Gregory J. Martin MD Tropical Medicine – Infectious Diseases

US Department of State Washington, DC

The Infectious Disease Smorgasbord: Hot ID Topics for Health Units

The Infectious Diseases Smorgasbord

Hot ID topics for Health Units: - Influenza

- Chikungunya

- Ebolavirus Disease

- Malaria update

- HIV PEP and PrEP

- Meningococcal vaccines and new recs

- PCR in the Health Unit: Biofire/FilmArray

Influenza 2015 Well publicized poor match between the Northern

Hemisphere vaccine and the circulating H3N2 has been associated with a robust, early flu season

First time in 3 years that the Northern and Southern Hemisphere vaccines are different:

Northern Hemisphere 2014-15 Influenza season vaccine components • A/California/7/2009 (H1N1)pdm09-like virus • A/Texas/50/2012 (H3N2)-like virus • B/Massachusetts/2/2012-like virus • B/Brisbane/60/2008-like virus (only in quadrivalent vaccines)

Southern Hemisphere 2015 Influenza season vaccine components • A/California/7/2009 (H1N1)pdm09-like virus; • A/Switzerland/9715293/2013 (H3N2)-like virus (A/South Australia/55/2014, A/Norway/466/2014, A/Stockholm/6/2014)

• B/Phuket/3073/2013-like virus. • B/Brisbane/60/2008-like virus. (only in quadrivalent vaccines)

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So what do we do about flu immunizations? These are my personal opinions NOT CDC recs

If staff received the 2014-15 Northern Hemisphere flu vaccine they are protected against some of the circulating strains and if infected with the new strain are less likely to have severe disease.

If you are in the Southern Hemisphere consider offering an approved Southern Hemisphere influenza vaccine: Strongly recommended for those who did not receive a Northern

Hemisphere flu vaccine earlier Should be encouraged for those with chronic respiratory disease or

other immunocompromising conditions, including age >65 y May be offered to those who received the Northern Hemisphere flu

vaccine and want added protection but should not be required

Neuraminidase Inhibitors Underutilized in HUs?

CDC has tested 139 influenza A and B isolates for resistance this season and 100% were sensitive to both oseltamivir (Tamiflu) and zanamivir (Relenza).

In Oct 2014 FDA approved peramavir (Rapivab) for IV Single dose of 600 mg IV

These antivirals are really only effective if initiated within 48 hours of symptom onset.

• Makonde for “that which bends up” • An alphavirus NOT related to dengue but gives a dengue like illness

with prominent joint pain, may last weeks – Neonates exposed intrapartum may develop severe or fatal dz

• African origin but now widespread in Asia and newly popping up in the Caribbean

• Incubation for 3-7 days post mosquito bite

• No treatment

• Avoid mosquito bites with topical repellants and permethrin

• Diminish breeding of mosquitoes

• Essentially identical efforts as should be used for dengue prevention

Chikungunya

Chikungunya Rarely fatal but you may feel like dying!

Tally of chikungunya cases in the Americas now exceeds a million cases. The continental US tally of locally acquired chikungunya cases is 11 - additional 2000+ travel-related cases.

Puerto Rico has 25,000 suspected autochthonous cases and the US Virgin Islands >1300.

172 attributed deaths in the Americas

The French have seen significant numbers with prolonged joint complaints - 80% at 3 m - 57% at 15 m - 5% chronic

Experimental Vaccine for Chikungunya passes first test

Chikungunya vaccine development Like Ebola, will move much faster as the US is affected

Ebolavirus Disease (EVD) DoS MED’s 2014 “Virus of the Year” is Still Performing

Cases Deaths Total: 21759 8668 Sierra Leone:10362 3153 Liberia: 8524 3136 Guinea: 2873 1879 Nigeria: 20 8 Mali: 8 6 US: 4 1 Spain: 1 1 Senegal: 1 0 UK: 1 0

Data from CDC 22 Jan 2014 http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html

Malaria Update Recs from the Malaria ALDAC 2013

Increase use of Personal Protective Measures: Topical Repellant Formulations approved by CDC available

from post Permethrin available for tents, clothing, etc Impregnated bednets provided by post Screened enclosures

Optimize adherence with chemoprophylaxis Preferable to have all meds available at HU without charge

or inconvenience to the patient Clarifying malaria risk at posts prior to bidding Require Acknowledgement of Malaria Risk to be signed Establishing reporting to leadership of malaria cases

Malaria Update Where we are in DoS since the Malaria ALDAC 2013

2013 2014

DoS Total Malaria cases 49 31 (24 confirmed)

Post provides: Atovaquone/proguanil (Malarone)

42% 54%

Topical repellants DEET (20-35%) Picaridin 20% Oil of Lemon Eucalyptus IR3535

60% 56% 4% 0 0

93% 84% 9% 0 0

Permethrin for clothing/fabric/furniture 29% 42%

Treated Bednets Permanet 3.0 Other treated net

56% 28% 28%

100% 67% 39%

HIV PEP and PrEP Well tolerated regimens and more people on ARVs

• Tenofovir/emtricitabine (Truvada) 300/200 mg po qd ($1300/month) plus

• Raltegravir (Isentress) 400 mg po bid ($1200/month) or

• Dolutegravir (Tivicay) 50 mg po qd ($1200/month)

All three of these drugs are exceptionally well tolerated; if dolutegravir is used require once daily dosing with a total of only 2 pills.

Occupational exposures require urgent medical evaluation. Initiate occupational PEP as soon as possible, ideally within 2 hours of exposure. A first dose of PEP should be offered while evaluation is underway. Do not delay for info about the source patient or the exposed worker's

baseline HIV.

Updated US Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis. Infec Control Hospital Epi, Sep 2013; 34:875-892

HIV Pre Exposure Prophylaxis (PrEP) Marked reduction in HIV transmission but when should it be used?

• Use of emtricitibine/tenofovir (Truvada) one tablet daily has been approved by the FDA for prevention of HIV infection in those at high risk and is covered by most insurance plans.

• Although this is effective there are concerns regarding: – Not using condoms and increasing other STIs – Side effects uncommon but need to check renal function initially – High cost (~$1000-1200 per month), although cheaper in some countries

• Discuss with patient requesting and have them ensure that their insurance will cover this.

– This should NOT be purchased and dispensed by the HU but can be Rx thru the mail order pharmacy – Do not use emergency PEP drugs for PrEP! – If patients request this they generally perceive they have risk and PrEP should probably be Rx.

Preexposure Prophylaxis for the Prevention of HIV Infection in the United States – 2014 Clinical Practice Guideline. US Public Health Service http://www.cdc.gov/hiv/pdf/PrEPguidelines2014.pdf

Meningococcal Quadrivalent vaccines Could it get any more confusing? YES!

MenACWY-CRM = Menveo, 2m to 55y. Oligosaccharide conjugate A,C, Y, W-135

2 m at series start: 4 doses at 2m, 4m, 6m, and 12 m 7-23 m at series start: 2 doses >3m apart; give 2nd dose at >2 y 2-10 y: 2 doses, may give 2nd dose >2m after 1st dose in pts 2-5 y if continued risk >11 y: first dose 11-12 y, then 2nd at 16 y >18-55 y: one dose repeat dose every 5 years for continued risk Preferred for immunosuppressed, asplenic, etc

MenACWY-D = Menactra >9m. Polysaccharide conjugate A,C, Y, W-135

9-23 m at series start: 2 doses 3 m apart 2-18 y: 1st dose at 11-12 y, then 2nd at 16 y; if 1st dose given at 13-15 y, give 2nd at

16-18 y >18 y: one dose, repeat dose every 5 years if needed Preferred for immunosuppressed, asplenic, etc

MPSV4 = Menomune, >2 y. Polysaccharide A,C, Y, W-135

Over age 2 and repeated every 5 years for those at continued risk Preferred for >55y who have not received MenACWY. Many travelers.

Ever more meningococcal vaccines! Six serotypes Neisseria meningitidis circulating:

A, B, C, Y, W-135 and X US polysaccharide and conjugate vaccines cover A,

C, Y and W-135 New vaccine covers B US FDA approved Oct 2014

• There are not clear US recs for use of the new mening B vaccine use except in outbreak settings – US vaccine FDA approved for use in 10-25 yo – Doses at 0, 2 and 6 months

• Some countries require mening B for school aged children

CDC. Recs of the ACIP on meningococcal vaccine. MMWR. 2014;63:527-530

The Good the Bad and the Ugly of PCR in Health Units Is the Biofire/FilmArray your new best friend or your worst enemy?

First FDA approved, user friendly multiplex PCR with rapid results

GI Panel Campylobacter Clostridium difficile Plesiomonas Salmonella Yersinia Vibrio spp Vibrio cholerae E.coli/Shigella

EAEC EPEC ETEC STEC E. coli O157 Shigella EIEC

Cryptosporidium Cyclospora Entamoeba histolytica Giardia lamblia Adenovirus F40/41 Astrovirus Norovirus GI/GII Rotavirus A Sapovirus

Upper Respiratory Panel Adenovirus Coronavirus HKU1 Coronavirus NL63 Coronavirus 229E Coronavirus OC43 Human Metapneumovirus Human Rhinovirus/Enterovirus Influenza A Influenza A/H1 Influenza A/H3 Influenza A/H1-2009 Influenza B Parainfluenza Virus 1 Parainfluenza Virus 2 Parainfluenza Virus 3 Parainfluenza Virus 4 Respiratory Syncytial Virus Bacterial Targets Bordetella pertussis Chlamydophila pneumoniae Mycoplasma pneumoniae

BioThreat Panel Bacillus anthracis Brucella melitensis Burkholderia Clostridium botulinum Coxiella burnetii Ebola virus (Zaire) EEE virus F. tularensis Marburg virus Ricinus communis Rickettsia prowazekii Variola virus VEE virus WEE virus Yersinia pestis Orthopox virus

Blood Culture ID Panel

Meningoencephalitis Panel (in development)

Lower Respiratory Panel (in development)

The dried reagents in the FilmArray pouch are reconstituted by the addition of 1 ml distilled water to the blue port (lower right of diagram), and the diluted sample is injected into the port shown in red.

Rand K H et al. J. Clin. Microbiol. 2011;49:2449-2453

Some examples for the GI Panel Age >3

BMs/24h Yes/No

Duration of symptoms

Patient reports blood in

stool Yes/No

Temp >100.5 F

(38 C) Yes/No

Film Array results Antibiotics

Prescribed

Yes/No

If antibx given, what drug and how many

days?

Stool culture performed?

Yes/No Results?

Stool microscopy performed?

Yes/No

43 Yes 2 days No Yes Shigella Yes Levofloxacin, single day

Yes, confirms Shigella

Yes, no pathogens

6 Yes 3 weeks No No EAEC, Giardia Yes Tinidazole single dose

Yes, no pathogens Yes, no pathogens, +WBC

59 No 5 months No No Clostridium difficile Yes Metronidazole 10days

No Yes, Blastocystis hominis

- Patient 1 with Shigella could be dx and tx very quickly with single dose therapy and has a pretty definitive diagnosis

- Patient 2 with EnteroAggregative E.coli and Giardia is confusing. 3 weeks of sx is most c/w Giardia and treating it is indicated. What about the EAEC? This is a common cause of peds diarrhea but it is also commonly seen without diarrhea in developing world kids. In this case I would probably NOT treat for EAEC.

- Patient 3 has chronic loose stools, 1-3x/ day and abdominal cramping. His film array comes up with C. diff but clinically his illness is not c/w C. diff and is more likely IBS or another noninfectious etiology. NOT treating him may have been a more appropriate answer and sending him for colonoscopy to make sure this isn’t neoplasia, inflammatory bowel disease, etc may be indicated.

Some examples for the Upper Respiratory Panel Age Temp

>100.5 F (38 C)

Yes/No

Cough Yes/No

Sputum Producing

Yes/No

Pharyngitis Yes/No

Duration of symptoms

Film Array results

Antibx or antiviral

Rx Yes/No

If antibx or antiviral, what drug and how many days?

Respiratory culture performed?

Yes/No Results?

Rapid flu test performed?

Yes/No Results

11 No Yes Yes No 18 days Rhinovirus No None No No 14 yes yes yes No 4 days Bordetella,

Rhinovirus Yes azithro x 10 d No No

18m

yes yes no ? 3 days RSV No no No No

32 yes yes no yes 1 day Influenza A yes oseltamivir x5d No Yes, positive 58 yes yes yes no 2 days Rhinovirus No - Yes,

Pneumococcus No

Patient 1: sick for 18d and PCR with rhinovirus only, was not given antibiotics.

Patient 2: patient 1’s brother, sick 4d, + pertussis on PCR as well as rhinovirus, gets tx for pertussis. This explains the prolonged sx in Pt 1 who has pertussis but no longer is PCR +, rhinovirus rarely causes sx this long. Pt 1 sx were attributed to a viral infection while a pertussis outbreak was ongoing.

Patient 3: diagnosed correctly with RSV early on, saved her from being empirically treated with antibx that would not have helped her and may give side-effects

Patient 4: diagnosed with Influenza A but a rapid Flu test <¼ the cost also made the dx. Flu RDTs are not incredibly sensitive but are quite specific. ? need for PCR

Patient 5: smoker with a febrile respiratory dz. PCR+ Rhinovirus so no antibx, 2 days later septic with RML pneumonia and Pneumococcus in blood cx. FilmArray does not test for Pneumococcus. Without the PCR results he may have been appropriately started on empiric antibx.

Yikes! 6 pathogens in one stool!

Thanks to Holly Strain in Mexico City

10 Days later: 3 of the same and 1 more!