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

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1900 1950

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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 <marcelacifuentesdiaz@gmail.com> [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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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