Current knowledge on Mycobacterium leprae transmission: a ...

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.


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


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


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


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


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,


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


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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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


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).


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.


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


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


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.


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.


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.


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.


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.


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.


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


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


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

.


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).


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.


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

.


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

.


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”.


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

.


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

.


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).


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.


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

.


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.


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.


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


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