Human-to-human transmission of leptospirosis: A global systematic review

Human-to-human transmission of leptospirosis: A global systematic review | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Human-to-human transmission of leptospirosis: A global systematic review Kaya Stollberg , Martin Richter , Ulrika Windahl , Olena Pyskun , Johanna F. Lindahl , View ORCID Profile Martin Wainaina doi: https://doi.org/10.1101/2025.09.02.25334635 Kaya Stollberg 1 Department of Biological Safety, German Federal Institute for Risk Assessment , Berlin, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site Martin Richter 1 Department of Biological Safety, German Federal Institute for Risk Assessment , Berlin, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ulrika Windahl 2 Department of Animal Health and Antimicrobial Strategies, Swedish Veterinary Agency , Uppsala, Sweden Find this author on Google Scholar Find this author on PubMed Search for this author on this site Olena Pyskun 3 Department of Organization of Scientific and International Work, State Scientific and Research Institute of Laboratory Diagnostics and Veterinary and Sanitary Expertise , Kyiv, Ukraine Find this author on Google Scholar Find this author on PubMed Search for this author on this site Johanna F. Lindahl 2 Department of Animal Health and Antimicrobial Strategies, Swedish Veterinary Agency , Uppsala, Sweden 4 Department of Medical Biochemistry and Microbiology, Zoonosis Science Center, Uppsala University , Uppsala, Sweden Find this author on Google Scholar Find this author on PubMed Search for this author on this site Martin Wainaina 1 Department of Biological Safety, German Federal Institute for Risk Assessment , Berlin, Germany Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Martin Wainaina For correspondence: markimwa{at}gmail.com Abstract Full Text Info/History Metrics Supplementary material Data/Code Preview PDF Abstract Background Leptospirosis is an important zoonotic disease that is widely distributed globally. Transmission typically occurs when a person is exposed to infected animals or contaminated environments through broken skin or mucous membranes, either direct or indirectly through occupational or recreational activities. Cases of human-to-human transmission of leptospirosis are reported non-systematically, and their public health implications are currently unknown. We therefore aimed to review cases of transmission between persons documented in medical literature. Methodology Systematic literature searches were performed on Embase, PubMed, Scopus, and Web of Science databases to identify relevant publications without any time or language restrictions. Possible modes of human-to-human transmission, namely, aerosols, blood transfusion, breastfeeding, coitus, direct mucosal contact, parturition, and tissue transplantation were considered during literature searches. Clinical data describing the index and secondary cases were extracted from the included publications. The strength of the evidence of transmission between persons was assessed using the following criteria: (i) laboratory-confirmed infections in both index and secondary cases (or laboratory-confirmed infections in foetuses/neonates only), (ii) a clear epidemiological link, (iii) temporal alignment of both infections, and (iv) biological plausibility of the transmission route. Results The search yielded 8257 results, of which 27 publications covering 34 suspected reports from years 1932-2022 were finally included. Twelve of these 34 cases met all 4 quality criteria (strong evidence), five fulfilled 3 criteria (moderate evidence), and seventeen satisfied 1-2 criteria (weak evidence). Strong (n=12), moderate (n=3) and weak (n=15) evidence was found for vertical transmission, occurring either transplacentally (n=28) or via lactation (n=2). Moderate and weak evidence for transmission via coitus (n=3), and weak evidence via blood transfusion (n=1) was found. No reports of human-to-human transmission through organ transplantation or aerosols was found. Conclusion Human-to-human leptospirosis transmission may play a role in leptospiral epidemiology, especially through vertical spread. Public health systems, especially in endemic and outbreak-prone areas, should remain vigilant of these less-reported modes of transmission to safeguard maternal and neonatal health, transfusion safety and sexual well-being. Robust One Health surveillance is required to improve detection and awareness, reduce underreporting and improve disease control for better public health outcomes. Author summary Leptospirosis is an important neglected tropical disease that is distributed globally. Transmission to humans is commonly through infected animals (zoonotic) or via contact with contaminated soil and water. Extreme weather events such as flooding and heavy rainfall caused by climate change can drive increased leptospirosis outbreaks. Human-to-human transmission is less reported and thought to be epidemiologically unimportant. However, with the increased number of cases globally, these rare transmission modes may become more noticeable in certain contexts. We therefore conducted this systematic literature review to investigate clinical evidence of transmission of leptospirosis between persons from global medical literature. We found 27 reports spanning 90 years that covered 34 suspected cases from 17 countries in all continents except Antarctica. Reports revealed strong evidence for vertical transmission of leptospirosis (mother to child), and a possibility of transmission via sexual intercourse and blood transfusion. Boosting surveillance and diagnostics in endemic areas is recommended to reduce disease burden and improve health outcomes. Introduction Leptospirosis is a globally important zoonotic disease with over one million reported human cases and 58,900 deaths annually [ 1 ]. It is caused by bacteria of the genus Leptospira ( L .) [ 2 ], which commonly infect animal hosts that can shed the pathogen in their urine. Small mammals, especially rats and other rodents, are important reservoirs for the pathogen. Infection in humans occurs when bacteria gain entry through interrupted skin or mucous membranes. This can occur through direct or indirect contact with infected animals or contaminated soil or water either occupationally (e.g., slaughterhouse workers, veterinarians, paddy field farmers), or recreationally (e.g., swimming, kayaking) [ 3 , 4 ]. Humans are accidental hosts and infections can vary from asymptomatic to acute, with incubation periods between 3 and 30 days. Fulminant forms that involve multiple organs, e.g., leptospirosis-associated pulmonary haemorrhage syndrome, meningitis/meningoencephalitis and Weil syndrome associated with jaundice, renal failure and myocarditis, can occur and often have high case fatality ratios [ 3 , 5 ]. Leptospirosis is often underreported due to inadequate diagnostic capacity in endemic areas, and has a clinical presentation that often lacks distinguishing features from other endemic acute febrile illnesses [ 6 , 7 ]. Diagnosis can be done directly using culture and PCR tests, or indirectly by detecting antibodies using serological tests such as the microscopic agglutination test (MAT) or ELISA [ 8 ]. There has been an increase in leptospirosis cases in various regions globally with time [ 9 , 10 ]. Extreme weather events such as flooding and heavy rainfall are thought to be important disease drivers, alongside population growth and urbanisation [ 11 ]. Human-to-human transmission is a less reported mode of leptospiral transmission that has historically been given little attention in leptospiral epidemiology. However, with the dynamic nature of these disease drivers and risk factors for human infection, it remains unclear whether these rare modes of transmission could play more important roles in disease transmission in the future. We therefore examined the literature to determine documented cases of transmission between persons and discuss the implications of the evidence to strengthen preparedness in the face of a changing disease landscape. Methods The literature search was conducted on 24 th September 2023 in leading databases which comprised Embase, PubMed, Scopus, and Web of Science. A review protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [ 12 ]. The review was registered on OSF registries [ 13 ]. The following search terms connected with Boolean operators were applied; (leptospira OR leptospirosis) AND (transfusion OR transplant OR vertical OR pregnan* OR human-to-human OR person-to-person OR sexual OR lactation OR aerosol OR mucosa) (S1 Data). No limitations on language or publication time were placed in the searches. The citations were imported into Endnote 21 (Thomson Reuters, Philadelphia, PA, USA) and duplicates were removed. All citations were screened using the titles and abstracts for relevance, and the DeepL translation tool [ 14 ] was used for non-English text. For initial screening, titles and abstracts were divided among all six authors, ensuring each record was independently reviewed by a second author. Discordant results were then resolved by MW. Two authors (KS and MW) conducted the data extraction from included publications. Peer-reviewed journal articles that reported possible transmission between humans were included. In cases of suspected vertical transmission but with no laboratory diagnosis, reports were excluded if it was clear that foetuses died from complications of maternal leptospirosis, or had positive outcomes with no indication of illness. Studies that reported leptospirosis in either index or secondary cases with the biological plausibility of transmission between persons were retained. Serological proof without accompanying clinical presentations consistent with leptospirosis were rejected as they were too speculative of potential transmission between people. The articles were screened independently by KS and MW and disagreements were discussed and resolved with co-authors. Quality assessment was done according to a tailor-made tool designed to assess the strength of evidence for human-to-human transmission ( Table 1 ) and summarised using the robvis tool [ 15 ]. View this table: View inline View popup Download powerpoint Table 1. A custom-made quality assessment tool used to gauge the strength of evidence for human-to-human transmission of leptospirosis Results Database search results A total of 8257 references were identified in the primary search, with Scopus giving 6085 hits, and Embase (n=996), PubMed (n=779), and Web of Science (n=397) following in decreasing order. The removal of duplicates from the combined search results gave 6326 remaining references which were screened for relevance by title and abstract. Ultimately, 27 studies comprising 34 reports were considered relevant for this review ( Fig 1 ). Download figure Open in new tab Fig 1. The study selection process utilised to identify relevant literature on human-to-human transmission of leptospirosis from leading electronic databases Study characteristics The studies were published between 1932 and 2022, with most being in English (17) and the rest in French (3), German (3), Chinese (1), Dutch (1), Hungarian (1) and Spanish (1). Most publications were from Europe (10), followed by Asia (8), South America (4), Africa (2), North America (2) and Oceania (1) in decreasing order. Lastly, most publications were case reports/series (22), while cross-sectional (4) and case-control (1) studies were fewer (S2 Data). Quality assessment of evidence We assessed the strength of the evidence for the transmission of leptospires between persons and revealed that overall, 12 reports (35.3%) had strong evidence of transmission, and 5 (14.7%) had moderate and 17 (50.0%) showed weak evidence ( Fig 2 ). Download figure Open in new tab Fig 2. Assessment scores of the strength of evidence for transmission between persons based on four criteria from 34 reports. A summary bar chart is also presented with the results categorised into weak, moderate and strong evidence of transmission. Vertical transmission Transmission from mother to child was indicated in 30 studies, among which 12 studies showed strong, 3 had moderate and 15 demonstrated weak evidence of transmission ( Table 2 , Fig 2 ). Most cases in the infant were acquired in utero , resulting in stillbirths/intrauterine death, and some cases were carried to term and resulted in neonatal death, or healthy/mildly affected neonates ( Fig 3 ). Two cases were reportedly transmitted via breastfeeding, and were backed by strong evidence where leptospires were detected from both maternal and neonatal samples, and weak evidence where leptospires were detected in breastmilk but without neonatal testing. Sepsis was a commonly reported clinical manifestation in the affected neonates. Two studies lacked testing from maternal samples ( Table 2 ), but Leptospira IgM antibodies and DNA were found in the neonates, indicating strong evidence of vertical transmission. View this table: View inline View popup Table 2. A summary of study characteristics of publications investigating human-to-human transmission of leptospirosis globally. Studies are presented according to the mode of transmission and evidence grade determined. Download figure Open in new tab Fig 3. Heatmaps of clinical findings in infants and mothers with disease outcomes of cases of vertical leptospiral transmission with strong evidence. Additionally, maternal clinical findings were diverse and resulted in maternal recovery with foetal death or recovery ( Fig 3 ). Fever, jaundice, myalgia and abdominal pain were common clinical presentations in infected mothers. Laboratory confirmation was done using the MAT, ELISA, PCR, culture, immunohistochemistry tests, on maternal, infant, or paired maternal-neonate samples ( Table 2 ). Where no laboratory testing was done on either index or secondary cases, clinical presentations or autopsy findings were relied upon to suspect transmission. Putative risk factors associated with maternal exposure were occupational exposure to infected livestock through veterinary practice and farming, contact with infected pets, travel to endemic regions, farming in paddy fields, living near water/lowlands, exposure to rodent reservoirs, and swimming (S2 data). Sexual transmission Three dated case reports were found reporting sexual transmission of leptospirosis between heterosexual partners, and the evidence was of moderate to weak strength ( Fig 2 ). Recreational exposure was a common risk factor in the index cases, and diagnosis was performed serologically using MAT and ELISA. Therefore, while sexual transmission was posited in the three reports, it was not proven by microbiological isolation of sexual fluids, bacterial typing beyond serovar identification, and robust contact tracing to ensure ruling out alternative sources of infection. Blood donation A cross-sectional study was found demonstrating pathogenic/intermediate leptospires via 16rRNA ( rrs gene) PCR from 8/42 (19%) healthy blood donors in Cajamarca, Peru ( Table 2 ). The area was described as rural with farming and exposure to rodent carriers as possible risk factors, and donors who were at risk of environmental and occupational exposure were included in the study, and thus not reflective of all blood donors. No transmission was established in blood recipients, but the demonstration of DNA in asymptomatic donors suggest subclinical carriage of the bacteria. The evidence for transmission was graded as weak ( Table 2 ). Other transmission modes No evidence was found for transmission between persons via aerosols and organ transplant. Discussion We reviewed global literature spanning more than 90 years to investigate evidence of leptospirosis transmission between humans, a less reported route. Strong evidence was found for transmission from mother to child either via the placenta or breastfeeding. Moderate to weak evidence for sexual transmission was observed and weak evidence was found for transmission through blood transfusion. We discuss the implications of these biologically plausible routes to current public health policy and call for future studies with stronger evidence to better understand the risk of transmission and the impacts on disease prevention and control. Entry of Leptospira during infection typically occurs through the interrupted skin and mucous membranes. Direct contact with the biological fluids of an infected animal such as urine, or indirect exposure to contaminated soil or water are responsible for most cases. Transmission between persons is biologically plausible via blood transfusion, tissue/organ transplant, vertically (during pregnancy or lactation), through sexual contact, through aerosols/droplets. However, sustained human-to-human transmission of zoonoses depends on the transmission route (e.g., airborne, contact, faecal-oral, and vector-borne transmission), host, pathogen, and environment [ 43 , 44 ]. Additionally, characteristics of the index and secondary persons, (e.g., immune function, infectious dose), and transmission amplifiers that act between the index and secondary cases (e.g., climate, human behaviour, cultural variation) are important [ 44 ]. Vertical transmission Vertical transmission generally refers to the transfer of an aetiological agent from either parent to offspring, occurring mostly via the mother across the placenta ( in utero ), during childbirth (intrapartum), or after birth (postpartum) by breast-feeding [ 45 ]. In our case, we observed mother-to-child transmission of leptospirosis occurring in utero (transplacentally) in most instances, with one case occurring via lactation with strong evidence. Vertical transmission has been demonstrated in some domestic animals, suggesting its likely importance in human hosts [ 46 – 50 ]. Most publications were case reports or case series, highlighting the case-based nature of this transmission mode of leptospirosis, and need for stronger evidence through superior study designs with more statistical power [ 51 ]. Still births and intrauterine deaths, congenital abnormalities (e.g., hypotrophy), low birth weight, and small for gestational age were observed in neonates of leptospirosis-positive mothers. Fever, anaemia, jaundice and myalgia, as well as severe outcomes such as maternal mortality and pregnancy loss were common features of maternal leptospirosis, and were consistent with a recent comprehensive review of leptospirosis during pregnancy [ 52 ] where cases were also acquired from environmental and zoonotic sources. Proving leptospirosis transmission during human gestation is not always conclusive, especially when there is no foetal/neonatal testing, a lack of obvious adverse foetal outcomes such as illness or death [ 53 – 61 ], or foetal death occurred from maternal complications from leptospirosis or otherwise [ 62 – 64 ]. Therefore, it is likely our review introduced a selection bias by excluding unclear cases of vertical transmission which may underrepresent the real-world limitations of leptospirosis diagnostics. Additionally, histological proof of leptospires after foetal death was not always successful due to tissue maceration and likely death of leptospires, which can render test results inconclusive [ 26 , 27 ]. However, proper treatment and patient management is recommended as vertical transmission is likely unreported, especially in endemic areas, and a likely source of reporting bias in this review. Lactation has been implicated as a possible transmission route in this review [ 38 ], a phenomenon observed in animal models too [ 65 ]. The Chinese Medical Association has recommended the pasteurisation of breastmilk from infected mothers during treatment as it remains more beneficial to the infant than formula milk. Clinical suspicion of leptospirosis in endemic areas is critical, and boosting surveillance and diagnostics in perinatal care is important in reducing disease burden which is likely underreported. Sexual transmission Diseases are sexually transmissible when the aetiological agent can be passed among persons via bodily fluids such as blood, semen and vaginal fluids during oral, anal, or genital sex with an infected partner [ 66 ]. Additionally, categorising diseases as Sexually Transmissible Infections (STIs) requires sexual contact as the primary mode of transmission [ 66 ]. Epidemiological comparisons of disease rates by sex, and molecular cluster analyses among sexually-linked samples can help recognise emerging STIs [ 67 ]. The three studies positing sexual transmission of leptospirosis [ 39 – 41 ] were published between 1932-1988, when identifying leptospires largely relied on serology and culture methods, and no PCR assays were available yet [ 68 ]. Consequently, no leptospires were demonstrated in the patients’ bodily fluids associated with sexual transmission, and only circumstantial evidence was provided, e.g., acute disease after sexual contact with partner with known exposure to partner with no discernible risk factor. This moderate evidence makes us conclude that sexual transmission of leptospirosis is currently not well proven. Studies are required to demonstrate leptospires and their survival in semen, vaginal fluids, genital and anal swabs, etc. from infected persons, and molecular analyses showing the phylogenetic relationship between linked cases are required to raise the understanding on this transmission mode. Providing detailed exposure history through contact tracing could help track cases, but using this approach is limited in STIs due to its associated intrusive nature and stigmatisation [ 69 ]. Ruling out other sources of exposure by animal and environmental sampling is critical in strengthening evidence of sexual transmission of leptospirosis. However, venereal leptospiral transmission has been observed in various domestic animals and murine models [ 48 , 70 – 73 ], and is therefore biologically plausible in humans. Transfusion-mediated transmission Various emerging and re-emerging pathogens that are not part of standard screening pose a risk to transfusion medicine [ 74 ]. The included study demonstrated leptospiral DNA in donated blood from high-risk donors in an endemic area in Peru, offering credible evidence of potential transmission [ 42 ]. Several studies demonstrating past infections in blood donors using serology also exist, showing the potential risk of transmission via blood transfusion [ 75 – 78 ]. Bacteriaemia is often associated with the initial leptospiraemic phase during the first 8 days of fever [ 3 ], but PCR positivity in asymptomatic blood donors suggest subclinical bacterial carriage, the risk of transmission of which is not clear. Eligibility criteria for blood donation that filter out febrile syndrome would do well in curbing transmission via transfusion of blood and blood products. However, blood donor eligibility varies substantially across nations, and criteria that are evidence-based are recommended [ 79 ]. Pathogen reduction technologies for donated blood such as irradiation could also play a role in reducing transmission of emerging pathogens [ 74 ]. Artificial oxygen carriers (artificial blood) are novel approaches that may help prevent transmission of emerging transfusion-mediated infections, especially in patients requiring repeat transfusions such as sickle cell anaemia and thalassemia. However, these therapies are not yet approved for use in several countries due to high toxicities [ 80 , 81 ]. Organ transplant-mediated transmission No reports of transmission via organ transplants were found. However, solid organ transplant guidelines in the endemic south Asian region have recommended leptospirosis screening in organ donors and recipients with significant epidemiological risk or exposure due to the possibility of transplant-mediated leptospirosis [ 82 ]. Additionally, donation should be deferred to 3 months after recovery, and treatment in recipients be done with as in immunosuppressed patients [ 82 ]. Case reports of liver and kidney transplant recipients who acquired leptospirosis due to immunosuppressed states have been reported, and the infections were attributed to contaminated environments and not donor-derived [ 83 , 84 ]. Aerosol transmission No reports of airborne transmission were found. Pulmonary involvement in leptospirosis is well documented, and characterised by chest pain, cough, dyspnoea and haemoptysis. Acute respiratory distress syndrome (ARDS) and severe pulmonary haemorrhagic syndrome (SPHS) are severe forms of leptospirosis that can lead to respiratory insufficiency and death [ 85 , 86 ]. Leptospires have also been detected in respiratory samples of patients with sudden worsening of chronic obstructive pulmonary disease (COPD) by amplicon sequencing of endotracheal aspirates [ 87 ]. Hamster models have shown that leptospires have predilection for lungs as evidenced by pulmonary lesions, haemorrhage, and elevated inflammation markers after experimental inoculation [ 88 ]. Consequently, the possibility of transmission via droplets from ill patients to surrounding persons cannot be ruled out. Conclusion We provide a comprehensive synthesis of reported cases of human-to-human transmission of leptospirosis. Despite exposure to contaminated environments and infected animals remaining the most important ways of acquiring leptospirosis in humans, credible evidence of vertical transmission, both transplacentally and via breastfeeding, was found. Evidence for sexual transmission was moderate to weak. Possible risk of transmission through blood-transfusion was found (weak evidence), and no reports of transmission via solid organ transplantation and aerosols between persons was found, despite being biologically plausible. These findings demonstrate the need to consider leptospirosis in maternal and neonatal healthcare, especially in endemic and outbreak-prone areas. As risk factors for exposure to the index cases of infections found in this review were zoonotic or environmental, robust surveillance systems that utilise integrated One Health approaches are required. Applying molecular diagnostics to determine the traceability of cases will help elucidate cases of transmission of leptospirosis between persons and better understand the risks posed to human health, especially in transplant and transfusion medicine, sexual wellbeing, and maternal and neonatal health. Data Availability All data produced in the present work are contained in the manuscript Declarations Ethical approval Not applicable Data availability All data related to this study are included in this published article and its supplementary information files. Competing interests The authors declare no conflicts of interest. Funding This work was supported by the German Federal Institute for Risk Assessment (BfR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author contributions Kaya Stollberg (Methodology, Formal analysis, Validation, Investigation, Data curation, Writing - Original draft, Writing - Reviewing); Martin Richter (Investigation, Writing - Reviewing); Olena Pyskun (Investigation, Writing - Reviewing); Ulrika Windahl (Investigation, Validation, Writing - Reviewing); Johanna F. Lindahl (Methodology, Investigation, Validation, Writing - Reviewing); Martin Wainaina (Conceptualisation, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Visualisation, Writing - original draft, Writing - review & editing) Supporting information legends S1 Data: Database search terms used to find literature on leading electronic databases. The PRISMA checklist is also given presented. S2 Data: A summary of the data extracted from the included studies. Acknowledgements We thank Dr. Jiaxin Ling (Uppsala University) for translating the traditional Chinese text. We also thank the authors of the included reports. References 1. ↵ Costa F , Hagan JE , Calcagno J , Kane M , Torgerson P , Martinez-Silveira MS , et al. Global morbidity and mortality of leptospirosis: A systematic review . PLoS Neglected Tropical Diseases . 2015 ; 9 ( 9 ): e0003898 . doi: 10.1371/journal.pntd.0003898 . OpenUrl CrossRef PubMed 2. ↵ Jorgensen JH , Carroll KC , Funke G , Pfaller MA , Landry ML , Richter SS , et al. Levett PN . Leptospira . In: Jorgensen JH , Carroll KC , Funke G , Pfaller MA , Landry ML , Richter SS , et al. , editors. Manual of Clinical Microbiology. 1 . Washington DC : ASM Press ; 2015 . p. 1028 – 36 . 3. ↵ Adler B Haake DA , Levett PN . Leptospirosis in humans . In: Adler B , editor. Leptospira and Leptospirosis. Current Topics in Microbiology and Immunology (CT MICROBIOLOGY, volume 387) Berlin, Heidelberg : Springer Berlin Heidelberg ; 2015 . p. 65 – 97 . 4. ↵ Baharom M , Ahmad N , Hod R , Ja’afar MH , Arsad FS , Tangang F , et al. Environmental and occupational factors associated with leptospirosis: A systematic review . Heliyon . 2024 ; 10 ( 1 ): e23473 . doi: 10.1016/j.heliyon.2023.e23473 . OpenUrl CrossRef 5. ↵ Sykes JE , Haake DA , Gamage CD , Mills WZ , Nally JE . A global one health perspective on leptospirosis in humans and animals . Journal of the American Veterinary Medical Association . 2022 ; 260 ( 13 ): 1589 – 96 . doi: 10.2460/javma.22.06.0258 . OpenUrl CrossRef PubMed 6. ↵ Wainaina M , Vey da Silva DA , Dohoo I , Mayer-Scholl A , Roesel K , Hofreuter D , et al. A systematic review and meta-analysis of the aetiological agents of non-malarial febrile illnesses in Africa . PLoS Neglected Tropical Diseases . 2022 ; 16 ( 1 ): e0010144 . doi: 10.1371/journal.pntd.0010144 . OpenUrl CrossRef 7. ↵ Wainaina M , Wasonga J , Cook EAJ . Epidemiology of human and animal leptospirosis in Kenya: A systematic review and meta-analysis of disease occurrence, serogroup diversity and risk factors . PLoS Neglected Tropical Diseases . 2024 ; 18 ( 9 ): e0012527 . doi: 10.1371/journal.pntd.0012527 . OpenUrl CrossRef 8. ↵ WOAH . Leptospirosis In: World_Organisation_for_Animal_Health, editor. Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. 13 ed: World Organisation for Animal Health ; 2021 . 9. ↵ Beauté J , Innocenti F , Aristodimou A , Špačková M , Eves C , Kerbo N , et al. Epidemiology of reported cases of leptospirosis in the EU/EEA, 2010 to 2021 . Eurosurveillance . 2024 ; 29 ( 7 ): 2300266 . doi: 10.2807/1560-7917.ES.2024.29.7.2300266 . OpenUrl CrossRef PubMed 10. ↵ Munoz-Zanzi C , Groene E , Morawski BM , Bonner K , Costa F , Bertherat E , et al. A systematic literature review of leptospirosis outbreaks worldwide, 1970–2012 . Revista Panamericana de Salud Pública . 2020 ; 44 : e78 . doi: 10.26633/RPSP.2020.78 . OpenUrl CrossRef 11. ↵ Lau CL , Smythe LD , Craig SB , Weinstein P. Climate change, flooding, urbanisation and leptospirosis: fuelling the fire? Transactions of The Royal Society of Tropical Medicine and Hygiene . 2010 ; 104 ( 10 ): 631 – 8 . doi: 10.1016/j.trstmh.2010.07.002 . OpenUrl CrossRef PubMed 12. ↵ Page MJ , McKenzie JE , Bossuyt PM , Boutron I , Hoffmann TC , Mulrow CD , et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews . BMJ . 2021 ; 372 . doi: 10.1136/bmj.n71 . OpenUrl FREE Full Text 13. ↵ Wainaina M. Human-to-human transmission of leptospirosis: A scoping review . OSF Registries . 2024 . doi: 10.17605/OSF.IO/3RJCK . OpenUrl CrossRef 14. ↵ DeepL . DeepL Translator 2024 [cited 2024]. Available from: https://www.deepl.com/en/translator . 15. ↵ McGuinness LA , Higgins JPT . Risk-of-bias VISualization (robvis): an R package and Shiny web app for visualizing risk-of-bias assessments . Research synthesis methods . 2021 ; 12 ( 1 ): 55 – 61 . doi: 10.1002/jrsm.1411 . OpenUrl CrossRef PubMed 16. Carles G , Montoya E , Joly F , Peneau C. [Leptospirosis and pregnancy . Eleven cases in French Guyana]. J Gynecol Obstet Biol Reprod (Paris) . 1995 ; 24 ( 4 ): 418 - 21 . PubMed Central PMCID: PMC7650320 . OpenUrl PubMed 17. Chung H-L , Ts’ao W-C , Mo Pe-s , Yen C. Transplacental or congenital infection of leptospirosis: clinical and experimental observations . Chinese Medical Journal . 1963 ; 82 ( 12 ): 777 - 82 . PubMed Central PMCID: PMC14100807 . OpenUrl PubMed 18. Cramer H , Wadulla H. Abortus bei Leptospirosis canicola . Archiv für Gynäkologie . 1950 ; 177 ( 2 ): 167 – 77 . doi: 10.1007/BF00981250 . OpenUrl CrossRef 19. Faine S , Valentine R. Leptospirosis hardjo in pregnancy . Medical Journal of Australia . 1984 ; 140 ( 5 ): 311 – 2 . doi: 10.5694/j.1326-5377.1984.tb104077.x . OpenUrl CrossRef PubMed 20. Gsell HO , Jr. , Olafsson A , Sonnabend W , Breer C , Bachmann C. [Intrauterine leptospirosis pomona . 1st reported case of an intrauterine transmitted and cured leptospirosis]. Deutsche Medizinische Wochenschrift . 1971 ; 96 ( 31 ): 1263 – 8 . doi: 10.1055/s-0028-1110120 . PubMed Central PMCID: PMC4934402 . OpenUrl CrossRef 21. Hope D , Businge S , Kyoyagala S , Bazira J. Prevalence of anti-leptospiral IgM and detection of pathogenic Leptospira species DNA in neonates presenting with clinical sepsis in Southwestern Uganda . European Journal of Medical Research . 2022 ; 27 ( 1 ): 268 . doi: 10.1186/s40001-022-00902-w . OpenUrl CrossRef PubMed 22. Lindsay S , Luke IW . Fatal leptospirosis (Weil’s disease) in a newborn infant: Case of intrauterine fetal infection with report of an autopsy . The Journal of Pediatrics . 1949 ; 34 ( 1 ): 90 – 4 . doi: 10.1016/S0022-3476(49)80206-X . OpenUrl CrossRef PubMed 23. Schiff SJ , Kiwanuka J , Riggio G , Nguyen L , Mu K , Sproul E , et al. Separating putative pathogens from background contamination with principal orthogonal decomposition: Evidence for Leptospira in the Ugandan neonatal septisome . Front Med (Lausanne) . 2016 ; 3 : 22 . Epub 20160613. doi: 10.3389/fmed.2016.00022 . PubMed PMID: 27379237 ; PubMed Central PMCID: PMCPMC4904006 . OpenUrl CrossRef PubMed 24. Teng C. Fetus with leptospirosis infection during pregnancy: a case report . Zhong Neike Z . 1960 ; 8 . 25. Topciu V , Manu E , Strubert L , Duma G , Levin S. Voie transplacentaire dans un cas de leptospirose humaine . Gynecol Obstet (Paris) . 1966 ; 65 : 617 – 20 . OpenUrl 26. ↵ Coghlan JD , Bain AD . Leptospirosis in human pregnancy followed by death of the foetus . British Medical Journal . 1969 ; 1 ( 5638 ): 228 – 30 . doi: 10.1136/bmj.1.5638.228 . OpenUrl Abstract / FREE Full Text 27. ↵ Colette C. [Fatal leptospirosis during pregnancy with severe jaundice] . Bull Fed Soc Gynecol Obstet Lang Fr . 1962 ; 14 : 437 – 40 . PubMed Central PMCID: PMC14022281 . OpenUrl PubMed 28. Gainder S , Singla R , Dhaliwal L , Suri V. Leptospirosis as a cause of intrauterine fetal demise: short report of rare presentation . Archives of Gynecology and Obstetrics . 2010 ; 281 ( 6 ): 1061 – 3 . doi: 10.1007/s00404-009-1266-y . OpenUrl CrossRef PubMed 29. Aker N , B. Je, M. JA, and Pasvol G. Leptospirosis in pregnancy: An unusual and relatively unrecognised cause of intrauterine death in man . Journal of Obstetrics and Gynaecology . 1996 ; 16 ( 3 ): 163 – 5 . doi: 10.3109/01443619609004093 . OpenUrl CrossRef 30. Bleier W , Lechtken F. [Leptospirosis canicola in man as a cause of spontaneous abortion] . Geburtshilfe und Frauenheilkunde . 1951 ; 11 ( 6 ): 538 - 44 . PubMed Central PMCID: PMC14849774 . OpenUrl PubMed 31. Cárdenas-Marrufo MF , Vado-Solis I , Peniche-Lara GF , Perez-Osorio C , Correa-Segura J. A cross sectional study of leptospirosis and fetal death in Yucatan, Mexico . Colombia Medica . 2016 ; 47 ( 1 ): 11 – 4 . doi: 10.25100/cm.v47i1.1975 . OpenUrl CrossRef PubMed 32. Rahimi R , Omar E , Soh TST , Nawi SFAM , Noor SM . Leptospirosis in pregnancy: A lesson in subtlety . The Malaysian Journal of Pathology . 2018 ; 40 ( 2 ): 169 - 73 . PubMed Central PMCID: PMC30173235 . OpenUrl PubMed 33. Trujillo Salgado JE , Martínez Torres A , Mármol Sóñora A. Leptospirosis, enfermedad de Weil y falla multiorgánica: Informe de 1 caso . Revista Cubana de Medicina . 1996 ; 35 ( 3 ): 212 – 5 . OpenUrl 34. Sharma KK , Madhvilatha P , Kalawat U , Sivakumar V. Leptospirosis-induced still birth and postpartum sepsis . Indian Journal of Pathology and Microbiology . 2011 ; 54 ( 2 ). doi: 10.4103/0377-4929.81617 . OpenUrl CrossRef PubMed 35. Shubhra , Yadav A , Goila AK , Kaur R. Management of leptospirosis in postpartum period in ICU . Saudi J Anaesth . 2022 ; 16 ( 1 ): 130 - 1 . Epub 20220104. doi: 10.4103/sja.sja_556_21 . PubMed PMID: 35261607 ; PubMed Central PMCID: PMCPMC8846237 . OpenUrl CrossRef PubMed 36. Suzuki K , Nakamura S , Watanabe H. A fatal case of Leptospira autumnalis infection in Lao PDR . Southeast Asian J Trop Med Public Health . 1997 ; 28 ( 2 ): 436 - 7 . PubMed Central PMCID: PMC9444037 . OpenUrl PubMed 37. Udawat M , Sumathi G , Nithyalakshmi J , Krishnan M. Clinical impact of leptospirosis on pregnancy: an analysis . J Evol Med Dent Sci . 2014 ; 3 ( 58 ): 13071 – 8 . doi: 10.14260/jemds/2014/3738 . OpenUrl CrossRef 38. ↵ Bolin CA , Koellner P. Human-to-human transmission of Leptospira interrogans by milk . The Journal of Infectious Diseases . 1988 ; 158 ( 1 ): 246 – 7 . doi: 10.1093/infdis/158.1.246 . OpenUrl CrossRef PubMed Web of Science 39. ↵ Doeleman F. Ziekte van Weil, rechstreeks overgebracht van mensch op mensch . Ned Tijdschr Geneeskd . 1932 ; 76 : 5057 – 8 . OpenUrl 40. Szalka A , Binder L. [A rare case of human-to-human infection of leptospirosis] . Orvosi Hetilap . 1974 ; 115 ( 26 ): 1531 - 2 . PubMed Central PMCID: PMC4840706 . OpenUrl PubMed 41. ↵ Harrison NA , Fitzgerald WR . Leptospirosis — can it be a sexually transmitted disease? Postgraduate Medical Journal . 1988 ; 64 ( 748 ): 163 – 4 . doi: 10.1136/pgmj.64.748.163 . OpenUrl Abstract / FREE Full Text 42. ↵ Pons MJ , Urteaga N , Alva-Urcia C , Lovato P , Silva J , Ruiz J , et al. Infectious agents, Leptospira spp . and Bartonella spp., in blood donors from Cajamarca, Peru. Blood Transfusion . 2016 ; 14 ( 6 ): 504 – 8 . Epub 20151201. doi: 10.2450/2015.0081-15 . PubMed PMID: 26674831 ; PubMed Central PMCID: PMCPMC5111371 . OpenUrl CrossRef PubMed 43. ↵ Richard M , Knauf S , Lawrence P , Mather AE , Munster VJ , Müller MA , et al. Factors determining human-to-human transmissibility of zoonotic pathogens via contact . Current Opinion in Virology . 2017 ; 22 : 7 – 12 . doi: 10.1016/j.coviro.2016.11.004 . OpenUrl CrossRef PubMed 44. ↵ de Graaf M , Beck R , Caccio SM , Duim B , Fraaij PLA , Le Guyader FS , et al. Sustained fecal-oral human-to-human transmission following a zoonotic event . Current Opinion in Virology . 2017 ; 22 : 1 – 6 . doi: 10.1016/j.coviro.2016.11.001 . OpenUrl CrossRef PubMed 45. ↵ Cason J , Mant CA . High-risk mucosal human papillomavirus infections during infancy & childhood . Journal of Clinical Virology . 2005 ; 32 : 52 – 8 . doi: 10.1016/j.jcv.2004.12.007 . OpenUrl CrossRef 46. ↵ Nogueira DB , da Costa FTR , de Sousa Bezerra C , Soares RR , da Costa Barnabé NN , Falcão BMR , et al. Leptospira sp. vertical transmission in ewes maintained in semiarid conditions . Animal Reproduction Science . 2020 ; 219 : 106530 . doi: 10.1016/j.anireprosci.2020.106530 . OpenUrl CrossRef PubMed 47. Magajevski FS , Gírio RJS , Meirelles RB . Pesquisa de Leptospira em fetos de vacas abatidas no estado de São Paulo, Brasil . Arquivos do Instituto Biológico . 2007 ; 74 ( 2 ): 67 – 72 . OpenUrl 48. ↵ Cilia G , Bertelloni F , Piredda I , Ponti MN , Turchi B , Cantile C , et al. Presence of pathogenic Leptospira spp . in the reproductive system and fetuses of wild boars (Sus scrofa) in Italy. PLoS Neglected Tropical Diseases . 2021 ; 14 ( 12 ): e0008982 . doi: 10.1371/journal.pntd.0008982 . OpenUrl CrossRef 49. Terayama Y , Maeda M , Hata Y , Kawasaki Y , Koizumi N. A probable cluster of premature birth and stillbirth caused by Leptospira interrogans serogroup Hebdomadis in an integrated swine farm in Nagasaki Prefecture, Japan . Journal of Veterinary Medical Science . 2024 ; 86 ( 10 ): 1040 – 4 . doi: 10.1292/jvms.24-0215 . OpenUrl CrossRef PubMed 50. ↵ da Costa Barnabé NN , Soares RR , Barros DK , Araújo Júnior JP , Malossi CD , Rodrigues Silva ML , et al. The role of transplacental infection in Leptospira spp. epidemiology in cattle in Caatinga Biome, Brazil . Microorganisms [Internet] . 2024 ; 12 ( 6 ). 51. ↵ Murad MH , Asi N , Alsawas M , Alahdab F. New evidence pyramid . Evidence Based Medicine . 2016 ; 21 ( 4 ): 125 . doi: 10.1136/ebmed-2016-110401 . OpenUrl Abstract / FREE Full Text 52. ↵ Selvarajah S , Ran S , Roberts NW , Nair M. Leptospirosis in pregnancy: A systematic review . PLoS Neglected Tropical Diseases . 2021 ; 15 ( 9 ): e0009747 . doi: 10.1371/journal.pntd.0009747 . OpenUrl CrossRef PubMed 53. ↵ Rathnaweera R. A death of a pregnant mother following leptospirosis . Medico-Legal Journal of Sri Lanka . 2015 ; 1 ( 3 ). doi: 10.4038/mljsl.v1i3.7303 . OpenUrl CrossRef 54. Shaked Y , Shpilberg O , Samra D , Samra Y. Leptospirosis in pregnancy and its effect on the fetus: Case report and review . Clinical Infectious Diseases . 1993 ; 17 ( 2 ): 241 – 3 . doi: 10.1093/clinids/17.2.241 . OpenUrl CrossRef PubMed 55. Dadhwal V , Bahadur A , Deka D. Leptospirosis as a cause of fever in pregnancy . International Journal of Gynecology & Obstetrics . 2007 ; 99 ( 3 ): 252 – 3 . doi: 10.1016/j.ijgo.2007.05.036 . OpenUrl CrossRef PubMed 56. Patel T , Pajai S , Patel N , Patel P. Leptospirosis manifesting as HELLP (Hemolysis, Elevated Liver Enzymes, and Low Platelets) Syndrome: A rare case of leptospirosis during pregnancy . Cureus . 2023 ; 15 ( 5 ): e39083. Epub 20230516. doi: 10.7759/cureus.39083 . PubMed PMID: 37332452 ; PubMed Central PMCID: PMCPMC10269396 . OpenUrl CrossRef PubMed 57. Tayade S , Madaan S , Kumar S , Talwar D , Chadha A. Tropical infections induced fulminant hepatitis in peripartum managed successfully: Tales of fate . Cureus . 2022 ; 14 ( 2 ): e22223 . Epub 20220215. doi: 10.7759/cureus.22223 . PubMed PMID: 35340480 ; PubMed Central PMCID: PMCPMC8928236 . OpenUrl CrossRef PubMed 58. Koe SL , Tan KT , Tan TC . Leptospirosis in pregnancy with pathological fetal cardiotocography changes . Singapore Medical Journal . 2014 ; 55 ( 2 ): e20 – 4 . doi: http://dx.doi.org/10.11622/smedj.2013194 . PubMed PMID : pmcid: 24712035 ; PubMed Central PMCID: PMCPMC4291937 . OpenUrl CrossRef PubMed Web of Science 59. Hicham S , Ihsane M , Abderahimel B , Brahim B , Labib S , Mustapha H , et al. Multivisceral organ failure related to leptospirosis in pregnant patient . Indian J Crit Care Med . 2013 ; 17 ( 1 ): 43 – 5 . doi: 10.4103/0972-5229.112143 . PubMed PMID: 23833476 ; PubMed Central PMCID: PMCPMC3701397 . OpenUrl CrossRef PubMed 60. Chedraui PA , San Miguel G. A case of leptospirosis and pregnancy . Archives of Gynecology and Obstetrics . 2003 ; 269 ( 1 ): 53 – 4 . doi: 10.1007/s00404-002-0415-3 . OpenUrl CrossRef PubMed 61. ↵ Gaspari R , Annetta MG , Cavaliere F , Pallavicini F , Grillo R , Conti G , et al. Unusual presentation of leptospirosis in the late stage of pregnancy . Minerva Anestesiologica . 2007 ; 73 ( 7-8 ): 429 - 32 . PubMed Central PMCID: PMC17637589 . OpenUrl PubMed Web of Science 62. ↵ Baytur YB , Cabuk M , Koyuncu FM , Lacin S , Ceylan C , Kandiloglu AR . Weil’s syndrome in pregnancy . European Journal of Obstetrics & Gynecology and Reproductive Biology . 2005 ; 119 ( 1 ): 132 – 3 . doi: 10.1016/j.ejogrb.2004.06.021 . OpenUrl CrossRef PubMed 63. Sutter T , Fehr T , Blume C , Kajdi M-E. Stillbirth and fulminant postpartum haemolysis: COVID-19 or leptospirosis or both? BMJ Case Reports . 2023 ; 16 ( 6 ): e252620 . doi: 10.1136/bcr-2022-252620 . OpenUrl Abstract / FREE Full Text 64. ↵ Tramoni G , Clément HJ , Lopez F , Viale JP . [An unusual case of post partum haemorrhage: leptospirosis infection] . Annales Françaises d’Anesthésie et de Réanimation . 2003 ; 22 ( 4 ): 363 – 5 . doi: 10.1016/S0750-7658(03)00061-3 . OpenUrl CrossRef PubMed 65. ↵ De Oliveira D , Figueira CP , Zhan L , Pertile AC , Pedra GG , GusmÃO IM , et al. Leptospira in breast tissue and milk of urban Norway rats (Rattus norvegicus) . Epidemiology and Infection . 2016 ; 144 ( 11 ): 2420 - 9 . Epub 2016/03/28. doi: 10.1017/S0950268816000637 . OpenUrl CrossRef 66. ↵ Allan-Blitz L-T , Gandhi M , Adamson P , Park I , Bolan G , Klausner JD . A position statement on Mpox as a sexually transmitted disease . Clinical Infectious Diseases . 2023 ; 76 ( 8 ): 1508 – 12 . doi: 10.1093/cid/ciac960 . OpenUrl CrossRef PubMed 67. ↵ Bernstein K , Bowen VB , Kim CR , Counotte MJ , Kirkcaldy RD , Kara E , et al. Re-emerging and newly recognized sexually transmitted infections: Can prior experiences shed light on future identification and control? PLoS Medicine . 2017 ; 14 ( 12 ): e1002474 . doi: 10.1371/journal.pmed.1002474 . OpenUrl CrossRef 68. ↵ Van Eys GJ , Gravekamp C , Gerritsen MJ , Quint W , Cornelissen MT , Schegget JT , et al. Detection of leptospires in urine by polymerase chain reaction . Journal of Clinical Microbiology . 1989 ; 27 ( 10 ): 2258 – 62 . doi: 10.1128/jcm.27.10.2258-2262.1989 . OpenUrl Abstract / FREE Full Text 69. ↵ Brandt AM . The history of contact tracing and the future of public health . American Journal of Public Health . 2022 ; 112 ( 8 ): 1097 – 9 . doi: 10.2105/AJPH.2022.306949 . OpenUrl CrossRef PubMed 70. ↵ Soares RR , da Costa Barnabé NN , Júnior JPA , Malossi CD , Ullmann LS , da Costa DF , et al. Investigation of the presence of Leptospira interrogans in urinary and genital tracts of male goats raised in the semiarid region of Brazil . Small Ruminant Research . 2023 ; 218 : 106880 . doi: 10.1016/j.smallrumres.2022.106880 . OpenUrl CrossRef 71. Hamond C , Martins G , Medeiros MA , Lilenbaum W. Presence of Leptospiral DNA in semen suggests venereal transmission in horses . Journal of Equine Veterinary Science . 2013 ; 33 ( 12 ): 1157 – 9 . doi: 10.1016/j.jevs.2013.03.185 . OpenUrl CrossRef 72. Loureiro AP , Lilenbaum W. Genital bovine leptospirosis: A new look for an old disease . Theriogenology . 2020 ; 141 : 41 – 7 . doi: 10.1016/j.theriogenology.2019.09.011 . OpenUrl CrossRef PubMed 73. ↵ Shetty A , Kundu S , Vernel-Pauillac F , Ratet G , Werts C , Gomes-Solecki M. Transient presence of live Leptospira interrogans in murine testes . Microbiology Spectrum . 2022 ; 10 ( 3 ): e02775 – 21 . doi: 10.1128/spectrum.02775-21 . OpenUrl CrossRef 74. ↵ Cardoso M , Ragan I , Hartson L , Goodrich RP . Emerging pathogen threats in transfusion medicine: Improving safety and confidence with pathogen reduction technologies . Pathogens . 2023 ; 12 ( 7 ). doi: 10.3390/pathogens12070911 OpenUrl CrossRef 75. ↵ Faddy H , Seed C , Lau C , Racloz V , Flower R , Smythe L , et al. Antibodies to Leptospira among blood donors in higher-risk areas of Australia: possible implications for transfusion safety . Blood Transfusion . 2015 ; 13 ( 1 ): 32 - 6 . Epub 20140619. doi: 10.2450/2014.0012-14 . PubMed PMID: 24960651 ; PubMed Central PMCID: PMCPMC4317087 . OpenUrl CrossRef PubMed 76. Ribeiro MA , Cliquet MG , Santos MGS . Leptospirosis: a problem for transfusion medicine? Serodiagnosis and Immunotherapy in Infectious Disease . 1997 ; 8 ( 3 ): 185 – 9 . doi: 10.1016/S0888-0786(96)01076-1 . OpenUrl CrossRef 77. Limothai U , Tachaboon S , Dinhuzen J , Singh J , Jirawannaporn S , Leewongworasingh A , et al. Seroprevalence of leptospirosis among blood donors in an endemic area . Scientific Reports . 2023 ; 13 ( 1 ): 12336 . doi: 10.1038/s41598-023-39461-3 . OpenUrl CrossRef PubMed 78. ↵ Nedunchelliyan S , Venugopalan AT . Blood transfusion and leptospirosis . Indian Veterinary Journal . 1997 ; 74 ( 9 ): 790 – 1 . OpenUrl 79. ↵ Karp JK , King KE . International variation in volunteer whole blood donor eligibility criteria . Transfusion . 2010 ; 50 ( 2 ): 507 – 13 . doi: 10.1111/j.1537-2995.2009.02392.x . OpenUrl CrossRef 80. ↵ Khan F , Singh K , Friedman MT . Artificial Blood: The History and Current Perspectives of Blood Substitutes . Discoveries (Craiova) . 2020 ; 8 ( 1 ): e104. Epub 20200318. doi: 10.15190/d.2020.1 . PubMed PMID: 32309621 ; PubMed Central PMCID: PMCPMC7086064 . OpenUrl CrossRef PubMed 81. ↵ Mohanto N , Park Y-J , Jee J-P. Current perspectives of artificial oxygen carriers as red blood cell substitutes: a review of old to cutting-edge technologies using in vitro and in vivo assessments . Journal of Pharmaceutical Investigation . 2023 ; 53 ( 1 ): 153 – 90 . doi: 10.1007/s40005-022-00590-y . OpenUrl CrossRef PubMed 82. ↵ Bansal SB , Ramasubramanian V , Prasad N , Saraf N , Soman R , Makharia G , et al. South Asian transplant infectious disease guidelines for solid organ transplant candidates, recipients, and donors . Transplantation . 2023 ; 107 ( 9 ). doi: 10.1097/tp.0000000000004521 . OpenUrl CrossRef 83. ↵ Song ATW , Abas L , Andrade LC , Andraus W , D’Albuquerque LAC , Abdala E. A first report of leptospirosis after liver transplantation . Transplant Infectious Disease . 2016 ; 18 ( 1 ): 137 – 40 . doi: 10.1111/tid.12490 . OpenUrl CrossRef PubMed 84. ↵ Gerasymchuk L , Swami A , Carpenter CF , Samarapungavan D , Batke M , Kanhere R , et al. Case of fulminant leptospirosis in a renal transplant patient . Transplant Infectious Disease . 2009 ; 11 ( 5 ): 454 – 7 . doi: 10.1111/j.1399-3062.2009.00415.x . OpenUrl CrossRef PubMed 85. ↵ Dolhnikoff M , Mauad T , Bethlem EP , Carvalho CRR . Pathology and pathophysiology of pulmonary manifestations in leptospirosis . Brazilian Journal of Infectious Diseases . 2007 ; 11 : 142 – 8 . doi: 10.1590/S1413-86702007000100029 . OpenUrl CrossRef PubMed Web of Science 86. ↵ Gulati S , Gulati A. Pulmonary manifestations of leptospirosis . Lung India . 2012 ; 29 ( 4 ). doi: 10.4103/0970-2113.102822 . OpenUrl CrossRef PubMed 87. ↵ Huang YJ , Kim E , Cox MJ , Brodie EL , Brown R , Wiener-Kronish JP , et al. A persistent and diverse airway microbiota present during chronic obstructive pulmonary disease exacerbations . OMICS: A Journal of Integrative Biology . 2010 ; 14 ( 1 ): 9 – 59 . doi: 10.1089/omi.2009.0100 . OpenUrl CrossRef PubMed Web of Science 88. ↵ Marinho Mr , Oliveira-Júnior IS , Monteiro CMR , Perri SH , Salomão R. Pulmonary disease in hamsters infected with Leptospira interrogans: Histopathologic findings and cytokine mRNA expressions . The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg . 2009 ; 80 ( 5 ): 832 – 6 . doi: 10.4269/ajtmh.2009.80.832 . OpenUrl CrossRef View the discussion thread. Back to top Previous Next Posted September 02, 2025. Download PDF Supplementary Material Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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