevant role on human health
• Neonates are characterized by an intestinal
microbiota that characterizes their infectious
risk
• Respiratory and gastrointestinal microbiota
appeared associated with recurrent infectious
diseases
• Microbiota seem to influence vaccines
immunogenicity

34. ANTIBIOTIC EXPOSURE IN CHILDHOOD
(Principi and Esposito, Int J Antimicrob Agents 2016)

35. • Macrolides
• Amoxicillin
• Cefdinir
• Vancomycin
• Tetracyclines
ANTIBIOTICS ASSOCIATED WITH THE RISK OF
WEIGHT GAIN
(Principi and Esposito, Int J Antimicrob Agents 2016)

36. FACTORS INFLUENCING GUT MICROBIOTA
(Principi and Esposito, Int J Antimicrob Agents 2016)
• Genetics
• Mode of delivery
• Diet
• Antibiotic adminisrtration

38. EXPOSURE TO ANTIBIOTICS IN THE FIRST
MONTHS OF LIFE AND WEIGHT GAIN
(Gerber et al., JAMA 2016)

39. EXPOSURE TO ANTIBIOTICS IN THE FIRST
MONTHS OF LIFE AND WEIGHT GAIN
(Gerber et al., JAMA 2016)

41. NUMBER AND TYPE OF ANTIBIOTIC PRESCRIPTIONS
(Scott et al., Gastroenterol 2016)

42. ANTI-ANAEROBIC ACTIVITY AND WEIGHT GAIN
(Scott et al., Gastroenterol 2016)

43. TIME OF FIRST ANTIBIOTIC
PRESCRIPTIONS AND WEIGHT GAIN
(Scott et al., Gastroenterol 2016)

44. EXPOSURE TO ANTIBIOTICS IN THE FIRST 2
YEARS OF LIFE AND WEIGHT GAIN
(Saari et al., Pediatrics 2015)

45. ODDS OF
BECOMING
OVERWEIGHT
AFTER FIRST
EXPOSURE TO
ANTIBIOTICS
(Saari et al.,
Pediatrics 2015)

46. TAKE HOME MESSAGES
• Antibiotic-related gut microbiota modifications are
associated with overweight and obesity in childhood
• A decrease in the number of microbes and their
substitution with others dramatically modifies
immune system development as well as glucose and
lipid metabolism
• Probiotics and prebiotics could play a role in
treating dysbiosis
• The judicious use of antibiotics is mandatory to
reduce their risks

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