The West Nile Virus (WNV) was first described in Africa in 1937.In a serosurvey of African trypanosomiasis in the West Nile District of Uganda, Kenneth C. Smithburn at the Rockefeller Institute encountered a febrile woman who otherwise felt well. Her blood was subsequently injected it into 10 Swiss albino mice, nine of whom died. Then, blood from the sick mice were injected again into healthy mice.These healthy mice also died.A virus was isolated and was subsequently shown to be a flavivirus. The Latin prefix “flavi” means yellow since the Yellow Fever virus was one of its most notorious members.In 1943 it was confirmed that mosquitoes were the vector for both birds and mammals for WNV.
In the 1950s, R.M. Taylor studied transmission patterns between ticks, birds, mice, and other arthropods and noted the ability of the virus to lay dormant within pools of insects and animals for years.Surprisingly, they found anti-WNV positive results in serologic samples from 1.4% in the Congo to 46.4% in Sudan.Serosurveys in the 1940s and 1950s in Egypt showed over 90% of individuals over 40 years old had anti-WNV antibodies.In Egypt, the virus was subsequently isolated from patients, birds, and mosquitoes.
Not until 1957 was West Nile Virus recognized as a major illness.An epidemic occurred in Israel with over 500 infected patients diagnosed with WNV infection over several months.Unlike previous cases in which symptoms were self-limiting, meningoencephalitis with mental status changes and neurologic manifestations was the primary clinical presentation. The mortality was 8.2% in elderly patients in nursing homes.Romania’s outbreak in 1996 led to an unprecedented number of CNS infections, with 762 out of 835 patients contracting encephalitis with 17 deaths.
The New York City Outbreak
By early 2000, WNV outbreaks seemed to increase in frequency across Europe and North America.A dramatic appearance of WNV occurred in 1999 in New York city. In the summer of 1999, physicians at Flushing Queens Hospital admitted an unprecedented number of patients with encephalitis and meningitis. These cases were reported to the Centers for Disease Control and Prevention in Atlanta (CDC). The CDC initially diagnosed the encephalitis-causing virus as the St. Louis Encephalitis (SLE) virus based on a weak antibody reaction to SLE virus.
From August 1999 to September 1999, 48 cases of meningoencephalitis of uncertain etiology were found in New York City. The brain samples from five patients were sent to Dr. Ian Lipkin, director of the Emerging Infections Laboratory of the University of California, Irvine. Lipkin had isolated a flavivirus from these samples and then sequenced the genome of the virus. Within 24 hours, they found the genome to be related to WNV.
Weeks prior to the human outbreak of WNV, 87 birds of various species were found dead in Central Park, NY. This anomaly was initially attributed to chemical poisoning until zookeepers at the Bronx Zoo and Queens Zoo discovered dead birds in their cages. The autopsy reports from these birds failed to reveal the cause of death; no known toxins, bacteria, or viruses were isolated.Similar to the New York patients, meningoencephalitis and myocarditis were found in autopsies of the birds as the cause of death.
In late August 1999, Dr. Beverly Schmitt at the U.S. Department of Agriculture National Veterinary Service Laboratory in Ames, Iowa found evidence of a virus in cell culture inoculated with tissue of birds that had died. The visualization of the virus by electron microscopy showed that it resembled flaviviruses or togaviruses. The CDC laboratory in Fort Collins identified the virus as WNV using stored anti-sera.
The Role of the Mosquito
Once in North America, the WNV infected native species of mosquitoes.Different types of mosquitoes were found to be responsible for the transmission of disease in humans.“Amplification” mosquitoes include Culex pipiens and Culex restuans.This mosquito feeds on birds and transmit the virus to other birds creating a large reservoir of WNV infection.The “bridging” species include Coquillettidia perturbans, and human biters include Aedes vexans.The latter 2 mosquitos feeds on both birds and humans and transmit the virus.The Asian Tiger mosquito (Aedes albopictus), a species native to Asia is a known vector for WNV.It was isolated in Baltimore, MD in 1999 and subsequently linked to WNV infections in birds and humans in the U.S.
Current Status
In 2000, one year after the New York city outbreak, 20 more patients were diagnosed with WNV infection in New York state and neighboring states. WNV infection has now been reported from all U.S. states. WNV has a broad ecological network of infection among birds, mammals and insects. Increasingly rainy springs paired with warmer summers allow mosquito populations to flourish. Bird migration patterns in spring and fall were thought to account for the spread of the virus throughout the US.Unlike the populations in Uganda and Egypt, North American populations were more vulnerable and the virus appeared more virulent.Before arriving in North America, transmission from person-to-person had never been documented.However, in the U.S., WNV transmission occurred via blood transfusion, organ transplant, intrauterine exposure, and breast feeding.By 2008, more than 28,000 Americans were infected by the virus; over 11,0000 contracted encephalitis and over 1,000 died.The emergence of WNV in North America correlated directly with the precipitating decline of the bird population.Since the 1999 New York city outbreak, 45% of the U.S. crow population has died.
References
Beran, G. W. & Steele, J. H. (Eds.). (1994). Handbook of zoonoses: Section B: Viral (2nd ed.). Boca Raton, FL: CRC Press.
Despommier D. West Nile Story. Apple Trees Productions, LLC, 2001. New York, NY.
Nash, D. et al. (2001). The outbreak of West Nile virus infection in the New York City area in 1999. New England Journal of Medicine, 344 (24), 1807 – 1814.
Newman W, Southam CM. Virus treatment in advanced cancer.A pathologic study of 57 cases.Cancer 1954;7:106-118.
Oldstone, M. B. A. (2010). Viruses, plagues, and history: past, present, and future. New York City: Oxford University Press.
Smithburn KC, Hughes TP, Burke AW, Paul JH. A neutropic virus isolated from the blood of a native of Uganda. Am J Trop Med. 1940;20:471-492.
University of Wisconsin-Madison Department of Bacteriology- West Nile Virus. Electron micrograph
West Nile Virus Lymphocytic Perivascular Infiltration
In 1903, international efforts to construct the Panama Canal were being threatened by the twin biological hazards of yellow fever and malaria. The French decided to leave the endeavor in the hands of the Americans after enduring more than 12,000 deaths and an estimated $40 million loss. Tropical diseases were a deadly enemy, and if American efforts were to succeed), these diseases needed to be overcome.
In that same year of 1903, Samuel Taylor Darling (Image) graduated from the College of Physicians and Surgeons of Baltimore and had trained in Louis Pasteur’s laboratory. He was thrust into the tropical hospitals of Panama when he accepted an internship at Ancon Hospital and joined the medical team headed by William Gorgas, whose mission was to control malaria and yellow fever. This 32 year old professor of pathology and histology at Baltimore City Hospital soon rose through the ranks to be appointed head of the Board of Health Laboratory in Panama.
While Walter Reed discovered the role of the mosquito in malaria transmission and William Gorgas successfully initiated a prevention campaign, Darling identified an apparently new disease process occurring at the Panama Canal. Three cases piqued Darling’s interest that a new disease was occurring. In 1905, he observed an unusual autopsy in a 27 year old black carpenter from the Caribbean island of Martinique who worked on the canal. His lungs were studded with granulomas, which Darling noted to be not as closely packed or as numerous as was found in military tuberculosis. Smears from white granulomas in the lung and from the spleen, liver, and bone marrow revealed an “intense invasion of large endothelial-like cells by small round or oval microorganisms”. In 1906, a second autopsy on another black canal laborer from Martinique revealed oval microorganisms mirroring the first case. The third autopsy case finding was a Chinese immigrant laborer living in Panama for fifteen years which also showed similar microorganisms.
These three patients also presented with symptoms of an irregular fever, cachexia, and splenomegaly common among canal workers; however, these cases were expressly different from yellow fever and malaria. These patients presented with pustular eruptions and ulcers often around the face and anus, ulcerations in the gastrointestinal tract, and lymph node, spleen, liver, and lung involvement. One of his lab assistants noticed how “completely [Darling] submerged everything for the benefit of his professional duty and ambition”, preferring to work in complete isolation while he studied celloidin sections, cultures, and autopsies. Darling examined the autopsy tissue samples in more patients who succumbed to this disease and granulomas were found in the lung. The oval microorganisms were seen within alveolar epithelial cells in the granulomas, while others appeared to be free in the spleen and bone marrow. These microorganisms were surrounded by a clear refractive nonstaining rim. M. tuberculosis could not be isolated. He proposed that the microorganism causing this newly-discovered disease was a protozoan and named the organism Histoplasmosis capsulatum because it invaded the cytoplasm of histiocyte-like cells and was enveloped by a capsule. Darling recorded his observations in six classical papers published from 1906 to 1909 describing the disease (Figure 1).
Darling also performed most of the autopsies in patients who died of malaria, the major disease of the Canal Zone, second only to pneumonia. He formulated the splenic index which measured the degree of infectivity as indicated by splenomegaly in a patient. Through Darling’s systematic collecting, feeding, and breeding of the Anopheles mosquito, he was able to observe the macrogametes within the mosquito. He identified the Anopheles albimanus as the main mosquito vector for both tertian (vivax) and estivo-autumnal (falciparum) fevers in Panama. With this finding, Darling initiated the first “species-specific” control system, in which sanitation efforts specifically targeted this species of mosquito, thus reducing the cost of sanitation and increasing its effectiveness. Another mosquito was later named in his honor: Anopheles darlingi, a significant vector of malaria in South America. Although Darling’s distinction originated from his work on malaria and the histoplasmosis, he also published noteworthy observations on amebiasis, trypanosomiasis, leishmaniasis, filariasis, schistosomiasis, piroplasmosis, strongyloidiasis, and uncinariasis.
Histoplasmosis became known as “Darling’s Disease”. Nonetheless, his findings had several flaws. Although the microorganism did reside in histiocytes, it was neither a protozoan nor was it encapsulated. He came to these erroneous conclusions after finding flagellated forms (most likely artifact) of the microorganism and comparing them to Leishmania, also elucidated in 1903.
Because the disease usually was not fatal and symptoms of histoplasmosis were so protean, the extent of the disease process and worldwide dispersion of histoplasmosis were unappreciated. In 1906, R.P. Strong also reported cases of histoplasmosis in the Philippines, although he also incorrectly linked it to Leishmaniasis. Over the following decades, reports of microorganisms with oval bodies in the mononuclear cells of the peripheral blood smear similar to those Darling described were recorded in patients throughout South America and later the rest of the world. In 1912, the Brazilian pathologist, Henrique da Rocha-Lima, obtained tissue from Darling’s Panama patients and compared the organisms to Leishmaniasis. By showing the microorganism’s similarity to Cryptoccocus farciminosus Rivolta, the cause of epizootic lymphangitis in horses, he concluded that Histoplamosis capsulatum was a fungus rather than a protozoon. (In 1985, Cryptococcus farciminosum was moved into the Histoplasmosis genera as H. capsulatum var. farciminosum).
References
Chaves-Carballa E. (2007). The tropical world of Samuel Taylor Darling: Parasites, pathology and philanthropy. Portland, OR: Sussex Academic Press.
Daniel TM, Baul GL. (2002). Drama and discovery: the story of histoplasmosis. Westport, CT: Greenwood Press.
Darling ST. A Protozoan general infection producing pseudotuberculosis in the lungs and focal necrosis in the liver, spleen, and lymph nodes. JAMA 1906;46:1283-1285.
Carlos Chagas was born in 1879 in a small town in Brazil, the eldest son of coffee plantation owners. His father died when Carlos was four; a physician-uncle became a paternal figure and stimulated Carlos’s lifelong interest in medicine.
In 1902 Chagas studied medicine in Rio de Janeiro under Oswaldo Cruz at the Manguinhos Institute (later renamed the Oswaldo Cruz Institute, now the Fiocruz Institute). Cruz was only seven years older than Chagas, but by the turn of the century was already a prodigy in the fields of parasitology and public health: he had studied at the Pasteur Institute, and brought a sophisticated understanding of germ theory to bear on outbreaks of yellow fever and malaria. Cruz identified Chagas as a promising student, and encouraged him during the writing of his medical student thesis on the “hematological aspects of malaria.” He also offered Chagas a junior faculty research position after graduation. But Chagas chose to enter family practice. Perhaps the financial choices faced by today’s medical school graduates were present then, too.
Two years later, however, Chagas left his private practice to work for the shipping industry. The burgeoning city of Sao Paulo needed better access to sea freight, and the nearby port of Santos was poised to fill this role. Unfortunately, Santos was so overrun with malaria that ship captains were reluctant to dock there, so the port owners hired Chagas to reduce disease transmission. He succeeded through a coordinated program of vector control and patient treatment that resembled a modern-day outbreak response. He clearly enjoyed this work, and subsequently relented to Cruz’s pressure by becoming an associate professor at Manguinhos Institute.
In 1908 he faced a similar challenge on behalf of the railroad industry. Connecting Rio to the heart of the Amazon basin by rail was another lucrative opportunity stymied by infectious disease. Untold numbers of slaves and laborers died in this pursuit, succumbing to malaria, yellow fever and other undiagnosed illnesses. So Chagas moved to the rough-and-tumble town of Lassance, at the end of the rail line in the sweltering Brazilian interior. Working from a clinic in a railway car, he encountered “A population complaining about irregular heartbeats and atypical arrhythmias, [with] indications of cardiac insufficiencies, frequently leading to sudden death… inexplicable!”
Chagas astutely surmised a link between the endemicity of myocardial failure and the triatomine bug. Called “barbieros” or “barber bugs” because of their predilection for drawing human blood, these large black insects were unheard of along the more civilized Brazilian coast. But the workers in the interior knew them well, and described to Chagas their nocturnal encounters with the creatures that would emerge from cracks in the mud walls and thatch roofs to feed upon their blood. Patients sometimes developed swollen bite sites near the eyelids and lips, and for this reason they called the insects “kissing bugs.” To discover whether they could serve as vectors for a novel infectious agent, Chagas dissected insects and inspected their gut flora with a simple light microscope.
He ultimately discovered a eukaryotic, flagellated protozoan, similar to the agent of African sleeping sickness—Trypanosoma brucei—described by Forde only six years earlier. Chagas named the protozoan after his mentor (Schizotrypanum cruzi, later renamed Trypanosoma cruzi). Next, he set out to prove his hypothesis that this organism was indeed passed to humans as a pathogen during feeding, presumably via the bug’s stool. He first demonstrated T.cruzi in the remains of a badly-bitten cat. Later, a little girl in the same household was bitten repeatedly by barbieros, and developed fever, generalized lymphadenopathy, hepatosplenomegaly, and right-sided heart failure. When she died, Chagas found T.cruzi in her bloodstream. This three-year-old child became the first microbiologically-documented case of American Trypanosomiasis. Subsequently, he infected monkeys with triatomine droppings: they developed the same clinical syndrome, establishing a link between trypanosomes and disease.
This work earned Chagas international fame, and the disease soon bore his name. At home he was revered as a hero. The score of Don Quixote was adapted with him as the protagonist, tilting at windmills of disease with his hypodermic syringe. His likeness even graced the national currency: the 10,000 Cruzado note depicted him and the life cycle of T.cruzi. It is ironic that his mentor, Oswaldo Cruz, figured on a note worth only 50 Cruzados.
References
1. Bastien JW. The Kiss of Death: Chagas’ Disease in the Americas. University of Utah Press, Salt Lake City, 1998. An excellent review of the discovery and quest to eradicate Chagas’ disease, including scientific, cultural, and economic perspectives.
2. Kropf SK, et al. Carlos Chagas Virtual Library (www4.prossiga.br/ Chagas/centro.html). Many of the images herein are copied from this extensive and handsome website, a publication of the Fiocruz Institute.
With each rejection, Mallon accrued notoriety. Eventually, the New York City Health Department became involved and sent an expert, Dr. Sara Josephine Baker, to speak with Mary, but “by that time she was convinced that the law was wantonly persecuting her when she had done nothing wrong.” After a few unsuccessful attempts to quarantine Mallon, Baker arrived at Mary’s place of work with several police officers and coerced her into custody. Mallon was held in isolation for three years at a hospital located in North Brother Island. Through a series of legal battles, Mallon’s personhood transformed into a medical concept and social stigma.
Eventually, Mallon was released from her quarantine but not as the same person. With little more than a tepid farewell from the government officials and an admonishment never to cook again, little social and financial support were offered to Typhoid Mary. She was offered a job as a laundress which paid lower wages than cooking, but more importantly, it distanced her from food which was in constant scarcity throughout her childhood. To avoid her alias, Typhoid Mary, she assumed the name “Mary Brown” and returned to her previous occupation as a cook. In 1915 she infected 25 people while working for the New York’s Sloane Hospital for Women; one of those infected died. Public health authorities again tracked down and arrested Typhoid Mary returning her to quarantine on the island. Typhoid Mary was confined there for the rest of her life. She became something of a minor celebrity and was interviewed by journalists who were forbidden to accept as much as a glass of water from her.
After spending the rest of her life exiled in quarantine, Mallon died on November 11, 1938 at the age of 69. The cause of death was pneumonia, coming six years after a stroke that had left her paralyzed. She was still infectious on the day she died, and an autopsy found evidence of live typhoid bacteria in her gallbladder. Her body was subsequently cremated and the ashes buried at Saint Raymond’s Cemetery in the Bronx. Although Mary Mallon died long before her physical death, the medical concept of the asymptomatic carrier and social stigma of Typhoid Mary remains even unto this day.
References:
Judith Walzer Leavitt. Typhoid Mary - Captive to the Public’s Health. Beacon Press, 1997.
Anthony Bourdain. Typhoid Mary- An Urban Historical. “There’s Something about Mary” Bloomsbury. 2001.
Mallon, seeking to make the most of her plight, became a cook in the New York City area between 1900 and 1907. She found herself with relative job instability because everywhere she went typhoid fever followed. In one incident, she cooked for a lawyer’s family where seven of the eight household members developed typhoid. Mary spent months helping to care for the people she made sick but it only further spread the disease. This cycle of ignorant contamination and willful compassion continued from household to household until 1906.
In 1906, epidemiologists and physicians were beginning to grasp the novel concept of an asymptomatic carrier. Modern times present asymptomatic carriers in the forms of HIV and recurrent viruses—EBV and CMV. In Mary Mallon’s case, the asymptomatic carrier was typhoid fever. The Salmonella typhi bacteria resided in her gallbladder and were secreted with the bile into her small intestine and excreted in her urine and feces. Without vigorous scrubbing and thorough disinfection with soap and hot water, the bacteria remained on her hands contaminating the food. This concept of a symptomless illness lay in the realm of absurdity for Mallon and most of the lay-public.
Thus, Mallon was utterly aghast when George Soper, a government epidemiologist, approached her with the news that she was possibly spreading typhoid. He coupled this news with the request for blood, urine, and feces samples from her for testing. Mary forcefully rejected this allegation by threatening Soper with her kitchen knife. Despite this minor setback, Soper persisted throughout the following weeks, but each inquisition was met with resolute rejection. These mounting refusals led the ill-advised epidemiologist to offer her royalties on a book deal (which he would later publish after Mallon’s death). In a fit of disgust and disbelief, she angrily rejected his latest proposal by locking herself in a lavatory until he left.
What do Stanford University, Theodore Roosevelt, and Mary Mallon have in common? The answer is typhoid fever—an endemic that terrorized the United States during much of the late 19th and early 20th centuries. It was during this time that the death of the Californian Governor’s only son, Leland Stanford Jr., brought about the prestigious Stanford University; the end of Alice Hathaway Lee Roosevelt’s life drove Theodore Roosevelt to hopeless reclusion; and national tabloids donned Mary Mallon as Typhoid Mary. All of these events are momentous in their own way, but none more so than the sorrowful irony that is Ms. Mallon’s life and death and the concept of the asymptomatic carrier.
At the time of Mallon’s birth in 1869, an exploited Ireland lay in shambles as a result of the Great Famine and Irish Holocaust. Like many young Irish adults, Mallon emigrated at the tender age of 18 to the United States in search of a better life free from government oppression and social deprivation. Upon arrival, many of the women could only make a living performing the filthiest and lowest tasks. Soon, they found themselves accepting servanthood as a fact of life. However, there was one benefit to servanthood in America compared to serfdom in Ireland—you were fed…
…Despite being aware of Cobbold’s designation of a similar worm as Filaria Bancrofti, Lewis retained the name originally applied to the embryo – Filaria sanguinis hominis - on the grounds that a new name would only lead to confusion. Cobbold therefore attached an appendix to his second paper on the subject of the adult worm:
“Since the above was written, Dr Lewis has himself furnished additional means of identification. His mature Filaria sanguinis hominis and my F. Bancrofti are clearly the same species….If Lewis’s trinomial name for the adult worm be adopted in place of Filaria Bancrofti, I have personally no objection.” (6)
Subsequently, female adult worms were found in patients in South America by da Silva Araujo on 16 October 1877 (15) and by dos Santos on 12 November 1877 (12), then by Manson in Amoy, China in 1881 (9).
It was not until 1888 that a complete specimen of a male worm was found. Brigade-Surgeon Sibthorpe at the Madras General Hospital, India, found worms in an amputated lymph scrotum and sent them off to Alfred Bourne, professor of biology in the Presidency College. Bourne found that one of the parasites was a male filaria. He published a brief record of the discovery in the British Medical Journal in 1888 (3), then a more detailed description incorporating Bourne’s written comments was published by Sibthorpe in the same journal in the following year (14).
Meanwhile, Bourne himself also published an extended, illustrated version in an Indian journal (4). Although Bourne and Sibthorpe claimed that this was the first time the complete male worm was described, Saboia in Bahia, Brazil in 1886 had found two filarial parasites in the right side of the heart of a boy who had died from an undisclosed illness. It is possible they were immature Dirofilaria immitis, although de Magalhães (8) sent a copy of this account, including figures, to Joseph Bancroft in Brisbane who accepted them as a female and male Filaria bancrofti, noting that this was the first time in which the male parasite had been described (1). On the other hand, Daniels considered the parasites distinct, giving them quite different dimensions (71).
Several other names apart from Filaria sanguinis hominis and Filaria bancrofti have been used to describe these parasites. Manson called it Filaria nocturna in order to distinguish it from the microfilaria which had a diurnal periodicity (which turned out to be Loa loa) (10), and Manson-Bahr proposed the name Wucheria pacifica for the aperiodic form of the parasite (11). In 1877, da Silva Araujo called the worm which he found in a lymph scrotum “Wuchereria Filaria” (15), but whether he meant to use “Wuchereria” as a true generic name is doubtful; more likely he was referring to “Wucherer’s filaria”. In any event, two years later, da Silva Araujo called the same worm Filaria wuchereri (16). In 1921, Seurat formally separated this parasite from the other filarial parasites on zoological grounds and adopted da Silva Araujo’s Wuchereria as the generic name, the worm henceforth being known as Wuchereria bancrofti (13).
REFERENCES1. BANCROFT J. On filaria. Transactions of the Intercolonial Medical Congress of Australasia, pp 49-54, 18892. BANCROFT J. Cited in 573. BOURNE AG. A note on Filaria sanguinis hominis: with a description of the male specimen. British Medical Journal i: 1050-1051, 18884. BOURNE AG. Transactions of the South Indian Branch of the British Medical Association 2: 396-398, 18885. COBBOLD TS. Discovery of the adult representative of microscopic filariae. Lancet ii: 70-71,18776. COBBOLD TS. On Filaria Bancrofti. Lancet ii: 495-496, 187771. DANIELS CW. Discovery of the parental form of a British Guiana blood worm. British Medical Journal i: 1011-1012, 18987. LEWIS TR. Filaria sanguinis hominis (mature form), found in a blood clot in naevoid elephantiasis of the scrotum. Lancet ii: 453-455, 18778. de MAGALHÃES PS. Filaria bancrofti. Gazeta Medica da Bahia, third series, 4: 97-100, 18869. MANSON P. Additional notes on Filaria sanguinis hominis and filaria disease. Discovery of adult F. bancrofti. China Imperial Maritime Customs. Medical Reports for the half year ended 30th September 1880, 20th issue, pp 13-15, 1881. Reprinted as: Lymph scrotum showing filaria in situ. Transactions of the Pathological Society of London 32: 285-302, 188110. MANSON P. The geographical distribution, pathological relations and life history of Filaria sanguinis hominis diurna and Filaria sanguinis hominis perstans in connexion with preventive medicine. Transactions of the Seventh International Congress of Hygiene and Demography, London, August 10-17, 1891 i: 79-97, 1892. Abstracted in Medical Press and Circular 103, new series, 52: 202-205, 1891 and Semaine Médecine 11: 342, 189112. MANSON-BAHR P. The nomenclature of the filaria of the Pacific region producing non-periodic embryos (Wuchereria pacifica). Tropical Diseases Bulletin 38: 361-367, 194112. dos SANTOS F. Filaria bancroft, verificação no Brazil da descoberto de Bancroft, no Australia. Progresso Medico, Rio de Janeiro 2: 95-100, 187713. SEURAT LG. Orthogénèse des filaires. Bulletin de la Société d’Histoire Naturelle de l’Afrique du Nord 12: 28-37, 192114. SIBTHORPE. On the adult male Filaria sanguinis hominis. British Medical Journal i:1334-1335, 188915. da SILVA ARAUJO AJ. Caso de chyluria, elephancia do escroto, escroto lymphatico, craw-craw e erysipela em um mesmo individuo, descobrimento da Wuchereria Filaria na lympha do escroto. Tratamento pela electricidade com excellentes resultados. Gazeta Medica da Bahia, second series, 2: 492-504, 187716. da SILVA ARAUJO AJ. Caso de chyluria, elephancia do escroto, escroto lymphatico, craw-craw e erysipela em um mesmo individuo, descobrimento da Filaria wuchereri na lympha do escroto. Tratamento pela electricidade com excellentes resultados. Gazeta Medica da Bahia, second series, 4: 455-465, 1879
… I collected the matter as usual in a small vessel. As a preliminary enquiry, the blood had to be inspected for embryonic filariae. This was the second case in which the blood contained the parasite in question. On examining the matter….a threadlike body came into view, under the microscope it was without doubt a worm, and embryos were seen coming out of its body. On March 21, the following year, I tapped a hydrocele, in an elderly patient with a trochar and cannula. On withdrawing, a lash of hairlike bodies was caught in the eyes of the instrument. At once suspecting their real nature, I put them in the hydrocele fluid when they began to move around with great activity. Embryos in abundance were found in the hydrocele fluid and in the patient’s blood.” (1)
Meanwhile, Bancroft sent the adult filariae to Cobbold who received them on 28 August 1877. Cobbold found four female worms and multitudes of ova and larvae which he described in some detail in a paper published on 6 October Filariasis 603 1877 (6). In this paper, he persisted in an error which he had made previously in believing that the microfilarial sheath was a commencing ecdysis.
In the previous issue (29 September 1877) of the same journal, Timothy Lewis also described his finding of two adult worms after spending eight hours searching through scrotal tissue removed at operation from a young man in Calcutta by Dr Gayer:
At last, however, whilst teasing a blood clot under a dissecting microscope, my eye was arrested by white thread-like objects in a state of great activity. These on being transferred for examination under a higher power, were found to be specimens of two mature filariae. One of these contained ova, with embryoes identical in appearance with the free embryoes in the blood.” (7)
One parasite was clearly a female worm. The other helminth was damaged and Lewis thought it may have been a fragment of a male worm, but the important caudal part was unfortunately missing. In contrast to Cobbold, Lewis recognized that the egg “shell” became the sheath of the microfilaria:
“It is….difficult to state whether they are to be considered as freed embryoes or not, as the egg-‘shell’ has become so extremely attenuated and translucent as can only with difficulty be distinguished….It would, however, appear probable that, even when the embryo acquires worm-like appearances, the envelope is usually not lost in this species as long as it continues in the blood.” (7)
Moreover, Lewis emphasized the diagnostic importance of this feature in differentiating these microfilariae from those found in the blood of dogs…
After Cobbold received a specimen of blood from Joseph Bancroft in Australia, he wrote to Bancroft suggesting that he look for the adult worms which Cobbold felt must be present in the human body. Cobbold was strengthened in this belief when he saw an empty egg shell which he interpreted as being the remnant of the egg from which the filarial larva had come (it is impossible in retrospect to say what in fact this was). Bancroft took up Cobbold’s suggestion and on 21 December 1876 found an adult worm. Subsequently, he found four more specimens and wrote to Cobbold on 20 April 1877 of his discovery:
I have laboured very hard to find the parental form of the parasite, and am glad to tell you that I have now obtained five specimens of the worm. The worm is about the thickness of a human hair, and is from three to four inches long. By two loops from the centre of its body it emits the filariae described by Carter in immense numbers. My first specimen I got on December 21st 1876 in a lymphatic abscess of the arm. Four others I obtained alive from a hydrocele. (2)
Cobbold sent Bancroft’s letter together with some explanatory notes to The Lancet wherein it was published on 14 July 1877. In his letter, Cobbold named the worm Filaria Bancrofti in honour of Bancroft: “Such Sir, is Dr Bancroft’s account of his ‘finds’, and from the brief description furnished I propose to call the adult nematode Filaria Bancrofti.” (5) Bancroft later described the circumstances surrounding his discovery in somewhat more detail:
I opened an abscess in the arm of a youth employed as a butcher…
Alexander Ogston (1844-1929) was a Scottish surgeon who in 1880 discovered the major cause of pus. Distressed with the high rate of post-operative mortality and unwilling to accept death as a likely outcome of surgery, Ogston was an early convert to the value of antisepsis advocated by Joseph Lister (1827-1912). Given the absence of inflammation in the wounds of Lister’s post-operative patients, Ogston abandoned the contemporary teaching that suppuration was a necessary stage in wound healing, and adopted the antiseptic techniques of Lister. Ogston lauded Lister for transforming the future of surgery from a “hazardous lottery into a safe and soundly based science.
However, it was Ogston who provided the explanation. Lister believed that air was the source of putrefaction. By applying carbolic acid (phenol) dressings to surgical wounds air was excluded, thereby preventing suppuration, a form of putrefaction. For Ogston, however, this explanation was insufficient. Often “meditating on the subject [he] became more and more convinced that there was a single cause, and that the cause was some special germ.” He opened the abscess of one of his patients, made a stained smear of the pus and examined it under a microscope.
“My delight may be conceived when there were revealed to me beautiful tangles, tufts and chains of round organisms in great numbers, which stood out clear and distinct among the pus cells and debris…”(1)
Ogston hypothesized that acute abscesses were caused by micrococci. After injecting pus from acute abscesses into guinea pigs and mice, he demonstrated that new abscesses formed, followed by signs of septicemia. Examining the blood of the septic animals he found micrococci. If, however, he pretreated the pus with heat or carbolic acid before injecting it, abscess formation was avoided. Ogston also designed a method for culturing micrococci by inoculating hens’ eggs with pus and incubating them. The contents of the infected eggs were found to have similar pyogenic activity to that of the original pus (2,3).
Although Ogston was not the first to examine pus microscopically and describe micrococci (from the Greek kokkos, meaning berry), those in chains had already been designated Streptococci by Billroth (1874). In 1882 Ogston named the clustered micrococci “staphylococci,” from the Greek staphyle, meaning bunch of grapes.
In 1884 Anton J. Rosenbach (1842-1923), a German surgeon, isolated two strains of staphylococci, which he named for the pigmented appearance of their colonies: Staphylococcus aureus, from the Latin aurum for gold, and Staphylococcus albus(now called epidermidis), from the Latin albus for white (5).
