|CHRONICLES OF MEDICINE - FRONTIERS IN COMMUNICABLE DISEASES
|Year : 2016 | Volume
| Issue : 3 | Page : 153-161
Enteric fever: Resurrecting the epidemiologic footprints
Yatish Agarwal1, Dipendra K Gupta2, Ravindra S Sethi3
1 Department of Radiodiagnosis, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
2 Department of Hematology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
3 Department of Nuclear Medicine, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
|Date of Web Publication||27-Feb-2017|
Prof. Yatish Agarwal
F-18 Green Park Main, New Delhi - 110 016
Source of Support: None, Conflict of Interest: None
A genetically monomorphic, human-restricted bacterial pathogen that causes 21 million cases of typhoid fever and 200,000 deaths each year, predominantly in southern Asia, Africa, and South America, Salmonella enterica subspecies serovar Typhi has a long and colored evolutionary history. Based on studies relating to the population genetic structure of Typhi by mutation discovery within 200 gene fragments from a globally representative strain collection of 105 strains, researchers have drawn up a phylogenetic tree for Salmonella typhi. It is surmised that the first ancestral strains of the bacteria appeared somewhere in Indonesia between 43000 and 10000BC. That despite the passage of millennia of years since the setting up of its first footprints on Mother Earth, Salmonella typhi has persisted as a highly homogeneous tribe, may have much to do with the asymptomatic carrier state in humans that they can dig into to survive. This process of neutral evolution and genetic buffering in Typhi coupled with the relatively more recent adaptive evolution, a sequel of rapid transmission of phenotypic changes through acute infections, has led to production of its antibiotic-resistant strains has made the task of public health physicians even more daunting and complex. These chronicles dwell on the historical truths and multihued accounts relating to the epidemiology of a disease that once changed the course of European history, battles, and wars, and, narrates, how, over time, the bacteriologists, pharmacologists, and physicians of the times came up trumps against the slayer bacteria.
Keywords: Adaptive evolution, antibiotic resistance, carrier, epidemiology, evolutionary history, genetic buffering, neutral evolution, vaccines, Salmonella enterica serovar Typhi, water-borne transmission
|How to cite this article:|
Agarwal Y, Gupta DK, Sethi RS. Enteric fever: Resurrecting the epidemiologic footprints. Astrocyte 2016;3:153-61
The “big daddy” strain
Rooted in elemental research that focused on the phylogenetic tree of Salmonella More Details Typhi, international research teams from Max Planck Institute, the Institut Pasteur, and the Wellcome Trust Sanger Institute have identified an ancestral strain of Salmonella Typhi, from which all current strains have descended. These study teams have deduced that this big daddy strain appeared sometime between 43000 and 10000BC once humans had migrated outside Africa, but before the settling of the Neolithic period. Based on the resurrected genetic footprints of the bacteria, researchers speculate that Typhi first evolved in Indonesia before it spread to different parts of the world. These isolates can be identified on the basis of the z66 flagellar antigen. Representative bacteria of this ancestral strain are still found today on several continents, suggesting that the bacterium would originally have persisted within small populations of hunter-gatherers.
The great Athens outbreak
The most devastating typhoid epidemic to hit Europe occurred around 430–424BC when the disease wiped out one-third of the population of Athens in ancient Greece and killed their leader Pericles. Recent DNA studies, conducted in 2006, corroborate this dramatic occurrence.
The epidemic changed the course of European history. With it, the Golden Age of Pericles ended, and the nucleus of power shifted from Athens to Sparta. Thucydides, a well-known historian of that era, also contracted the disease, but survived to write about the devastating outbreak.
Nov 2, 1612
Typhoid fever strikes royalty
Henry Prince of Wales, the oldest son of King James I, died at age 18 after a “short illness” which was not identified or described other than as a fever. In 1882, Norman Moore, MD, published “The Illness and Death of Henry Prince of Wales in 1612.” Based on his studies of the autopsy on the prince as well as detailed descriptions of the illness, Moore surmised that the prince had died of typhoid fever. This well might be the earliest English case of typhoid fever on record.
Christening the disease
The name “typhoid fever” was first proposed by the French physician Pierre Charles Alexandre Louis. Between 1822 and 1827, he studied a total of 138 patients with typhoid fever, of whom 50 succumbed to the disease. The postmortem findings of these patients were compared with the autopsy findings of 83 other dead who had passed away due to other causes. This idea of meticulous documentation, the use of controls. and numerical analysis of the data were an important milestone in medical history.
A groundbreaking discovery
Dr. William Budd, an English doctor, pioneered in 1853 the groundbreaking work on water-borne transmission of typhoid fever.
While investigating an outbreak of the disease in a small Welsh border town of Cowbridge, he found that during the local race week, eight people had developed typhoid fever. They all had celebrated at a local inn where a dinner ball had been organized. Each of the eight victims, who succumbed to their illness, had consumed lemonade prepared with water from the local well. This well was close to the septic pit of the inn. Based on these observations, Dr. Budd concluded that the poison, as he then called it, was present in the excretions of the infected and could be transmitted to healthy people through contaminated water consumption.
Dr. Budd reinforced his theory in 1866 when he and a colleague, Dr. Grace, traced a similar outbreak in several farm cottages. With this, Dr Budd propounded the theory that typhoid fever was disseminated via the faeco-oral route, a new and revolutionary concept at that time.
Queen loses her consort
Prince Albert, the consort of Queen Victoria, died of typhoid fever in 1861. During the Victorian era, an estimated 50000 typhoid fever cases occurred per year in England.
Discovery of the bacillus
German bacteriologist and physician Karl Joseph Eberth – a student of Rudolf Virchow – discovered the bacillus in the abdominal lymph nodes and spleen in 1879. After he had published his observations in 1880 and 1881, his discovery was subsequently confirmed by German physician, Robert Koch.,, In 1884, another German bacteriologist Georg T. A. Gaffky confirmed that the bacillus is the agent of typhoid fever and named the bacillus Eberthella typhi.
Devising a serodiagnostic test
French physician and bacteriologist, Georges Ferdinand Isidore Widal, developed an agglutination test for diagnosing typhoid fever. The test was based on the principle that, if a homologous antibody is present in the patient's serum, it will react with the respective antigen in reagent and demonstrate visible clumping on the test card and agglutination in the tube. The antigens used in the test were “H” and “O” antigens of Salmonella typhi and “H” antigen of Salmonella paratyphi. The paratyphoid “O” antigen were not employed as they cross-react with typhoid “O” antigen due to the sharing of factor 12. While “O” antigen is a somatic antigen, “H” antigen is flagellar antigen.
The description of this test was presented to the Medical Society of the Hospitals in Paris, in June 1896. An English communication by Widal appeared in Lancet after the preliminary report in Paris. He called it “Sero-diagnosis by which typhoid fever could almost be instantly recognized, by simply observing microscopically, how the serum of the patient acted on the culture of Eberth's bacillus.”
The first anti-typhoid vaccinations
Several research teams stepped up work to develop a vaccine against typhoid fever in the 1890s. In Germany, the lead was taken by Richard Pfeiffer and Wilhelm Kolle, who demonstrated in 1896 that a human inoculation of killed typhoid bacteria could produce immunity against typhoid.
Just a few months later, British pathologist Almroth Edward Wright published a paper with similar findings. Wright introduced a crude system of anti-typhoid inoculation for military use in 1896. This made a significant improvement to the health of soldiers at war, who were more likely to be killed by typhoid than in combat at that time.
The case of a notorious carrier
The title of “the most notorious carrier of typhoid fever in history” goes to the New Yorker, Mary Mallon. Better known as Typhoid Mary, she was the first American to be identified and traced as a typhoid fever carrier in 1907.
Mary worked as a cook in New York, and was associated with 53 cases and 3 deaths. Public health authorities told Mary to give up working as a cook or have her gall bladder removed. Mary quit her job but returned later under a false name. She was detained and quarantined after another typhoid outbreak. She died of pneumonia after 26 years in quarantine.
Coleman and Buxton blood culture technique
Since Eberth's discovery of the etiological agent of enteric fever in 1879, blood culture has been the gold standard of enteric fever diagnosis. Whereas early culture techniques had low yield, an improved approach using larger quantities of blood (10 mL) and broth and adding Ox-bile, which lyses blood cells and inhibits antibacterial activity, was developed by Coleman and Buxton.
Among the most commonly used blood culture media today are tryptone soy broths, with automated systems used in settings with sufficient resources. The majority of positive cultures are evident within 48 hours, and nearly all are positive by 5 days.
US military eliminates typhoid
In 1909, Frederick F. Russell, a U.S. Army physician, developed the first U.S. typhoid fever vaccine. Two years later, his vaccination program became the first in which an entire army was immunized. It eliminated typhoid as a significant cause of morbidity and mortality in the U.S. military.
Fulfilment of Koch's postulate
In 1911, Elie Metchnikoff fulfilled the Koch's postulate by reproducing typhoid fever in chimpanzees following throat inoculation with Salmonella typhi.
Killer disease of the rich and famous
The disease claimed the lives of many rich and famous people. These include the hero of the American Revolution, Tadeusz Kosciuszko (1817); the First Lady of the United States, Abigail Adams, who died on October 28, 1818; William Wallace Lincoln, third son of Abraham Lincoln, the 16th President of the United States, who died on February 20, 1862; celebrated Italian soprano, Eugenia Tadolini, who died in Paris in 1872; Leland Stanford Jr., who died in 1884 of enteric fever and whose parents founded the Stanford University in his memory; Dr HJH Tup Scott, captain of the 1886 Australian cricket team that toured England, who died in 1910; one of the famous Wright Brothers, Wilbur Wright, who died on May 30, 1912; and the physician who first identified autoimmune thyroiditis, Hashimoto Hakaru, who died on January 9, 1934.,,,,,
Launch of the first public typhoid vaccine
By 1914, typhoid vaccination had moved beyond the military forces in the United States and into use for the general public. Parke, Davis and Company sent a letter to a Philadelphia physician advocating the use of typhoid vaccine for travelers. The text of the letter read as follows:
Your patients, many of them, will soon be leaving for their vacations and unless protected by vaccination they may incidentally be in some danger of contracting Typhoid Fever.
As a preventive of Typhoid Fever the value of Typhoid Vaccine is now well established. It has been used extensively in our own and other great armies with very satisfactory results. Consequently in the U.S. Army anti-typhoid vaccination of recruits is now compulsory.
It is a simple matter to use Typhoid Vaccine Prophylactic (P.D. and Co). Three doses are given, injected subcutaneously at ten-day intervals. It is offered in packages containing enough for the protective treatment of one person – three doses in three bulbs, three doses in three syringes or three doses in one graduated syringe. It may also be had in a larger package known as the “hospital size” and containing enough for ten persons.
The interesting and important subject of typhoid vaccination is presented concisely in the enclosed booklet which we commend to your careful attention and we shall be very glad to supply additional information if you desire it. Supplies of Typhoid Vaccine Prophylactic, (P.D. and Co.), may be obtained through pharmacists.
Very truly yours,
Parke, Davis and Co.
Chloromycetin makes its mark
Introduced in 1949, antibiotic chloramphenicol makes its mark in clinical practice under the trade name of Chloromycetin. Originally derived from the bacterium Streptomyces venezuelae, and first isolated by David Gottlieb, it is hailed as the first major breakthrough against typhoid fever.
July 16, 1952
Launch of new typhoid vaccine
A new heat-phenol inactivated typhoid vaccine becomes available. The vaccine is licensed to multinational pharmaceutical Wyeth.
Salmonella develops chloramphenicol-resistance
Following its introduction in clinical practice in 1949, the first chloramphenicol resistant strains of Salmonella were quick to emerge and could be found within 2 years of its launch in clinical practice. However, despite the development of such resistant strains, the first major outbreak of typhoid fever in India occurred only in 1972.
Waging a poll war with Salmonella
The Rajneesh cult of Antelope, Oregon purportedly contaminated salad bars in local restaurants with Salmonella enterica serovar typhi murium in an attempt to influence the outcome of a local election. Seven hundred and fifty people were affected and the outcome of the operation was the collapse of the cult.
1980s and Later
Emergence of antibiotic-resistant strains
The wanton widespread use of amoxicillin resulted in the emergence of TEM1, a plasmid-borne β-lactamase strain of Salmonella which was capable of hydrolyzing penicillin but not extended-spectrum cephalosporins. The use of co-trimoxazole also promoted the development of resistance. By the end of the 1980s, multidrug-resistant typhoid (MDRT), defined as isolates resistant to amoxicillin, co-trimoxazole, and chloramphenicol, was raging throughout India. Although there are no countrywide surveillance data from this period, individual studies from all regions of India showed the emergence and rise of MDRT during the late 1980s and 1990s.,,,
Following the rise of MDRT, ciprofloxacin became the drug of choice in typhoid fever. However, point mutations in the Quinolone Resistance Determining Region (QRDR) of DNA gyrase gave rise to decreased ciprofloxacin susceptibility (DCS), identified in vitro by nalidixic acid resistance. DCS strains were associated with delayed fever clearance and an increase in the rate of complications and clinical failure. Accumulation of further mutations in QRDR, with or without added efflux pumps, resulted in high level ciprofloxacin resistance, rendering even fourth-generation fluoroquinolones, such as gatifloxacin, obsolete.
The first oral vaccine
With field trials being run among schoolchildren in Santiago, Chile since 1984, Ty21a, a live, oral typhoid vaccine, marketed under the brand name of Vivotif Berna was licensed by the Swiss Serum Institute in 1989.
Supplied in enteric coated capsules, primary vaccination with live-attenuated Ty21a vaccine consists of one enteric-coated capsule taken on alternate days (day 0, 2, 4, and 6), for a total of four capsules. The capsules must be kept refrigerated (not frozen). Each capsule should be taken with cool water no warmer than 98.6°F (37.0°C) approximately 1 hour before a meal. All doses should be completed at least 1 week before potential exposure. The vaccine carries a protection rate between 50% and 80%, and boosters are recommended every 2 years.
May 5, 1992
New injectable polysaccharide vaccine
Injectable Typhoid Vi capsular polysaccharide vaccine Typhim Vi was licensed by Aventis Pasteur. Given intramuscularly in a single dose, it induces protection in about 7 days. In geographic areas at risk, the protective efficacy 1.5 years after vaccination is approximately 72%; and after 3 years is approximately 50%. The vaccine is licensed for individuals of ages 2 years and more. To maintain protection, revaccination is recommended every 3 years.
Birth of new serological tests
Since the mid-1990s several serologic tests have been developed for point-of-care diagnosis of enteric fever. The two that have been most widely studied are TUBEX TF (IDL Biotech, Sweden) and Typhidot (Malaysian Biodiagnostic Research, Malaysia).
TUBEX TF assays for antibodies to Salmonella typhi LPS (O9) by quantifying inhibition of binding between O9 monoclonal antibodies and LPS-coupled magnetic particles.
Typhidot is a miniaturized dot-blot ELISA that detects IgM and IgG antibodies to a 50 kD Salmonella typhi outer membrane protein (OMP). Typhidot-M uses the same approach to detect IgM to OMP after removal of total serum IgG to improve specificity for recent infection.
A recent systematic review and meta-analysis of TUBEX TF and Typhidot found sensitivity of 56–95% and 56–84%, respectively, with specificity of 72–95% and 31–97%.
October 2, 2014
Launch of Clean India Mission
Control of enteric fever relies predominantly upon three interventions: improvement in living conditions with enforcement of safe water supply and food hygiene, typhoid immunization in disease prevalent areas, and maintaining a check on antibiotic resistance through a vigilant antibiotic policy.
The launch of the national campaign Swachh Bharat Abhiyan (Clean India Mission) on Oct 2, 2004 by the Prime Minister of India, Shri Narendra Modi, focuses on the first key intervention. The campaign aims to improve municipal solid waste management, create awareness and change attitudes to sanitation, and eliminate open defecation by providing 1.2 billion toilets for households and communities by 2019. As of August 2015, an estimated 800,000 toilets had been constructed, although there are reports that changing attitudes to open defecation in rural areas has been difficult. There are also a number of initiatives to teach hygiene and hand washing in schools and communities.,, In fact, Madhya Pradesh, a state in central India, created a world record in hand washing on Oct 15, 2014. On this day, a simultaneous hand washing program was held at 13196 places and included a total of 1,276,425 students.
March 27, 2015
CDC published new ACIP recommendations for typhoid vaccination.
New National Treatment Guidelines
The National Centre for Disease Control in India (NCDC) published the National Treatment Guidelines for Antimicrobial Use in Infectious Diseases. Azithromycin is advocated as favored antibiotic in patients with uncomplicated disease, whereas Ceftriaxone is recommended for patients requiring intravenous therapy. Oral third-generation cephalosporin, Cefixime, can also be used for uncomplicated disease under the guidelines of NCDC and Indian Association of Pediatricians.
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