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Current knowledge on Mycobacterium lepraetransmission: a systematic literature review†
MARTIN W. BRATSCHI*,**,# ,
PETER STEINMANN*,**,# , ANNA WICKENDEN*** &
THOMAS P. GILLIS***
*Swiss Tropical and Public Health Institute, Basel, Switzerland
**University of Basel, Basel, Switzerland
***effect:hope, Markham, Canada
Accepted for publication 24 May 2015
Summary
Background: The transmission pathways of Mycobacterium leprae are not fully
understood. Solid evidence exists for an increased risk for individuals living in close
contact with leprosy patients, but the existence of zoonotic leprosy, environmental
reservoirs and trauma-related transmission has also been established.
Purpose: To assess the current state of knowledge on M. leprae transmission, we
conducted a systematic review of the peer-reviewed literature pertaining to this topic.
Method: Major electronic bibliographic databases were searched for relevant
peer-reviewed articles published up to January 2014. No restrictions on study types,
participants and location were applied, and all outcomes demonstrated to contribute
to the transmission of M. leprae were considered. Included studies were grouped by
mode of transmission, namely (i) human-to-human via aerosols or direct contact;
(ii) direct inoculation (e.g. injury); and (iii) transmission to humans from
environmental or zoonotic reservoirs, and by insects. The importance of the different
transmission pathways and the strength of the evidence were assessed considering the
number of publications describing similar findings, the consistency of the findings
and the methodological quality of the studies.
Results: A total of 79 relevant articles were retained out of 3,805 hits resulting from
the application of the search strategy. Solid evidence for transmission among contacts
exists, and for zoonotic leprosy in the southern States of the USA. Based on the extant
evidence, skin-to-skin contact, aerosols/droplets and shedding of bacteria into the
environment and subsequent infection, e.g. through dust or small wounds, all remain
possible options.
Conclusion: No study has unequivocally demonstrated the mechanisms by which
M. leprae bacteria travel from one case of leprosy to another.
†Work carried out at Swiss Tropical and Public Health Institute, Basel, Switzerland.Correspondence to: Thomas Gillis, effect: hope, Markham, Ontario, Canada (e-mail: [email protected])
#Authors contributed equally
Lepr Rev (2015) 86, 142–155
142 0305-7518/15/064053+14 $1.00 q Lepra
Introduction
Leprosy (Hansen’s disease) is caused by a chronic infection with Mycobacterium leprae of
the skin, peripheral nerves and often the mucosa of the upper respiratory tract. If untreated,
the infection can lead to damage of the skin, eyes and peripheral nerves.1 Early diagnosis and
completion of multi-drug therapy (MDT) are essential to preventing permanent disability.
With the use of MDT and changes in disease recording, the worldwide prevalence of leprosy
has fallen by 90% since the early 1990’s. Globally, the number of leprosy cases is now below
the elimination threshold of one case per 10,000 people as defined by the World Health
Organization (WHO).1However, in several countries and sub-national regions, the number of
leprosy cases remains above this threshold. Furthermore, despite near-universal use of MDT,
the annual number of newly detected cases, including children, has remained fairly constant
at around 200,000 – 300,000 cases in recent years.2 These observations indicate that current
control measures have not succeeded in halting the transmission of leprosy.3,4
Despite repeated attempts over the past decades to identify transmission patterns among
affected communities, a full understanding of the transmission pathways ofM. leprae has not
been reached. Epidemiological studies have identified an increased risk for individuals living
in close contact with leprosy patients. However, many new cases cannot identify an index
case from whom they may have acquired the infection. Evidence for zoonotic leprosy in the
USA and the discovery ofM. leprae DNA in the environment are complicating the traditional
paradigm that M. leprae is transmitted solely from human to human. To assess the current
state of knowledge onM. leprae transmission, we conducted a systematic review of the peer-
reviewed literature pertaining to this topic.
Methods
DATABASES, KEYWORDS AND SEARCH STRATEGY FOR STUDY IDENTIFICATION
The following electronic bibliographic databases were searched using the terms ‘leprosy’,
‘Hansen’s disease’, ‘Mycobacterium leprae’, ‘transmission’ and ‘reservoir’ in appropriate
combinations: (i) PubMed: (Leprosy or Hansen’s disease or Mycobacterium leprae) AND
(transmission or reservoir); (ii) Virtual Health Library (VHL): (tw:(Leprosy OR Hansen’s
disease OR Mycobacterium leprae)) AND (tw:(transmission OR reservoir)); (iii) Web of
Science: ((Leprosy or Hansen’s disease or Mycobacterium leprae) AND (transmission or
reservoir)); (iv) Science Direct: ((Leprosy OR Hansen’s disease OR Mycobacterium leprae)
AND (transmission OR reservoir)). The last search was stratified by content type groups to
circumvent limits on the number of hits that can be downloaded from each search.
The search was last repeated on 23.01.2014 and no restrictions with regard to language
and time of publication were applied.
CRITERIA FOR CONSIDERING STUDIES
The review focused on the transmission pathway ofM. leprae to humans, including potential
reservoirs (in animals or the environment), mechanisms for transmission (methods for
propagation such as vectors, droplets and direct contact), and situational risk factors for
infection (risk factors about which some level of control exists, e.g. housing conditions).
Studies with ‘transmission’ or ‘reservoir’ (environmental or animal) mentioned in the title
Transmission of M. leprae 143
were initially considered. Further, original research articles were included if the title
contained one of the following key concepts referring to M. leprae transmission that have
been identified in a step-wise approach by screening and classifying the result of an initial
search for ‘leprosy AND transmission’ in PubMed: (i) source and route of M. leprae
infection; (ii) spatial and temporal epidemiology of M. leprae transmission; (iii) risk factors
for M. leprae transmission.
The following topics were not included in the systematic review despite being related to
M. leprae transmission: development of new methods (e.g. diagnostics), mathematical
modeling, risk factors inherent to the host (e.g. host genetics), mere signs of exposure to
M. leprae (e.g. sero-conversion), the experimental infection of laboratory animals, and
speculations about transmission.
Only peer-reviewed publications were considered but no restrictions on study types,
participants and location were applied. All outcomes demonstrated to contribute to the
transmission of M. leprae were considered.
IDENTIFICATION OF POTENTIALLY RELEVANT STUDIES ,
FINAL SELECTION AND ANALYSIS
All references identified by applying the search strategy described above were downloaded
and imported into a single EndNote X6 database, and duplicates were eliminated with the
relevant automatic function. The titles of the articles in the resulting database were screened
to identify additional duplicates, non-peer reviewed publications (e.g. letters), and articles
pertaining to diseases other than leprosy.
Potentially relevant studies were then identified by screening the titles of the retained
references, followed by the screening of abstracts for the presence of the term “transmission”
or a synonymous expression (e.g. ‘route of infection’, ‘source of infection’) which were taken
to indicate that the publication contained information that was relevant to this review. Both
screenings were implemented by two reviewers, and the results compared. Discrepancies
were resolved by jointly reviewing discordant results. Finally, the full texts of the
provisionally included studies were scrutinised against the inclusion criteria to compile the
final list of studies to be included in the review.
Using specifically designed forms, the following data were extracted from all included
publications: (i) reference details (title, authors, journal, year of publication); (ii) study details
(site, design, sample size); and (iii) main findings.
The retained publications were summarised in summary tables, grouping studies by the
mode of transmission that was investigated: (i) human-to-human via aerosols or direct
contact; (ii) direct inoculation (e.g. injury); (iii) transmission to humans from environmental
or zoonotic reservoirs, and by insects.
The importance of the different transmission pathways and the strength of the evidence
were assessed considering the number of publications describing similar findings, the
consistency of the findings and the methodological quality of the studies. The latter was
evaluated according to the following criteria: selection process of study participants to ensure
representativeness of the study population, sample size calculation and adherence,
participation, outcome assessment (diagnostic approach) and data analysis approach. When
information in the publication was not sufficient, this was mentioned as such. No study was
excluded based on the methodological quality.
M.W. Bratschi & P. Steinmann, et al.144
No ethical approval was required as the review focused on published evidence.
The selection of the papers was performed by the authors MWB and PS, without interference
or involvement from the funding agency. The current manuscript was written jointly by all
co-authors.
Results and Discussion
The implementation of the search strategy resulted in a total of 3,805 records (Figure 1)
identified from PubMed (n ¼ 904); VHL (n ¼ 515); Web of Science (n ¼ 1,181) and Science
Direct (n ¼ 1,205).
Automatic elimination of duplicates and manual identification of further duplicates,
non-peer reviewed literature and publications not related to leprosy led to the elimination of
2,687 items. The screening of the remaining 1,118 titles resulted in the identification of 273
Records identified throughdatabase searching
(n = 3805)
Records excluded(n = 2687)
Title screening: Records after removal ofduplicates, non-peer-reviewed literature and
non-leprosy literature(n = 1118)
Records excluded(n = 845)
Abstract assessed foreligibility(n = 229)
Full texts assessed foreligibility(n = 90)
Studies included inqualitative synthesis
(n = 79)
Records excluded:non-peer reviewed
(n = 44)
Records excluded:reviews, non-peer
reviewed, duplicates,models, methods etc.
(n = 139)
Records excluded:(n = 11)
See excluded studies
Iden
tific
atio
nS
cree
ning
Elig
ibili
tyIn
clud
ed
Title screening of recordsrelated to transmission
(n = 273)
Figure 1. PRISMA Flow Diagram of systamtic literature review on on Mycobacterium leprae transmission.
Transmission of M. leprae 145
that met the inclusion criteria. Among them, another 44 records were eliminated as non-peer
reviewed, leaving 229 abstracts which were screened for inclusion. A total of 139
publications were removed at this step due to a variety of reasons, most notably for being
reviews or non-peer reviewed publications - not identified as such in the title screening, or
describing models and methods, or not identifying actual hypotheses for transmission. The
full texts of three records could not be obtained. The full texts of the retained 90 articles were
then scrutinised, resulting in the elimination of another 11 publications which did not contain
relevant data.
HUMAN-TO-HUMAN TRANSMISSION
The 37 publications investigating human-to-human transmission of M. leprae reported
findings from 36 studies (online Supplementary Table 1).5–41
With regard to design, most studies could be classified as cohort studies
(14 prospective;6,13,14,16,18,21–23,28,31,34,36,38,40 seven retrospective9,10,12,20,24,33,39). Eleven
studies followed a cross-sectional design,5,7,8,15,19,25–27,32,37,41 three were case-control
studies11,29,35 and twowere case reports.17,30 In terms of countries, the highest number of studies
were conducted in India (13 studies reported in 14 publications8,15–18,20–23,31,32,36,38,40),
followed by Brazil (five studies5,9,26,34,35), Bangladesh (four studies11,14,28,33), Indonesia
(three studies6,19,39) and Thailand33,37). One study was conducted in each of the following
countries: USA,24Cuba,12Colombia,27Venezuela,10Ghana,29Malawi,13Malaysia,7Bhutan30
and China.41 One study had been conducted in a laboratory.25 The publication date ranged
between 1956 and 2012, and 18 articles had been published in 2000 or later.
In addition to the risk of acquiring leprosy from other people through direct contact (e.g.
skin-to-skin) or via aerosols, most studies investigated risk factors like household size, socio-
economic status including education and sanitation, and the nutritional situation. Contact
stratification by case type, nasal carrier status, closeness of contact, number of family
members with leprosy and duration of contact was also common. The relative importance of
contacts in high- and low-endemic areas has been assessed in one study.33 The type of leprosy
in secondary cases in relation to the primary case has also been investigated.32 Most studies
focused on household contacts but some studies also considered social contacts.11,12,28,34,39
One study tracked the movement of leprosy bacteria through the skin to its surface17 and one
investigated the precise location of bacteria in the skin and its adnexa.25 Another study
focused on the release of bacteria from the nose.30 Multiple studies investigated the
specific site where bacteria were shed by cases, namely the skin as well as the nasal and oral
mucosa.5,19,23 The molecular identity of M. leprae strains in index cases and infected
household contacts has been studied in two publications,37,41 and the protective effect of the
BCG vaccination in four.8,9,29,36 Many large epidemiological studies made direct or indirect
reference to the classical study of leprosy transmission conducted in the Philippines over
several decades by Guinto and co-workers.42
Ample evidence exists for the clustering of leprosy cases. The relevant studies find an
elevated risk of leprosy among contacts of index cases, both within the household and in
social contacts. A clear stratification of the risk of disease emerged, with household contacts
of lepromatous or multibacillary cases being at higher risk than household contacts of
tuberculoid or paucibacillary cases, and individuals with more intensive social contact or
living closer to leprosy cases being at higher risk than their peers without these
characteristics. It was also found repeatedly that the risk of household members of contracting
M.W. Bratschi & P. Steinmann, et al.146
leprosy correlated with the number of leprosy cases in a household and the bacterial load of
the index case. Of note, most secondary cases were of the paucibacillary/tuberculoid type.
When interpreting this observation, the very long incubation period and the temporal
limitations that most studies face as well as the ethical imperative to treat patients as soon as
they have been detected, must be considered.
Presence of, and exposure to,M. leprae as determined by PCR or serology appeared to be
dynamic over time, and links to clinical disease were suggestive of the possibility of
transmission by subclinical cases. The notion of subclinical cases contributing to
transmission is supported by the findings over recent years that treating index cases alone
has been insufficient to halt transmission of leprosy on a global scale.4 Molecular evidence
showed that cases within households were often due to the same strain ofM. leprae and that a
variety of strains existed in the same area. However, a large proportion of the newly
diagnosed cases could not be attributed to any known index case. The proportion of
non-attributable cases was found to be higher in high-transmission areas compared to areas
with a low number of incident cases, suggesting again that transmission might happen in the
absence of overt disease, or that other contact patterns than long-term and close exposure to a
source of infection were sufficient for transmission. An alternative explanation for these
results is the presence of a large pool of undiagnosed cases that are sources of infection.
The quality of the identified studies varied considerably. Several large-scale prospective
cohort studies, including entire communities, provided high-quality data (see for
example28,34) while other designs or studies only focusing on household contacts, offered
evidence of lower quality, due to issues with recall bias, unclear matching/absence of
controls, neglect of the exposure history or small sample size. The studies establishing the
skin as a source of bacteria shed into the environment were small17,25 but studies focusing on
the nose or buccal cavity as the location of entry and exit of M. leprae and asymptomatic
nasal carriers offered high-quality evidence.5,19,26,30,31,36 Of particular relevance were
high-quality studies relying on molecular tools to identify M. leprae carriers and leprosy
infections, and changes in their status.
DIRECT INOCULATION
Among the 11 publications focusing on the possible transmission of leprosy through direct
inoculation into the skin43–53 (online Supplementary Table 2), seven were case reports while
another one summarised 31 cases arguably all linked to the same transmission source.44
A cross sectional study,52 a retrospective cohort study53 and a cross-sectional study of
injuries in feral armadillos47 were also identified. Six of the publications reported cases from
India, two a case each from Ethiopia43 and France;48 the cohort study was conducted in
Micronesia, the case control study was global in reach, and the study focusing on animals was
conducted in Louisiana, USA. With the exception of the report from France published in 1934
and the case control study published in 1953, all publications dated from 1985 and later,
including seven from the period 2002 to 2013.
The nature of the relevant injuries included tattooing (three studies, among them the case
series involving 31 cases44,50,51), followed by falls (two studies43,46) and injuries involving
objects (two studies45,49). Last, a case of inoculation in a medical setting through a
contaminated needle was reported,48 while the animal study implicated thorns pricking
armadillos in the nose and ears.47 The case-control study focused on the Buddhist practice of
Transmission of M. leprae 147
shaving the scalp of newborn infants and the cohort study on skin injuries sustained when
sleeping on pandanus fibre mats.
Numerous further cases of inoculation of M. leprae are reported in the literature, mostly
as case reports (often published as letters or other non-peer-reviewed formats). Of particular
concern appear to be tattooing (mostly in India) but vaccination scars,54,55 general injuries
(major ones resulting from accidents (see for example56) as well as minor ones (e.g. in
children57), and animal bites (see for example58) are also mentioned.
The identified studies point to the possibility of transmitting M. leprae through
inoculation of M. leprae into wounds. This possibility has been recognised since at least the
1930s, and relevant observations have been made in different settings. The bacteria causing
the infection in the injured individual appeared to be either environmental (e.g. in the case
of skin abrasions and injuries contaminated with soil or dust) or mechanically transferred
from infected people (e.g. with needles used in medical or aesthetic procedures).
However, none of the studies succeeded in irrevocably proving the origin and means of
transmission of arguably injury-related M. leprae infections and ruling out alternative
transmission pathways. The case-control study that found much higher rates of alopecia
leprotica in people affected by leprosy in Buddhist countries52 and the study that implicated
sleeping on pandanus mats,53 point to small injuries as an important route of infection.
Others have discussed whether traumata, especially in children, might play a more
prominent role in M. leprae transmission than usually accepted.57 Overall, the available
evidence suggests that injuries as a mode of transmission are the exception rather than the
norm. Epidemiologically, this transmission pathway thus appears to be insignificant but
since high-quality studies systematically assessing the role of small injuries of children
are lacking, a significant role of mechanical inoculation or wound contamination with
M. leprae shed by infected individuals cannot be ruled out. From a hygiene and public
health perspective, transmission by contaminated tattoo instruments appears to be
a particular concern.
The strength of the evidence from these studies was generally low. The prime argument
for direct inoculation into the skin was the close spatial proximity of an injury and the
localization of the clinical manifestation of leprosy. However, some cases were not diagnosed
bacteriologically; none were confirmed with PCR, and for some cases, the locational
congruence between the injury and the leprosy manifestation was not perfect. Also, studies
generally did not comment on exposure to other possible sources of infection.
ZOONOTIC OR ENVIRONMENTAL RESERVOIRS , AND TRANSMISSION FROM
INSECTS
A total of 14 studies focused on zoonotic reservoirs59–72 while seven studies investigated
environmental reservoirs73–79 (online Supplementary Table 3). Transmission by insects was
the topic of 4 studies80–83 (Table 3).
All but one of the animal-related studies investigated the role of nine-banded armadillos
(Dasypus novemcinctus) in the epidemiology of leprosy in the Americas. The remaining
study focused on non-human primates in India.67 The studies on M. leprae infections in
armadillos were conducted in Brazil,59 Colombia62 and Mexico70 while the nine studies
focusing on the risk of armadillo contact for humanM. leprae infection were conducted in the
USA (five studies61,63,66,68,69), Brazil (three studies64,65,71) and across multiple countries (one
study72). In terms of design, these studies included one cohort study,61 five case-control
M.W. Bratschi & P. Steinmann, et al.148
studies,63–66,71 two case reports68,69 and one cross-sectional study.72 All studies had been
published after 1977 and nine were published in the year 2000 or later.
The identified studies focusing on the detection of zoonotic reservoirs attempted to
establish the presence of M. leprae or acid-fast bacilli in cross-sectionally, but sometimes
unsystematically, sampled animals by different means, including PCR. Studies endeavouring
to identify a zoonotic origin of human leprosy infections considered contact patterns with
armadillos and monkeys of varying degree (including injuries caused by armadillos) and
eating armadillo meat. The possible role of injuries sustained while handling armadillos is
highlighted repeatedly (see for example61).
The existence of a zoonotic M. leprae reservoir among the nine-banded armadillo is well
established since the 1970s, at least for the southern States of the USA. Multiple studies have
identified infected armadillos and have plausibly linked human cases to armadillo contact.
The situation is less clear for other parts of the Americas where conflicting evidence exists:
studies among armadillos generally failed to establish M. leprae infections but contact with
armadillos has repeatedly been identified as a risk factor forM. leprae infection. Of particular
interest is a high-quality study reporting the presence of a distinctive molecular pattern in
M. leprae obtained from armadillos and leprosy cases residing in areas where infected
armadillos live. That pattern was not observed in M. leprae isolated from humans in other
parts of the Americas and in reference strains.72 No good evidence exists for zoonotic
reservoirs in other animals, and reported attempts to experimentally infect other animals,
including primates, often failed.
Most studies pertaining to the risk of M. leprae transmission from a zoonotic reservoir
were small in terms of sample size, samples were not always collected systematically or even
randomly, and diagnostic methods were not always sufficiently sensitive or specific. Also,
‘controls’ of individuals with armadillo contact were often not matched with regard to key
characteristics, contact to human leprosy cases was not systematically investigated, and
evidence for leprosy among local armadillo populations was not always provided.
Numerous other publications focus on leprosy among armadillos, mostly in the southern
States of the USA, but without direct reference to transmission of M. leprae to humans (see
for example84–87). Another series of publications pertains to the experimental infection of a
wide range of animals with leprosy, mostly primates and rodents but also frogs, fish and
amoeba (see for example88–99). The few reports of naturally occurringM. leprae infections in
primates relate to captive animals (see for example100).
Studies exploring the role of potential environmental reservoirs include experiments to
demonstrate the viability of M. leprae outside the human body73,74 and investigations
focusing on bacteria in soil and water.75–79 Additional studies were conducted in the
laboratory.73–75 In the other studies, soil and water samples collected in endemic areas in
India76,77,79 and Indonesia78 were tested for the presence of M. leprae. The studies were
published between 1977 and 2012.
Laboratory studies relied on the mouse footpad model to determine viability ofM. leprae
exposed to different conditions with regard to drying, humidity, temperature and sunlight
exposure. All studies investigating the presence of M. leprae in soil and water samples used
molecular techniques to detect bacterial DNA or RNA. In two studies, soil samples from
patient areas were studied77 or compared to samples from non-patient areas.76 The opposite
approach was pursued in another study that investigated the prevalence of leprosy among
people using positive and negative water sources for bathing and washing.78 Lastly, one study
compared soil samples from washing and bathing areas with samples collected close to the
Transmission of M. leprae 149
houses of leprosy patients, and compared genetic characteristics of M. leprae from these
sources with M. leprae obtained from local patients.79
The identified studies investigating a possible environmental reservoir of M. leprae
showed that the bacteria can survive for several days in soil and water samples, and that they
tolerated different climate conditions. However, the studies failed to establish the presence of
a true environmental reservoir as long-term survival or replication of the bacteria could not be
demonstrated. The viability of bacteria in field-collected samples remain unclear as do links
between the human cases and evidence for M. leprae in the environment: none of the
identified studies had convincingly linked a human case to exposure to such an environmental
reservoir. Interestingly, one study found the same SNP-type of M. leprae in the soil as in
patients living in the same area. With regard to environmental reservoirs, multiple studies
only focused on the detection of M. leprae in vegetation, soil and water samples (see for
example101–103). Of note, in several studies ‘acid fast bacilli’ were detected while M. leprae
identification remained elusive.
The insect-related publications reported data from studies involving flies, mosquitoes and
bedbugs, and focused on the question whether M. leprae could be taken up by insects and
remain viable long enough to be transferred to humans.80–83 All publications reported
experimental studies conducted in the laboratory; one also included a small cross-sectional
study.81 The publications dated from 1914 to 1985.
Different insects appear to be potential carriers ofM. leprae but no evidence for the actual
transmission of M. leprae via insects to humans and subsequent development of leprosy has
been published. Scientific interest in the role that insects potentially play in the epidemiology
of leprosy appears to have waned as the last relevant study dates to 1985. The studies
generally relied on microscopic identification of acid fast bacilli and thus neither established
the precise nature of the observed bacteria nor their viability.
Several publications reviewed the extant evidence (see for example104) or dealt with the
mechanical limits ofM. leprae transmission by different groups of insects, mostly in terms of
their ability to penetrate the intact skin (see for example105) or the likelihood that they bite or
sting humans (see for example106).
ECOLOGICAL STUDIES , SOCIOECONOMIC SITUATION AND NO HYPOTHESIS
Six studies focusing on socio-economic and ecological risk factors107–111 or failing to
identify a source or means of transmission112 (online Supplementary Table 4), had been
conducted in Brazil, Bangladesh108 and Malawi.110
Studies found that a low socio-economic status was a risk factor for leprosy. The socio-
economic status was assessed in these studies by a variety of indicators including housing,
water supply, educational status and food shortage. Besides their significance for signaling
crowded conditions and difficult access to health care (both resulting in a higher chance to be
in contact with untreated leprosy cases), these conditions might be a proxy for a weakened
immune status and exposure to environmental transmission sources.
Conclusions
This review of the peer-reviewed literature on the transmission ofM. leprae identified studies
documenting the transmission of M. leprae over different pathways (e.g. direct contact,
M.W. Bratschi & P. Steinmann, et al.150
inoculation) and from various sources (e.g. man-to-man, armadillo-to-man). The identified
evidence is of varying quality, and many studies have serious methodological shortcomings
that undermine our confidence in the value of their findings. This is particularly noteworthy
if we consider how fundamental the question is for the control of leprosy. This shortage in
high-quality evidence probably is not least attributable to the challenges involved in the
study of the epidemiology of leprosy, including: (i) difficulties in detecting M. leprae
infections before the occurrence of clinical signs; (ii) the best animal model, armadillo, is not
widely available nor easily studied for elements of human disease; (iii) the inability to culture
M. leprae in vitro; (iv) the lack of a simple technique to determine the viability of M. leprae
and (v) the presence of environmental Mycobacteria in many potential transmission sources
and reservoirs.
In sharp contrast to the ample documentation ofM. leprae transmission among contacts of
leprosy cases is the dearth of information on the actual mode of transmission. No study has
unequivocally demonstrated the mechanisms by which bacteria travel from one case to
another. Based on the extant evidence, skin-to-skin contact, aerosols/droplets and shedding of
bacteria into the environment and subsequent infection, e.g. through dust or small wounds, all
remain possible options. The nose, the oral cavity and the skin have been tentatively
identified as entry and exit points ofM. leprae. The role of the nose inM. leprae transmission
has found particular attention and the topical treatment of nasal carriers with the explicit aim
of reducing leprosy transmission has been attempted.113 The evidence for an increased risk
of leprosy among close contacts provides the basis for post-exposure chemo- and
immune-prophylaxis, the former of which has shown repeatedly to provide a degree of
protection for limited periods.114,115
The results of this review combined with the conclusions reached at an International
Symposium (see companion publication: Developing Strategies to Block the Transmission of
Leprosy, Mensah-Awere, Bratschi, Steinmann, Fairley and Gillis. Leprosy Review (2015)
86, 156–164) revealed the extent of the gap that exists in the knowledge we have about the
transmission of M. leprae. It also demonstrated the potential over-reliance on a limited
number of studies that undergird many of the accepted paradigms about the transmission
of M. leprae and that inform and shape the global response to leprosy. Without
significant investment and commitment to address these crucial gaps, evidence-based control
program implementation and targeted interventions will be limited to a strategy that is
reactive to infection rather than preventative in nature. Accordingly, current approaches
will not be sufficient to change the dynamic of continued transmission within populations
around the globe.
Acknowledgements
We would like to thank effect:hope (The Leprosy Mission Canada) for funding the literature
review.
Competing interest statement
Funding and initial terms of reference for the review were provided by effect:hope (The
Leprosy Mission Canada) to produce the literature review from which this manuscript was
Transmission of M. leprae 151
derived. MWB and PS selected and analysed papers for the literature review, independently
and without input from effect: hope, which has assisted in the final preparation of the
manuscript.
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Transmission of M. leprae 155
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to3
mon
ths
of
trea
tmen
t).
Bak
ker
eta
l.;
20
06
6R
isk
fact
ors
for
dev
elo
pin
gle
pro
sy-
ap
op
ula
tio
n-b
ased
coh
ort
stud
yin
Ind
on
esia
Indones
iaP
rosp
ecti
ve
coh
ort
49
03
HH
con
tact
san
d9
4in
dex
case
sF
rom
the
coh
ort
,4
4p
erso
ns
dev
elo
ped
lep
rosy
wit
hin
4y
ears
.L
ivin
gin
ah
ou
seh
old
wit
hm
ore
than
7m
emb
ers
enta
iled
a3·1
tim
esh
igh
erri
skfo
rle
pro
syco
mp
ared
toh
ou
seh
old
so
f1
–4
mem
ber
s.C
on
tact
so
fM
Bca
ses
had
incr
ease
dri
sk(a
dju
sted
haz
ard
rati
o4·6
)an
dco
nta
cto
fp
atie
nts
wit
hP
CR
po
siti
ve
nas
alsw
abs
had
even
hig
her
risk
(adju
sted
haz
ard
rati
o9·6
).C
on
tact
so
fm
ore
than
on
ep
atie
nt
also
had
anin
crea
sed
risk
,b
ut
low
erth
anif
nas
alse
cret
ion
so
fth
ein
dex
case
wer
eP
CR
po
siti
ve.
Mu
ltiv
aria
tean
alysi
sid
enti
fied
sex
,h
ou
seh
old
size
,se
rolo
gic
alst
atu
sat
bas
elin
ean
dco
nta
ctst
atus
asst
atis
tica
lly
sig
nifi
can
t.H
ou
seho
ldco
nta
cts
of
pat
ien
tsw
ho
did
no
tca
rry
On
lyh
ou
seh
old
con
tact
sco
nsi
der
ed.
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le1
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
M.
lep
rae
inth
eir
no
sed
idn
ot
hav
ean
incr
ease
dri
sk.
Th
est
ud
yfo
un
dth
atse
rop
osi
tiv
ity
may
be
am
ark
erfo
rtr
ansm
itte
rs.
Mo
etet
al.
;2
00
628
Ph
ysi
cal
dis
tan
ce,
gen
etic
rela
tionsh
ip,
age,
and
lepro
sycl
assi
fica
tion
are
indep
enden
tri
skfa
cto
rsfo
rle
pro
syin
conta
cts
of
pat
ients
wit
hle
pro
sy
Ban
gla
des
hP
rosp
ecti
ve
coh
ort
1037
case
s;21870
conta
cts
155
case
sw
ere
dis
cover
ed.
Con
tact
so
fP
Bp
atie
nts
wit
h2
–5
lesi
on
san
dth
ose
of
MB
pat
ien
tsh
ada
hig
her
risk
of
dev
elo
pin
gle
pro
syth
and
idco
nta
cts
of
pat
ien
tsw
ith
sing
le-l
esio
nP
Ble
pro
sy.
Th
eco
reh
ou
seh
old
gro
up
has
ah
igh
erri
skth
ano
ther
con
tact
sli
vin
gu
nd
erth
esa
me
roo
fan
dn
ext
do
or
nei
gh
bo
rsh
ada
hig
her
risk
than
nei
gh
bo
rso
fn
eigh
bo
rs.
Dis
ease
clas
sifi
cati
on
of
the
index
pat
ien
tan
dp
hy
sica
lan
dg
enet
icd
ista
nce
wer
ein
dep
end
entl
yas
soci
ated
wit
hth
eri
skof
aco
nta
ctac
qu
irin
gle
pro
sy.
Con
tact
sli
vin
gu
nd
erth
esa
me
roo
fb
ut
usi
ng
ad
iffe
ren
tk
itch
enas
wel
las
tho
seu
sin
gth
esa
me
kit
chen
bu
tli
vin
gu
nd
era
dif
fere
nt
roo
fd
idn
ot
sho
wa
stat
isti
call
ysi
gn
ifica
nt
dif
fere
nce
inri
skco
mp
ared
toso
cial
con
tact
s.
No
crit
ical
issu
es.
Sm
ith
eta
l.;
20
04
36
An
app
roac
hto
un
der
stan
din
gth
etr
ansm
issi
on
of
Myc
ob
act
eriu
mle
pra
eu
sin
gm
ole
cula
ran
dim
mu
nolo
gic
al
Mah
aras
tra,
Ind
iaP
rosp
ecti
ve
coh
ort
25
52
vil
lager
s1·6
%o
f2
55
2n
asal
swab
sw
ere
po
siti
ve
for
M.
lep
rae
DN
Aan
dD
NA
po
siti
vit
yd
idn
ot
per
sist
ov
erti
me.
Rep
eate
dsa
mp
lin
g(a
lso
of
the
init
iall
yp
osi
tiv
ein
div
idual
s)n
ot
alw
ays
M.W. Bratschi & P. Steinmann, et al.
Su
pp
lem
enta
ryT
ab
le1
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
met
ho
ds:
Res
ult
sfr
om
the
MIL
EP
2st
ud
yP
osi
tiv
ity
was
hig
hes
tin
the
wet
seas
on
.6
8%
of
sali
va
sam
ple
sw
ere
po
siti
ve
for
ML
-Ig
AB
CG
and
ho
use
ho
ldco
nta
ctst
atu
sw
asas
soci
ated
wit
hth
em
uco
sal
imm
un
ere
spo
nse
.
incl
ud
ing
the
sam
ein
div
idual
s.
Hal
der
eta
l.;
20
01
18
Role
of
pau
cibac
illa
ryle
pro
syin
the
tran
smis
sio
no
fd
isea
seW
est
Ben
gal
,In
dia
Pro
spec
tive
coh
ort
94
4co
nta
cts
of
ind
exP
Bca
ses;
76
0n
on
-cas
eco
nta
cts
56
(incl
udin
g4
MB
)ca
ses
occ
urr
edam
on
gth
eco
nta
cts
of
PB
case
san
d2
case
so
ccu
rred
amon
gth
en
on
-co
nta
cts
(dif
fere
nce
stat
isti
call
ysi
gn
ifica
nt)
.C
on
tact
so
fin
dex
case
sw
ere
ath
igh
erri
sko
fh
avin
gle
pro
sy.
Am
on
gth
eca
seco
nta
cts,
risk
of
con
trac
ting
lep
rosy
was
hig
hes
tam
on
gth
ose
shar
ing
the
sam
eb
edas
the
ind
exca
se.
Co
ntr
ol
ho
use
ho
lds
ill
defi
ned
(su
spec
ted
lep
rosy
case
sw
hic
hnev
erdev
eloped
dis
ease
)an
dn
om
atch
ing
of
con
tro
lh
ou
seh
old
s.
Vij
ayak
um
aran
etal.
;1
99
840
Do
esM
DT
arre
sttr
ansm
issi
on
of
lep
rosy
tohouse
hold
conta
cts?
Kar
igir
i,In
dia
Pro
spec
tive
coh
ort
10
94
and
56
7H
Hco
nta
cts
of
33
7M
Bp
atie
nts
65
new
case
sw
ere
det
ecte
dam
on
gth
eco
nta
cts.
Th
ein
cid
ence
was
hig
her
inch
ild
ren
(5·1
%)
com
par
edto
adu
lts
(2·9
%).
Ifth
eb
acte
rial
index
of
the
pri
mar
yca
sew
asm
ore
then
2,th
eri
skw
asin
crea
sed
by
3.0
1ti
mes
.T
he
risk
was
also
incr
ease
dif
dis
ease
du
rati
on
of
the
ind
exca
sew
asm
ore
than
on
ey
ear.
Th
ep
rese
nce
of
co-p
rev
alen
tca
seal
mo
std
ou
ble
dth
eri
skin
ho
use
ho
ldco
nta
cts.
Peo
ple
join
ing
ah
ou
seh
old
afte
rth
ep
rim
ary
case
inth
athouse
hold
was
star
ted
on
Alt
ern
ativ
eso
urc
eso
fin
fect
ion
not
inves
tigat
ed(e
.g.
com
mu
nit
yo
rso
cial
con
tact
s).
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le1
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
MD
T,
wer
eo
ver
4ti
mes
more
lik
ely
toco
ntr
act
lep
rosy
com
par
edto
the
gen
eral
po
pu
lati
on
.F
ine
eta
l.;
19
97
13
Ho
use
ho
ldan
dd
wel
ling
conta
ctas
risk
fact
ors
for
lepro
syin
nort
her
nM
alaw
i
No
rth
ern
Reg
ion,
Mal
awi
Pro
spec
tive
coh
ort
1’8
87
case
s,8
0’4
51
at-r
isk
ind
ivid
ual
s3
31
new
lep
rosy
case
sw
ere
dia
gn
ose
d.
Liv
ing
ina
ho
use
ho
ldw
ith
aM
Bca
sein
crea
sed
the
risk
5–
8ti
mes
wh
erea
sli
vin
gw
ith
aP
Bca
sein
crea
sed
the
risk
app
rox
imat
ely
2ti
mes
.S
pec
ula
teth
atP
Bca
ses
may
not
be
sourc
eof
infe
ctio
nbut
indic
atio
nth
atth
eh
ou
seh
old
has
com
ein
con
tact
wit
hso
me
ou
tsid
eso
urc
eo
fin
fect
ion
.O
nly
15
%o
fth
isst
udy
of
the
case
so
ccurr
edam
on
gre
cog
niz
edh
ou
seh
old
con
tact
s.
Dy
nam
ich
ou
seh
old
stru
ctu
res
may
lead
toan
un
der
esti
mat
eo
fth
ep
rop
ort
ion
of
new
case
sam
on
gh
ou
seh
old
con
tact
s.Is
sues
wit
hth
ecl
assi
fica
tion
of
con
tact
sw
hic
hco
uld
hav
ele
dto
mis
clas
sifi
cati
on
of
the
con
tact
stat
us.
Ram
apra
sad
eta
l.;
19
97
31
Tra
nsm
issi
on
and
pro
tect
ion
inle
pro
sy:
ind
icat
ion
so
fth
ero
leo
fm
uco
sal
imm
un
ity
Mir
aj,
India
Pro
spec
tive
coh
ort
204
(133
re-t
este
d)
sML
IgA
posi
tivit
y:
66%
of
trea
ted
pat
ien
ts,
76
%o
fle
pro
syw
ork
ers,
72
%h
ealt
hy
con
tact
s,3
3n
egat
ive
con
tro
ls.
PC
Rp
osi
tiv
ity
:2
%o
fh
ou
seh
old
con
tact
s,5
%n
egat
ive
con
tro
ls.
Su
bcl
inic
alM
.le
pra
etr
ansm
issi
on
wit
htr
ansi
ent
no
sein
fect
ion
:3
PC
Rp
osi
tiv
ein
div
idual
sw
ere
neg
ativ
eaf
ter
1y
ear
bu
t2
out
of
94
neg
ativ
esbec
ame
po
siti
ve.
22
chan
ged
fro
msM
LIg
Ap
osi
tiv
eto
neg
ativ
ean
d1
2fr
om
neg
ativ
eto
po
siti
ve.
Sm
all
sam
ple
size
.C
on
tact
stat
us
of
neg
ativ
eco
ntr
ols
pro
ne
tom
is-r
epo
rtin
g.
No
pro
of
of
actu
altr
ansm
issi
on
by
nas
alca
rrie
rs.
M.W. Bratschi & P. Steinmann, et al.
Su
pp
lem
enta
ryT
ab
le1
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
Geo
rge
eta
l.;
19
93
16
Intr
afam
ilia
ltr
ansm
issi
on
of
lep
rosy
inV
ello
reT
ow
n,
Ind
ia
Tam
ilN
adu
Sta
te,
Ind
iaP
rosp
ecti
ve
coh
ort
41
0H
Hco
nta
cts;
21
0in
dex
case
s;1
4co
-pre
val
ent
case
s
Inth
eco
urs
eo
fth
est
ud
y14
case
sd
evel
oped
lepro
sy.
Fo
un
dn
osi
gn
ifica
nt
dif
fere
nce
inth
ein
cid
ence
rate
bet
wee
nco
nta
cts
of
MB
and
PB
pat
ien
ts(t
ren
dto
hig
her
inci
den
ceam
on
gco
nta
cts
of
MB
case
s).
No
add
edri
skfo
rco
nta
cts
liv
ing
inm
ult
i-ca
sefa
mil
ies.
Sp
ecula
teth
atri
sko
fin
fect
ion
ism
ain
lyfr
om
wit
hin
the
fam
ily
rath
erth
anfr
om
ou
tsid
e.
On
lyco
nsi
der
edh
ou
seh
old
con
tact
s.
Su
nd
arR
aoet
al.
;1
98
938
Imp
act
of
MD
To
nin
cid
ence
rate
so
fle
pro
syam
on
ghouse
hold
conta
cts.
Par
t1.
Bas
elin
ed
ata
Tam
ilN
adu
Sta
te,
Ind
iaP
rosp
ecti
ve
coh
ort
86
42
case
s;4
06
25
con
tro
lsT
her
ew
ere
12
25
co-
pre
val
ent
case
san
d715
inci
den
tca
ses
wit
han
inci
den
cera
teo
f4
.06
per
10
00
per
son
yea
rsat
risk
amon
gh
ou
seh
old
con
tact
s(6
·40
inco
nta
cts
of
MB
pat
ien
tsan
d3
.48
inco
nta
cts
of
PB
pat
ien
ts).
Chil
dco
nta
cts
had
ast
atis
tica
lly
sign
ifica
ntl
yh
igh
erin
cid
ence
rate
then
adu
ltco
nta
cts.
On
lyco
nsi
der
edh
ou
seh
old
con
tact
s.
Jesu
das
anet
al.
;1
98
421
Tim
etr
end
sin
the
anal
ysi
so
fin
cid
ence
rate
of
lep
rosy
amo
ng
ho
use
ho
ldco
nta
cts
Tam
ilN
adu
Sta
te,
Ind
iaP
rosp
ecti
ve
coh
ort
95
98
HH
con
tact
so
f1
61
4pri
mar
yca
ses
22
8in
cid
ent
case
sw
ere
det
ecte
dd
uri
ng
the
foll
ow
-up
per
iod
.In
cid
ence
rate
du
ring
the
1st
yea
ro
ffo
llo
w-u
pw
as3·8
per
10
00
per
son
-yea
rso
fri
skan
daf
ter
10
yea
rso
rm
ore
,it
bec
ame
3p
er1
00
0p
erso
n-y
ears
of
risk
.N
osi
gn
ifica
nt
fall
inth
ein
cid
ence
rate
wit
hti
me
Sam
ed
ata
asn
ext
pu
bli
cati
on
.22
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le1
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
among
conta
cts
of
non
lep
rom
ato
us
and
lep
rom
ato
us
case
sw
aso
bse
rved
even
afte
rtr
eatm
ent
of
the
pri
mar
yca
ses.
10
yea
rsaf
ter
trea
tmen
tin
itia
tio
nam
on
gp
rim
ary
case
s,th
ein
cid
ence
rate
of
house
hold
conta
cts
was
twic
eth
ato
fth
eg
ener
alp
op
ula
tio
n.
Jesu
das
anet
al.
;1
98
422
Inci
den
cera
tes
of
lep
rosy
amo
ng
ho
use
ho
ldco
nta
cts
of
“pri
mar
yca
ses”
Tam
ilN
adu
Sta
te,
Ind
iaP
rosp
ecti
ve
coh
ort
1564
case
s;9162
HH
conta
cts
22
8in
cid
ent
case
s.In
cid
ence
rate
amo
ng
ho
use
ho
ldco
nta
cts
of
lep
rom
ato
us
pri
mar
yca
ses
was
5p
er1
00
0p
erso
n-y
ears
of
risk
and
3.2
per
10
00
per
son
-yea
rso
fri
skfo
rtu
ber
culo
idp
atie
nt
con
tact
s.C
om
par
edto
indiv
idual
snot
expose
dto
lep
rosy
,h
ou
seh
old
con
tact
so
fn
on
-lep
rom
ato
us
pat
ien
tsh
ada
2fo
ldin
crea
sed
rela
tiv
eri
sk.
Th
ein
cid
ence
rate
was
hig
her
amon
gh
ou
seh
old
con
tact
so
fbac
teri
olo
gic
ally
posi
tive
(sig
nifi
can
tly
hig
her
for
pri
mar
yca
ses
wit
ha
bac
teri
alin
dex
of
2p
lus
com
par
edto
pri
mar
yca
ses
wit
ha
neg
ativ
ebac
teri
alin
dex
)p
atie
nts
,am
on
gcl
ose
lyre
late
dco
nta
cts
and
inh
ou
seh
old
sw
ith
mu
ltip
leca
ses.
No
info
rmat
ion
abo
ut
pas
tle
pro
syca
ses
inth
eh
ou
seh
old
of
pri
mar
yca
ses.
Sam
ed
ata
asp
rev
iou
sp
ub
lica
tio
n.2
1
M.W. Bratschi & P. Steinmann, et al.
Su
pp
lem
enta
ryT
ab
le1
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
Ric
har
du
set
al.
;2
00
533
Clo
seco
nta
cts
wit
hle
pro
syin
new
lyd
iagn
ose
dle
pro
syp
atie
nts
ina
hig
han
dlo
wen
dem
icar
ea:
com
par
ison
bet
wee
nB
ang
lades
han
dT
hai
land
Ban
gla
des
han
dT
hai
lan
dR
etro
spec
tiv
eco
ho
rtB
ang
lades
h:
13
33
case
s;T
hai
land:
129
case
sA
ver
age
new
case
det
ecti
on
rate
ov
er1
0y
ears
:5
0p
er1
00
,00
0g
ener
alp
op
ula
tio
np
ery
ear
inB
angla
des
h,
and
1·5
per
10
0,0
00
inT
hai
lan
d.
Inth
eh
igh
end
emic
area
25
%o
fn
ewly
det
ecte
dca
ses
wer
ek
no
wn
tob
elo
ng
too
ne
of
3co
nta
ctg
rou
ps
and
inlo
wen
dem
icar
ea6
2%
of
new
lyd
etec
ted
case
sb
elo
ng
edto
aco
nta
ctg
rou
p.
Just
ov
erh
alf
of
the
nea
rest
index
case
sw
ere
fou
nd
wit
hin
the
imm
edia
tefa
mil
yu
nit
(‘kit
chen
’in
Ban
gla
des
h;
‘ho
use
’in
Th
aila
nd).
No
crit
ical
issu
es.
Jain
eta
l.;
20
02
20
Ch
ild
ho
od
lep
rosy
inan
urb
ancl
inic
,H
yd
erab
ad,
Ind
ia:
clin
ical
pre
senta
tion
and
the
role
of
ho
use
ho
ldco
nta
cts
Hy
der
abad
,In
dia
Ret
rosp
ecti
ve
coh
ort
30
6ca
ses
Con
tact
his
tory
in3
8.8
%o
fp
atie
nts
(95
%o
fth
emar
efa
mil
yco
nta
cts)
.3
8%
of
index
case
sw
ere
PB
and
the
rest
MB
.
No
con
tro
lsin
clu
ded
.H
osp
ital
-bas
edst
ud
yw
ith
poss
ible
sele
ctio
nbia
s.
de
Mat
os
eta
l.;
19
99
9L
epro
syep
idem
iolo
gy
ina
coh
ort
of
ho
use
ho
ldco
nta
cts
inR
iode
Janei
ro(1
98
7–
19
91)
Rio
de
Jan
eiro
Sta
te,
Bra
zil
Ret
rosp
ecti
ve
coh
ort
88
PB
case
s;6
70
con
tact
sw
ith
out
sym
pto
ms
MB
ind
exca
sean
dim
mu
ne
stat
us
of
the
con
tact
wer
efo
un
dto
be
sign
ifica
nt
indic
ato
rsfo
rd
evel
op
ing
lep
rosy
inh
ou
seh
old
con
tact
s.N
ot
bei
ng
vac
cin
ated
wit
hB
CG
incr
ease
dth
eri
sko
fle
pro
syam
on
gh
ou
seh
old
con
tact
s.
Poss
ible
sele
ctio
nbia
s:ac
cess
toth
efa
cili
tyth
atm
anag
esth
eco
ho
rtis
lim
ited
.N
oin
form
atio
nab
ou
td
rop
ou
tsfr
om
the
coh
ort
.
van
Bee
rs,
Hat
ta,
Kla
tser
;1
99
939
Pat
ien
tco
nta
ctis
the
maj
or
det
erm
inan
tin
inci
den
tle
pro
sy:
imp
lica
tio
ns
for
futu
reco
ntr
ol
No
rth
Su
law
esi,
Ind
ones
iaR
etro
spec
tiv
eco
ho
rt1
01
case
sC
ases
wer
ecl
ust
ered
inh
ou
seh
old
s.7
9%
of
the
case
sco
uld
be
clas
sifi
edas
hav
ing
had
lep
rosy
con
tact
inth
ep
ast
(28
%h
adh
ou
seh
old
No
crit
ical
issu
es.
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le1
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
con
tact
;2
4%
had
con
tact
wit
ha
dir
ectl
yad
jace
nt
nei
gh
bo
r).
Ris
ko
fle
pro
syw
ash
igh
est
for
ho
use
ho
ldm
ember
sof
MB
case
s(1
3·7
tim
esb
asic
risk
),fo
llo
wed
by
the
risk
of
nei
gh
bo
rso
fM
Bh
ou
seh
old
san
dh
ou
seh
old
con
tact
of
PB
pat
ien
ts.
Mo
reM
Bth
anP
Bp
atie
nts
cou
ldb
eid
enti
fied
asth
ein
dex
case
for
more
than
on
ep
atie
nt.
Fer
raT
orr
es,
Car
raza
na
Her
nan
dez
;1
99
712
Mea
ns
of
det
ecti
on
and
sou
rce
of
infe
ctio
no
fth
ein
cid
ence
so
fle
pro
sy
Cam
agu
ey,
Cub
aR
etro
spec
tiv
eco
ho
rt8
1ca
ses
So
urc
eo
fin
fect
ion
:n
eig
hb
ors
(19
.8%
),fa
mil
y(1
4·8
%).
Sp
ou
ses
wer
en
oso
urc
eo
fin
fect
ion
s.
So
urc
eo
fa
larg
efr
acti
on
of
the
infe
ctio
ns
undet
erm
ined
.
Esc
uder
Nav
arro
;1
96
110
Co
nsi
der
atio
ns
on
the
con
tag
ion
of
lep
rosy
inco
nv
ivia
lan
dn
on
-con
viv
ial
gro
up
s
Boli
var
Sta
te,
Ven
ezuel
aR
etro
spec
tiv
eco
ho
rt3
32
lep
rosy
case
s(2
71
pri
mar
yan
d66
seco
ndar
y);
14
08
clo
seco
nta
cts
47
.3le
pro
syca
ses
per
10
00
incl
ose
con
tact
sv
ersu
s2·6
per
10
00
inth
eg
ener
alp
op
ula
tio
n.
Co
nta
cts
no
tcl
earl
yd
efin
ed.
Klu
th;
19
56
24
Lep
rosy
inT
exas
;ri
skof
con
trac
ting
the
dis
ease
inth
eh
ou
seh
old
Tex
as,
US
AR
etro
spec
tiv
eco
ho
rt1
52
2co
nta
cts
of
lep
rom
ato
us
case
s;4
95
con
tact
so
fn
on
-lep
rom
ato
us
case
s
40
case
s(2
·6%
)w
ere
found
among
conta
cts
of
lep
rom
ato
us
case
s.1
case
(0·2
%)
among
conta
cts
of
no
n-l
epro
mat
ou
sca
ses.
No
tal
lco
nta
cts
wer
efo
llo
wed
-up
and
itis
pro
bab
leth
atn
ot
all
case
sam
on
gth
en
ot
foll
ow
ed-u
pco
nta
cts
wer
ed
iagn
ose
dan
dre
po
rted
.H
atta
eta
l.;
19
95
19
Dis
trib
uti
on
and
per
sist
ence
of
Myc
ob
act
eriu
mle
pra
en
asal
carr
iag
eam
on
ga
po
pu
lati
on
inw
hic
hle
pro
syis
end
emic
inIn
do
nes
ia
So
uth
Su
law
esi,
Ind
ones
iaR
epea
ted
cross
sect
ion
al
41
8lo
cal
inhab
itan
tsP
rese
nce
of
M.
lep
rae
DN
Ain
2·9
%o
fsu
rvey
edp
op
ula
tio
n.
PC
Rp
osi
tiv
ity
was
no
tp
ersi
sten
to
ver
2y
ears
(all
the
PC
Rp
osi
tiv
ep
erso
ns
inth
efi
rst
surv
eyw
ere
neg
ativ
ein
the
seco
nd
on
e).
Wid
esp
read
nas
alca
rria
ge
inth
eg
ener
alp
op
ula
tio
nb
ut
nas
al
No
cau
sali
tyb
etw
een
nas
alco
lon
izat
ion
and
tran
smis
sio
n.
No
pro
of
of
via
bil
ity
of
colo
niz
ing
bac
teri
aan
dth
atth
eyar
eof
the
sam
eg
eno
typ
eas
dis
ease
cau
sing
on
es.
M.W. Bratschi & P. Steinmann, et al.
Su
pp
lem
enta
ryT
ab
le1
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
colo
niz
atio
nw
asin
con
sist
ent
inp
lace
and
tim
e.N
od
iffe
ren
cein
PC
Rp
osi
tiv
ity
was
det
ecte
din
pat
ients
plu
sth
eir
nei
gh
bo
rin
gh
ou
seh
old
san
do
ther
ind
ivid
ual
sli
vin
gin
mo
red
ista
nt
ho
use
ho
lds.
Pat
ien
tsd
iag
no
sed
wit
hle
pro
syat
the
2-y
ear
foll
ow
-u
pw
ere
all
init
iall
yn
egat
ive
inte
rms
of
nas
alco
lon
isat
ion
.R
aoet
al.
;1
97
532
Tra
nsm
issi
on
of
lep
rosy
wit
hin
ho
use
ho
lds
Gu
diy
ath
amT
aluk
,T
amil
Nad
u,
Ind
ia
Rep
eate
dcr
oss
-se
ctio
nal
50
88
fam
ilie
sw
ith
22
652
conta
cts
Sec
ond
ary
atta
ckra
te:6·8
per
10
00
per
son
-yea
rs(6
3.8
%tu
ber
culo
id,
9·5
%le
pro
mat
ou
s,9·7
%b
ord
erli
ne,
16·8
%in
det
erm
inat
e).
Po
pu
lati
on
inci
den
ce:
0·8
per
10
00
per
son
-yea
rs.M
ales
ath
igh
erri
skth
anfe
mal
es,
hig
hes
tat
tack
rate
sin
5–
9y
ear
old
s.R
isk
do
uble
sif
ther
ear
e2
or
more
pat
ien
tsin
the
ho
use
ho
ld.
Rel
ativ
ely
mo
rele
pro
mat
ou
sca
ses
inad
ult
s,m
ore
tuber
culo
idca
ses
inch
ild
ren
.H
igher
risk
ifin
dex
case
isle
pro
mat
ou
sth
anif
itis
tub
ercu
loid
No
n-h
ou
seh
old
con
tact
sn
ot
con
sid
ered
.
Ara
ujo
eta
l.;
20
12
5U
nv
eili
ng
hea
lth
yca
rrie
rsan
dsu
bcl
inic
alin
fect
ion
sam
on
gh
ou
seh
old
con
tact
so
fle
pro
syp
atie
nts
wh
op
lay
po
ten
tial
role
sin
the
dis
ease
chai
no
ftr
ansm
issi
on
Min
asG
erai
sS
tate
,B
razi
lC
ross
sect
ion
al4
44
case
san
d1
35
2co
nta
cts
By
PC
R,
34·
2%
of
the
pat
ien
tsan
d4
.7%
of
the
con
tact
ste
sted
po
siti
ve
for
M.
lep
rae
DN
Ain
nas
alsw
abs.
No
stat
isti
call
ysi
gnifi
cant
corr
elat
ion
bet
wee
nth
ed
etec
tio
no
f
No
pro
of
of
tran
smis
sio
nfr
om
pat
ien
tsto
con
tact
s,e.
g.
by
typin
gca
rria
ge
and
dis
ease
stra
ins.
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le1
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
M.
lep
rae
and
the
clin
ical
form
of
the
index
case
.S
ignifi
cant
asso
ciat
ion
bet
wee
nn
asal
swab
PC
Ran
dan
ti-P
GL
-1se
rolo
gy
(63·3
%o
fth
ep
atie
nts
and
13·3
%o
fth
eco
ntr
ols
wer
ese
rop
osi
tiv
e).
Fee
nst
raet
al.
;2
01
211
So
cial
con
tact
pat
tern
san
dle
pro
syd
isea
se:
aca
se-
con
tro
lst
ud
yin
Ban
gla
des
h
Ran
gp
ur
Div
isio
n,
Ban
gla
des
h
Cro
ssse
ctio
nal
(cas
eco
ntr
ol)
90
case
s;199
contr
ols
Lep
rosy
was
asso
ciat
edw
ith
am
ore
inte
nse
con
tact
pat
tern
inth
eh
om
e(O
R1·0
9)
and
inth
en
earb
yn
eig
hb
orh
oo
d(O
R1·0
7).
Th
em
ean
soci
alco
nta
ctsc
ore
(in
sid
eth
eh
om
ean
dw
ith
inth
en
eig
hb
orh
oo
d)
of
pat
ien
tsw
ash
igh
erth
anth
ato
fco
ntr
ols
.S
oci
alco
nta
ctp
atte
rns
var
ied
by
gen
der
.C
on
clu
de
that
soci
alco
nta
cts
ou
tsid
eo
fth
eh
ou
seh
old
are
imp
ort
ant
for
the
tran
smis
sio
no
fM
.le
pra
e.
Co
ntr
ols
are
no
tm
atch
ed.
Sel
f-re
port
ing
of
soci
alco
nta
ctw
ith
po
ten
tial
issu
eso
fre
call
bia
s.
Mar
tin
ezet
al.
;2
01
126
Ora
lm
uco
saas
aso
urc
eo
fM
yco
ba
cter
ium
lep
rae
infe
ctio
nan
dtr
ansm
issi
on,
and
impli
cati
ons
of
bac
teri
alD
NA
det
ecti
on
and
the
imm
un
elo
gic
alst
atu
s
Ub
rlan
dia
,B
razi
lC
ross
sect
ion
al3
34
case
s;1
22
8H
Hco
nta
cts
18
.3%
of
pat
ien
tsan
d6
.8%
of
con
tact
sh
adM
.le
pra
eD
NA
po
siti
ve
bu
ccal
swab
s.P
osi
tiv
ity
of
bu
ccal
swab
sin
crea
sed
tow
ards
the
MB
form
of
lepro
syre
achin
g4
2·7
%in
lep
rom
ato
us
case
s.M
.le
pra
eD
NA
was
also
det
ecte
din
the
ora
lca
vit
yo
ftu
ber
culo
idp
atie
nts
,in
dic
atin
gth
atth
em
ou
thm
igh
tfu
nct
ion
asp
oin
to
fen
try
of
the
infe
ctio
n(p
arti
cula
rly
inP
Bpat
ients
).
No
info
rmat
ion
on
the
via
bil
ity
of
the
dis
char
ged
bac
teri
a.
M.W. Bratschi & P. Steinmann, et al.
Su
pp
lem
enta
ryT
ab
le1
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
Ofo
su,
Bo
nsu
;2
01
029
Cas
eco
ntr
ol
stu
dy
todet
erm
ine
the
fact
ors
asso
ciat
edw
ith
lepro
syin
the
Sen
ed
istr
ict,
Bro
ng
Ah
afo
reg
ion
of
Gh
ana
Sen
eD
istr
ict,
Bro
ng
Ah
afo
Reg
ion,
Gh
ana
Cro
ssse
ctio
nal
(cas
eco
ntr
ol)
24
case
s;4
8co
ntr
ols
Con
tact
wit
hso
meo
ne
wit
hle
pro
syin
the
sam
eh
ou
sean
dn
ot
hav
ing
BC
Gvac
cinat
ion
was
found
tobe
asso
ciat
edw
ith
hav
ing
lep
rosy
.C
lose
con
tact
faci
lita
tes
tran
smis
sio
n.
Du
rati
on
of
con
tact
isn
ot
sign
ifica
ntl
yas
soci
ated
wit
hle
pro
sy.
Sm
all
sam
ple
size
.
San
tos,
Cas
tro
,F
alq
uet
o;
20
08
35
Ris
kfa
cto
rsfo
rle
pro
sytr
ansm
issi
on
Jag
uar
e,E
spır
ito
San
to,
Bra
zil
Cro
ssse
ctio
nal
(cas
eco
ntr
ol)
90
case
s,2
70
con
tro
lsR
isk
of
lep
rosy
:o
dd
sra
tio
of
2·9
ifcu
rren
tca
seo
fle
pro
syam
on
gre
lati
ves
exis
tsan
do
dd
sra
tio
of
5·0
ifo
ldca
seo
fle
pro
syam
on
gre
lati
ves
.
No
n-h
ou
seh
old
con
tact
sn
ot
con
sid
ered
.
Sri
sun
gn
gam
eta
l.;
20
07
37
Ty
pin
go
fT
hai
clin
ical
isola
tes
of
Myc
ob
act
eriu
mle
pra
ean
dan
aly
sis
of
lep
rosy
tran
smis
sio
nb
yp
oly
mo
rph
ism
of
tan
dem
rep
eats
Th
aila
nd
Cro
ssse
ctio
nal
10
0ca
ses
Pat
ien
tsin
mult
i-ca
sefa
mil
ies
wer
ein
fect
edw
ith
asi
ng
lest
rain
of
M.
lep
rae
inea
chfa
mil
yb
ut
stra
ins
dif
fere
db
etw
een
fam
ilie
s(b
ased
on
TT
Cre
pea
tsty
pin
g).
Inst
rain
sfr
om
pat
ien
tsin
sin
gle
case
fam
ilie
sd
iffe
ren
ces
inth
eco
py
nu
mb
ero
fth
eT
TC
repea
tsw
ere
ob
serv
ed.
No
info
rmat
ion
on
rou
teo
fin
fect
ion
.
Wen
get
al.
;2
00
741
Iden
tifi
cati
on
and
dis
trib
uti
on
of
Myc
ob
act
eriu
mle
pra
eg
eno
typ
esin
are
gio
no
fh
igh
lepro
sypre
val
ence
inC
hin
a:a
3-y
ear
mole
cula
rep
idem
iolo
gic
alst
ud
y
Qiu
bei
cou
nty
,Y
un
nan
pro
vin
ce,
P.R
.C
hin
a
Cro
ss-
sect
ion
al6
8ca
ses
Mu
ltip
le-l
ocu
sv
aria
ble
-n
um
ber
tan
dem
-rep
eat
anal
ysi
s(M
LV
A)
was
use
dto
trac
kle
pro
sytr
ansm
issi
on.
Mu
ltip
lecl
ust
ers
wer
efo
un
din
Ch
ina,
and
mult
i-ca
sefa
mil
ies
wer
eco
mm
on
:2
3o
fth
e6
8p
atie
nts
wer
efr
om
11
fam
ilie
s.In
tra-
fam
ilia
l
Sm
all
sam
ple
size
.N
od
iscr
imin
atio
nb
etw
een
tran
smis
sio
nin
tra-
ho
use
ho
ldan
db
etw
een
soci
alco
nta
cts.
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le1
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
VN
TR
pro
file
scl
ose
lym
atch
edw
ith
insi
xfa
mil
ies,
bu
tw
ere
dif
fere
nt
bet
wee
nfa
mil
ies.
VN
TR
pat
tern
sre
late
dto
tho
sefo
un
din
som
em
ult
i-ca
sefa
mil
ies
wer
eal
sod
etec
ted
inp
atie
nts
inth
esa
me
or
adja
cent
tow
nsh
ips,
sug
ges
tin
gso
cial
con
tact
so
nv
illa
ge
mar
ket
sas
tran
smis
sio
nsi
tes.
Mel
end
ez,
Fu
ente
s,R
od
rigu
ez;
20
06
27
Co
nju
gal
lep
rosy
Atl
anti
coD
epar
tmen
t,C
olo
mb
ia
Cro
ssse
ctio
nal
96
3le
pro
syca
ses
Con
jug
alle
pro
syis
no
tfr
equen
tan
dre
qu
ires
sev
eral
yea
rsto
dev
elo
pin
the
seco
nd
per
son
.L
epro
mat
ous
lep
rosy
inin
dex
case
sin
crea
sed
the
risk
of
lep
rosy
inth
eco
up
le.N
oM
Ble
pro
syocc
urr
edin
the
seco
ndar
yca
ses.
No
con
tro
ls.
Sel
ecti
on
bia
s(f
acil
ity
bas
ed)
and
info
rmat
ion
bia
s(r
eco
rds-
bas
edst
ud
y).
Geo
rge
eta
l.;
19
90
15
Th
ero
leo
fin
trah
ou
seh
old
conta
ctin
the
tran
smis
sion
of
lep
rosy
Tam
ilN
adu
Sta
te,
Ind
iaC
ross
sect
ion
al7
2ca
ses;
21
6co
nta
cts
Per
son
sw
ith
intr
a-h
ou
seh
old
lep
rosy
con
tact
had
asi
gn
ifica
ntl
yh
igh
erri
sko
fac
qu
irin
gle
pro
syco
mp
ared
wit
hth
ose
wh
od
idn
ot
(ris
kra
tio
2·5
1).
On
lyin
clu
ded
ho
use
ho
ldco
nta
cts
wit
ha
case
atth
eti
me
of
the
stu
dy
,i.
e.h
isto
ryo
fco
nta
ctn
ot
con
sid
ered
.
Ch
en;
19
88
7L
on
gh
ouse
dw
elli
ng
,so
cial
conta
ctan
dth
epre
val
ence
of
lep
rosy
and
tub
ercu
losi
sam
on
gn
ativ
etr
ibes
of
Sar
awak
Sar
awak
Sta
te,
Mal
aysi
aC
ross
sect
ion
al4
67
resi
den
tsin
sin
gle
dw
elli
ng
s;3
15
inlo
ng
hou
ses
Pre
val
ence
of
lepro
syw
assi
gn
ifica
ntl
yh
igh
eram
on
glo
ng
ho
use
dw
elle
rs(1
06·
4p
er1
00
’00
0)
com
par
edw
ith
sing
leh
ou
sed
wel
lers
(47·9
per
10
0’0
00
).It
was
also
fou
nd
that
long
ho
use
dw
elle
rso
cial
gro
ups
ten
dto
be
larg
er(h
igh
erp
rop
ort
ion
of
gro
up
sex
ceed
ing
8p
erso
ns)
Mat
chin
gn
ot
po
ssib
le,
i.e.
dif
fere
nce
sin
ho
usi
ng
are
asso
ciat
edw
ith
eth
nic
gro
up
and
oth
erd
iffe
ren
ces.
M.W. Bratschi & P. Steinmann, et al.
Su
pp
lem
enta
ryT
ab
le1
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
and
per
sist
for
mu
chlo
ng
erco
mp
ared
tosi
ng
leh
ou
sed
wel
lers
.D
ave,
Ag
raw
al;
19
84
8P
rev
alen
ceo
fle
pro
syin
chil
dre
no
fle
pro
syp
aren
tsC
hh
atti
sgar
hS
tate
,In
dia
Cro
ssse
ctio
nal
21
2ch
ild
ren
of
lep
rosy
case
s;2
40
chil
dre
nfr
om
no
n-l
epro
us
fam
ilie
s
Inth
ele
pro
us
fam
ilie
s25
case
sw
ere
iden
tifi
edco
mp
ared
to2
case
sin
the
con
tro
lg
rou
p(p
rev
alen
ce1
4·2
tim
esh
igh
er).
Inle
pro
us
fam
ilie
s,th
ep
rev
alen
cew
as3
tim
esh
igh
erin
fam
ilie
sw
her
eth
ere
was
more
than
on
ele
pro
syp
atie
ntco
mp
ared
tosi
ng
lep
atie
nt
fam
ilie
s(s
tati
stic
ally
signifi
cant)
and
1·5
tim
esh
igh
erif
lep
rom
ato
us
lep
rosy
case
sas
op
pose
dto
no
n-l
epro
mat
ou
sca
ses
wer
ep
rese
nt.
No
ne
of
the
iden
tifi
edch
ild
ren
wit
hle
pro
syh
adle
pro
mat
ou
sdis
ease
.B
CG
vac
cinat
ion
pro
vid
es50%
pro
tect
ion
amon
gch
ild
con
tact
s.
No
crit
ical
issu
es.
Ko
ttee
swar
an,
Ch
acko
,Jo
b;
19
80
25
Sk
inad
nex
ain
lep
rosy
and
thei
rro
lein
the
dis
sem
inat
ion
of
M.
lep
rae
Lab
ora
tory
Cro
ssse
ctio
nal
20
case
sM
.le
pra
ear
efo
un
din
larg
en
um
ber
sin
swea
tg
land
s,sw
eat
du
cts,
seb
aceo
us
gla
nd
s,h
air
foll
icle
san
dar
rect
or
pil
im
usc
les.
Stu
dy
sho
wed
that
M.
lep
rae
are
dis
char
ged
and
dis
sem
inat
edfr
om
un
bro
ken
skin
.O
nly
few
bac
illi
wer
eo
bse
rved
inth
esk
ino
ftu
ber
culo
idp
atie
nts
.
No
info
rmat
ion
on
the
via
bil
ity
of
the
dis
char
ge
bac
teri
a
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le1
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
Gh
orp
ade;
20
11
17
Tra
nse
pid
erm
alel
imin
atio
no
fM
yco
ba
cter
ium
lep
rae
inh
isto
idle
pro
sy:
aca
sere
po
rtsu
gg
esti
ng
po
ssib
lepar
tici
pat
ion
of
skin
inle
pro
sytr
ansm
issi
on
Chh
atti
sgar
hS
tate
,In
dia
Cas
ere
po
rt1
case
Aci
dfa
stb
acil
lifo
un
din
the
der
mis
and
epid
erm
is.
Su
gg
est
mov
emen
to
fb
acte
ria
wit
hu
ltim
ate
elim
inat
ion
fro
mth
est
ratu
mco
rneu
min
toth
een
vir
on
men
t.S
pec
ula
teth
atsk
inis
the
po
rtal
of
bo
then
try
and
exit
of
the
bac
illi
.
Via
bil
ity
of
bac
teri
anot
asse
ssed
.
Ped
ley
,G
eate
r;1
97
630
Do
esd
rop
let
infe
ctio
np
lay
aro
lein
the
tran
smis
sio
no
fle
pro
sy?
Bhu
tan
Cas
ere
po
rts
2ca
ses
Pat
ien
tsw
ith
un
trea
ted
or
rela
psi
ng
lep
rom
ato
us
lep
rosy
rele
ase
larg
en
um
ber
so
fM
.le
pra
eu
pto
ad
ista
nce
of
30
cmu
po
nsn
eezi
ng
,an
dsm
alle
rn
um
ber
su
pto
50
cm.
Tal
kin
g,
sno
rin
gan
dp
anti
ng
did
no
tre
sult
inm
easu
reab
lere
leas
eo
fM
.le
pra
e.
Via
bil
ity
of
rele
ased
bac
teri
an
ot
asse
ssed
.N
oco
mp
arab
leex
per
imen
tsw
ith
pat
ien
tsw
ith
hea
vy
infe
ctio
nin
vo
lvin
gth
eo
ral
cavit
y.
HH
:h
ou
seh
old
M.W. Bratschi & P. Steinmann, et al.
Su
pp
lem
enta
ryT
ab
le2
.P
eer-
rev
iew
edst
ud
ies
focu
ssin
go
nM
.le
pra
etr
ansm
issi
on
thro
ug
hd
irec
tin
ocu
lati
on
;li
sted
by
stu
dy
des
ign
and
yea
ro
fp
ub
lica
tio
nw
ith
mo
reri
goro
us
des
igns
and
more
rece
nt
studie
sli
sted
firs
t.
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
Lie
ber
,L
ieber
;1
98
753
So
cial
and
dem
og
rap
hic
asp
ects
of
ale
pro
syep
idem
ico
na
Po
lynes
ian
ato
ll:
imp
lica
tio
ns
of
pat
tern
Kap
ing
ama-
ram
gi
Att
oll
,M
icro
nes
ia
Ret
rosp
ecti
ve
coh
ort
13
6ca
ses
Tra
nsm
issi
on
mig
ht
be
thro
ug
hfl
oo
ran
dsl
eep
ing
mat
s,th
esu
rfac
efi
bre
of
wh
ich
can
pu
nct
ure
the
skin
.F
urt
her
fou
nd
that
M.
lep
rae
tran
smis
sio
nap
pea
rsto
dep
end
on
pat
tern
so
fp
erso
nal
mo
bil
ity
(var
ied
by
gen
der
and
age)
and
dem
og
rap
hy
.
No
con
trols
,st
ud
yis
ob
serv
atio
nal
and
spec
ula
tiv
e.
Job
,H
arri
s,A
llen
,H
asti
ngs;
19
86
47
Th
orn
sin
arm
adil
loea
rsan
dn
ose
san
dth
eir
role
inth
etr
ansm
issi
on
of
lep
rosy
Lo
uis
ian
a,U
SA
Cro
ssse
ctio
nal
Ear
sfr
om
49
4w
ild
arm
adil
los
and
nose
sof
22
4ar
mad
illo
s
10
/49
4an
imal
sh
adle
pro
mat
ou
sg
ran
ulo
ma.
23
%an
d3
7%
had
tho
rns
inth
eea
rsan
dn
ose
,re
spec
tiv
ely
.In
on
ean
imal
,th
ere
was
evid
ence
tosu
gges
tth
atM
.le
pra
een
tere
dth
eti
ssu
eth
roug
hth
orn
pri
cks,
i.e.
had
only
acid
-fas
tbac
teri
ain
the
no
seat
the
site
of
the
tho
rnan
dn
on
ein
the
ears
.
Myco
bac
teri
aid
enti
fied
mic
rosc
opic
ally
,co
uld
be
M.
lep
rae
or
oth
erm
yco
bac
teri
a(a
uth
ors
stat
eth
atu
sin
gth
eir
stai
nin
gfo
rac
id-f
ast
bac
teri
ath
eyca
nd
iffe
ren
tiat
eb
etw
een
M.le
pra
ean
doth
erm
yco
bac
teri
a).
Not
atr
ue
cross
-sec
tional
study
but
chan
cese
lect
ion
(ro
ad-k
ill)
.C
lev
e,P
ruit
t;1
95
352
Alo
pec
iale
pro
tica
-it
sre
lati
on
ship
totr
ansm
issi
on
of
lep
rosy
Jap
an,
Ko
rea,
Fo
rmo
sa(T
aiw
an),
No
n-B
ud
dh
ist
cou
ntr
ies
Cro
ssse
ctio
nal
(cas
eco
ntr
ol)
Bu
dd
his
t:1
35
8C
on
trols
:1
25
85
Th
ep
rev
alen
ceo
fal
opec
iale
pro
tica
was
35·3
%in
Bud
dh
ist
cou
ntr
ies
and
0.3
%in
the
con
tro
lco
ho
rtfr
om
no
n-
Bud
dh
ist
cou
ntr
ies
(Mex
ico
,V
enez
uel
a,P
hil
ippin
es,
Su
mat
ra,
Eg
ypt,
Pal
esti
ne,
No
rway
,S
ou
thA
fric
a,A
rgen
tin
a,U
SA
).S
ince
Bud
dh
ists
shav
eth
esc
alp
of
new
bo
rns,
ali
nk
wit
hth
isp
ract
ice
isp
ost
ula
ted
.
Cas
esan
dco
ntr
ols
wer
ese
lect
edbas
edon
the
countr
yo
fo
rig
in.
No
evid
ence
that
the
case
sh
adu
nd
ergo
ne
scal
psh
avin
gis
avai
lab
le,
and
no
dat
ao
nsc
alp
shav
ing
inco
ntr
ols
isav
aila
ble
.
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le2
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
Gh
orp
ade;
20
02
44
Ino
cula
tio
n(t
atto
o)
lep
rosy
:a
repo
rto
f3
1ca
ses
Ch
hat
tisg
arh,
Ind
iaC
ase
seri
es3
1ca
ses
Des
crip
tion
of
31
pat
ien
tsw
ho
dev
elo
ped
lep
rosy
10
–2
0y
ears
afte
rg
etti
ng
ata
tto
ofr
om
aro
adsi
de
tatt
oo
arti
st.
25
of
the
pat
ien
tsh
adle
sio
ns
on
lyat
the
site
of
the
tatt
oo
and
29
pat
ien
tsd
evel
op
edP
Ble
pro
sy.
Pat
ien
tsar
efr
om
ale
pro
syen
dem
icar
ea,
bu
tth
efa
ctth
atth
ed
isea
ses
star
ted
atth
esi
teo
fth
eta
tto
ois
ast
ron
gin
dic
atio
nth
atth
eta
tto
oin
gw
asin
stru
men
tal
intr
ansm
issi
on.
Gh
orp
ade;
20
13
46
Po
sttr
aum
atic
bo
rder
lin
etu
ber
culo
idle
pro
syo
ver
kn
eein
anIn
dia
nm
ale
Ind
iaC
ase
rep
ort
1ca
seL
epro
syle
sio
nd
evel
op
edat
asi
tew
ith
ahis
tory
of
trau
mat
icin
jury
(fel
lw
hil
ep
layin
gfo
otb
all)
afte
r2
yea
rs.
Lo
sso
fse
nsa
tio
nan
dh
isto
log
ical
fin
din
gs
sug
ges
tiv
eo
fle
pro
syw
ith
no
oth
ersy
mp
tom
so
rac
idfa
stb
acil
lib
ein
gre
po
rted
.
No
info
rmat
ion
on
con
tact
his
tory
wit
hle
pro
syca
ses.
Cli
nic
alpre
senta
tion
not
ver
ycl
ear
wit
hd
iag
no
sis
bas
edo
nh
isto
log
y.
Gh
orp
ade;
20
09
45
Po
st-t
raum
atic
ino
cula
tio
ntu
ber
culo
idle
pro
syaf
ter
inju
ryw
ith
ag
lass
ban
gle
Ind
iaC
ase
rep
ort
1ca
seIn
dia
nw
om
anw
ho
dev
elo
ped
lep
rosy
afte
rab
ou
t2
yea
rsat
the
site
of
anin
jury
ob
tain
edfr
om
her
gla
ssb
ang
le.
Dia
gno
sis
by
clin
ical
eval
uat
ion
,h
isto
pat
ho
logy
and
bas
edo
nth
etr
eatm
ent
resp
on
se.
Sh
arm
a,B
har
dw
aj,
Kar
;2
00
949
Ino
cula
tio
nle
pro
syan
dH
IVco
-in
fect
ion
:a
rare
case
wit
hn
erv
ein
volv
emen
tp
rece
din
gd
evel
op
men
to
fsk
inp
atch
and
type
1re
acti
on
asim
mune
reco
nst
itu
tio
nsy
ndro
me
foll
ow
ing
anti
retr
ov
iral
ther
apy.
Ind
iaC
ase
rep
ort
1ca
seL
epro
syd
evel
op
edcl
ose
tosi
teo
flo
cal
trau
ma
(sh
arp
wo
od
eno
bje
ct)
inH
IVp
osi
tiv
ep
atie
nt
afte
ran
incu
bat
ion
per
iod
of
13
–1
4y
ears
.
Lep
rosy
lesi
on
not
exac
tly
atsi
teo
ftr
aum
ab
ut
atsi
teco
nn
ecte
dw
ith
ath
ick
ened
cuta
neo
us
ner
ve.
Sin
gh;
20
09
51
Tat
too
san
dp
auci
bac
illa
ryle
pro
syJh
ark
han
d,
Ind
iaC
ase
rep
ort
1ca
seP
atie
nt
dev
elo
ped
lep
rosy
atsi
teo
fta
tto
oan
do
ther
loca
tio
ns
(firs
tle
sio
nat
site
of
tatt
oo
)af
ter
anin
cub
atio
np
erio
do
fap
pro
xim
atel
y4
0y
ears
Dia
gno
sis
on
clin
ical
gro
un
ds.
Ver
ylo
ng
incu
bat
ion
per
iod
(rec
all
bia
s).
M.W. Bratschi & P. Steinmann, et al.
Su
pp
lem
enta
ryT
ab
le2
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
Bra
ndsm
aet
al.
;2
00
543
Lep
rosy
acqu
ired
by
inocu
lati
on
from
ak
nee
inju
ry.
Eth
iop
iaC
ase
rep
ort
1ca
seD
utc
hg
irl
liv
ing
inE
thio
pia
dev
elo
ped
lep
rosy
atth
esi
teo
fa
skin
inju
rysh
eo
bta
ined
wh
ile
pla
yin
gat
sch
ool.
Wo
und
was
ori
gin
ally
dre
ssed
ata
lep
rosy
ho
spit
al.
Incu
bat
ion
per
iod
was
4y
ears
and
infe
ctio
nap
pea
red
tob
elo
cali
zed
toth
esi
teo
fth
esc
ar.
Infe
ctio
nw
asco
nfi
rmed
clin
ical
lyan
db
yla
bora
tory
exam
inat
ion
.
Sin
gle
case
wit
hg
oo
dev
iden
ceth
atM
.le
pra
ew
aslo
cali
zed
toth
esi
teo
fsk
inin
jury
.H
ow
ever
,th
eg
irl
had
mult
iple
exp
osu
res
tole
pro
sy:
fath
erp
rev
iou
sly
dia
gn
ose
dw
ith
sub
clin
ical
lep
rosy
wit
hen
larg
edn
erv
esan
dsh
eli
ved
atth
eA
llA
fric
aL
epro
sy,
Tu
ber
culo
sis
and
Reh
abil
itat
ion
Tra
inin
g(A
LE
RT
)C
entr
ein
Eth
iop
ia.
Sin
gh,
Tu
tak
ne,
Tiw
ari,
Du
tta;
19
85
50
Ino
cula
tio
nle
pro
syd
evel
op
ing
afte
rta
tto
oin
g-
aca
sere
po
rtM
ahar
ash
tra
Sta
te,
Ind
iaC
ase
rep
ort
1ca
seP
atch
wit
hlo
sso
fse
nsa
tio
nan
dh
isto
log
ysu
gg
esti
ve
of
lep
rosy
(no
bac
teri
afo
un
d)
atsi
teo
fta
tto
oaf
ter
anin
cub
atio
np
erio
do
f2
yea
rs.
Pat
ien
tw
asal
sota
tto
oed
ata
dif
fere
nt
loca
tio
no
nh
isb
od
yat
the
sam
eo
ccas
ion
wit
hth
esa
me
nee
dle
bu
tle
pro
syd
idn
ot
dev
elo
pat
that
site
.
No
bac
teri
olo
gic
alev
iden
ce.
No
info
rmat
ion
on
con
tact
tole
pro
syp
atie
nts
.
Mar
cho
ux
;1
93
448
Un
cas
d’i
no
cula
tio
nac
cid
ente
lle
du
bac
ille
de
Han
sen
enp
ays
no
nle
pre
ux
Par
is,
Fra
nce
Cas
ere
port
1ca
seA
ccid
enta
lin
ocu
lati
on
of
M.
lep
rae
by
med
ical
pro
fess
ion
alu
sin
ga
nee
dle
.1
0y
ear
incu
bat
ion
per
iod.
Go
od
evid
ence
that
pat
ien
tw
asin
fect
edb
yac
cid
enta
ln
eed
lep
rick
assy
mp
tom
sw
ere
focu
ssed
on
site
of
pri
ck.
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le3
.P
eer-
rev
iew
edst
ud
ies
focu
ssin
go
nM
.le
pra
etr
ansm
issi
on
from
zoonoti
cor
envir
onm
enta
lre
serv
oir
s,an
dby
inse
cts;
list
edby
study
des
ign
and
yea
rof
publi
cati
on
wit
hm
ore
rigoro
us
des
igns
and
more
rece
nt
studie
sli
sted
firs
t.
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
Zo
on
oti
cre
serv
oir
an
dtr
an
smis
sio
nC
lark
eta
l.;
20
08
63
Cas
e-co
ntr
ol
stu
dy
of
arm
adil
loco
nta
ctan
dH
anse
n’s
dis
ease
Tex
as,
US
AR
etro
spec
tiv
eca
seco
ntr
ol
28
pat
ien
tsan
d5
9co
ntr
ols
An
imal
exp
osu
re(c
lean
ing
rabbit
s;ea
ting
arm
adil
los)
and
hav
ing
liv
edin
Mex
ico
wer
esi
gn
ifica
ntl
y(p
,0·0
5)
asso
ciat
edw
ith
lep
rosy
.H
avin
gli
ved
inM
exic
ow
asth
em
ost
imp
ort
ant
risk
fact
or
(po
ssib
leco
nta
ctw
ith
unch
arac
teri
zed,
env
iro
nm
enta
lre
serv
oir
).
Cle
anin
gra
bb
its
and
liv
ing
inM
exic
om
ayb
eco
nfo
un
der
sfo
ru
nid
enti
fied
env
iro
nm
enta
lri
skfa
cto
rs.
Con
tro
ls(s
uff
erin
gfr
om
TB
infe
ctio
n)
no
tm
atch
ed.
Dep
set
al.
;2
00
864
Con
tact
wit
har
mad
illo
sin
crea
ses
the
risk
of
lep
rosy
inB
razi
l:A
case
contr
ol
study
So
uth
ern
Bra
zil
Ret
rosp
ecti
ve
case
con
tro
l506
pat
ients
and
594
contr
ols
Dir
ect
exposu
reto
arm
adil
los
was
fou
nd
tob
ea
risk
fact
or
(rou
gh
lyd
ou
bli
ng
the
risk
;p
,0·0
01)
for
lep
rosy
.
Un
mat
ched
con
trols
wit
ho
ther
chro
nic
dis
ease
s.N
oco
ntr
oll
ing
for
pla
ceo
fre
sid
ence
.C
on
trols
no
tas
ked
about
conta
ctw
ith
lepro
syca
ses.
Dep
set
al.
;2
00
465
Ep
idem
iolo
gic
alfe
atu
res
of
the
lep
rosy
tran
smis
sio
nin
rela
tion
toar
mad
illo
exposu
re
Esp
ırit
oS
anto
Sta
te,
Bra
zil
Ret
rosp
ecti
ve
case
con
tro
l136
pat
ients
and
173
contr
ols
Arm
adil
lom
eat
consu
mpti
on
iden
tifi
edas
po
ssib
leso
urc
eo
fM
.le
pra
ein
fect
ion
(90·4
%o
fp
atie
nts
ver
sus
15
%o
fco
ntr
ols
had
eate
nar
mad
illo
mea
tb
efo
reth
ed
iag
no
sis)
.A
rmad
illo
conta
ctm
ight
be
par
ticu
larl
yim
po
rtan
tfo
rth
ose
wh
od
idn
ot
hav
eco
nta
ctto
oth
erle
pro
syp
atie
nts
(96·1
%o
fth
emre
po
rted
hav
ing
eate
nar
mad
illo
mea
t).
Con
tro
lsar
en
ot
mat
ched
.N
ost
atis
tica
lan
alysi
s,h
igh
chan
ceo
fco
nfo
un
din
g.
Fil
ice,
Gre
enb
erg
,F
rase
r;1
97
766
Lac
ko
fo
bse
rved
asso
ciat
ion
bet
wee
nar
mad
illo
con
tact
and
lep
rosy
inh
um
ans
Lo
uis
ian
a,U
SA
Ret
rosp
ecti
ve
case
con
tro
l1
9p
atie
nts
and
19
con
trols
No
dif
fere
nce
inth
en
atu
rean
dfr
equen
cyof
arm
adil
loco
nta
ctb
etw
een
pat
ien
tsan
dco
ntr
ols
was
fou
nd
.
Ag
ean
dg
end
erm
atch
edco
ntr
ols
.E
xcl
ud
edp
atie
nts
that
had
exte
nd
edco
nta
ctw
ith
oth
erle
pro
syp
atie
nts
.
M.W. Bratschi & P. Steinmann, et al.
Su
pp
lem
enta
ryT
ab
le3
.co
nti
nu
ed
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
All
case
sd
evel
op
edle
pro
syb
efo
re1
97
5an
dso
me
asfa
rb
ack
as1
94
1(r
ecal
ler
ror)
.T
rum
anet
al.
;2
01
172
Pro
bab
lezo
on
oti
cle
pro
syin
the
sou
ther
nU
nit
edS
tate
sS
outh
ern
US
AC
ross
sect
ion
alM
.le
pra
efr
om
33
arm
adil
los,
50
hu
man
sfr
om
Lo
uis
ian
a,64
hum
ans
from
Ven
ezuel
a,an
d4
refe
ren
cest
rain
s
Iden
tifi
eda
un
iqu
ean
dh
igh
lyd
isti
nct
ive
SN
P-V
NT
Rp
atte
rnw
hic
his
pre
sen
tin
most
arm
adil
los
(28
of
33)
and
most
of
the
pat
ien
ts(2
5o
f3
9)
wh
oh
ada
his
tory
of
resi
den
cein
area
sw
her
eex
po
sure
toar
mad
illo
-bo
rne
M.
lep
rae
isp
oss
ible
.L
ack
of
div
ersi
tyo
fM
.le
pra
ein
the
arm
adil
los
sug
ges
tsth
atin
ters
pec
ies
tran
sfer
of
M.
lep
rae
isu
nco
mm
on
and
inef
fici
ent
and
hap
pen
edre
centl
y.
Pro
vid
eso
lid
evid
ence
that
cert
ain
pat
ien
tsin
the
sou
ther
nU
SA
are
infe
cted
wit
hth
esa
me
stra
ino
fM
.le
pra
ew
hic
hal
soo
ccu
rsin
nat
ura
lly
infe
cted
wil
dar
mad
illo
sin
the
sam
ear
ea.
No
causa
lity
for
the
lin
kbet
wee
nhum
anan
dar
mad
illo
case
s.
Bar
boza
Ped
rin
iet
al.
;2
01
059
Sea
rch
for
Myc
ob
act
eriu
mle
pra
ein
wil
dm
amm
als
Sao
Pau
loan
dM
ato
Gro
sso
do
Sul,
Bra
zil
Cro
ssse
ctio
nal
54
anim
als
No
nat
ura
lly
infe
cted
arm
adil
los
wer
efo
un
d.
Sam
ple
size
issm
all
and
sam
pli
ng
no
tra
nd
om
(road
kil
l).
Sch
mit
tet
al.
;2
01
071
Arm
adil
lom
eat
inta
ke
was
no
tas
soci
ated
wit
hle
pro
syin
aca
seco
ntr
ol
stu
dy
,C
uri
tib
a(B
razi
l)
Par
ana
Sta
teo
fB
razi
lC
ross
sect
ion
al(c
ase
con
tro
l)
12
1p
atie
nts
and
24
2co
ntr
ols
Th
efr
equ
ency
of
arm
adil
lom
eat
inta
ke
(use
das
ap
rox
yfo
ro
ther
form
so
fd
irec
tar
mad
illo
conta
ct)
did
not
var
yb
etw
een
pat
ien
tsan
dag
ean
dg
end
er-m
atch
edco
ntr
ols
afte
rad
just
ing
for
dem
og
rap
hic
and
soci
oec
on
om
icco
var
iate
s.A
lso
no
asso
ciat
ion
wh
enan
alysi
ng
on
lyth
eca
ses
wit
hn
ok
no
wn
con
tact
tole
pro
sy
Hig
h-q
ual
ity
case
con
tro
lst
ud
y,
bu
tca
ses
no
tm
atch
edfo
rh
om
eto
wn
and
soci
oec
on
om
icst
atu
s.N
oev
iden
cefo
rin
fect
edar
mad
illo
sin
stu
dy
area
pre
sen
ted
.
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le3
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
pat
ien
ts.
Dif
fere
nce
so
bse
rved
bet
wee
np
atie
nts
and
con
tro
lsin
clu
ded
:h
om
eto
wn
po
pula
tio
nsi
ze,
fam
ily
inco
me,
and
con
tact
wit
hle
pro
syp
atie
nts
and
acce
ssto
trea
ted
wat
er.F
ound
that
pre
vio
us
lep
rosy
con
tact
and
soci
oec
on
om
icin
dic
ato
rs(p
ov
erty
and
po
ssib
lyp
oo
rsa
nit
atio
n,
nu
trit
ion
and
hea
lth
care
)w
ere
rela
ted
tole
pro
sy.
Car
don
a-C
astr
oet
al.
;2
00
962
Det
ecti
on
of
Myc
ob
act
eriu
mle
pra
eD
NA
inn
ine-
ban
ded
arm
adil
los
(Da
syp
us
no
vem
cin
ctu
s)fr
om
the
An
dea
nre
gio
no
fC
olo
mb
ia
Colo
mb
iaC
ross
sect
ion
al22
arm
adil
los
41%
of
the
arm
adil
los
wer
ep
osi
tiv
efo
rM
.le
pra
eb
yP
CR
.M
.le
pra
ese
quen
ces
wer
eal
lid
enti
cal.
No
evid
ence
that
arm
adil
los
had
clin
ical
lep
rosy
and
that
they
carr
ied
via
ble
bac
teri
a.
Bru
ceet
al.
;2
00
061
Arm
adil
loex
posu
rean
dH
anse
n’s
dis
ease
:A
nep
idem
iolo
gic
surv
eyin
sou
ther
nT
exas
Tex
as,
US
AC
ross
sect
ion
al1
01
pat
ien
ts7
1%
of
no
n-A
sian
pat
ien
tsre
po
rted
dir
ect
or
ind
irec
tar
mad
illo
con
tact
(no
ne
of
the
Asi
anp
atie
nts
rep
ort
edsu
chco
nta
ct).
So
me
no
n-A
sian
pat
ien
tsh
adv
ery
exte
nsi
ve
conta
ctw
ith
arm
adil
los
and
som
eo
fth
emre
po
rted
lep
rosy
star
tin
gat
site
of
inju
rysu
stai
ned
du
ring
dir
ect
exposu
reto
arm
adil
los.
Con
clu
de
that
dir
ect
tran
smis
sio
no
fM
.le
pra
efr
om
arm
adil
lois
lik
ely
inn
on
-Asi
ans
and
that
the
Asi
anp
atie
nts
wer
ein
fect
edin
thei
rre
spec
tiv
eco
un
trie
so
fo
rig
in.
No
con
tro
lsin
clu
ded
.1
0o
fth
e6
9n
on
-Asi
anp
atie
nts
also
had
con
tact
wit
ho
ther
lep
rosy
pat
ien
ts.
So
me
Asi
anp
atie
nts
had
bee
nd
iagn
ose
dal
read
yb
efo
reco
min
gto
the
US
Aan
dar
eth
eref
ore
no
tre
ally
suit
able
as“c
on
tro
ls”.
M.W. Bratschi & P. Steinmann, et al.
Su
pp
lem
enta
ryT
ab
le3
.co
nti
nu
ed
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
Qu
esad
a-P
ascu
alet
al.
;1
99
970
Do
esle
pro
syin
Mex
ico
occ
ur
asa
zoo
no
sis
bet
wee
nw
ild
arm
adil
los
(Da
syp
us
nove
mci
nct
us)
?
Mex
ico
Cro
ssse
ctio
nal
13
4ar
mad
illo
sA
cid
fast
bac
illi
wer
en
ot
det
ecte
din
secr
etio
ns
or
tiss
ue
imp
rin
tso
fan
yo
fth
ete
sted
arm
adil
los.
Met
hod
for
the
det
ecti
on
of
M.
lep
rae
infe
ctio
nin
the
arm
adil
los
has
quit
ea
low
sen
siti
vit
y(a
nd
spec
ific)
and
infe
ctio
ns
cou
ldh
ave
bee
nm
isse
d.
Bla
ke
eta
l.;
19
89
60
Ear
thw
orm
sn
ear
lep
rosy
pat
ien
ts’
ho
mes
are
neg
ativ
efo
rac
id-f
ast
bac
illi
by
fite
stai
n,
pro
vid
ing
no
lin
kb
etw
een
lep
rou
sar
mad
illo
s(D
asy
pus
nove
mci
nct
us)
and
hu
man
lep
rosy
Lo
uis
ian
a,U
SA
Cro
ssse
ctio
nal
38
wo
rms
No
ne
of
the
test
edea
rth
wo
rms
wer
ep
osi
tiv
efo
rac
idfa
stb
acil
li.
Sm
all
sam
ple
size
.
Hag
stad
;1
98
367
Lep
rosy
insu
b-h
um
anp
rim
ates
:p
ote
nti
alri
skfo
rtr
ansf
ero
fM
.le
pra
eto
hu
man
s
Ind
iaC
ross
sect
ion
al26
ow
ned
monkey
sD
espit
ea
pre
val
ence
of
98·6
/10
00
amon
gth
eh
um
ans
inco
nta
ctw
ith
the
mo
nk
eys,
no
ne
of
the
mon
key
sh
adan
yev
iden
cefo
ra
curr
ent
infe
ctio
nw
ith
M.
lep
rae
(6ea
rlo
be
smea
rso
fm
on
key
sw
ith
kn
ow
nco
nta
ctw
ith
lep
rosy
pat
ien
ts,
26
clin
ical
exam
inat
ion
so
fm
on
eys)
.
Lim
ited
nu
mb
ero
fm
on
key
sex
amin
ed;
risk
of
mis
sin
gsu
bcl
inic
alin
fect
ion
san
din
fect
ion
sw
ith
neg
ativ
esk
insm
ears
.
Lu
mp
kin
,C
ox
,W
olf
;1
98
369
Lep
rosy
infi
ve
arm
adil
loh
and
lers
Tex
as,
US
AC
ase
seri
es5
pat
ien
tsR
epo
rto
ffi
ve
pat
ien
tsw
ith
exte
nsi
ve
and
chro
nic
arm
adil
loco
nta
ctan
dno
oth
erk
no
wn
risk
fact
or
(in
clu
din
gn
oco
nta
ctw
ith
lep
rosy
pat
ien
ts).
Fo
ur
of
the
pat
ien
tsh
adp
osi
tiv
eac
idfa
stb
acil
list
ain
san
dth
ree
of
them
dev
elo
ped
lep
rom
ato
us
lep
rosy
.C
on
tact
wit
har
mad
illo
sw
asver
ycl
ose
incl
ud
ing
get
ting
cuts
and
bei
ng
bit
ten.
All
pat
ien
tsh
adcl
inic
alle
sio
ns
on
the
han
ds.
Cas
ese
ries
wit
hn
oco
ntr
ols
.
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le3
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
Lan
eet
al.
;2
00
668
Bord
erli
ne
tuber
culo
idle
pro
syin
aw
om
anfr
om
the
stat
eof
Geo
rgia
wit
har
mad
illo
exp
osu
re
Geo
rgia
,U
SA
Cas
ere
port
1pat
ient
Lep
rosy
case
wit
hno
know
nco
nta
ctw
ith
oth
erp
atie
nts
bu
tw
ho
wo
rked
for
man
yy
ears
ina
gar
den
wh
ere
arm
adil
los
bu
rro
wed
or
wer
eb
uri
ed.
His
tolo
gic
alca
seco
nfi
rmat
ion
wit
hdet
ecti
on
of
acid
fast
bac
illi
.A
uth
ors
spec
ula
teab
ou
tin
ocu
lati
on
from
the
soil
into
the
skin
thro
ug
htr
aum
ao
rb
yin
hal
atio
n.
Sin
gle
case
.In
dir
ect
evid
ence
of
zoo
nosi
s.
Envi
ronm
enta
lre
serv
oir
and
transm
issi
on
Tu
ran
kar
eta
l.;
20
12
79
Dy
nam
ics
of
Myc
ob
act
eriu
mle
pra
etr
ansm
issi
on
inen
vir
on
men
tal
con
tex
t:d
ecip
her
ing
the
role
of
env
iro
nm
ent
asa
po
ten
tial
rese
rvo
ir
Wes
tB
engal
,In
dia
Cro
ssse
ctio
nal
20
7so
ilsa
mp
les
In3
4%
of
soil
sam
ple
sD
NA
was
det
ecte
dan
din
39
%o
fth
em(1
4%
of
tota
l)M
.le
pra
e1
6S
rRN
Aw
asal
sod
etec
ted
.In
18
%o
fth
esa
mp
les
coll
ecte
dn
ear
was
hin
gan
db
athin
gp
lace
sR
NA
was
det
ecte
dan
din
7%
of
sam
ple
sco
llec
ted
nea
rh
ou
ses
of
lep
rosy
pat
ien
tsR
NA
was
fou
nd.
SN
Pty
pin
gof
sele
cted
soil
sam
ple
ssh
ow
edth
atse
quen
ces
wer
eof
the
sam
eg
eno
typ
eas
the
M.
lep
rae
isola
ted
fro
mth
elo
cal
pat
ien
t.
Det
ecte
db
acil
lin
ot
test
edfo
rv
iabil
ity
(e.g
.b
ym
ou
sefo
otp
adin
ocu
lati
on
).
Lav
ania
eta
l.;
20
08
76
Det
ecti
on
of
via
ble
Myc
obact
eriu
mle
pra
ein
soil
sam
ple
s:in
sig
hts
into
po
ssib
leso
urc
eso
ftr
ansm
issi
on
of
lep
rosy
Utt
arP
rad
esh,
Ind
iaC
ross
sect
ion
al4
0so
ilsa
mp
les
each
fro
mp
atie
nt
and
no
n-p
atie
nt
area
sIn
55
%o
fth
eso
ilsa
mp
les
coll
ecte
din
pat
ien
tar
eas,
16
SrR
NA
was
det
ecte
dv
ersu
sin
15
%fr
om
no
-pat
ien
tar
eas.
Als
oth
em
ean
cop
yn
um
ber
so
fth
eM
.le
pra
eta
rget
Lim
ited
nu
mb
ero
fsa
mp
les.
Det
ecti
on
of
DN
Aan
dR
NA
isn
oab
solu
tep
roo
fo
fv
iabil
ity
.
M.W. Bratschi & P. Steinmann, et al.
Su
pp
lem
enta
ryT
ab
le3
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
sequen
ces
inth
esa
mple
sfr
om
the
pat
ien
tar
eaw
her
esi
gn
ifica
ntl
yh
igh
erco
mp
ared
toth
esa
mple
sfr
om
non-p
atie
nt
area
s.C
oncl
ude
that
M.le
pra
eca
nb
efo
un
din
the
soil
wh
ich
cou
ldb
eth
eso
urc
eo
fco
nti
nu
ou
str
ansm
issi
on
.L
avan
iaet
al.
;2
00
677
Det
ecti
on
of
Myc
ob
act
eriu
mle
pra
eD
NA
from
soil
sam
ple
sb
yP
CR
targ
etin
gR
LE
Pse
quen
ces
Utt
arP
rad
esh,
Ind
iaC
ross
sect
ion
al1
8so
ilsa
mp
les
In3
3·3
%o
fso
ilsa
mp
les
coll
ecte
dfr
om
area
sin
hab
ited
by
lep
rosy
case
s,M
.le
pra
eD
NA
was
det
ecte
db
yco
nv
enti
on
alP
CR
.
DN
Ad
etec
tio
n:
risk
of
cro
ss-
con
tam
inat
ion
wit
hco
nv
enti
on
alP
CR
,u
ncl
ear
spec
ifici
tyof
targ
etse
quen
cew
ith
resp
ect
too
ther
env
iro
nm
enta
lm
yco
bac
teri
a,n
oin
form
atio
nab
ou
tth
ev
iabil
ity
of
the
det
ecte
dm
yco
bac
teri
a.N
osa
mple
sfr
om
no
n-l
epro
syen
dem
icar
eas.
Mat
suo
ka
eta
l.;
19
99
78
Myc
obact
eriu
mle
pra
eD
NA
ind
aily
usi
ng
wat
eras
ap
oss
ible
sou
rce
of
lep
rosy
infe
ctio
n
No
rth
Mal
uk
up
rov
ince
,In
do
nes
ia
Cro
ssse
ctio
nal
44
wat
erso
urc
esIn
48
%(2
1/4
4)
of
the
wat
erso
urc
este
sted
,M
.le
pra
eD
NA
was
det
ecte
db
yP
CR
.T
he
pre
val
ence
of
lep
rosy
was
hig
her
amon
gth
ep
eop
leu
sin
gth
ep
osi
tiv
ew
ater
sou
rces
for
bat
hin
gan
dw
ash
ing
com
par
edto
tho
seu
sin
gth
en
egat
ive
on
es(1
2%
ver
sus
4%
;p
-val
ue
,0
.00
1).
No
such
dif
fere
nce
was
det
ecte
dw
hen
look
ing
atth
ew
ater
sou
rce
for
dri
nk
ing
(wat
erw
asre
po
rted
toal
way
sb
eb
oil
edto
avo
idg
astr
oin
test
inal
No
asse
ssm
ent
of
via
bil
ity
of
the
M.
lep
rae
bac
illi
wh
ich
wer
ed
etec
ted
by
PC
R.
No
causa
lity
can
be
esta
bli
shed
(no
tcl
ear
wh
eth
erle
pro
syp
atie
nts
con
tam
inat
edth
ew
ater
or
bec
ame
infe
cted
by
usi
ng
this
wat
er).
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le3
.co
nti
nu
ed
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
infe
ctio
n).
Con
clu
de
that
wat
erco
uld
be
are
serv
oir
and
sou
rce
of
infe
ctio
nw
ith
M.
lep
rae.
Des
ikan
,S
reev
atsa
;1
99
574
Ex
ten
ded
stud
ies
on
the
via
bil
ity
of
Myc
ob
act
-eri
um
lep
rae
ou
tsid
eth
eh
um
anb
od
y
Lab
ora
tory
Lab
ora
tory
NA
Aft
erd
ryin
gM
.le
pra
ew
asv
iable
(as
asse
ssed
by
ino
cula
tio
nin
tom
ou
sefo
otp
ad)
for
up
to5
mo
nth
s;o
nw
etso
ilfo
r4
6d
ays;
insa
lin
eat
roo
mte
mp
erat
ure
for
60
day
s;w
ith
thre
eh
ou
rso
fd
irec
tsu
nli
gh
tev
ery
day
for
7d
ays;
at48C
for
60
day
s;at
27
08C
for
28
day
s.B
acte
ria
wer
era
pid
lyk
ille
dif
exp
ose
dto
anti
sep
tics
.H
um
idit
yd
uri
ng
dry
ing
app
ears
top
lay
aro
le:
bac
teri
adri
edat
72-8
0%
hu
mid
ity
surv
ived
for
.¼
28
day
sw
her
eas
tho
sed
ried
at4
4–
28
%h
um
idit
ysu
rviv
ed,¼
14
day
s.
En
vir
on
men
tal
con
dit
ion
sn
ot
con
tro
lled
for.
Har
ris
eta
l.;
19
90
75
Via
bil
ity
of
Myc
ob
act
eriu
mle
pra
ein
soil
,w
ater
and
deg
ener
atin
gar
mad
illo
tiss
ue
and
its
sig
nifi
can
ce
Lab
ora
tory
Lab
ora
tory
NA
M.
lep
rae
can
surv
ive
(as
asse
ssed
by
the
mo
use
foo
tpad
mo
del
)ex
po
sure
toso
ilan
dw
ater
for
up
toth
ree
day
so
ru
pto
21
day
sin
ster
ile
tub
es.
Ex
posu
reto
lig
ht
resu
lted
ina
dra
mat
icd
ecre
ase
inth
ev
iabil
ity
of
the
bac
illi
.
No
crit
ical
issu
es.
M.W. Bratschi & P. Steinmann, et al.
Su
pp
lem
enta
ryT
ab
le3
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
Des
ikan
;1
97
773
Via
bil
ity
of
Myc
ob
act
eriu
mle
pra
eo
uts
ide
the
hu
man
bo
dy
Lab
ora
tory
Lab
ora
tory
NA
M.le
pra
ere
mai
ned
infe
ctio
us
(as
asse
ssed
by
ino
cula
tion
into
mou
sefo
otp
ad)
for
atle
ast
9d
ays
(as
ad
ried
susp
ensi
on
kep
tat
24
–3
98C
).
Ex
per
imen
to
nly
ran
for
9d
ays.
Inse
cts
an
dtr
an
smis
sio
nH
on
eij,
Par
ker
;1
91
481
Lep
rosy
:fl
ies
inre
lati
on
toth
etr
ansm
issi
on
of
the
dis
ease
:(a
pre
lim
inar
yn
ote
)
Un
kn
ow
nL
abo
rato
rycr
oss
sect
ion
al
12
flie
sO
fth
e1
2fl
ies
cap
ture
din
the
roo
ms
of
lep
rosy
pat
ien
tso
nly
two
sho
wed
acid
fast
bac
illi
inex
cret
a.T
he
excr
eta
of
six
flie
sal
low
edto
feed
on
lesi
on
so
fp
atie
nts
wer
eneg
ativ
e.E
xcr
eta
of
flie
sal
low
edto
feed
on
pu
stu
les
wer
efo
un
dto
be
freq
uen
tly
po
siti
ve
for
acid
fast
bac
illi
.
Th
en
um
ber
of
sam
ple
sco
llec
ted
fro
mth
ep
rox
imit
yo
fp
atie
nts
was
lim
ited
and
acid
fast
bac
illi
wer
eo
nly
iden
tifi
edb
ym
icro
sco
py
.
Sah
aet
al.
;1
98
583
Via
bil
ity
of
Myc
ob
act
eriu
mle
pra
ew
ith
inth
eg
ut
of
Aed
esa
egyp
tiaf
ter
they
feed
on
mu
ltib
acil
lary
lep
rom
ato
us
pat
ien
ts-
ast
ud
yb
yfl
uore
scen
tan
dE
lect
ron
mic
rosc
op
es
Lab
ora
tory
Lab
ora
tory
NA
Aci
dfa
stb
acil
liin
the
gu
to
fm
osq
uit
oes
allo
wed
tofe
edo
nle
pro
mat
ou
sp
atie
nts
bec
ame
no
n-v
iab
leaf
ter
4d
ays
of
blo
od
mea
ls;
som
em
ult
ipli
cati
on
of
via
ble
bac
illi
was
det
ecte
dd
uri
ng
the
earl
yd
ays.
Co
ncl
ud
eth
atth
ep
oss
ibil
ity
of
M.
lep
rae
tran
smis
sio
nb
ym
osq
uit
ob
ites
toh
um
ans
seam
sre
mo
teb
ecau
seo
fth
esh
ort
via
ble
tim
eo
fth
eb
acil
lian
dth
eq
uic
kfr
agm
enta
tio
nan
del
imin
atio
no
fth
ein
ges
ted
bac
teri
afr
om
the
gu
t.F
urt
her
more
,th
est
ud
y
Via
bil
ity
was
only
asse
ssed
by
mic
rosc
opy
and
met
ho
ds
use
dd
idn
ot
clea
rly
dif
fere
nti
ate
bet
wee
nv
iable
bac
teri
aan
ddea
dbac
illi
.In
crea
sein
bac
teri
anum
ber
sis
slig
ht
and
no
tv
ery
stro
ng
evid
ence
for
actu
alm
ult
ipli
cati
on
.S
mal
ln
um
ber
so
fm
osq
uit
os
exam
ined
.
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le3
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
con
clu
des
that
rep
lica
tio
nin
mosq
uit
os
isu
nli
kel
ysi
nce
repli
cati
on
tim
eo
fM
.le
pra
eis
lon
gco
mp
ared
toth
eli
fesp
ano
fth
ein
sect
s.G
eate
r;1
97
580
Th
efl
yas
po
ten
tial
vec
tor
inth
etr
ansm
issi
on
of
lep
rosy
Lab
ora
tory
Lab
ora
tory
NA
Mu
sca
(ho
use
fly
),C
all
iph
ora
(blu
ebo
ttle
)an
dS
tom
oxy
s(b
itin
gst
able
fly
)w
ere
able
tota
ke
up
larg
en
um
ber
so
fac
idfa
stb
acil
lifr
om
musc
us
and
skin
lesi
on
so
fle
pro
mat
ou
sp
atie
nts
(bac
teri
afo
un
din
gu
t).
Mu
sca
and
Ca
llip
ho
raco
uld
dep
osi
tbac
teri
aat
ad
ista
nt
surf
ace.
Sto
mo
xys
mou
thp
arts
wer
eco
nta
min
ated
(po
ssib
ilit
yfo
rd
irec
tin
ocu
lati
on
).
Bac
illi
just
iden
tifi
edm
icro
scopic
ally
(contr
ols
wer
eal
lac
idfa
stb
acil
lifr
ee).
McF
adze
an,
Mac
donal
d;
19
61
82
An
inves
tigat
ion
of
the
po
ssib
lero
leo
fm
osq
uit
oes
and
bed
bu
gs
inth
etr
ansm
issi
on
of
lep
rosy
Lab
ora
tory
Lab
ora
tory
NA
Fo
un
dn
oev
iden
ceth
atm
osq
uit
oes
or
bed
bu
gs
cou
ldta
ke
up
M.
lep
rae
from
lep
rom
ato
us
pat
ien
tsan
din
tro
du
ceth
emin
toth
esk
ino
fan
oth
erin
div
idu
al.
Ino
cula
tio
no
fM
.le
pra
ew
asev
aluat
edb
yb
iop
sies
,w
hic
hw
ou
ldli
kel
yn
ot
det
ect
smal
ln
um
ber
so
fin
tro
duce
db
acil
li.
M.W. Bratschi & P. Steinmann, et al.
Su
pp
lem
enta
ryT
ab
le4
.P
eer-
revie
wed
studie
sfo
cusi
ng
on
soci
o-e
conom
icri
skfa
ctors
for
M.
lep
rae
tran
smis
sio
no
rn
osp
ecifi
ctr
ansm
issi
on
hy
poth
esis
;li
sted
by
stu
dy
des
ign
and
yea
ro
fpubli
cati
on
wit
hm
ore
rigoro
us
des
igns
and
more
rece
nt
studie
sli
sted
firs
t.
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
Po
nn
igh
aus
eta
l.;
19
94
110
Ex
ten
ded
sch
ooli
ng
and
go
od
ho
usi
ng
con
dit
ion
sar
eas
soci
ated
wit
hre
duce
dri
skof
lepro
syin
rura
lM
alaw
i
Kar
on
ga
Dis
tric
t,M
alaw
i
Pro
spec
tiv
eco
ho
rt7
1,4
99
ind
ivid
ual
s;3
58
inci
den
tca
ses
Rat
era
tio
dec
reas
edm
arked
lyw
ith
incr
easi
ng
du
rati
on
of
schooli
ng.
Lep
rosy
inci
den
cera
tera
tio
sin
crea
sed
asth
est
andar
do
fh
ou
sin
gfe
ll.
Sel
f-re
port
ing
of
sch
ooli
ng
.
Wes
tet
al.
;1
98
8112
Lep
rosy
insi
xis
ola
ted
resi
den
tso
fn
ort
her
nL
ou
isia
na.
Tim
e-cl
ust
ered
case
sin
anes
sen
tial
lyn
on
-en
dem
icar
ea
No
rther
nL
ou
isia
na,
US
A
Ret
rosp
ecti
ve
coh
ort
6ca
ses
No
risk
fact
ors
for
infe
ctio
nco
uld
be
iden
tifi
ed.
Con
sid
ered
wer
eco
nta
ct,
trav
el,re
sid
ence
and
exp
osu
re(e
.g.
toar
mad
illo
s)ri
skfa
cto
rs.
Sm
all
sam
ple
size
.N
oco
ntr
ols
.
Fee
nst
raet
al.
;2
01
1108
Rec
ent
foo
dsh
ort
age
isas
soci
ated
wit
hle
pro
syd
isea
sein
Ban
gla
des
h:
aca
se-c
ontr
ol
study
Ran
gp
ur
Div
isio
n,
Ban
gla
des
h
Cro
ssse
ctio
nal
(cas
eco
ntr
ol)
90
pat
ien
ts;
19
9co
ntr
ols
Rec
ent
per
iod
of
foo
dsh
ort
age
(red
uce
dn
um
ber
of
mea
lso
rre
du
ced
inta
ke
of
foo
ds
oth
erth
anri
ce)
and
no
tp
ov
erty
per
seo
rfo
od
sho
rtag
eat
any
tim
ein
life
was
iden
tifi
edas
the
on
lyso
cio
eco
no
mic
fact
or
asso
ciat
edw
ith
the
clin
ical
man
ifes
tati
on
of
lep
rosy
(OR
1.7
9).
Fo
un
da
no
n-s
ign
ifica
nt
tren
do
fd
ecre
asin
gle
pro
sypre
val
ence
wit
hin
crea
sing
soci
o-e
cono
mic
stat
us.
Sp
ecula
teth
atla
cko
fn
utr
ien
tsle
ads
toch
ang
esin
imm
un
ity
allo
win
gM
.le
pra
eto
cau
secl
inic
ald
isea
se.
Mu
ltip
leri
sks
of
bia
s:e.
g.
self
-rep
ort
edfo
od
sho
rtag
e.S
tudy
excl
uded
case
sth
atre
po
rted
chan
ges
inec
on
om
icst
atu
so
rli
vin
gco
nd
itio
ns
du
eto
the
dis
ease
.
Ker
r-P
on
tes
eta
l.;
20
06
109
So
cio
eco
no
mic
,en
vir
on
men
tal,
and
beh
avio
ura
lri
skfa
cto
rsfo
rle
pro
syin
Nort
hea
stB
razi
l:re
sult
sof
aca
se-c
ontr
ol
study
Cea
raS
tate
,B
razi
l
Cro
ssse
ctio
nal
22
6ca
ses;
85
7co
ntr
ols
Lep
rosy
sign
ifica
ntl
yas
soci
ated
wit
hlo
wed
uca
tio
nal
lev
el,
ever
hav
ing
exp
erie
nce
dfo
od
sho
rtag
e,b
ath
ing
wee
kly
ino
pen
wat
ers
10
yea
rsp
rev
iou
sly
and
alo
w
Po
ten
tial
of
reca
llb
ias
asex
po
sure
tori
skfa
cto
rsd
ated
10
yea
rsag
o.
Transmission of M. leprae
Su
pp
lem
enta
ryT
ab
le4
.co
nti
nued
Au
tho
r;Y
ear
Tit
leS
tud
yS
ite
Stu
dy
Des
ign
Sam
ple
Siz
eM
ain
Fin
din
gs
Qu
alit
yA
sses
smen
t
freq
uen
cyo
fch
ang
ing
bed
lin
ens.
No
env
iro
nm
enta
lo
rd
emo
gra
phic
var
iab
les
wer
eas
soci
ated
wit
han
incr
ease
dri
sko
fle
pro
sy.
Pre
sen
ceo
fa
BC
Gv
acci
nat
ion
scar
was
pro
tect
ive.
de
An
dra
de,
Sab
roza
,d
eA
raujo
;1
99
4107
Fac
tors
asso
ciat
edw
ith
ho
use
ho
ldan
dfa
mil
yin
lep
rosy
tran
smis
sion
inR
iod
eJa
nei
ro,
Bra
zil
Rio
de
Jan
eiro
Sta
te,
Bra
zil
Cro
ssse
ctio
nal
Cas
es:
20%
of
HH
wit
ha
case
;co
ntr
ols
per
case
:4
nei
gh
bo
rh
ou
ses,
5h
ou
ses
fro
ma
sect
or
wit
ho
ut
any
case
s
Th
efo
llo
win
gh
ou
seh
old
char
acte
rist
ics
wer
eas
soci
ated
wit
hle
pro
sy:
less
than
2ro
om
s,n
on
-per
man
ent
bu
ild
ing
mat
eria
l,d
irt
flo
or,
no
th
avin
ga
wat
erso
urc
ein
sid
eth
eh
ou
se.
Lo
wed
uca
tio
nal
lev
elal
soin
crea
sed
lep
rosy
risk
.
Un
ito
fan
aly
sis:
Ho
use
ho
ldU
ncl
ear
ifco
ntr
ols
are
mat
ched
.
Xav
ier
Sil
va
eta
l.;
20
10
111
Han
sen
’sd
isea
se,
soci
alco
nd
itio
ns,
and
def
ore
stat
ion
inth
eB
razi
lian
Am
azon
Bra
zili
anA
maz
on
Eco
logic
alA
llca
ses
report
edin
2006
The
new
case
det
ecti
on
rate
was
po
siti
vel
yco
rrel
ated
wit
hth
eto
tal
def
ore
sted
area
and
the
per
cen
to
fh
ou
seh
old
sw
ith
rud
imen
tary
sep
tic
tan
ks,
and
inver
sely
wit
hth
eh
um
and
evel
op
men
tin
dex
.
No
actu
alre
fere
nce
toth
eso
urc
eo
rro
ute
of
tran
smis
sio
n.
HH
:h
ou
seh
old
M.W. Bratschi & P. Steinmann, et al.