Vital Infections: Is There A Benefit To Infectious Disease?
So much effort of public health programs is spent on the prevention of infectious diseases. The goal to prevent and even eradicate infectious germs, while it may sound noble and heroic, could also be fundamentally misguided.
For one, there’s little attention placed on the short and long term consequences of “preventing” these infections. (Remember throughout history the precedent has always been the various manmade cures and treatments were worse than the disease itself.)
For two, why not spend more energy examining the particular set of conditions that make some “hosts” more attractive than others, ie. malnutrition and other modifiable risk factors? Why not focus on individual patient-specific care, rather than this one-size-fits-all regiment?
Third, this whole goal gets complicated when the same germ can live in a healthy person and cause no disease, or if it does, it may serve some benefit in the long run. Upsetting the balance within the ecosystem, microbiome, environment due to bias, fear, or misunderstanding can result in worse outcomes in the long run. We need to learn from our mistakes as a society and culture.
Good or Bad, or Neither?
There is a whole other side of microbes that has been unfolding for the last several decades. For example, the word bacteria obviously had a bad connotation because researchers had to coin the term good bacteria in the year 2000 just to try to talk about the beneficial traits of bacteria. Seriously, the term was first mentioned in Pubmed in 2000. Can you believe that? That’s when the microbiome research really started attracting scientific attention. It would turn out that bacteria has so many beneficial purposes and functions for the human body, including keeping us healthy, and reducing our overall risk of numerous diseases and conditions, allergies, asthma, cancer, autism and more.
The oddest thing to me is that supposedly pathogenic bacteria can live in a healthy human body causing no problems, no symptoms of disease. For example, Neisseria meningitidis is a human commensal bacteria that lives in the upper respiratory tract without causing disease. At any given time it’s carried in the nasopharynx of between 10% to 35% of adults. This same bacteria can cause meningitis and other forms of meningococcal disease, including sepsis, very rarely. So then the question is: what are the unique set of conditions that enable this common bacteria to become invasive when it rarely does? Rather than vaccinate everyone against every strain or type of meningitis, what if we paid closer attention to the triggers of the rare event?
Meningitis as a complication of tonsillectomy
We present a case of meningitis complicating a tonsillectomy procedure, in a 7-year-old girl.
Meningococcemia Following Tonsillectomy
A 22-y-old male developed fever, arthralgias and skin rash 2 d after tonsillectomy. Blood culture grew Neisseria meningitidis.
We found that ear, nose and throat surgery had an 11-fold, and neurosurgery a sevenfold, increased risk compared to the reference group in the first 10 days following surgery. Streptococcus pneumoniae was the pathogen most often involved.
Aseptic meningitis after vaccination of the BNT162b2 mRNA COVID-19 vaccine
The unbalanced distribution of reports of meningitis in the first 6 weeks after vaccination is suggestive of the possibility that some cases may be triggered by vaccination.
Neisseria meningitidis on Sinonasal Culture for Sinusitis: A Case Series and Literature Review
Four patients developed N. meningitidis sinusitis. Case report writes they were not “appropriately vaccinated” according to the CDC, however, I’d like to point out all 4 cases had at least one dose of an anti-meningitis vaccine: case 1 had 1 MenB dose; case 2 had 1 MenACWY dose; case 3 had 3 doses of MenACWY; case 4 had 2 doses of MenACWY and 1 dose of MenB. And they still all had a sinus infection caused my Neisseria Meningititis.
Could it be that humans are creating conditions that allow microbes to become invasive? And for some reason the germ itself is being blamed for something that is technically due to human error? This phenomenon reminds me of what happened in the late 1940s and 1950s with the sudden uptick of paralytic poliomyelitis which in and of itself is not a contagious, communicable disease, but rather the rare, fewer than 1% of all polio infections, chance, wayward response of the poliovirus. By definition, there should not be “outbreaks” of such a chance event, unless the trigger is also shared by the at risk group.
It will become common knowledge soon that we were wrong about viruses, too. There are already some mainstream stories about it, for example how the adaptation of the human placenta is probably the result of an ancient retroviral infection. And how part of our human genome is of viral original.
Here are some things you may not have known about infectious diseases:
Many Viral Infections Are Asymptomatic
While we often equate viral infections with symptoms of disease, a good portion of the time infections are asymptomatic. We just don’t know or realize this because we aren’t usually testing asymptomatic people. But when we do, we find all sorts of evidence that healthy, asymptomatic people have evidence of prior exposure to viral infections, despite no record or memory of the infection.
For example, a 2016 meta-analysis sought to identify the fraction of influenza infections which are asymptomatic, meaning an infection with no signs or symptoms.
In outbreak investigations where infections were virologically confirmed, we found a pooled mean of 16% (95% CI: 13%, 19%) of infections were asymptomatic, whereas in longitudinal studies in which infections were identified using serology the point estimates of the asymptomatic fraction adjusted for illness from other causes fell in the range 65%–85%.
A study in Vietnam did include both of these strategies, estimating the asymptomatic fraction as 45% (17%–77%) in outbreak investigations versus 86% (82%–89%) in the longitudinal serologic analysis.
It makes sense that a large portion of influenza infections every year would be asymptomatic when you figure in that a person with some prior immunity would have some immunological memory which would prevent a full-blown infection.
But other viruses seem to work in the same way. For example: varicella zoster, the virus that causes chickenpox, is one of the viruses that after infection remain dormant in the body, specifically the dorsal root ganglia of the brain, and may reactivate later as shingles (herpes zoster) during times of stress.
You may think that since we vaccinate for wild chickenpox now and have since 1996, that children would no longer have latent wild varicella virus in their brain. We would assume the vaccine prevents the latency of the wild virus. But we were wrong. This case series reveals otherwise. Researchers examined brain specimens from 10 children who died suddenly between November 2008 and May 2009 for the presence of vaccine or wild type varicella zoster. The 3 children who were under the age of 1 had no history of vaccination or varicella infection, and had no evidence of varicella virus DNA/RNA in their ganglia.
However, of the 7 older children, ranging from almost 2 years to 10 years of age, 6 had history of vaccination, and none had history of varicella infection: yet all 7 had varicella virus in their ganglia.
The most surprising part was that 6 of the 7 cases had wild varicella zoster DNA or RNA in their brain, not vaccine strain.
Authors concluded:
The results of our study of autopsied children were surprising, not only in that many ganglia on both sides of the body were found to contain latent VZV, but also because the virus was overwhelmingly WT, despite vaccination and the absence of a history of varicella. These observations suggest that although varicella vaccine may successfully prevent clinical varicella, it does not necessarily prevent subclinical infection or superinfection of individuals with WT VZV or the ability of WT VZV to establish latency. Presumably, infection with WT VZV was suppressed sufficiently by vaccine-derived immunity for the vaccinee to remain asymptomatic, but nevertheless allowed WT VZV to disseminate, possibly via viremia, and replace vOka.
We see the same pattern with measles. At least 23% of nonimmunized individuals had evidence of measles genome by RT-PCR test, despite being asymptomatic and healthy.
This 2020 study found serological evidence of measles infection in completely unvaccinated populations, with no record of disease. This study of children 6-59 months of age in the Democratic Republic of Congo remarkably found that 40% of the unvaccinated children were seropositive for measles despite no history of measles infection.
So given that viruses circulate regardless of vaccinations, perhaps there is something else to understand about these childhood infections? In the absence of malnutrition, is there any observed benefit to these tiny microbes for the human host?
Benefits of Childhood Infectious Diseases
Immunity
The first obvious benefit is some kind of immunity. An infection results in immunity to the specific microbe, but also to related microbes. This cross-reactivity is what Edward Jenner saw with the cowpox vaccine he created. Each subsequent exposure to the microbe results in a “boost” of that immunity.
But besides protection from having the same illness twice, there may be other benefits as well…such as resetting or recalibrating the immune system, protecting from allergies, asthma, cancer, and even causing a spontaneous remission of disease. And of course protecting our newborns by transferring passive immunity to them through the placenta and our breastmilk.
Glioma
A 2016 international case-control study sought to understand the association between history of chickenpox and glioma risk, as prior research has consistently found an inverse relationship between chickenpox infection and glioma, a brain tumor.
Using two-stage random-effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65-0.96). Furthermore, the protective effect of chickenpox was stronger for high-grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental.
A 2005 study examined whether viruses or immunologic factors might cause or prevent human brain cancer, building on previous findings that statistically significant inverse associations of adult glioma with history of chickenpox and immunoglobulin G antibodies to varicella-zoster virus have been reported.
Cases were less likely than controls to report a history of chickenpox (for self-reported cases vs. controls: the age-, gender-, and ethnicity-adjusted odds ratio = 0.59, 95% confidence interval: 0.40, 0.86)
Cardiovascular
A 2015 Japanese paper examined whether exposure to infections during childhood could decrease risk of atherosclerotic cardiovascular disease. Women and men both benefited with lower risks for atherosclerotic cardiovascular disease, myocardial infarction (heart attack) and stroke.
Measles and mumps, especially in case of both infections, were associated with lower risks of mortality from atherosclerotic CVD.
Leukemia
A 2013 Italian study aimed at investigating the association between common childhood infectious diseases (measles, chickenpox, rubella, mumps and pertussis) and the risk of developing leukaemia in an adult population.
A protective effect of at least one infection (OR = 0.66, 95% CI: 0.45-0.97), measles (OR = 0.57, 95% CI: 0.39-0.82) and pertussis (OR = 0.66, 95% CI: 0.45-0.98) was observed for chronic lymphoid leukaemia (CLL). The number of infections was strongly inversely associated with the risk of CLL (p = 0.002, test for trend). With regard to the other types of leukaemia, only a protective effect of pertussis was observed for AML (OR = 0.52, 95% CI: 0.32-0.87). Our results pointed out a protective role of childhood infectious diseases on the risk of CLL in adults. Although a specific antioncogenic effect of some infectious disease, especially measles, cannot be ruled out, the observed decrease of risk with increasing number of infections suggests that a more general “hygiene hypothesis” could be the most likely explanation of the detected association. The protective role of pertussis remains to be elucidated.
Allergy / Asthma
A 2012 paper examining children in New York between January 2000 and December 2007 described how wild-type varicella zoster infection up to 8 years of age protects against atopic dermatitis, asthma, allergic conjunctivitis, and cases with history of disease had decreased total serum IgE levels compared to varicella vaccine recipients.
The results of this study suggest that children with WTVZV are less likely to have allergic sensitization, have persistently lower total serum IgE levels, and decreased numbers of circulating lymphocytes, monocytes, and basophils. These findings may help explain the protective role of WTVZV against AD and asthma. WTVZV-mediated suppression of IgE production may be translatable into novel therapeutic strategies for atopic disorders.
Cancer
A 1998 study performed in Switzlerland investigated the hypothesis that febrile infectious childhood diseases (FICDs) are associated with a lower cancer risk in adulthood, since biographical considerations are of great importance in anthroposophic medicine.
The strongest associations were found between patients with non-breast cancers and rubella respectively chickenpox. A strong association was also found with the overall number of FICD both ‘classical’ (measles, mumps, rubella, pertussis, scarlet-fever and chickenpox) and ‘other’.
Our retrospective study showed a significant association between FICD and the risk of developing cancer. The number of FICD decreased the cancer risk, in particular for non-breast cancers.
Coronary Heart Disease
A 2007 study aimed to explore whether exposure to microbial agents determines the prevalence of acute coronary events. The paper found that while enterovirus (EV), herpes simplex virus (HSV) and Chlamydia pneumoniae are associated with increased risk for coronary heart disease (CHD), classic childhood contagious diseases (varicella, scarlet fever, measles, rubella, mononucleosis and mumps) (n=6) had a protecting effect against CHD (odds ratio 0.86, p=0.013).
The risk for acute coronary events decreased significantly with increasing number of childhood contagious diseases (p=0.007).
Protection from infections usually suffered during the childhood before the era of MMR vaccination may predispose the individual to CHD.
Hodgkin’s lymphoma
A 2004 paper sought to examine the current role of childhood social environment, specifically the markers of markers of delayed infection with common childhood pathogens, in the development of Hodgkin’s lymphoma in young adults.
The paper found:
A novel association was detected between attendance of nursery school or day care and reduced risk of Hodgkin’s lymphoma among individuals ages 15 to 54 years. The odds ratio (95% confidence interval) for having attended preschool for at least 1 year was 0.64 (0.45-0.92).
And concluded:
Early exposure to other children at nursery school and day care seems to decrease the risk of Hodgkin’s lymphoma in young adults, most likely by facilitating childhood exposure to common infections and promoting maturation of cellular immunity.
Spontaneous Remission
There are amazing case reports of spontaneous remissions of various conditions. I find this totally fascinating:
Measles induced remission of psoriasis
A 6-year-old girl suffering from severe psoriasis had been treated unsuccessfully by various conventional methods. She developed measles and, on recovery from measles, the psoriasis soon cleared up and now, 6 months later, she still has had no further recurrence. The basic defect in psoriasis, basal cell hyperplasia and defective keratinization, may well be immunologically mediated. Measles virus, by its immunosuppressive effect can lead to remission of psoriasis.
Influenza A (H1N1) virus induced long-term remission in a refractory acute myeloid leukaemia
There have been reports of haematological cancer patients achieving spontaneous remission after being infected with the influenza A or SARS-COV-2 virus. Here, we present the first case of long-term complete remission (CR) induced by influenza A (IAV, H1N1 subtype) in a refractory AML patient and have functionally validated this finding in two different animal disease models. We observed a significant increase in the proportion of helper T cells in the patient after IAV infection. The levels of cytokines, including IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α, were higher in IAV-infected patients compared with control groups. These findings indicate that the anti-tumour effects induced by IAV are closely related to the modification of the immune response. Our study provides new evidence of the anti-tumour effects of IAV from a clinical practice perspective.
Varicella causing remission of Cushing’s disease
An 18-year-old male with Cushing’s disease presented with generalised skin eruptions and backache. He was diagnosed with varicella infection. During the course of the illness, he developed persistent vomiting. Hormonal evaluation suggested adrenal insufficiency. MRI of brain showed features of pituitary apoplexy. Initially, he required hydrocortisone replacement. Later on his hypothalamic-pituitary-adrenal axis recovered and he is currently asymptomatic without any treatment.
A Case of Nephrotic Syndrome that Resolved with Influenza B Infection
This case report describes an 18 year old woman who experienced spontaneous remission of nephrotic syndrome (INS) within 2 weeks of an influenza b infection.
Spontaneous improvement of intractable epileptic seizures following acute viral infections
This case series out of Japan sent surveys to pediatric neurologists who cared for children with epilepsy, and they found:
…seizures disappeared within 2 weeks subsequent to viral infections such as, exanthema subitum, rotavirus colitis, measles and mumps. The disappearance of intractable epileptic seizures following acute viral infections might be related to the inflammatory processes or the increased levels of antibodies after viral infections.
There are several studies that look at the phenomenon that autism symptoms improve during febrile illness, or during a fever.
Data-driven dissection of the fever effect in autism spectrum disorder
In conclusion, there are many unknowns when it comes to how viral infections affect and even benefit the human body. There may be reasons underpinning the circulation of viruses through the human population that have certain immune benefitting and recalibrating functions which aid in the health and maintenance of our bodies. It makes sense that anything that biologically evolved alongside, both inside and outside the human body would have a symbiotic relationship with us–a relationship that is not known until it’s been removed.
