REVIEWS OF INFECTIOUS DISEASES. VOL. 9. NO.3.

MAY-JUNE 1987
© 1987 by The University of Chicago. All rights reserved. 0886-0I62/87/0903-00II$02.00

Environmental Nonhuman Sources of Leprosy

Leslie A. Blake, Burton C. West, Cynthia H. Lary, From the Section of Infectious Diseases, Department of
and John R. Todd IV Medicine, Louisiana State University School of Medicine,
Shreveport, Louisiana

Leprosy has been considered to occur only after exposure to a human case. However,
evidence has been accumulating that this conventional view is wrong and that an environ-
mental nonhuman source is critical to some human infections with Mycobacterium leprae.
Observations, some of which date back to the nineteenth century, support soil, vegeta-
tion, water, arthropods, and armadillos (Dasypus novemcinctusi as environmental sources
of leprosy. Disparate clinical, epidemiologic, and microbiologic evidence has been criti-

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cally reviewed in light of the fact that 50010-70070 of sporadic cases of leprosy in well-
studied populations occur in persons who have had no known contact with human leprosy.
Historical data and current information alike substantiate the concept of nonhuman sources
of the disease; recent observations with monoclonal antibody have shown that phenolic
glycolipid-I antigen, which is unique to the M. leprae cell wall, is present in soil. In the
absence of a technique for in vitro cultivation, indirect methods and the body of observa-
tions reviewed here persuasively favor but do not prove the existence of environmental
nonhuman sources of M. leprae.

Close human contact has been the traditionally ac- merly unknown aspects of the disease, while further
cepted mode of infection with Mycobacterium biochemical tests have contributed to specific
leprae; throughout history, those stricken with methods of identifying the bacillus [7-10]. The de-
leprosy have been cast out and subjected to segrega- velopment of these tests and of animal models of
tion and shunning. However, both impressions and leprosy is especially important because no culture
statistics argue that such proverbial transmission of medium for M. leprae yet exists and the bacillus has
M leprae through close contact is the exception therefore only indirectly fulfilled Koch's postulates.
rather than the rule. In fact, as many as 70% - and In a consideration of the environmental sources
no fewer than 50070 - of patients with leprosy have of leprosy, the epidemiology of the disease must be
no history whatsoever of contact with another examined. Leprosy is a chronic disease with a spec-
known leprosy patient [1, 2]. It is in this curious con- trum of manifestations and a host specificity limited
text that other potential sources of M. leprae, par- to humans, armadillos, and certain primates. M. lep-
ticularly environmental foci, become significant. rae multiplies in 12-14 days; thus it is the slowest-
The leprosy bacillus itself was discovered by Han- growing bacterial pathogen known. It follows that
sen in 1873. In fact, leprosy was the first disease to the incubation period for leprosy, though widely
be correctly attributed to a specific microorganism. variable, is measured in years. The infection is charac-
Only since 1941 has effective sulfone therapy been terized by nerve, skin, and upper respiratory tract
available [3]. New findings pertaining to the microbi- involvement and appears to disseminate via the
ology of the bacillus and its potential effects on the bloodstream [3].
host's immune status [4-6] have shed light on for- Today, 90% of leprosy cases are found in sub-
Saharan Africa and southern Asia, although in the
past the disease has been prevalent as far north as
Received for publication September 29, 1986, and in revised
form December 24, 1986. the Arctic Circle. It is also found in South and Cen-
This work was supported in part by medical student research tral America, the United States, eastern Canada, the
funds from the Department of Medicine at Louisiana State Univer- Pacific islands, Australia, and (to a lesser extent)
sity School of Medicine and by the Ed E. and Gladys Hurley Foun- northern Europe and Mediterranean regions [3]. In-
dation.
cidence rates are difficult to calculate, as the time
We thank Tommie Lue Maddox for secretarial assistance.
Please address requests for reprints to Dr. Burton C. West, Sec- of onset of disease is often not known, and preva-
tion of Infectious Diseases, Department of Medicine, LSU Med- lence rates vary widely throughout the world, rang-
ical Center, P.O. Box 33932, Shreveport, Louisiana 71130-3932. ing from 0.1% to 1070 in countries where the disease

562
Nonhuman Sources of Leprosy 563

is endemic [3]. Among children there is little differ- pears likely that droplets of different sizes could af-
ence between the sexes in the type of leprosy that fect the nasal mucosa or the lungs differently, as in
is prevalent, while among adults the lepromatous tuberculosis [13].
form is clearly more prevalent in men. No real sex- A 24-hr specimen of nasal mucus from a patient
related distinction is seen in tuberculoid leprosy. The with untreated lepromatous leprosy can contain up
age of onset is difficult to establish; however, the to 2.4 X 108 M. /eprae organisms, and M. /eprae can
peak incidence in most countries is seen between the survive in desiccated nasal secretions for up to seven
ages of 10 and 29 years. The incidence of cases of days (longer in moist soil) [17]. Thus, prolonged,
adult onset plateaus and then declines after the age close contact with an open case may not be a pre-
of 50 years [3]. The age of onset is lower in coun- requisite for transmission, despite what has tradition-
tries where leprosy is highly endemic than in those ally been thought. Broad implications arise for cer-
where the disease is rare [11]. tain leprosy-endemic countries such as India, where

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Historically, skin-to-skin contact has been consid- the custom of depositing nasal secretions on the
ered the means of spread of leprosy, in part because ground is commonplace [18]. Moreover, between
of the obvious cutaneous lesions expressed in both 50% [18] and 70070 [1, 2] of new leprosy cases can-
primary and secondary cases. This concept was sup- not be traced to a known contact. Speculation also
ported by the tendency of leprosy to cluster in groups exists about potential asymptomatic or "carrier"
of people; the incidence of the lepromatous type is states in leprosy [1]. Chatterjee in 1975 found acid-
higher among persons exposed at home than among fast bacilli in 5.8070 of earlobe skin samples from a
those not so exposed [3]. Yet within familial or close clinically normal population in India. He followed
associations are many shared factors that contrib- persons with positive test results to see whether they
ute to disease spread, such as living standards, en- developed the disease; he noted that these individu-
vironmental exposure, and genes. Furthermore, the als seemed to develop leprosy at the same rate, or
body sites frequently affected by leprosy (hips, but- at even higher rates, than did contacts of leprosy pa-
tocks, thighs, and arms) do not correspond to areas tients [19]. Conclusive evidence of the infectivity of
frequently touched in any society [12]. Recent studies these subclinical states is still lacking.
in nude mice have cast doubt on the facility of in- Pedley reported the presence of 2 x 106 acid-fast
fection through contact with skin lesions unless the bacilli in 120 ml of human breast milk, leading to
lesions contain significant quantities of viable bacilli, speculation about transmission by afflicted nursing
as in untreated lepromatous cases [13]. Even if the mothers [20]. No cases of pharyngeal or intestinal
bacillus were shed, it could not penetrate intact skin, infection are known, however, and there has been
as the organism is inert, nonmotile, and nontoxic; no confirmation of distant spread from the gastroin-
instead, it would enter through existing lesions [14]. testinal tract. There is also the possibility of urogen-
Lately, the concept of airborne infection, which ital or venereal spread, as acid-fast bacilli have been
received some consideration at the beginning of the found in the testes of patients with lepromatous dis-
twentieth century, has returned to favor. As in tuber- ease, but not in semen or urine [21]. In addition,
culosis, the portal of entry is thought to be the up- there are accounts of leprosy following tattooing
per respiratory tract, to which M /eprae is trans- [22], trauma [23], and vaccination with bacille Cal-
ported by aerosolized droplets from nasal secretions mette-Guerin [24]. Whilepostinoculation leprosy has
or sputum [15]. Fourteen months after using a Hen- been witnessed experimentally, it cannot be verified
derson apparatus to simulate airborne infection with in any case whether the inoculum caused disease or
M. /eprae in nude mice, Rees and McDougall found whether the disease was present subclinically and was
that 33% of the mice had countable numbers of acid- precipitated by the trauma and subsequent immune
fast bacilli in the lungs and at such distant sites as response.
the ears, footpads, and nose [16]. Chehl et al. ex- These possible modes of transmission of M. /ep-
posed groups of nude mice to M. /eprae by ad- raetacitly support the premise that infection requires
ministering an inoculum in several ways: into the direct and extensive human contact. Yet many cases
nose, lungs, mouth, or stomach; onto intact or do not fit that mold. In Colombia there are accounts
abraded skin; and into subcutaneous tissue [13]. Only of casas malditas, or "cursed houses," where persons
those mice with nasal exposure or subcutaneous in- have contracted leprosy merely by spending the night
oculation developed disseminated diseae [13]. It ap- [25]. A sequence of events that occurred on a small
564 Blake et al.

island in the Baltic Sea is also relevant. Only one fam- among household contacts of patients increases by
ily at a time lived in the sole house on the island. more than fivefold for the polar lepromatous type
In succession, four families came and went, all from and by more than threefold for the polar tuberculoid
different regions of Finland, in none of which leprosy type over the incidence among persons not so ex-
was endemic; in succession, the wives in each of the posed [26]. Although the concept of direct spread
four households contracted leprosy [25]. These from an active human case has caused some investi-
events give new meaning to biblical advice; Leviti- gators to ascribe all new cases to unremembered
cus exhorts the priests to destroy houses where sources or unwitting exposure to undiagnosed cases,
leprosy comes again (Lev. 14:33-47). The "house- the existence of one or more environmental foci of
bound" nature of the disease implies a human ori- M. leprae is a distinct possibility. Leprosy can be
gin without direct spread. The bacilli appear to have "housebound." On the other hand, a male prepon-
entered an environmental reservoir from which they derance among patients with leprosy (male-to-female

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infect susceptible human beings at a point separated ratio, 3:2 [27]) follows the pattern of environmen-
in time and space from the original active case. tal/occupational diseases such as tularemia [28] and
We do not contest human-to-human contact as scrub typhus [29], which are related to exposure to
critical to some cases of leprosy. Human-to-human organisms outdoors. Furthermore, various accounts
transmission has been demonstrated as well as non- suggest rural environmental sources; many observers,
culture methods permit. The incidence of leprosy including Irgens, Leiker, and Guinto, have com-

Table 1. Soil, water, and vegetation as sources of leprosy-like diseases and possibly of leprosy.
Source, Refer-
associated finding Description Location Test method (result) ence(s)

Soil
Noncultivable AFB 1 of 4 soil samples positive Bombay, India Mouse footpad inoculation, histopathologic 34
tests, and MAB to PGL-I antigen
(positive)
Noncultivable AFB Soil from 2 of 12 armadillo Pointe Coupee MAB to PGL-I antigen (positive) 35*
burrows positive Parish, La.
Water
Lepra bubalorum Mycobacterial leprosy-like disease Indonesia Histopathology of nodules and macro- 36
of water buffaloes scopic observations (positive); cultivation
attempts (negative)
Noncultivable AFB Organism in pond water Ivory Coast Mouse footpad inoculation, armadillo 37
inoculation, pyridine and DOPA
oxidase (positive)
AFB in well water 17 samples tested: cultivable Bombay, India Mouse footpad inoculation, histopathologic 34
and noncultivable AFB tests (positive)
Vegetation
Buruli disease Organism as saprophyte on Uganda Characteristic growth on Lowenstein- 38
(Mycobacterium grass, entry via skin lesions Jensen medium
ulcerans)
Cultivable AFB Optimal qualities of sphagnum Germany, Culture on sphagnum moss medium; 39,40
moss for growth of AFB Sweden, and identification by standard biochemical
Norway and taxonomic methods
Noncultivable AFB Thought to exist in sphagnum Norway DOPA oxidase, pyridine, and mouse 37, 41
footpad tests (positive)
Unknown
Batrachian leprosy Lepra-like granulomas in Bolivia Stains for AFB and histopathology 42
tree frogs (positive); cultures for AFB (negative)
Leprosy in two Chimpanzee and mangabey Sierra Leone Histopathology and biochemical analysis 43
primates monkey and Nigeria (positive); cultures (negative)
NOTE. Abbreviations: AFB = acid-fast bacilli; MAB = monoclonal antibody; PGL-I = phenolic glycolipid-I; DOPA =
3,4-dihydroxyphenylalanine.
* Personal communication, R. W. Truman.
Nonhuman Sources of Leprosy 565

mented on the rural distribution of the disease (cited werewater and dung; however, no acid-fast bacteria
in [3]). Perhaps M. leprae can survive in plants, wa- were found in tested samples [42]. Whether this
ter, and soil as well as in dust, fomites, furniture, batrachian leprosy is the same as human leprosy has
and clothing. Moreover, insects and other arthropods not been explored, and the source of the acid-fast
have been extensively investigated as potential vec- bacilli has not yet been established. In light of how
tors and sources of M. leprae. In addition, the ar- ubiquitous mycobacteria are in nature, this infection
madillo, now the prize experimental model for might be caused by another species altogether.
leprosy, has been shown to harbor a disease indis- Nevertheless, the appearance of the disease is sug-
tinguishable from human leprosy [30]; to the ar- gestive of leprosy.
madillo has been attributed the ability to infect In 1970 Barker et al. reported that M. ulcerans
humans, particularly men who handle the animal could exist as a saprophyte on certain grasses and
[31- 33]. These three broad types of environmental that the Ugandan Buruli disease was contracted by

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sourcesof M lepraewillnow be consideredseparately. the contact of broken skin with grass. This concept
was reinforced by the location of the lesions on the
lower legs, the age and sex of those most often af-
Soil, Vegetation, and Water
fected, and the geographic distribution of the dis-
As relatively"inert" substances, soil, water, and vege- ease [38]. These findings were significant as M ulce-
tation have not received much notice as possible sites rans had never before been isolated from a
for M leprae, but throughout this century pieces of nonhuman source. A parallel mode of transmission
evidence have supported their roles as sources (ta- of M. leprae may exist in India, where early lesions
ble 1). As early as 1910, Dr. Sand from Norway on the feet are found more often in patients from
postulated at the Second Leprosy Congress that hilly and stony districts than in patients from allu-
leprosy is not transmitted by direct contact but indi- vial regions [12]. Broken skin or trauma appears to
rectly through a natural medium such as soil (cited play a role in transmission.
in [34]). In 1930 Lobel described a leprosy-like dis- Other animals also have been found to have a dis-
ease in Indonesian water buffaloes. Named "lepra ease indistinguishable from leprosy. A chimpanzee
bubalorum," it manifested itself with skin nodules, from the Sierra Leone and a mangabey monkey from
nasal ulcers, and granulations of the nasal mucous Nigeria developed the disease a few years after en-
membranes. Globi of acid- fast bacilli were seen in tering the United States [43]. It is suspected that they
the skin, nasal mucous membranes, and lymph contracted it through human contact in their native
nodes. Attempts at cultivation were made, but no countries, although other sources of leprosy - such
growth was observed over two years. While its iden- as animals, insects, water, or vegetation - cannot be
tity was not established definitively, a close resem- discounted.
blance existed between this disease and human lep- The quest for inanimate or plant sources of M lep-
rosy [36]. The photographs showed nodules and rae falls short when compared with the more appar-
ulcers located at points where water or mud would ent findings in arthropods and armadillos. Yet the
come into contact with the animals: legs, belly, very fact that M. leprae can be found in insects and
neck, and head were all affected, whereas the rest certain feral animals posits-the existence of a more
of the body was spared. Although no environmen- fundamental source as a reservoir. Recent studies re-
tal cultures or stalns were done, these findings sug- vealed that soil samples from two of 12 armadillo
gested that the pathogenic organism existed in wa- burrows in Pointe Coupee Parish, Louisiana, were
ter or mud [30]. positive for the apparently species-specific phenolic
In 1954 Machicao and La Placa noted lepra-like glycolipid-I (POL-I) antigen of M. leprae. These
granulomas in Bolivian tree frogs. Closer investiga- studies capitalized on unique characteristics of the
tion of skin, liver, and gastrointestinal organs re- POL-I antigen, identifying it by ELISA and by its
vealed that the granulomas contained noncultivable reaction with a specific monoclonal antibody ([35]
acid-fast bacilli arranged in globi in macrophages and R. W. Truman, personal communication). The
and foamy histiocytes. Because the frog's diet con- possibility of cross-reacting antigens is nearly ex-
sists of insects, an intestinal route of transmission cluded because of the specific nature of the test; thus,
to the frogs was suggested when acid-fast bacilli were the results strongly support the identity of the or-
found in the local insect population. Also suspected ganism as M. leprae in the soil. The POL-I antigen
566 Blake et 01.

may be a remnant from excretions or secretions of (DOPA) oxidase test and a pyridine extraction of
infected armadillos. On the other hand, the antigen acid-fastness. On the other hand, two samples from
may be part of viable bacilli that could serve as a other sites in Norway and the Ivory Coast produced
source of infection for armadillos and human beings. extensive mycobacteriosis in armadillos and grew in
The work of Kazda and associates sheds new light mouse footpads but were negative for DOPA oxi-
on potential sources of M. leprae. These researchers dase and pyridine extraction [37]. Although their
established that the sphagnum vegetation of moor identification is incomplete, perhaps the latter bacilli
biotopes provides a suitable environment for the serve as cofactors with the M. leprae-like bacillus.
reproduction of mycobacteria. Heat accumulates un- Additional studies of water and soil were per-
der the surface of the vegetation, raising the tem- formed in Bombay in 1981 through the mouse foot-
perature to a level 28°C higher than the surround- pad technique and growth on sphagnum nutrient
ing air, and nutrients circulate easily in this acidic substrate. Noncultivable samples were tested by

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environment, creating favorable conditions for the DOPA oxidase and pyridine decoloration and ulti-
growth of mesophilic organisms [39]. Fifty percent mately were analyzed through screening for the
of the tested sphagnum samples in northwestern Ger- M. leprae-specific PGL-I antigen with monoclonal
many contained cultivable acid-fast bacteria [40]. In antibodies. One soil sample contained noncultiva-
moors in southern Sweden and on the west coast of ble acid-fast bacilli that were consistent with
Norway (an area where leprosy was formerly en- M leprae in tests with monoclonal antibody to PGL-
demic), one-third of the samples tested contained I [34].
cultivable acid-fast bacteria, and the varieties of both Are these environmental organisms indeed
sphagnum and mycobacteria differed in the two M. leprae? If environmental organisms are con-
countries [39]. firmed to be M. leprae, are they viable pathogens?
In 1980 Kazda et al. initiated an indirect test for Does their presence mean that individuals could be
the presence of M. leprae in Norway. Since M leprae exposed to M leprae while walking, washing, or
has a characteristic growth pattern in mouse foot- drinking water? The epidemiology of leprosy in Nor-
pads that is distinct from the growth patterns of all way indicates that, in the past, close contact with
cultivable acid-fast bacteria [41],these investigators sphagnum enhanced the risk of infection by a fac-
tested samples that contained acid-fast bacilli and tor of at least four [44]. However, viable acid-fast
that were culture-negative by inoculating them into bacilli closely resembling M. leprae persist today in
footpads. From 122samples, 21070 of 759 inoculated sphagnum moss, while leprosy has been eradicated
footpads demonstrated growth typical of M. leprae, from Norway. Either the source played but a small
with 105-106 acid-fast bacilli per footpad. Auto- part in the disease or the significance of its role has
trophic enzymatic properties that help the organism changed. Convention argues that improvement in liv-
maintain viability were also identified. As yet, the ing standards, better nutrition, and possibly immu-
organism has not been identified, but biochemical nity have contributed to the decline of leprosy [3].
analysis and armadillo inoculation continue [41]. How much exposure would cause disease in a sus-
The most comprehensive of Kazda's studies in- ceptible individual? If the organism is M leprae and
volved samples of soil, water, and vegetation from is ubiquitous in nature, one might expect more cases
sites throughout the world in which leprosy was en- of leprosy, particularly in countries where the prev-
demic or had been endemic. Noncultivable acid-fast alence of the disease is low. With a potential attack
bacilli were found in Norway, the Ivory Coast, Por- rate of 5070 [45] but a much lower actual prevalence,
tugal, Peru, India, and Louisiana. No acid-fast bacilli this discrepancy is unresolved. Certain environmen-
were found in Sweden, Scotland, or Germany. Af- tal sources may be more infective than others, and
ter many noncultivable acid-fast bacilli were tested pathogenicity may depend more on the innate sus-
in mouse footpads, armadillos, and biochemical sys- ceptibility of a population than on the mere exis-
tems, the organisms from a sphagnum sample from tence of M. leprae in other sources. Newell suggests:
Norway and a water sample from the Ivory Coast "One must conclude from these dissimilar ex-
were found to be indistinguishable from M. leprae; periences that the presence of M. leprae, although
they showed characteristic growth in mouse footpads, probably essential for the development of leprosy,
produced typical disease in armadillos, and gave must be placed in conjunction with other facto 's that
positive results in both a 3,4-dihydroxyphenylalanine might be of dominating importance in influencing
Nonhuman Sources of Leprosy 567

the occurrence of the disease in a population. . . . ing conditions were such a tremendous part of the
By exclusion, one is left with the conclusion that the quotidian reality that the prevailing view was that
method of spread and environmental factors must "to be without lice was a sign of bad health" [46].
be dominant" [12]. Newell speaks of environmental In Iceland, too, when the standard of living rose and
"factors," while wespeak of environmental "sources"; arthropod infestation was reduced, leprosy disap-
both environmental factors and environmental peared [46].
sources appear to be important to an understand- In East Africa, Innes describes yet another rela-
ing of leprosy. tionship between leprosy and scabies: "Where there
is much gross, untreated scabies, there is liable also
to be much leprosy in the community, and instances
Arthropods
are numerous of the two diseases being coincident
It has been observed that leprosy coexists with low in the same person .... The explanation of the corre-

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standards of living, contributing factors being mal- lation may be that chronic scabies means chronic
nourishment, poor hygiene, crowding, and infesta- scratching and, altogether, many minute abrasions
tions by lice, fleas, ticks, flies, and mosquitoes (ta- through which the causal germs of leprosy are in-
ble 2). The relationship between arthropods and oculated, repeatedly and frequently" [47]. Other
leprosy appears to be strong, if only by negative as- authors have noted the association of scabies and
sociation: Ockland points out that fleas and un- leprosy in Norway (Danielson and Boeck, 1847)and
hygienic conditions were the norm in Norway when in Brazil (Bassewitz, 1905), as cited by Dungal [46].
leprosy was endemic, but when living conditions im- In light of these observations, the possibility that
proved, both the fleas and the leprosy vanished (cited mites (Sarcoptes [formerly Acarus] scabieii serve as
in [25]). Similarly, Dungal states that leprosy in Ice- a vector or an intermediate host for the leprosy ba-
land at the turn of the century went hand in hand cillus does not seem far-fetched.
with squalor, scabies, lice, and fleas [46]. These liv- As early as 1911 an interest in arthropods and

Table 2. Possible arthropod sources of leprosy.

Finding Description Location Test method and result Reference(s)

Association of leprosy Leprosy and scabies; leprosy Iceland, Norway, Surveys 25, 46-49
with arthropods and fleas; leprosy and Africa,
mosquitoes Martinique
Leprosy and fleas Fleas and larvae from Bogota, Colombia Stain positive for AFB and Cited in 46
homes of cases: positive monkey "inoculation"
forAFB
Mycobacterium leprae AFB available to blood- United States and 5 x l()3 to 5 X lOs bacillilml 50,51
bacteremia sucking insects India of blood
Acquisition of AFB Culex and Cimex species India Stain positive for AFB and 52
from blood by mos- fed on untreated patients mouse footpad test positive
quitoes and bedbugs
M. leprae in Field-collected arthropods India Stain positive. for AFB and 53,54
arthropods mouse footpad test positive;
culture for AFB negative
Flies as vectors AFB (from mucus) India Stains of fly gut, mouthparts, 55
deposited elsewhere and legs sometimes positive
Mosquitoes as vectors Infection of mouse footpads India Histopathology of mouse 56
via mosquitoes footpad tests positive and
characteristic
Viability of M. leprae Test of duration of AFB India Mouse footpad test positive 57
in mosquitoes viability in mosquitoes for maximum of 42-144 hr
after a blood meal
Possibility of arthropod Proboscis length vs, depth United States Measurement of proboscis 58
transmission of lepromatous leprosy length of various species
skin infiltrate

NOTE. AFB = acid-fast bacilli.

568 Blake et 01.

leprosy was manifest. Ehlers et al. caused arthropods posure is sufficient to cause disease. As the child re-
to bite lepromatous patients, then dissected and ceived sulfone treatment, the possibility that leprosy
stained the stomach contents of the arthropods. Only would have developed is a matter of speculation.
one of 21 fleas and one of 12 mosquitoes were posi- Dungal also compares the insect populations of
tive for acid-fast bacilli, while 53 bedbugs and 16 42 leprosy-endemic territories with that of Iceland,
head lice were negative (cited in [25]). In 1912 Sandes whose insect population is sparse. If all countries
allowed insects to bite patients and found one of 80 shared the same insect vectors, the candidate spe-
mosquitoes, 20 of 60 fleas, and 20 of 75 bedbugs cies would be limited to lice (Pediculus capitis and
positive for acid-fast bacilli. He also found a mac- Phthirus [formerly Pediculus] pubis), fleas (Pulex
ule that developed where a bedbug had bitten one irritansi, and mites (S. scabieii [46].This survey does
patient, but it is impossible to determine whether not establish a definitive vector, as these four insects
the bedbug caused the macule or whether the already are plentiful allover the world, nor does it preclude

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leprous patient responded to the bite with the erup- the possibility of different vectors existing in in-
tion of a new lesion (cited in [25]). dividual countries, but it does provide a worthwhile
The most compelling early work on this subject starting point.
is that done by Munoz-Rivas in the 1940s. Noting While M. leprae bacteremia has been scrutinized
that leprosy patients from around Bogota, Colom- in attempts to establish the severity of leprosy, this
bia, tended to livein huts where fleas were abundant, condition also becomes a significant premise with
he looked for evidence of acid-fast bacilli in fleas. regard to the insect vector's role in the spread of dis-
In an area near an antileprosy dispensary, he found ease. An interest in leprosy bacteremia existed be-
that 16070 of 200 fleas contained acid-fast bacilli; he fore the turn of the century, and later studies doc-
found no acid-fast bacilli in fleas collected from umented precise figures. Drutz et al, demonstrated
places free of leprosy, and he found these bacteria lOS bacteria/ml of blood [50], while Manja et al.
in 11070 of fleas allowed to bite lepromatous patients. noted between 5 x 103 and 5 x lOS viable bacilli/ml
In studying larvae of fleas from contaminated places, of blood [51]. Although the number of bacilli con-
he found that 2% of the progeny contained acid- stituting an infectious dose has yet to be established,
fast bacilli. He also found that when fleas that had these studies showthe high concentration of M /eprae
bitten patients were subsequently allowed to bite that is accessible to a biting insect and that could be
monkeys, two of four monkeys developed a leprosy- picked up and transmitted to another human being.
like disease (cited in [46]). It is unfortunate that more In India Narayanan et al. observed that laboratory-
specific tests for the identification of this acid-fast reared mosquitoes (C.jatigans) and bedbugs (Cimex
bacillus were not available to confirm an associa- hemipterus) harbored acid-fast bacilli taken up from
tion between leprosy and fleas. The implications of the blood of untreated lepromatous patients; 70070
these findings, however unpolished, are great: fleas and 50%, respectively, of these two insect species
can live severalhundred days and can bite everynight were positive. The typical growth pattern of the
for a month. With their longevity and the potential bacilli from a homogenate injected into mouse foot-
infectiveness of their larvae, they may serve as an in- pads and the absence of growth on LOwenstein-
visible reservoir of the bacillus, contributing to a Jensen medium suggest that these wereviable leprosy
base-line level of endemic leprosy. bacilli [52]. We do not know, however, how many
Dungal cites a case in Martinique in which the mosquitoes or bites it would take to cause a similar
child of a mother with leprosy received nine infection in the mouse footpad.
mosquito bites. From fluid in one bite, great num- Narayanan et al. also collected arthropods from
bers of acid-fast bacilli, apparently M. leprae, were dwellings of lepromatous patients and dwellings of
recovered. The house was infested with both Culex controls. Mosquitoes were taken from inside the
fatigans and Aedes aegypti, and one Culex mosquito dwellings; bedbugs weretaken from furniture, walls,
contained numerous acid-fast bacilli [46]. Circum- and floors; and lice and mites were collected from
stantial evidence points to the mosquito as the vec- individuals. These authors found acid-fast bacilli in
tor for the bacillus; however, inoculation by a small both the leprosy and the control pools; in fact, the
insect bite does not necessarily indicate transmission bacilli were commoner in samples from unaffected
of the disease; while the bacillus is vital for infec- persons' homes. A few mycobacteria were cultiva-
tion, we do not yet know what degree or type of ex- ble in virtually all samples. When homogenates were
Nonhuman Sources of Leprosy 569

injected into mouse footpads, organisms in two sam- lepromatous patient, via the medium of fly trans-
ples from Culex species grew in a manner character- mission, from becoming the source of infection for
istic of M leprae; one sample was from a control 100 people in a single day, up to a range of 8 km
dwelling and the other from a leprosy-affected home from the patient."
[53]. The distribution is accounted for either by a Proven transmission of M leprae has been shown
ubiquity of M leprae, which would consequently be best by Narayanan et al., who observed the multipli-
picked up by mosquitoes, or by the ability of mosqui- cation of acid-fast bacilli in mouse footpads on
toes to move easily among homes of patients and which mosquitoes (A. aegyptii were allowed to feed
controls. Either scenario suggests a potential for up to 48 hr after they had fed on lepromatous pa-
transmission of leprosy throughout the range of the tients [56}. The persistence of solid bacilli in differ-
mosquito. The acid-fast bacilli found in the other ent parts of the insect declines rapidly, as docu-
arthropods may not be M leprae or may be nonvia- mented by the presence of bacilli that are less intact

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ble M leprae. Pools negative for acid-fast bacilli oc- at later times. In A. aegypti, solid bacilli are found
casionally contained organisms that multiplied in in the proboscis after 96 hr, in the gut after 48 hr,
mouse footpads; this finding suggests that the foot- and in the fecesafter 42 hr. In C fatigans, solid bacilli
pad method is more sensitive than staining - a com- are found in the proboscis after 144hr and in the gut
mon observation in clinical microbiology. Another after 48 hr but are not found in the feces [57]. This
detailed survey of noncultivable acid-fast bacilli in short-lived viability is not considered sufficient to
arthropods collectedwithout regard to their proximity permit multiplication of the bacillus in mosquitoes,
to leprosy cases also seems to indicate that these non- but mechanical transmission of M lepraeby mosqui-
cultivable acid-fast bacilli could be M leprae [54]. toes could nonetheless occur [57]. These elegant
Additional innovative work was accomplished studies not only demonstrate that mosquitoes can
by Geater in East Bhutan. He allowed three genera be infective but also establish a tentative time frame
of flies to feed on the nasal mucus of untreated for transmission and possible infection.
lepromatous patients. No control fliesharbored acid- In 1983 McDougall and Cologlu related the depth
fast bacilli; however, all flies from each genus took of penetration of the biting apparatus of certain ar-
up acid-fast bacilli from the mucus. The bacilli were thropods (particularly those that had already been
found mostly in the guts of the insects but also oc- implicated in the possible transmission of M. leprae)
casionally on their mouthparts and legs. Flies al- to the depth of the cellular infiltrate and bacillary
lowed to bite intact skin did not take up any acid- mass found in the skin of lepromatous leprosy pa-
fast bacilli except when placed on the earlobes of tients. Among the arthropods that these researchers
patients. In contrast, most of the flies that fed on studied were A. aegypti, Culex moles/us, Anopheles
ulcerated skin took up acid-fast bacilli. Finally, atroparvus, Pediculus humanus, S. scabiei, Cimex
Geater established that flies could deposit acid-fast lectularius, and flies of the Stomoxys species. As
bacilli on a receptor surface: he placed sugar cubes M leprae cannot survive in the epidermis or in the
on albumin-covered slides near some patients' mu- subepidermal "free zone," it would have to be inocu-
cus. The flies fed on both sources, tracking back and lated to the deeper level of the cellular infiltrate and
forth. After 2 hr, nine of 10 slides showed acid-fast bacillary mass. The findings indicate a feasible rela-
bacilli [55]. tionship between the position of the affected cellu-
That flies can take up acid-fast bacilli from ulcer- lar infiltrate and the .depth of penetration of the
ated skin and nasal mucus and deposit the organ- mouthparts except in the case of S. scabiei [58].
isms on distant surfaces creates a dispersed pool Other investigators have attempted to implicate
of M leprae in the environment, although the in- arthropods in the transmission of leprosy [48, 49,
fectious dose remains unknown. Davey [18] notes 59]. It is uncontested that several genera of arthro-
that "in endemic countries the nasal discharge is pods can take up M. leprae from a heavily bacillifer-
commonly deposited on the ground whenever the ous patient's blood or nasal mucus, that they can
nose is cleared" and states that the potential for trans- both deposit the bacilli on distant surfaces and in-
mission of M. leprae through flies should not be fect mouse footpads, and that the mycobacteria can
taken lightly: "Bearing in mind the millions of via- retain their viability long enough to be transmitted.
ble M. leprae that may be involved, there is nothing While the public health risks are obvious, it is un-
to prevent the nasal discharge from a single untreated clear how these facts relate to human disease. To
570 Blake et al.

infect humans, an insect would have to feed long mal model for leprosy, investigators met many ob-
enough to retain sufficient viable bacilli, and it would stacles. The appropriate animal would be naturally
be restricted to a certain area by its range and life- susceptible to the disease in the same manner as hu-
span. Perhaps the "housebound" nature of leprosy man beings, would not be subject to immunosup-
can be partly explained by the range of the infected pression, and would develop a spreading infection
insect, while certain flying insects with larger ranges with the bacteriologic and histopathologic charac-
could introduce distant cases. teristics of leprosy in humans. Binford's attempts
Positive evidence notwithstanding, the arthropod with monkeys, chimpanzees, hogs, dogs, and fruit
vector theory has been widely criticized. Some bats were unsuccessful (cited in [60]), while Shepard's
authors argue that transmission by insect vectors re- mouse footpad experiments demonstrated charac-
lies on open cases of leprosy in the community as teristic disease limited to the site of inoculation [61].
sources and is hindered by the segregation of infected Using thymectomized, whole-body-irradiated mice,

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individuals. For example, Newell states: "In a given Rees et al. were able to increase the yield of bacilli
area, the local segregation of the clinically ill appar- per footpad by as much as 100-fold [62].
ently decreases the risks of infection to the commu- Kirchheimer and Storrs first identified the nine-
nity, although it is still exposed to the same vectors. banded armadillo (Dasypus novemcinctus) as a
M. leprae cannot apparently pass over walls" [12]. model for leprosy research [60]. Its advantages are
While the existence of special hospitals for the treat- readily apparent: it has a long life-span (about 12
ment of leprosy has generally been associated with years, compared with two years for the mouse),
a decreased incidence, in the Philippines and on St. which is compatible with the long incubation period
Croix this has not been the case [25]. Moreover, one of leprosy; it has a body temperature of 30°C-36°C,
might question whether the disease decreases sec- which is in keeping with the optimal temperature for
ondary to segregation alone or in response to segre- the growth of M leprae,· and it givesbirth to monozy-
gation along with conditions that result in improved gous quadruplets, which are ideal for long-term
immunity - e.g., improved nutrition or living stan- genetic studies [63]. Moreover, when infected with
dards. Currently, segregation is instituted primarily M. leprae, 800/0 of armadillos develop a disseminated
for the purpose of treatment, with a resultant de- infection that closely resembles human disease: der-
crease in the availability of viable bacilli to any vec- mal nerve invasion, spread to uninoculated sites,
tor. Perhaps because of treatment or because of the acid-fast bacilli in blood, great numbers of bacilli
hygienic conditions in hospitals and leprosaria, the in tissue, and a positive DOPA oxidase test [64]. The
disease is rare among members of hospital staffs [11]. organisms from human leprosy have been proven to
Other critics of the arthropod vector theory main- be identical to comparable organisms from a leprous
tain that the geographic distribution of leprosy does armadillo by DNA homology studies [65]. In addi-
not conform to the distribution of anyone vector. tion, armadillo-derived lepromin is now a substitute
This situation calls for either a cosmopolitan vector for human lepromin [66]. While the nine-banded ar-
(e.g., bedbugs, fleas, mites) or a uniquely nonspecific madillo has become the focus of contemporary
relationship between bacterium and arthropod. Per- leprosy research (table 3), the Venezuelan armadillo
haps different countries harbor different vectors, as [81] and the seven-banded armadillo [67, 68] have
has been noted for the vectors of Borrelia recurren- also proven susceptible to infection with M leprae.
tis. Furthermore, while arthropod vectors may not The armadillo is a member of the subclass Eu-
function in every country with leprosy, they may theria, the order Edentata, and the family Dasypod-
maintain prominence, particularly in regions with idae. Most of the nine genera are confined to South
low standards of living and poor sanitation. Con- America, but the naked-tailed armadillo reaches
sistent with this concept is the disappearance of Guatemala and the nine-banded armadillo reaches
leprosy from Norway and Iceland when fleas, ticks, North America [82]. The latter species appears to
and lice were controlled (albeit in conjunction with have migrated from Mexico to Texasabout 150years
other improvements). ago and has continued to migrate northward and
eastward ever since [83]. Armadillos were observed
in Louisiana before 1920, and their range has ex-
Armadillos
tended to southern Kansas and Missouri and east
When efforts were being made to establish an ani- through Mississippi, Alabama, and Georgia into
Nonhuman Sources of Leprosy 571

Table 3. Armadillos as sources of leprosy.

Refer-
Study Description Location Test method ence(s)
Experimental leprosy in Armadillos inoculated with Louisiana and Inoculation of Dasypus 60, 63, 64,
armadillos Mycobacterium leprae Venezuela novemcinctus, Dasypus 67-69
sabanicola, and Dasypus
hybridus
Cultivable AFB in armadillos Prevalence of cultivable AFB Colombia and Stain for AFB and culture 70-72
in healthy and leprous Belgium positive
armadillos
Natural leprosy in wild Seven armadillos with disease Louisiana Histopathology identical 30
armadillos indistinguishable from to that of M. leprae;

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leprosy culture negative
Identification of natural Histopathologic and micro- Louisiana Culture negative; DOPA 73,74
leprosy in wild armadillos biologic studies; armadillo oxidase and pyridine
lepromin tested with 146 extraction positive;
lepromatous patients classic Mitsuda reaction
Survey of armadillo disease Positive: 47 of 459 armadil- Louisiana, Positive skin and ear 74,75
in the wild (1977) los in Louisiana, 1 of 88 in Texas, Mis- specimens, histopathol-
Texas; all negative in Mis- sissippi, and ogy, and lepromin
sissippi and Florida Florida reaction
Survey, 1978 Two of 20 armadillos positive Louisiana Culture negative, but his- 76
in French Acadiana topathology and pyridine
extraction test positive
Survey, 1983 Armadillos (21 of 457) posi- Texas Histopathology, base 65
tive along Texas Gulf Coast ratios, and DNA
homology positive
Survey, 1984 One of 96 armadillos positive Mexico Culture negative; histologic 77
and mouse footpad
studies positive
Survey, dead roadside Positive: 10 (2070) of 494 Louisiana Histopathology of both 77A
armadillos, 1984-1985 ears; pyridine extraction
positive
Isolated cases of armadillo One case each at CDC, Originally Histopathologic, mouse 43
leprosy San Diego Zoo from Texas footpad, and lepromin
studies positive
Armadillo contact as risk No association with contact Louisiana Indigenous leprosy cases 78
in leprosy found compared with controls
Cases of leprosy due to arma- Seven men (no other risk) Texas and Years of armadillo contact: 31-32A
dillo exposure developing leprosy South hunting, skinning, and
Carolina handling
Thorns as source of Thorns embedded in 25% Louisiana Characteristic histo- 79
armadillo infection of infected ears pathology
Armadillo sera containing Sera collected in 1961-1964 Louisiana Detection ofantibody by 80
antibodies to M. leprae positive for aritibody ELISA using PGL-I
antigen

NOTE. Abbreviations: AFB = acid-fast bacilli; DOPA = 3,4-dihydroxyphenylalanine; CDC = Centers for Disease Control;
PGL-I = phenolic glycolipid-I.

Florida. For the most part, the nine-banded ar- sosia carinii, a thorny-headed worm unique to the
madillo eats insects, grubs, dirt, and only occasion- armadillo. Flukes and tapeworms can also infect the
ally amphibians, reptiles, mammals, or bird eggs. armadillo [69].
Covered by a carapace, it is free from ectoparasites Both Dasypus sabanicola and D. novemcinctus
except for some ticks and fleas. It can be infected have also been found to harbor cultivable acid-fast
with Trypanosoma cruzi, Borrelia, Rickettsia, and bacteria: of 35 armadillos, 86070 contained "environ-
helminths, particularly nematodes, including Travas- mental mycobacteria." Five of six ticks from ar-
572 Blake et al.

madillos (Amblyommacajennense) were also posi- man leprous contact, or contact with experimentally
tive for cultivable acid-fast bacteria. Cultivable inoculated armadillos?
acid-fast bacteria were found in three of four ar- This discovery quickly prompted a survey of wild
madillos inoculated with M. leprae [70]. Noting the armadillos in the southern United States. Examina-
widespread distribution of acid-fast bacilli in the en- tion of ear specimens indicated that 47 of 459
vironment of the armadillo, Munoz-Rivas states that animals from 11 locations in Louisiana, two from
"in almost everything that they [armadillos] use as unknown locations in Louisiana, and one of 88 from
alimentation [I] have been able to isolate saprophytic Texas had the natural infection. None of 178 animals
mycobacteria" (translation, L. A. Blake) [70, 71]. from Mississippi and none of 76 from Florida were
Recently, Portaels et al. also isolated cultivable infected [75]. Prevalence rates were established for
mycobacteria from both healthy armadillos and ar- some locations in Louisiana; however, differences in
madillos inoculated with M. leprae. These authors the sample sizes at each location made comparisons

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found Mycobacterium avium-Mycobacterium intra- difficult.
cellulare-Mycobacterium scrofulaceum complex, Further studies narrowed the identity of the or-
Mycobacterium gordonae, and Mycobacterium ter- ganism to M. leprae. Binford et al. performed histo-
rae. In fact, tissues from M. leprae-infected arma- pathologic and microbiologic studies of the affected
dillos appeared to contain more cultivable acid-fast tissues, including cultures for mycobacteria, pyridine
bacilli than those from healthy animals; this find- abolishment of acid-fastness, and the ability to oxi-
ing implied that the presence of M. leprae may favor dize DOPA. (The last result is difficult to interpret
multiplication of other species. Of greater impact, conclusively since normal armadillo tissue has the
perhaps, was the discovery of three new, unclassi- ability to oxidize DOPA.) These tests revealed no dis-
fied cultivable mycobacterial strains. These organ- tinctions between the mycobacteria and M. leprae
isms, designated armadillo-derived mycobacteria, are [73]. Similarly, Meyers et al. assayed lepromins pre-
distinct from other species isolated and have been pared from six armadillos with natural disease in
found only in a specific colony of inoculated ar- tests with 146leprosy patients and observed the clas-
madillos [72]. Armadillo-derived mycobacteria- sic pattern of Mitsuda reactions [74]. As M. leprae
along with the human tissue mycobacteria of Bapat is the only organism known to fulfill all of these
[84] and Skinsnes et al. [85], the propionibacteria criteria, it appeared unlikely that the "natural dis-
of Barksdale ([86], cited in [87]), the corynebacteria ease" was caused by another bacillus.
of Barksdale and Delville (cited in [87]), and leprosy- Efforts to establish the range of this "natural dis-
derived corynebacteria [87A] - are found in combi- ease" continued. In an independent study of wild
nation with certain cases of M. leprae infection. They armadillos in French Acadiana (Louisiana) in 1978,
may "share common antigens with M. leprae and Smith et al. found two of 20 armadillos positive for
may shelter [it] in the tissues under the umbrella of acid-fast bacteria that were indistinguishable from
immune unresponsiveness associated with the dis- M. leprae [76]. Later, armadillos along the TexasGulf
ease" [87]. Since these observations have not been Coast were screened; positive animals were killed,
confirmed, they are of uncertain significance. and specimens were cultured and studied histopatho-
Still other bacteria have had an impact on the ar- logically. Base ratio and DNA homology determi-
madillo. In 1975 Walsh et al. discovered a natural nations indicated that these bacteria were identical
leprosy-like infection in seven armadillos at sites to M. leprae. Of 451 animals, 21 (4.6070) were positive
17-39 miles from the Gulf South Research Institute for natural infection [65]. Local prevalences varied
in New Iberia, Louisiana. Acid-fast bacilli were and increased along the coast toward Mexico, mir-
found in skin, lymph nodes, spleen, liver, and der- roring the distribution of endemic human leprosy [65,
mal nerves, with heavily infiltrated macrophages. 88]. Isolated reports of natural cases have come from
The fact that the bacilli were not cultivable raised the San Diego Zoo and from the Centers for Dis-
questions about the identity of this organism vis-a- ease Control (CDC) in Atlanta [43], although both
vis M leprae [30]. Was this natural infection the same of the armadillos involved were originally from
as that caused experimentally by M. leprae, or was Texas. In Mexico one of 96 armadillos was posi-
it due to a different noncultivable acid-fast bacillus tive for acid-fast bacteria that appeared to be
with similar manifestations? If the infectious agent M. leprae [77].
was indeed M. leprae, was the source soil, water, hu- These discoveries have generated public health
Nonhuman Sources of Leprosy 573

concerns. What does leprosy in armadillos have to ticular animal there was no evidence of systemic in-
do with human leprosy? In 1977 Filice et al. com- fection, macrophages surrounding the thorn were re-
pared the armadillo contact of persons who had in- plete with acid-fast bacilli [79]. It is tempting to
digenous leprosy in Louisiana with that of matched ascribe a direct relationship between the illness of
controls, finding no significant difference in the na- these animals and their ear or nose thorns, as the
ture or frequency of contact [78]. Yet while casual characteristic ear involvement lends credence to the
contact may not prove significant, intense and infectivity of the thorn. A base-line value for thorn
prolonged contact - as in the hunting, skinning, and prevalence is necessary to establish a link in this en-
wrestling of infected armadillos - may predispose a vironmental chain.
person, particularly one with breaks in the skin, to We do know that armadillos are not responsible
infection transmitted via a leprous armadillo. The for introducing leprosy into Louisiana: leprosy was
acquisition of leprosy by seven men who had no risk reported there as early as 1766, and its presence

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factors besides extensive armadillo contact supports resulted in the opening of a leprosy hospital in New
this argument [31-32A]. Indeed, contact with ar- Orleans in 1785 [2]. Recent work with armadillo se-
madillos has been considered a risk factor since 1976, rum collected between 1961 and 1964demonstrated
as indicated by the inclusion of this category on the that at least 20010 of samples contained antibodies
CDC surveillance form for leprosy [27]. to the species-specific PGL-I capsular antigen. This
Of late, more attention has been focused on the finding indicates that M. /eprae was enzootic in ar-
origin of the disease in armadillos. One potential madillos of southern Louisiana as early as 1961 and
source is the untreated lepromatous patient, who that the original infection could not have occurred
most likely would transmit the disease in a rural area by environmental contamination in experiments
where armadillos have access to contaminated cloth- starting in 1968 [80]. In precluding the possibility
ing, dressings, or human remains. In marshy south- that experimentally infected armadillos are the
ern Louisiana, where leprosy has been endemic for source of leprosy in wild armadillos, this informa-
over 150 years [89], the burial of bodies of lepers in tion leaves investigators with uncertainty about the
graves too shallow to prevent their being eaten as car- origin(s) of leprosy in the armadillo and the possi-
rion by burrowing armadillos may have been a fac- ble role of the armadillo in human leprosy.
tor in exposure. On the other hand, armadillos in
all places can burrow, yet no armadillos in other
Conclusions
leprosy-endemic areas of Central and South America
appear to have been affected (with the exception of Close inspection of the literature on nonhuman
the animal recently found in Mexico). This pattern sources of leprosy makes it apparent that research-
leads to the suspicion that some unique natural ele- ers are severely limited by certain characteristics of
ment in Louisiana (soil, water, fauna) may be a con- the leprosy bacillus itself. First, a favorable culture
tributing environmental source of leprosy. Insects, medium for the growth and unequivocal identifica-
as the main component of the armadillo diet, may tion of M /eprae is lacking. While the sphagnum
be a source of infection, either through ingestion or nutrient medium introduced by Kazda [37] may
through surface bites [90]. In a recent preliminary prove to be a valuable toolin the future, at the pres-
study, earthworms (a component of the armadillo's ent time investigators are restricted to time-con-
diet) were taken from household "worm farms" ad- suming and expensive inoculation of animals or
jacent to the homes of three patients with leprosy biochemical tests that can only be presumed to be
in northern Louisiana, an area where leprosy is not specific. The clumsiness of the available methods and
endemic and where armadillos are common. No the relative inaccessibility of promising biochemi-
acid-fast bacilli were found in the worms [91]. cal tests are major stumbling blocks in studies of this
In a recent survey, 3.1010 of the Louisiana ar- sort. Unfortunately, this complicated state of affairs
madillos sampled manifested acid-fast bacilli within undermines much of the careful research done ear-
the nerves of the ear; these bacilli were identified as lier in this century; we are forced to interpret it as
M. /eprae. A more remarkable finding was that mere observation, not proof.
25.3010 of the infected ear specimens had thorns im- Second, other variables hark back to the enigmatic
paled within them. In another animal, sections of nature of leprosy itself. It is a disease with a long
thorns were found in the nose. Although in this par- incubation period, a low attack rate, and a mecha-
574 Blake et al.

nism of transmission that may vary from case to case. nutrition, in which a weakening of cell-mediated im-
In addition, the immune status of the host deter- munity enhances the risk of infection by intracellu-
mines to a great extent whether or not infection will lar pathogens such as M. leprae [92].
occur and, indeed, what degree of infection will be The armadillo is the most firmly established non-
encountered. Because the necessary infective load is human reservoir of leprosy; the animal sustains a
still largely a matter of speculation, predictions of natural infection and, with especially intense con-
infection are virtually impossible. tact, probably can infect humans. It is suspected that
In light of so many unanswered questions about humans contract the disease from armadillos by way
leprosy, the introduction of yet another variable- of droplet inhalation or through breaks in the skin
environmental sources - does not seem altogether and that infection can be transmitted to armadillos
unjustified. Our critical review indicates that it is not from humans via similar routes; in effect, humans
only possible but likely that the presence of the ba- and armadillos may pass the disease back and forth.

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cillus in one or several nonhuman sources has been It is, however, equally possible that human beings
a key factor in infection. Environmental sources are and armadillos share an environmental niche with
suggested by many of the patterns of leprosy. The a third component that is infected with or harbors
disease frequently has a rural prevalence, is often as- M. leprae. Environmental mycobacteria-not only
sociated with farming, and tends to occur in youn- M leprae- appear to contribute to infection and the
ger persons in rural than in urban settings [3]. Like- response to infection in armadillos.
wise, the numerical predominance of male patients The associations of leprosy and its causative or-
with lepromatous leprosy strongly favors an environ- ganism with soil, water, vegetation, arthropods, and
mental reservoir, because men traditionally have armadillos are compelling. However, the broad dis-
more environmental contacts than women. M leprae tribution of leprosy, with accompanying wide vari-
may possibly enter the body through sites of trauma ations in climate, population, and prevalence, defies
on the feet and legs; a soil or plant source could ac- facile conclusions. Therefore, proof of one or several
count for the observed distribution and could ex- environmental sources for specific clinical cases of
plain the often asymmetrical location of lesion sites. leprosy awaits either the application of currently
In addition, environmental cofactors - and even available techniques to identification of the specific
other environmental mycobacteria - could predis- PGL-I capsular antigen or (as is more likely) the de-
pose an individual who might otherwise not be sus- velopment of a less labor-intensive and time-con-
ceptible to infection with M. leprae. The latter pos- suming method by which M. leprae isolation and
sibility is underscored by leprous armadillos in which identification can be accomplished.
cultivable mycobacteria, including the unique
armadillo-derived mycobacteria, are present in References
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madillos. in leprosy. Int J Lepr 1965;33:716-31
Many of the above observations also apply to the 2. Joseph BZ, Yoder LJ, Jacobson RR. Hansen's disease in
potential role of arthropod vectors in the transmis- native-born citizens of the United States. Public Health
sion of leprosy, as environmental exposure would cer- Rep 1985;100:666-71
3. Fine PEM. Leprosy: the epidemiology of a slow bacterium.
tainly increase exposure to insects. However, insect Epidemiol Rev 1982;4:161-88
populations respond dramatically to changes in hab- 4. Nath I, Jayaraman J, Sathish M, Bhutani LK, Sharma AK.
itat, and one must consider that developments in the Inhibition of interleukin-2 production by adherent cell fac-
past 100 years have significantly altered the role of tors from lepromatous leprosy patients. Clin Exp Immunol
insects in any disease, save in countries with poverty 1984;58:531-8
5. Bloom BR. Learning from leprosy: a perspective on immu-
and squalor. Unlike the aforementioned environmen- nology and the third world. J Immunol 1986;137:i-x
tal sources, insects have been proven to have the abil- 6. Nathan CF, Kaplan G, Levis WR, Nusrat A, Witmer MD,
ity to pick up M. leprae from the blood, maintain Sherwin SA, Job CK, Horowitz CR, Steinman RM, Cohn
it, deposit it, and even infect mouse footpads with ZA. Local and systemiceffects of intradermal recombinant
it. Although their prevalence is highly variable from interferon-y in patients with lepromatous leprosy. N Engl
J Med 1986;315:6-15
country to country, insects may prove responsible for 7. Young DB, Harnisch JP, Knight J, Buchanan TM. Detec-
a significant number of infections. This possibility tion of phenolic glycolipid 1 in sera from patients with
is particularly significant in the context of severemal- lepromatous leprosy. J Infect Dis 1985;152:1078-81
Nonhuman Sources of Leprosy 575

8. Cho S-N, Hunter SW, Gelber RH, Rea TH, Brennan PJ. 31. Freiberger HF, Fudenberg HH. An appetite for armadillo.
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