RECENT TOP PAPERS IN PEDIATRIC INFECTIOUS DISEASES: PEDIATRIC

INFECTIONS

Susanna EspositoPediatric Highly Intensive Care Unit,

University of Milan, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico

Milan, Italy

AGENDA

• Zika virus and fetal/neonatal microcephaly

• Microbiota, infections and immune responseto vaccines

• Antibiotic use and weight gain in childhood

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

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

WEEK OF GESTATION ATTHE TIME OF INFECTION AND US FINDINGS

(Brasil et al., 2016)

NEONATAL CHARACTERISTICS AFTER ZIKA INFECTION DURING PREGNANCY

(Brasil et al., 2016)

FINDINGS IN A FETUS WHOSE MOTHER ACQUIRED ZIKA INFECTION DURING

PREGNANCY(Mlakar et al., N Engl J Med 2016)

ELECTRONIC MICROSCOPY OF ZIKA VIRUS IN FETAL BRAIN

(Mlakar et al., N Engl J Med 2016)

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)

SYMPTOMS AND CHARACTERISTICS IN A ZIKA-INFECTED PREGNANT WOMEN

(Driggers et al., N Engl J Med 2016)

HISTOPATHOLOGICAL FINDINGS IN FETAL BRAIN AFTER ZIKA INFECTION AQUIRED In

PREGNANCY (Driggers et al., N Engl J Med 2016)

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

TAKE HOME MESSAGES

• In human-dominated crowded world, human behaviors with human-caused microperturbationsin ecologic balance can cause infectious agent to emerge

• Broad and integrated research is needed for the understanding of the complex ecosystems in whicagents of future pandemics are evolving

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

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

Wei et al., BMC Infect Dis 2015

MICROBIOTA COLONIZATION IN NASOPHARYNX IN HEALTHY CHILDREN

(Biesbroek et al., AMRCCM 2014)

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

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

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

IMMUNE RESPONSE

TO VACCINES

(Pulendran, PNAS 2015)

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

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

• Macrolides

• Amoxicillin

• Cefdinir

• Vancomycin

• Tetracyclines

ANTIBIOTICS ASSOCIATED WITH THE RISK OF WEIGHT GAIN

(Principi and Esposito, Int J Antimicrob Agents 2016)

FACTORS INFLUENCING GUT MICROBIOTA(Principi and Esposito, Int J Antimicrob Agents 2016)

• Genetics

• Mode of delivery

• Diet

• Antibiotic adminisrtration

EXPOSURE TO ANTIBIOTICS IN THE FIRST MONTHS OF LIFE AND WEIGHT GAIN

(Gerber et al., JAMA 2016)

EXPOSURE TO ANTIBIOTICS IN THE FIRST MONTHS OF LIFE AND WEIGHT GAIN

(Gerber et al., JAMA 2016)

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

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

TIME OF FIRST ANTIBIOTIC PRESCRIPTIONS AND WEIGHT GAIN

(Scott et al., Gastroenterol 2016)

EXPOSURE TO ANTIBIOTICS IN THE FIRST 2 YEARS OF LIFE AND WEIGHT GAIN

(Saari et al., Pediatrics 2015)

ODDS OF BECOMING

OVERWEIGHT AFTER FIRST EXPOSURE TO ANTIBIOTICS

(Saari et al., Pediatrics 2015)

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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