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Zoonoses research at OUCRU Vietnam
Juliet Bryant�Oxford University Clinical Research Center, Vietnam�Thimpu, Bhutan �September 2013 �
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H5N1 Avian influenza�Streptococcus suis�
An exclusive focus on zoonoses misses the whole concept of One Health
…and misses the point of why research on animal health is fundamentally important
ONE HEALTH framework
Maudlin, et al 2009 Phil Trans R Soc�
Disease burden of zoonoses
Beyond zoonoses: new ways to conceptualize the interdependence of human and animal health
Although the majority of pathogens may be zoonotic (>60%), the burden of disease from most zoonoses is negligible when compared to human-adapted infectious diseases. �
Why are zoonoses interesting to study?
1) the emergence potential; 2) the complexity of control options; 3) associations with poverty and
development.
The Animal – Human interface
Wellcome Trust Strategic Award 2012-2016
Pathogen discovery
Rule out known pathogens
novel pathogens
Dx Unknown Origin
Next generation seq
Hospital-based syndromic surveillance (3 yrs, N = 12,000 )
Cross-species transmission Community-based cohorts
Vietnam Initiative on Zoonotic Infections (VIZIONS)
sera & swabs
Periodic sampling
Specimen banking
Responsive sampling to clinical episodes
Catchment area
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Baseline sampling at enrollment�
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Which pathogens will we look for ?
What we said we would do: �Retrospective serosurveys on 5 most common zoonotic viruses, using baseline and closeout human sera�
Target pathogens�
Specimen banking �� priorities pending results from hospital surveillance�
[Influenza]�Rotavirus�Hepatitis E�Coronavirus�Hantavirus �
What are we currently pursuing: �
Viral zoonoses Rotavirus�• 96% seroconversion by 2 yrs�• Primary infection usually symptomatic�• 0.5-1% of all human infections may be zoonotic�
Hepatitis E�• 1/3 of the world population is seropositive�• Primary infection usually asymptomatic�• Fraction attributable to zoonotic origin UNKNOWN; all one serotype �
Coronavirus�• 4 known human-adapted CoV species account for 10% of hospitalized acute respiratory infections�• Other than SARS and EMC, no known zoonotic CoV�• No known human enteric CoVs; no known primate CoV�
Hantavirus �• 1-3% seroprevalence in Vietnam; much higher elsewhere in northern Europe �• STRICTLY zoonotic; ~10 human cases confirmed in Vietnam in the last decade �
Is the reservoir of rotavirus diversity within domestic animals of epidemiological relevance ?�
Does the advent of pediatric RoV vaccination make the zoonotic reservoir more or less important ?�
Rotavirus prevalence on pig farms, Dong Thap
Ct < 36 167For 454 seq 92
Rotavirus
Hum
an�
Pig�
HCM
C�D
T�
Tra My, et al 2011�
Hepatitis E
Is there a measurable burden of clinical disease associated with HEV in Vietnam ?�
Meng,XJ et al 2010�
…and what fraction of cases might be zoonotic in origin?�
Drexler, JF et al 2012�
Hepatitis E virus prevalence in swine, Dong Thap
5 samples with Ct<27�sent to Sanger for WGS�
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Hepatitis E � Zoonotic transmission through direct contact with swine�
Increased HEV sero prevalence among occupational exposures (vets, butchers, slaughterhouse)�USA � �26% (Meng et al 2002)�Sweden � �13% (Olsen et al 2006)�Moldavia �51% (Drobeniuc et al 2001)�Netherlands �11% (Bouwknegt et al 2007)�
Preliminary results from cohort serology�
Hantavirus Are there food safety risks associated with the rodent trade? �
What is the prevelance and distribution of Hantaviruses circulating in Vietnam?�
Setting up in-house molecular & seroassays� Available ref positive controls [Seoul, Hantaan]� 3 generic pan-hanta assays � Klempa et al, 2004 [L segment]� IFA spotslides [just received pos cntrl sera]�
Market rats (n=150)� Homogenized lungs� pooled (5 rats/pool) � extracted� 11 of 30 pools positive� Individuals re-extracted � � � L and S segment � Seoul virus� R. argentiventer not a known host for any Hantas�
Field-trapped rats (n=136)� IFA results for multiple viruses�
Initial screening�
Hantavirus
IFA microscopy [collab w/Finland Forest Research Inst, Metla]�
Hantavirus
Coronavirus
Porcine Epidemic Diarrheal virus: potential for zoonotic transmission ? �• Suspect pig outbreaks within our VIZIONS study province�• Anecdotal evidence of human diarrheal infections�
1) Mol screening pediatric diarrhea cases for PEDv�2) Generate an isolate � set up IFA�3) Neutralizing antibodies?�
Campylobacter Campylobacter sp.� C. jejuni� C. coli�
> 92% resistant to cephalosporins, erythromycin and nalidixic acid�
Antimicrobial resistance
Antibiotic resistance research: a need for surveillance
Heiman Wertheim Oxford University Clinical Research Unit – Hanoi VINARES WORKSHOP
A delicate balance
Antibiotic effectiveness is a valuable natural resource, like clean water or forests. �
All antibiotic use, appropriate or not, ‘uses up’ some of the effectiveness. �
But antibiotics are also lifesavers and we need access to them.�
Variable resistance rates of Klebsiella pneumoniae�First report on antibiotic use and resistance in Vietnam 2009, MoH�
Preliminary Resistance Data High resistance rates amongst Gram-negatives�First report on antibiotic use and resistance in Vietnam 2009, MoH�
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GARP National surveillance system at the Ministry of Health Observational study in 15 rural and 15 urban pharmacies of antibiotic sales in
comparision to all drug sales Assessing treatment costs of resistant blood stream and CNS infections (national
WHOnet data)
Klebsiella Characterisation of blood culture isolates / WGS Sanger Cross-sectional population study
Acinetobacter phage therapy C-reactive protein RDT intervention study VINARES
The three arms of VINARES
ICU: characterise Hospital-Acquired Infections on ICUs
• Prevalence, aetiology, resistance • Red flags
Pharmacy: assess antibiotic consumption Appropriateness of prescribing on ICUs
Microbiology: enhance laboratory capacity
• Quality • Appropriateness
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Hospital Number of beds in
2008 Bed occupancy rate
2008,%
Bach Mai Hospital 1500 176.6
National Hospital of Pediatrics 650 180.0
National Hospital of Tropical Diseases 170 101.0
National TB hospital 448 92.5
Saint-Paul Hospital 539 156.2
Thanh Nhan Hospital 673 96.0
Vietnam-Germany Hospital 763 106.0
Vietnam-Sweden Uong Bi Hospital 583 100.8
General Binh Dinh hospital 818 152.0
General Da Nang hospital 852 186.0
Hue Central General 2006 106.6
Cho Ray Hospital 1531 157.0
General Dong Thap hospital 824 99.2
Ho Chi Minh Children Hospital 1 969 139.0
Hospital of Tropical Disease (HTD) 500 107.5
Antibiotic consumption for systemic use (J01) by ATC class in 15 hospitals in 2008�
Treatment guidelines • Most treatment guidelines outdated • Recommendations for AB do not match local current
resistance data A need for good local resistance data!
• Take into account local epidemiology S. suis common cause meningitis K. pneumoniae common in severe pneumonia
Lab issues for resistance testing in Vietnam
Quality control often not place No standard procedures No confirmation of unlikely resistances Errors in CLSI guideline translations Lack of knowledge/training Lack of funding
Transfer of AMR?�Transfer of Salmonella?�
VIBRE: bacterial zoonoses and AMR
Diarrhoea patients (N=500) �
Chickens�• Backyard farms (N=102)�• Medium farms (N=102)�Development of AMR E. coli ? �Presence of Salmonella?�
Chicken farmers�• Backyard farms (N=102)�• Medium farms (N=102)�
• Knowledge and use of antimicrobials:�-Treatment poultry diseases�-Feed additives�
• Bio-security�
• Use of antimicrobials�• Contact with chickens�• Food habits�
Transfer of AMR?�Transfer of Salmonella?�
• Use of antimicrobials�• Food habits�
Non-farmers (N=204)�
• Not involved in poultry farming�• Matched by commune, age/sex to farmer�
• Use of antimicrobials�• Food habits�
Chicken farm�
PROVINCIAL HOSPITAL�
RURAL (3 districts)� URBAN (My Tho)�
Urban inhabitants (N=102)�• Not involved in poultry farming�• Living in urban centre of My Tho�
VIZIONS: �Established a framework for studying viral zoonoses, risk, and ‘the human-animal interface’�
ANTIMICROBIAL RESISTANCE:�Significant expertise on the clinical side�
CHALLENGE: linking the analysis of hospital-based and community-based data �
Perspectives
Many thanks to many many people
Le Nguyen Truc Nhu Nguyet Lam Anh Pham Hong Anh Do Tien Duy Nguyen Van Cuong Ngo Thi Tue Nguyen Thi Diep Ngo Thi Hoa Jim Campbell Juan Carrique-Mas