sign in sign up
<<
Home , Brucella, Brucella melitensis

Le Infezioni in Medicina, n. 1, 77-86, 2016 Infections in the history of medicine 77

Historical perspective of : a microbiological and epidemiological overview

Orhan Akpınar Department of Microbiology, Faculty of Dentistry, Suleyman Demirel University, Isparta, Turkey

SummaRY The historical process of brucellosis extends back to Hippocrates’ time, brucellosis has been characterized by humankind’s first contact with animals. Although bru- fever. Our aim is to investigate selfless work undertaken cellosis is a sporadic disease observed in animals in cer- by scientists on the epidemiology, diagnosis and clinical tain regions of the world, it is an important disease in findings of brucellosis until today, and to gain a histori- humans that can affect many organs and systems due cal perspective about the disease that is as old as human to the consumption of contaminated milk or milk prod- history, still has importance today, causes economic ucts. Studies have shown that the presence of losses in treated animals and harms human health. dates back to 60 million years ago. In 450 BC, Hippo- crates described a disease similar to brucellosis. Since Keywords: brucellosis, historical perspectives.

n INTRODUCTION the risk that may occur due to other in- fectious diseases [2, 3]. The disease is generally rucellosis, which is primarily an animal dis- transmitted to humans by eating cheese, made Bease, is a zoonosis that is transmitted to hu- from , and milk products such as cream mans from infected animals’ meat, milk, urine, and butter. Brucella can protect their vitality for body fluids, and pregnancy material, as well as 1-2 months in fresh cheese, 4 months in butter, from milk products prepared by infected milk 1 month in ice cream, and 6 months in cream. [1, 2]. Brucellosis is an infection seen all over the Therefore, brucellosis is not transmitted in cheese world, especially in the Mediterranean countries, aged for at least three months. Brucella cannot live the Arabian Peninsula, India, Mexico, and Cen- in [2, 3]. The disease may also be transmit- tral and North America. In developed countries, ted by eating animals’ reticuloendotelial organs, the infection has been eradicated from animals, such as the and , without proper cook- but developing countries still have significant ing. In addition, it may be transmitted by way of morbidity [1-3]. Brucella species cause mild or as- infected secretions coming into contact with skin ymptomatic diseases in animals, which are their cracks, conjunctiva, or the inhalation of dust in natural hosts. Eritriol, located in animals’ breasts, stables. Therefore, breeders, , labo- uterus, placenta, and epididymis, is a growth ratory workers, and abattoir workers are occupa- factor for these . For this reason, Brucella tional risk groups for the disease’s dairy form [2, can lead to abortion and sterility in animals. Due 4, 5]. to absence of eritriol in the human placenta, the The history of the disease extends back to people’s abortion risk due to brucellosis is not higher than first contact with animals. Studies have demon- strated that the presence of brucellosis in humans and animals is ancient. Moreno et al. reported the Corresponding author presence of and Orhan Akpinar in double-hoofed animals around twenty million E-mail: [email protected] years ago in their study. The study also suggested 78 O. Akpınar

that seals, otters, and wild rodents may have be- Studies have demonstrated that, in ancient times, come natural hosts for in the process fresh cheese and other milk products were often of evolution [6]. We do not know exactly when part of the regional diets for communities living people first encountered this disease. However, in Albania and other countries surrounding the the disease’s historical process, which is as old as Mediterranean basin [9]. People living in these human history, extends to people’s first contact communities might have lived in contact with with animals. Thus, the assumption of the pres- contaminated milk products and infected ani- ence of Brucella infections in the earliest periods mals. Capasso showed a correlation between milk of human history is not wrong. Archaeological products and brucellosis in his research, which and anthropological studies confirm our opinion. was performed in the ancient city of Herculane- Views performed on a human skeleton (Australo- um [10]. The presence of Brucella spp. was clearly pithecus africanus) in South Africa from 2.4-2.8 shown by morphological, and molecular analy- million years ago shows that lytic bone lesions ses done on skeletons found in Albania (ancient detected in the lumbar vertebrae (L4-L5) overlap Butrint) (Figure 3) [9]. with brucellosis radiologically, macroscopically, In the middle of the 17th century, George Cleg- and microscopically (Figure 1) [7]. horn (1716-1789) identified cases of recurrent fe- Bone lesions that are typical of brucellosis have brile seizures in Minorca while on duty [11]. As been found in anthropologic studies performed in a surgeon in the British army, Cleghorn served adult skeletons found in the ruins of an old Ro- in Minorca between the years 1736-1749, and col- man city destroyed by a volcanic eruption in 79 lected data about the most common diseases on AD; additionally, the presence of cocci-like forms, the island while treating not only British troops morphologically similar to Brucella, were found but also the local community [12]. in an embedded carbonized cheese analysis per- Manuel Rodríguez Caramazana (1765-1836), a formed with an electron microscope (Figure 2) [8]. surgeon in the Spanish army, was appointed as

Figure 1 - Human skeleton in South Africa from 2.4-2.8 million years ago shows the lytic bone lesions detected in the lumbar vertebrae (L4–L5). Historical perspective of brucellosis: a microbiological and epidemiological overview 79

Figure 2 - Cocci-like bacterial particles in the Herculaneum carbonized cheese (79 AD).

chief surgical clinician at Minorca Military Hospi- tal in 1802. In 1803, he clearly described Malta fe- ver and distributed an eight-page brochure about this title in Minorca. This brochure was not met favorably by the authorities, due to its recommen- dation of stringent measures to protect people from the disease [11]. Brucellosis was first described by Jeffery Allen Marston (Figure 4) in 1860. As a surgical assis- tant in the Royal Academy of Medicine in the UK, Marston was the first to define brucellosis; he wrote his findings in detail and defined the disease as “gastric remittent fever” [13]. Marston wrote to the medical department in the same year, but the report was only published in 1863. Although Marston did not know the exact form of the causative agent of the disease, he made a distinctive definition from other Mediterranean fevers [11-14]. Several years before Marston’s disease, Florence Nightingale (Figure 5), the founder of modern nursing (1820-1910), also caught brucellosis dur- ing the Crimean War [15-16]. During the war years, she worked in hospitals in Istanbul (Üskü- Figure 3 - Vertebrae from Butrint, 17-21-year-old male. dar) and Crimea (Balaclava) and provided im- Displayed are T4–T8, T10–T12, and L1. 80 O. Akpınar

Figure 4 Jeffery Allen Marston.

portant services. She became sick while stationed in Crimea in 1855, and her high fever and severe symptoms confined her to bed. In the following weeks, the typical symptoms of Figure 5 - Florence Nightingale the founder of modern brucellosis (undulant fever) appeared. Nightin- nursing gale felt better in the morning, yet her situation became much worse in the afternoon. Doctors at the time believed that the situation was induced She was probably infected in a hospital in Usku- by her fatigue and psychological situation. In the dar (Figure 6). 20th century, scientists who examined her life After returning from Crimea, Florence Nightin- have concluded that she had chronic brucellosis. gale suffered many of the symptoms related to

Figure 6 - During the war years, F. Nightingale worked in hospitals in Istanbul (Üsküdar) Historical perspective of brucellosis: a microbiological and epidemiological overview 81

Figure 7 - Sir Figure 8 David Bruce. Danish vet- Discoverer erinarian of Brucella Bernard Lau- melitensis ritz Frederik (Brucellosis). Bang.

chronic brucellosis. She had five major attacks which were termed Micrococcus due to being small, during the course of the disease, which were from the of five British soldiers, who died probably the usual symptoms of bacteremic epi- of a fever in Malta. Due to the disease being seen sodes. The attack in 1861 was contained the spe- for the first time in Malta, the organisms’ name is cific symptoms of brucellosis. In 1863, she had derived from the word “melita,” meaning Malta severe spinal pain, caused by spondilitis, which in Latin (Micrococcus melitensis) [12]. continued until her death. Nightingale spent the In 1895, the Danish Bernard Lauritz last six years of her life bedridden [17]. Frederik Bang (Figure 8) isolated microorganisms, In 1887, the Scottish physician Sir David Bruce called Bacillus abortus, from giving birth as (1855-1931) identified the first disease factor (Fig- low factors of cattle placenta, fetus, and uterine ure 7). He isolated gram-negative coccobacili, wall secretions [2].

Figure 9 - Members of the Mediterra- nean Fever Commission. Photograph circa 1907. Standing: Dr Themi Zammit, Capt Crawford Kennedy, Major J G Mc- Naught. Front row seated: Major J C Weir, Dr J W H Eyre, Col D Bruce, Maj T McCulloch, Staff Surgeon E A Clayton. 82 O. Akpınar

In 1897, Wright and Smith explained that brucel- Zammit discovered that were reservoirs of losis was a zoonotic disease, after detecting spe- brucellosis, so he enabled a rapid decline in in- cific antibodies ofBrucella melitensis in human fection and death among military personnel by and animal serum agglutination tests. The diag- preventing the use of unpasteurized ’s milk. nosis of the disease using the serum agglutination The sale of milk at the door was banned after de- test, which is currently used, was carried out for termining that humans caught disease from raw the first time here [18]. The Mediterranean Fever goat’s milk. Milk vendors protested and held Commission was established in 1904. Between banners describing their victimization through- 1904 and 1907, several reports were published on out Malta by going on strike in 1906 (15 May to 1 the epidemiology, bacteriology, and pathology June). During this period, milk came from canned brucellosis (Figure 9) [19]. milk imports from the UK. During this period, as In 1905, Themistocles Zammit (1864-1935) iso- a result of strikes by milk workers, people became lated B. melitensis from goat’s milk and urine; he aware of the potential harm and did not return to explained that goats hosted B. melitensis and that their old habits [19]. people intake it from raw milk and milk products. Jacob Traum detected Brucella suis from prema- He showed the presence of the bacteria in infect- turely born piglets’ , stomachs, and kidneys ed goat’s milk, urine, and blood to prove this hy- in the state of Indiana in the United States in 1914 pothesis by doing experiments and epidemiologi- [19-21]. cal studies. Then, he developed the test used by In 1918, the American bacteriologist Alice Evans other investigators [20]. (Figure 11) showed that Malta fever and Bang dis- At the time, the Maltese distributed milk directly ease had highly homologous factors with each other. from goats at the door, and they consumed raw She explained that the three factors observed in milk. According to a rumor, there were modern goats, and cattle only had antigenic differ- villas in front and single-story farmhouses just ences, but no morphological, cultural, or bio- behind them along the narrow coastal strip in a chemical differences. A short time later, Evans region known as Medine. Goats and cattle were stated that they were in the same , after usually fed on farms; the goats and cows were comparing the two diseases’ morphological, cul- then herded in front of the luxury villas, stopping tural, and biochemical properties; in memory of in front of each house, where freshly milked milk Sir David Bruce, it was called the Brucella genus was then drunk (Figure 10). [1]. Evans offered evidence that raw cow’s milk

Figure 10 - Maltese goat herds and milkmen, who for centuries had driv- en their herds through the streets to deliver their milk fresh on the door- steps of their customers. Historical perspective of brucellosis: a microbiological and epidemiological overview 83

mally outbreaks in hunting , it was found in a female patient in 1977 [1-22]. In 1994, Brit- ish and American researchers, independently of each other, isolated previously unknown Brucella organisms from mammals’ carcasses and Cali- fornia in the Scottish coast. They iso- lated differential metabolic profiles, paint, and phage sensitivities; identical sensitivities were found in what was named B. maris [25]. Ewalt, Ross, and colleagues isolated two new Brucella species from , dolphins and seals called Brucella pinnipediae and Brucella ceteace [26, 27]. Marine mammals are contaminated from dam- aged skin, direct contact with mucous mem- branes, ingesting other infected marine mam- mals, and infected mother’s fetal tissue and milk Figure 11 - American bacteriologist Alice Evans. [28]. As experimentally demonstrated in cattle, Brucella species can also infect terrestrial mam- mal species [29]. Information about the transmis- was a factor of brucellosis in humans. She found sion of brucellosis from marine mammals to hu- that B. melitensis in people and B. abortus in cows mans is available in the literature. Among labo- were associated with undulant fever [22]. During ratory workers, transmission has been reported this work, Evans also became infected. Despite to occur after occupational exposure. In another taking every precaution while doing her research, case, infection was reported in a patient with she became infected; Brucella were isolated from spinal in New Zealand [30-31]. Fi- her blood in 1922. The possible modes of trans- nally, in 2008, was isolated from mission were expected to be from the respiratory field mice in Central Europe and the mandibular tract. Although her disease was associated with lymph nodes of a wild by Scholz et al. remission and relapse, it sometimes affected her This species has not been shown to cause disease health very negatively. In 1927, she was elected in humans but is a potential risk, especially for as president of the Society of American Bacte- hunters [32]. riologist (American Society for Microbiology, In these aforementioned studies, the isolation of ASM); however, she was bedridden due to her Brucella from different animals and humans by relapsed brucellosis and could not attend the so- researchers has elucidated the epidemiology of ciety’s meeting. In 1943, Evans developed a hy- Brucella, which is an anthropozoonosis, and sheds persensitivity to the Brucella antigen and could light on the present studies. no longer work with live cell cultures. However, In our country, the first studies to determine Bru- as a patient with chronic brucellosis, she shared cella’s factors began with the isolation of B. meli- valuable information from her own experiences. tensis in a soldier, who was treated at the Kuleli Thus, the evidence related to chronic brucellosis Military Hospital (Figure 12) by Doctor Hüsamet- was identified in the first half of the 20th century tin Kural (Figure 13) and Mahmut Sami Akalın in [22-24]. 1905. In 1924, B. abortus infections in humans were re- In our country, the first isolation in cattle was re- ported by Orpen in England. In Puerto Rico, simi- ported by Zühtü Berke in 1931-32. lar studies were conducted by Morales-Otero. In B. melitensis in was first detected in 1944 by 1953, in sheep was described by Van Aktan and Köylüog˘lu at the Bandırma Merinos Drimmelen. In 1957, Brucella neotoma was isolated farm [33]. In Turkey, Brucella were detected with from a wood tick in the state of Utah, in the Unit- serological methods in humans and animals by ed States, by Stoenn and Blackman [22]. Golem in 1943 [34]. B. canis factor in dogs was de- In 1968 was isolated in beagle dogs termined serologically by Istanbulluoglu et al. in by Carmichael and Bruner. Although B. canis nor- 1983. In Turkey, the most comprehensive study on 84 O. Akpınar

.Figure 12 - Kuleli Military Hospital in Istanbul. Today it is used as a military school.

the epidemiology of brucellosis in humans was trace in the disease’s clinical course, the disease made by Çetin et al. between 1984–1987, with the was called “undulant fever”. In Turkey, due to B. help of The Scientific and Technological Research melitensis contamination from sheep to humans, Council of Turkey (TUBITAK) [35]. the disease is called “sheep disease”; due to dis- The historical names of brucellosis include “un- ease transmission from animals to humans, it is dulant fever”, “Bang’s disease”, “Gibraltar dis- called “cost disease” or “cheese disease”; how- ease”, “Mediterranean fever”, Malta fever”, ever, the most commonly used name is brucel- “Constantinople fever” and “Crete fever”. When losis [2, 3]. the disease was first detected in the island of Malta, the disease was named “Malta fever” or “Mediterranean fever.” Due to the typical fever n CONCLUSION

Although brucellosis historically goes back to Figure 13 people’s first contact with animals, it is still an Türkish bac- endemic, zoonotic infectious disease in many teriologist Dr. Hüsamet- countries today. Studies have shown evidence tin Kural. that brucellosis occurred in animals 60 million years ago and in humans nearly 3 million years ago. The present anthropological, morphologi- cal, and molecular studies provide evidence re- lated to the presence of the disease in Mediter- ranean countries during the first century AD and the 13th and 14th centuries. Some scientists who have engaged in research related to the disease were infected during their studies and gave im- portant information about brucellosis by explain- ing their clinical condition or isolating the disease factor from their blood. At the same time, they have contributed to science by developing tests to diagnose the disease. Additionally, epidemio- Historical perspective of brucellosis: a microbiological and epidemiological overview 85

logical studies of the disease and the discovery R., Capasso L . Possible brucellosis in an early hominin of new species have provided us with valuable skeleton from Sterkfontein, South Africa. Plos one. 4, 7, information that sheds light. We commemorate 2009. all of them here. [8] Capasso L. Bacteria in two-millennia-old cheese, From a historical perspective, brucellosis was and related epizoonoses in Roman populations. J. Infec- tion. 45, 122-127, 2002. detected first in domestic mammals, then it was [9] Mutolo M.J., Jenny L.L., Buszek A.R. Osteological detected in wild mammals, and finally in marine and molecular identification of brucellosis in ancient mammal species. Butrint, Albania. Am. J. Phys. Anthropol. 147, 254-263, Although limited publications about bird species 2012. that are not affected by the disease are available, [10] Capasso L. Brucellosis at Herculaneum (79 AD). we believe that detailed research, especially about Int. J. Osteoarchaeol. 9, 277-288, 1999. birds of prey that feed on meat and birds fed [11] Hoover D.L., Friedlander A.M. Brucellosis. In: with parasites from animals, are needed [36]. We Medical aspects of chemical and (Za- should be conducting studies with the support of jtchuk R, Bellamy RF Eds). Office of the Surgeon Gen- technological facilities, since scientists who study eral; Borden Institute. 1997, 513-521. Washington D.C. [12] Vassallo D.J. The saga of brucellosis: controversy this disease have limited opportunities. Public over the credit for linking Malta fever with goat’s milk. health experts, veterinarians, infectious disease Lancet. 348, 804-808, 1996. specialists, and microbiologists have serious du- [13] Marston J.A. Report on fever (Malta). Great Britain ties regarding this issue. Army Med. Dept. Rep. 3, 486, 1861. Our aim was to highlight the scientists’ selfless [14] Johnson E.W. Brucellar bursitis. J. Bone Joint Surg. work on the epidemiology, diagnosis, and clini- Am. 36, 133-139, 1954. cal findings of brucellosis until today, as well as [15] Gill C.J., Gill G.C. Nightingale in Scutari: her lega- to collect a historical perspective about a disease cy reexamined. Clin. Infect Dis. 40, 1799-1805, 2005. that is as old as human history and still has im- [16] McDonald L. Florence Nigthingale and the early portance today, since it causes economic losses origins of evidence-based nursing. Evid. Based Nurs. 4, 68-69, 2001. through animal and human health. We hope [17] Young D.A. Florence Nightingale’s fever. Brit. Med. that these efforts have shown guidance in acting J. 311, 1697-1700, 1995. against Brucella. [18] Wright A.E., Smith F. On the application of the se- rum test to the differential diagnosis of typhoid fever and Malta fever. Lancet. 1, 656-659,1897. n REFERENCES [19] Vassallo D.J. The Corps Disease: Brucellosis and its historical association with the Royal Army Medical [1] Young E.J. Brucella species, In: Principles and Prac- Corps. J. R. Army Med. Corps. 138,140-150, 1992. tice of Infectious Diseases. (Mandell G.L., Bennett J.E., [20] Wyatt H.V. How Themistocles Zammit found Mal- Dolin R., Eds.) 2005, 2669-2674 6th ed. Churchill Living- ta fever (brucellosis) to be transmitted by the milk of stone, Philadelphia. goats. J. Royal Soc. Med. 98, 451-454, 2005. [2] Sözen T.H. Brucellozis. In Enfeksiyon Hastaliklari ve [21] Mantur B.G., Amarnath S.K. Brucellosis in India-a Mikrobiyolojisi. (Topçu Willke A, Söyletir G, ˘anay review. J. Biosci. 33, 539-547, 2008. M.,. Eds.) 2002, pp 636-641 Nobel Tip Kitapevleri press, [22] Pappas G., Akritidis N., Bosilkovski M., Tsianos E. Istanbul. Brucellosis. N. Engl. J. Med. 352, 2325-2336, 2005. [3] Medical Microbiology (Murray P.R., Rosenthal K.S., [23] Evans A.C. Difficulties in the diagnosis of chronic Pfaller M.A., Eds.) 2009, 361-363 6th ed. Mosby Else- brucellosis. Am. J. Trop. Med. 19, 319-325,1939. vier, Philadelphia. [24] Piqueras M. Microbiology: a dangerous profes- [4] Corbel M.J. Brucellosis in humans and animals. sion? Int. Microbiol. 10, 217-226, 2007. (World Health Organization). 2006, 14-15 Geneva, (Pr. [25] Foster G., Osterman B.S, Godfroid J., Jacques I., WHO/CDS/EPR/2006.7). Cloeckaert A. sp. nov. and Brucella pinni- [5] Bruselloz. Zoonotik Hastalıklar Hizmet içi Eg˘itim pedialis sp. nov. for Brucella strains with cetaceans and Modülü katılımcı kitabı (Buzgan T, Erkoç Y, Çom S, Ir- seals as their preferred mak H, Pelitli TS Eds.) 2011, 29-51. T.C. Sag˘lık Bakanlıg˘ı hosts. Int. J. Syst. Evol. Microbiol. 57, 2688-2693, 2007. Sag˘lık Bakanlıg˘ı Bas¸ak Matbaacılık press Ankara. [26] Brew S.D., Perrett L.L., Stack J.A., MacMillan A.P., [6] Moreno E., Cloeckaert A., Moriyon I. Brucella evolu- Staunton N.J. Human exposure to Brucella recovered tion and . Vet. Microbiol. 90, 209-227, 2002. from a sea mammal. Vet. Rec. 17, 483, 1999. [7] D’Anastasio R., Zipfel B., Moggi-Cecchi J., Stanyon [27] Ewalt D.R, Payeur J.B, Martın B.M, Cummins D.R, 86 O. Akpınar

Miller W.G. Characteristics of a Brucella species from a nal osteomyelitis in New Zealand. J. Clin. Microbiol. 44, bottlenose (Tursiops truncates). J. Vet. Diagn. In- 4, 363-370, 2006. vest. 6, 448-452, 1994. [32] Scholz H.C., Hofer E., Vergnaud G., et al. Isolation [28] Hernandez-Mora G., Guzmán-Verri C., Chaves- of Brucella microti from mandibular lymph nodes of red Olarte E., et al. Characteristics of a Brucella species from foxes, Vulpes vulpes, in lower Austria. Vector Borne Zoo- a bottlenose dolphin (Tursiops truncates). Em. Infect. Dis. notic Disease. 9, 2, 153-155, 2009. 14, 1430-1433, 2008. [33] Erog˘lu M. Türkiye’deki Bruselloz tipleri. [29] Rhyan J.C., Gidlewski T., Ewalt D.R., Hennager Uluslararası Brusellozis Sempozyumu (18-20. Ekim S.G., Lambourne D.M., Olsen S.C. Seroconversion and 1988). Pendik Hayvan Hast. Merk. Arast. Enst. Istandul. abortion in cattle experimentally infected with Brucella 9, 28-35,1989. sp. isolated from a Pacific harbor seal (Phoca vitulina [34] Golem S.B. Memleketimizdeki insan ve ehli hay- richardsi). J. Vet. Diagn. Invest. 13, 379-382, 2001. vanlarda Brucella bakımından serolojik Aras¸tırma. Türk [30] Sohn A.H., Probert W.S., Glaser C.A., et al. Human Hıfsız ve Tecr. Biol Mec. 1, 105-116, 1943. neurobrucellosis with intracerebral granuloma caused [35] Çetin E.T., Çoral B., Bilgiç A. Türkiye’de insanda by a marine mammal Brucella spp. Emerg. Infect. Dis. 9, bruselloz insidansının saptanması. Dog˘a-Turk. J. Med. 485-488, 2003. Sci. 14,324-334,1990. [31] McDonald W.L., Jamaludin R., Mackereth G., et [36] Kumar S., Kulshrestha R.C., Bhatia K.C., Kaushik al. Characterization of a Brucella sp. strain as a marine- R.K. Brucellosis in poultry - an experimental study. Int. mammal type despite isolation from a patient with spi- J. Zoonoses. 2,133-138, 1984.