Effectiveness and need for diphtheria, pertussis and tetanus vaccines

The most recent summary on the D/P/T vaccine was published by CDC in the MMWR of April 2018:

https://www.cdc.gov/mmwr/volumes/67/rr/pdfs/rr6702a1-H.pdf

There are graphs in the MMWR article showing how cases of all three diseases covered by the vaccine have changed over time.

These graphs show that there are almost no tetanus or diphtheria cases in the US now.  There were 2 diphtheria cases reported in the entire US between 2004 and 2016.*   While diphtheria can theoretically spread between people, it does not seem to do so in the US, presumably due to adequate herd immunity.

Tetanus is caused by bacteria that infect a wound or incision, form an abscess and produce a toxin that is a nerve poison.  Tetanus is a potentially life-threatening illness, but can usually be prevented by proper care of wounds.  There are about 30 cases and 1-6 deaths/year in the US from tetanus.* It does not spread from person to person.

Pertussis is a disease that looked like it, too was going to be nearly wiped out during the 1980s.  But the pertussis component of the (whole cell) DPT vaccine being used in those days was very toxic, causing many serious reactions and some deaths in infants and children.  So a newer, less toxic vaccine was introduced, DTaP.  This reduced the number of serious reactions, but the new vaccine was later discovered to be less effective at preventing pertussis than the old one. Per CDC:

"...reported rates of pertussis have been observed to be significantly lower among children who had started their vaccination series with DTP than among those who had started with DTaP (151,152)."

 In the approximately 23 years since its US introduction, pertussis cases have risen dramatically.  CDC says,

A growing body of evidence strongly suggests that the change in vaccines in the late 1990s from whole-cell pertussis vaccines to acellular pertussis vaccines in the childhood vaccine series has caused the age-specific increases in pertussis incidence among children aged 7–10 years observed in the mid-2000s because of waning immunity (Figure 2) (28–30).

The CDC decided to add another dose (the 6th dose) of a different DTaP vaccine (Tdap) at age 12, and uptake of this additional dose is at desired levels:

Since the introduction of Tdap in 2005, coverage with Tdap in adolescents aged 13–17 years has increased substantially, from 10.8% in 2006 to 86.4% in 2015 (33,34). Tdap coverage among adolescents has met the Healthy People 2020 target of 80% (35).

But Tdap vaccine did not provide the immunity boost CDC desired.  For the first year after a Tdap vaccination, effectiveness against pertussis is estimated about 67%, but by 4 years later effectiveness was only 9%.  The WHO says,

The disease, caused by the bacterium Bordetella pertussis, is endemic in all countries. Epidemic cycles have been occurring every 2 to 5 years (typically 3 to 4 years), even after the introduction of effective vaccination programmes and the achievement of high vaccination coverage.

In fact, it is possible that Tdap, or DTaP, actually increases susceptibility to pertussis.  According to pertussis expert Dr. James Cherry in 2019, because current acellular pertussis vaccines contain only a few antigens, "all children who were primed by DTaP vaccines will be more susceptible to pertussis throughout their lifetimes, and there is no easy way to decrease this increased lifetime susceptibility."   And according to pertussis studies performed by the FDA in baboons, those vaccinated with the current vaccine could still be infected with pertussis, and spread it for longer than baboons vaccinated with the older vaccine, and longer than unvaccinated baboons.

Most children who develop pertussis (80% in a Kaiser study) are fully vaccinated.  Herd immunity cannot be achieved due to poor effectiveness of current vaccines, even if 100% of the population is fully vaccinated.

Conclusion: 

Overall, children who lack DTap and Tdap vaccines pose no appreciable additional risk of infection to other children.  This is because there is virtually no risk of contracting diphtheria in the US, there is no person-to-person spread of tetanus, and current pertussis vaccines provide limited immunity but also the likelihood of enhanced spread.  These two effects likely balance out the transitory benefit of pertussis vaccination.


Meryl Nass, MD

  

*Centers for Disease Control and Prevention, Epidemiology and Prevention of Vaccine-Preventable Diseases, 13th Edition. Appendix E.

Babies get much higher doses of 

Diphtheria, Tetanus and Pertussis 

toxins in vaccines than adults!

	Tdap		DTaP
	Adults, Pregnant Women, 12 year olds		2, 4, 6 months 18 months 5 years
	Boostrix	Adacel	Infanrix	Daptacel
Tetanus Toxoid	5 Lf *	5 Lf	10 Lf	5 Lf
Diptheria Toxoid	2.5 Lf	2 Lf	25 Lf	15 Lf
Pertussis Toxin	8 mcg	2.5 mcg	25 mcg	10 mcg
FHA	8 mcg	5 mcg	25 mcg	5 mcg
Pertactin	2.5 mcg	3 mcg	8 mcg	3 mcg
Fimbriae protein    (types 2 & 3)	0	5 mcg	0	5 mcg
Aluminum Phosphate	-	+	-	+
Formaldehyde	+	+	+	+
Polysorbate 80	+	-	+	-
Aluminum Hydroxide	+	-	+	-
Glutaraldehyde	-	+	-	+
Phenoxyethanol	-	+	-	+
Pregnancy Category †	C	C	-	-

* Flocculating units

     ^† Risk not ruled out: "Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks."

    All information provided in the table comes directly from the label for each vaccine.  The label is a legal document specifying the use of the product, ingredients, and other information, which has been agreed through collaboration between the manufacturer and FDA/ 

   Table created by Meryl Nass, MD

FIGURE 2. Annual incidence* of pertussis, by age group — United States, 1990–2016

Sources: National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance System.

* Per 100,000 population.

Infection prevention

At this time, it appears that COVID-19 can spread by droplet, aerosol, fomites (objects) and through intestinal secretions.

The incubation period, it seems, may be up to 14 days.  Or much longer.  People who recover may still be able to spread virus--this is unclear (it depends on their viral load) but adds another problem to the attempt to contain the virus.

I am of the impression the virus cannot be contained.  Now that CDC and FDA will permit new tests to be used (as of late 2/28) and will stop restricting testing to those with a very strong China connection and compatible disease symptoms, we should get a better idea about asymptomatic cases and the period during which cases are contagious.

CDC has still failed to commit itself to precisely what disinfectants can be used to effectively decontaminate objects/surfaces. 

https://www.cdc.gov/coronavirus/2019-ncov/infection-control/control-recommendations.html

CDC evades the issue by recommending EPA-approved products. Then CDC provides a link to a page designed for manufacturers to help get their products approved by EPA.

https://www.epa.gov/pesticide-registration/guidance-registrants-process-making-claims-against-emerging-viral-pathogens

The information on decontamintion that is available is general, lacking the benefit of testing against COVID-19.

https://www.cdc.gov/hai/pdfs/resource-limited/environmental-cleaning-508.pdf#page30

This is unforgiveable.  For SARS, virus testing revealed the potential for virus to remain viable longer than a week under some environmental conditions. 

The main thing we can do is to know exactly where our hands are all the time and keep them away from all our mucus membranes.  I suggest people start to practice this.  Wash hands frequently with soap and water (proven to work) and use moisturizers as needed to avoid getting cracks in your hands.  Work from home if you can.

Consider using a plastic barrier (like the bags supplied by grocery stores for fruits and veggies-- for most of us who don't have an infinite supply of gloves) when touching surfaces used by others.

I think the WHO's recommendations are quite reasonable.  Except that 3 feet distance away from someone coughing/sneezing is not sufficient to avoid smaller droplets; CDC now says stay 6 feet away, and even that may not be enough for a powerful expulsion of virus.

https://www.who.int/docs/default-source/coronaviruse/getting-workplace-ready-for-covid-19.pdf

Meryl Nass, MD

Finally real COVID-19 testing to begin

From today's (2/29/20) NYT:

The U.S. Food and Drug Administration announced Saturday that it was authorizing American laboratories to develop their own coronavirus tests, which should significantly increase the country’s testing capacity.
The effect could be rapid. About 80 labs and private companies have applied for emergency approval for tests they have already created. If they have submitted evidence that the tests work, the labs and companies will be able to use them immediately, rather than wait for the F.D.A. to complete reviews and issue approvals.
“This action today reflects our public health commitment to addressing critical public health needs and rapidly responding and adapting to this dynamic and evolving situation,” the F.D.A.’s commissioner, Stephen M. Hahn, said in a statement.
Experts have been frustrated with the limited availability of coronavirus tests in the U.S., which until now could only be provided by the Centers for Disease Control and Prevention. Broader testing will enable more rapid detection and isolation of people who have the coronavirus to help contain the spread of disease.

Why did this take so long?

What about antibody tests?

From the Jerusalem Post:

The US Centers for Disease Control and Prevention (CDC) may have harmed the country's ability to track and detect the spread of the COVID-19 disease due to a series of missteps, including refusing to use the tests recommended by the World Health Organization (WHO), according to ProPublica. 

As the virus began to spread, the CDC decided to start creating its own, more complicated test instead of using the test guidelines provided by the WHO. The test was made to check for a variety of different viruses. When the test was sent to labs across the country, it didn't work and falsely flagged the presence of other viruses in harmless samples.

Update:  From the WaPo of April 5, a detailed chronology of how our two public health agencies totally screwed up testing for Coronavirus in the US.

Good advice on infection prevention from the WHO, and a great deal of caution

I think all the advice provided here (dated today 2/27/20) is sound, and is not alarmist. This virus has spread remarkably quickly, frequently triggers lethal illness, and there has not been anything like it since the 1918 flu.   COVID-19 must be spreading within the US in ways we don't know yet.  The lack of available testing massively exacerbates this problem.

WHO has issued simple but practical guidelines for how to do the best we can given the current situation, even if people lack access to masks, gloves, etc.

https://www.who.int/docs/default-source/coronaviruse/getting-workplace-ready-for-covid-19.pdf

The only WHO advice that I am not sure is correct is the advice to use hand sanitizer (generally 70% alcohol).  I have not seen any country guidance that says alcohol sanitizer has been tested on COVID-19 and works.  The only decontaminant that US and UK authorities recommended is bleach, at a specified dilution.  Be aware that viral killing might require more than a quick swipe with a "wipe" that has been wet with dilute bleach.  So far we have not been told the details on how to effectively decontaminate surfaces, although testing should have been done by now.

I should note that while China has been widely criticized for hiding or underreporting COVID cases, the US is doing the same thing by withholding testing from all but a tiny number of potential patients.  Furthermore, lack of clear identification of potential cases opens the door to massive spread, as noted in this piece today by Helen Branswell of STAT:

... Eventually, more than 10 days after she went into hospital, the CDC agreed she could be tested. Dozens of health workers who may have come into contact with her at NorthBay VacaValley Hospital, in Vacaville, Calif., are now being monitored.California Gov. Gavin Newsom was critical of the testing debacle in a press conference on Thursday. His state has only 200 kits to test for the new coronavirus, he said.
“Testing protocols have been a point of frustration for many of us,” Newsom said. He added that, based on conversations with the CDC, states have been informed new protocols are coming and they have been promised an “exponentially” increased capacity to test.
Indeed, on Thursday the CDC announced a new testing protocol that will greatly expand the number of people who should be tested.
Requests for comment from the CDC on Thursday went unanswered... 

Here's what we need to know about COVID-19 testing

The problem of highly restricted testing in the US

The COVID-19 virus is quite deadly (mortality appears to be between 2 and 10% as discussed in my last post) though since we don't know how many asymptomatic or mildly symptomatic cases there are, we still can't be sure of this.

Why don't we know the number of cases?  In the US, so far you can't order the PCR (or any other test) without CDC approval.  Approval is contingent upon meeting a high bar, including known exposure.

Thus we are missing lots of cases, who are not being asked to self-quarantine if the cases are mild, and are thus likely to spread disease.

Why aren't we testing broadly to get a sense of actual case numbers?  The best guess is that CDC does not trust its own test, and that by restricting testing to those who are almost certainly positive to start with, they will make fewer diagnostic errors.  

Tests kits were sent to state labs by CDC, then recalled, with the excuse that there was a problem with a "reagent".  A reagent could be any component of the test. CDC has not replaced the reagent or the test kits.  States are begging for them.

Dr. Messonier (head of Vaccines and Respiratory Diseases at CDC) says CDC is keeping up with testing, there is no backlog, they can test 400 samples together, and turnaround is overnight.  That should clue you in that relatively few are being tested.

Some other countries are reporting large numbers of new cases daily.  Do they have better tests?  Has any journalist looked into the relative sensitivity and specificity of tests being used around the world?

PCR is a rapid screening test, which when positive almost always connotes a true positive.  Negatives may actually be positive if the sample does not contain enough virus or is collected or transported incorrectly.

What is also needed are viral culture tests, which could theoretically pick up cases missed by PCR.  Such cultures might also be used to test the effects of drugs on the virus.  What work is being done to develop COVID  viral culture techniques?  Might such tests already exist, since they would probably be very similar to those for SARS and MERS?

Update March 30:  FDA says it is not their fault that tests were not available for novel coronavirus.  Between the lines, I am reading, "It was the CDC, not us, and we accept none of their blame."

Update Feb. 27:  Australia developed viral cultures; so has CDC:

Akst J. Australian Lab Cultures New Coronavirus as Infections Climb. The Scientist. https://www.the-scientist.com/news-opinion/australian-lab-cultures-new-coronavirus-as-infections-climb-67031. 
CDC has grown the COVID-19 virus in cell culture, which is necessary for further studies, including for additional genetic characterization. The cell-grown virus was sent to NIH’s BEI Resources Repository for use by the broad scientific community.

If there is a bat or other animal model for this virus, so much the better for testing drugs that might show efficacy against COVID-19.  What work is being done on developing or using animal models?

I assume one gains immunity after infection with COVID-19, which usually occurs after infections, but not always.  The next test needed is an antibody or T-cell test that will accurately identify immunity to the virus.  People who have recovered should be studied to identify markers of immunity.  Then, we will be able to identify those who can safely care for infected individuals without catching the disease themselves.

Let me reiterate:  with the limited testing now being performed in the US, we are definitely missing many cases, and missing the opportunity to appropriately use quarantines to limit the rapidity of spread.  Slowing spread is critical to producing enough masks, gowns, ventilators, ECMO machines, training hospital staff, building hospitals just for COVID-19 cases, etc.   

We need an accurate test, probably a PCR test, NOW.  What is holding it up?

Update Feb. 27, from WHO:

Ensuring ongoing test availability. WHO has procured a commercial assay (manufactured under ISO:13485) with strong performance data and shipped to over 150 laboratories globally as an interim measure for Member States requesting support. The main goal is to strengthen global diagnostic capacity for detection of the COVID-19 virus. Support is now also provided to ensure the quality of testing through the implementation of an External Quality Assurance mechanism.

Update March 27:  China has a monkey animal model of disease as well as antibody tests. 
Update:  New CDC Testing Criteria, issued 2/27
Criteria to Guide Evaluation of PUI for COVID-19

Local health departments, in consultation with clinicians, should determine whether a patient is a PUI for COVID-2019. The CDC clinical criteria for COVID-19 PUIs have been developed based on available information about this novel virus, as well as what is known about Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). These criteria are subject to change as additional information becomes available.

Clinical features and epidemiologic risk

Clinical Features	&	Epidemiologic Risk
Fever1 or signs/symptoms of lower respiratory illness (e.g. cough or shortness of breath)	AND	Any person, including health care workers2, who has had close contact3with a laboratory-confirmed4 COVID-19 patient within 14 days of symptom onset
Fever1 and signs/symptoms of a lower respiratory illness (e.g., cough or shortness of breath) requiring hospitalization	AND	A history of travel from affected geographic areas5 (see below) within 14 days of symptom onset
Fever1 with severe acute lower respiratory illness (e.g., pneumonia, ARDS) requiring hospitalization4 and without alternative explanatory diagnosis (e.g., influenza)6	AND	No source of exposure has been identified

Update 2/28:  Initial CDC testing info and interpretation protocol:

2019-nCoV rRT-PCR Diagnostic Panel Results Interpretation

2019 nCoV_N1	2019 nCoV_N2	2019 nCoV_N3	RP	Result Interpretationa
+	+	+	±	2019-nCoV detected
If only one, or two, of three targets is positive			±	Inconclusive Result
–	–	–	+	2019-nCoV not detected
–	–	–	–	Invalid Result

Assay Limitations

• Analysts should be trained and familiar with testing procedures and interpretation of results prior to performing the assay.
• A false negative result may occur if inadequate numbers of organisms are present in the specimen due to improper collection, transport or handling.
• RNA viruses in particular show substantial genetic variability. Although efforts were made to design rRT-PCR assays to conserved regions of the viral genomes, variability resulting in mis-matches between the primers and probes and the target sequences can result in diminished assay performance and possible false negative results.

Update 2/28:  NPR reports that China and Singapore have an antibody test they are using to detect recovered or asymptomatic cases.  ZeroHedge reports that CDC has only tested a total of 466 people in the US, as of past 2 days, while UK has tested 6,000.  If so, CDC needs to get off its behind and get a reliable test and make it available to all labs in the US with rtPCR capability.  Who knows how much community spread is ongoing when CDC refused to test people unless they had a close association with China and were sick with an illness consistent with COVID.

Is Trump aware that the head of the COVID response at CDC, Lisa Messonier, is the sister of Rod Rosenstein, the Deputy AG who suggested secretly recording Trump?

CORONA VIRUS update: Fomites, PPE, Mortality

Fomites  

These are inanimate objects like doorknobs, shared computer keyboards, surfaces where droplets from coughs and sneezes land, or where hands have touched, which may transmit the virus.

Questions that the authorities should be making every attempt to answer include the following.  

a)  What % of infections are transmitted via fomites?  (In other words, how careful should you be when touching things, including objects you cannot avoid touching, like subway turnstiles, where virus may be present?)  The danger is touching a contaminated surface, then touching your eye, nose or mouth (mucous membranes) with enough live virus to cause infection.  Good patient histories and testing of COVID survival under different environmental conditions should shed more light on this.

b)  How many viral particles are needed to cause infection?  (The authorities claim COVID was transmitted from animals.  If so, there should be an animal model of infection, enabling lab testing of infectious dose, modes of transmission, etc.)

c)  How long does this virus live on objects, under different conditions of temperature, humidity, and surface type?  This can be easily tested, and CDC should stop guessing..

d)  What kills this virus on surfaces?  Alcohol hand rub (~70%) works to destroy some viruses but not others.  It is unreliable for Norovirus, for example.  Is coronavirus killed when alcohol rub is used for, say, 20 seconds on hands?  Why hasn't CDC given us this information?  

How are hospital rooms being decontaminated effectively in China?  

Personal protective equipment 

The photos of Chinese doctors in full gear worry me more than anything.  They are dressed in maximal containment suits--identical to what would be used if the patients had Ebola.  While it is said that COVID is less contagious than SARS, which China had a lot of experience with, the PPE suits suggest they believe it is extremely contagious.

Mortality

According to the South China Post, where the photo below also came from, the mortality rate is actually 10%.  This article explains why estimates of mortality rates for COVID-19 could be too high or too low at this point. 

Let me explain.  There are 20,833 recovered cases, and 2360 deaths.  Another 55,000 people are still being treated.  So adding the number of recovered plus number of deaths you have 23, 193 people whose illness is over.  Of this total, 90% recovered and 10% died.  I don't know if these numbers are accurate, but they are what has been reported from China.  They are not encouraging.  This looks to me like the repeat of the 1918 flu (except it is a coronavirus, not influenza virus).  Hopefully I will be proven wrong as we learn more, but the degree of rapid spread and the potential for prolonged incubation periods (suggesting quarantines are of limited value), the lack of effective drug treatment, and the mortality rate suggest otherwise.

We are unlikely to have enough masks and gear to deal with it.  Best thing to do right now is to practice not touching your face with your hands, and to become aware of what your hands touch, and how to touch things in ways that place yourself at less risk.  In other words, by a) using gloves, b) handwashing before touching your mucus membranes, c) perhaps using napkins or paper towels or other disposable items to shield your hands in public areas like buses, subways, toilets to avoid contamination.  Whether it will be possible to maintain a minimum 6 feet of distance between yourself and someone who is coughing or sneezing is another question. 

Corona virus epidemic

January 31, 2020

I keep being asked about the coronavirus, and have been noncommittal about it, because there was not a lot of information to go on.

But now there is more information, so I will say a little.

1.  Anthony Fauci, head of the NIH's infectious disease branch, said the death rate is 1-2% and that this may be compared to an average influenza virus, which has a mortality rate of 0.1%.

If his numbers are based on reported estimates that 100,000 are infected and 1500 have died, his mortality estimate is too low.  You have to look at one whole group that was infected at the same time, then look at the total number of them who died, after the rest have recovered, to estimate mortality.  I am not aware of good stats on this yet.

2.  I heard the R zero number (an estimate of how many people are, on average, infected by a single person with coronavirus) is 3-4.  If so, the coronavirus is less infectious than measles and roughly as infectious as many other infections.

3.  What is the mechanism by which the virus kills?  This needs to be answered in order to devise effective treatments.

A Chinese article published this week suggested that cytokine levels are higher in coronavirus patients than controls.  But are patients dying from cytokine storm?  This was not revealed.

During the 2009 swine flu pandemic, pregnant women in Australia were reported to be dying as a result of thick, infected mucus plugging their airways, preventing gas exchange in the lungs.  (Gas exchange involves carbon dioxide leaving the blood and oxygen entering the blood as it traverses the lungs.)

While there was not much media attention given to the topic, the use of ECMO to temporarily fill in for the lungs, until the body can repair itself, saved a number of lives then.  ECMO stands for extracorporeal membrane oxygenation, in other words, oxygenating the blood using a machine.

There are not many of these machines around, likely only a few in every state.  If patients with good lungs are dying due to temporary respiratory failure, then ECMO might be a lifesaver.

Here is a list of ECMO sites.  822 centers with the devices are listed.


UPDATE Feb 8:  from a Straits Times interview with a doctor of acute medicine at Wuhan University south central hospital:

"How do you treat serious and life-threatening cases?

Peng: For serious and life-threatening cases, our main approach is to provide oxygen, high-volume oxygen. At first noninvasive machine-pumped oxygen, followed by intubated oxygen if conditions worsen. For life-threatening cases, we use Ecmo (extracorporeal membrane oxygenation, or pumping the patient's blood through an artificial lung machine). In four cases, we applied Ecmo to rescue patients from the verge of death."

4.  Is this novel Coronavirus something that escaped from a lab, or perhaps was deliberately released?  You know as much as I do about that one.  If sufficient information is available in the future, I will comment on it then.

So how good is the flu shot really?/ Clinical Infectious Disease

CDC says flu vaccines prevent flu, on average 40% of the time, but even if you do get flu, the vaccine makes it less severe.  But when these two claims were tested in Australia, neither was found to be true.  The Australian study found  that (in 17 hospitals over 7 recent flu seasons) there was no reduction in flu symptom severity in those who had been vaccinated versus those who had not.

The study also found, using a case-control design, that the vaccine averaged 31% effectiveness at preventing the flu.  Earlier flu studies have been rightly criticized for ignoring the "healthy vaccinee"  effect.  The healthy vaccinee effect refers to the fact that, overall, elders who receive flu vaccine in the US are a healthier group than elders who do not receive flu vaccine... possibly because their doctors felt they were too frail to risk a side effect.  If the authors did not take this factor into account (and the whole article is behind a paywall so I could not read the details) then the actual efficacy might be considerably lower.

Influenza Vaccine Effectiveness against influenza-related mortality in Australian hospitalized patients:  a propensity score analysis.

Monica L Nation, Robert Moss, Matthew J Spittal, Tom Kotsimbos, Paul M Kelly, Allen C Cheng on behalf of the FluCAN Investigators

Clinical Infectious Diseases,  https://doi.org/10.1093/cid/ciz1238

Published:  06 January 2020

Background

Data on influenza vaccine effectiveness (IVE) against mortality is limited, with no Australian data to guide vaccine uptake. We aimed to assess IVE against influenza-related mortality in Australian hospitalized patients; assess residual confounding in the association between influenza vaccination and mortality; and assess whether influenza vaccination reduces the severity of influenza illness.

Methods

Data were collected between 2010–2017 from a national Australian hospital-based sentinel surveillance system using a case-control design. Adults and children admitted to the 17 study hospitals with acute respiratory symptoms were tested for influenza using nucleic acid testing; all eligible test-positive cases were included, and a subset of test-negative controls. Propensity score analysis and multivariable logistic regression were used to determine the adjusted Odds Ratio (aOR) of vaccination, with IVE= 1–aOR x 100%. Residual confounding was assessed by examining mortality in controls.

Results

Over eight seasons, 14038 patients were admitted with laboratory-confirmed influenza. The primary analysis included 9298 cases and 6451 controls, with 194 cases and 136 controls dying during hospitalization. Vaccination was associated with a 31% (95%CI: 3–51%, p=0.033) reduction in influenza-related mortality, with similar estimates in the National Immunisation Program target group. Residual confounding was identified in patients ≥65 years old (aOR: 1.92 (95%CI: 1.06–3.46); p=0.031). There was no evidence that vaccination reduced the severity of influenza illness (aOR: 1.07 (95%CI: 0.76–1.50); p=0.713).

Conclusions

Influenza vaccination is associated with a moderate reduction in influenza-related mortality. This finding reinforces the utility of the Australian vaccination program in protecting those most at risk of influenza-related deaths.