Our study shows that leptospirosis is a common cause of febrile illness among inpatients in northern Tanzania. The high seroprevalence among patients without confirmed or probable leptospirosis, combined with the proportion of patients with confirmed or probable leptospirosis, suggests that the disease is endemic in northern Tanzania. Leptospirosis is difficult to distinguish clinically from other etiologies of febrile illness, such as malaria and bacteremia, which have received more attention in sub-Saharan Africa.37
Furthermore, diagnostic tests for leptospirosis are not readily available and consequently the infection is rarely diagnosed by clinicians or managed with specific antimicrobial therapy.
The predominant reactive serogroups among participants with confirmed or probable leptospirosis were Mini and Australis. Among those with evidence of exposure to pathogenic leptospires, serogroups Mini, Australia, and Autumnalis were most prevalent. Although MAT is not a serovar-specific test, MAT may broadly indicate the common serogroups present in the local population38,39
and may in turn provide clues to important animal reservoirs. Serogroup Mini has not been previously well described in East Africa, but potential local reservoirs include cattle, dogs, and hedgehogs.17–19
Serogroup Australis has been described in cattle, sheep, rats, donkeys, dogs, and hedgehogs.20–27
Serogroup Autumnalis has been described in cattle, rats, mice, sheep, pigs, goats, and dogs.3,17,20,22
On the basis of the most common reactive serogroups in the study population, likely local reservoirs include livestock, rodents, dogs, and potentially hedgehogs. Further studies are needed in northern Tanzania to define animal reservoirs and human risk factors for disease. These may include epidemiologic studies of persons with and without leptospirosis and animal studies to isolate and identity Leptospira
Although our study was not designed to comprehensively examine risk factors for leptospirosis in northern Tanzania, consistent with other studies we showed that residence in a rural area is associated with increased risk for leptospirosis.40
The importance of livestock-based agriculture and pastoralism in rural Tanzania,4,41
and the predominance of reactivity to livestock-associated serovars identified by MAT underscore the possibility of an important role of livestock in leptospirosis transmission. Furthermore, persons living in rural areas in Tanzania are more likely to have exposure to surface water,4
a recognized risk factor for leptospirosis in other studies.42
In contrast with some studies,43
we did not find a relationship between the rainy season and prevalence of acute leptospirosis. This may be because the available rainfall data are for one location in the region, whereas the various districts may have actually experienced varied rainfall patterns and totals. Another possibility is that the exposure risk in this environment does not change substantially based on the season.
A substantial proportion of patients with confirmed leptospirosis in this study also had evidence of infection with another pathogen, most commonly spotted fever group rickettsiosis, brucellosis, or bacterial bloodstream infection. Possible explanations for these observations include true co-infection, cross-reactivity of the MAT, cross-reactivity of other serological tests (spotted fever group rickettsioses, Brucella
) in the setting of leptospirosis, non-specific polyclonal immunoreactivity, or laboratory error. Although MAT specificity has been estimated at 96–98%,44
cross-reactivity in the setting of other infections has been demonstrated.1,44
Alternatively, other studies also using conventional standard diagnostic tests, including identification of Leptospira
, and Brucella
species by culture and molecular methods, have found evidence of simultaneous infections with more than one pathogen.45–47
In these studies, similar to ours, most patients with evidence of co-infection lived or worked in rural, agricultural settings.45,46
Although our study is unable to determine whether apparent co-infections represent true simultaneous infection or immunologic cross-reactivity, the environmental exposures experienced by persons living in northern Tanzania provide increased risk for several etiologic agents of febrile illness.
The clinical presentation of leptospirosis in this study was non-specific making clinical diagnosis challenging. Thrombocytopenia was the only laboratory marker associated with leptospirosis in adolescents and adults. In infants and children, no laboratory marker was specific for leptospirosis. This, combined with the focus on empiric treatment algorithms for febrile illness on malaria and sepsis,48,49
mean that leptospirosis is rarely diagnosed or treated with specific therapy in northern Tanzania. The consequences for patients of underdiagnosis of leptospirosis are difficult to measure. Because a confirmed diagnosis of leptospirosis requires acute and convalescent serum to be tested, estimating case fatality rate for patients with leptospirosis is difficult. For this reason, no patient with confirmed leptospirosis in our study died. Among those with an acute MAT titer of ≥ 800, 5 (16.7%) died. However, all deaths were among adult patients with co-morbidities, making it difficult to attribute death to leptospirosis in these cases. A diagnostic test for leptospirosis with high sensitivity and specificity on an acute specimen would greatly assist with directing the antimicrobial management of patients and would provide a means to more accurately estimate the case fatality rate. Real-time polymerase chain reaction (PCR) is a promising method to assist with diagnosis in the acute leptospiremic phase,50,51
and should be further studied in Africa where local circulating Leptospira
isolates need to be determined to optimize PCR performance.52
In summary, leptospirosis is an important cause of febrile illness in northern Tanzania, where it appears to be endemic. MAT reactivity is most common to serogroups Mini, Australis, and Autumnalis. The serogroup reactivity, combined with rural residence as a risk factor, may suggest that livestock are important reservoirs in this area. Leptospirosis was difficult to distinguish clinically from other causes of febrile illness in this study and was never diagnosed or specifically treated. Greater awareness of leptospirosis among clinicians and efforts to develop a rapid and reliable diagnostic test that could be applied to acute specimens would improve patient management and facilitate estimation of the burden of morbidity and mortality. Further research is needed in northern Tanzania to define risk factors for human leptospirosis and to further define animal reservoirs to develop evidence-based prevention strategies.