Showing posts with label vaccinations. Show all posts
Showing posts with label vaccinations. Show all posts

Sunday, February 15, 2026

Community Acquired Pneumonia - and How To Avoid it

 


Disclaimer:  Like all posts on this blog this is intended for educational and commentary purposes and is not medical advice in any form.  All medical decisions need to be made in collaboration with your personal physician who knows your history.  For reasons stated below - vaccination information and recommendations are also less clear than they have ever been due largely to political influences that can also affect physicians.

 

This a strategic post about pneumonia.  By strategic I mean I hope to clarify what it is and how to prevent it.  This is not about diagnosing and treating it.  Most people reading this blog either don’t need to know that or know a lot more than me about it. Instead, I hope to address three things – misinformation about it, barriers in the modern healthcare system to acute care, and how to prevent it.

My focus will be on community acquired pneumonia (CAP).  It is a term I am very familiar with dating back 40 years to med school and my medical internship. As an intern I carried around my copy of Sanford’s antimicrobial therapy and the relevant section of Phantom Notes which was basically an outline of the leading Internal Medicine text at the time.  Thirty percent of the people I admitted to the hospital had some kind of pulmonary problem.  Depending on who you read chronic obstructive pulmonary disease (COPD) is as high as the third leading cause of death worldwide.  Exacerbations of COPD were very common reasons for hospital and ICU admission. 

CAP by definition is acquired in the community and not in a hospital setting.  It can be cause by a range of microorganisms and host factors.  It can also develop in people with no known risk factors. Conventional wisdom used to be that the lung was sterile territory but now we know that it contains a low biomass microbiome consisting of bacterial, viral, and fungal elements that are there via microaspiration of mouth contents.  Local physiological changes can occur to change the microbiome, or pathogens can be inhaled that establish primary infections (1).   Certain lung diseases like COPD and asthma can also lead to selective proliferation of elements of the microbiome. 

The ability of the lung to repair itself after injury or infection is controversial. Some research suggested that the lung was permanently changed by infection.  One example would be the association of asthma with previous rhinovirus infection. More recent work suggests there is room for optimism if the regenerative capacity of the lung can be activated (2).  

My motivation for this post was a clinical trial I read in the New England Journal of Medicine.  It was about treating CAP in East Africa.  The research question was whether adding glucocorticoids to antibiotic treatment as usual would improve outcomes.  That study quotes the mortality of CAP as 25-30%. The study was conducted in Kenya.  2,180 study patients were randomized to standard care versus glucocorticoids.  All patients were admitted to a hospital and CAP was defined as “the presence of at least two of the following signs and symptoms for less than 14 days: cough, fever, dyspnea, hemoptysis, chest pain, or crackles on chest examination.”  Imaging was not a criterion for study entrance because it was not available in many settings.  They were started on the protocol within 48 hours of admission. Glucocorticoids were provided for free as one of five glucocorticoids in bioequivalent doses for a total of 10 days (including after discharge) in addition to standard care (6 mg of dexamethasone, 160 mg of hydrocortisone, 30 mg of methylprednisolone, 50 mg of prednisolone, or 50 mg of prednisone).  Standard care was antibiotic therapy per World Health Organization (WHO) guidelines (beta lactam and macrolide antibiotics). Exclusion criteria are available in the paper.

30-day mortality was the primary endpoint in an intent-to-treat analysis.  To get to the treatment population a total of 46,224 patients were screened.  Of the 2,180 patients mortality was 530 (24.3%) at 30 days.  246 of 1089 (22.6%) were in the glucocorticoid group and 284 of 1091 (26.0%) in the glucocorticoid group.  That translates to a hazard ratio of 0.84.  The authors explain the limitations (comorbid illnesses – HIV, hypertension) and advantages (large N, lower media age) of their study.  That seems like a slight reduction in mortality for the intervention, but the authors point out that several other studies had better results up to a 50% reduction in mortality with glucocorticoids and it is a low tech readily available intervention.

In looking at the side effects of glucocorticoids   Pulmonary tuberculosis and hyperglycemia were the most common adverse effects in the glucocorticoid treated group.  Pulmonary tuberculosis and acute kidney injury were the most common adverse effects in the standard care group. 

The striking part of this study for me are the mortality figures. Although the researchers emphasized throughout their study that this was a pragmatic trial in a healthcare system with fewer resources – the estimated mortality for community acquired pneumonia in the United States is 6% at 30 days for hospitalized patients but that increases to 34% at 30 days for patients who do not initially improve initially (4).  There are treatment guidelines for primary care physicians about who can or cannot be treated on an ambulatory basis.  Age is a risk factor for increased incidence of pneumonia with the rate increasing from 248 (all adults) to 634 (ages 65 to 79) to 16,430 per 100,000 after the age of 80 (5).  Pre-existing COPD increases the risk of hospitalization 9-fold.

There are characteristic patterns of pneumonia by pathogen based on the immune response.  Bacterial infections elicit an infiltration of neutrophils into the alveolar space in a pattern of lobar or bronchopneumonia that results in an exudate of dead cells and phagocytes in the alveolar space.  Viral infections cause an interstitial pattern of inflammation with lymphocytic cell infiltrates.  Identification of the pathogen is largely done on a clinical basis due to difficulty identifying the pathogens.  Indirect methods can be used like determining acute and convalescent phase antibodies to specific viruses. Both types of infection compromise normal physiology and can lead to hypoxia and in the case of bacteria secondary infections - like meningitis.      

Recent sporadic and annual viral pandemics have created a confluence of factors at the hospital that are best avoided.  The first is the use of broad-spectrum antibiotics.  Since a significant portion of people admitted with viral pneumonia develop hospital acquired secondary bacterial infections – antibiotics are given prophylactically to prevent that complication.  Increasing exposure to increasingly potent antibiotics leads to multiple drug-resistant bacteria.  The best pathway is to avoid getting the respiratory infection in the first place. 

The absolute best way to avoid is vaccinations.  Vaccinations are currently available for influenza, COVID-19 (Sars-CoV-2), respiratory syncytial virus (RSV), and Streptococcus pneumoniae (pneumococcal pneumonia and meningitis).  They have all been tested and offer relative protection (rather than absolute) against serious illness, hospitalization, and death, especially for adults 65+ years of age.  Vaccinations have become a mixed bag of accessibility.  On the one hand you can get them from pharmacies and that is a recent development.  On the other hand we have an elected government that has appointed a well known antivaccination promoter as the head of Health and Human Services – Robert F. Kennedy, Jr.  So far there have been restrictions on the COVID vaccination to people who are 65+ or have an underlying health condition.  Since the administration is apparently making health decision based on politics and ideology many states and professional organizations are publishing their own guidelines.  As an example here is a list of respiratory virus vaccination guidelines from the American Academy of Family Practice (AAFP).  The CDC still has pneumococcal vaccination recommendations for children less than the age of 5 and adults over the age of 50.

The University of Minnesota Center for Infectious Disease Research and Policy (CIDRAP) program has a good brief on the vaccine controversy and chaos introduced by the Trump administration and the lack of scientific origins at this link.

Apart from vaccinations risk factor modification should be considered.  If you were born and raised in American culture – it is important to realize that you have been socialized to expect to get sick in the wintertime.  I did not realize that until I was getting sick 2-3 times a year on the inpatient unit where I worked.  They were viral illnesses that took 2-3 weeks to recover from.  The building was made in an era where preservation of heat was the primary design goal.  There was minimal circulation of clean air or filtration.  My suggestions to improve the air quality were ignored.  The mini-epidemics were made worse by admitting people who were ill with respiratory viruses and not using any precautions to prevent the spread of those viruses.  The new personal time off (PTO) policies that make no distinction between vacation and sick days also lead to increased exposure to sick employees who would rather work sick than use PTO days for sick time.  Since the COVID pandemic even outpatient clinics ask questions every time they see you to minimize staff exposure to respiratory viruses.

Masks work.  They must be N95 masks and fit correctly but there is no doubt that they work.  These days it is common to see political arguments and in the extreme ridicule heaped on people who use them. Large scale uncontrolled studies are often cited as evidence that they are a weak intervention.  These studies are almost all self report with no measures of actual adherence to masking.  The best studies are done in a lab that look at filtering virus sized particles and there is no doubt they are equal to that test.  

Risk factor modification is probably important.  Cardiopulmonary diseases are significant risk factors for pneumonia – so maintaining the best possible treatment for those conditions is important.  Weight control and activity level are also important.  There is at least one study showing that 65+ year olds who maintain high activity levels have better immunity than those who do not.  The specific dose of exercise for that effect is unknown currently. 

Expert advice on vaccine allergies is an important point.  I have personal history of an anaphylactic reaction to anti-rabies duck embryo vaccine in 1975.  For the next 30 years I did not get a single vaccine against influenza because it was egg based.  I had innumerable episodes of viral illness that was probably influenza and decided to see an immunologist to see if I could be desensitized to eggs so I could get the flu vaccine.  When he confirmed that I could eat eggs without a problem he said that I would probably not have any problems with the vaccine.  He was correct and I have not missed an annual dose since.

Look for respiratory infection season onset and peaks.  They are typically available through your state public health department and the CDC. When I notice it – I change my routine to shop at nonpeak hours and wear a mask in stores.  In addition to protection from the airborne transmission route hand washing is also important.  Shopping carts, door handles, and other high traffic areas are unavoidable areas for direct contact transmission. That may include being in a public bathroom any time somebody flushes a toilet.  Keep in mind that there are number of circulating common cold viruses that include 4 coronaviruses that can make you very ill.

What about barriers to care in the current healthcare non-system in the US?  There are many since businesses have taken over health care in the past 40 years.  Healthcare is rationed by both businesses and governments with only a very grudging nod to quality. The most obvious example is avoidance of the emergency department if you need it.  Anyone with previous experience knows about waits in emergency departments and delays in care.  People avoid paramedics and ambulances out of fear they will be billed for that service.  If you expect that you are ill beyond a typical cold and have additional warning signs like shortness of breath – seek help immediately.  I have given that advice to many people and it is included in the final paragraph of this AMA information sheet.   Keep in mind that pneumococcal infection can also cause meningitis which is even a more significant emergency and those symptoms can include a severe headache and neck stiffness.  Maintain a low threshold for checking these symptoms out with your primary care physician’s office during working hours and their call line after hours. But if that is not available or able to give you an answer call 911 and get a paramedic there in person to advise you and advocate for you getting timely care.  Even in our fragmented healthcare system you do not have to go it alone.  

Finally – you must realize that the infectious disease space has been infiltrated by many people who do not belong there.  They have mixed agendas involving politics and health and wellness profits.  In some cases, they are just promoting themselves.  This varies from a kernel of truth rhetoric (eg. “most people who get this virus do not die”) to outright lies (eg. “this vaccine has never been adequately tested”).  There are many points in between such as “He died of pneumonia not COVID”.  In outrageous cases they have attacked and threatened public health officials.  It is important to recognize who these people are and why they must be ignored to preserve your interest and that is your personal health. 

I attached a list of the main respiratory pathogen vaccinations as a supplementary below. The indications are taken directly from the FDA approved package insert that is in turn based on clinical trials for efficacy and safety. There are significant differences between the FDA approved indications and eligibility as determined by various organizations. There are also links to those graphics in the appended material. Note that for the COVID vaccinations especially the eligibility can vary based on age, susceptibility status, and what has been referred to as mutual decision making. In my opinion this is basically slow walking vaccine denial in as eligibility. Essentially all medical decisions are based on informed consent as mutual decision making. I did not get a single influenza vaccine for 30 years because of mutual decision making that was based on inadequate information. I asked an Internist about what he would recommend in the cased of COVID-19 vaccinations and he said: “Definitely recommend for over 65. Recommend for patients with multiple comorbidities. Recommend for healthy young adults if they were healthcare workers, teachers or in an occupation with lots of exposure to the public.” Why are the eligibility criteria not that simple?  As far as I can tell the answer is politics.

That is my overall strategy to avoid pneumonia.  It is most important as you age into categories where your risk doubles (65+ yrs old) and increases 25-fold (80+ yrs old).  I use these strategies myself and have found them to be very effective.  And remember the overall strategy is to avoid the physical virus or bacteria if at all possible and failing that make sure your immune system is activated by a vaccination to attack it if you are infected.

 

George Dawson, MD, DFAPA

 

References:

1: Li, R., Li, J. & Zhou, X. Lung microbiome: new insights into the pathogenesis of respiratory diseases. Sig Transduct Target Ther 9, 19 (2024). https://doi.org/10.1038/s41392-023-01722-y 

2:  Ainsworth C. Lung, heal thyself. Nature. 2026 Jan 29;649:S9 – S11.

3:  Lucinde RK, Gathuri H, Mwaniki P, et al. A Pragmatic Trial of Glucocorticoids for Community-Acquired Pneumonia. N Engl J Med. 2025 Dec 4;393(22):2187-2197. doi: 10.1056/NEJMoa2507100. Epub 2025 Oct 29. PMID: 41159889; PMCID: PMC12659994.

4:  Peyrani P, Arnold FW, Bordon J, et al. Incidence and mortality of adults hospitalized with community-acquired pneumonia according to clinical course. Chest. 2020;157(1):34-41.    

5:  Jain S, Self WH, Wunderink RG, et al.; CDC EPIC Study Team. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015;373(5):415-427.


Graphic:

Pages from my trusty copy of Phantom Notes that I used on wards as a medical student.  I went back to check to see if community acquired pneumonia was a thing back then and it was not.  If you can read it they do discuss where it was acquired under Classification (D3).   According to PubMed that term was used just twice in 1981 - but became progressively more popular in the 1990s.


Note also that we have an expanded list of viral pathogens compared with 1981.

Phantom Notes Medicine 79-80 edition copyright Joe D. Glickman, Jr, MD All Rights Reserved.  


A Shocking Anecdote about Pneumococcus:

When I was an intern on neurology (1983) I was called down to the emergency department to assess a 70 year old woman for "agitation".   That was all they could tell me aside from the fact that her labs and exam were normal.  She was unresponsive, groaning softly and rolling from side to side on the bed.  I proceeded with my examination and found that she had a stiff neck and pus draining out of her left ear.  I called my two senior neurology residents and they came sprinting to the ED.  A quick gram stain of the pus showed gram positive cocci and we gave her 1 gram of IV chloramphenicol, did a lumbar puncture and transferred her to the Neurology ICU.  She subsequently developed ARDS and required transfer to the medical ICU for ventilatory support.  She was discharged a month later and was completely deaf as a result of pneumococcal meningitis.


Vaccines for Respiratory Tract Infections: Indications versus Eligibility:

 

Vaccine

Indication (From Package Insert)

Eligibility (From CDC)

Influenza

FLUARIX is a vaccine indicated for active immunization for the prevention

of disease caused by influenza A subtype viruses and type B virus contained

in the vaccine. FLUARIX is approved for use in persons aged 6 months and older. (1)

 - Fluzone High-Dose is a vaccine indicated for active immunization for the prevention of disease caused by influenza A subtype viruses and type B virus contained in the vaccine. (1) Fluzone High-Dose is approved for use in persons 65 years of age and older. (1)

Annual all adults

CDC Guidance

COVID

Moderna - SPIKEVAX is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

SPIKEVAX is approved for use in individuals who are:

• 65 years of age and older, or

• 6 months through 64 years of age with at least one underlying condition that puts them at risk of severe outcomes from COVID-19

 

Pfizer - COMIRNATY is a vaccine indicated for active immunization to prevent

coronavirus disease 2019 (COVID-19) caused by severe acute respiratory

syndrome coronavirus 2 (SARS-CoV-2). (1)

COMIRNATY is approved for use in individuals who are:

 65 years of age and older, or

 5 years through 64 years of age with at least one underlying condition

that puts them at high risk for severe outcomes from COVID-19. (1)

Adults should discuss with their health care provider to see if this vaccine is right for them.

CDC Guidance

RSV

-Active immunization of pregnant individuals at 32 through 36 weeks gestational age for the prevention of lower respiratory tract disease (LRTD) and severe LRTD caused by respiratory syncytial virus (RSV) in infants from birth through 6 months of age. (1.1)

- Active immunization for the prevention of LRTD caused by RSV in individuals 60 years of age and older. (1.2)

-Active immunization for the prevention of LRTD caused by RSV in individuals 18 through 59 years of age who are at increased risk for LRTD caused by RSV

Adults 75+

Adults 50-74 at increased risk

CDC guidance

Pneumococcus

Pneumococcal Conjugate Vaccines (PCV)

 

PCV15 (Vaxneuvance): Protects against 15 types of pneumococcal bacteria.  is indicated for active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F in individuals 6 weeks of age and older.

 

PCV20 (Prevnar 20): Protects against 20 types of bacteria; it has largely replaced the older PCV13 (Prevnar 13). Prevnar 20 is a vaccine indicated for

• active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F in individuals 6 weeks of age and older. (1)

• active immunization for the prevention of otitis media caused by S. pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F in individuals 6 weeks through 5 years of age. (1)

• active immunization for the prevention of pneumonia caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F in individuals 18 years of age and older. (1)

The indication for the prevention of pneumonia caused by S.pneumoniae serotypes 8, 10A, 11A, 12F, 15B, 22F, and 33F in individuals 18 years of age and older is approved under accelerated approval based on immune responses as measured by opsonophagocytic activity (OPA) assay.

 

PCV21 (Capvaxive): A newer vaccine approved in 2024 for adults, protecting against 21 types, including several strains not covered by other vaccines. CAPVAXIVE™ is a vaccine indicated for:

• active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A,

11A, 12F, 15A, 15B, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B in individuals 18 years of age and older. (1)

• active immunization for the prevention of pneumonia caused by S. pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A,15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B in individuals 18 years of age and older. (1)

The indication for the prevention of pneumonia caused by S. pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B is approved under accelerated approval based on immune responses as measured

by opsonophagocytic activity (OPA).Continued approval for this indication may be contingent upon verification and description of clinical

benefit in a confirmatory trial. (1)

Pneumococcal Polysaccharide Vaccine (PPSV)

PPSV23 (Pneumovax 23)

PNEUMOVAX 23 is a vaccine indicated for active immunization for the prevention of pneumococcal disease caused by the 23 serotypes contained in the vaccine (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F,14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F). (1.1)

PNEUMOVAX 23 is approved for use in persons 50 years of age or older

and persons aged ≥2 years who are at increased risk for pneumococcal disease. (1.1, 14.1)

Adults aged 50 or older according to CDC

 

 *High risk for severe outcomes:  For the comprehensive list of underlying medical conditions that place a person at risk for severe outcomes from COVID-19 see this CDC document: https://www.cdc.gov/covid/hcp/clinical-care/underlying-conditions.html

 FDA Vaccine, Blood, and Biologics Web Page:  https://www.fda.gov/vaccines-blood-biologics

 FDA Vaccines Licensed for Use in the United States:  https://www.fda.gov/vaccines-blood-biologics/vaccines/vaccines-licensed-use-united-states

CDC Vaccine Schedule with graphic:  https://www.cdc.gov/vaccines/imz-schedules/adult-easyread.html

COVID recommendation:  “Adults should talk to their health care provider to decide if this vaccine is right for them”.

 AAFP Adult Vaccination Schedule with graphic:  https://www.aafp.org/dam/AAFP/documents/patient_care/immunizations/2025%20adult%20Schedule_NOV.pdf

COVID recommendation:  “1 – 2 or more (age >65) does of the updated 2025-2026 vaccine”.

 Minnesota Department of Health Adult Vaccination Schedule with graphic: https://www.health.state.mn.us/people/immunize/resprecs.pdf

COVID recommendation:  “All adults especially 65+ (2 doses)”.

 



 

Monday, February 3, 2020

Adventures In Vaccine Reactions



This area of erythema appeared on day 3 - only on the arm where the Pneumovax was placed




This post is about vaccinations for old people.  It is a mix of science and anecdotes because that is all there is out there right now. A lot of the information I elicited by posting my experience getting the Shingrix Zoster Vaccine and the Pneumovax 23 Vaccine. It illustrates the concept of biological heterogeneity that I post about on this blog. Many people can seem confused about that, particularly the idea that practically every biological system in the human body has significant heterogeneity and the immune system is no exception.

I don’t work on Fridays anymore so last Friday afternoon I headed down to a primary care clinic to get some problems checked out. The primary care doctor was clearly knowledgeable, reassured me that I had no major problems, and asked me if there is anything else that he could do for me. At that point the conversation went something like this:

Me:  “Well I keep being told every other visit that I need a second Pneumovax vaccination and I need the second Shingrix vaccination. Is it possible get those today?”

MD:  “That should not be a problem”

Me:  “Is there any problem with getting them on the same day?”

MD:  “No you can get them both on the same day.”

At that point he pulled up the EHR and verified that I had a Pneumococcal Conjugate Vaccine (PCV13) on 1/11/2016 and a Pneumococcal polysaccharide vaccine (PPSV23) on 9/8/2010 and a previous Shingrix vaccine on 10/30/2019. He explained the rationale for the second PPSV23 vaccination.

MD: “Did you have any reactions to the first vaccinations?”

Me:  “Just a little pain at the injection site but nothing major.”

The nurse came in the room and asked me if I wanted the shots in the same arm or different arms.  She gave me the Shingrix injection in the left arm and the PPSV23 injection the right arm. I noted the time was 2 PM.  I have a history of anaphylactic reactions and an anaphylactic reaction to a second dose of anti-rabies duck embryo vaccine when I was in the Peace Corps. I forgot to bring an EpiPen, but there is a coffee shop just down the street. I spent an uneventful 40 minutes there (to get through that window) and then headed home.

About six hours later I started to get more intense muscle pain in both arms that eventually extended into the back and down the back. A short time later I started to get a headache. By 9 o’clock that night I was taking acetaminophen for those symptoms. I also noted that I was feeling physically ill and fatigued. The next morning I did not feel any better and continued to take the acetaminophen and added naproxen.  By 1 o’clock the next day - nearly 24 hours after the injection I started to get intense chills. It took my temperature and it was normal. I had put on outdoor clothing and sat next to the fireplace. I was shaking. It reminded me of when I had malaria back in 1975. In those days I had a cheap sleeping bag and crawled into that but eventually crawled across the floor into a tub of hot - water dragging the sleeping bag with me.  I had better resources now. I developed some tachycardia and felt very physically ill until about the 60 hour mark. At that point the chills stopped and the tachycardia resolved.

In the meantime I had solicited a number of medical and nonmedical opinions. One of the best internists I know told me that he advises patients take Shingrix vaccination but that they should plan on being out of commission for 2 to 3 days. He also does not recommend any other vaccinations with it because of the severity of the reaction. Several other primary care physicians have given me similar advice. I posted my experience on a listserv for psychiatrists and my Facebook site and several people had similar experiences. The physical illness caused by the immunizations was intense enough to take sick leave from work.

When I left the doctor’s office I was given “Vaccine Information Statements” that were both CDC documents.  One was entitled “Pneumococcal PolysaccharideVaccine - What You Need to Know” and the other was “Recombinant Zoster (Shingles)Vaccine: What You Need to Know”.  For the shingles vaccine the risk of reaction to the vaccine was listed as mild to moderate arm pain in 80% of people and side effects that prevented 1 of 6 people from doing regular activities that included fatigue, muscle pain, headache, shivering, fever, stomach pain, and nausea. The side effects were supposed to resolve in 2 or 3 days. By comparison the pneumococcal vaccine states that “less than 1/100 people develop a fever, muscle aches, or more severe local reactions”.

At a theoretical level it is interesting to consider the differences between both vaccines. In order to generate an immunological response, vaccinations need to create inflammation at the injection site. That typically requires an adjuvant. Adjuvants like aluminum compounds result in local cell death that leads to release of IL-1 family cytokines and danger-/damage associated molecular patterns (DAMPS). That in turn leads to T cell response and immunity (3). 

The adjuvants for these vaccines are significantly different.  The PPSV23 adjuvant is a standard alum based.  The Shingrix adjuvant is an ASO1B that is described as “ f 3-O-desacyl-4’-monophosphoryl lipid A (MPL) from Salmonella minnesota and QS-21, a saponin purified from plant extract Quillaja saponaria Molina, combined in a liposomal formulation. The liposomes are composed of dioleoyl phosphatidylcholine (DOPC) and cholesterol in phosphate-buffered saline solution containing disodium phosphate anhydrous, potassium dihydrogen phosphate, sodium chloride, and water for injection.” By comparison Zostavax the original shingles vaccine was live attenuated varicella-zoster virus without an adjuvant.  The Zostavax vaccination is much less effective, leading the CDC to recommend both doses of Shingrix, even if there is a significant non-allergic reaction to the first injection. 
Flu-like symptoms are an area great interest to me into a large extent they are cytokine mediated.  The top flow sheet at this post gives common cytokines that can cause flu like illness.  Given the complexity and sheer number of cytokines the scope of inflammatory cytokines triggering these reactions is not known.  Of the known cytokines from the Shingrix inflammatory reaction (4) it is likely that IFN- γ is a cause. The other interesting aspect of this response is that it is hypothalamically mediated.  The preoptic anterior hypothalamic area (POAH) has networks for heat production (shivering) and dissipation (vasodilation) (5) and both were affected in my situation. This area is described as being sensitive to a number of compounds including cytokines.  Other  cytokines may explain the associated flushing and sweating.

At the time this was posted I have been seen in the Urgency Room last night because my health plan was concerned about tachycardia and flushing.  The ED doc thought it was all a post vaccine reaction and did not do any further testing.  He said to come back if I got a rash, bloody urine, or a temp of 100.5.  I had the chills for about 8 hours at that point. I went to bed at midnight and woke up at 3AM sweating.  By 7AM, the tachycardia and flushed sensation and appearance were gone. Things were going well until this afternoon when I noticed the redness on the arm where I had received the Pneumovax (see photo).  I was seen in Urgent Care this time.  They had an alternate explanation for the inflammatory response, if the needle is withdrawn too quickly some of the vaccine and adjuvant gets deposited in subcutaneous tissue and leads to a broad inflammatory response.  They recommended an antibiotic (cephalexin) and prednisone just in case. I declined the prednisone and could not get the antibiotic filled anyway.  The pharmacy I use closes at 7PM and I got out of Urgent Care at 7:07.

What are the lessons from this adventure in vaccinations?  First off, as I have said repeatedly on this blog there are no guarantees in medicine. Everything is a probability statement.  In the case of Shingrix, I am taking a vaccination that may be 90% effective in preventing shingles but the trade off is that in clinical trials as many as 1 person out of 6 gets disabling side effects for at least 2-3 days. I have heard from some people where it lasts for 10 days.  Second, even though those are significant side effects shingles is potentially far, far worse. In the people I have treated, that includes months of disabling neuropathic pain, eye complications, facial nerve complications, and in some cases extensive testing just to find out what the problem was.  As an example, a 79 year old man had extensive testing for severe abdominal pain that was thought to be a malignancy that was ultimately diagnosed as shingles.  In the case of Pneumovax it is pneumonia, meningitis, sepsis and death. Case closed.  My memorable case there was an elderly patient who presented to the emergency department with "agitation".  As the intern on Neurology I was called to see her.  By the time I arrived she was unresponsive.  Upon examination she had pus running out of her ear and nuchal rigidity. A lumbar puncture showed pneumococcal meningitis.  She survived a complicated course including acute respiratory distress syndrome (ARDS) but became completely deaf from the meningitis. Third, it is probably reasonable to not get both vaccinations at once. The physicians writing to me at this point have all been affected by complications they have seen in their patients who got Shingrix and they have seen it as a vaccine that has more than the ordinary amount of adverse effects compared with typical adult vaccinations.  Finally, what about the issue of repeat Pneumovax vaccinations?  It only comes up in cases where a person has COPD or asthma (me) and gets a vaccination before the age of 65 on that basis. Clearly, the arm rash here seems to indicate more of an inflammatory response on the Pneumovax side than the Shingrix in my case. Was it because of a robust antibody response after the initial vaccination?  I don’t have the answer to that question but if there are any immunologists reading this post – I would be very interested in your comments.

That is it for now.  Hopefully I am heading into work tomorrow morning.


George Dawson, MD, DFAPA




References:

1.  SHINGRIX (Zoster Vaccine Recombinant, Adjuvanted), suspension for intramuscular injection.  FDA Package Insert   https://www.fda.gov/media/108597/download

2.  PNEUMOVAX® 23 (pneumococcal vaccine polyvalent) Sterile, Liquid Vaccine for Intramuscular or Subcutaneous Injection.  FDA Package Insert  https://www.fda.gov/media/80547/download

3.  Muñoz-Wolf N, Lavelle EC. A Guide to IL-1 family cytokines in adjuvanticity. FEBS J. 2018 Jul;285(13):2377-2401. doi: 10.1111/febs.14467. Epub 2018 May 3. Review. PubMed PMID: 29656546.



4. Cunningham AL, Heineman TC, Lal H, Godeaux O, Chlibek R, Hwang SJ, McElhaney
JE, Vesikari T, Andrews C, Choi WS, Esen M, Ikematsu H, Choma MK, Pauksens K, Ravault S, Salaun B, Schwarz TF, Smetana J, Abeele CV, Van den Steen P, Vastiau I, Weckx LY, Levin MJ; ZOE-50/70 Study Group. Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older. J Infect Dis. 2018 May 5;217(11):1750-1760. doi: 10.1093/infdis/jiy095. PubMed PMID:29529222.


5. Swaab DF. Autonomic Disorders in Handbook of Clinical Neurology, Vol. 80
(3rd Series Vol. 2) The Human Hypothalamus: Basic and Clinical Aspects, Part II,
2004, Elsevier, Amsterdam, pp351-370.




Supplementary 1:

Did not make it into work as expected on February 4. Went to see my primary care MD instead.  The erythema (redness) had not gone down and actually extended farther down the arm (I drew a line around it the night before).  No systemic symptoms but more redness.  Needed to know if the antibiotic needed to be changed and if prednisone was a good idea.

His conclusion - not an infection but inflammation from a reaction to the vaccine.  He has only seen a couple of reactions like this with Pneumovax and pointed out that it is given to immunocompromised people every ten years starting at a younger age.  He said to keep taking the cephalexin for a week but no prednisone: "I give prednisone to people with life threatening problems - not a red arm.  More medicine is not necessarily good medicine."

Work tomorrow. 

Supplementary 2:

New CDC Guidelines on Pneumococcal Vaccinations:



New Pneumococcal Vaccine Recommendations for Adults Aged ≥65 Years Old

PCV13. PCV13 vaccination is no longer routinely recommended for all adults aged ≥65 years.
Instead, shared clinical decision-making for PCV13 use is recommended for persons aged ≥65 years
who do not have an immunocompromising condition, CSF leak, or cochlear implant and who have
not previously received PCV13 (Table 1).

CDC guidance for shared clinical decision-making. When patients and vaccine providers engage
in shared clinical decision-making for PCV13 use to determine whether PCV13 is right for the specific individual aged ≥65 years, considerations may include the individual patient’s risk for exposure to PCV13 serotypes and the risk for pneumococcal disease for that person as a result of underlying medical conditions (Box).

If a decision to administer PCV13 is made, it should be administered before PPSV23 (5).
The recommended intervals between pneumococcal vaccines remain unchanged for adults without
an immunocompromising condition, CSF leak, or cochlear implant (≥1 year between
pneumococcal vaccines, regardless of the order in which they were received) (5). PCV13 and PPSV23 should not be coadministered.

ACIP continues to recommend PCV13 in series with PPSV23 for adults aged ≥19 years
(including those aged ≥65 years) with immunocompromising conditions, CSF leaks, or
cochlear implants (Table 1) (2).

PPSV23 for adults aged ≥65 years. ACIP continues to recommend that all adults aged ≥65 years
receive 1 dose of PPSV23. A single dose of PPSV23 is recommended for routine use among all adults aged ≥65 years (1). PPSV23 contains 12 serotypes in common with PCV13 and an additional
1 serotypes for which there are no indirect effects from PCV13 use in children. The additional
11 serotypes account for 32%–37% of IPD among adults aged ≥65 years (22). Adults aged ≥65 years
who received ≥1 dose of PPSV23 before age 65 years should receive 1 additional dose of PPSV23 at
age ≥65 years (2), at least 5 years after the previous PPSV23 dose (Table 1) (5).


Note:  In the above case of the vaccine reaction I received 1 dose of PPSV23 before the PCV13 and one dose after by a period of 4 years.  That is not consistent with the guideline but they  were not coadministered and there was a period of at least one year between injections (PPSV23 in 2010, PCV13 in 2016, and PPSV23 in 2020).