\'oluine 67, Number 4Printed in1he U.S.A.

(ISSN 0145-916X)

INTERNAI 10NAI. JOURNAI. 01. 1.1 l'It0SY

INTERNATIONAL JOURNAL OF LEPROSYand Other Mycobacterial Diseases

OFFICIAI, ORGAN OF THE INTERNATIONAL LEPROSY ASSOCIATION

EDITORIAL OFFICEGillis W. Long Hansen's Disease Center

at Louisiana State UniversityBaton Rouge, Louisiana 70894, U.S.A.

VOLUME 67, NUMBER 4^ DucEmBER 1999

EDITORIALEditorial opinions expressei! are Mose of the writers.

The Paleoepidemiology of Leprosy: an Overyiew*

Introduction: paleoepidemiology and theecology of diseases

The paleoepidemiology of an infectiousdisease should ideally start by tracing itsorigin, that is, the prime encounter of manwith the germ, its reservoirs and its vectors,in a long-vanished ecology. Next, the sub-sequem interplay of the host and the para-site should be followed as they travel to-gether through ages and places, overtakingfresh populations.

For diseases of recent emergence, thematter is often hard enough. But at least,throtuzh observation and experimentation,some hypotheses on their origins and mech-anisms of transmission can be tested. Forancient diseases, however, the approach ispurely speculative. Let us take cutaneousleishmaniasis as an example. In a recentbook on the history of tropical diseases,' thefollowing account is given of its origin:

* Presented at the OCEPID: Past and Present ofLeprosy, Bradford, U.K., July 1999.

' Miles, NI. A. (1996): New World leishmaniasis. InCox, E E. G.: The Wellcome Trust Musa-orca HiSiOnof Tropical Diseases. The N,Vellcome Trust PubI., Poli-dor]; 206-229.

"Sandllies have been in existence for 30million years and, feeding on the juice ofplants in which flagellate protozoa live,they presumably became infected with theancestors of Leishmania parasites, . . .lizards, and later, small rodents became thesandflies' chosen prey . (then) man as ahunter-gatherer, became infected when hecame into contact with these rodents

The more complex the natural history ofa disease, the easier it becomes to proposesome sort of sensible scenario for its origin.This may seem a paradox, but the reason,however, is simple. The epidemiologicalfactors to be taken into account, such as thebiology of an obligatory vector, the disper-sion of an intermediate host, or the biotopeof an animal reservoir, raise many con-straints which curtail our freedom to makehypotheses. Concerning leprosy, this ill-famed, centuries-old, epitome of allscourges, there is no hint to lead us to rea-sonable guesswork, no mosquito and no ex-tra-human reservoir, but for an occasionalmonkey or an exotic mammal such as thearmadillo. Unless further evidence provesotherwise, man is the only host as well asthe only reservoir for the etiological agent,

460

67, 4^ Editorial^ 461

Mvcobacterium leprae. Since the bacillushas never been cultivated in vitu), it looksas though it has lost the genetic machineryrequired to grow outside the human body. ltmay thus be safely assumed that it is an oldmycobacterium that lias diverged and be-came an obligatory parasite of man early inthe course of evolution. The nearly com-pleted deciphering of its genome and thecomparison of it with that of M. 1111)cl-calo-sis and possibly of other mycobacteriashould hei J) to elucidate lis origin.

The transmission is rather unimagina-tive: people to people, from an infected in-dividual to a susceptible person. Leprosy isa cosmopolitan disease. Notwithstandingdifferences in climates and environments, atune moment or another it has been occur-ring in all types of habitats occupied byman. While there is no suggestive paleonto-logical evidence regarding its transmissionin protohistoric populations, lis spread andgeographic distribtaion over the centuriesshow a number of singularities. Yet, histor-ical observations may possibly provi&some chies to broaden the debate.

Early reeords of leprosy at the dawnhistory

Written records of diseases with symp-toms resembling those of leprosy suggestthat it could have existed in ancient times inEgypt, India, and China.

In Egypt, Huspati (Horus-Dên), a quasi-mythical Thinite king of the First Dynasty(-3500 BC), is reported in papyrus datingfrom ±1500-1200 BC as having sufferedfrom a disease whose signs are evocative ofleprosy. In India, a precise clinicai descrip-tion was given in a compilation of writingsdating from about 600 BC (SushrakaSamhita).` In China, the Nei Ching, a col-lection of medicai texts assembled betweenLhe Sth and the 3rd centuries BC, but attrib-uted to Huang-Ti, a legendary emperor wholived around 2600 BC,' lists amon,g thesymptoms the Loss of eyebrows togetherwith nodules and ulcerations of the skin.

= Brugsch. Quoted in Senti, 11.1-1. (ref. 10).1)harinendra (1978): Ilistory .S'pread and De-

cline of Lepro.sx. Dhartnendra, ed. Kothari Med. Pub-lish. Ifouse, 1-3(Mthtly; 7-21.

' Skinsnes, O. (1985): Understanding of Ieprosy inaneient (_Thina. Int. J. Leia. 53; 289-307.

That the records attesting to the exis-te= of leprosy in earlier times were acto-ally compiled much later does not necessar-ily preclude their veracity, for they weregenerally meant to be a recollection of tra-ditional knowledge.

The congruence of the given descriptionwith the clinicai signs of the disease is amuch more delicate issue. For example, ac-cording to Biblical experts, the conditiondescribed in Leviticus under the term of'Za'raath does not refer specifically to lep-rosy but is said to encompass a large varietyof skin diseases or blemishes of all kinds.'II is, therefore, very doubtful whether lep-rosy was brought to Canaan by the Jews re-turning from Egypt, despite an anthropo-morphic jar reminiscent of a leonine (lepro-matous) facies excavated in Palestine andcontemporaneous \vith the Exodus (1400—1300 BC).'

Anecdotal evidence is perhaps at timesmore convincing than ofticial chronicles.That leprosy was confinou around the 4thcentury BC in China is suggested by a liar-rative of the time vividly relating how, inorder to elude arrest, a banclit cleverly dis-guised himself as a patient by varnishinghis skin and shaving his eyebrows!"

Artifacts suggestive of leprosy datingfrom these early perimis are few. Apartfrom the clay ware found in Palestine, stat-ues conceivably exhibiting mutilationswere discovered in the Indus Valley. InEgypt, indisputable evidence of the exis-te= of leprosy is relatively recent. Fourskulls from the 2nd century BC present le-sions of the nasal bones specitic to leprosy.'Evidence in two Coptic mummies with bonelesions of the extremities comes from a much!ater period, well imo the Christian era.'

' Jeanseline. H. (1934): Lu Lepre. G. 1)oinParis.

Coehrtine. R. G. (1964): The history of leprosyand its spread throughout the xvorld. In: Coeltrane,R. G. Leprox.v in^cru(' l'racli(e. John N■'rightSons. Bristol; 1-12.

M. (1955): A facies [comina of leprosy ouan ancient Canatinite jar. J. Hist. Nled. 10; 331.

'1)fierzykray-Itogalski (1980): Paltieopathologythe Ptolernaic inhabit-ants of Dakhlelt Oasis (1:ttvpt). J.

Evol. 9:71-74. Quoteil in SansaiTieq, II. (rei. 42).Antlerson, J. O. (1969): Studies in the medieval

diagnosis of leprosy. (Thesis for Doctor of N1eclieine)Dai-t. Med. Bull. 16 (Suppl. 16).

462^ International foliou!' of. Leprosy^ 1999

In which of those arcas did leprosy firstmake its appearance? There is no strzk.,litanswer. If we trust the legacy of traditionsas embodied in later recuais, leprosy couldwell have been prevalent in ali three regionsat the dawn of their respective histories.That the possible presence of the diseasewas attested to earlier in Egypt is no argu-mem. The chronology of historical eventshas often more to do with the presence ofhistorians than with the occurrence of theevents themselves, as is the case ffir somany phenomena.

There is therefore no conclusive argu-ment to settle the issue of leprosy's first ap-pearance. Egypt comes to mind, however,as a good candidate, although it has beenclaimed that studies conducted ou munirá-fied remains run contrary to this statement.lndeed, among 1844 mummies from 600BC to 600 AD examine(' by Moller-Chris-tensen for pathognomonic signs, only twopresented bone lesions indicative of the dis-ease." This argument is not convincing. Forosteological evidence of leprosy to show upin a significant number of remains, severalconditions must be filled: a high prevalenceof the disease, a large proportion of patientswith bone lesions, the fact that leprosy wasnot less frequent in the social classes whereembalming was more likely to take place,and that there was no negative selection re-garding these funeral practices because ofdisease.

If leprosy was present in Egypt's proto-history, possibly serving as a relay to itsspread eastward to India and China, wherethen did it come from? h is known that veryearly in history, commercial exchangeswere already most active with Nubla andDarfur (now the Sudan), countries that weresituated at the gales of the huge Africanhinterland. Negro slaves were imported intoEgypt at the time of Ramses II (circa 1300BC)." Could leprosy have then been intro-duced into Egypt from deeper regions in the

Scott, Il. H. (1943): The inlluence of the slavetrade in the spread of tropical disease. Trans. R. Soc.Med. ilyg. 37; 169-188.

" Trauttnan, J. R.: The history of leprosy. In Flast-ings, R. C. (ref. 54).

12Lucretius: De Remi)] Minera V/. Les Belles Let-Ires Ed., 1948, Paris, 1114-1115.

belt of land extending from Abyssinia toNigeria?

At this stage, it is tempting to make alink with what occurred some six or seventhousand years later. Between 1500 to themid-18th century, leprosy was prevalentamong those unfortunate enough to be cap-tured in the interior of the African comi-nem, taken to the coast and exported toAmerica as slaves. It is difficult to acceptthat "131ack Africa" 'ias free of leprosy un-til Arab traders and Portuguese navigatorsimported it between the 101h and 15th cen-hirtes AD." The disease had probably beenpresent in the heart of the continent formany centuries.

Could it be thus that the cradle of leprosycould be found where the first mudem n hu-mans made their appearance eons ago?

As in so many instances, Lucretius'(99-44 BC) was perhaps correct in his in-tuition when he wrote ".. elepha.s. morbasqui propter Nili gignitur Aegyptomedia, negue praeterea u.s.quam . . from Egypt, along the Nile, and nowhereelse

Exwmsion of leprosy in historical timesand invasion of Europe

While leprosy presumably already ex-iste(' in Egypt and further east in early bis-tory, it made a belated entry into Greeceand Rome.

Literary sources of Greek and Latin ori-gins raise peculiar problems of semantics.The group of skin conditions referred to aslepra in the Hippocratic texts does not ap-parently include the disease we carne toknow in mudem parlance as leprosy. Con-versely, the disease entity most preciselyand accurately described by the Latin au-thors Celsus (25 BC-37 AD) and especiallyAreteius of Cappadocia (circa 200 AD) thatwe may recognize as leprosy is designatedby the term "elephantiasis."'

According to Pliny the Elder (23-79AD), elephantiasis, by now designating lep-rosy, was introduced in Rume around 62BC by the ztrmies of Pompey returningfrom the campaign against Mithridates,King of Pont."

That the ailment was not common inRome may be surmised from the fact that itwas not included in those defects rescindingthe sale of slaves, as was the case for phthi-

67,4^ Editorial^ 463

sis (tuberculosis), fevers, eyesores andmental disorders.5

Following the Roman conquests, leprosyspread to Gaul as well as to Germany,where Galen (±150 AD) signals its pres-ence, and thereafter to the whole of Europeduring the Middle Ages,'" although the pos-sibility of a prior contamination of Spain bythe Phoenicians as early as the 10th centuryBC has been theorized by some authors»The Vikings brought it to Scandinavia. Inlceland, a bishop was to be deposed in 1413because bis deformities prevented him fromcelebrating mass. At the time of the Cru-sades, the bacillus shuttled back and forthbetween Europe and the Near East.

The fear of contagion was great. Gloomyrituais were sei up to exclude the patientsfrom social life. Lazarets were built fromSpain to Scotland, which at least attest to awide dissemination of the disease." At unetime or another, Beltlium would havecounted 42 lazarets, Enr-land 99, Normandy318, and the whole of France over 2000.Figures of that soo can be misleading. In alllikelihood, judging from their ruins, most ofthese institutions housed a small number ofpatients at a time, and most probably not allsuffered from leprosy. That ai least some ofthe people consigned to these !azareis wereactually affected with leprosy is contirmedby the excavations conducted in Denmarkby Moller-Christensen in the 1950s, whichdemonstrated characteristic bone changesin a number of skulls.'' In addition, this au-thor identified specitic alterations in themaxillary bones which, after having beenvalidated radiologically in pa-tients,'". '7 can now be used as a standard toverify the diagnosis of leprosy in osteo-ar-chaeological material.

" Chaussinand, R. (1955): Lu /Aviv. ExpansionScientique Francaise, Paris.

"Contreras, F. anel Miguel, R. (1973): Historia deIa lepra en Espana. Gratica Ilergon, Madrid.

Moller-Christensen, V., et al. (1952): Changes inthe anterior nasal spine and the alveolar process of thetnaxillary bone in leprosy. Int. J. Lepr. 20; 335-340.

Melsom, R. S. (1953): CharRICS ill the maxillarybone in leprosy; a clinicai and roet-ngenological exato-ination. VI C0115.11VSS Internacional de Leprologia,Madrid; 747-750.

Lechat, M . F. anel Chardotne, J. (1955): Atter-ations radiologiques eles os ele la face chez les lepreuxCongolais. Ann. Soc. Belg. Med. Trop. 35; 603-611.

While it cannot be doubted that leprosywas widely disseminated in Europe duringthe Middle Ages, it is impossible to evenhazard a guess about its actual prevalence,its distribution or its relative frequency intowns as compared to the countryside. It ispossible that, because of the fear it inspiredand the morbid stigma attached to its name,the prevalence of leprosy has been grosslyexaggerated. II has been suggested that inthe 13th century the number of patients inEngland did not exceed a few thousand.'sIndeed, more is known about the epidemi-ology of the lazarets than about the epi-demiology of the disease itself!

In contemporary Europe, two localizedoutbreaks are worth mentioning. Onestarted in Memel (now Klaipeda, Lithuania)in 1840, the other occurred in the island ofOesel (now Saaremaa, Estonia) at the turnof the century.'. In Oesel, the spread fol-lowed a panem of slow diffusion, propagat-ing from village to village, farm to farm.

There are two main conclusions to thisstory. Firstly, it is most likely that leprosywas not introduced into Europe by the Indo-Europeans during successive waves of mi-grations, be it the Celts, the Germans, theGreeks or the Italians. Either the disease didnot, or did not yet, exist at the site wherethese migrations originated, somewherethe steppes or the plateaus of Central Asia,7000 or 8000 years ago, or the conditionsfor its transmission were not met during thelong westward trek, meaning that M. /epraegot lost "en route."

Second, there is no climatic or other geo-graphic factor determining the distributionof leprosy. From the sun-scorched banks ofthe Nile to the frost of Iceland, the deter-mi ning factor responsible for the travelingof the bacillus is man.

Leprosy in the New WorldAfter having reached its peak in Europe,

leprosy worked its way to fresh ground ohthe American continent. There is no recordof the disease beira; prevalent among theFirst Nations people before the arrival ofthe Europeans. Since the Conquistadors andthe first colonizers carne from regions of

Richards, P. ti 9 7 7 ) : The medieval leper and itsnorthern heirs. Quoted in Hl, S. R. (ref. 55).

464^ Intermilional lournal of Leprosy^ 1999

Europe, mainiy Spain and Portugal, whereleprosy was not uncommon, and were inaddition accompanied by physicians andpriests supposediy well acquainted with itssymptoms, it is unlikely that cases of thedisease among the natives would have es-caped attention. Even at present, leprosy isonly exceptionally, if at ali, observed in in-digenous people. To the best of our knowl-edge, it has never been reported in tribeswith no previous contact with strangers.

Anthropomorphic earthenware from thepre-Colombian era once believed to repre-sent leprosy lesions are now said to suggest,rather, leishmaniasis ("espia/c/ia-) or Nas-tomycosis.'

In conclusion, it can be accepted that theMongoioid people who migrated across theBering Strait !and bridge some 14,000years ago did ilot carry the leprosy bacilluswith them. II first carne to the Americaswith the European invaders, then with theslaves from Africa and, finally, with labor-ers imported from China.

Among the Conquistadors and the firstcolonizers, Jimenez de Quesada, thefounder of Bogota, was affected andcontaminated some persons of his en-tourage.''

It is the slave trade which apparentiypiayed the major role in the introduction ofleprosy into the New World. The number ofsiaves deported from trading stations inAfrica between 1511 and 1787 oscillatesbetween 10 milhou and 50 milhou, the lat-ter figure' according to the British Admi-raity. Most of the slaves were importedfrom the western coasts of Africa, extend-ing from Senegambia (Senegal) toBenguella (Angola), and from as far awayas Mozambique on the Indian Ocean. II isilot known how common leprosy was atthat time in that part of the world. Judgingfrom the high prevalence recorded a fewcenturies later during the Colonial period, itcan be presumed that the disease had been

Krumbach, 1-1. (1986): Zur Frage der Lepra impra.-und post-kolumbischen Amerika. 1:1 Aussat:::Lepra; liansen-Krankheit. Eu n menshen.sproblemWandel. Vol. 2. Wolf, J. 1-1. ed. DAM, Wurzburg;201-209.

Gonzalez Prendes, M. A. (1963): Hisforia de IaLepra eu Cuba. Academia de Ciencias de Ia Republicade Cuba. La 11 abana.

widely disseminated in Africa for a longtime, as ai ready mentioned.

The number of these so-called involun-tary migrants who ultimately reached theAmerican shores was, however, much lessthan Mose captured in the African hinter-land. "Sanitary control- was carried out be-fore shipment to exciude people in poorhealth or with visible defects, although it isreported that in later years, as the contra-band trade developed, the prevalence ofdiseases among smuggied siaves increasedsharply.'" Of Mose embarked, it is said thata large proportion, at times up to more thanmie half of the ship load, died or were oth-erwise disposed of during the ocean cross-ing, or the "Middie Passage" as it carne tobe called, insurance policies being an addi-tional incentive no1 to keep sick patients onboard untiltermination of the journey.'" De-spite the above checks, the number of lep-rosy patients among the siaves delivered totheir destination would ilot have been in-significant. In addition, some of them stillin the latent stage, having been infected intheir homeland, were bound to deveio') theclinicai disease after arrival.

That the disease was present among theAfrican siaves is attested by the fact that inCuba the bilis of sale stipuiated that for lep-rosy, and likewise for mental disorders,contrary to olhem ailments, the buyer hadthe license to return the object of the trans-;Action within 2 months if found to be af-fected by these conditions="

The immigration of Chinese laborers toCuba, at the time a coiony of the SpanishCrown, began in 1847, the very same yearthe siave trade was officially abolished. Inthe 27 years that followed, an estimated132,000 Chinese entered the island, manyof them originating from Guang-Dong andYunnan, provinces where leprosy wasprevalent. From 1800 to 1899, out of 1393patients hospitalized in the San Lazaro Hos-pital in Havana, 202 (14.5%) were nativesof China (the first Chinese national havingbeen admitted not earlier than 1850).2"

Migrations and secluded, remote orotherwise singular arcas

SIOW diffusion in contiguous arcas andmosaic patterns. The spread of leprosy inarcas adjacent to each other was observedas recentiy as the present century among

67,4^ Editorial^ 465

the Aborigines of Wandammen Bay, IrianJaya and in the Northern Territory of Aus-tralia.' " In Western Australia, the diseasewas reportedly imported by crews of pearl-fishing boats and was propagated inlandfrom the coast with successive intervals set-ting up small foci along the rivers.23

This pattern of diffusion may explain theslow dispersion of leprosy in prehistorictime, the disease remaining sequestered insecluded populations for untold centuriesuntil some social break up set it free to fiareelsewhere. The more compartmentalizedthe group, the slower will be the diffusion.

Different opportunities for contact couldalso explain the fragmented distribution ofthe disease observed in some parts ofAfrica, where strongly contrasted preva-lences ranging from high to low may coex-ist in adjacent areas. The same differencesare mentioned for tribes of Papua NewGuinea living in adjacent valleys. Althoughthe suggestion is admittedly quite specula-tive, this panem of mosaic or patchworkcould reflect, up to the present, some ves-tige of the respective isolation of tribes un-til the recent past. The more exchanges be-tween contiguous arras, through trade orotherwise, the faster will be the spread ofleprosy and the more homogeneous will be-come the distribution of prevalence.

Transmigration. There are historicalrecords of the transmigration of populationswith a high prevalence of leprosy into anenvironment already occupied by othergroups with low or no prevalence. Suchtransplantations may be regarded as experi-ments where the spread of the disease canbe observed as the two populations comeinto contact.

The transmigration of leprosy patientsdoes not necessarily result in the dissemina-tion of the disease in the new location.Transmission may remain largely limited

21Leiker, D. L. and Sloan, N. R. (1954): Leprosyin Netherlands New Guinea. Int. J. Lepr. 22;431-439.

"Hargrave, J. C. (1980): Leprosr in the NorthernTerritory of Australia with Particular Reference to theAborigenes of Arnhem Latad and the Regions of theNorthern Territory. Government Printer of the North-em Territory.

"Lechat, M. F. (1986): Prospect for eradication ofleprosy. Conference for the closing of the last leprosyhospital in Austral ia, Peri h, WA, 1986.

to, and persist for generations within, theimmigrant groups if these do not minglewith the host population. It is then culturalisolation, reducing the opportunities for in-fective social contacts, rather than geo-graphic confinement, which will restraintransmission to the outside.

An example of such migration is givenby the French colonists who settled in Tra-cadie, New Brunswick, Canada, and Loui-siana, U.S.A., following their expulsionfrom Nova Scotia at the time of the "GrandDérangement" in 1755. The Acadian focus,which is scattered among the parishes ofLouisiana, has been active up to this day,with many cases still occurring in the Cajunpopulation." (This direct importation of thedisease from Canada to Louisiana has how-ever been contested. II is now claimed thatthe Acadians picked up the disease in theCaribbean during the 181h century.")

An outbreak of high prevalence was alsoobserved in the penal institutions of FrenchGuiana.'5 From 1852 until 1939, 71,667male convicts were transported to thisFrendi territory. The two first cases of lep-rosy were diagnosed in 1883. The numberof cases which have occurred since then hasnot been recorded. II has however been re-ported that for the period 1939-1948, theprevalence averaged 4.6%. A recalculationof the incidence for the decennium1939-1948 yields a figure of 4.15 cases per1000 person-years. That ali ethnic groups,European, Arab, Asian and African, wereindiscriminately affected militates in favorof social factors, such as living in over-crowded and unhygienic conditions, as asignificant determinant in the transmissionof the disease.

According to a different pattern, the ar-rival of patients in a previously unaffectedarca does not result in the production ofnew foci. It could be that the newcomerswill adopt the mode of life of the host pop-ulation—as ill-defined as the term mightbe—which in some way will curb the trans-

2 Feldman, R. A. and Sturdivant, M. (1973): 100years of leprosy in Louisiana: an epidemiologicalanalysis. 10th International Leprosy Congress,Bergen, 1973, Ahstractsi 116-117.

" Floch, 1-1. (1951): La lepre au hagne Guyanais:sou evolution durant un siecle (1852-1950); ses par-ticularites. Int. J. Lepr. 19; 283-295.

466^ International Journal of Leprosy^ 1999

mission of the bacillus. Illustrative of this isthe story of the Scandinavian immigrantswho settled in the Upper Mississippi Valleyin the 19th century.2"." The disease died outafter the second generation. Social and eco-nomic factors have been invoked to explainthis observation.

Although not sufficiently documented,these observations seern to confirm that so-cial contact is a determining factor in gov-eming the transmission of the disease. Bothof these patterns would be difficult to rec-oncile with a supposed intervention of anextra-human reservoir.

Virgin communities; the Pacific is-lancis. The Pacific islands constante a sortof laboratory in which one can watch the in-troduction of leprosy in hitherto virgin pop-ulations. The diffusion of leprosy in a num-ber of those islands reveals two principalepidemiological patterns, i.e., outbreaks ofleprosy, and transmission limited to a fewfamilies.

Outbreaks are characterized by a rapidlyincreasing incidence following the occur-rence of the first cases. After a few years, alarge part of the population may be af-fected—one-third of the natives in NauruIsland in 1929," one-fifth in Reao andPukarna Island, Tuamotus, French Polyne-sja 1936. Other sites of epidemics arethe Northem group of the Cook Islands andAitutaki, in the Southem group,'" and NewCaledonia.31These outbreaks are often sub-sequent to the arrival of a particular indi-vidual said or known to have had leprosy. Ifthe legend of introduction of leprosy intopreviously unaffected communities by Chi-nese laborers and crews of whaling ships

Washburn, W. L. (1950): Leprosy zunongScandinavian settlers in the Upper Nlississippi Valley,1864-1932. Bull. Hist. Med. 24; 123-148.

" Doull, J. A. (1962): The epidemiology of lep-rosy; present status and problems. Int. J. Lepr. 30;48-66.

=" Wade, II. W. and Ledowsky, Y. (1952): The lep-rosy epidemic at Nauru: a review with data ou the sta-tus since 1937. Int. J. Lepr. 20; 1-29.

'''Lonie, D. A. (1959): Trends in leprosy in the Pa-cific. Technical Info. Circular No. 32 (mitneograph),South Pacific Commission, NOUIlled.

'Numa, J. (1953): The prevalence of leprosy inthe Cook Islands. Int. J. Lepr. 21: 151-160.

" Ragusin. R. (1951): I,e lepre eu Nouvelle-Cale-doMe et dependances. Int. J. Lepr. 19; 413-421.

(Hawaii," Western Samoa") must be ac-cepted with caution, more interesting exam-pies are those in which the first case isclearly defined, sometimes with the nameand the medicai history clearly recorded.

The unparalleled story of the Nauru epi-demics is truly remarkable." The introduc-tion of leprosy to this island, at that time aGerman colony, is ascribed to a woman na-tive of the Gilbert archipelago (now the Re-public of Kiribati), who arrived in Nauru in1911 or 1912. Recognized on arrival ashaving leprosy and barred from entry forthat reason by the medicai officer in charge,she was however allowed to stay by theGovernor. She took a 13-year-old girl as aservant, and died 2 years later. In 1920, thegirl, by then 22, in [um developed leprosy.Soon thereafter three additional cases weredetected. Ali were isolated. A few monthslater, the pandemic of Spanish influenzareached Nauru, killing 30% of the popula-tion as well as all the leprosy patients butone. The next year, 1922, 25 new cases ap-peared. By the end of that year, after a sur-vey had been conducted among the entireNauruan population of 1113 persons, thenumber of cases diagnosed had increased to139, yielding a prevalence of 125 per 1000.Soon, almost every family had at least onemember affected. By the end of 1929, nofewer than 438 cases had occurred amongthe autochthonous population, which corre-sponds to a 7.5-year period—a prevalence(1922–mid-1929) of 36.5%. The epidemicthereafter subsided, partly due to the forcedemigration of the population to the island ofTruk (now Chuuk, Micronesia) and partlyto the elimination of the patients during theSecond World War occupation by the Japa-nese militar)'. II is, however, not yet com-pletely extinct. The latest information re-ports an average of two cases detected peryear between 1982 and 1994 (1994 popula-tion 9900), in spite of early detection andeffective multiple chemotherapy»

Wayson, N. E. and Rhea, T. K. (1934): Leprosy,ohservations ou its epidemiology m Hawaii. Publ.Health Bull. 212; 1-32.

"Sloan. N. R. (1954): Leprosy in Western Samoaand the Cook Islands. Technical Paper No. 69 (mimeo-graph), South Pacific Commission. Notunea.

" WHO Regional Office for the Western Pacific(1995): Epidismiological review of leprosy in the West-ern Pacific Rgion 1982-1994. WIIO-WPRO, Manila.

67,4^ Editorial^ 467

In other islands the spread of leprosy isreported to have been limited to a few fam-ilies, as in Niue Island and Eastern (Ameri-can) Samoa.

In Niue, where the disease was report-edly introduced by a resident returningfrom Hawaii, 30 cases only have been reg-istered in 70 years (up to 1949) among apopulation of approximately 5000, leprosybeing almost wholly confined to two familygroups." No new cases have been reportedin recent years. In American Samoa, 41 outof 45 known cases in 1953 were from onlythree family groups.'"

These island outbreaks raise interestingpoints. To what extent may genetic or envi-ronmental factors expiam n these differentpatterns? This remains an unansweredquestion. As bewildering is the fact that inNauru the large majority of patients wereaffected by the tuberculoid (now calledpaucibacillary) type of the disease, a clini-cal fbrm that is reputedly not or only veryslightly contagious.

That leprosy continued being transmittedin Nauru until the beginning of the war inthe Pacific remains also witriout a satisfac-tory explanation, especially in view of thefact that ali of the patients except one (thegirl who was contaminated by the indexcase) had succumbed to the influenza pan-demics, and notwithstanding the early en-forcement of isolation.

Colonia Tovar, a genetie isolate. Colo-nia Tovar, a small and until recently iso-lated community in Venezuela, presents astrange illustration of high prevalence cou-pled with high inbreeding.

Between 1843 and 1856, 146 immirantsfrom Germany settled in this isolated valleyin the state of Aragua.37.-" In 1950, about acentury later, a survey of 1126 inhabitants,

" Dempster, G. O. L. (1949): Lcprosy lo NineIsland; a note on the history of the disease. Int. J.Lepr. 17:411-414.

Sloztn, N. R. (1954): Leprosy in AmericanSamoa. Technical Paper No. 62 (mimeograph), SouthPacific Conunission, Noumezi.

"Convit, J., et al. (1952): Estudios sobre Ia lepraen el grupo etnico aleman de Ia Colonia Tovar. Int. J.Lepr. 20; 185-193.

" Lechat, M. ei al. (1967): A Study of bloodgroups and leprosy in the population of Colonia "F)var,Venezuela. Int. J. Lepr. 35; 488-493.

almost the entire resident population, dis-closed a prevalence of 100 per 1000 (113cases) in sharp contrast with the rest of thestate of Aragua, where the prevalence didnot exceed 1.35 per 1000.

The original site of contamination re-mains unknown. Did the disease stem froma contact with an occasional case in theCreole population upon arrival in America,or was it present in the immigrant popula-tion at their place of origin in the Black For-est'? Did the high prevalence result from theexistence of some environmental peculiar-ity specific to the valley, which incidentallyseems to benetit from a microclimate and isrumored to have an unusual ecology?""Could inbreeding have played a role, whichwould suggest the intervention of geneticfactors in the susceptibility to leprosy?'Was the containment of the disease in thepopulation doe to geographic as well as cul-tural isolation, verging on spontaneous seg-regation? These questions remain unan-swered.

Leprosy on the declineIn Western Europe, after having reached

a peak in the 12th and 13th centuries, lep-rosy then started to decline until it had allbut disappeared by the turn of the 20th cen-tury. Residual foci persisted in the Balticstates, in Greece, in the Iberian Peninsulaand in the Balkans.

The very term "decline" is however mis-leading, since it may apply to two quite dis-tinct epidemiological indicators: preva-lence, depending ou the number of patientsaffected with the disease at a given nm-ment, or incidence, corresponding to thenumber of new cases occurring during aninterval of time.

Taking as an example two of the Balticcountries, the number of patients (preva-lence) in Latvia dropped from 977 cases in1900 to 207 in 1933, a more than 75% de-crease, and in Estonia from 3 16 in 1920 to113 in 1940.-"' No conclusion, however, canbe drawn as to the pace at which leprosy"declined," or when this "decline" started.Only incidence, reflecting transmission,will tell.

Lechat, M. E Personal observation.Leprosy 13riers (1957): 8; 37-38, Leonard W'ood

Memorial, Washington, I).C.

468^ International Journal gif Leprosy^ 1999

An exhaustive study of the annual inci-dence rates (and cohort-based incidencerates recording the year of birth) for the pe-riod 1855-1920 lias been carried out inNorway by Irgens.' In the coastal part ofthe country where 97.8% of the 6652 pa-tients with year of onset within the observa-tion period were living, the prevaience fellfrom 35.2 per 10,000 in 1855 to 1.2 ia1920. During the same period, the inci-dence declined 100 times from 33.4 to 0.3per 100,000.

What was the cause of the decline? Sev-eral reasons have been put forward to ex-plain the downturn in Europe ia the lateMiddie Ages, such as higher fittality rates inleprosy patients during piague epidemics(the Black Death) in the 14th century, themoditication of eating patterns, or the de-velopment of immunity associated with thespread of tuberculosis." This last hypothe-sis deserves more than a cursory mention.Numerous studies have demonstrated somedegree of association in the cell-mediatedimmunity against 1W. leprae (Mitsuda test)and M. tuberculosis (PPD). After much de-bate, there is mounting evidence that vacci-nation by a combination of BCG with kiliedM. leprae confers a significant degree ofprotection against leprosy.43.44 Competitionbetween the two bacilli couid therefore ac-count, at least in part, not oniy for the reces-sion of leprosy, but ais° for the variationsobserved in its spread and its distribution.

One may further indulge in sorne specu-lation. A number of observations in animaishave led to the general acceptance that ex-posure to given mycobacteria influencessubsequent responses to other mycobacte-rial species.45 For example, the observed

Irgens, L. M. (1981): Leprosy in Norway: anepidemiological study based on a national patientregistry. Lepr. Rev. 51 (Suppl. 1); 1-130.

" Sansarricq, H. (1995): Histoire de la lepre. InSansarricq, H. (ref. 57).

Karonea Prevention Trial Group (1996): Ran-domised cjntrolled trial of single BCG, repeatedBCG, or combined BCG and kiiled Myrobacteriunzleprae vaccine for prevention of leprosy and tubercu-losis in Malawi. Lancet 348; 17-21.

44 Gupte, M. D., et al. (1998): Comparative leprosyvaccine trial in South India. Indian J. Lepr. 70;369-388.

-'5Stanford, J. L. (1978): The importance of envi-ron mental mycohacteria. 1n Chatterjee (ref. 56).

protection against tubercuiosis imparted byBCG is influenced by previous exposure toenvironmental mycobacteria. Such expo-sure could either enhance or reduce the sus-ceptibility to 114. leprae. In this respect, itshouid be noted that vaccination by a prepa-ration of M. avium-intracellulare (ICRCvaccine) has been found to conter a degreeof protection against leprosy similar to thatproduced by the combination of BCG withkilled M. leprae."Mycobacteria are ubiqui-tous in the environment. They couid possi-bly modulate transmission not only by in-creasing or lowering the resistance to infec-tion by M. leprae, but aiso by acting on thepoorly elucidated immunological mechan-isms which govern the transformation ofthe subclinical infection into an overt dis-case, either by shortening or lengtheningLhe duration of the latent stage and/or by ai-tering the reiative proportion of individuaiswho respectively deveiop the multibacillary(with high infectivity) or the paucibacillary(with lo‘v infectivity) clinicai types.

The distribution of a large range ofmycobacteria could, therefore, have piayeda determinant role in the susceptibility ofindividuais and popuiations to infection byM. leprae and, as a consequence, couldhave exerted an effect on the disseminationof the disease and its time trends. Thepaleoepidemiology of leprosy could thus bereduced to a chapter in the immunogenicityof mycobacteria, past and present.

In recent centuries, the improvement ofsocioeconomic standards might to some ex-tent expiain the decline of leprosy (as ex-emplified by the Scandinavian settlers inMinnesota, although, to quoteFine, "Whether the responsible factor issoap or nutrition or living conditions orcrowding or ciothing no one knows."4'

Due to the large-scale implementation ofhighiy effective drugs for the treatment andcure of leprosy, it is becoming impossibieto study the decline of incidence undernatural conditions. Even the Norwegianstudy, the best of its kind, is not devoid ofsuch a bias, for segregation could ais° haveplayed a role.

Fine, P. (1992): Reflections on the elimination ofleprosy. Int. J. Lepr. 60; 71-80.

67,4^ Editorial^ 469

Conclusions: from the past to the futureA worldwide program of treatment with

a combination of highly effective drugs(multiple drug therapy, MDT) has beenlaunched in the context of the 1991 WorldHealth Assembly (WHA) Resolution on the"Elimination of Leprosy as a Public HealthProblem.' The target of this program is todetect and cure such a large number of pa-tients that the prevalence will be broughtdown to rates below 1 case per 10,000 pop-(dation. At such a low levei of prevalence, itis assumed that the proportion of infectivepatients in the population will become in-sufficient to sustain transmission. The inci-dence will then tend to zero, and the diseasewill ultimately die out.

Over the last 15 years or so, some 10.7million patients have indeed been dis-charged." The number of registered pa-tients has fallen from 5.4 milhou worldwidein 1985 to about 800,000 at the start of1998.4"

Nevertheless, in a number of countries,and in spite of a considerable decline inprevalence, the number of cases detected inrecent years remains quite high.' Severalexcellent reasons of an operational natureare at hand to explain this observation. Thesituation, however, continues to give causefor concern and is by no means elucidated.

Several questions may be raised. Is thenatural decline of leprosy as observed in thepast a warrant for a similar decline undertoday's conditions of MDT'? Is the generalassumption underlying the present strategythat man is the only reservoir and source ofinfection a valid one? Should alternativestrategies be envisaged in special situationsin order to accelerate elimination or ulti-mately ensure eradication?

Regarding the first question, the ongoingelimination program postulates that, whenit reaches very low leveis of prevalence, the

-'' World Health Assembly (1993): Handbook ofResolutions of the WHA and the Executive Board,Vol. III, 1985-1992. 3rd edn. W110. Geneva;117-118.

World Ilealth Organization (1998): Action Pro-gramme for the Elimination of Leprosy; Status Report.Geneva, WHO/LEP/98.2, 1998.

-"World Health Organization (1998): Progress to-wards leprosy elimination. Wkly. Epidemiol. Rec. 73;188-190.

disease should gradually fade away, repli-cating the pattern of natural recession al-legedly observed in some countries.'" Itshould be stressed, however, that lowprevalence may refer to two contrasting sit-uations, that is, "natural low prevalence" asobserved in the past before the advent of ef-fective treatment on the °lie hand, and "in-duced low prevalence" as engineered by thesuccessful implementation of effectivetreatment on the other.5' The two dynamicsare fundamentally different. Untreated lep-rosy "au naturel" is a life-long ailment. II isonly after some delay, refiecting the ex-pectancy of life and death rates of the pa-tients, that a decline in prevalence will foi-low a decline in incidence. Ou the otherhand, leprosy treated with MDT is a rela-tively short disease whose duration does notexceed by definition the maximum of 2years required by the standard treatment.The decline in prevalence, resulting fromdischarging cured patients, will thereforeprecede the decline in incidence. In simpleterms, in the first scenario, prevalence is theeffect and incidence is the cause. In the sec-ond one, prevalence is the cause and inci-dence is the effect. II is therefore deceptiveto expect that a decline in prevalence engi-neered by MDT will, at low leveis, neces-sarily "plug in" to the dynamics of the natu-ral recession referred to above.

As case-detection rates tend to approxi-mate to incidence rates, with the pro-gressive clearing of the backlog of long-standing undetected cases, the number ofnew cases should gradually start to de-crease. If not, the situation would then be-come °lie of real worry. II would perhapscall for a reassessment of many of the cen-tral assumptions of the current strategy, in-cluding those of man being the exclusivereservoir of M. leprae and the clinicai pa-tient being the sole source of infection.

Is the vexing possibility of an extra-hu-man reservoir of M. leprae in animais, inthe vegetation, or in the soil to be rejected

Noordeen, S. K. ( 1995): Eliminating leprosy as apublic health problem: why the optimism is justitied.Int. J. Lepr. 63; 559-566.

Lechat, M. F. (1999): Taking home lessons. Pro-ceedini2, of the 15th International Congress of Leprosy,Beijing-, 1998. Int. J. Lepr. 66; 562-566.

470^ International feitorai of Leprosy^ 1999

off hand? For a while, sphagnum moss bogswere incriminated as a potential microhabi-tat for M. leprae. However, the spread ofleprosy at ali latitudes throughout history,its distribution in clusters, and its dissemi-nation closely ldlowing human move-ments, make it unlikely that a universal ex-tra-human reservoir is involved.

Could it be then that individuais withsubclinical infection act as a source of con-tamination and, therefore, transmit the dis-ease? If so, it could explain why leprosymay continue to be rampant in a population.The outbreak in Nauru provides a sort ofnatural experiment, suggesting that infectedindividuais could indeed serve as a sourceof infection before the onset of clinicaimanifestations.

Advances in the knowledge of themolecular biology of M. leprae and the de-velopment of adequate tools for identifyingsubclinical infection or a carrier state couldhelp to answer those questions.

Conditions which in the past were shownto be associated with the spread of Icprosy,such as geographical or social isolation, mi-gration, overcrowding, inbreeding or primeexposure, could call for the development ofmethods of primary prevention, such aschemoprophylaxis or immunoprophylacticvaccination."

Finally, in spite of the large-scale imple-mentation of MDT, there are still perhapssome enclaves, "fossils" of primeval lep-rosy so-to-speak, where the natural epi-demiology of the disease may be observed.

" Kzizda, R., et al. (1981): Occurrence of non-cultivable sphagnum bogs acid-fast bacilli in theenvironment and the ir relationship with Myco-bacterium leprae. Lepr. Rev. 52, (Suppl. 1); 85-91.

Fine, P. (1996): Primary prevention of leprosy.Int. J. Lepr. 64 (Suppl.); S44-S49.

Hastings, R. C., ed. (1994): Leprosy. 2nd edn.Churchill Livingstone, Edinburgh.

"Ell, S. R. (1994): Leprosy ia history. In I Iastings,R.C. (ref. 54).

Chatterjee, B. R. (1978): Lepro.s.y; EtiobiologyManikstations, Treannem and Control. StatesmanCommercial Press, Calcutta.

"Sansarricq, I-1. (1965): La Lepre. Ellipses, Paris.

In the context of the WHO program, a mostinnovative initiative was launched underthe title of SAPEL (Special Action Proj-ects). It consists in the identitication of pop-ulations for which imaginative and unusualapproaches should be designed in order toreach and treat the patients. SAPEL proj-ects include, among others, pygmies inequatorial forests, nomads in subsaheliandeserts, settlers in virgin territories, riverinepopulations of the Amazon basin, and tribesin the hills of South-East Asia. Bridging thepresent with the past, epidemiological in-formation collected during these projectscould improve our understanding of the dy-namics of leprosy in remote and little-known human groups. These communitieslive under conditions which at times stillbear some resemblance to the ecology ofthe past. Their study could contribute both abetter knowledge of the paleoepidemiologyof leprosy and to an improved managementof the control of the disease in the years tocome.

The study of the epidemiolo,gy of thepast should not only bring with it an intel-lectual gratification, but also stimulate us tobe better prepared for new developments inthe future.

—Prof. Michel F. LechatPresident EmerimsInternational Leprosr Association109 Rue des Trois TilleulsB-1170 Brussels, Belgium