Leptospirosis has been described as the most geographically widespread and prevalent zoonosis in the world.1–3 It is caused by infection with different serovars of bacteria of the genus Leptospira. Human infection can lead to a range of clinical manifestations, from mild or asymptomatic infections to severe, life-threatening illness. Human disease is severely under reported as patients commonly present with non-specific symptoms, such as fever, headache and myalgia, and infection is difficult to diagnose by using either clinical or laboratory diagnostic criteria.2,4 Consequently, in many parts of the world, the public health impact of leptospirosis is largely undocumented.5–8 However, when leptospirosis is considered in clinical and epidemiologic evaluations of febrile populations, significant disease burdens are frequently demonstrated.4,9–11 Data from studies of febrile illness in many tropical regions indicate that leptospirosis can account for considerable proportions of febrile illnesses.

Among patients hospitalized with acute febrile illness in northern Tanzania, 33.3% of 832 patients showed evidence of exposure to leptospires and 8.8% of 453 patients with paired serum samples had acute leptospirosis based on a ≥ 4-fold increase in microscopic agglutination test titer.4 Similarly, 15.5% of 773 febrile patients presenting at a hospital in Sri Lanka and 16% of patients in Egypt with acute febrile illness had acute leptospirosis based on seroconversion or the equivalent of a ≥ 4-fold increase in titer using an IgM enzyme-linked immunosorbent assay.10,12

In the Kibera informal settlement, where this study was conducted, acute febrile illness is a common syndrome, with an average of 2.7 episodes per person/year for children < 5 years of age and 0.58 episodes for persons ≥ 5 years of age based on household visit data.13 However, the proportion of febrile illnesses that are attributable to leptospirosis at this site is currently unknown. The published data on leptospirosis in Kenya are also limited. The World Health Organization Global Alert and Response System described a laboratory-confirmed outbreak that occurred at two schools in western Kenya in 2004 that involved more than 141 suspected cases and 8 deaths.14 Several patients assessed during an outbreak of acute febrile illness in northeastern Kenya in 2005 were positive for antibodies against Leptospira.15 Other published data on leptospirosis in Kenya date back to the 1960s and 1970s and describe human cases in several provinces,16–18 as well as isolation of Leptospira from rodents trapped in the Coastal Province and detection of antibodies against Leptospira in cattle, sheep, and donkeys sampled across the country.19

Leptospirosis is maintained through chronic renal infection of maintenance hosts, which shed leptospires in their urine. Leptospira serovars can infect several host species and different host species can carry several serovars.3 Rodents are believed to be the most important maintenance hosts for a variety of serovars, but a wide range of mammals, including domestic dogs, cattle, pigs and sheep, can also act as hosts for human pathogenic leptospires.2

Globally, leptospirosis is recognized as a re-emerging infection and has been described as a paradigm for an urban health problem emerging as a consequence of the growth of slums.20 The un-planned nature of slums with their poor sanitation infrastructure often creates conditions that promote the presence of rodents and favors the maintenance of leptospirosis.20,21 The risk of human leptospirosis infection can vary within slum environments. Studies conducted in Salvador, Brazil indicate that exposure risk clusters at the household level22 and that rat sightings in and around the household are a risk factor for exposure to leptospires.20,23

As a starting point for advancing our understanding and awareness of leptospirosis in the Kibera settlement in Nairobi, Kenya, we performed a study to determine patterns of Leptospira infection in rodent hosts and human-rodent interactions. Specifically, the objectives were to identify the rodent species that were present at this site, detect the presence of pathogenic Leptospira spp. in the Kibera rodent population, and describe the nature and frequency of contacts between humans and rodents.

Pathogenic leptospires were identified in the Kibera rodent population. Nearly one in five rodents trapped within houses in Kibera had pathogenic leptospires in their kidneys and were thus potentially capable of shedding leptospires into the environment. The questionnaire data showed sightings of multiple rodents and their excreta within households on a daily basis by most study respondents. Previous studies at other urban slum sites have identified rodent sightings around the household as a risk factor for human Leptospira exposure.20,23 As humans acquire leptospirosis through direct or indirect contact with the urine of an infected host, these data, together indicate that the risk of human exposure to pathogenic Leptospira spp., is likely to be substantial in Kibera.

According to the results obtained with the Taqman PCR, all positive samples belonged to clade 1, consisting of L. interrogans, L. kirschneri, L noguchii, and L. meyeri. Pathogenic strains of L. meyeri and L.noguchii are predominantly confined to the Americas and have not been demonstrated in Africa and/or are of minor importance for the epidemiology of leptospirosis. Thus, for samples from Africa, placement within clade 1 will support classification as either L. interrogans or L. kirschneri. Consistent with these results, phylogenetic analysis showed that strains belonging to the species L. interrogans and L. kirschneri are carried by the Kibera Mus population. Phylogenetic speciation of Leptospira based on analysis of the secY gene used in this study has been described and is highly discriminatory.27,28,34 Confirmation of the range of pathogenic Leptospira maintained in Kibera animal populations will be an important area for future research.

The probability of Leptospira infection was significantly higher in Mus trapped in Kibera than in Rattus. Most previous studies of urban leptospirosis have implicated rodents, and specifically Rattus spp., as the maintenance reservoirs for human pathogenic Leptospira spp.23,35–37 The use of Sherman traps may provide one explanation for the relatively low prevalence in the Rattus population sampled in this study. These traps may select for smaller (and younger) Rattus rodents, in which the Leptospira infection prevalence in kidneys may be lower than in adults.38–40 The mass of the R. norvegicus and R. rattus rodents trapped in this study ranged from 25 to 194 grams and from 12.5 to 122 grams, respectively, indicating that all of the Rattus rodents trapped were juveniles.39,40 The prevalence of infection detected in Rattus rodents in this study may therefore be an underestimate of the prevalence in the Rattus population as a whole. Interestingly, the qPCR data showed a high infection prevalence in rodents of the genus Mus, which may be important hosts in the epidemiology of leptospirosis in Kibera. This finding highlights the complex multi-host epidemiology of leptospirosis and the importance of considering the role of rats, mice, and other animal hosts in the maintenance and transmission of infection when evaluating human risks.

There is a large population of domestic dogs in Kibera and their density within this study site has been estimated at 740–1,086 dogs/km².41 The capacity for dogs to act as reservoir hosts for leptospirosis is well described in other settings,2 and the possible role of dogs and other potential reservoirs in the epidemiology of urban leptospirosis should not be discounted.42 Our study focused on rodent presence and sightings in and around the household environment, which have been identified as risk factors for human exposure risks in slum settings. Previous studies in urban areas have also identified contaminated surface waters as a source of human exposure risk36,43 and household flooding risk and proximity to sewers as predictors of human exposure risk.20 The routes of indirect exposure of humans to leptospires shed into environmental water sources by animal hosts should also be considered in future studies to evaluate human disease risks.

The multivariate model indicates that rodents trapped in zones D and E, to the east of the site, were significantly more likely to be positive than rodents trapped in the reference zone A (Figure 1). The total area of the population-based infectious disease surveillance study site, within which these five trapping areas were established, is just 0.38 km² 2,13 and these data indicate substantial variation in the prevalence of leptospirosis in rodents, even over the relatively short distances. This zone effect was seen when the rodent genus variable was also included in the model, indicating that this effect is not entirely attributable to differences in the distribution of these different hosts between zones. Within the Kibera site, the terrain slopes down towards a river, which runs along the southern boundary of the site, and much of the eastern part of the site is at lower elevation than the western part. Fine-scale spatial variation in human exposure risk has been demonstrated at other slum sites20,22 and geographic variables, such as reduced elevation, flooding risk, proximity to drainage, and proximity to rubbish dumps, have been described as risk factors for human exposure to Leptospira spp.20,23 The influence of geographic variables upon animal and human infection risk at the Kibera site and the spatial correspondence between rodent prevalence and human risk warrant further investigation.

This study had some limitations. The kidney extracts were diluted to reduce the influence of qPCR inhibitors present in these kidney tissue samples. This dilution step, as well as the effect of any residual inhibition in tissue extracts, could result in false-negative qPCR results. Therefore, 18.3% is considered to be a conservative estimate of true prevalence in the Kibera rodent population. Renal colonization as high as 80.3% has been detected by culture (83.9% by PCR) among rats sampled in an urban setting in Salvador, Brazil.39 Other studies have reported carriage rates of 35.3% in urban rodent populations in Madagascar through combined use of molecular, serologic, and culture approaches;44 20% in urban R. norvegicus trapped in Colombia by culture;37 21.7% R. norvegicus trapped in an urban slum in Peru by PCR;36 and 20% of rodents trapped near urban areas in Peru by PCR.45 Culture and isolation of Leptospira strains were beyond the scope of this study but are essential to enable isolate typing and are a priority for future research at this site. Characterization of Leptospira serovars present in animal populations in Kibera may help to shed light on the relative importance of different maintenance hosts in this setting, as well as contributing to the development and validation of locally appropriate diagnostic tests for clinical use.

In this study, we have demonstrated the presence of pathogenic leptospires in the Kibera rodent population. Although the epidemiology of leptospirosis is complex and humans can acquire infection through indirect or direct contacts with a variety of animal reservoir hosts, rodents are frequently identified as important reservoirs in urban slum settings particularly, and household rodent sighting frequencies have been shown to correlate with human exposure risks in other urban slum settings. Our findings, which are consistent with reports from slum sites in South America20 and Asia,11 indicate that human exposure to pathogenic Leptospira spp. may be considerable in Kibera. These data contribute to the growing body of evidence suggesting that leptospirosis may be an under-recognized but important cause of human illness, specifically in urban slum populations.

Despite increasing recognition of the clinical threat posed by leptospirosis, the impact of leptospirosis on the health and productivity of animal and human populations continues to be widely unrecognized and under-reported. In many human populations, including Kibera, the burden of undifferentiated febrile illness is significant.13 Broader diagnostic testing, including consideration of acute leptospirosis, is needed to determine the causes of these illnesses. Ultimately, these data will be useful to raise awareness of leptospirosis among clinicians and promote appropriate clinical management of cases.