Epidemiological Modeling of Brucellosis in India GLORIA KANG, L. GUNASEELAN, KAJA ABBAS

OBJECTIVE • To develop an epidemiological model of brucellosis transmission dynamics among livestock cattle in India • To estimate the impact of different prevention and control strategies • Transmission reduction • One-time vaccination

BRUCELLOSIS “…the disease rarely kills anybody, but it often makes a patient wish he were dead.” - Time Magazine, 1943

Humans – 500,000 cases/year globally • Brucellosis, undulant fever, Bang’s disease, Malta fever • Systemic disease, variable clinical signs, severe complications, chronic and debilitating

Animals – (cattle, buffalo, sheep, goats, pigs, dogs) • Bovine brucellosis: Abortion, retained placenta, birth to dead/weak calves, low milk yield

Economically important, livestock, occupational… and a neglected disease

MICROBIOLOGY • Facultative, intracellular bacteria of genus Brucella scitechdaily.com/images/brucella-bacterium.jpg

• Brucella spp. resist environmental stresses in phagocytic cells and modify intracellular trafficking • Compromise host immune responses • Long-term survival sustains chronic infections • Pregnant uterus = immunologically-privileged • Extremely efficient in avoiding immune recognition and manipulating host cell physiology • Yet, poorly understood

ECOLOGY • Emerging, re-emerging, and constantly changing geography • Dynamic disease ecology

Year

Brucella species

1887 1897 1914

B. melitensis B. abortus B. suis

1947 1950s 1960s 1990s 1990s 2008 2010

B. neotomae B. ovis B. canis B. ceti B. pinnipedialis B. microti B. inopinata

Biovars 1–3 1 – 6, 9 1, 3; 2; 4; 5

Preferential host(s) Sheep, goat Cattle Pig; wild boar, hare; reindeer, caribou; rodents Desert wood rat Ram Dog Cetaceans Pinnipeds Soil, vole, fox Unknown

Pathogenicity for humans High High High (pig, reindeer, caribou) Moderate Unknown Unknown Unknown High

TRANSMISSION • Routes • Direct contact, ingestion, inhalation • Transmission • Bodily fluids, aborted fetal material, milk and dairy products • Source is almost always from an animal reservoir

BRUCELLOSIS IN INDIA • First in 1942, now endemic • Unknown human prevalence • Great environment for zoonotic transmission • ~80% agrarian lifestyle

• Frequent herd mixing and movement, varying geo-agroclimatic zones • Cross-infection and epidemiological complexity occurring throughout India

PUBLIC HEALTH SIGNIFICANCE • Risk factors • Farm management practices, vaccination status, herd movement, hygiene

• Disease management • Test-and-slaughter, mass vaccination, surveillance/notification

• In India • Ban on cow slaughter, no disease management, weak surveillance • Top producer of milk and exporter of beef products • Epidemiological modeling!

QUESTIONS FOR PUBLIC HEALTH POLICY AND PRACTICE

• What is the epidemiological impact: prevalence, incidence, mortality, morbidity • What is the geographic/spatial distribution? • What is the demographic distribution? • How reliable is surveillance? • How to conduct hypothesis testing of different scenarios for risk/potential for spread and transmission dynamics? • What interventions are warranted for prevention and control? • When to introduce the interventions? • What is the quantum and period of interventions?

EPIDEMIOLOGICAL MODEL

Part I Epidemiology and disease ecology

MATHEMATICAL MODEL

Part I Epidemiology and disease ecology

Part II Mathematical modeling

Source: Alexey Voinov (2008)

SUSCEPTIBLE – INFECTIOUS – RECOVERED SIR EPIDEMIC MODEL

dS = m - b SI - m S dt dI = b SI - m I dt dR = pvS0 - m R dt

• No recovery • No disease-induced mortality • No waning immunity

DATA • Madras Veterinary College in Chennai, India • Animal seroprevalence • Varies by geography, diagnostic test, cattle breed, production system •

Overall 5% cattle, 3% buffalo (Renukaradhya et al., 2002)

• • •

From 6.6% in Madhya Pradesh to 60% in Assam (Mehra et al., 2000; Chakraborty et al., 2000) Tamil Nadu – 9.3% cattle, 0.5% buffalo, varies from farm to farm, region to region (Renukaradhya et al., 2002; Anandh, 2005; Sulima et al., 2006) Higher in crossbreeds (10.3%), intensive production systems (10.3%), and artificially inseminated herds (10.3%) (ICAR, 2012; Mohmand, 2014)

• Now – about 13.5% seroprevalence, endemic stability (ICAR, 2013)

MODEL PARAMETERS

Parameter

Value

Susceptible proportion, S (endemic stability)

0.865

Infected proportion, I (endemic stability)

0.135

Transmission rate, β Birth/death rate, μ

S19 vaccine efficacy

0.1156 / year 0.1 / year

70%

TRANSMISSION RATE 0.15

Reducing Transmission Rate

0.10

Parameter

0.05

Prevalence

Reduced Transmission Rate 0% 20% 40% 60% 80%

Susceptible (S)

0.865

Infected (I)

0.135

Transmission rate (β) 0.1156

0.00

Birth/death rate (μ)

0

50

100 Time (years)

Value

150

0.1

VACCINATION 0.15

Vaccination

Prevalence

0.10

Parameter

0.05 0.00

50

100 Time (Years)

Susceptible (S)

0.865

Infected (I)

0.135

Transmission rate (β) 0.1156

Proportion Vaccinated 0% 20% 40% 60% 80% 100%

0

Value

150

Birth/death rate (μ)

0.1

Vaccine efficacy

70%

INTERPRETATION

• Reducing transmission rates lowered endemically stable levels of brucellosis prevalence correspondingly • One-time vaccination lowered prevalence initially, but rebounded with influx of new susceptible births

LIFE HISTORY CHARACTERISTICS Reducing Transmission Rate

0.05

Prevalence

Reduced Transmission Rate 0% 20% 40% 60% 80%

0.00

• Life expectancy and birth rate • Assumption: 10 years and 0.1 • No mortality data

0.10

0.15

• Anything that affects the life table (mortality table)

• Other livestock systems

0

50

100

150

Time (years)

• Reproductive rate = ~3 • Life expectancy = 5 years

0.05

Proportion Vaccinated 0% 20% 40% 60% 80% 100%

0.00

• Foundation for disease management

Prevalence

0.10

0.15

Vaccination

0

50

100 Time (Years)

150

LIMITATIONS • Deterministic model is not representative • Assumptions • No age, sex, or risk structure • Direct contact only, no environmental component • Data limitations • Weak surveillance and diagnostic variability • Life history traits and census data • Population dynamics of livestock cattle in India? • Expected population effects from brucellosis •

No direct mortality, but inhibits birth

FUTURE WORK • For this model – • • • •

Refine spatial focus Age/sex-structure Effect of density constraints; multiple vaccinations Environmental component

• New model – • Metapopulation model

PUBLIC HEALTH IMPLICATIONS • The value of mathematical models • Outcomes •

Intervention: For developing countries where conventional methods are impossible

• Processes •

Surveillance: What is the data (and lack of data) telling us?

• Local issues, global impact • Biosecurity, agro-terrorism • Evolutionary ecology • Interdisciplinary collaboration; “One Health”

REFERENCES •

Alexander KA, Blackburn JK, Pesepane R, et al. Buffalo, bush meat, and the zoonotic threat of brucellosis in Botswana. PLoS One 2012; 7:3.

•

Alexander, K. A., Lewis, B. L., Marathe, M., Eubank, S. & Blackburn, J. K. Modeling of Wildlife-Associated Zoonoses: Applications and Caveats. Vector Borne Zoonotic Dis 12, 1005–1018 (2012).

•

Godfroid J, Scholz HC, Barbier T, Nicolas C, Wattiau P, et al. Brucellosis at the animal/ecosystem/human interface at the beginning of the 21st century. Prev Vet Med 2011;102:118-131.

•

Godfroid J, Dahouk SA, Pappas G, et al. A “One Health” surveillance and control of brucellosis in developing countries: moving away from improvisation. Comparative Immunology, Microbiology and Infectious Diseases 2013; 36:241-248.

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Sulima M. Serological and molecular detection of brucella infection in cattle. 2006

•

Mohmand N. Evaluation of zoonotic brucellosis in animal population and occupational groups. Master of Veterinary Science Thesis. Department of Veterinary Public Health and Epidemiology, Madras Veterinary College, Chennai, Tamil Nadu Veterinary and Animal Sciences University.

•

Pappas G. The changing Brucella ecology: novel reservoirs, new threats. Int J Antimicrobial Agents 2010; S8-S11.

•

Renukaradhya GJ, Isloor S, Rajasekhar. Epidemiology, zoonotic aspects, vaccination and control/eradication of brucellosis in India. Veterinary Microbiology 2002;90:183-195.

•

World Organisation for Animal Health. Handistatus II: zoonoses (human cases): global cases of brucellosis in 2004.

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Zinsstag J, et al. A model of animal-human brucellosis transmission in Mongolia. Prev Vet Med 2005; 69:77-95.

ACKNOWLEDGEMENTS • Madras Veterinary College • Department of Veterinary Public Health and Epidemiology • • •

Faculty Scientists Students

• Big Data for Computational Epidemiology • Conference organizers • •

Jiangzhuo Chen Sandeep Gupta

THANK YOU! • Contact: Gloria Kang • [email protected]