Immunization

What’s the connection between flu vaccination and lower risk of Alzheimer’s Disease?

FA Manian MD, MPH, , , , , , , , , , , , , , Leave a comment

As far fetched that it may sound, there is growing evidence that flu vaccination is associated with lower risk of being diagnosed with Alzheimer’s Disease (AD).1

The most compelling evidence to date comes from a 2022 retrospective, propensity-matched study involving a nationwide sample of over 2 million U.S. adults ≥ 65 years old.1  This study found a 40% reduction in the risk of incident AD during the 4-year follow-up period when individuals receiving at least 1 dose of flu vaccine were compared to those who did not receive flu vaccination during the study period (number needed to treat-NTT 29.4). 

Despite its limitations, the results of the above study were concordant with those of several smaller studies that found an association between flu vaccination and lower risk of dementia of any cause.1-3  A 2022 meta-analysis also concluded that flu vaccination was associated with significantly lower risk (33%) of dementia among older people. Interestingly, in a study involving veterans, receipt of ≥6 doses of flu vaccines (not fewer) was associated with lower risk of dementia.4

Several hypotheses have been posited to explain the potential beneficial impact of flu vaccination on the risk of dementia, including: 1. Influenza-specific mechanisms, such as mitigation of damage secondary to influenza infection and/or epitopic similarity between influenza proteins and AD pathology; 2. Non-influenza-specific training of the innate immune system; and 3. Non-influenza-specific changes in adaptive immunity via lymphocyte-mediated cross-reactivity.1

So, in addition to its protective effect against severe influenza,5 and its association with lower risk of hospitalization for cardiac disease and stroke and reduction in death due to combined cardiovascular disease events (eg, heart attacks/strokes),  flu vaccination may be protective against AD! Who would have thought that a simple vaccine may have far reaching health benefits?

Bonus Pearl: Did you know that mice infected with non-neurotropic influenza strains have been found to have excessive microglial activation and subsequent alteration of neuronal morphology, particularly in the hippocampus, and that in APP/PS1 transgenic mice, peripheral influenza infection induces persistent elevations of amyloid- (A) plaque burden?1  Intriguing indeed!!!

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References

  1. Bukhbinder AS, Ling Y, Hasan O, et al. Risk of Alzheimer’s disease following influenza vaccination: A claims-based cohort study using propensity score matching. Journal of Alzheimer’s Disease 2022; 88:1061-1074. https://pubmed.ncbi.nlm.nih.gov/26945371/  
  2. Liu JC, Hsu YP, Kao PF, et al. Influenza vaccination reduces dementia risk in chronic kidney disease patients: A population-based cohort study. Medicine (Baltimore) 2016 95 :32868. https://pubmed.ncbi.nlm.nih.gov/26945371/
  3. Wiemken TL, Salas J, Hoft DF, et al. Dementia risk following influenza vaccination in a large veteran cohort. Vaccine 2021;39:5524-5531. https://pubmed.ncbi.nlm.nih.gov/34420785/
  4. Veronese N, Demurtas J, Smith L, et al. Influenza vaccination reduces dementia risk: A systematic review and meta-analysis. Ageing Res Rev 2022;73:101534. https://pubmed.ncbi.nlm.nih.gov/34861456/
  5. Godoy P, Romero A, Soldevila N, et al. Influenza vaccine effectiveness in reducing severe outcomes over six influenza seasons, a case-cae analysis, Spain, 2010/11 to 2015/16.  Euro Surveill 2018;23:1700732. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208006/
  6. Hosseini S, Michaelsen-Preusse K, Schughart K, et al. Long-term consequences of non-neurotropic H3N2 influenza A virus infection for the progression of Alzheimer’s Disease symptoms. Front. Cell. Neurosci 28 April 2021; https://doi.org/10.3389/fncel.2021.643650 https://www.frontiersin.org/articles/10.3389/fncel.2021.643650/full

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

What’s the connection between flu vaccination and lower risk of Alzheimer’s Disease?

My patient with COPD on prednisone with recurrent pneumonia has a low serum IgG level.  Can corticosteroids lower serum immunoglobulin levels?

FA Manian MD, MPH, , , , , , , , , , , , , Leave a comment

Yes! Both exogenous and endogenous hypercortisolism may be associated with a drop in serum immunoglobulin levels, particularly IgG, which may persist even after discontinuation of steroid treatment.1-4 This means that a low serum IgG level in a patient on corticosteroids should be interpreted with caution and may not necessarily suggest primary antibody deficiency.

Although some early studies did not find a significant impact of corticosteroids on immunoglobulin levels, several subsequent studies found otherwise.  A 1978 study involving atopic asthmatic patients (averaging 16.8 mg prednisone daily) found that mean serum IgG significantly decreased (-22%) with milder drop in IgA levels (-10%) and no drop in serum IgM levels.2 Of interest, IgE level increased significantly initially but later dropped as well. More importantly, mean serum IgG levels remained significantly decreased an average of 22 days after corticosteroids were discontinued.

More recently, in a study involving patients with giant cell arteritis and polymyalgia rheumatica on corticosteroids, 58% developed antibody deficiency with the great majority involving IgG, either alone or along with other immunoglobulins.3 The reduction of IgG persisted even after discontinuation of corticosteroids in nearly 50% of patients, and observed in nearly one-quarter of patients for at least 6 months! Whether low serum immunoglobulins due to corticosteroids alone significantly increase susceptibility to infections is unclear, however.

In our patient with COPD on prednisone, if serum IgG level is found to be low and a primary antibody deficiency is still suspected, a functional assessment of the antibody production after active immunization (eg, polysaccharide pneumococcal vaccine, tetanus toxoid) may be necessary. 1 An adequate antibody response to active immunization makes primary immunodeficiency unlikely. 

 

Bonus Pearl: Did you know that corticosteroid-induced hypogammaglobulinemia may be in part related to reduced IgG production as well as an increase in IgG catabolism?1,4

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References

  1. Sarcevic J, Cavelti-Weder C, Berger CT, et al. Case report-secondary antibody deficiency due to endogenous hypercortisolism. Frontiers in Immunology 2020;11:1435. https://www.frontiersin.org/articles/10.3389/fimmu.2020.01435/full
  2. Settipane GA, Pudupakkam RK, McGowan JH. Corticosteroid effect on immunoglobulins. J Allergy Clin Immunol 1978;62: 162-6. https://www.jacionline.org/article/0091-6749(78)90101-X/pdf
  3. Wirsum C, Glaser C, Gutenberger S, et al. Secondary antibody deficiency in glucocorticoid therapy clearly differs from primary antibody deficiency. J Clin Immunol 2016;36:406-12. https://link.springer.com/article/10.1007/s10875-016-0264-7
  4. McMillan R, Longmire R, Yelenosky R. The effect of corticosteroids on human IgG synthesis. J Immunol 1976;116:1592-1595. https://www.jimmunol.org/content/116/6/1592

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My patient with COPD on prednisone with recurrent pneumonia has a low serum IgG level.  Can corticosteroids lower serum immunoglobulin levels?

What’s the latest on second Covid vaccine boosters and should I recommend them to my adult patients?

FA Manian MD, MPH, , , , , , , , , Leave a comment

On March 29, 2022, the CDC and the FDA approved second booster shots of Pfizer and Moderna Covid vaccines for everyone 50 years of age or older as well as people 12 years of age or older with moderate to severe immune deficiencies to be given at least 4 months following the first booster.1-3  This means a 4th dose of an mRNA vaccine for many adults and a 5th dose for those with moderate to severe immune deficiencies. 

Admittedly, these recommendations are made in the context of many uncertainties, including when the next Covid surge will arrive, what will be the predominant variant, and how will our immunity hold up if a surge occurs. 

Nevertheless, in discussing the merits of a 2nd booster, I would emphasize several “talking points”:

  • Covid hasn’t gone away with new cases still diagnosed daily, some still  requiring hospitalization, albeit at lower frequency than recent past. 
  • Our immunity against Covid wanes in the absence of boosters or natural infection.
  • SARS-CoV-2 has been unpredictable in its surges, as well as emergence of new variants with frequent changes in its virulence and ease of transmission. This means we don’t know when the next surge will hit us (summer, fall or later) and how the predominant variant will behave.
  • But let’s not get too hung up on surges! The fact is that as long as Covid is circulating around, maintaining a robust immunity against infection is the best way to avoid getting infected and the best way to do this is through boosters!
  • As more people go around without masks, the risk of unprotected exposure to SARS-CoV-2 is also likely to increase, particularly in indoor public gatherings.  Boosters may allow us the freedom to go maskless more often!
  • The risk of Long Covid even following mild infection is still real even between surges. This means even if we don’t get very sick from Covid, we are placing ourselves at risk of Long Covid. Remember, no Covid, no Long Covid!
  • Irrespective of whether it’s mild or even asymptomatic, Covid infection  can cause significant disruption in our lives, whether it be isolation at home, not being allowed to return to work or just the anxiety of having it or having passed it to others. This means that, at least currently, it’s premature to consider this virus as “just another respiratory virus.”  It’s impact on our everyday lives is still a lot different than typical respiratory viruses. 
  • mRNA vaccine boosters have been proven to be as safe as primary series. 
  • Last, but not the least, a preprint Israeli study involving volunteers 60 to 100 years old found a 78% reduction in mortality from Covid following a 2nd booster dose of Pfizer mRNA vaccine compared to those who only had 1 booster.4  This study has several limitations including self-selected volunteers who may already be at lower risk of Covid mortality due to their healthier lifestyle. Nevertheless, the data is very encouraging!

Ultimately, the decision to get a second booster, particularly during non-surge periods, will depend a lot on not only available facts but the individual’s threshold for acceptable risk of even mild disease, concern over transmission to others and more recently the cost of the vaccine, among other factors.  

Bonus Pearl: Did you know that each year there are plenty of uncertainties around which influenza A or B subtypes will be the predominant seasonal strain or what month they may surge but these questions never keep us from recommending the annual flu vaccine to the public as a means of reducing influenza cases and saving lives?   

 

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References

  1. D.A. Allows Second Covid Boosters for Everyone 50 and Older – The New York Times (nytimes.com)
  2. Coronavirus (COVID-19) Update: FDA Authorizes Second Booster Dose of Two COVID-19 Vaccines for Older and Immunocompromised Individuals | FDA
  3. CDC Recommends Additional Boosters for Certain Individuals | CDC Online Newsroom | CDC
  4. Arbel R, Sergienko R, Friger M, et al. Second booster vaccine and Covid-19 mortality in adults 60-100 years old. Preprint, posted March 24, 2022. 24514bba-2c9d-4add-9d8f-321f610ed199.pdf (researchsquare.com)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

What’s the latest on second Covid vaccine boosters and should I recommend them to my adult patients?

Should patients with prior Covid receive Covid vaccine?

FA Manian MD, MPH, , , , , Leave a comment

Yes, as recommended by the CDC.  The weight of the evidence to date suggests that previously infected individuals should receive Covid vaccine to minimize their risk of acquiring Covid again for many reasons, including the following:

First, depending on the population and the variant of SARS-CoV-2 (the agent of Covid) studied, a significant proportion of infected individuals— from 5% to >35% based on some studies— fail to produce antibodies against SARS-CoV-2.1 In 1 study, lack of antibody production was associated with younger age, lower viral load and a trend toward milder symptoms.1

Second, the body of the evidence for infection-induced immunity is much more limited with less consistent findings than that for vaccine-induced immunity.2

Third, vaccination against Covid has been shown to enhance the immune response and reduce the risk of infection even in those with prior Covid.2 In fact, 1 study reported that the risk of reinfection is more than twice among those who were previously infected but not vaccinated compared to those who got vaccinated after having Covid.3  In another study, the risk of infection in adults was more than 5 times higher in unvaccinated but previously infected individuals compared to the vaccinated person who had not had an infection previously.4

Some authors5 who oppose routine vaccination of individuals previously infected with Covid have invoked a recent CDC study6 which showed that when Delta was the predominant strain, persons with prior Covid had lower rates of infection than persons who were vaccinated alone.  However, this study was performed when booster doses of Covid vaccine were not yet available to most people and before Omicron became the predominant variant. 

Bonus Pearl: Did you know that following Covid infection, neutralizing antibodies  have a biphasic decline with an initial half-life of 2-3 months followed by a slower decline thereafter?2

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References

  1. Liu W, Russell RM, Bibollet-Ruche F, et al. Predictors of nonseroconversion after SARS-CoV-2 infection. Emerg Infect Dis 2021;27:2454-58. Predictors of Nonseroconversion after SARS-CoV-2 Infection – Volume 27, Number 9—September 2021 – Emerging Infectious Diseases journal – CDC
  2. Science brief: SARS-CoV-2 infection-induced and vaccine-induced immunity. October 29, 2021. Science Brief: SARS-CoV-2 Infection-induced and Vaccine-induced Immunity | CDC
  3. Cavanaugh AM, Spicer KB, et al. Reduced risk of reinfection with SARS-CoV-2 after Covid-9 vaccination-Kentucky, may-June 2021. MMWR 2021;70:1081-83. Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination – Kentucky, May-June 2021 – PubMed (nih.gov)
  4. Laboratory-confirmed Covid-19 among adults hospitalized with Covid-19-like illness with infection-induced or mRNA vaccine-induced SARS-CoV-2 immunity—Nine states, January-September 2021. MMWR 2021;70:1539-44. Laboratory-Confirmed COVID-19 Among Adults Hospitalized with COVID-19–Like Illness with Infection-Induced or mRNA Vaccine-Induced SARS-CoV-2 Immunity — Nine States, January–September 2021 | MMWR (cdc.gov)
  5. Makary M. The high cost of disparaging natural immunity to Covid. Wall Street Journal. January 26, 2022. The High Cost of Disparaging Natural Immunity to Covid – WSJ
  6. Leon Tm, Drabawila V, Nelson L, et al. Covid-19 cases and hospitalizations by Covid-19 vaccination status and previous Covid-19 diagnosis-California and New York, May -November 2021.  MMWR 2022;71:125-31 COVID-19 Cases and Hospitalizations by COVID-19 Vaccination Status and Previous COVID-19 Diagnosis — California and New York, May–November 2021 (cdc.gov)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Should patients with prior Covid receive Covid vaccine?

How effective are the mRNA Covid-19 vaccines in reducing the risk of hospitalization among adults 65 years of age or older?

FA Manian MD, MPH, , , , , , , , Leave a comment

The mRNA vaccines by Pfizer and Moderna seem very effective in not only reducing risk of symptomatic Covid-19 but also risk of hospitalization among adults 65 years of age or older.   A CDC study published on April 28, 2021, showed a vaccine efficacy of 94% among fully immunized and 64% among partially immunized adults ≥ 65 years of age  with approximately one-half of subjects  ≥75 years old.1

This study was carried out in 24 hospitals in 14 states in the U.S. during January 1, 2021-March 26, 2021, and involved 417 patients: 187 case-patients with Covid-19 and 230 controls with negative SARS-CoV-2 PCR test.  Among patients with Covid-19, 10% were partially immunized (vs 27% among controls) and 0.5% were fully immunized (vs. 8% among controls). 1

An Israeli study in a nationwide mass vaccination setting involving persons (28% ≥ 60 y) receiving Pfizer mRNA vaccine similarly found a vaccine efficacy of 74% for hospitalization for partially immunized and 87% for fully immunized persons.2

The high effectiveness of mRNA vaccines against more severe Covid-19 requiring hospitalization is great news, of course, as advanced age is by far the greatest risk factor for death from Covid-19, independent of underlying comorbidities.3   

Bonus Pearl: Did you know that prior to the availability of effective Covid-19 vaccination, adults over 65 years of age represented 80% of hospitalizations and had a 23-fold greater risk of death than those under 65?3

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References

  1. Tenforde MW, Olson SM, Self WH, et al. Effectiveness of Pfizer-BioNTech and Moderna vaccines against COVID-19 among hospitalized adults aged ≥65 years-United States, January-March 2021. https://www.cdc.gov/mmwr/volumes/70/wr/mm7018e1.htm?s_cid=mm7018e1_w
  2. Dagan N, Barda N, Kepten E, et al. BNT162b2mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med 2021;384:1412-1423. https://www.nejm.org/doi/10.1056/NEJMoa2101765
  3. Mueller AL, McNamara MS, Sinclair DA. Why does COVID-19 disproportionately affect older people. Aging (Albany NY) 2020;12:9959-9981. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288963/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How effective are the mRNA Covid-19 vaccines in reducing the risk of hospitalization among adults 65 years of age or older?

Are NSAIDS contraindicated in patients with 2019 novel Coronavirus infection (Covid-19)?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , 1 Comment

Despite recent internet reports of the association of non-steroidal anti-inflammatory drugs (NSAIDs) with worsening symptoms among patients with Covid-19 (1), firm clinical evidence to support such claims is currently lacking. However, there are some theoretical reasons why it may still be best to avoid NSAIDs in this condition due to their potential adverse impact on the innate and adaptive immune responses as well as their antipyretic properties (2-9).

 
Blunting of the innate immune response: Certain NSAIDs (eg, ibuprofen, naproxen and celecoxib) inhibit cyclooxygenase enzyme-2 (COX-2) and impair production of several pro-inflammatory cytokines important in fighting infections, such as tumor necrosis factor, interleukin 1 and 6, as well as interferon, an antiviral cytokine (2,6,8). COX-2 has been shown to be important in controlling viral replication in influenza (4). Ibuprofen has been associated with inhibitory effects on a variety of polymorphonuclear functions, including chemotaxis (2).

 
Impact on adaptive immune response: COX-2 inhibition may be associated with impaired neutralizing antibody production (3,4,8). Potential mechanisms include modulation of cytokine expression, nitric-oxide production, and antigen processing/presentation and T lymphocyte activation (3,8).

 
Antipyretic effect: NSAIDs are often given for treatment of fever which is an evolutionary host response to infection. A meta-analysis of animal studies evaluating the impact of antipyretics (including aspirin, NSAIDs, and acetaminophen) in influenza found lower survival in animals treated with antipyretics (9). Longer duration of viral shedding has also been associated with the use of aspirin or acetaminophen in rhinovirus infection (9).

 
Formal epidemiologic and experimental studies are sorely needed to evaluate the safety of NSAIDS in Covid-19.  

 

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References
1. Kolata G. Is ibuprofen really risky for Coronavirus patients? NY Times, March 17, 2020. https://www.nytimes.com/2020/03/17/health/coronavirus-ibuprofen.html
2. Graham NMH, Burrell CJ, Douglas RM, et al. Adverse effects of aspirin, acetaminophen and ibuprofen on immune function, viral shedding, and clinical status in rhinovirus-infected volunteers. J Infect Dis 1990;162:1277-1282. https://academic.oup.com/jid/article/162/6/1277/918184
3. Culbreth MJ, Biryunkov S, Shoe JL, et al. The use of analgesics during vaccination with a live attenuated Yersinia pestis vaccine alters the resulting immune response in mice. Vaccines 2019;7, 205; doi:10.3390/vaccines7040205 https://www.mdpi.com/2076-393X/7/4/205
4. Ramos I, Fernandez-Sesma A. Modulating the innate immune response to influenza A virus:potential therapeutic use of anti-inflammatory drugs. Frontiers in Immunology. July 2015. Volume 6. Article 361. https://www.ncbi.nlm.nih.gov/pubmed/26257731
5. Falup-Pecurariu O, Man SC, Neamtu ML, et al. Effects of prophylactic ibuprofen and paracetamol administration on the immunogenicity and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugated vaccine(PHID-CV) co-administered with DTPa-combined vaccines in children:An open-label, randomized, controlled, non-inferiority trial. Human Vaccines & Immunotherapeutics 2017;13: 649-660. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360152/
6. Housby JN, Cahill CM, Chu B, et al. Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes. Cytokine 1999;11:347-58. https://www.ncbi.nlm.nih.gov/pubmed/30186359
7. Agarwal D, Schmader KE, Kossenkov AV, et al. Immune response to influenza vaccination in the elderly is altered by chronic medication use. Immunity & Ageing 2018;15:19. https://www.ncbi.nlm.nih.gov/pubmed/30186359
8. Bancos S, Bernard MP, Topham DJ, et al. Ibuprofen and other widely used non-steroidal anti-inflammatory drugs inhibit antibody production in human cells. Cell Immunol 2009;258:18-28. https://www.ncbi.nlm.nih.gov/pubmed/19345936
9. Eyers S, Weatherall M, Shirtcliffe P, et al. The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analysis. J R Soc Med 2010;103:403-11. https://www.ncbi.nlm.nih.gov/pubmed/20929891

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Are NSAIDS contraindicated in patients with 2019 novel Coronavirus infection (Covid-19)?

Should I continue to vaccinate my 65 years or older patients with pneumococcal conjugate vaccine (PCV13)?

FA Manian MD, MPH, , , , , , , Leave a comment

The 2020 U.S. Advisory Committee on Immunization Practices (ACIP) has revised its previous 2014 guidelines from routinely vaccinating all adults 65 years or older with PCV13 to a more selective vaccination approach based on shared clinical decision-making in the absence of immunocompromising conditions, cerebrospinal fluid leak or cochlear implant. 1

More specifically, ACIP recommends that we “regularly” offer PCV13 for patients 65 years or older who have not previously received PCV13 in the following settings:

  • Residents of nursing homes or other long-term care facilities
  • Residents of settings with low pediatric PCV13 uptake
  • Travelers to settings with no pediatric PCV13 program

ACIP also recommends that we consider offering the PCV13 to patients with chronic heart, lung, or liver disease, diabetes, or alcoholism, those who smoke cigarettes, or those with more than 1 chronic medical condition.

Why the change in recommendations? The primary reason is sharp declines in pneumococcal disease in unvaccinated children and adults due to the widespread use of PCV7 and PCV13 in children, resulting in prevention of transmission of vaccine-type strains.  

These recommendations do not apply to the pneumococcal 23-valent polysaccharide vaccine (PPSV23), however. All adults 65 years or older should continue to receive a dose of PPSV23. 

Bonus Pearl: If a decision is made to administer PCV13 to an adult 65 years old or older, PCV13 should be administered first, followed by PPSV23 at least 1 year later.

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References

  1. Freedman M, Kroger A, Hunter P, et al. Recommended adult immunization schedule, United States, 2020. Ann Intern Med 2020; [Epub ahead of print 4 February 2020]. Doi: https://doi.org/10.7326/M20-0046.
  2. Matanock A, Lee G, Gierke R, et al. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥65 years: updated recommendations of the advisory committee on immunization practices. MMWR 2019;68:1069-75. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6871896/pdf/mm6846a5.pdf

 

Should I continue to vaccinate my 65 years or older patients with pneumococcal conjugate vaccine (PCV13)?

Should my hospitalized patient with ulcerative colitis flare-up receive pneumococcal vaccination?

FA Manian MD, MPH, , , , , , Leave a comment

There are at least 2 reasons for considering pneumococcal vaccination in hospitalized patients with ulcerative colitis flare.

First, these patients are often on immunosuppressants (eg, glucocorticoids) or biological agents (eg, infliximab) that qualifies them for both 13-valent conjugate (PCV13) and 23-valent polysaccharide (PPSV23) pneumococcal vaccines under the Advisory Committee on Immunization Practices (ACIP) Guidelines’ “Immunocompromised persons” risk group.1-4

Another reason is the possibility of  UC patients having coexisting hyposplenism, a major risk factor for pneumococcal disease. Although this association has been described several times in the literature since 1970s, it is relatively less well known.  In a study of patients with UC, hyposplenism (either by the presence of Howell-Jolly bodies in the peripheral blood smear or prolongation of clearance from blood of injected radioactively labelled heat-damaged red blood cells) was found in over one-third with some developing life-threatening septicemia in the early postcolectomy period.5

Another study found the majority of patients with UC having slow clearance of heat damaged RBCs despite absence of Howell-Jolly bodies in the peripheral smear.6 Fulminant and fatal pneumococcal sepsis has also been reported in patients with UC.7

Although the immunological response to pneumococcal vaccination may be lower among immunosuppressed patients in general, including those with UC, it should still be administered to this population given its potential benefit in reducing the risk of serious pneumococcal disease. 2,3  

References

  1. CDC. Intervals between PCV13 and PSV23 vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2015;64:944-47. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6434a4.htm
  2. Carrera E, Manzano r, Garrido. Efficacy of the vaccination in inflammatory bowel disease. World J Gastroenterol 2013;19:1349-53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602493/
  3. Reich J, Wasan S, Farraye FA. Vaccinating patients with inflammatory bowel disease. Gastroenterol Hepatol 2016;12:540-46. http://www.gastroenterologyandhepatology.net/archives/september-2016/vaccinating-patients-with-inflammatory-bowel-disease/
  4. Chaudrey K, Salvaggio M, Ahmed A, et al. Updates in vaccination: recommendations for adult inflammatory bowel disease patients. World J Gastroenterol 2015;21:3184-96. https://www.ncbi.nlm.nih.gov/pubmed/25805924
  5. Ryan FP, Smart RC, Holdworth CD, et al. Hyposplenism in inflammatory bowel disease. Gut 1978;19:50-55. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1411782/
  6. Jewell DP, Berney JJ, Pettit JE. Splenic phagocytic function in patients with inflammatory bowel disease. Pathology 1981;13:717-23. https://www.ncbi.nlm.nih.gov/pubmed/7335378
  7. Van der Hoeven JG, de Koning J, Masclee AM et al. Fatal pneumococcal septic shock in a patient with ulcerative colitis. Clin Infec Dis 1996;22:860-1. https://www.ncbi.nlm.nih.gov/pubmed/8722951

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Should my hospitalized patient with ulcerative colitis flare-up receive pneumococcal vaccination?

How should I interpret a positive urine pneumococcal antigen when my suspicion for pneumococcal disease is very low?

FA Manian MD, MPH, , Leave a comment

The popular urine pneumococcal antigen (UPA) (based on the C-polysaccharide of Streptococcus pneumoniae cell wall) has been a valuable diagnostic tool in diagnosing invasive pneumococcal infections, but may be associated with up to nearly 10% rate of false-positivity in hospitalized patients1.  Three factors have often been cited as the  cause of false-positive UPA results: a. Nasopharyngeal carriage; b.Prior invasive pneumococcal infection and;  c. Pneumococcal vaccination.

Among adults with nasopharyngeal carriage of S. pneumoniae, particularly those with HIV infection, 12-17% of positive UPA tests may be false-positive1. In patients with recent invasive pneumococcal disease, UAP may remain positive in over 50% of patient at 1 month and about 5% at 6 months1,2.

Among persons receiving the 23-valent polysaccharide pneumococcal vaccine (PPV), over 20% may have a positive UPA up to 30 hours following immunization, some potentially longer1.  In fact, the manufacturer of UPA assay recommends that UPA not be obtained within 5 days of receiving PPV. There is reason to believe that conjugated pneumococcal vaccine may be associated with the same phenomenon3.

So in a hospitalized patient with low suspicion for pneumococcal disease but a positive UAP, it would be wise to first exclude the possibility of PPV administration earlier during hospitalization before the sample was obtained1,4.

 

References

  1. Ryscavage PA, Noskin GA, Bobb A, et al. Incidence and impact of false-positive urine pneumococcal antigen testing in hospitalized patients. S Med J 2011;104:293-97.
  2. Andre F, Prat C, Ruiz-Manzano J, et al. Persistence of Streptococcus pneumoniae urinary antigen excretion after pneumococcal pneumonia. Eur J Clin Microbiol Infect Dis 2009;28:197-201.
  3. Navarro D, Garcia-Maset Leonor, Gimeno C, et al. Performance of the Binax NOW Streptococcus pneumoniae urinary assay for diagnosis of pneumonia in children with underlying pulmonary diseases in the absence of acute pneumococcal infection. J Clin Microbiol 2004; 42: 4853-55.
  4. Song JY, Eun BW, Nahm MH. Diagnosis of pneumococcal pneumonia: current pitfalls and the way forward. Infect Chemother 2013;45:351-66.

 

How should I interpret a positive urine pneumococcal antigen when my suspicion for pneumococcal disease is very low?

What’s the latest on vaccination of adults 65 years old or over with conjugated pneumococcal vaccine?

FA Manian MD, MPH, Leave a comment

Since August, 2014, the Advisory Committee on Immunization Practices (ACIP) has recommended routine use of 13-valent pneumococcal conjugated vaccine (PCV13, Prevnar) in adults ≥ 65 years, in addition to the traditional 23-valent pneumococcal polysaccharide vaccine (PPSV23, Pneumovax) (1).   The approval of PCV13 was based on a large randomized, double-blind, placebo-controlled trial (CAPITA) that found PCV13 effective in preventing vaccine-type pneumococcal, bacteremic, and nonbacteremic community-acquired pneumonia and vaccine-type invasive pneumococcal disease (2).

Due to the potential  for mutual interference with immunogenecity, these 2 vaccines should be spaced apart. When PPSV23 is administered first, PCV13 should be held for 1 year or longer. On the other hand, when PCV13 is administered first, PPSV23 can be given within 6-12 months (minimum 8 weeks). So it makes sense to give PCV13 first in our older pneumococcal vaccine-naive patients.

 

1. Tomczyk S, Bennett NM, Stoecker C, et al. Use of 13-valent pneumococcal conjuage vaccine and 23-valent penumococcal polysaccharide vaccine among adults aged ≥65 years: recommendations of the Advisory Committe on Immunization Practices (ACIP). MMWR;2014:63: 822-25.

2. Bonten MJM, Huijts, M, Bolkenbaas C, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med 2015;372:1114-25.

 

What’s the latest on vaccination of adults 65 years old or over with conjugated pneumococcal vaccine?