Two stories on Brucellosis in Kenya

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Two stories on Brucellosis in Kenya Presented by Eric Fèvre www.zoonotic-diseases.org Twitter: @ZoonoticDisease Institute for Infection and Global Health (IGH), University of Liverpool and International Livestock Research Institute, Nairobi

Brucellosis in Kenya - Epidemiology and Human Burden of a Neglected Zoonotic Disease Matilda Brink and Eric Fèvre (with the collaboration of Eric Osoro and Stella Kiambi, ZDU)

Kenya national scale Kenya s District Health Information System (DHIS) (www.hiskenya.org) All public hospitals and most private clinics Number of brucellosis diagnoses on yearly basis was extracted for each of the 286 administrative districts listed in DHIS. Datasets were MOH 705A&B 2011 and 2012 (the only years that had a report rate above 70%) 286 districts was merged into 157 districts present at 2009 census Cases were assumed to have been infected and diagnosed in their district of residence. Denominator population: Rural Urban Population by Age, Sex, and by District 2009 from opendata.go.ke

Frequency of districts reporting Brucella in 2012 77,973 cases of human brucellosis were reported to the Kenyan Health Information System 75,256 of these cases came from the population >5 Majority of districts reported less than 250 cases (uneven national distribution)

Spatial distribution of reported brucella (2012) A over 5s; B under 5s Spatial scan statistic to detect spatial clustering (and its location) Clustering analysis revealed several significant spatial clusters of cases In the over-5 age group in 2012, the primary cluster included 26 districts in the Rift Valley area Secondary clusters consisted of single districts

Annual incidence Could not use data for prevalence no estimate of population at risk The annual incidence rate of brucellosis diagnosis in Kenya 2012 was 202 per 100,000 people Uneven: 0-1469 cases per 100,000 people Incidence standardized by age structure no significant impact

DALY for Brucella in Kenya Based on a reported number of 77,937 brucellosis cases in 2012 DALYs estimated for males, females and for the total population Assuming an average disease duration of six months Disability weight of 0.19, but no mortality

DALY for Brucella in Kenya Total DALYs lost were 7352, or 0.190 DALYs per 1000 people Explored DALYs lost with under-reporting estimates Under-reported assumed to be in the community and not treated DALYs lost DALYs per 1000 people Males 4862 0.253 Females 2490 0.128 Total 7352 0.190

DALY for Brucella in Kenya Burden of malaria 2,062,605 DALYs (9,332,421 reported outpatient cases) Typhoid fever 163,440 DALYs (632,129 reported cases) Schistosomiasis 313 DALYs (35,420 reported cases) Degree of underestimation 0% 5% 20% 50% 75% 99% Number of cases 77973 81872 93568 116960 136453 155166 Number of deaths 0 8 31 78 117 154 DALYs lost 7352 9941 17656 33097 45930 58254 DALYs per 1000 people 0.190 0.257 0.457 0.857 1.19 1.51

DALY for ssa based on Kenya Extrapolating Kenyan incidence data to sub-saharan Africa Disease Burden in Sub-Saharan Africa (DALYs) Brucellosis a (reported cases only) 140,220 Brucellosis a (incl. 50% underestimation) 632,400 Brucellosis a (incl. 90% underestimation) 1,114,000 Malaria b 30,900,000 Schistosomiasis b 1,500,000 Hook-worm disease b 377,000 Hepatitis B b 355,000 Leishmaniasis b 328,000 Leprosy b 25,000

Summary Brucellosis widespread in Kenya Incidence higher than most countries reported in a recent systematic review (Dean 2012) but did not report much African data (which is itself a problem) Inclusion of Brucella in the DHIS is a great start for passive surveillance Some active surveillance is also required for such diseases that are believed to be severely under-ascertained and underreported (WHO, 2011) Report rates in DHIS were 73% in 2011, 90% in 2012 Work towards a mathematical model of under-detection based on existing data and models (eg rabies, trypanosomiasis.) There is an urgent need to validate the currently available tests against each other Which test is most appropriate for use under Kenyan conditions Need for guidance on false positives/false negatives and confirmatory test

Caveats Numbers reported here regarding cases, incidence and DALYs must be interpreted with caution Parameters for DALY calculation remain a little uncertain (duration, disability weight.) We need a good spatial dataset to represent the DHIS in the new administrative system!

The (short) story of brucellosis in western Kenya Eric Fèvre and William de Glanville www.zoonotic-diseases.org Twitter: @ZoonoticDisease Institute for Infection and Global Health (IGH), University of Liverpool and International Livestock Research Institute, Nairobi

Acknowledgments Funded by: Wellcome Trust (UK) CGIAR A4NH BBSRC MRC The 15-strong PAZ team: James Akoko, Omoto Lazarus, Lorren Alumasa, Daniel Cheriyot, Jenipher Ambaka, Fred Opinya, John Mwaniki, Hannah Kariuki, Gideon Mwali, George Omondi, Alice Kiyong a, Lilian Abonyo, Maseno Cleophas, Fred Ambaka, Velma Kivali, Lian Thomas, Annie Cook Collaborators: Delia Grace, Phil Toye, Steve Kemp (Liverpool), Heinrich Neubauer, Lisa Sprague (FLI), Dorte Dopfer (UW Madison), Greg Gray (Florida), Desiree LaBeaud (CHORI) The Department of Veterinary Services Kenya, the Zoonotic Diseases Unit, Kenya

Western Kenya The People, Animals and their Zoonoses project (PAZ)

Neglected zoonoses Under-represented in terms of knowledge, research, policy and funding Lack of epidemiological and other data Lack of adequate technologies and treatments Lack of acknowledgement and attention from professional groups Occur in marginalised communities and individuals Zoonoses with clear link to poverty Fascioliasis Rabies Cysticercosis Q-fever Echinococcus RVF Leptospirosis Brucellosis Anthrax Trypanosomiasis Bovine TB

What research is needed? - WHO Field epidemiological studies in humans and livestock the number of cases and number of deaths number of new infections age-and sex-specific disability weights for zoonoses Estimates/models of under-reporting Much recent progress: rabies, sleeping sickness Case studies to gather an evidence-base Multi-disease studies what is the overall burden of zoonoses as a group on communities Public health Economics Field-level diagnostics Cost-effectiveness studies dual medical/veterinary benefits Pathogen and host ecology (its not just about drugs and vaccines)

People, Animals and their Zoonoses (PAZ) Integrated research programme that addresses this lack of data and these scientific aims Aims to address both (veterinary) public health and biological questions Epidemiology population scale Framework that can be repeated elsewhere in different communities and ecologies Food chain Domestic animals Humans Peridomestic wildlife Environment

Study site Field site is the Western Province of Kenya 2000 km 2 zone (500,000 cattle, 67,000 pigs, ~1 million people) Small-holder crop-livestock production system in the Lake Victoria Crescent (highest human and livestock densities in East Africa) Intensively and comprehensively sampled over 2.5 years Cluster design (random household), organised by sub-location units All sublocations in the study site to be sampled, proportionally by cattle population distribution

The project is focused on

Field site (Busia field station) Established with Wellcome Trust project funding - diagnostic laboratory in rural western Kenya Joint human and animal field teams and laboratories housed together Mainly parasitology, microbiology and sample preparation, networked data entry Recent addition of molecular and ELISA capability at the field lab High-end laboratory infrastructure (up to BSL-3) in Nairobi

A lateral flow assay was used as primary screening test for brucellosis in sympatric animals and people. - Rapid and simple - Good performance - Animal and human tests - A bit expensive

We found: 2116 people in 416 homesteads LFA : 0.71% (95% C.I. 0.38 1.17) RBT : 0.06% (95% C.I. 0.0014 0.32) 893 cattle in 230 homesteads LFA : 0.31% (95% C.I. 0.06 0.89) No relationship between animal and human sero-status at the household level

Further surveillance based on central point sampling Seroprevalence based on RBT < 0.5%

But, brucellosis apparently a common diagnosis in district and sub-district hospitals in study area...

So, we went to investigate. Rose Bengal +ve Brucella Agglutination Test Lateral Flow Assay

A population of 827 brucellosis suspects

A population of 827 brucellosis suspects BAT: 19.7%

A population of 827 brucellosis suspects RBT: 0.6%

5% of reactive BAT confirmed on LFA

So, brucellosis appears to be rare and over-diagnosed using current diagnostic approaches in western Kenya. Limits use of people as sentinels for zoonotic disease in animals.... one-health

Thank you. Eric Fèvre eric.fevre@liverpool.ac.uk Will de Glanville w.a.de-glanville@sms.ed.ac.uk www.zoonotic-diseases.org