Recently, investigators for the first time showed that M. This suggests that the strains in chimpanzees did not originate from humans but exist in another animal reservoir or in soil.
If there are additional natural reservoirs of M. This Research Topic aims to identify additional niches of M. Due to the inability to cultivate these microorganisms in artificial media, the full array of available tests should be utilized wherever possible to support the findings in a biologically plausible manner: PCR or qPCR; identification of strains by whole genome sequencing WGS , SNP or VNTR typing; serology; histopathology; identification of acid-fast bacilli or use of other staining techniques to identify mycobacteria in situ.
We encourage scientists to contribute with the following article types: original research, review, mini-review, perspective, and opinion. At only 3. Lesions on patients are usually found in cooler areas of the skin. Viability of M. Most animals readily clear the bacilli and cannot be experimentally infected with M. Limited replication can be achieved after inoculation of M. However, the bacilli will not grow when inoculated systemically and exponential increases in growth require many months to attain.
The only animal that reliably recapitulates leprosy as seen in humans, and develops extensive neurological involvement with M. Other than humans, armadillos are also the only natural hosts of M. Armadillos are exotic-looking animals about the size of house-cats Fig. With thick, tough skin and a hard, flexible carapace armouring most of their body, Rudyard Kipling suggested that armadillos were a blend of a tortoise and a porcupine. They are mammals of the order Xenarthra , and related to sloths and anteaters.
Experimental infection of armadillos with M. The remarkable quantities of M. Subsequent surveys confirmed that wild armadillos are a large reservoir for M. Leprosy was not present in the New World during pre-Colombian times, and it is reasonable to assume that armadillos must have acquired the infection from humans sometime in the last few centuries.
They are now recognised as the only non-human reservoir of M. Recent reports indicate that zoonotic transmission of M. The role that armadillos may play in perpetuating leprosy in the Americas is now being investigated.
However, evidence is accumulating that an occult reservoir of pre-clinical asymptomatic cases, and perhaps armadillos or other environmental hosts, may play a more important role in the ecology of the disease, and leprosy probably cannot be eliminated through drug therapy alone. Infected larvae were attached to rabbit skin for a five day maturation feeding period. Afterwards, up to 10 3 viable M. The study showed an ecological cycle of M. The research group also performed the first successful cell culture of M.
This systematic review assessed publications of possible non-human environmental reservoirs and transmission pathways of M. The results show a wildlife reservoir of M. The diagnosis of leprosy in captive non-human primates is limited to case-reports, and it is unknown to what degree species are infected.
Screening for the presence of these mycobacteriae in other species has been negative, except for the finding in of genetic material of M. Possible routes of transmission are schematically visualized in Fig 2. It is justified to ask whether or not we can speak of an environmental reservoir. RNA indicating the presence of viable M.
In addition, it was found that amoebae are capable of taking up M. Inside amoebae, M. This mechanism might contribute to environmental survival in the absence of a mammalian host. Moreover, M. This gives amoebae a possible role as a vector in transmission. The only studies on vegetation reservoirs were on sphagnum species by Kazda Table 4.
Humans and armadillos in the Southern United States share a specific M. It is unclear whether transmission risk by rate of exposure to infected mammals is confounded by rate of exposure to an infected environment. This could be caused by shedding of leprosy bacteria by infected mammals. At this moment, there is no evidence for a role for vectors in transmission. However, recent laboratory studies have shown a potential role for insects. Kissing bugs can defecate after biting, and defecation near the bitten area transmits viable T.
In the same study, it was found that M. It also has been shown that M. Larvae from hatched eggs in turn are able to transmit viable M. Animals can be affected by leprosy-like diseases, caused by pathogens phylogenetically closely related to M. Insights from the transmission and reservoirs of members of the M. Currently, knowledge on the exact transmission mechanisms of M. Using insights on related pathogens is a potentially efficient way to progress.
The studies included in this review differ in methods to determine the causative microorganism of leprosy. Techniques have developed over time from identifying unspecified non-cultivable acid-fast bacteria to specific DNA sequencing. The ability to detect M. The variety of and changes in analysis methods for detection of M.
This is also relevant for studies on M. Studies on zoonosis and prevalence should be performed with sample sizes determined by the population sizes. Results of these studies have to be reported with confidence intervals, as this would substantiate the extrapolation value of the studies.
Many studies in this review lack this method of sample size determination. Geographic origins of the animals are described clearly in most armadillo prevalence studies. It is seen that prevalence fluctuates strongly between neighboring geographic regions. This limits the value of spatially and temporally randomly acquired frozen samples in screening studies, which often do not represent a wildlife sub population.
Seldom are internal control standards like those normally used in clinical laboratories incorporated. This lack of rigor contributes to the anecdotal assessment sometimes given to molecular studies reporting M. Standardization in environmental studies should be increased by first developing appropriate definitions and sample criteria. This systematic review underscores that human-to-human transmission is not the only way leprosy can be acquired.
The transmission of this disease is probably much more complicated than was thought before, as indicated in Fig 2. Transmission of M. Fig 2 shows the animal and environmental factors that might play a role in the persisting prevalence of leprosy.
The proposed factors and mechanisms transgress the disciplines of human healthcare. Therefore, to increase our understanding of the intricate picture of leprosy transmission, a One Health transdisciplinary research approach is required.
In addition, geographically tailored methods—combining epidemiological, laboratory, and anthropologic data—are needed to better understand the ecological differences between leprosy pockets. The authors would like to thank Marja Kik for her feedback on an earlier version of this paper and Toon van der Gronde for his feedback on the methodological section.
Furthermore, we would like to thank Nathalie Kuijpers for her English manuscript correction services. In addition, we would like to thank Frank-Jan van Lunteren for his comprehensive graphics See, Fig 2.
Abstract Leprosy is a chronic infectious disease caused by Mycobacterium leprae M. Author summary Leprosy is a chronic infectious disease caused by Mycobacterium leprae M. Funding: The author s received no specific funding for this work. Method A systematic review was conducted targeting leprosy transmission research data using PubMed and Scopus as sources. Download: PPT. Table 1. Prevalence of M. Armadillos in other parts of the Americas see Table 2. Table 2. Squirrels see Table 3. Table 3.
Nonhuman primates. Screening for new animal species. Leprosy-like disease. Environmental reservoirs see Table 4 The environment is defined as any location outside the host, where M.
Table 4. Environmental reservoirs of M. Zoonotic and anthroponotic transmission Filice et al. Potential vectors see Table 5 Attempts at discovering vectors for M.
Discussion This systematic review assessed publications of possible non-human environmental reservoirs and transmission pathways of M. Supporting information. S1 Text. Acknowledgments The authors would like to thank Marja Kik for her feedback on an earlier version of this paper and Toon van der Gronde for his feedback on the methodological section.
References 1. Leprosy exposure, infection and disease: a year surveillance study of leprosy patient contacts. Mem Inst Oswaldo Cruz. Clin Infect Dis. High frequency of M. BMC Infect Dis. Leprosy now: epidemiology, progress, challenges, and research gaps. Lancet Infect Dis. Hansen GA. Nor Mag Laegervidenskaben. View Article Google Scholar 7. On the Etiology of Leprosy. Br Foreign Medico-chirurgical Rev.
View Article Google Scholar 8. Shepard CC. The experimental disease that follows the injection of human leprosy bacilli into foot-pads of mice. J Exp Med. Multiplication of Mycobacterium leprae in the foot-pad of the mouse. Int J Lepr. View Article Google Scholar Attempts to establish the Armadillo Dasypus novemcinctus linn. Histopathologic and bacteriologic post-mortem findings in lepromatoid leprosy in the Armadillo. Leprosy in the armadillo: new model for biomedical research. A new Mycobacterium species causing diffuse lepromatous leprosy.
Am J Clin Pathol. Massive gene decay in the leprosy bacillus. Primary neural leprosy: systematic review. Arq Neuropsiquiatr. On the origin of leprosy. Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae. Nat Commun. Ancient genomes reveal a high diversity of Mycobacterium leprae in medieval Europe. PLOS Pathog. Current knowledge on Mycobacterium leprae transmission: a systematic literature review. Lepr Rev. Zoonotic Leprosy in the Southeastern United States.
Emerg Infect Dis. Oklahoma: University of Oklahoma Press; Assembling evidence for identifying reservoirs of infection. Trends Ecol Evol. Scollard DM. Editorial: Infection with Mycobacterium lepromatosis. Am J Trop Med Hyg. Red squirrels in the British Isles are infected with leprosy bacilli.
Leprosy-like disease occurring naturally in armadillos. J Reticuloendothel Soc. Naturally acquired leprosy-like disease in the nine-banded armadillo Dasypus novemcinctus : recent epizootiologic findings. Naturally acquired leprosy-like disease in the nine-banded armadillo Dasypus novemcinctus : histopathologic and microbiologic studies of tissues. Naturally acquired leprosy-like disease in the nine-banded armadillo Dasypus novemcinctus : reactions in leprosy patients to lepromins prepared from naturally infected armadillos.
Studies on the inoculation of mycobacterium leprae into monkeys. Skinsnes OK. The mechanism by which bacteria are transmitted from one organism to another has not been unequivocally demonstrated 8.
However, based on existing evidence, skin-to-skin contact, aerosols as well as shedding of bacteria into the environment subsequently followed by infection of other individuals remain the most obvious options for human leprosy 8 , 9.
Still these routes provide no explanation for the occurrence of leprosy in individuals without known contact to leprosy patients or in areas without any reported new cases 9 , Through PCR amplification of M.
The viability of M. Moreover, viability of M. Additionally, if environment—free living amoebic cysts cultured in the laboratory are artificially infected with M.
Recently, M. Phylogenetic analyses determined that the M. Zoonotic transmission of M. Furthermore, although the prevalence of leprosy in nonhuman primates NHP seems to be quite low, M.
In this study, we aimed to explore whether besides humans and animals, environmental sources may function as a reservoir of M. For this purpose, we investigated the presence of M. As a negative control soil was obtained from the surroundings of the Leiden University Medical Centre The Netherlands and spiked with 10 8 cells of M. To detect the presence of M. DNA from M. PCR to detect M. To determine the genotype 1, 2, 3 or 4 of M. PCR products were resolved by agarose gel electrophoresis as explained above.
To determine whether M. PCR products were electrophoresed in a 3. Soil samples collected in Bangladesh are represented in the graph by dots and sorted based on RLEP PCR results and bacillary load of the patient living in the household where the soil was collected. DNA of M. Inhibition was observed in 7 of the 10 soil samples from Brownsea Island, 8 out of the 10 from the Isle of Arran and 1 out of the 28 from Suriname.
For the soil from Suriname the genotype was narrowed down to either 1 or 2 since only sequencing of locus 3 Suriname 2, 3 and 6 and locus 1 Suriname 6 were identified. For the RLEP positive sample from Brownsea Island it was not possible to obtain sequence information for any of the polymorphic loci to assign a genotype.
This was most likely due to the small amount of M. SNP analysis of loci 1, 2 and 3 from a representative M. SNP positions are based on the M. Vertical bars indicate the polymorphic base. Human leprosy still poses a considerable health threat in developing countries where transmission is generally assumed to take place via aerosol droplets from nasal cavities of untreated M. As paleopathological evidence of leprosy in pre-Columbian America is lacking, leprosy was very likely introduced to the continent by European colonists or the African slave route 28 also resulting in transmission to armadillos.
However, nowadays infected armadillos may even be responsible for new cases in human individuals who have never had contact with leprosy patients nor travelled to leprosy endemic areas 10 , In addition, another living host that could potentially represent an environmental reservoir for M. Thus, amoebas or other protists might represent an intermediate host which would allow indirect infection with M.
In this study, M. However, this study did not asses viability of the bacteria and since M. Understanding how M. Although human leprosy was eradicated from the British Isles centuries ago, Eurasian red squirrels have remained a reservoir for M. This indicates that M. However, M. Because the genome of M.
Added to the fact that M. In Bangladesh, M. At those locations more bacteria are shed and thus the likelihood of encountering bacteria in the soil is higher. The higher percentage of RLEP positive soil in Bangladesh is likely due to a more targeted selection of the sample location in the houses of leprosy patients as well as the higher leprosy prevalence.
In previous phylogeographic analysis genotype 1 was identified as the predominant strain type in South Asia 35 , 36 and was likely introduced to South Asia from other parts of that continent The genotype found in soil samples from Bangladesh 1 is therefore in accordance with previous phylogeographic data In summary, this study demonstrates the presence of M.
Further research is needed, however, to confirm whether M. Thus, strategies aimed at prevention of transmission by administration of post-exposure prophylaxis to infected individuals should, besides human reservoirs of M. World Health Organization. Global leprosy update, accelerating reduction of disease burden.
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