Thread by @TxID_Edu, 1/18Growing up in Tucson and going to med school @UAZMedTucson, I thought [...]

1/18
Growing up in Tucson and going to med school @UAZMedTucson, I thought I knew a lot about #coccidioidomycosis. Definitely not!

Here we discuss history, epidemiology, ecology, some cool facts about #Cocci, and reasons why #fluconazole may not be the best drug for Cocci.

2/
In 1892 in Argentina, Alejandro Posadas wrote the first report of a pt w/ disseminated cutaneous cocci

Shortly after, a laborer in San Joaquin valley also had skin lesions

Skin biopsies of both pts revealed protozoa-like orgs, similar to Coccidia

https://academic.oup.com/cid/article/44/9/1202/328906">https://academic.oup.com/cid/artic...

3/
Here are images of the first patient diagnosed with #Cocci, Domingo Escurra, by Alejandro Posadas

@StanDeresinski

https://www.ncbi.nlm.nih.gov/pubmed/30690606 ">https://www.ncbi.nlm.nih.gov/pubmed/30...

4/
Gilchrist, Rixford & Stiles named the org after its morphologic & clinical features:

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🍄" title="Pilz" aria-label="Emoji: Pilz">Coccidioides (“resembling Coccidia”) immitis (“not mild”)

It is interesting that all 3 US dimorphics (Histo, Blasto, Cocci) were initially mistaken as protozoa

https://academic.oup.com/cid/article/44/9/1202/328906">https://academic.oup.com/cid/artic...

5/
Charles Smith had amazing observations about Cocci:

https://abs.twimg.com/emoji/v2/... draggable="false" alt="1⃣" title="Tastenkappe Ziffer 1" aria-label="Emoji: Tastenkappe Ziffer 1">Incubation period 1-3 weeks

https://abs.twimg.com/emoji/v2/... draggable="false" alt="2⃣" title="Tastenkappe Ziffer 2" aria-label="Emoji: Tastenkappe Ziffer 2">People rarely got re-infected

https://abs.twimg.com/emoji/v2/... draggable="false" alt="3⃣" title="Tastenkappe Ziffer 3" aria-label="Emoji: Tastenkappe Ziffer 3">No transmission from person-person

https://abs.twimg.com/emoji/v2/... draggable="false" alt="4⃣" title="Tastenkappe Ziffer 4" aria-label="Emoji: Tastenkappe Ziffer 4">Occurred in summer and fall- other months were more wet & farmers didn& #39;t work in winter & spring

https://www.ncbi.nlm.nih.gov/pubmed/30690606 ">https://www.ncbi.nlm.nih.gov/pubmed/30...

5/Charles Smith had amazing observations about Cocci:https://abs.twimg.com/emoji/v2/... draggable=

Incubation period 1-3 weekshttps://abs.twimg.com/emoji/v2/... draggable="false" alt="2⃣" title="Tastenkappe Ziffer 2" aria-label="Emoji: Tastenkappe Ziffer 2">People rarely got re-infectedhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="3⃣" title="Tastenkappe Ziffer 3" aria-label="Emoji: Tastenkappe Ziffer 3">No transmission from person-personhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="4⃣" title="Tastenkappe Ziffer 4" aria-label="Emoji: Tastenkappe Ziffer 4">Occurred in summer and fall- other months were more wet & farmers didn& #39;t work in winter & spring https://www.ncbi.nlm.nih.gov/pubmed/30..." title="5/Charles Smith had amazing observations about Cocci:https://abs.twimg.com/emoji/v2/... draggable="false" alt="1⃣" title="Tastenkappe Ziffer 1" aria-label="Emoji: Tastenkappe Ziffer 1">Incubation period 1-3 weekshttps://abs.twimg.com/emoji/v2/... draggable="false" alt="2⃣" title="Tastenkappe Ziffer 2" aria-label="Emoji: Tastenkappe Ziffer 2">People rarely got re-infectedhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="3⃣" title="Tastenkappe Ziffer 3" aria-label="Emoji: Tastenkappe Ziffer 3">No transmission from person-personhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="4⃣" title="Tastenkappe Ziffer 4" aria-label="Emoji: Tastenkappe Ziffer 4">Occurred in summer and fall- other months were more wet & farmers didn& #39;t work in winter & spring https://www.ncbi.nlm.nih.gov/pubmed/30..." class="img-responsive" style="max-width:100%;"/>

6/
The genus consists of 2 species: immitis and posadasii

Natural reservoir of #Cocci is in soil of SW US, Mexico, Central, and South America

In the US, most cases are found in AZ and CA

Animal reservoir has not been identified

https://www.ncbi.nlm.nih.gov/pubmed/31648806

https://www.ncbi.nlm.nih.gov/pubmed/31... href=" https://www.ncbi.nlm.nih.gov/pubmed/30690599 ">https://www.ncbi.nlm.nih.gov/pubmed/30...

https://www.ncbi.nlm.nih.gov/pubmed/30..." title="6/The genus consists of 2 species: immitis and posadasiiNatural reservoir of #Cocci is in soil of SW US, Mexico, Central, and South AmericaIn the US, most cases are found in AZ and CAAnimal reservoir has not been identified https://www.ncbi.nlm.nih.gov/pubmed/31... href=" https://www.ncbi.nlm.nih.gov/pubmed/30690599 ">https://www.ncbi.nlm.nih.gov/pubmed/30...">

7/
Why do we see more cases in drier seasons?

When there is moisture, cocci grows as mold with hyphae

When the soil dries, cells

https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Pfeil nach rechts" aria-label="Emoji: Pfeil nach rechts">arthroconidia, break off & release

If the early Summer is filled with rains

https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Pfeil nach rechts" aria-label="Emoji: Pfeil nach rechts">lower incidence of Cocci in later summer

https://www.ncbi.nlm.nih.gov/pubmed/31648806 ">https://www.ncbi.nlm.nih.gov/pubmed/31...

7/Why do we see more cases in drier seasons?When there is moisture, cocci grows as mold with hyphae When the soil dries, cellshttps://abs.twimg.com/emoji/v2/... draggable=

arthroconidia, break off & releaseIf the early Summer is filled with rainshttps://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Pfeil nach rechts" aria-label="Emoji: Pfeil nach rechts">lower incidence of Cocci in later summer https://www.ncbi.nlm.nih.gov/pubmed/31..." title="7/Why do we see more cases in drier seasons?When there is moisture, cocci grows as mold with hyphae When the soil dries, cellshttps://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Pfeil nach rechts" aria-label="Emoji: Pfeil nach rechts">arthroconidia, break off & releaseIf the early Summer is filled with rainshttps://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Pfeil nach rechts" aria-label="Emoji: Pfeil nach rechts">lower incidence of Cocci in later summer https://www.ncbi.nlm.nih.gov/pubmed/31..." class="img-responsive" style="max-width:100%;"/>

8/
We know that fungus don& #39;t like to grow in really hot temperatures, how come Cocci is endemic in SW US?

https://abs.twimg.com/emoji/v2/... draggable="false" alt="1⃣" title="Tastenkappe Ziffer 1" aria-label="Emoji: Tastenkappe Ziffer 1">theory: Soil is sterilized by high temps, but Cocci survives by growing deep into soil. Then, when it rains, Cocci can grow back to soil surface https://www.ncbi.nlm.nih.gov/pubmed/30898028 ">https://www.ncbi.nlm.nih.gov/pubmed/30...

The mysterious desert dwellers: Coccidioides immitis and Coccidioides posadasii, causative fungal...

The genus Coccidioides consists of two species: C. immitis and C. posadasii. Prior to 2000, all disease was thought to be caused by a single species, C. immitis. The organism grows in arid to...

https://www.ncbi.nlm.nih.gov/pubmed/30898028

9/
Here comes the inevitable...

Over the years, temperature will increase, precipitation patterns will change

By 2100-

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🌎" title="Amerika auf dem Globus" aria-label="Emoji: Amerika auf dem Globus">Cocci endemic area will double

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🍁" title="Ahornblatt" aria-label="Emoji: Ahornblatt">17 states will be affected

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🌲" title="Immergrüner Baum" aria-label="Emoji: Immergrüner Baum"># of cases will increase by 50%

https://agupubs.onlinelibrary.wiley.com/doi/epdf/10.1029/2019GH000209">https://agupubs.onlinelibrary.wiley.com/doi/epdf/...

9/Here comes the inevitable...Over the years, temperature will increase, precipitation patterns will changeBy 2100- https://abs.twimg.com/emoji/v2/... draggable=

Cocci endemic area will doublehttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🍁" title="Ahornblatt" aria-label="Emoji: Ahornblatt">17 states will be affectedhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🌲" title="Immergrüner Baum" aria-label="Emoji: Immergrüner Baum"># of cases will increase by 50% https://agupubs.onlinelibrary.wiley.com/doi/epdf/..." title="9/Here comes the inevitable...Over the years, temperature will increase, precipitation patterns will changeBy 2100- https://abs.twimg.com/emoji/v2/... draggable="false" alt="🌎" title="Amerika auf dem Globus" aria-label="Emoji: Amerika auf dem Globus">Cocci endemic area will doublehttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🍁" title="Ahornblatt" aria-label="Emoji: Ahornblatt">17 states will be affectedhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🌲" title="Immergrüner Baum" aria-label="Emoji: Immergrüner Baum"># of cases will increase by 50% https://agupubs.onlinelibrary.wiley.com/doi/epdf/..." class="img-responsive" style="max-width:100%;"/>

10/
60% of patients are asymptomatic

Most recover without dissemination or sequelae

Those that do can develop CNS, skin, MSK, and other complications

https://www.ncbi.nlm.nih.gov/pubmed/31572393 ">https://www.ncbi.nlm.nih.gov/pubmed/31...

11/
Did you know...

In endemic areas, 20-30% of CAP can be secondary to Cocci...that& #39;s wild!! https://www.ncbi.nlm.nih.gov/pubmed/16707052 ">https://www.ncbi.nlm.nih.gov/pubmed/16...

Coccidioidomycosis as a common cause of community-acquired pneumonia - PubMed

The early manifestations of coccidioidomycosis (valley fever) are similar to those of other causes of community-acquired pneumonia (CAP). Without specific etiologic testing, the true frequency of...

https://www.ncbi.nlm.nih.gov/pubmed/16707052

12/
What do we do about primary pulmonary cocci?

2016 @IDSAInfo guidelines recommend therapy for:
- dissemination
- debilitating illness
- frail 2/2 age or comorbidities
- immunosuppressed
- African/Filipino decent
- extensive pulmonary involvement https://academic.oup.com/cid/article/63/6/e112/2389093">https://academic.oup.com/cid/artic...

2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of...

Abstract. It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended t

https://academic.oup.com/cid/article/63/6/e112/2389093

13/
Similar to #crypto, should we do LPs on pts with newly diagnosed Cocci?

2016 @IDSAInfo guidelines- do LP in patients w/:

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🍏" title="Grüner Apfel" aria-label="Emoji: Grüner Apfel">unusual, worsening, or persistent HA

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🍎" title="Roter Apfel" aria-label="Emoji: Roter Apfel">AMS

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🍐" title="Birne" aria-label="Emoji: Birne">unexplained N/V

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🍊" title="Mandarine" aria-label="Emoji: Mandarine">new focal neuro deficit after CNS imaging https://academic.oup.com/cid/article/63/6/e112/2389093">https://academic.oup.com/cid/artic...

2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of...

Abstract. It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended t

https://academic.oup.com/cid/article/63/6/e112/2389093

14/
#Fluc is recommended in guidelines

But is it the best drug?

There is

https://abs.twimg.com/emoji/v2/... draggable="false" alt="1⃣" title="Tastenkappe Ziffer 1" aria-label="Emoji: Tastenkappe Ziffer 1">comparative trial- Fluc vs Itra
#Itra was better for bone/joint disease, and may have been better overall!

https://www.ncbi.nlm.nih.gov/pubmed/11074900

It">https://www.ncbi.nlm.nih.gov/pubmed/11... is interesting that IDSA first line for #Histo & #Blasto is ITRA.

14/ #Fluc is recommended in guidelinesBut is it the best drug?There ishttps://abs.twimg.com/emoji/v2/... draggable=

comparative trial- Fluc vs Itra #Itra was better for bone/joint disease, and may have been better overall! https://www.ncbi.nlm.nih.gov/pubmed/11... is interesting that IDSA first line for #Histo & #Blasto is ITRA." title="14/ #Fluc is recommended in guidelinesBut is it the best drug?There ishttps://abs.twimg.com/emoji/v2/... draggable="false" alt="1⃣" title="Tastenkappe Ziffer 1" aria-label="Emoji: Tastenkappe Ziffer 1">comparative trial- Fluc vs Itra #Itra was better for bone/joint disease, and may have been better overall! https://www.ncbi.nlm.nih.gov/pubmed/11... is interesting that IDSA first line for #Histo & #Blasto is ITRA." class="img-responsive" style="max-width:100%;"/>

15/
Just wait for it...

A 2017 in-vitro study noted increased fluconazole MIC for 37% of isolates, raising concerns for therapy in serious infections!

https://www.ncbi.nlm.nih.gov/pubmed/28096163 ">https://www.ncbi.nlm.nih.gov/pubmed/28...

16/

A retrospective review of 35 patients who initially received fluconazole, looked at treatment of refractory cases with #Vori and #Posa

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🎻" title="Violine" aria-label="Emoji: Violine">21 changed to #Vori -> 67% improved

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🪕" title="Banjo" aria-label="Emoji: Banjo"> 16 changed to #Posa -> 75% improved

https://www.ncbi.nlm.nih.gov/pubmed/22045955 ">https://www.ncbi.nlm.nih.gov/pubmed/22...

$16/A retrospective review of 35 patients who initially received fluconazole, looked at treatment of refractory cases with #Vori and #Posa https://abs.twimg.com/emoji/v2/... draggable=$ 21 changed to #Vori -> 67% improvedhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🪕" title="Banjo" aria-label="Emoji: Banjo"> 16 changed to #Posa -> 75% improved https://www.ncbi.nlm.nih.gov/pubmed/22..." title="16/A retrospective review of 35 patients who initially received fluconazole, looked at treatment of refractory cases with #Vori and #Posa https://abs.twimg.com/emoji/v2/... draggable="false" alt="🎻" title="Violine" aria-label="Emoji: Violine">21 changed to #Vori -> 67% improvedhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🪕" title="Banjo" aria-label="Emoji: Banjo"> 16 changed to #Posa -> 75% improved https://www.ncbi.nlm.nih.gov/pubmed/22..." class="img-responsive" style="max-width:100%;"/>

17/
Here is a nice table of the available antifungals with the benefits, weaknesses, and adverse effects

There are novel therapies coming (just to name a few):
#Fosmanogepix
#Olorofim
#SUBA-itra
#nikkomycin Z
#rezafungin ( @DxRxEdu)
#ibrexafungerp

https://www.ncbi.nlm.nih.gov/pubmed/31572393 ">https://www.ncbi.nlm.nih.gov/pubmed/31...

18/
Summary:

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🌛" title="Zunehmender Viertelmond mit Gesicht" aria-label="Emoji: Zunehmender Viertelmond mit Gesicht">60% asympt, others have CAP

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🌜" title="Dreiviertelmond mit Gesicht" aria-label="Emoji: Dreiviertelmond mit Gesicht">95% recover w/o sequelae

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⭐️" title="Mittelgroßer Stern" aria-label="Emoji: Mittelgroßer Stern">Infxn results in lifelong immunity

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🌟" title="Leuchtender Stern" aria-label="Emoji: Leuchtender Stern">

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">Temp & change in precipitation will expand endemic regions

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💫" title="Symbol für Benommenheit" aria-label="Emoji: Symbol für Benommenheit">Fluconazole may not be the best

https://abs.twimg.com/emoji/v2/... draggable="false" alt="✨" title="Funken" aria-label="Emoji: Funken">Other triazoles may be better

https://abs.twimg.com/emoji/v2/... draggable="false" alt="☄️" title="Komet" aria-label="Emoji: Komet">We need prospective & randomized studies!

EXTRA:
Would love to hear how others tackle #Cocci.

@InduPartha
@GRThompsonMD
@Valleyfeverkc
@AlobaidiMD
@DrValleyFever
@DrH_flu
@Darcy_ID_doc
@DocSaimaAslam
@jschaenman
@AnnieC_ID_MD
@abaseenafghan

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