Onchocerciasis VECTOR TALK - MVCAC · 10/11/2012 2 Onchocerca? What is that? Time to crack open the books... 4 Onchocerciasis aka “River Blindness” • Caused by filarial worm-Onchocerca

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OnchocerciasisDr. Emily Beeler, DVM, MPH

Veterinary Public Health ProgramLos Angeles County

Department of Public Health

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“Do you want to hear about a case of eyeworm?”

• March 2012 email from local vet• 8 yr old Boxer dog from Tarzana • Ulcers in corneas both eyes

– Surgery to patch ulcers– Also removed 1/2 cm “incidental”

painless mass stuck to side of right eyeball

• Mass sent to Univ of Wisconsin for histopathology

• Filled with worms• Some species of “Onchocerca”

Photo Courtesy of Dr Bruce Silverman

Komnenou et al 2002. used with Dr K’s permission

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Onchocerca?What is that?

Time to crack open the books...

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Onchocerciasis aka “River Blindness”• Caused by filarial worm- Onchocerca volvulus

– Distantly related to heartworm parasite of dogs and cats Dirofilaria immitis

– Both contain endosymbiont bacteria Wolbachia• 2nd leading cause of infectious blindness worldwide• Vector: Black flies (Simulium spp)

– breed in rivers and streams• Humans are the definitive host

– Reservoir and victim

(Merck Manual)

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Epidemiology and Control of River Blindness• Endemic in Africa and Latin America, and in Yemen

– 40 million infected (99% in Africa)– Worst hit villages - 1/3 of adults blinded

• Control Programs– 1974 – WHO’s Onchocerciasis Control Program

(OCP) • first large scale control effort in W Africa: Vector

control for first decade - partial success• 1987 - Drug company began free donations of

ivermectin: mass distribution - much greater success

– 1992 Onchocerciasis Elimination Program for the Americas (OEPA)

– 1995 African Programme for Onchocerciasis Control (APOC)

(Rodriguez-Perez et al. 2011, Resnikoff et al. 2008, Adler et al 2010)

6http://www.stanford.edu/class/humbio103/ParaSites2006/Onchocerciasis/Epidemiology.html

River Blindness endemic in 36 countries

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Onchocerca volvulus Life Cycle• Bite from infected black fly introduces L3 larvae into skin • Larvae develop into adult worms in 12 to 18 months• Adults live ~15 years

– Females: ~50 cm – Males: ~5 cm

• Adults gather in painless nodules under skin and elsewhere in body

• Mature female worms produce microfilariae (mff)– Many 1000s per day

• Mff migrate over whole body through the skin and lymph system, invade eyes

• Dying adults or mff release Wolbachia bacteria, trigger inflammatory reaction from host.

(Merck Manual)

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Diagnosis of River Blindness• Palpate for nodules

– remove surgically and examine for adult worms• Skin Snip

– Cut 3-5 grams of skin, place in saline or culture media for 4 hours, examine for mff coming out visually or by PCR. Estimate parasite load.

• Slit Lamp Eye Exam– Look for mff floating in eye

• Mazzotti Test or DEC patch test– Give dose of drug DEC which kills mff. – Intense itching in 2 hours if lots of mff dying

• ELISA blood test for antibodies against Onchocerca– Can’t tell difference betw current and past infection

http://www.stanford.edu/class/humbio103/ParaSites2006/Onchocerciasis/Diagnosis.html

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Symptoms and Treatment of River Blindness

Symptoms– Severity depends upon # of parasites in the body – Painless nodules under skin packed full of adult worms.

Usually over skull, ribs, ankles.– Microfilariae (mff) migrate through skin all over body.– Skin: thickening, scaly, itchy, patches of depigmentation,

premature aging– Eyes: mff migrate through cornea, dying mff trigger severe

inflammation in eye.

Treatment– First 100 years: Only surgical removal of adult worms– Since 1988: ivermectin to kill mff stops parasite life cycle

Rodriguez-Perez et al, 2011

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Nodules formed by adult worms

(FILARIA-EU)

(USAF - PH Source)

(Pugh Parasitology Collection)

(Zerah Eye Center)

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(Christoffel-Blinden Mission, Nigeria, in Resnikoff et al, 2008)

Opacification of corneas and blindness

TextUN-EP

Skin rash from by migrating and dyingmicrofilariae(FILARIA-EU)

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Vector: Black Flies

epa.gov

NO, it’s not acne.

http://blog.timesunion.com/outdoors/the-black-flies-are-coming-the-black-flies-are-coming/2337/

Black Flies and Onchocerca volvulus

• 1926 First proven as vector for onchocerciasis• No Simulium species feeds exclusively on humans • In Africa

– Simulium damnosum spp complex– High affinity for humans– Best known vector for onchocercisis

• Central, South America: – S. ochraceum, S. metallicum and S. exiguum spp

complexes

(Adler et al 2010, Rodriguez-Perez et al 2011, Service 2012, Riley & Johanssen 1915)

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Black Flies• 3 Genera, 2000+ species

– Among top 4 most import arthropod vectors

– Vector for 28 pathogens– Simulium spp most

medically important • Males and females consume

plant juices• Females take blood meals before

oviposition.• Attack in daytime• Mouth parts inflict cuts that

lacerate capillaries (ouch!).• Oozing blood sucked up

– Onchocerca mff ooze from skin, ingested.

Illustrations from: Service 2012. Adler et al 2010, Rodriguez-Perez et al 2011, Service 2012, Riley & Johanssen 1915

Body is 1.5 - 4mm long.

16Photo: Pan American Health Organiza

Black Fly Life Cycle• Sticky eggs

– laid in moving water– on submerged rocks or vegetation– 100-900 per batch– Hatch in 1-4 days

• Mature larvae sticky pad of saliva– Feed on microorganisms in water

• Pupates in silken cocoon 2-6 days

• Adults emerge en masse – float to surface in air bubbles, fly immediately– 15-20 generations / year– Large rivers: up to billion flies/km of river/day– Parts of Amazon - black flies kill livestock, agriculture

impossibleer et al 2010, Rodriguez-Perez et al 2011, Service 2012, Riley & Johanssen 1915)

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Univ Maryland

Rich Merritt, MSU Entomology

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River Blindness in Latin America• Latin America

– Simulium vectors widespread – Onchocerca volvulus only known in 13 foci in 6 countries

• Most heavily populated area at risk: Mexico-Guatemala border– 39 communities hyperendemic

• Onchocerciasis Elimination Program for the Americas (OEPA)• Mass provision of ivermectin• Success in 8 of 13 foci controlled

– Southern Mexico (Oaxaca, Chiapas): » 1995: 600,000 at risk» 2009: 150,000 at risk

– population at risk reduced from almost 5 million to about 1/2 million

(Rodriguez-Perez et al 2011, Adler et al 2010)

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19Map from - Rodriguez-Perez et al, 2011

Simulium ochraceum is not an efficient vector. Buccopharyngeal “teeth” lacerate the mff when ingested....BUT, it readily bites people, and currently feeds on a lot of infected people. ~1% of flies infected in endemic area.

Rodriguez-Perez et al, 2011

2009: PAHO vows to reduce onchocerciasis to insignificant levels by 2015

Many areas in Amazon are “hyperendemic” - >60% infected.

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Investigating Onchocerciasis in Los Angeles County Dogs

1. Is there a particular species of Onchocerca regularly found in dogs?

2. Have there been other cases in Southern California dogs?

3. Can the dog-infecting species of Onchocerca also infect people?

• Answers: YES, YES, and….YES!

Onchocerciasis in AnimalsHorses•O. cervicalis in horses

– Adult worm nodules: in nuchal ligament of neck– Vector: Culicoides spp (biting midges)– Present in US

Cattle•O. lienalis and O. gutterosa in cattle

– Adult worm nodules: in abdomen (lienalis) and nuchal ligament (gutterosa)

– Vector: Simulium spp.– Present in US

22Merck Veterinary Manual

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Onchocerciasis in AnimalsDogs•O. lupi

– Adult worm nodules: anywhere inside eye socket• 0.5-2.5 cm

– Vector: undetermined– Most common clinical signs (seen in dogs in Greece)

• Swelling around eye, watery eye, discharge, eyeball and 3rd

eyelid pushed out, pain, sensitivity to light, corneal lesions, granulomas

– 1967 – first described as a parasite found in wolves in Russia– Many cases well-documented in Greece and Hungary.– In US? Yes! We’ll come back to that….

23Rodonaja 1967, Komnenou et al 2002

Can O. lupi infect people?Case #1•18 year old girl in Turkey.•Painful fly bite on upper eyelid •30 days later - painless redness in left eye

– 5mm mass under conjunctiva of one eyeball.

•28 d later, pain in eye, mass still there.– part of a female nematode extracted.

No mff in worm. – Identified morphologically and by PCR

as O lupi.

•No other tx described. •5 months later – normal.

24Otranto et al, 2011

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Can O. lupi infect people?Case #2•26 yr old male in Turkey •Lived in city, only travel had been a summer vacation of 10 days prior summer 2011. Dogs lived in patients home area. No fly bites reported.•Irritation/itching of right eye progressing over 2 weeks. 5x5mm mass seen in conjunctiva.

– CT scan of eye showed nothing else. – Tx 1 wk of topical steroid and antibiotic,plus oral antibiotic. – No improvement.

•Exploratory surgery found nematode tightly packed in mass. Parasites stuck to tissue. Removed in pieces

– Worm total length – 10 cm, female. No mff inside.

– Identified morphologically and by PCR as O lupi.

25Otranto et al, 2012

Can O. lupi infect people?Case #3•8 year old child in irrigated agricultural area of Tunisia. No travel. No fly bite reported.•Dogs, cats, and lots of livestock in area. •4 weeks of pain in right eye. •8mm subconjunctival mass excised completely. •Immature female worm coiled inside. •Identified morphologically as O. lupi.

26Otranto et al, 2012

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Are there other Onchocerciasis cases in pets

in the US?

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Year Location Case Details Citation

1991 San Gabriel Mts, LA County, CA

Grew masses in both eyes, both eyes removed. Gravid female worm(s) seen. Morphology compared to O.lienalis.

Orihel et al, 1991

1993 LA County, CA Corneal lesion and mass on iris – eye removed. Adult male and gravid female worms embedded in sclera. Morphology compared to O. volvulus and O. lienalis.

Gardiner et al, 1993

2000 Lancaster, CA Eye removed. Worm in large nodule behind eyeball . Gravid female worm(s) seen. Morphology compared to O.lienalis.

Eberhard et al, 2000

2000 Yuma, AZ Worm living in corneal lesion. Gravid female worm(s) seen. Morphology compared to O.lienalis.

Eberhard et al, 2000

2005 California Red eye that grew painful. Eye removed. Worm in 1.5 cm mass. Single female worm, not gravid. Morphology compared to O. lienalis and O.lupi .

Zarfoss et al, 2005

2005 California, Washington, Idaho, Nevada.

Glaucoma, eyeball enlargement, corneal ulcers. Male and female worms seen, not gravid.

Zarfoss et al, 2005

2011 Utah, Nevada FeLV + cat. Uncontrollable glaucoma. Eye removed. Gravid female worms embedded in tissue in back of eye. Second eye – same. Confirmed by PCR as O. lupi.

Labelle et al, 2011

2011 Utah, SouthernCalifornia

FeLV + cat. Corneal ulcer. Gravid female worms embedded in tissue in back of eye. Confirmed by PCR as O. lupi.

Labelle et al, 2011

2012 New Mexico ½ cm mass removed from conjunctiva of eye. Gravid female worms seen. Compared to O. lupi.

Sanchez et al, 2012

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Ongoing research on Onchocerca lupi in the USA

• Dr. Richard Dubielzig, Univ of Wisconsin, College of Vet Med

• Dr Amber Labelle, Univ of illinois, College of Vet Med– Many PCR-confirmed O. lupi cases from around So Cal – to be

published….

29All data courtesy of Dr. Richard Dubielzig

Location # of cases confirmed in dogs by biopsy, 1994-2012(most since 2004)

San Diego County 7Los Angeles County 5San Luis Obispo County 1Arizona 4Also has individual cases from TX, OK, MN, UT

Ongoing research on Onchocerca lupi in the USA

• Dr. Thomas Nutman of Laboratory of Parasitic Diseases at the National Institutes of Health (NIH)– Offered to perform PCR testing on fixed tissue samples from So Cal in Dr

Dubielzig’s collection at request of LA County VPH

• GLACVCD agreed to collect black flies from the LA River – near the 2012 canine Tarzana case

• Dr. Thomas Unnasch of Univ of South Florida agreed to PCR test black flies collected by GLACVCD.

30All data courtesy of Dr. Richard Dubielzig

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Photo Courtesy of Dr Bruce Silverman31

2012 LA County case

• 8 yr old Boxer dog from Tarzana • Ulcers in corneas both eyes

– Surgery to patch ulcers– Also removed 1/2 cm “incidental”

painless mass stuck to side of right eyeball

• Dr Dubielzig reported mass to contain Onchocerca

• Dr Nutman running PCR test on fixed tissue.

Komnenou et al 2002

2006 LA County case

• Labrador Mix from Los Angeles, 90068

• Mass on Sclera of left eye.

• Surgery to remove mass – contained

• Dr. Nutman running PCR test on fixed tissue.

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2004 LA County case

•Australian Shepherd from Juniper Hills•Both eyes•conjunctival swelling. •Right eye only •corneal degeneration •glaucoma. •Small biopsy of conjunctival -only inflammation.•Dx obtained after eye removed– worms seen•No tissue available for PCR in 2012.

Photo courtesy Dr Bruce Silverman

2012 San Diego County case

• 4 year old Pitbull Mix• Two masses firmly adherent to sclera in

one eye– 1 cm– 0.8 cm

• Surgically removed• Diagnosed as Onchocerca spp on

Biopsy by Dr. Dubielzig.

• Confirmed by PCR as O. lupi by Dr Thomas Nutman. Very similar to O. lupi in Hungary.

Photo Brian Reisinger

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GLACVCD’s Black Fly Control Program

• 1994 - infestation severe along 18 mile stretch of LA River S. vittatumprimarily. Occasional S. virgatum, and S. piperi

• Control Plan: 1.Monitor larval abundance2.Monitor black fly larvae abundance3.Apply Bti when larval #s above thresholds4.Monitor effectiveness of treatment

• Bti=Bacillus thurigiensis israeliensis• soil bacteria• safe to humans and wildlife• kills simuliid and mosquito larvae when ingested• available as slow-release briquettes or powder that is mixed with water

and sprayed on larval habitats• no multiplication of the bacteria - must repeat application

(Dr. Susanne Kluh , http://www.glacvcd.org/Contents/Vector-Services-Info/Black-Flies.aspx, Service 2012 )

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Questions?

Dr. Emily Beeler, DVM, MPH213-989-7060

[email protected] publichealth.lacounty.gov/vet

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39More Onchocerca lupi cases in Greece. Shared with permission, from Dr Anastasia Komnenou

Tumor-like massDischarge, hair loss, redness, bulging eye and 3rd eyelid

Surgery to remove nodule mass Severe corneal ulcer and nodule

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Consult with a Public Health Veterinarian!

[email protected]

publichealth.lacounty.gov/vet

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References• Adler PH, Cheke RA, Post RJ (2010). Evolution, epidemiology, and population genetics of black flies (Diptera: Simuliidae). Infect Genet

Evol 10: 846-865. • Australian Society for Parasitology. Pugh Parasitology Collection. Accessed 10/8/12 from: http://parasite.org.au/pugh-

collection/Onchocerca%20volvulus%2004.jpg_Index.html• Centers for Disease Control and Prevention. Parasites and Health; Filariasis Life Cycle. Accessed 10/8/1 from:

http://www.dpd.cdc.gov/dpdx/HTML/Frames/A-F/Filariasis/body_Filariasis_o_volvulus.htm• Center for Genomics and Bioinformatics Wki Collaboration Center. Accessed 10/8/12 from:

https://wiki.cgb.indiana.edu/display/grp/Overview• Choffnes ER and Relman DA. (2011). THE CAUSES AND IMPACTS OF NEGLECTED TROPICAL AND ZOONOTIC DISEASES

Opportunities for Integrated Intervention Strategies. National Academies Press Accessed 9/27/2012 from: http://www.ncbi.nlm.nih.gov/books/NBK62507/pdf/TOC.pdf

• Eberhard ML, Ortega Y, Dial S, Schiller CA, Sears AW, and Greiner E. (2000) Ocular Onchocerca infections in two dogs in western United States. Vet Parasitol 90:333-338.

• FILARiA-EU. Filariasis in Africa: Research in Action with the European Union. Symptoms. Accessed 10/8/1 from: http://www.filaria.eu/treat/treat/oncho/symptoms.html

• Johanssen OA & Riley. (1915) Handbook of Medical Entomology [Kindle Edition]. Comstock Publishing Company, Ithaca, NY.• Komnenou A, Eberhard ML,Kaldrymidou E, Tsalie E and Dessiris A (2002) Subconjunctival filariasis due to Onchocerca sp. in dogs: report

of 23 cases in Greece. Vet Ophthalmol. 5(2):119-126• Labelle Al, Daniels JB, Dix M, and Labelle P (2011). Onchocerca lupi causing ocular disease in two cats.• Merck Manual - For Professionals. Filarial Nematode Infections. Accessed 10/8 12 from:

http://www.merckmanuals.com/professional/infectious_diseases/nematodes_roundworms/filarial_nematode_infections.html#v1014152• Merck Veterinary Manual. Accessed 10/9/12 at:

http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/71804.htm&word=onchocerca%2ccervicalis• Orihel TC, Ash LR, Holshuh HJ et al. Onchocerciasis in a California dog. American Journal of Tropical Medicine and Hygiene 1991;

44:513–517.

References• Otranto D, Sakru N, Testini G et al (2011). Case Report: First Evidence of Human Zoonotic Infection by Onchocerca lupi (Spirurida,

Onchocercida). Am J Trop Med Hyg 84:55-58.• Otranto D, Dantas-Torres F, Cebeci Z et al (2012). Human ocular filariasis: further evidence on the zoonotic role of Onchocerca lupi. Parasit

Vector 5:84• Pan American Health Organization. Onchocerciasis webpage. Accessed 10/7/12 from:

http://new.paho.org/hq/index.php?option=com_content&view=category&layout=blog&id=3793&Itemid=4048• Resnikoff S, Kocur I, Etya’ale DE, and Ukety TO. (2008). Vision 2020 - the Right to Sight. Ann Trop Med Parasitol. 102 (Suppl):S3-S5.• Rodríguez-Pérez MA, Unnasch TR, Real-Najarro O. (2011) Assessment and monitoring of onchocerciasis in Latin America. Adv Parasitol.

2011;77:175-226.• Rodonaja TE. (1967). A new species of nematode, Onchocerca lupi sp. nov., from Canis lupus cubanensis. Soobshcheniya Akademii Nauk,

Gruzinksaya S.S.R.; 45: 715–719 (in Russian).• Sánchez MD, Orita VM; and Nolan TJ. (2012). Pathology in practice. J Am Vet Med Assoc. 240(4): 385-387.• Sreter T, Szell Z, Egyed Z, and Varga I. Ocular Onchocercosis in dogs: a review. Vet Rec 151:176-180• Scott G. The Black Flies are Coming!! The Black Flies are Coming!! The Times Union Outdoors Blog. Accessed 10/8/12 from

http://blog.timesunion.com/outdoors/the-black-flies-are-coming-the-black-flies-are-coming/2337/• Service M (2012). Medical Entomology for Students - Fifth Edition. Cambridge University Press, New York [Kindle Edition].• United Nations - Environment Programme. Natural Habitatis, Accessed 10/812 from: http://www.unep.org/yearbook/2004/097.htm• US Air Force. Public Health Source. Filariasis Information. Accessed 10/8/12 at

http://www.phsource.us/PH/HELM/PH_Parasites/Filariasis.htm• University of Maryland. Math Bench Biology Modules. Accessed 10/8/12 from: http://www.mathbench.umd.edu/modules/env-

science_mountaintop/page10.htm• Zarfoss MK, Dubielzig RD, Eberhard ML, and Schmidt Sk (2005). Canine ocular onchocerciasis in the United States: two new cases and a

review of the literature. Vet Ophthalmol, 8(1):51-57.• Zerah Eye Center - Gallery. Accessed 10/8/12 from: http://zeraheyecenter.com/gallery.html