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Home , Justus von Liebig, Silvering

THE BARON JUSTUS VON UEBlG MEMOR1AL LECfURE 1997 - the gatekeeper of

Professor W.H. Brock, BSc, MSc, PhD Department of History, University of Leicester, Leicester, UK

While travellin g around Au stralia in 1989 I was repea tedly ex plosive sil ver , a salt of fulminic ac id. Cyani c acid made aware of th e presence of Justu s vo n Liebig ( 1803-73), was then being analysed in Berzelius's Stockholm laboratory Near Ali ce Sprin gs I came across Mt Li ebig. in the Port by the YOllllg Friedrich Wohler ( 1800-1882), who showed that Curti s di stri ct of New South Wal es I learned of a Li ebig its compos ition was identical wi th Liebi g's fu lminic aci d. After County, as we ll as a Li ebi g Street in Warrnambool on the the two young chemi sts had met at Frankf11l1 in 1826 and gone Great Ocean Road 10 the south west of Melbourne. through their respecti ve preparations and ana lyses And at Irra w

The work on , together wi th <.l Inceting wi th the influent ia l Germ an traveller, A lexander von Humboldt ( 1769- 1859), who then lived in Paris and who was always on the loo k out for young tal ent, led LO Liebig's appointment La a Chair at the small uni versity ofGiessen in May 1824. As Liebig lalcr observed in a fragmentary autobiography, 'al a !m:1Jc r university. or ill a larger IOWIl. Illy energies would !/(fI'C been divided alld dis,\';paled, (lnd it \IIould have beell Above: Liebig's analytic;.1 laboratory (after:. drawing by Tr.llltschold). Right: I h" "me Pictu res counesy of Wilhelrn Lewicki. Liebigiana Ludwigshafen. Justus Liebig Society i /II/((.:h more difficult, perhaps impossible. 10 reach my goal.·2 This goal was to cxp'lIld and inst itutionalisc the lcaching - attracted by Liebig's techniques, reputation and the low fees of chemi stry (w hi ch hitherto in Germ an uni versiti es had made possible by the Hcssen government's subsidy of the been mere ly an adj unct of pharmacy For apo thecaries and laboratOly- Liebig had to expand his facilities and to syslematise medical student s) by placing it upon a thoro ughl y practi cal Lh e tndnillg he gave to students. Two or his students, Heinri ch (or laboratory) basis and by concentrating attention upon the Wi ll (18 12- 90) and Carl Remigills Freseni us (18 18-1897) were little-cult ivated arCH of organic chemi stry. As a teacher, cncouraged to publish tex tbooks on qualitative and quantitative Li ebig hnd initiall y conccntrated on pharmacy through a analysis whjch were translated into severaJ languages. Liebig's private school that the University authorities all owed hi m to Im-ge number or roreign students (on average at least ten every conduct as part of hi s professorial duties. This school was semester) also ensured ~1a t his emphasis upon laboratory-based eventually absorbed into the Philosophy FaculL y in the teaching and researc h was copied in other cOUlmies and Gelman 1830s. It was pharmacy and the difficul ties with th e analyses states-ror example, at the Royal College of ChemisLIy founded or th e alk aloids, that di rected Li ebig's atte nti on to thc need in London in 1845, and 's large laboratory at 10 speed tip and to sim plify th e basic copper ox ide techn ique Leipzig in Saxony in 1868.3 of organi c analysis th at he devised in 1830. The perfection Liebig remained 28 years in , where the Duke of of this method led to a decade of in tensive in vest igati on o f Hesse Drumstadt made hi m a Baron in 1845. in 1852, worn out org'.IIli c compounds by Li ebig and his students, Li ebig by teaching, he moved to the University of where he no himself publishing an average of thi rty papers each year longer gave practical instnlcli on, but plirsued his own interests betwee n 1830 and 1840. Several of the se we re to be of the and did a great amount or popular lecturing and writing. greatest significance for the theory and practi ce o f organi c chemistry, nota bly an extensive series of papers on th e Farming cont ent of bases, the joint work with Wohler on th e benzoyl radical ( 1832), and on the degradat ion products of Sickened by ted ious di sputes conceming the consLitlition of IIrea (1837), the discovery of chlora l (trichloroethanol, organic compounds, and cOllvi nced that orgrutic chenustry could 1832). the identilieati on of the eth yl radica l ( 1834), the be used as a tool to investigate ti ving processes, Liebig preparation of ace taldehyde (eth anol, 1835), and the abandoned pure chemj sLIy from about 1840 in an attempt to polybasic theory of organic ac ids (1838). solve aglicultural and physiological questions. in lhat year he The radical theOlY, together with growing experience of publi shed Die orgallische Chemie ill ilire,. Amvendllllg all! organic analysis, gave Liebig and Wohler the confidence to AgriclIlllIr IIlld Plly.\·;ologie (Braunschweig, 1840). Simul­ analyse urine betwecn 1837 and 1838 and to identi fy, anal yse taneously translated into Engli sh and French, thi s book sLI"Cssed an d classify its inllu merable constituents and degradation that because 'perfect agricullure is the tme foundation of aU products. such as urca (carbamide), uri c acid . allantoin and trade and indusuy ... a rati onal system of agricultm"C cannot be uramil. which they believed to be produced by 'innunlcrablc ronncd without U)Capplicalion of scientific principles.' Only the Ill l..:t amoqJhoscs' of uric acid - itselr a degradati on product, as chemist, he claimed somewhat dogmatically, could teIJ the thcy supposed. of nesh and blood. This magnirieen,t_ farmer the best means of feed ing vegetables, the nalure or the investigation. which galvanised British chemists when Liebig different and the actjon of different manures upon them, By n..:portcd it to the British Association during his first visit to analysing s Liebig showed that the prevailing ' theolY' Britain in 1837, gave contcmponuy doctors a new in sight into in which a plant 's carbon was supposed to origi nate principaUy the pathology or kidney and bladder diseases. Later, in 1852, from leaf mould, and not from the atmosphere by Liebig provided clini cian s with simple chemical procedures ror photosynthesis, was rallacious. On the other hand, Liebig argued the quantitative determination of the urea in urine, and or the incorrectly ror many years that nitrogen in the fo rm of oxygen content of the air by its adsorption in an alka li ne atmospheric and nitrates in the soil were more solution or pyrogallol (benzene-I ,2,3-tri ol). impo l 1~lIl t direct sources of plant niu'ogen than manures, whose As more and more students nocked to Giessen in the 18305 principal function he saw ns providing trace minerals after

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accumulated . Liebig's views of metaboli sm, pathology and di sease also offered powerful propaganda for reformers who wanted to introduce practical chemi suy and biochemi stry into the medical cun·i cululll. This is to be seen clearly in the pages of the Blitish medical weekly, The umcel, where Liebig's name IS repeatedly found in the 1840s in admiring contexts.

today. Left: Liebi g's old laboratory or 1825. ,md Ihc Liebig Memori,d Exhibiliofl 1998.

in the soil. It was 10 provide these s more Liebig was much interested in th e chemi stry of fo od, effi ciently that in 1845 Li ebi g developed 'chemical manures'­ especiall y in the best way to cook meat to preserve its the f1rst of several commercial ventures made by him. nutritional qualities. In 1847, in a fUlther book, Cllemisclle Agricutural chemi stry led Li ebig into a long and ill­ Untersuchungen fiber das Fleisch, he described an 'extract of mannered polemic with th e wealthy landowner, Sir John meat' (extraclUIIl car/lis) prepared by low pressure evaporation Bennet Lawes (18 14- 1899), and hi s assistant, Joseph Gilbert of the soup from lean meat, and claimed that il would be a ( 18 17-190 J), a fanner student of Liebig's (It Gicssen. Long­ valuable restorative for tho sick, wounded (lnd ill -nourished. In term fi eld ex periment s on Lawes' estate at Rothamsted in later editions of hi s popular Chemische Brie/e, or Familiar Hertfordshire showed catego ri cally that Liebi g's fe rtili sers LeUer,\" 0 11 Chellli,\"/ly as they were called in English, he pointed

~ I led to no marked improvement in crop yields. For some ou t that in countries where cattle were chi efl y slaughtered for years Li ebi g refu sed to accept this conclusion and it was their hides or tall ow (as in SOllth America and Australia), such only after 1850, when John Thomas Way demonstrated th e a food could be prepared extremely economicall y. action of topsoil in withdrawing soluble sa lts from solution This suggesti on was taken up in the I 860s by the German (ground absorption) thaI U ebig recognised thaI he had been railway engineer, Georg Giebert, who wilh Liebig 's mi staken to make hi s mineral manures difficu lt to di ssolve. promotional assistance marketed ' Li ebig's Extract of Meat' Meanwhile, Lawes' independent researches led him to as a nutritious food for invalids and the labouring classes. In develop ammoniated and superphosphate fertili sers, a th e same decade Li ebig also developed commercial suggestion already made by Li ebi g in hi s Agriculturchemie. processes for an artif"ic ial milk for babies, lhe improved Their manufacture, which demanded a significant scaling up of baking or wholemeal bread, and for th e sil ve ring of . sulphuric acid production, soon became an impoJ1ant accelerant of Ihe induslriali sati on of Europe and of the veltical integration Liebig and the British of chemical industri es. Li ebig's aphorism of 1843, thaI the measure of a coun tIY's civilisation lay in the amount of Liebi g e l~ oyed a particularl y close relationship with Great sulphuric acid it produced evclY ye;.u·, has become famous. Both Britain, which he visited six times and whose pattern of directl y and indirectly, Li ebig was an influential fi gure in the scientifi c educati on, agriculture and medical practice he helped developmenl of scientific agriculture and hence in increasing to change. In 1843, several of hi s Engli sh friends tried to fo od supplies at a time when a ri sing European population was persuade him to apply for the vacant chair of chemi stlY at undergoing urbanisati on and industrialisation. King's Coll ege, London, but the College's affiliation with the Church of England precluded any seri ous olrer being made to Disease and Food him, and the position went instead to Li ebi g's erstwhile Engli sh pupil , William Allen Miller. Two years' later, wilen the Royal Ln 1842 Liebig published a sequel, Die OIgallischer Chefllie ill College of Chemi stlY was about to be established, it was again ihrer Amvelldul1g at!f Physi%gie ulld Pal/lOlogie. In thi s, by hoped that Liebig mi ght personall y come to London to means of analyses and highly speculative equations, he auempfed superintend il and to recreate hi s Giessen teaching and research to unravel the metabol.ic routes by which foodslufl's wer';­ laboratory in Oxford Street; in the event, the post of Director transformed in/a nesh and blood, and whereby tissues were was given, on Liebig's personal recommendation, (0 hi s beS(­ degraded into animal heat, muscular work, and n0I111al or known pupil, Hofmann (1818-1892), who spent twenty frui tful abnolmal secretions and excretions. His claim that fell1lentation years in London. Together with Liebi g's fifty or so other Briti sh and putrefacti on were merely dynamic reshuillings of the pupils who held industrial or academic posts throughollt the constituent parts of chemical substances also led many doctors to British Isles, Hofmann ensured that Liebi g's name and work espouse a chemical theolY of di sease wh ich both challenged and were kept prominentl y before the public eye. Liebig's name made more sophisticated the predominanl sanitarian view that was also kept before the pub li c through his commercial di sease was sprend by a poisonolls miasma which arose from aCLivi ti es with the Li ebig Extract of Meat" Company ancl

3 Culture Vol 19 No 2

Liebig's Coneen~llted Milk Baby Food. Liebig looked to Britain and practice would benefit from some chemical feltiliscr. Once for a respecrful and sympathetic audience for his ide..1S on, and done, these boundary sciences wouJd not only make more sense di sCQVC I;CS in , chemical science. Here was an overse.l'i audience and prove more fmi tful , but would enable important new which, though frequclllly provoked into controversy by his work, interdiscipiines to emerge. was often more sympathetic towards it than ones in the Gelman Liebig 's cenlralmessnge was so extremely succcssfu l that it nations. Equally, young professionali sing groups of British now takes some effolt to understmld that despite the glamorous chemists, doctors, engineers and educators, found 'Liebig' an propag~U1da of twentieth-celllury cosmologists mld physicists or clTccli ve publicity slogan, agelll and figurehead in their ci.unpaigns molecular biologists, chemisuy really is the most fundamentally to reverse the individualistic and utilitarian tendencies in British eentral and useful of all tile scienees. Liebig's aphorism that soap culture and socicly.4 Gust like sulphuric acid) is a measure of civilisation is reall y a metaphor of the fact that our modem complex societies Ga tekeeper of Chemistry canIlot fun cti on wi thout chemi sts and the understanding of chemistry. Li ebi g coul d be irascib le, pi g-headed, Liebig's eareer, therefore, deserves attention today quan'elsomc, and sometimes deviolls, but he not only beeause he helped to ~n s fo'm the never occame quirky, obstreperous and an teaching of chemistry and created the modem cmixUl'aSsmcnl. QU

New 12 Place Disc Dispenser

Oxoid Ltd has in troduced a 12 place di sc di spenser to the Oxoid Ant im icrobial Suscept ibi lity Testing (AST) range. It provides added convenience and fl ex ibility in clinical microbiology laboratories by accollllllodati ng the precise positioning of up to 12 discs on a 150111111 plate. Oxoid di sc di spensers .Ire now available in 6. 8 and 12 place formats. suitable for use with 90, 100 or 150mm plates. respectiVely. The dispensers enhance the complete Oxoid AST System which incorporates: Th e widest range of antimicrobial di scs manufactured to the highest internat ional standards (DIN) Hi gh performance culture media (Oxoid Muell er-Hinton Agar and Oxoid I so~Se n s it est Agar) for cl ear. sharp zones of inhi bition and reproducib le results The new Oxoid Turbidometer for inoculuTll density standardisation (I ura - an electronic zone size measurement fa cility linked to a species-specifi c database and powerful interpretive software. For further il/form(ltiol/ COI/lact: Valerie Kane. Oxoid Limited, Wade Road. Basingstoke. Hants RG24 8PW, England. Tel: (01256) 841144. Fax: (01 256) 463388. e- mail: [email protected]

4 CuitureVol19 No 2

European tick-borne infections Professor Marta Granstrom, MD, PhD Professor in Clinical Microbiology, Karolinska Institute S-171 76 Stockholm, Sweden

~l A large number of infections are kn own to be tick­ more outdoor acti viti es. Children show both higher lransmillcd zoonoses, i.e. infections transmitted fro l11 incidence rates and a different distribution of manifestations, animals to human s. The present article focuses on those e.g. more neurological disease, than adults. infections wh ich arc prevalent in large parts of Europe, i.c. Treatment strategies for LB vary between countries and Lyme borreli os is (LB), ti ck-borne encephalitis (TBE), physicians but several regimens are useful. Prevention is ehrlichiosis and babesiosis, with special emphasis on the currently based on protection against ti ck-bite but two two lalter, emerging infecti ons. vacci nes, both based on the outer surface protein A (Osp A), have been tested in the US and preliminary reports indicate LYME BORRELlOSIS ~85% efficacy. It is likely that a vaccine will eventually be available also in Europc althougb production will be more complex sin ce the vaccine wi ll have to include Osp A from Lyme borreli osis (LB) is the most common arthropod­ all three genospecies in Europe compared with the one in the transmitted zoonosis in both Europe and North America. LB US trial. is caused by a new species of the genus Borrelia (family The most commonly used diagnostic method for LB is Spirochaetaceae), transmitted by hard ticks (Ixodidae) of the serology by ELISA, including antibody detection in genus Ixodes. In Western Europe, the vector is Ixodes ricinus cerebrospinal fluid, supplemented in some laboratories by (Figure 1). Animal reservo irs are rodents but large animals, immunoblot. e.g. deer, caule and horses, are important for the life cycle The European Union, recognising the need for a joint effort of the tick. LB has a wider clinical spectrum in Europe than in the field of Lyme disease, supported a Concerted Action on in the US , due to the presence in Europe of at least three Lyme Borreliosis (EUCAI,.B). This network of scientists and genospecies of B. burgdO/Jeri sensu lato, i.e. B. aIzelii, B. clinicians from seventeen European countries investigated2 garinii and B. burgdOlferi sensu striclO compared with the many aspects of the disease and disease transmiss ion then one genospecies, B. bIlrgdOlJeri sensu stricto, in the US. made the information all European LB available on the The most common cl inical manifestations of Lyme Internet (http://www.dis.strath.ac.uk/vie/LymeEUI). borreli osis in Europe are erythema migrans (EM) and neuroborreliosis I. LB has been reported from all European countries but incidence data are mainly estimates, ranging TICK-BORNE ENCEPHALlnS (THE) from 3 per 100,000 in the UK to 120- 130 per 100,000 in Austria and Slovenia. The infection shows a gradient of The disease3.4 is caused by tick-borne encephaJiti s vi rus increasing incidence from west to east, although pockets of (TBEY) of the family Flaviviridae, genus Flavivirlls high-endemic areas are present also in low-endemic (formally group B arbovirus), a family including many other countries. known arthropod-borne viruses, e .g. those causing yellow Disease incidence rates are also increased in certain fever, dengue and Japanese encephalitis. 1\vo SUbtypes of occupations, e.g. forestry workers and in some recreational TBEY are recognised, one European and one Par Eastern, occupations, e.g. ori enteers. Incidence rates are higher in transmitted by Ixodes ricinus and Ixodes persu!carus, males, presumed lo be due to higher occupational ri sks and respectively. The distribution of the two related tick species overlap in north-eastern Europe but in general the vector ofTBEV is I. ricinus in western and central Europe and I. persulcaflls in Russia. Tick-borne encephalitis is a major cause of morbidity in central, eastern and northern Europe. West of a sharp limit from mid Sweden though mid France, the disease is rare or non-existent. As for LB, disease incidence rates increase from west to east, with the highest reported rate of 184 per 100,000. The majority of LB infections (60-70%) are subclinical. In clinical cases, the incubation period is 7-14 days and the first viraemic stage with flu­ like symptoms lasts 2-8 days. This first phase is reported by 60-70% of patients who later go on to develop the second, neurological stage. The second stage is found in 5-30% of cases with clinical disease and the manifestations vary from

pure meningitis to meningo-encephalitis t with or without paralysis. Reported mortality rates for the Figure I. l.rodes ricillllS - main vet tor of Lyme disease (Lyme borreliosis) in western europe. western TBEY infection vary between 0 and 4%.

5 Culture Vol 19 No 2 •••••••••••••••••••••••••••••IIII!

common clini cal manifestati on is a fl u-li ke illness wi th fever, malaise and myalgia. Common laboratory findi ngs include leukopeni a, thrombocytope ni a, anaemia and e levated li ver transaminases. The treatment o f cho ice is doxycyclin . Severe disease man ifestati ons that have been reported are adult respiratory distress syndrome (A RDS), re nal failure and severe hepati c disease. Serious neuro logical involvement is mani fested by seizures, coma and CNS lesions. Persistent in fecti on, a characteristi c of ehrlicllial in fec ti ons in animals, has also been demonstrated. No cases of blood-tra nsfu sion transmitted infections are known. Annual incidence rates of3- 5 per 100,000 have been estimated in the endemic areas o f sOllthern US. In fection rates in ticks of up to 32.5% have been reported. Fij.\uI'"C 2. Characte ri stic inclusion body (momla) seen next 10 the nucleus o f .. gr .. nulocytc in a In Europe, virtuall y nothing is known of either blood smear from 01 horse infected with the BGE agent. Momhlc arc diagnostic for granulocytic the incidence or the prevalence of the d isease but chrlichios is in hwmms also but infected gr.mul ocylcs arc much less of a common fi nding in hu man than in veterinary medicine. a few serological cases of E. chaffeells;s infec ti on have been reported. No certain clinical case has been identified. The vector is unknown. The di sease, in children, is relati vely mild and both the In th e US, th e vector most consistentl y associated wi th severity of the disease and the ri sk of perm anent sequelae the di sease is Amblyol1lma americalllll1l, the lone star ti ck, in crease with age. The reported rates of long-term sequelae whi ch is not present in Europe. Ehrlichi ae have been shown va ry betwee n 2 and II % for perm anent paresis, 7- 14% for by PCR in adult Al1Iblyol1la al1ler iCaflwn ti cks (bu t not in heari ng defccts and 0- 24% for cerebellar dysfuncti on. nymphs) and in Dermacentor variabilis (th e A merican dog Carefull y conducted fo ll ow-up studies indicate moderate to ti ck) in one case. severe postencephal itic symptoms in 36-58% of pat ient s. The animal reservoirs and susceptible hosts are, as yet, Laboratory diagnosis of the disease re li es on serology. not fu ll y identifi ed. The white-tai led deer is susceptible to The most widely used assay is a commercially avail able ex perimental infecti on and popul ations of deer show high ELI SA for IgM and IgG anti bodies. rates of antibodies to E. chaJJeeli sis in endemic areas. No specific treatment is available. Prophylax is and post­ Ex perimenta ll y in fec ted dogs, like th e white-tail ed deer, exposure prop hylax is with specifi c immunoglobulin can be show persistent in fection. The role of rodents in the given up to the fourth day of presumed exposure. An transmi ssion cycle remai ns to be elucidated. e ffi cient vacc ine against TBEV is available frol11 two Diagnosis is confirmed by pe R and serology by manu facturers and is widely used in endemi c areas. im munofluorescence (IF) with commerciall y available Vacci nati on should be offered to those who

6 CultureVol 19 No 2 not been full y elucid ated. The white-tailed deer seems to Diagnosis of B. divergells infec tion can be made on blood represent a likely reservoir and the rol e of rodent s re mains to smears when many parasites are presem (as shown in Figure 3). be clarifi ed. Lnoculation of gerbil s can also give the diagnosis. Serological Human HGE infecti on in Europe was first identified by diagnos is of B. di vergens is made by IF on smears from serology in LB patient s fro m Switzerland, UK and Norway. ex perimentall y infected animals. Antibodies seem to decrease to A seroprevalence study8 in a general population of south­ base-line levels within a year. B. divergens can be cultured in western Sweden showed 21 /1 85 (11 .4%) HGE seropositi ves eryth rocytes (Figure 3). Neither an ELISA for anti bodies to B. where the rate for LB seropositi ves was 25/ 185 ( 13.5%). diverge ns in human sera nor a peR have been published. Recentl y, four cl ini cal cases have been found in Slovenia9 but unpublished cases are known both from Scandin av ia and oth er part s of Europe. Babesia mi croti The presence of th e HGE agent in Europe was first demonstrated in Swedish Ixodes ricifltls lO. The animal The Eu ropean situation with a rare but severe in fecti on in reservo irs have not yet been full y established but the HGE immunocompromised individuals differs markedly from the agent has been identi fie d as a common calise of cl inical US, where many hundreds of cases of B. microti infection have been described, the majority in immunocompetent disease in Swedish dogs and horses II, The diagnosis of HGE is based on pe R and serology by individuals. IF. Anti bodies measured by IF seem to return, as for E. Recent seroepidemi ological slUdi es in eastern US have chajJeel1sis, to base-li ne level within two years of infecti on. indicated in fecti on rates for B. miaOli varyin g from 2% in Commercia l slides using a recent human HGE isolate are asymptomatic indivi duals to 7.5% in individuals with a ava il able. No ELlS A has been described. hi story of Li ck biLe and fever. Another populati on study showed seroprevalence rates for B. microti infecti on of 9% in adulls and 12% in children. BABES10S1S In Europe, virtuall y nothing is known about 8. micrOli infecti ons. Sporadic reports have cl aimed asympLOmatic The c<:lllsati ve agents, Babesia species (phylum Apicomplexa), seroposit ives for B. microli in Europe (France, southern named after Victor Babes, are pear-shaped, malaria- li ke, Germany) but no systemati c studies have been conducted. It protozoan paras ites. The pi roplasms arc represented by two is likely that the in fect ion occurs in immunocompetent families, the Babesiidae and the Theileriidae. The two differ individuals also in Europe, especially as B. microli was in target cell s and also in the mode of replicati on in ticks. isolated, several decades ago, from rodents in both Germany Some of the agents currentl y classified as babesiae are more and the UK. I2 14 closely re lated [0 theileriae - . In the US, the most severe, often fa tal, infections of B. More than 100 species of Babesia are known but onl y microti have been descri bed in spl enectomised patients. B. two, B. divergel1 s in Europe and B. micro,i in the US, have micrOli causes 1110re severe disease in older individuals than until recentl y been show n to cause disease in humans. Of in children, a parall el to the clinical spectrum seen in these, B. divergells belongs to the classical Babesia while B. veterinary medicin e. The symptoms in immunocompetent microli is a more Theileria-like organism. In 199 1, a human individuals are uncharacteri stic or flu-like as in ehrlichiosis, pathogen, WA I, was found in California and shown to be a with malaise, fa tigue, fe ver, headache, myalgia, arthralgia, new species, related to but different from B. gibsoni. In vomit ing, depression and emoti onal lability as major 1996, a strain (MO I) resembling but not identi cal to B. sympLO ms. Dark urine is common as are mild increases in dive/gem' caused a fa tal disease in a spl enectomised patient transaminases. Babesiosis has been associated with a late­ in Missouri, US. onset adull respi ratory distress syndrome (ARDS). Chronic infec tions in untreated or inadequately treated pati ents are Ba bes ia diverg ens not uncommon.

Th e first human case of babes iosis was described in 1957 from Yugoslavia, a fatal case of B. , . divergells infection in a splenectomi sed fanner. Since then, some 25 clinical cases of B. divergells in fection, a majority in splenectomised pat ients, ,or have been described from all pan s of Europe. The mort ality rate has been aroun d 50%. , The disease is characterised by fever, mya lgia, haemolytic anae mi a and haemoglobulinuria, with re nal failure and sometimes pulmonary oedema in • the most severe cases. The disease has recent ly ...-) been successfull y treated with qui nine and • ~ '.! clindamycin, in combination with exchange • transfusion in severe cases. • Ahhough B. divergell s is an important - pathogen in cattle all over Europe, B. divelgell s • infecti on in immun ocompetent individuals has not .. been investigated. A few serological studi es, presented as case or congress reports, indicate the , possibili ty of infec ti on. I. ricin li S. the vector of B. bltlgdOl/eri, is also a Figure 3. Babesia llil'crgclIs infection in red blood cells. Note multiple forms (including the typical "Mallesc cross") which will havc to be differcntiatcd from malarial parasites in blood smears. The vector fo r B. divergell s bu t others cannot be rul ed high degree of parasiJacmia. as shown in these orgallisms culwrcd in human red blood cells. is Dilly out. Catt le represent the obvious reservoir. found in immunocornpromised palienls.

7 Culture Vol 19 No2

Asymptomatic cases o f B, miclVti appear to recover the US. In veterinary medicine, however, the aggravating spontaneously but the severely ill patients need treatment with effect of concurrent infection of loup ing·ill vinls (related to a combination of clindamyci n and oral quinine, which seems TBEV) and £. phagocylOphila has been kn own fo r a long to be the most effecti ve regimen. Treatment of milder cases time. The aggravalion is due \0 the immunosuppressive effecl with doxycyclin is currently bei ng investi gated in the US. of both ehrlichia l and babesial in fec ti ons. Chron ic in fecti on in asymptomatic ind iv idu als with a low Co-in fec ti ons with two or three tick-borne agents have grade parasitaemi a has been shown to be tra nsmitted by recentl y been suggested in serological studies both from the blood transfusion. More than 20 cases have until now been US and from Europe. Seropositi vity, especially in LB , does, doc umented from the US , including a fatal case of blood however, not necessa ri ly mea n a current in fecti on. transmitLed infecti on with a laIc-onset ARDS. Nevertheless, a well -designed study from th e US showed The vector for 13. lIIicroti is Ixodes scapularis in th e US, that, in patients with cli ni cal LB, concurrent B. micro!i the same as for B. burgdOlferi and fo r HOE. Rodent s have seropositi vity resulted in a more severe cl ini cal pi cture with been shown to be a major reservoir of B. micro,i in endemi c a longer disease duration than LB alone ls. areas. In Europe, one of the known vectors of B. microti is I. These ti ck-born e zoonoses and the role of co·in fec tions ricinus, alongside I. Irianguliceps. need to be investigated in Europe and th e network Slides fo r B. microt; serology, unlike B. divergells, are established within the Concerted Acti on on Lyme borreliosis commercially available. Anti bodies decrease to base· li ne intends to expand its scope o f acti on to inclu de ali lhese ti ck­ levels within a year in a majority of cases. PCR for B. borne zoonoses in Eu rope. The newly founded European micro li is widely lIsed in diagnosis of current infection. Society for Emergi ng In fecti ons (ESEI), whi ch will hold its Attempts to culture 13. microli ill vitro have so fa r been I st conference September 13- 16, 1998, has also th e goal of un successful. No ELI SA for B. microli has been publ ished. establishing interdisciplinary coll aborat ions to promote internatio nal efforts for the stu dy of these infecti ons. Other babesioses References The cli ni cal pi ctu re descri bed for the WA I has shown the same type and ra nge of symptomS, from asympto mat ic to I. Stane k. G. O ' Connell. S . Ci l11l11o no. M "/ fll. ( 1996). Wie" Klill. 1\'tx:hclI.)·chr. . ION: 741 -47. severe clinical di sease, as has been described for B. microli. 2. Whole issue: (1998) ZeI/I.h1.lIl1k/l'I"jol . 287: [73-276. The most severe clinical di sease. as for oth er babesial 3. II Hglund. M. Forsgren. "''I.. Lilldh. G. Li ndquist. 1_. ( 1996). SI:wul. J. lnfet'l. m .I',. in fections, occurred in a splenectomi sed indiv id ua l. The 28: 2 17- 24. 4. Chri stmann. D. Staub·Schmidt. T. (1996). I're.l·.I'e Met! .. 25: 420-23. onl y case of MO I was a falal infection. 5. Dumlcr. JS. Bakken. J.S. (1995). G ill. IlIfct:!. Dis .. 20: 1102- 10. The presence of WA I in Europe was suggested by a 6. Schaffn er. W. St:mdaert. 5.1\,1. (1996). Nell' /:."/Igl. J. /11('(1.. 334: 262-63. 7. Walke r. DH. Dumler. JS (1996). !;im'rgi"g IlIji.. ': I. Dis .. 2: 18-29. J congress report but it has to be noted that the IF for WA gives 8. Dumler. JS. Do t.::val L L. Gu s t : , fs..~o n . R. Granstrom . M. (1997). 1. IlIfecl. I)i.~ .. 175: a one-way, extensive cross·reaclivily to other babesial species. 720-22. 9. Petrovec. M. Lotric Furlan. S. Acsic Zupanc. T el (II. (1997) J. Cli". Microbiol.. 35 : 1556-59. 10. von Slcdingk. LV. GUrtclschrn id. M. Gustafson. I~ 1'1 111. (1997). elill. Microbiol. CO -TRANSM1SS10N AND CO-1NFECTlON IIlf('cl.. 3: 573-74. t l. Ol s~ on Ell g.vall. E. Pe ller s ~ o n. 13. l'cn;son. M ('I (II. (1996). J. e lill. MimJbiol.. 34: 2170- 74. Cotransmi ssioll of two or several of these agents have been 12. Persin g. DH. COllmd. PA (1 995). /l1/('CI. A J.:cIIIJ Dis .• 4: 182- 95. reported both from the US and from Europe e.g. for TBE and 13. Pn lthi. RK. Ma rshall. WF. Wiltsie. JC. l'ersing. OU ( 1995). Ml/yo Cli/!. Pmc .. 70: 853- 62. LB . As fo r the other agents, Eh rlicllia and Babesia, clinical 14. LQulan. L. (1995). Sd",·I'i:. Mt·fl. 11 0dl (,I/ .~c hr. . 125: 886- 89. investigations in human medicine in Europe lag vastl y behi nd 15. Kmu ~ e . P.J .. l elfonl. S. R.. Spicl m.m. A. 1:1 (/1. ( 1996). JAMA 275: 1657- 60.

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