Chagas Disease: Why a Neglected Tropical Disease Matters for US Clinicians (Heindel, 3/5/25)

 A recording of this presentation is available HERE. 

Dr. Leah Heindel gave a wonderful Grand Rounds presentation this week on Chagas Disease. Perhaps the most important moment of the presentation was this slide:

"Look," Dr. Heindel, urged, "look at how this little "kissing bug" (aka triatomine) creates a cascade that has impact on immigrant health justice, reproductive health, whole-family care, global health, and how we think of screening and prevention in the US in 2025. This is family medicine."

Family medicine, indeed, is all of these.

Epidemiology and Disease Burden

Chagas Disease, which infects 7-8 million people worldwide, mostly in Latin America, presents a health burden seven times higher than malaria in the Western Hemisphere. There are an estimated 300,000 people living in the US with Chagas disease, many of whom are immigrants from Mexico, El Salvador, Guatemala, and Honduras. Unfortunately, only about 1% of those have been identified. Both vector and vertical transmission occurs in the US (22-100 cases congenital chagas in the annually).

Chagas disease has both an acute and indolent phase. The overwhelming majority of people infected with Chagas disease (90%) will be asymptomatic in the acute phase, but chronic impacts (especially GI, cardiac) typically appear 20-30 years after initial infection. 

Seroprevalence in immigrants from endemic countries is believed to be about 1% in the general population, though it varies widely depending on how these estimates are made. For example, you can see in the table below from the IDSA that there is a MUCH higher seroprevalence in immigrant patients from endemic areas with otherwise unexplained non-ischemic cardiomyopathy (13-19%). 

Vertical transmission occurs in 2-13% of cases, most congenital infection is asymptomatic, but Chagas has been associated with preterm delivery, low birthweight and low APGAR scores. 

Clinical manifestations

Chagas disease is generally spread via the bite of the "kissing bug", usually on the neck and face at night while people are sleeping; the same bug defecates close to that area, then the disease is transferred to the bloodstream via scratching at the site and introduction of bug feces to the broken skin. The acute phase of Chagas (only in about 10% of people infected) presents as a non-specific viral syndrome, including fever malaise, and anorexia. One pathognomonic sign of acute Chagas is Romaña's sign, pronounced swelling of the eyelid (as seen in image below). Domesticated and farm animals serve as reservoirs of the disease, and thatched roofs are a known risk factor in endemic areas.

After decades long latency, most common manifestations include cardiac (sudden cardiac death as #1 cause of death from Chagas, 55-60% of people, also HFrEF (25-30%) and embolic disease (10-15%). It seems that the parasite has a particular predilection for the electrical and conducting system. 

GI effects are also well-documented and occur in 10-21% of people with chronic Chagas, including both esophageal and colonic manifestations. In the esophagus, dysphagia and regurgitation are common; in the colon sigmoid rectal dilatation and progressive constipation. 

Neurologic effects including peripheral neuropathy and even dementia have been suggested. In addition there is a reactivation syndrome that can affect people with transplant or other immunosuppression.

Screening and Diagnosis 

The earlier Chagas is detected, the better the outcomes. Once someone has chronic cardiac or GI effects, treatment has shown to be unhelpful.

Diagnosis is done via is a serum IgG test with reflex to confirmation (goes to CDC), which is available through most laboratories. 

Both the CDC and IDSA recommend targeting screening based on risk factors, in particular being born in or lived in endemic areas, having a family member with Chagas Disease. 

Screening during pregnancy has been shown to be cost effective and may be something we should be integrating locally in our at-risk population-- more on this to come. Options for pregnancy-screening include pre-pregnancy screening (this MOST preferred because cannot treat during pregnancy) vs. routine OB screening vs. L&D serum IgG vs. newborn cord blood or PCR and even the possibility of universal newborn screening.

Diagnostic testing is warranted in patients who come from endemic areas AND present with electrocardiogram abnormalities (wide range, including 1st degree AV block, afib, PVCs, RBB, low voltage), thromboembolic phenomenon, HFrEF otherwise unexplained, and megacolon or megaesophagus.

Treatment

There are two approved treatments for Chagas Disease, both for extended duration (see image below for dosing)

1) Benznidazole x 60 days

2) Nifurtimox 90 days

Both treatments have high side effect profiles (GI, CNS, marrow suppression). They are contraindicated in pregnancy, though safe in lactation, and contraindicated in severe hepatic and renal dysfunction. These medications also may be hard to come by locally.

The IDSA offers guidelines for who should and should NOT be treated. On the list for who should be treated includes: anyone with acute Chagas, all children with acute/chronic infection, reproductive age women, and people with impending immunosuppression. On the list of people NOT to treat, includes adults with advance cardiac and/or GI manifestations (treatment doesn't reverse these), unless people have impending immunosuppression. Also, not during pregnancy and not in severe hepatic or renal dysfunction. 

Finally, Dr. Heindel recommends this book, The Kissing Bug, written by a first generation immigrant journalist and author, whose family was directly impacted by this disease and who follows the socio and geopolitical forces that influence the management of Chagas in the US immigrant population today.

Global Health (Carmen - 4/26/23)

 A recording of this presentation can be viewed HERE. 

Elimination of TB in the US: 2021 Updates (Toub, 8/4//2021)

Many thanks to Dr. Danny Toub, a family physician, teacher, and public health professional-- who so often bridges the impossible gaps that exist between individual patient care conundrums and public health. While this bridge may seem intuitive, it is often rickety and not always clear how to begin to build it-- look to Dr. Toub, though, he always shows us the way. 

A recording of his presentation is available HERE. 

This week's topic was Tuberculosis (TB), a global behemoth; the original and ever-present airborne illness that still kills 1.4 million people worldwide per year, more than HIV/AIDS While we sit in the middle of a harrowing COVID-19 Pandemic and the words N-95 have become every day jargon, TB is still global problem. And while we have made great progress in the US with TB eradication, TB still unnecessarily killed 542 Americans in 2018, 200 of which were right here in California.

TB, much like COVID, disproportionately affects people who are living in poverty, people of color, and those who have less access to stable housing and health care services.

What is our responsibility as primary care providers?

• Screen ALL patients for TB Risk
• Screen HIGH RISK patients with a Tuberculin Skin test (TST) or interferon gamma release assay (IGRA)
• Treat Latent TB infections (LTBI)
• Report to Public Health any active TB cases and/or any LTBI in children or recent converters (<2 years)
• Oh, and don't forget to have TB on your ddx for other acute/subacute illness presentations!

If we break that down,

1) Screen ALL patients for TB Risk using the California TB Risk Assessment Tool which can be found HERE and is pictured below as well. 

Remember to AVOID testing low risk folks for LTBI (this form alone counts as a screen!) and if you have limited resources, prioritize those who are most likely to convert from LTBI to active TB. Key risk factors include being foreign born/immigrant from certain regions, immunosuppression, and those who have been in close contact with someone with TB. 

Important additional risk factors include, recent conversion, substance use disorder, patients with DM, patients with CKD, those with autoimmune conditions, people who smoke, people with cancer, and more. 

The point of screening is to prevent a future conversion to active TB by treating people before they get sick. Low risk patients have ~10% lifetime risk of converting. Higher risk (e.g. people with diabetes) have ~ 30% lifetime risk, and highest risk folks (e.g. HIV + LTBI) have a 7-10% per year risk of converting. 

2) Screen HIGH risk patients with TST or IGRA. The best TB test depends on your pretest probability. Here is a good cheat sheet.

• Low risk patient--> do not screen
• Asymptomatic child--> use the California Pediatric TB Risk Assessment
• Asymptomatic adult--> use the CA Adult TB Risk assessment
• Volunteer for school without risk factors--> use the CA Schools TB Risk Tool
• College or University student--> use the CA College tool
• Health care worker--> use CDC guidelines#
• Pregnant woman--> pregnancy itself is not a risk factor
• 2 year old foreign-born patient--> TST*
• Foreign born >2 year old, hx BCG--> IGRA**
• Patient experiencing homelessness--> IGRA
• Patient to start TNF alpha blocker--> IGRA
• Patients with >4 weeks cough, 5 pound weight loss--> Chest Xray
• SE Asian smoker with RUL cavity, and a1c>9%--> sputum (x-pert MTB)+

#Note that the CDC no longer recommends annual TB testing for healthcare workers!! Official recommendations released in 2019 are available here and recommend a risk based technique. Maybe that means YOU don't need that annual TST!

*TST: tuberculin skin test, **IGRA: interferon gamma release assay (often referred to as quantiferon gold). There is limited data in IGRA in children <5. IGRA are more specific than TST in pts with a history of a BCG vaccine.

+Remember, a negative IGRA or TST does NOT rule out active TB (you need sputum!)

3) Treat LTBI infection. Treatment for LTBI has been shortened and simplified over the last decade. It does not involve routine lab work (except in high risk folks) or directly observed therapy (DOT). 

Dr. Toub recommends this handy LTBI pocket card to help simplify your decision-making and treatment regimen planning. The image below to too small to actually read, but follow the link for specifics on indications, completion criteria, considerations, etc. 

Briefly, prior to initiating LTBI treatment, you want to be sure to r/o pregnancy, check for pre-existing peripheral neuropathy (which can be a side effect of tx), screen for liver disease risk factors (e.g. alcohol use disorder, NASH, HCV). 

Baseline LFTs are only indicated for patients with HIV, known liver disease, regular alcohol use, pregnancy or < 3 months postpartum, and other risks for liver disease.

And, Dr. Toub reminded us to remind your patients that EVERYthing will be orange (sweat, tears, and urine). Also be sure to check for drug drug interactions on any tool that you use for this purpose, as there are many. 

4) Report to SoCo Public Health any active TB cases and/or any LTBI in children or recent converters (<2 years). 

5) Oh, and don't forget to have TB on your ddx for other acute/subacute illness presentations! Remember TB can show up just about anywhere. 

For local assistance, you can utilize the Sonoma County TB Control Guidelines, which you can find at the bottom of this webpage. And if you ever have any TB questions, reach out to our local TB Control program at 707-565-4567.

And, finally, a list of trusted resources from Dr. Toub:

COVID-19 Update (Green 3/11/2020)

Great thanks to Dr. Gary Green, Infectious Disease specialist, for a well-attended Grand Rounds this week on COVID-19. Dr. Green's blend of  virology, epidemiology, and calm-ology left me feeling more confident and less panicky about our current situation with COVID-19. Hope you all feel the same!

Here's the down and dirty (recognizing that this is a dynamic situation-- it's very likely that information shared here will be out of date in a matter of days).

COVID-19 in our Community
As of 3/11/2020, Sonoma County has only three confirmed cases of COVID-19:

• 1 case of previously diagnosed COVID-19 transferred from Travis Air Force Base associated with the original Diamond Princess Cruise (Japan)
• 2 cases of COVID-19 associated with the Grand Princess Cruise (SF to Mexico)

As of this writing, there have been NO additional confirmed cases of COVID-19 in Sonoma County.

In fact, in the last two weeks, Dr. Green himself has tested 15 high risk symptomatic patients (high risk because of direct contacts to known COVID-19 cases and/or recent high risk travel history). All of these patients were symptomatic (i.e. cough, shortness of breath, fever) and all resulted NEGATIVE.

Dr. Green reassured us that currently, we have no evidence in Sonoma County of community transmission-- unlike many counties, including Santa Clara, San Francisco and Los Angeles. It doesn't mean we won't have community transmission in Sonoma County; we just don't yet.  

What Happened in Wuhan, China?

China "went through the wall first" explained Dr. Green--that is, because this novel Coronavirus originated in China, patients and healthcare workers have been literally on the front lines of a brand new disease. For this, they have suffered.

It has now been over three months since COVID-19 was first recognized, and we know a lot more about this virus than those brave healthcare workers-- many of whom gave their lives taking care of sick patients. 

China's experience is NOT necessarily our experience, but we can learn from them! 

• Chinese healthcare workers in Wuhan first recognized a string of strange respiratory cases and unusual pneumonias in early December 2019
• Just a few weeks later their scientists were able to identify a novel Coronavirus, and by January 7 the virus had been sequenced and shared with the world.
• Of note, SARS (2002-2003) and MERS (2012) were both novel Coronavirus outbreaks. Tons of Chinese research and prep done in response to these outbreaks are improving the global response to COVID-19.
• By Dr. Green's estimation, "this virus started in the right place"-- had such a virus emerged almost anywhere else in the world, we would not have been equipped to recognize it, identify it and study it so quickly. 

Healthcare Workers, what is our risk?
Of note, in China, over 3000 healthcare workers (HCW) have been infected with COVID-19, and at least 18 have died.  This scares many of us in the healthcare field. In one hospital, 29% of 138 confirmed cases were in HCW. This is likely because of inappropriate personal protective equipment (PPE) and underprepared infection control measures at the time COVID-19 was emerging. Also there was a tremendous strain on healthcare resources. Simultaneously, there was an abundance of community transmission in China due to insufficient infection control practices and large numbers of patients in crowded clinics in a crowded city.

(By the way, in the SARS epidemic, over 1/5 of confirmed cases were in healthcare workers).

In contrast, at Queen Mary Hospital in Hong Kong (a huge 1706-bed hospital) reported 42 COVID-19 confirmed cases. Of the 413 HCW who cared for confirmed cases, 11 had documented unprotected exposure. These HCW were all quarantined x 14 days. 

This is important: in this hospital, despite its massive size and the number of cases:

• No HCW becomes infected with COVID-19
• There were ZERO nosocomial transmission in the hospital

Dr. Green's take home: We can do this! We do this every year for flu and seasonal respiratory illness: wash your hands, don't come to work sick, use appropriate PPE and infection control practices when caring for sick patients. 

Flu vs. COVID-19: How worried should we be?

Dr. Green wants us to keep this in perspective. While COVID-19 is indeed a serious illness with global repercussions, the actual numbers of deaths (in the US and worldwide) are far lower than seasonal flu. And remember-- there have been no recorded pediatric deaths.

While initial studies from China were reporting a 2-3% mortality rates from COVID-19 those numbers now appear to be much much lower (on the order of ~0.6% from Korea). Initial reports were probably higher because China was really reporting a "case fatality" rate rather than a "mortality rate". While 0.6% is much higher than influenza mortality rates (typically ~0.1%), it is markedly lower than SARS, MERS or the Flu Pandemic of 1918.

See the slide below for the actual numbers, comparing (on the top) SARS, MERS and COVID-19 and (underneath the line) the 1918 flu pandemic and our current 2019-20 seasonal flu. Of note, in the US 136 children and over 20,000 people have died of influenza so far this season  (2018-2019, 80,000 people in the US died). Get your flu shot, please!

(sorry slide credit to Dr. Green, the formatting is a little off. First column=mortality rate, Second column= Ro; measure of infectivity (the higher the more infective), third column=case fatalities are actual counts of deaths)

What does COVID-19 actually look like?

While it does look a little like a common cold, there are a few things to note about COVID-19:

• This is primarily a virus of the LOWER respiratory tract (i.e. lungs), unlike most coronavirus infections, which are UPPER respiratory tract infections (i.e. head colds)
• This means that very few have rhinorrhea (aka a runny noses), ~4%
• Unlike influenza, which comes on abruptly, symptoms of COVID-19 seem to come on gradually over several days with worsening shortness of breath being a primary symptom after about 5 days of illness
• Fever is often present but often not very high 
• Cough is usually dry

We also know now that about 80% of people infected with COVID-19 have mild illness, 14% have severe and 5% have critical illness.

By far, the people most at risk are elderly with other chronic health conditions (especially cardio-pulmonary health conditions).

Who to test for COVID-19? (as of 3/8/2020)

Persons with symptoms (fever (T>100.3), cough, breathing difficulties or sore throat)

AND
Prioritize people who meet CDC criteria (https://www.cdc.gov/coronavirus/2019-ncov/travelers/index.html)

• any symptomatic person, including HCW with close contact with +COVID-19 patient in the last 14 days, including Grand Princess cruise ship passengers
• any symptomatic person who traveled to geographic area with CDC travel advisory 2/3 in the last 14 days of sx onset (China, Iran, Italy, Japan, South Korea)
• any person hospitalized with lower respiratory tract infection sx where an alternative etiology has not been identified

Don't test asymptomatic people!

US Healthcare system preparation:
Dr. Green assured us that even though we haven't experienced community transmission yet, COVID-19 will be coming to a community near you. Just like flu and RSV seasons. But this is going to be a long slog. We are just about the wrap up flu season, too bad, time to keep up the hard word. ,

Key goals for the US healthcare system per the CDC. These are our goals too in our local community!

1. Reduce morbidity and mortality
2. Minimize disease transmission
3. Protect healthcare personnel
4. Preserve our healthcare system functioning

So, healthcare workers, stay safe, wash your hands, wear PPE, don't come to work sick, and don't panic. 

A few extra super-interesting goodies:

On a vaccine: 

• During the 2002 SARS epidemic (which was also a novel coronavirus), there was a tremendous amount of work done to create a SARS vaccine. By the time the vaccine was ready, 20 months had passed, and the epidemic had died down. 
• However, the very substrate with which that vaccine was created is being used to fast-track a vaccine for COVID-19.
• That puts the world 20 months ahead of the game. 
• Look for vaccine trials for COVID-19 to start in the next couple months!

On antiviral medications: 

• During the SARS epidemic, it was noted that HIV+ patients on antiretrovirals (ARVs)-- particularly Kaletra-- did better than their counterparts, despite assumptions that they should be immunocompromised and do worse.
• This led to experimental use of ARVs for the SARS coronavirus
• Also, during the last Ebola outbreak, a new ARV was created (Remdemsivir), which didn't have great effect on Ebola but may work for coronavirus
• SO, in the US, China and other countries (and even locally) new and old ARVs are being used (experimentally) to treat people infected with COVID-19. So far with some good outcomes. So cool!

And finally, some additional resources

• Great map from Johns Hopkins with global data (but we can all agree that the black and red is a little overly dramatic, just what we don't need right now), Click here to go to live map: https://coronavirus.jhu.edu/map.html
• Local Sonoma County Department of Public Health website: https://socoemergency.org/emergency/novel-coronavirus/