Thread by @TxID_Edu

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

academic.oup.com/cid/article/44…

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

@StanDeresinski

ncbi.nlm.nih.gov/pubmed/30690606

4/
Gilchrist, Rixford & Stiles named the org after its morphologic & clinical features:
🍄Coccidioides (“resembling Coccidia”) immitis (“not mild”)

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

academic.oup.com/cid/article/44…

5/
Charles Smith had amazing observations about Cocci:
1⃣Incubation period 1-3 weeks
2⃣People rarely got re-infected
3⃣No transmission from person-person
4⃣Occurred in summer and fall- other months were more wet & farmers didn't work in winter & spring

ncbi.nlm.nih.gov/pubmed/30690606

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

ncbi.nlm.nih.gov/pubmed/31648806

ncbi.nlm.nih.gov/pubmed/30690599

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➡️arthroconidia, break off & release

If the early Summer is filled with rains➡️lower incidence of Cocci in later summer

ncbi.nlm.nih.gov/pubmed/31648806

8/
We know that fungus don't like to grow in really hot temperatures, how come Cocci is endemic in SW US?

1⃣theory: 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

ncbi.nlm.nih.gov/pubmed/30898028

9/
Here comes the inevitable...

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

By 2100-
🌎Cocci endemic area will double
🍁17 states will be affected
🌲# of cases will increase by 50%

agupubs.onlinelibrary.wiley.com/doi/epdf/10.10…

10/
60% of patients are asymptomatic

Most recover without dissemination or sequelae

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

ncbi.nlm.nih.gov/pubmed/31572393

11/
Did you know...

In endemic areas, 20-30% of CAP can be secondary to Cocci...that's wild!!

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

academic.oup.com/cid/article/63…

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

2016 @IDSAInfo guidelines- do LP in patients w/:
🍏unusual, worsening, or persistent HA
🍎AMS
🍐unexplained N/V
🍊new focal neuro deficit after CNS imaging

academic.oup.com/cid/article/63…

14/
#Fluc is recommended in guidelines

But is it the best drug?

There is1⃣comparative trial- Fluc vs Itra
#Itra was better for bone/joint disease, and may have been better overall!

ncbi.nlm.nih.gov/pubmed/11074900

It is interesting that IDSA first line for #Histo & #Blasto is ITRA.

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!

ncbi.nlm.nih.gov/pubmed/28096163

16/

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

🎻21 changed to #Vori -> 67% improved

🪕 16 changed to #Posa -> 75% improved

ncbi.nlm.nih.gov/pubmed/22045955

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

ncbi.nlm.nih.gov/pubmed/31572393

18/
Summary:
🌛60% asympt, others have CAP
🌜95% recover w/o sequelae
⭐️Infxn results in lifelong immunity
🌟⬆️Temp & change in precipitation will expand endemic regions
💫Fluconazole may not be the best
✨Other triazoles may be better
☄️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