“bugs are bringing bugs” - health sciences...

“Bugs are Bringing Bugs” Mosquito and Tick-borne Diseases

Greenville Postgraduate Seminar

April 11, 2014

Eric Brenner, MD Email: [email protected]

Mosquito Tick Louse Flea Fly

Virus

Arboviruses

WNV Yellow Fever

Dengue EEE WEE SLE LACV

Chikungunya

Powassan (POW)

TBE (Tick borne

encephalitis)

Bacteria

Lyme Disease

RMSF

Anaplasmosis

Ehrlichiosis TBRF

Tularemia

Typhus

LBRFPlague

Trachoma

Tularemia

Protozoa Malaria Babesiosis Leishmaniasis

Metazoa Dog heartworm Onchocerciasis

(*) Examples only, thus not a complete list

Examples of Vector-borne Diseases (*)

Vector

Typ

e o

f P

ath

oge

n

Hence, in SC had fatal “bubonic”, “septicemic” and “pneumonic” plague… acquired not abroad, but in New Mexico!

Another SC Case Presentation

• 36 yo male c/o fever x 4 days with chills, headache and

general malaise. No special “cyclical fever pattern” noted.

• Pt. had just returned from overseas tour as a Peace Corps

Volunteer

• Had been working in Malawi (East Africa) for 9 months.

• PMH: no significant past or present co-morbidities

• Medications: Had been taking weekly mefloquine for anti-

malarial prophylaxis x 8 months. DC’ed meds just in last

few weeks prior to departure home.

• Other travel history: Thailand, Malaysia, Honduras,

Nicaragua within the last 6-7 years.

Physical Exam

• Healthy-looking patient, afebrile

• Ox3. No nucal rigidity or neuro deficits

• No pallor

• No organomegaly

• No petechiae or muco-cutaneous stigmata of endocarditis or HIV

What is the Presumptive / Working Diagnosis?

Medical Decision Priorities

• Malaria until proven otherwise

• How to confirm diagnosis – Blood smear (traditional!)

– Rapid blood tests (newer… but are they available?)

• What species?

• Parasitemia level?

• Cerebral malaria? Other complications?

• Labs to check for complications (Hb, glucose, creatinine, LFTs…)

• IV vs. po treatment

• Is hospitalization required?

“Ring-form” trophozoites Banana-shaped gametocytes

Morphology confirms infection due to Plasmodium falciparum

What does one need to know about malaria Rx?

1. On the tropical medicine board exam?

2. In every day front-line primary care practice?

• Nuances, doses, options for routes of administration of all the antimalarials as might be used singly or in combination

• CDC clinicians on-call 24/7 to provide advice to clinicians re malaria Dx/Rx.

• Malaria Hotline 770-488-7788 (or toll free 855-856-4713) M-F 9-5.

• Off-hours, weekends, and holidays => 770-488-7100 and ask for malaria clinician on-call.

Or more simply: Daytime main CDC Number: 404-639-3311 Nights/weekends: 404-639-2888

Malaria Perspectives

• Malaria (and YF) common in SC in colonial days

• Endemic local transmission now eliminated, though the insect vectors remain (Anopheles for malaria; Aedes for YF)

• Cases now thus seen only in: 1. Internationals arriving from endemic countries

2. Americans who have travelled to malarious areas and fail to take proper anti-malarials

3. VFRs (“Visiting Friends and Relatives”): i.e. Internationals going “home” on vacation who do not take prophylaxis and who – for several reasons -- are at high risk of disease!

SC VBDs in Perspective (2004-2013)

RMSF

Lyme

Disease Babesiosis Malaria Dengue

WN

Fever

WNV -

Neuro-

invasive EEE

2004 68 6 10 1 2 1

2005 50 12 12 2 4 1

2006 47 18 9 1 1

2007 65 34 8 3 2 2

2008 58 33 8 1 2

2009 23 47 7 2 3

2010 18 28 6 16 1

2011 40 40 8 2 1

2012 68 42 9 2 19 10

2013 56 26 1 10 9 6

Total 493 286 1 87 37 37 18 2

Tick-borne Mosquito-borne

Year

Why is this a good time to think about “vector-borne diseases”?

• Just getting into lovely spring & summer weather

– Outdoor activities

– Summer holidays

– Hikes and woods

– Mosquito & tick season!

• April 7: WHO’s World Health Day this year focuses on vector-borne diseases under the theme: “Small bite, big threat”

• Theme echoed world-wide… e.g. at PAHO, CDC etc.

www.who.int/campaigns/world-health-day/2014/en/

(www.who.int)

WHO World Health Day 2014 Posters re Vector-borne

Diseases

CDC world Health Day Flyer

www.cidrap.umn.edu

www.cdc.gov/ticks

Reported Lyme Disease Cases 2012 (CDC)

We have Ixodes scapularis ticks in Connecticut AND in South Carolina…. So, why the difference in incidence in Lyme Disease?

??

Southern Tick-Associated Rash Illness (STARI)

Reported Cases of Rocky Mountain Spotted Fever (RMSF) 2012

Ehrlichia Chaffeensis- 2012

Anaplasma phagocytophilium-2012

Distribution of Key Tickborne Diseases, 2012 (CDC)

Lyme Disease • Caused by spirochete Borrelia burgdorferi

• Caused by Ixodes ticks

• ~30,000 cases reported annually in US

• Studies about to appear suggest actual number of annual infections may be closer to ~300,000 (!!) – BUT… this “jump” largely indicative of under-

reporting and NOT of increase

– Main geographic foci not greatly changing (though there has been a gradual “southward extension” from previous mainly New England hyper-endemic focus

– This “revised estimate” based on surveys of “medical visit coding”, “laboratory test results” and other “indirect counting & extrapolation” methods

Life Cycle of Ixodes Scapularis (CDC)

Primary Dis. Transmitted • Lyme disease • Anaplasmosis • Babesiosis • Powassan disease • STARI • Ehrlichiosis • Tularemia • RMSF

Erythema Migrans (EM)

• Seen in ~ 70-80% of cases • ~1-2 weeks after tick bite • Expands over days • Rarely painful • Distinguish from allergic

reaction ?

Atypical EM Presentations

Disseminated and Late Lyme Disease Facial Palsy • Summer months • May be bilateral • +/- CSF pleocytosis

Arthritis • Intermittent • Oligoarticular • Swelling >> pain

Late-stage neurologic • Peripheral neuropathy • Encephelopathy

(MMWR Dec 13, 2013)

(MMWR Aug 16, 2013)

(JSCMA June 2013)

Comparison: In one case deaths from cardiac complications of unrecognized tick-bites… whereas here we have rabies death following an unrecognized bat bite

Sensitivity of Two-Tiered Serologic testing (*)

Lyme Diseae Stage Sensitivity (%)

EM rash (acute) 38

EM rash (convalescent) 67

Early Neurologic 87

Late Neurologic 100

Arthritis 97

(*) Specificity of two-tiered testing generally >95

Bottom Line: • Two-tiered testing performs well in late stages of disease • Testing of EM patients not generally necessary (?!)

Possible “red flags” for “alternate labs” (CDC)

• Tests offered are not FDA approved

• Laboratory claims to “specialize” in Lyme and other tick-bone disease testing

• Do not accept insurance => patient pays out of pocket (e.g. $500 - $1000 ++)

http://en.wikipedia.org/wiki/Mosquito-borne_disease

The Nile

River Basin Uganda: West

Nile District

NY Times Sept 4, 1999

Unusual Encephalitis Cluster

in Northern Queens, 1999

NYT April 8,

2013

What does this

story about a single

(just 1!) case of polio in

Baghdad have to do with WNV?

• 44% Participation among households selected by cluster

sampling

• Estimated seroprevalence : 2.6% (95% CI: 1.2 – 4.1%)

• 20% of seropositive individuals reported febrile illness.

Primary symptoms included:

- Myalgias (100%) - Fatigue (87%)

- Headache (89%) - Arthralgias (76%)

• Overall “neuroinvasive infection to “asymptomatic

infection” ratio ~ 1:200-300.

Household-based Serosurvey Conducted in 2x2

Mile area in Northern Queens in Persons 5+ y.o.

A “natural history pyramid” with essentially the same shape and compartment proportions as we find in polio (!!)… with similar consequences about how we may consider what is “really happening” when we have even one person with polio paralysis or WNV neuro-invasive disease.

• Migrating viremic bird?

• Imported viremic bird (legally or illegally)?

• Viremic human traveler?

• Imported mosquitoes (airplane or ship)?

• Intentional release?

Potential Sources of Introduction

of WNV into NYC (?)

• Need to always remain open-minded to the possibility

of the unexpected

• Importance of strong relationships between the medical

community and public health.

• Need to engage nontraditional public health partners

(e.g., veterinarians, wildlife experts)

• Unusual events in animals/birds may be an early

warning for human disease outbreaks

• Newly introduced West Nile virus may become

endemic in the US

West Nile Outbreak 1999:Lessons Learned / Conclusions

Countries with reported local transmission of Chikungunya virus (as of 2-10-2014)

www.cdc.gov/chikungunya/geo/americas.html

Chickungunya Virus - 1

• Single stranded RNA virus

• Related to Mayaro, O’nyong-nyong and Ross River viruses

• Predominantly spread by Aedes aegypti and Aedes albopictus (same vectors as for Dengue!)

• Aggressive daytime biters

• Most (~72-97%) infected develop symptoms: typically abrupt fever >39.0C + often severe polyarthralgia

• Also variable: headache, myalgia, conjunctivitis, NV, maculopapular rash

• Risk factors for hospitalization or atypical disease: neonates, older age, underlying conditions

Chickungunya Virus - 2

• Dx assays (e.g. through DHEC and CDC)

– Viral culture (<= 3days)

– RT-PCR <=8days)

– IgM Ab >= 4 days

• Treatment

– No specific antiviral

– Supportive care / rest /fluids / NSAIDS

Some Final Thoughts and Questions?

• Will range of Chickungunya transmission extend up from Caribbean to Florida (where Dengue is already established, and thence (also with Dengue) up the SE Coast where Aedes mosquitoes are already present!

• Might these new virus go “coast to coast” in a few years…. Just as did WNV?

• Will society be willing to invest in government run community-wide mosquito control programs -- or leave backyard spraying to the private sector?

• What consequences of emerging VBDs for front-line medical practice?

• Will global warming extend the “eco-range” of various mosquito (and other) vectors, and hence radically change the epidemiology and distribution of VBDs!?

“bugs are bringing bugs” - health sciences...

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