- Email: [email protected]
Reservoir rats
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MICINF4194_proof ■ 19 September 2014 ■ 1/4
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Microbes and Infection xx (2014) 1e4 www.elsevier.com/locate/micinf
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Reservoir rats*
Keywords: Leptospira; Leptospirosis; Animal reservoir; Rats; Ecotourism
Don't you go where the husky's go, don't you eat that yellow snow, is the advice the Eskimo Nanook gets from his mother in the “Don't Eat The Yellow Snow Suite” from 1974, a delirious musical product of the insane and brilliant mind of the satirical, anti-mainstream composer and performer Frank Zappa. Later, Nanook clashes with a “strictly from commercial” fur trapper, and husky urine-soaked snow turns out to be a dangerous weapon. Zappa got this actually right, even if maybe not for this reason, as Leptospira, the causative agent of leptospirosis is transmitted via the urine of animal reservoirs, rats in pole position, which carry the bacteria in their renal tubules and shed them continuously into water and soil [2,3]. The first time I remember having heard about leptospirosis was under Paris. Not in, but under, literally, in the ancient quarries, exaggeratedly generalized as the catacombs, in order to increase their shiver factor [4]. Of course we are not talking about the legal tourist trip to visit some bone wall, but about the forbidden labyrinth of galleries and caves stretching out under a huge part of Southern Paris e maintained, sculpted, painted and expanded on a regular basis by hundreds of “cataphils”. Upon nightfall, dark figures wearing boots and headlamps appear, quickly check the surroundings and swiftly open some metal cover in the pavement, an access to an electrical gallery, and disappear into another world, a humid world without light or time, where the motionless air is at 18 C all the year, with small stalactites over your head, leftovers of German bunkers at your feet and squeaking rodents in the dark. They gather in a huge room and take the wine and sound system out of their backpacks. There are countless candelabra on the ceiling, candles, plastic flowers, curtains, fake skulls, accumulated over time, the walls are covered in graffiti and psychedelic artwork, someone has painted the notes of Chopin's funeral march on the stone. Eventually, they will cook some sausages on a camping stove or roam the tunnels with garbage bags, cleaning up after the * Article highlight based on “Leptospira-rat-human relationship in Luzon, Philippines” by Sharon Yvette Angelina M. Villanueva et al. [1].
weekend's party visitors, who only come once. Around 5 am, they re-emerge in front of a bakery diffusing the smell of fresh croissants, discretely close the manhole cover and quickly disperse, returning to their other lives as a mobile phone customer consultant, rope access technician or biologist. Only a couple of faint muddy footprints remain on the asphalt. Going underground has become a must have been there of the young Parisian intellectuals. Pseudo-adventurers, I fully assume being part of, filled with pre-historical nostalgia, take an irrational pleasure in walking kilometers in ankledeep water, crossing the fog of smoke-bombs and compensating the sleep deprivation by liters of coffee. It seems that when the living standard crosses a certain level, the neglected reward system triggers the sudden urge for artificial hardships and dangers, and in the comfortable era of Roombas and pizza delivery services, some fans of Bear Grylls absolutely want to cross snow fields and Piranhafilled rivers. So, during one of my first descents into the catacombs, a regular told me casually about the possibility to contract leptospirosis. Indeed, there are rats, the natural needs of the rats, water and the skin of one's feet rendered all wet and permeable [3]. And of course I just had a quick look at my wrecked sneakers and shrugged, a certain disrespect, allowedly, for a discrete genus that should be nominated for a range of categories of the prize of successful pathogenic bacteria. For being the world's most spread zoonosis, for example, as Leptospira are everywhere, on all continents and in all mammalian species [2,5]. For their survival and cooperation skills in various environmental conditions in soil or water, maybe in form of aggregates or biofilms [3]. And on top of all, for being quite a pain at bench and bedside: growing slowly, demanding in medium conditions [6], they tend to loose their virulence in subcultures [5]. The next difficulty resides in determining the lipopolysaccharide mosaic on the bacterial surface among 24 serogroups and over 260 pathogenic serovars, which actually have nothing to do with a Russian device for tea making [5,7].
http://dx.doi.org/10.1016/j.micinf.2014.09.002 1286-4579/© 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. Please cite this article in press as: H€afner S, Reservoir rats, Microbes and Infection (2014), http://dx.doi.org/10.1016/j.micinf.2014.09.002
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Highlight / Microbes and Infection xx (2014) 1e4
The gold standard, the microscopic agglutination test (MAT), requires all the things that are rare in tropical and subtropical countries, where lepospirosis is endemic [8] e time, money and material like panels of local Leptospira serovars kept in culture [5,6] e and is only slowly replaced by easier detection methods based on qPCR and sequencing [5,6,8]. Due to the diversity of clinical signs, diagnosis is equally difficult for physicians. Vaccines have been developed for nearly a century [5], but they require an annual revaccination, are serovarrestricted [5,6] and tend to upset animal welfare companies for the sake of Golden Syrian Hamsters [9]. But Leptospira excel most in the art of mystery keeping. A huge part of reviews in their honor is about the things we do not know, and compared to other bacterial pathogens, this is a lot [2,5]. The cellular and molecular basis for pathogenesis are barely understood, virulence, adhesion factors and membrane topology not identified [5] and potential gene transfer and eventual regulatory small RNA mechanisms not elucidated [2,5]. The recent use of comparative genomics between pathogenic and saprophytic species has added more questions than answers: over 900 genes are proper to pathogenic Leptospira species interrogans and borgpetersenii, but 80% and 60% respectively of those are genes of unknown function and vice versa, among the proteins of known functions are no homologs of other bacterial virulence factors [2]. In a nutshell, Leptospira displays a high degree of genome plasticity and possesses unique, unknown virulence determinants. Even more recent application of mutagenesis directed against potential virulence factors turned out likewise frustrating and mainly proved the high degree of redundancy in leptospiral proteins [2,5] and the inadequacies of current simulations of in vivo conditions [2]. Part of the lack of knowledge is certainly due to a certain lack of interest [7]. As a consequence, genetic tools were applied late and there are no high throughput screening methods available yet [2,5]. The challenge of the peculiarities of Leptospira alone is apparently not motivating enough. Maybe, leptospirosis is not deadly enough, and for sure, it will be tricky to arouse much interest in it right now, in the shadows of the current outbreak of Ebola in Western Africa. Maybe it usually happens far away, in some filipino rice fields. However, maybe the catalyst to promote research on Leptospira & Co. will be the adventurers of the 21st century, for whose the curious concept of “recreational exposure” had to be created, which incidence is increasing in the western world while the one of occupational exposure decreases [3]. Ecotourism, adventure races and outdoors sports involving fresh water activities such as triathlons, rowing, bathing in rivers, canoeing and fishing have become the local rice fields [3,6,7]. And while mosquitoes travel to the Europeans thanks to climate change, Europeans travel to the mosquitoes thanks to countless adventure agencies [10]. Leptospirosis is not an individual case, the same goes for leishmaniasis [11,12] or tick-borne diseases [13,14] for example and
several studies deemed necessary to point out that washing contact lenses in rivers is a bad idea and going “Kitty!” when spotting a tiger, even in private zoo, not an adequate reaction [15]. There are largely broadcasted cases like the death of the Olympic rower Andy Holmes [7] in 2010 from leptospirosis and anecdotical ones like the family father who became ill after his vengeful daughter had cleaned the petmouse cage with his toothbrush after an argument [3] e they may, as a side effect, direct attention to regions like the Philippines and disadvantaged inner-city environments even in Europe [6], where little is officially known concerning the incidence, prevalence and geographical distribution of animal reservoirs and serovars, thus severely hampering vaccination programs [5,6,8]. In parallel to deciphering the molecular mechanisms of Leptospira virulence, much work has to be done in terms of surveillance, reporting and generating the big picture of connections between humans, animal reservoirs and environmental data such as flooding [1,7]. Nota bene, after crossing the Corsican mountains with a hammock, several kilos of pasta and a Nutella jar e drinking directly from any river is not a good idea either. Q2 Biosketch Dr. Villanueva finished her Science Bachelor in Public Health in 1997 at the University of the Philippines in Manila and got her Master of Medical Sciences in Bacteriology in 2006 and her PhD in Medical Sciences in 2010 both at the Kyushu University of Fukuoka (Japan). Currently, she is completing a postdoctoral fellowship there at the Department of Bacteriology. Dr. Villanueva has been working on Leptospira and leptospirosis since 1998. Her research interests include serological and molecular epidemiology, pathogenesis and immunology of Leptospira, leptospirosis and other infectious diseases.
Interview with Sharon Y.A.M. Villanueva What triggered your interest in the link between Leptospira, humans and rats? As it is common knowledge, leptospirosis is one of the zoonoses that is widely spread around the world. Our country, Philippines, is known to be endemic for this zoonosis. Rodents, especially rats, are known to be the most important
Please cite this article in press as: H€afner S, Reservoir rats, Microbes and Infection (2014), http://dx.doi.org/10.1016/j.micinf.2014.09.002
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reservoirs of pathogenic leptospires that cause this infection. In the Philippines, although leptospirosis is considered to be a public health menace, not much has been publicized regarding this zoonosis. Furthermore, the Leptospira-rat-human relationship has not been well elucidated. Based on these, we became interested in exploring this relationship. What was your first reaction when you faced the results? Did you expect them? We had mixed reactions when we saw the results of our study. Although we were sort of expecting the results, we were also surprised especially when we consolidated and analyzed our data. How will the project go on? There is still a lot to do with regards to leptospirosis research, especially in the Philippines. As I have mentioned earlier, much has yet to be elucidated especially on the prevailing serovars in the Philippines. In our current and previous publications, we collected our samples in limited areas. But, we do hope to expand our surveillance hopefully throughout the Philippines in order to have a better picture of leptospirosis in the country. Aside from rats, we would like to collect samples from other animals that are known to be reservoirs of leptospires such as dogs, pigs, cows, water buffaloes, etc. We would also like to collect environmental samples. In fact, this is what we are currently doing in our collaborative research between Kyushu University, Chiba Institute of Science, and the University of the Philippines Manila. We hope that with our current collaborative research, we will be able to contribute to the prevention and control of leptospirosis through development of accurate and rapid diagnostic kits as well as vaccines. What is the take-home message of the article? The take-home message of our article is that the major circulating Leptospira among rats are the same types that are also infecting humans in the selected study sites in the Philippines. Thus, rats are considered to be the major transmitters of leptospires to humans. Furthermore, 2 of the major circulating Leptospira serovars (i.e., Manilae and Losbanos) have been present in the country for decades. Since we were able to identify the prevailing serovars among humans and rats, we hope that this would help the public health managers in developing preventive and control measures against leptospirosis.
3
What advice would you give to the young next-generation scientists? I feel like I am not that old and experienced enough to be giving advice to young scientists. But, similar to my answer in #5, I would advice them not to easily give up when things do not go the way they expect them to. There may be bumps along the way but these should not derail or hinder them from focusing on and reaching their goals. They should “enjoy” the stumbling blocks because sometimes, these are miracles along the way that may aid them in finding the answers. Lastly, in everything that you do, you should not only think only of yourself but also think of what you can contribute to the world, especially of what you can do for the good of mankind. What is your favorite hang-out method after a tough day at the lab? Sleep is too precious for me, so when I have time, I try to get as much sleep as I can. On other days, I spend it with my close friends and their families or do cross-stitching, coloring books, reading pocketbooks, or watching TV. Lastly, since I am living away from my family, talking to them (especially my parents) everyday is my best “destressor.” In your opinion, what are the three most important (scientific) discoveries of the last decade? Internet, smartphones, iPS cells. If you could travel back in time e what historical personality would you like to meet and what scientific discovery to assist to? If I could travel back in time, I would like to meet a lot of historical personalities but if given only one choice, I would like to meet Profs. Inada and Ido, and their colleagues. They were former professors in Kyushu University where I am currently doing my post doctorate. And, they discovered pathogenic leptospires as the causative agent of Weil's disease. It would be interesting to know first-hand how they were able to discover Leptospira, which are the bacteria that I have been working on for 16 years already. If you could travel forth in time e what eventual invention would you like to check out?
Do you have a personal motto, quote or leading sentence? When things are not going the way I expect them to be, especially my experiments, I always remind myself of this quotation from an anonymous writer: “The moment you think about giving up, think of the reason why you held on so long.” So am I.
With the recent events that are happening around the world and if given the chance to travel forth in time, I would like to see: the total eradication of communicable and noncommunicable diseases; environmental restoration; a machine or invention that would create and maintain world peace and harmony.
Please cite this article in press as: H€afner S, Reservoir rats, Microbes and Infection (2014), http://dx.doi.org/10.1016/j.micinf.2014.09.002
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Highlight / Microbes and Infection xx (2014) 1e4
References Background - Leptospira, a genus of spirochetes, are thin, helical and mobile bacteria, comprising 14 pathogenic and 6 saprophytic species divided into over 300 serovars in total - They are present worldwide, especially in tropical regions, and infect virtually all mammals. The main animal reservoirs are rodents, domestic and production animals which carry the bacteria in their proximal renal tubules and shed them via urine - Pathogenic Leptospira can cause leptospirosis, whose symptoms range from subclinical to a severe infection with renal and hepatic failure, pulmonary distress and death (Weil's disease) - Infection occurs through direct contact with contaminated urine, water or soil. The bacteria enter the organism through small cuts, abrasions, mucosa or wet skin - Annually, between 500 000 and 1 million cases of leptospirosis are reported, case fatality ranges between 5 and 20% depending on the start of treatment and reaches 70% in the case of severe pulmonary hemorrhagic syndrome
In a nutshell - 40 clinical isolates from leptospirosis patients and Leptospira strains from wild rats were obtained in Luzon (Philippines) during the same period - All isolates are pathogenic Leptospira interrogans and belong mainly to the serogroups Pyrogenes, Bataviae and Gryppotyphosa and to serovars Manilae and Losbanos - Different Leptospira strains are predominant in different geographic regions - Identical serotypes were isolated from humans and rats in the same regions and from close time points - These results suggest that 3 predominant Leptospira groups are circulating since decades among rats in Luzon, the main source of transmission to humans
[1] Villanueva SYAM, Saito M, Baterna RA, Estrada CAM, Rivera AKB, Dato MC, et al. Leptospira-rat-human relationship in Luzon, Philippines. Microbes Infect 2014. http://dx.doi.org/10.1016/j.micinf.2014.07.001. [2] Adler B, Lo M, Seeman T, Murray GL. Pathogenesis of leptospirosis: the influence of genomics. Vet Microbiol 2011;153(1e2):73e81. [3] Monahan AM, Miller IS, Nally JE. Leptospirosis: risks during recreational activities. J Appl Microbiol 2009;107(3):707e16. [4] en.wikipedia.org/wiki/Catacombs_of_Paris. [5] Adler B, de la Pe~na Moctezuma A. Leptospira and leptospirosis. Vet Microbiol 2010;140(3e4):287e96. [6] Guerra MA. Leptospirosis: public health perspectives. Biologicals 2013;41(5):295e7. [7] Dupouey J, Faucher B, Edouard S, Richet H, Kodjo A, Drancourt M, et al. Human leptospirosis: an emerging risk in Europe? Comp Immunol Microbiol Infect Dis 2010;37(2):77e83. [8] Villanueva SYAM, Ezoc H, Baterna RA, Yanagihara Y, Muto M, Koizumi N, et al. Serologic and molecular studies of Leptospira and leptospirosis among rats in the Philippines. Am J Trop Med Hyg 2010;82(5):889e98. [9] Walker A, Srinivas GB. Opportunities and strategies to further reduce animal use for Leptospira vaccine potency testing. Biologicals 2013;41(5):332e7. [10] Wang G, Innes JL, Wu SW, Krzyzanowski J, Yin Y, Dai S, et al. National park development in China: conservation or commercialization? Ambio 2012;41(3):247e61. [11] Carvalho BM, Maximo M, Costa WA, de Santana AL, da Costa SM, da Costa Rego TA, et al. Leishmaniasis transmission in an ecotourism area: potential vectors in Ilha Grande, Rio de Janeiro State, Brazil. Parasit Vectors 2013;6(1):325. [12] Pavli A, Maltezou HC. Leishmaniasis, an emerging infection in travelers. Int J Infect Dis 2010;14(12):e1032e1039. [13] Roch N, Epaulard O, Pelloux I, Pavese P, Brion JP, Raoult D, et al. African tick bite fever in elderly patients: 8 cases in French tourists returning from South Africa. Clin Infect Dis 2008;47(3):e28e35. [14] Jensenius M, Parola P, Raoult D. Threats to international travellers posed by tick-borne diseases. Travel Med Infect Dis 2006;4(1):4e13. [15] Shepherd SM, Mills A, Shoff WH. Human attacks by large felid carnivores in captivity and in the wild. Wilderness Environ Med 2014;25(2):220e30.
Sophia H€afner* Q3 Univ. Paris Diderot, Sorbonne Paris Cite, UMR 7216 CNRS, Epigenetics and Cell Fate, 75013 Paris, France *UMR7216 Epigenetics and Cell Fate, Claire Rougeulle Team, Inactivation of the X chromosome, 35 Rue Helene Brion B^atiment Lamarck, Room 422, 75205 Paris Cedex 13, France. Tel.: þ33 (0)1 57 27 89 30. Q1 E-mail address: [email protected] 27 August 2014
Please cite this article in press as: H€afner S, Reservoir rats, Microbes and Infection (2014), http://dx.doi.org/10.1016/j.micinf.2014.09.002
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MICINF4194_proof ■ 19 September 2014 ■ 1/4
MODEL
Microbes and Infection xx (2014) 1e4 www.elsevier.com/locate/micinf
Highlight
Reservoir rats*
Keywords: Leptospira; Leptospirosis; Animal reservoir; Rats; Ecotourism
Don't you go where the husky's go, don't you eat that yellow snow, is the advice the Eskimo Nanook gets from his mother in the “Don't Eat The Yellow Snow Suite” from 1974, a delirious musical product of the insane and brilliant mind of the satirical, anti-mainstream composer and performer Frank Zappa. Later, Nanook clashes with a “strictly from commercial” fur trapper, and husky urine-soaked snow turns out to be a dangerous weapon. Zappa got this actually right, even if maybe not for this reason, as Leptospira, the causative agent of leptospirosis is transmitted via the urine of animal reservoirs, rats in pole position, which carry the bacteria in their renal tubules and shed them continuously into water and soil [2,3]. The first time I remember having heard about leptospirosis was under Paris. Not in, but under, literally, in the ancient quarries, exaggeratedly generalized as the catacombs, in order to increase their shiver factor [4]. Of course we are not talking about the legal tourist trip to visit some bone wall, but about the forbidden labyrinth of galleries and caves stretching out under a huge part of Southern Paris e maintained, sculpted, painted and expanded on a regular basis by hundreds of “cataphils”. Upon nightfall, dark figures wearing boots and headlamps appear, quickly check the surroundings and swiftly open some metal cover in the pavement, an access to an electrical gallery, and disappear into another world, a humid world without light or time, where the motionless air is at 18 C all the year, with small stalactites over your head, leftovers of German bunkers at your feet and squeaking rodents in the dark. They gather in a huge room and take the wine and sound system out of their backpacks. There are countless candelabra on the ceiling, candles, plastic flowers, curtains, fake skulls, accumulated over time, the walls are covered in graffiti and psychedelic artwork, someone has painted the notes of Chopin's funeral march on the stone. Eventually, they will cook some sausages on a camping stove or roam the tunnels with garbage bags, cleaning up after the * Article highlight based on “Leptospira-rat-human relationship in Luzon, Philippines” by Sharon Yvette Angelina M. Villanueva et al. [1].
weekend's party visitors, who only come once. Around 5 am, they re-emerge in front of a bakery diffusing the smell of fresh croissants, discretely close the manhole cover and quickly disperse, returning to their other lives as a mobile phone customer consultant, rope access technician or biologist. Only a couple of faint muddy footprints remain on the asphalt. Going underground has become a must have been there of the young Parisian intellectuals. Pseudo-adventurers, I fully assume being part of, filled with pre-historical nostalgia, take an irrational pleasure in walking kilometers in ankledeep water, crossing the fog of smoke-bombs and compensating the sleep deprivation by liters of coffee. It seems that when the living standard crosses a certain level, the neglected reward system triggers the sudden urge for artificial hardships and dangers, and in the comfortable era of Roombas and pizza delivery services, some fans of Bear Grylls absolutely want to cross snow fields and Piranhafilled rivers. So, during one of my first descents into the catacombs, a regular told me casually about the possibility to contract leptospirosis. Indeed, there are rats, the natural needs of the rats, water and the skin of one's feet rendered all wet and permeable [3]. And of course I just had a quick look at my wrecked sneakers and shrugged, a certain disrespect, allowedly, for a discrete genus that should be nominated for a range of categories of the prize of successful pathogenic bacteria. For being the world's most spread zoonosis, for example, as Leptospira are everywhere, on all continents and in all mammalian species [2,5]. For their survival and cooperation skills in various environmental conditions in soil or water, maybe in form of aggregates or biofilms [3]. And on top of all, for being quite a pain at bench and bedside: growing slowly, demanding in medium conditions [6], they tend to loose their virulence in subcultures [5]. The next difficulty resides in determining the lipopolysaccharide mosaic on the bacterial surface among 24 serogroups and over 260 pathogenic serovars, which actually have nothing to do with a Russian device for tea making [5,7].
http://dx.doi.org/10.1016/j.micinf.2014.09.002 1286-4579/© 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. Please cite this article in press as: H€afner S, Reservoir rats, Microbes and Infection (2014), http://dx.doi.org/10.1016/j.micinf.2014.09.002
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Highlight / Microbes and Infection xx (2014) 1e4
The gold standard, the microscopic agglutination test (MAT), requires all the things that are rare in tropical and subtropical countries, where lepospirosis is endemic [8] e time, money and material like panels of local Leptospira serovars kept in culture [5,6] e and is only slowly replaced by easier detection methods based on qPCR and sequencing [5,6,8]. Due to the diversity of clinical signs, diagnosis is equally difficult for physicians. Vaccines have been developed for nearly a century [5], but they require an annual revaccination, are serovarrestricted [5,6] and tend to upset animal welfare companies for the sake of Golden Syrian Hamsters [9]. But Leptospira excel most in the art of mystery keeping. A huge part of reviews in their honor is about the things we do not know, and compared to other bacterial pathogens, this is a lot [2,5]. The cellular and molecular basis for pathogenesis are barely understood, virulence, adhesion factors and membrane topology not identified [5] and potential gene transfer and eventual regulatory small RNA mechanisms not elucidated [2,5]. The recent use of comparative genomics between pathogenic and saprophytic species has added more questions than answers: over 900 genes are proper to pathogenic Leptospira species interrogans and borgpetersenii, but 80% and 60% respectively of those are genes of unknown function and vice versa, among the proteins of known functions are no homologs of other bacterial virulence factors [2]. In a nutshell, Leptospira displays a high degree of genome plasticity and possesses unique, unknown virulence determinants. Even more recent application of mutagenesis directed against potential virulence factors turned out likewise frustrating and mainly proved the high degree of redundancy in leptospiral proteins [2,5] and the inadequacies of current simulations of in vivo conditions [2]. Part of the lack of knowledge is certainly due to a certain lack of interest [7]. As a consequence, genetic tools were applied late and there are no high throughput screening methods available yet [2,5]. The challenge of the peculiarities of Leptospira alone is apparently not motivating enough. Maybe, leptospirosis is not deadly enough, and for sure, it will be tricky to arouse much interest in it right now, in the shadows of the current outbreak of Ebola in Western Africa. Maybe it usually happens far away, in some filipino rice fields. However, maybe the catalyst to promote research on Leptospira & Co. will be the adventurers of the 21st century, for whose the curious concept of “recreational exposure” had to be created, which incidence is increasing in the western world while the one of occupational exposure decreases [3]. Ecotourism, adventure races and outdoors sports involving fresh water activities such as triathlons, rowing, bathing in rivers, canoeing and fishing have become the local rice fields [3,6,7]. And while mosquitoes travel to the Europeans thanks to climate change, Europeans travel to the mosquitoes thanks to countless adventure agencies [10]. Leptospirosis is not an individual case, the same goes for leishmaniasis [11,12] or tick-borne diseases [13,14] for example and
several studies deemed necessary to point out that washing contact lenses in rivers is a bad idea and going “Kitty!” when spotting a tiger, even in private zoo, not an adequate reaction [15]. There are largely broadcasted cases like the death of the Olympic rower Andy Holmes [7] in 2010 from leptospirosis and anecdotical ones like the family father who became ill after his vengeful daughter had cleaned the petmouse cage with his toothbrush after an argument [3] e they may, as a side effect, direct attention to regions like the Philippines and disadvantaged inner-city environments even in Europe [6], where little is officially known concerning the incidence, prevalence and geographical distribution of animal reservoirs and serovars, thus severely hampering vaccination programs [5,6,8]. In parallel to deciphering the molecular mechanisms of Leptospira virulence, much work has to be done in terms of surveillance, reporting and generating the big picture of connections between humans, animal reservoirs and environmental data such as flooding [1,7]. Nota bene, after crossing the Corsican mountains with a hammock, several kilos of pasta and a Nutella jar e drinking directly from any river is not a good idea either. Q2 Biosketch Dr. Villanueva finished her Science Bachelor in Public Health in 1997 at the University of the Philippines in Manila and got her Master of Medical Sciences in Bacteriology in 2006 and her PhD in Medical Sciences in 2010 both at the Kyushu University of Fukuoka (Japan). Currently, she is completing a postdoctoral fellowship there at the Department of Bacteriology. Dr. Villanueva has been working on Leptospira and leptospirosis since 1998. Her research interests include serological and molecular epidemiology, pathogenesis and immunology of Leptospira, leptospirosis and other infectious diseases.
Interview with Sharon Y.A.M. Villanueva What triggered your interest in the link between Leptospira, humans and rats? As it is common knowledge, leptospirosis is one of the zoonoses that is widely spread around the world. Our country, Philippines, is known to be endemic for this zoonosis. Rodents, especially rats, are known to be the most important
Please cite this article in press as: H€afner S, Reservoir rats, Microbes and Infection (2014), http://dx.doi.org/10.1016/j.micinf.2014.09.002
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reservoirs of pathogenic leptospires that cause this infection. In the Philippines, although leptospirosis is considered to be a public health menace, not much has been publicized regarding this zoonosis. Furthermore, the Leptospira-rat-human relationship has not been well elucidated. Based on these, we became interested in exploring this relationship. What was your first reaction when you faced the results? Did you expect them? We had mixed reactions when we saw the results of our study. Although we were sort of expecting the results, we were also surprised especially when we consolidated and analyzed our data. How will the project go on? There is still a lot to do with regards to leptospirosis research, especially in the Philippines. As I have mentioned earlier, much has yet to be elucidated especially on the prevailing serovars in the Philippines. In our current and previous publications, we collected our samples in limited areas. But, we do hope to expand our surveillance hopefully throughout the Philippines in order to have a better picture of leptospirosis in the country. Aside from rats, we would like to collect samples from other animals that are known to be reservoirs of leptospires such as dogs, pigs, cows, water buffaloes, etc. We would also like to collect environmental samples. In fact, this is what we are currently doing in our collaborative research between Kyushu University, Chiba Institute of Science, and the University of the Philippines Manila. We hope that with our current collaborative research, we will be able to contribute to the prevention and control of leptospirosis through development of accurate and rapid diagnostic kits as well as vaccines. What is the take-home message of the article? The take-home message of our article is that the major circulating Leptospira among rats are the same types that are also infecting humans in the selected study sites in the Philippines. Thus, rats are considered to be the major transmitters of leptospires to humans. Furthermore, 2 of the major circulating Leptospira serovars (i.e., Manilae and Losbanos) have been present in the country for decades. Since we were able to identify the prevailing serovars among humans and rats, we hope that this would help the public health managers in developing preventive and control measures against leptospirosis.
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What advice would you give to the young next-generation scientists? I feel like I am not that old and experienced enough to be giving advice to young scientists. But, similar to my answer in #5, I would advice them not to easily give up when things do not go the way they expect them to. There may be bumps along the way but these should not derail or hinder them from focusing on and reaching their goals. They should “enjoy” the stumbling blocks because sometimes, these are miracles along the way that may aid them in finding the answers. Lastly, in everything that you do, you should not only think only of yourself but also think of what you can contribute to the world, especially of what you can do for the good of mankind. What is your favorite hang-out method after a tough day at the lab? Sleep is too precious for me, so when I have time, I try to get as much sleep as I can. On other days, I spend it with my close friends and their families or do cross-stitching, coloring books, reading pocketbooks, or watching TV. Lastly, since I am living away from my family, talking to them (especially my parents) everyday is my best “destressor.” In your opinion, what are the three most important (scientific) discoveries of the last decade? Internet, smartphones, iPS cells. If you could travel back in time e what historical personality would you like to meet and what scientific discovery to assist to? If I could travel back in time, I would like to meet a lot of historical personalities but if given only one choice, I would like to meet Profs. Inada and Ido, and their colleagues. They were former professors in Kyushu University where I am currently doing my post doctorate. And, they discovered pathogenic leptospires as the causative agent of Weil's disease. It would be interesting to know first-hand how they were able to discover Leptospira, which are the bacteria that I have been working on for 16 years already. If you could travel forth in time e what eventual invention would you like to check out?
Do you have a personal motto, quote or leading sentence? When things are not going the way I expect them to be, especially my experiments, I always remind myself of this quotation from an anonymous writer: “The moment you think about giving up, think of the reason why you held on so long.” So am I.
With the recent events that are happening around the world and if given the chance to travel forth in time, I would like to see: the total eradication of communicable and noncommunicable diseases; environmental restoration; a machine or invention that would create and maintain world peace and harmony.
Please cite this article in press as: H€afner S, Reservoir rats, Microbes and Infection (2014), http://dx.doi.org/10.1016/j.micinf.2014.09.002
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References Background - Leptospira, a genus of spirochetes, are thin, helical and mobile bacteria, comprising 14 pathogenic and 6 saprophytic species divided into over 300 serovars in total - They are present worldwide, especially in tropical regions, and infect virtually all mammals. The main animal reservoirs are rodents, domestic and production animals which carry the bacteria in their proximal renal tubules and shed them via urine - Pathogenic Leptospira can cause leptospirosis, whose symptoms range from subclinical to a severe infection with renal and hepatic failure, pulmonary distress and death (Weil's disease) - Infection occurs through direct contact with contaminated urine, water or soil. The bacteria enter the organism through small cuts, abrasions, mucosa or wet skin - Annually, between 500 000 and 1 million cases of leptospirosis are reported, case fatality ranges between 5 and 20% depending on the start of treatment and reaches 70% in the case of severe pulmonary hemorrhagic syndrome
In a nutshell - 40 clinical isolates from leptospirosis patients and Leptospira strains from wild rats were obtained in Luzon (Philippines) during the same period - All isolates are pathogenic Leptospira interrogans and belong mainly to the serogroups Pyrogenes, Bataviae and Gryppotyphosa and to serovars Manilae and Losbanos - Different Leptospira strains are predominant in different geographic regions - Identical serotypes were isolated from humans and rats in the same regions and from close time points - These results suggest that 3 predominant Leptospira groups are circulating since decades among rats in Luzon, the main source of transmission to humans
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Sophia H€afner* Q3 Univ. Paris Diderot, Sorbonne Paris Cite, UMR 7216 CNRS, Epigenetics and Cell Fate, 75013 Paris, France *UMR7216 Epigenetics and Cell Fate, Claire Rougeulle Team, Inactivation of the X chromosome, 35 Rue Helene Brion B^atiment Lamarck, Room 422, 75205 Paris Cedex 13, France. Tel.: þ33 (0)1 57 27 89 30. Q1 E-mail address: [email protected] 27 August 2014
Please cite this article in press as: H€afner S, Reservoir rats, Microbes and Infection (2014), http://dx.doi.org/10.1016/j.micinf.2014.09.002
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