Dr. John Manzella's Microbial World

Dr. John Manzella

So, say you are in the seventh grade and the assignment is to write a book report on a famous person. And say this is the late 1950s.  And maybe your favorite uncle was a doctor.  And maybe your uncle miraculously cured your mother’s “quinsy” (a painful abscess next to the tonsil)  a few years ago.  And maybe you were bowled over by that.  Well, you go to the school library and you look for a biography that engages your interest.  If you are John Manzella you read about Louis Pasteur and you think, “This guy is really cool!”  

A Children's Book

The French microbiologist (1822-1895) was the first to blame micro-organisms for spoiling of beer, wine, and milk.  He found that he could prevent this, and the economic losses it was causing, by heating the liquids.  Hence...pasteurization.  

In 1859 (the year of Darwin’s “On the Origin of Species”) he proved the “germ theory” by showing that a heat-sterilized liquid without further exposure to the air remains sterile (that is, life only comes from life).  He created vaccines for prevention of rabies and anthrax.  When he claimed that microbes spread diseases among humans the scientific community was skeptical.

Dr. Manzella didn’t tell me what grade he got on his book report (we will assume it was an A+) but it had a lasting impact.  In high school he liked biology and in medical school he, in his words, “became totally smitten with microbiology."  He attended Canisius College (like his uncle) and went to the SUNY University at Buffalo medical school.  He moved away from snow and went to  the University of North Carolina for residency training in internal medicine (and for basketball).  Two of his most impressive attendings were infectious disease specialists.  The emotional and intellectual connection could not be ignored and he took a fellowship in infectious diseases.  

He joined the York Hospital staff in 1979 and enjoyed his practice as he diagnosed and treated acute infections.  Infection control including rigorous hand-washing was stressed, and all was well.  But then something happened.  

Dr. Manzella faced a frightening situation as young men, men close in age to him, were struck with infections that were not supposed to occur in formerly-healthy individuals. The appearance of AIDS in 1981 forever changed his practice.  Several very intense years ensued as patient after patient suffered and died without explanation.  But in 1984 Dr. Gallo with the NIH and Professor Luc Montagnier from the Pasteur Institute in France (there’s Louis again!) shared in identifying the HIV virus causing AIDS, and there was hope.

However, there was no treatment for the underlying immune deficiency until 1987 when AZT was taken off the shelf and repurposed.  Dr. Manzella was hugely gratified that “something” could now be done.  As he cared for individuals with a chronic viral infection the long-term relationships changed him.  This was, he noted, the most singular experience he had in his life in medicine.  

After highly-active antiretroviral therapy became available in 1995 HIV truly became a “manageable” illness.   But where had this threat to society come from?  

Drop in Deaths after HAART

HIV/AIDS is a zoonosis, an infectious disease caused by an organism that changed and made the leap from a non-human animal host to a human victim.  The HIV virus evolved from a virus infecting chimpanzees in West-Central Africa.   

Zoonotic diseases can be due to viruses, bacteria, fungi, protists, parasites, worms, or misfolded proteins called prions.  They include scary things like rabies, Ebola, Zika, SARS,  MERS, Mad Cow, West Nile, plague, and bird flu, but also common food-borne salmonella and certain E. coli infections.  Zoonoses are fostered by our close connections with the natural world, with other living creatures (as exhaustively reported in David Quammen's "Spillover").

"Spillover" 

Lyme disease is another zoonosis endemic in our area and many of us know someone touched by it (or the fear of it).

One early summer day about fifteen years ago my husband had a circular red rash above his belt-line; he recalled no tick bite but it was itchy.  He had not been in the woods or around deer and he didn’t feel sick, but I said (with absolutely no experience to back it up), "You have Lyme disease!"  

He looked at a photo of the typical bull‘s-eye rash in one of his medical books and thought it dis not quite match.

Bull's eye rash of acute Lyme infection

But by the third day he was not feeling so great and I made an appointment for him to see Dr. Manzella.  He resisted (of course) but he listened and he was immediately put on doxycycline for three weeks.  No blood testing was done since he was seen early, before the diagnostic (IgM) antibodies would appear.   

Within 24 hours the spirochetes responsible for the sickness were being killed off and he developed fever, chills, shaking, and muscle pain of the so-called Jarisch-Herxheimer reaction, confirming Dr. Manzella’s clinical diagnosis.  We were relieved.  But my husband was still achy and tired for about two months.  Adequate treatment, we are told, almost always eradicates the disease, but it took time to feel better.  What if the rash is missed and treatment is delayed?  What then?  

I asked Dr. Manzella.  With early widespread infection, there may be nervous system involvement with headache, stiff neck, and facial paralysis.  There may be a heart arrhythmia, or acute arthritis (usually of the knee).  The neurologic and cardiac problems resolve with the standard treatment of two to four weeks of antibiotics.  But the joint symptoms may remain troublesome for a few years despite therapy, even though bacteria are no longer found in the joint.  Why do people then talk of chronic Lyme?     

Dr. Allen Steere (who was the first to identify Lyme disease in 1976) in a recent review notes that “In about 10% of patients with erythema migrans (the rash), and perhaps a higher percentage of patients with neurologic Lyme, fatigue, cognitive complaints, and musculoskeletal pain can persist for more than six months, or even years, after antibiotic therapy.”  He notes that placebo-controlled, randomized treatment trials of antibiotics (the gold standard) in patients with this syndrome have not demonstrated clinical benefit, and that evidence for the persistence of infection has not (to date) been found (Steere 2017).  

Dr. Manzella said that he is in agreement with these thoughts, conclusions also supported by the Infectious Disease Society of America.  He warns that prolonged antibiotic therapy has substantial risks including the development of resistant organisms, the nasty C. diff diarrheal syndrome, and indwelling catheter-related infections.  As Dr. Steere says, “Additional studies are needed to better understand the pathogenesis of persistent symptoms and to determine the best approaches for symptomatic relief.”  We don’t have all of the answers, and we need to be careful while we are looking for them.

(For example, a pending legal suit against the CDC argues that it suppressed a DNA test for Lyme that is many times more sensitive than the ELISA and Western Blot tests that are

currently used. The scientific community is still grappling with the limits of the technique and we need to be patient as we wait for the answer.)

So how did my husband get his Lyme?  In the garden.  We “knew” of "deer ticks" and the local deer problem, but it turns out that it was the black-legged tick carried by white-footed mice that transmitted the bug.  The busy housing construction in our neighborhood disturbed their natural habitats and they ended up invading our property.  Or did we invade theirs?  

Where will the next zoonosis come from? And will we be able to manage it? And who will be there to help us? 

Maybe somebody who is busily writing and stressing over a middle-school book report.  

By Anita Cherry 1/27/18

Addendum for those of us worried about ticks and acute Lyme disease (having weathered the expected zoonotic pandemic), the Infectious Disease Society of America, the American College of Rheumatology, and the American Academy of Neurology note:

We recommend that prophylactic antibiotic therapy be given only to adults and children within 72 hours of removal of an identified high-risk tick bite, but not for bites that are equivocal risk or low risk (strong recommendation, high-quality evidence). Comment: If a tick bite cannot be classified with a high level of certainty as a high-risk bite, a wait-and-watch approach is recommended. A tick bite is considered to be high-risk only if it meets the following three criteria: the tick bite was from (a) an identified Ixodes spp. vector species, (b) it occurred in a highly endemic area, and (c) the tick was attached for ≥36 hours. 

From: AAN/ACR/IDSA 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease. Clinical Infectious Diseases, Volume 72, Issue 1, 1 January 2021, Pages e1-e48. (A reliable and complete reference,)

AC and SC 4/12/24