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Malattie infettive emergenti e ri-emergenti:
Una sfida senza frontiere
Prof. Francesco Castelli, MD, FRCP (London), FFTM R CPS (Glasgow)Professor of Medicine (Infectious Diseases)Director, Institute for Infectious and Tropical DiseasesUniversity of Brescia (Italy)Director, WHO Collaborating Center for the implementation of TB/HIV collaborative activitiesSite Director, Geosentinel and EuroTravNet Surveillace sites in Brescia
University of Brescia (Italy)WHO Collaborating Center
for the implementation of TB/HIV collaborative activities
2
FIGURE 1. Crude death rate for infectious diseases - United States, 1900 - 1996.
… it is time to close the book on infectious diseases. The war against pestilence is over…
William Stewart, Surgeon General
in a message to Congress, 1969
Outline
• Cosa è una infezione emergente /ri-emergente?
• Mobilità umana (… e non solo)
• Emerging infections:
• Conclusions and acknowledgements
• Emerging infectious disease:
An infectious disease that has newly appeared in
a population or that …
• Re-emerging infectious disease:
has been known for some time but is rapidly
increasing in incidence or geographic range.
http://www.medterms.com/script/main/art.asp?articlekey=22801
Examples of emerging and reemerging infectious diseases throughout the world.
Fauci A. Academic Medicine: December 2005 - Volume 80 - Issue 12 - pp 1079-1085
New kids on the block
TSS
EHEC H5N1
HIV
HEV
Lyme
BSE
HCV
Hanta
West Nile
nvCJD
SARS
Chikungunya
H1N1
http://www.medmicro.wisc.edu/undergraduate/courses/554/index.html
Infectious causes of chronic diseases
DiseaseCervical cancerChronic hepatitis, liver cancerLyme disease (arthritis)Whipple’s diseaseBladder cancerStomach cancerPeptic ulcer disease
Atherosclerosis (CHD)Diabetes mellitus, type 1Multiple sclerosisInflammatory bowel disease
CauseHuman papilloma virusHepatitis B and C virusesBorrelia burgdorferiTropheryma whippeliiSchistosoma haematobiumHelicobacter pyloriHelicobacter pylori
Chlamydiae pneumoniaeEnteroviruses (esp. Coxsackie)Epstein-Barr v, herpes vv?Mycobacterium avium sub-spp.Paratuberculosis, Yersinia
• Microbial adaptation and change
• Human susceptibility to infection
ageing, HIV, IV drugs, transplantation, transfusion
• Population growth and density
• Urbanization, crowding – social and sexual relations
• Globalization of travel and trade
• Live animal markets
• Intensified livestock production
• Misuse of antibiotics (humans & domestic animals)
• Changes to ecosystems (deforestation, biodiversity loss)
• Global climate change
Factors in Emerging/Re -emerging Infectious Diseases
Baseline 2000 2025 2050 2075 2100Source: Kris Ebi
MALARIA IN ZIMBABWE, UNDER CLIMATE CHANGE
Baseline 2000 2025 2050 2075 2100Source: Kris Ebi
Baseline 2000 2025 2050 2075 2100Source: Kris Ebi
Outline
• Cosa è una infezione emergente /ri-emergente?
• Mobilità umana (… e non solo)
• Emerging infections:
• Conclusions and acknowledgements
Wor
ldPo
pula
tion
inbi
llion
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umna
v iga
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)th
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lobe
Year1850
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400
350
300
250
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150
100
50
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0
1900 1950
1
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Speed of Global Travel in Relation to World Populat ion Growth
• http://flowingdata.com/2008/10/08/commerc
ial-air-traffic-seen-around-the-world/
Territory size shows the relative levels of net immigration in all territories (immigration less emigration).
http://knowledge.allianz.com/demographics/migration_minorities/?668/real-earth-population-patterns-demographics-worldwide
• International migrants = 214 million
• In the world 1 person out of 33 is a migrant
• 5° most populous country in the world
Are migrants too many?
� Chi viaggia?
Persone
Vettori
Ospiti intermedi
Batteri, virus, parassiti
Alimenti
GRAM NEGATIVE BACILLI, MULTIDRUG RESISTANT - CHILE: ex ITALY KPC,NOSOCOMIAL****************************************************************************A ProMED-mail post<http://www.promedmail.org>ProMED-mail is a program of theInternational Society for Infectious Diseases<http://www.isid.org>
Date: Sun 18 Mar 2012From: Marcela Cifuentes <[email protected]> [edited]
We report the 1st isolation in our country [Chile] of _Klebsiella pneumoniae_ carbapenemase (KPC)-producing [microorganism] in a patient admitted from Italy. The patient has non-Hodgkin lymphoma treatment and renal failure on hemodialysis, and he was hospitalized several times in Italy. On 28 Feb [2012, he was] admitted to a hospital in Santiago [Chile] to continue treatment. During hospitalization, he developed fever and microbiological studies were performed. _K. pneumoniae_ was isolated from urine. The antibiogram showed resistanceto quinolones, aminoglycosides, cephalosporins, and carbapenems and susceptible only to tigecycline and colistin.
The presence of this bacterium in urine was interpreted as asymptomatic bacteriuria, as central venous catheter-associated blood stream infection due to another organism (_Achromobacter denitrificans_) was demonstrated.
http://healthmap.org/geosentinel/
Outline
• Cosa è una infezione emergente /ri-emergente?
• Mobilità umana (… e non solo)
• Emerging infections:
• Conclusions and acknowledgements
malariaMarburg hemorrhagic fevermeaslesmeningitismonkeypoxMRSA (Methicillin Resistant Staphylococcus aureus)Nipah virus infectionnorovirus (formerly Norwalk virus) infectionpertussisplaguepolio (poliomyelitis)rabiesRift Valley feverrotavirus infectionsalmonellosisSARS (Severe acute respiratory syndrome)shigellosissmallpoxsleeping Sickness (Trypanosomiasis)tuberculosistularemiavalley fever (coccidioidomycosis)VISA/VRSA - Vancomycin-Intermediate/Resistant Staphylococcus aureusWest Nile virus infectionyellow fever
drug-resistant infections (antimicrobial resistance)bovine spongiform encephalopathy (Mad cow disease) and variant Creutzfeldt-Jakob disease (vCJD)campylobacteriosisChagas diseasecholeracryptococcosiscryptosporidiosis (Crypto)cyclosporiasiscysticercosisdengue feverdiphtheriaEbola hemorrhagic feverEscherichia coli infectiongroup B streptococcal infectionhantavirus pulmonary syndromehepatitis Chendra virus infectionhistoplasmosisHIV/AIDSinfluenzaLassa feverlegionnaires' disease (legionellosis) and Pontiac feverleptospirosislisteriosisLyme disease
http://www.cdc.gov/ncidod/diseases/eid/disease_sites.htm
Economic Impact of Selected Infectious Diseases
1996 1997 1998 1999 2000 2001 2002 2003
$50bn
$40bn
$30bn
$20bn
$10bn
Figures are estimates and are presented as relative size.
Est
imat
ed C
ost
1994 1995 2004
BSE UK, $10-13bn Foot & Mouth
Taiwan, $5-8bn
Foot & MouthUK
$25–30bn
Avian Flu Asia,$5–10bn
BSE U.S., $3.5bn
BSE Canada$1.5bn
Avian Flu, NL$500m
SARSChina, Hong Kong,Singapore, Canada
$30-50bn
Nipah, Malaysia$350-400m
Classical Swine Fever, Netherlands
$2.3bn
BSE Japan $1.5bn
2005 2006
HPAI, Italy$400m
Outline
• Cosa è una infezione emergente /ri-emergente?• Mobilità umana• Emerging infections
– Air borne infections• Tuberculosis• Influenza, SARS
– Sexually transmitted infections• HIV infection• Resistant STIs
– Vector borne diseases• Malaria, Leishmaniosis• Chikungunya, WNV
– Vertically transmitted infections• Chagas
– Blood borne and transplant related infections / reactivations• Chagas, Malaria• Strongyloidiasis
• Conclusions and acknowledgements
Country: Italy – Source: EuroTB 2010
ReactivationNew infection
Reactivation
>70% of cases within
5 yrs since arrival
Many migrants come from the 22 countries with highest TB-disease burden which make up 80% of global TB cases and a substantial proportion of MDR and XDR TB cases
Clustering of TB among foreign borne
persons in Italy
Clusters are more common among Senegalesethan among Italians (OR=5.9, CI 1.4-23.9
Only 3 mixed clusters identified: in two of them the index case was likely to be Italian
Among senegalese clusters are associated to area of residence (OR=3.5, CI 1.3-9.3)
Matteelli A et al., Int J Tub Lung Dis 2003; 7: 967-72
The global rise of extensively drug-resistant tuber culosis:is the time to bring back sanatoria now overdue?
The 3500 bed Sondalo Tuberculosis Hospital in Italy
Keertan Dheda, Giovanni B Migliori, Lancet 2012; 379: 773–75
Hotel MHong Kong
Guangdong Province,
China A
A
H,JA
H,J
Hong Kong SAR
95 HCW
>100 close contacts
United States
1 HCW
I, L,M
I,L,M
K Ireland
0 HCWK
Singapore
34 HCW
37 close contacts
C,D,E
C,D,E
B
B
Vietnam
37 HCW
21 close contacts
F,G
Canada
18 HCWF,G
11 close contacts
Effect of Travel and Missed Cases on the
SARS EpidemicSpread from Hotel M, Hong Kong
Index Case
(Mother)
Admitted to SGH
Patient A
(Son)
SGH
Friday, March 7 th
Night of March 7 th
Observation Unit ER SGH
Patient A
Patient C
Patient B
Hi Guys:
A quick heads up - we have just had 2 deaths and 3 secondary cases (2 now in ICU) from an acute respiratory disease in recent travellers to Hong Kong. Early diagnostic tests for influenza A and B and other respiratory viruses are NEG. Anyone else having similar cases??
Respiratory isolation- no health care workers ill (yet?). We are putting any febrile person recently returned from HK or VN on resp isolation and of course any febrile contact of the known cases.Apparently one of the cases now in hospital here, also recently traveled to ATLANTA for 2 days and became symptomatic there before flying home to Toronto.
One death was in a 44 yo male (not 30 as I mentioned earlier) No evidence hemorrhage, renal disease, other organ system involvement - he is having an autopsy now. Everything so far NEG - including sputum, blood cultures NEG. Negative EIA, DFA, 5 day culture neg for flu A and B, and DFA resp screen.NPs, blood, autopsy tissue going for chlamydia/myco PCR, hantavirus and resp viruses, RT PCR for adeno, H1/H3/H5 etc.
Kevin
GeoSentinel
Role ofHyperTransmitters
• Hong Kong index case was MD from Guangdong
– Infected 9 others staying on same floor of Metropole hotel
– Some of these became the index cases for Toronto and Singapore outbreaks
• Singapore index case
– Mother, father now dead of SARS, grandmother ill
– Pastor who spent only 20 minutes dead of SARS
Il serbatoio animale
1. Diffusione?
2. Rischio epidemiologico per l’uomo?
3. Mantenimento del virus in natura?
Cronologia di comparsa
delle principali pandemie influenzali
20-40 million deaths
1-4 million deaths
1-4 million deaths
24 Febbraio 2009
Primo paziente = bambina di 6 mesi nel nord del Messico
(Cohen J. Swine flu outbreak, day by day. ScienceInsider. July 17, 2009. )
3 Marzo 2009
I primi casi a Messico City.
6 Aprile 2009
Outbreak nel paese di La Gloria, Mexico, con un tasso di attacco del 60%.
15 Aprile 2009
Primi casi virologicamente confermati in Messico. In California primo caso
fuori dai confine del Messico= ragazzo di 10 anni
26 Aprile 2009
Gli Stati Uniti dichiarano l‟emergenza sanitaria
Timeline
della pandemia influenzale da virus 2009 A/H1N1
HIV infection in Europe
Likatavicius G, van de Laar MJ. Euro Surveill. 2011;16(48):pii=20030. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20030
Daniel J Morgan. Non-prescription antimicrobial use worldwide: a systematic review, Lancet Infect Dis 2011; 11: 692–701
Etiologic agents of human malaria
• Plasmodium falciparum
• Plasmodium vivax
• Plasmodium ovale
• Plasmodium malariae
• *Plasmodium knowlesi
*Human infections with P. knowlesi are not new in Southeast Asia.
P. knowlesi infections are primarily a zoonosis with wild macaques
as the reservoir hosts. Ongoing ecological changes resulting from
deforestation, with an associated increase in the human population
is enabling this species to switch to humans as the preferred host.
Global Distribution (Robinson Projection) of Domina nt or Potentially Important Malaria VectorsFrom Kiszewksi et al., Am. J. Trop. Med. Hyg., 2004; 70:486-498.
http://www.cdc.gov/malaria/about/biology/mosquitoes/map.html
Vector borne infections:
- Malaria
- Chikungunyia
A systematic review of the donor's charts revealed that he was a 30-yr-old
black male who had returned to Italy from Ghana 1 month before his sudden
death in a road traffic accident.
Blood films: P. falciparum trophozoites
NOTE: two kidney recipients from the same donor also developed malaria (1 in Brescia)
In non endemic areas, P. falciparum malaria recrudescence may occours during immune suppression conditions such as pregnancy, splenectomy and tumors
50CIRM, january 20th, 2012
Da Baldelli e Poglayen, 2008
Biglino et al, JCM, 2010; 48: 131-6
Biglino et al, JCM, 2010; 48: 131-6
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23-Jun 30-Jun 7-Jul 14-Jul 21-Jul 28-Jul 4-Aug 11-Aug 18-Aug 25-Aug 1-Sep 8-Sep 15-Sep
No.
of c
ases
Other location
Cervia
Castiglione di Cervia andCastiglione di Ravenna
Epidemic Curve by
Presumed Place of Infection
Rezza G, et al., Lancet. 2007 Dec 1; 370 (9602): 1840-6.
Secondary clusters:
Cervia (9 Km) 19 cases
Ravenna (23 Km) 9 cases
Cesena (19 Km) 15 cases
Bologna (90 Km) 5 cases
Rimini (49 Km) 6 cases
Current known distribution of Aedes albopictus
Prevalence of IgM and IgG antibodies to West Nile virus among blood
donors in an affected area of north-eastern Italy, summer 2009
Abstract. Following reports of West Nile neuroinvasive disease in the north-eastern
area of Italy in 2009, all blood donations dating from the period between 1 August
and 31 October 2009 in the Rovigo province of the Veneto region were routinely
checked to exclude those with a positive nucleic acid test for West Nile virus
(WNV). Only one of 5,726 blood donations was positive (17.5 per 100,000
donations; 95% confidence interval (CI): 0.4–97.3). In addition, a selection of 2,507
blood donations collected during the period from 20 July to 15 November 2009
were screened by ELISA for IgG and IgM antibodies against WNV. A positive result
was received for 94 of them. The positive sera were further evaluated using
immunofluorescence and plaque reduction neutralisation test (PRNT), in which
only 17 sera were confirmed positive. This corresponds to a prevalence of 6.8 per
1,000 sera (95% CI: 4.0–10.9). In a case-control study that matched each of the 17
PRNT-positive sera with four negative sera with the same date of donation and
same donation centre, we did not find a significant association with age and sex of
the donor; donors who worked mainly outdoors were significantly more at risk to
have a positive PRNT for WNV.
Pezzotti P. et al. Euro Surveill. 2011;16(10):pii=19814. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19814
Abstract. Following reports of West Nile neuroinvasive disease in the north-eastern
area of Italy in 2009, all blood donations dating from the period between 1 August
and 31 October 2009 in the Rovigo province of the Veneto region were routinely
checked to exclude those with a positive nucleic acid test for West Nile virus
(WNV). Only one of 5,726 blood donations was positive (17.5 per 100,000
donations; 95% confidence interval (CI): 0.4–97.3). In addition, a selection of 2,507
blood donations collected during the period from 20 July to 15 November 2009
were screened by ELISA for IgG and IgM antibodies against WNV. A positive result
was received for 94 of them. The positive sera were further evaluated using
immunofluorescence and plaque reduction neutralisation test (PRNT), in which
only 17 sera were confirmed positive. This corresponds to a prevalence of 6.8 per
1,000 sera (95% CI: 4.0–10.9). In a case-control study that matched each of the 17
PRNT-positive sera with four negative sera with the same date of donation and
same donation centre, we did not find a significant association with age and sex of
the donor; donors who worked mainly outdoors were significantly more at risk to
have a positive PRNT for WNV.
• Seroprevalence of West Nile virus-specific antibodies in a
cohort of blood donors in northeastern Italy.
Pierro A. et al
• Abstract
IgG and IgM levels against West Nile virus (WNV) were measured in 20,033
serum samples that were obtained between October 2008 to September
2009 from 9913 blood donors in the district of Ferrara, northeastern Italy.
As confirmatory test, a microneutralization assay was used to detect the
presence of neutralizing antibodies against WNV. Sixty-eight subjects
(0.69%) were positive for anti-WNV by immunofluorescence assay. Large
differences in the prevalence of antibodies to WNV were noted between
towns in the area evaluated
Vector Borne Zoonotic Dis. 2011 Dec;11(12):1605-7. Epub 2011 Aug 25.
Evidence of West Nile virus lineage 2 circulation
in Northern Italy
Savini G. et a., Veterinary Microbiology xxx (2012) xxx–xxx
T. cruzi transmission modalities(mainly during the indeterminate, low parasitaemia, phase of the disease
� Vector – borne
� Oral
� Blood transfusion (Single 500 ml unit risk: 12-20%)
� SOT (Kidney from infected donor: 35%)
� Immune-depression (Risk of reactivation: 30%)
� Mother to Child (Risk of transmission: 0.1-12%)
Main blood/SOT transmissible tropical infections
Blood borne or transplant-related infections:� Blood (es. malaria);�Transplanted organ (es. HTLV-1);�Reactivation of latent infection (es. strongyloidiasis, HTLV1, T. cruzi, malaria);�De novo infection in the immunosuppressed host (es. visceral leishmaniasis)
Maryin-Davila et al. CMR, 2008; 21: 60-96
HTLV-I/II, West Nile Virus
(WNV), SARS, ChikungunyaVirus
Tuberculosis and non TB mycobacteria
Plasmodium spp, Leishmania
spp, Trypanosoma cruzi,
trongyloides stercoralis,
Schistosoma spp,
Echinococcus spp.
Coccidioides immitis,
Histoplasma capsulatum
Presentation planning
• Migrants: definition and epidemiological overview
• Migrants’ health
• Migration and emerging infections:
• Conclusions and acknowledgements
• Human fight against infection is not over yet (will it
ever be?)
• Humans, domestic animals and wildlife are
inextricably linked by epidemiology of infectious
diseases (IDs).
• IDs will continue to emerge, re-emerge and spread.
• Human-induced environmental changes, inter-species
contacts, altered social conditions, demography and
medical technology affect microbes’ opportunities.
Summary