Zoonoses research at OUCRU Vietnam. Juliet Bryant Oxford University Clinical Research Center, Vietnam Thimpu, Bhutan September 2013

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1 Zoonoses research at OUCRU Vietnam Juliet Bryant Oxford University Clinical Research Center, Vietnam Thimpu, Bhutan September 2013

2 H5N1 Avian influenza Streptococcus suis

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4 ONE HEALTH framework 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

5 Disease burden of zoonoses 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. Maudlin, et al 2009 Phil Trans R Soc Beyond zoonoses: new ways to conceptualize the interdependence of human and animal health

6 The Animal Human interface Wellcome Trust Strategic Award

7 Vietnam Initiative on Zoonotic Infections (VIZIONS) Pathogen discovery Hospital-based syndromic surveillance (3 yrs, N = 12,000 ) Cross-species transmission Community-based cohorts Rule out known pathogens Dx Unknown Origin Periodic sampling Next generation seq sera & swabs novel pathogens Responsive sampling to clinical episodes Specimen banking

8 Catchment area

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13 Baseline sampling at enrollment

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27 Which pathogens will we look for?

28 Target pathogens What we said we would do: Retrospective serosurveys on 5 most common zoonotic viruses, using baseline and closeout human sera What are we currently pursuing: [Influenza] Rotavirus Hepatitis E Coronavirus Hantavirus Specimen banking priorities pending results from hospital surveillance

29 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

30 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?

31 Rotavirus prevalence on pig farms, Dong Thap Ct < For 454 seq 92

32 Pig Human Rotavirus DT HCMC Tra My, et al 2011

33 Hepatitis E Is there a measurable burden of clinical disease associated with HEV in Vietnam? and what fraction of cases might be zoonotic in origin? Meng,XJ et al 2010 Drexler, JF et al 2012

34 Hepatitis E virus prevalence in swine, Dong Thap 5 samples with Ct<27 sent to Sanger for WGS

35 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

36 Hantavirus Are there food safety risks associated with the rodent trade? What is the prevelance and distribution of Hantaviruses circulating in Vietnam?

37 Hantavirus Initial screening 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

38 Hantavirus IFA microscopy [collab w/finland Forest Research Inst, Metla]

39 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?

40 Campylobacter Campylobacter sp. C. jejuni C. coli > 92% resistant to cephalosporins, erythromycin and nalidixic acid

41 Antimicrobial resistance

42 Antibiotic resistance research: a need for surveillance Heiman Wertheim Oxford University Clinical Research Unit Hanoi VINARES WORKSHOP

43 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.

44 Preliminary Resistance Data High resistance rates amongst Gramnegatives First report on antibiotic use and resistance in Vietnam 2009, MoH Variable resistance rates of Klebsiella pneumoniae First report on antibiotic use and resistance in Vietnam 2009, MoH

45 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

46 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

47 Hospital Number of beds in 2008 Bed occupancy rate 2008,% Bach Mai Hospital National Hospital of Pediatrics National Hospital of Tropical Diseases National TB hospital Saint-Paul Hospital Thanh Nhan Hospital Vietnam-Germany Hospital Vietnam-Sweden Uong Bi Hospital General Binh Dinh hospital General Da Nang hospital Hue Central General Cho Ray Hospital General Dong Thap hospital Ho Chi Minh Children Hospital Hospital of Tropical Disease (HTD)

48 Antibiotic consumption for systemic use (J01) by ATC class in 15 hospitals in 2008

49 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

50 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

51 VIBRE: bacterial zoonoses and AMR RURAL (3 districts) Chicken farm Knowledge and use of antimicrobials: -Treatment poultry diseases -Feed additives Bio-security Chickens Backyard farms (N=102) Medium farms (N=102) Development of AMR E. coli? Presence of Salmonella? Transfer of AMR? Transfer of Salmonella? Use of antimicrobials Contact with chickens Food habits Chicken farmers Backyard farms (N=102) Medium farms (N=102) Use of antimicrobials Food habits Non-farmers (N=204) Not involved in poultry farming Matched by commune, age/sex to farmer Transfer of AMR? Transfer of Salmonella? URBAN (My Tho) Use of antimicrobials Food habits Urban inhabitants (N=102) Not involved in poultry farming Living in urban centre of My Tho PROVINCIAL HOSPITAL Diarrhoea patients (N=500)

52 Perspectives 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 communitybased data

53 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

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