Role of Diagnostics in Epidemiology, Management, Surveillance, and Control of Leptospirosis

Abstract

A One Health approach to the epidemiology, management, surveillance, and control of leptospirosis relies on accessible and accurate diagnostics that can be applied to humans and companion animals and livestock. Diagnosis should be multifaceted and take into account exposure risk, clinical presentation, and multiple direct and/or indirect diagnostic approaches. Methods of direct detection of Leptospira spp. include culture, histopathology and immunostaining of tissues or clinical specimens, and nucleic acid amplification tests (NAATs). Indirect serologic methods to detect leptospiral antibodies include the microscopic agglutination test (MAT), the enzyme-linked immunosorbent assay (ELISA), and lateral flow methods. Rapid diagnostics that can be applied at the point-of-care; NAAT and lateral flow serologic tests are essential for management of acute infection and control of outbreaks. Culture is essential to an understanding of regional knowledge of circulating strains, and we discuss recent improvements in methods for cultivation, genomic sequencing, and serotyping. We review the limitations of NAATs, MAT, and other diagnostic approaches in the context of our expanding understanding of the diversity of pathogenic Leptospira spp. Novel approaches are needed, such as loop mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR)-based approaches to leptospiral nucleic acid detection.

A global one health perspective on leptospirosis in humans and animals

“…In addition to widespread subclinical infection in an enormous variety of animal reservoir hosts, pathogenic leptospires cause disease in dogs, cattle, horses, pigs, camelids, small ruminants, and wildlife species. 27,28 The clinical picture of leptospirosis in dogs resembles that in humans, in that most infections are subclinical, but when disease occurs, it is typically characterized by signs of lethargy, fever, inappetence, and polyuria/polydipsia, then multiorgan dysfunction with acute kidney injury, cholestatic hepatic dysfunction, pancreatitis, variable degrees of pulmonary hemorrhage, myositis, and, in some cases, uveitis. 29,30 In cattle, the spirochete is a major cause of abortion, neonatal illness, and production loss such as decreased milk production worldwide.…”

Understanding leptospirosis: application of state-of-the-art molecular typing tools with a One Health lens

“…6 However, culture of leptospires has been challenging because leptospires are fastidious, often inactivated during transport to the laboratory, and require special media and prolonged incubation times for growth. Serotyping is laborious and time consuming; serotyping to the serogroup and serovar level is performed using reference antisera and monoclonal antibodies and requires an experienced laboratory that maintains antisera, 7 yet worldwide the number of laboratories with this capability is limited. Manipulation of live pathogenic leptospires during typing efforts also represents a hazard to laboratory workers.…”

“…However, by virtue of the conserved nature of the lipL32 gene sequence, this method lacks discriminatory power, 20,22 and P2 leptospires are not detected using lipL32 gene PCR because of sequence variation. 7 Three different 6-or 7-loci MLST schemes have been most widely used in the literature (Table 1). 20 A simplified 3-locus (adk, lipL41, mreA) scheme for direct application to clinical specimens was recently described, 26 although this still requires gel electrophoresis followed by sequencing, which is not practical in a routine clinical laboratory setting.…”

“…Although the results of serologic testing using the microscopic agglutination test (MAT) have been widely used to predict the identity of an infecting serogroup in both incidental and reservoir hosts, this approach is not reliable because of paradoxical serologic cross-reactivity and the potential for omission of the infecting serogroup from the panel. 7,[31][32][33] Inclusion of local serovars isolated from the kidneys and urine of domestic animals and wildlife species in Tanzania in the MAT was reported to increase leptospiral seroprevalence in humans from 0.26% to 10.75% and in rodents from 1.9% to 16.9%. 34 The revised panel included serovars Sokoine, Kenya, Lora, Canicola, Grippotyphosa, Hebdomadis, Pomona, and Hardjo, while historical results used a panel that contained serovars Icterohaemorrhagiae, Canicola, Pyrogenes, Hardjo, and Grippotyphosa.…”

Ocular leptospirosis: lack of awareness among ophthalmologists and challenges in diagnosis

“…The annual global burden is estimated to be 1.03 million cases and 59 800 fatalities [2] The estimated 1.03 million cases annually mark approximately 2.90 million disability-adjusted life years [3]. Although it is a potentially lethal disease involving animals and humans, it has no national surveillance systems and it is not even a notifiable disease in many countries [1 ▪▪ ]. On the contrary, it has numerous as well as varying clinical manifestations, clinician may easily miss the diagnosis [4,5].…”