Trends in Parasitology
Volume 34, Issue 10, October 2018, Pages 881-890
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Review
Advances toward Diagnostic Tools for Managing Zoonotic Visceral Leishmaniasis

https://doi.org/10.1016/j.pt.2018.07.012Get rights and content

Highlights

VL is an important disease of dogs and humans, with dogs being the primary domestic reservoir of L. infantum parasites.

Detection of diseased, infected, and parasite-transmitting ‘super-spreader’ dogs is likely critical for control.

Dependent upon scale, direct and indirect detection methods can be used for surveillance.

Novel molecular assays with point-of-care potential are emerging.

New antigen targets are being characterized to enhance performance of serological assays.

Adaptation to provide point-of-care serological tests to permit Leishmania detection and facilitate large-scale screening programs.

Visceral leishmaniasis (VL) is a life-threatening outcome of Leishmania infantum or Leishmania donovani infection. Dogs are the primary domestic reservoir of L. infantum parasites, and ownership of infected dogs increases the risk of human VL. Controlling infection within dog populations is regarded as critical to VL management in endemic countries, both preventing progression of canine disease and limiting parasite transmission to humans and dogs. Here we discuss various strategies that are used to diagnose canine visceral leishmaniasis (CVL) and the possibilities of adapting these for use within population screening and control programs. In addition, given the variable transmissibility of L. infantum to the sand fly vector, we outline some possibilities for the preferential identification of ‘super-spreader’ dogs among the overall infected population.

Section snippets

Leishmania Infection and VL

Visceral leishmaniasis (VL) (see Glossary) is a vector-borne disease characterized by prolonged fever, wasting, splenomegaly, and hepatomegaly, resulting in >90% case-fatality within 2 years in the absence of treatment [1]. Estimates of the number of new human VL (HVL) cases per year range from 25 000 to 200 000 accounting for under-reporting 2, 3, and although therapeutic drug options are available, the control portfolio to prevent transmission is limited. VL due to L. donovani is considered

Diagnosing Infection and CVL

The clinical signs of CVL are quite general and therefore not particularly useful for detecting symptomatic infection or differentiating Leishmania from other etiologies [16]. Numerous tools are, however, available to aid the diagnosis of both canine and human infection, covering an array of direct and indirect detection methods (Figure 2). Direct methods include xenodiagnosis and parasite observance in ex vivo cultures, or recognition of amastigotes following biopsy or microscopy. Parasite

Detecting Leishmania Infection in Surveillance and Control Programs

VL surveillance programs and epidemiological studies that aim to detect Leishmania infection pertinent to either HVL or CVL control require tests with high sensitivity. Under specific conditions, such as reservoir control programs that deploy a test-and-slaughter policy, low compliance by dog owners fearing the potential removal of their apparently healthy but seropositive dogs has a major impact on program success. Thus, high specificity to differentiate clinically suspect cases from other

Identifying Infectious Individuals as a Means toward Controlling Transmission

A major question for HVL control efforts on the Indian subcontinent is whether people with asymptomatic infection are sufficiently infectious to sand flies to represent a significant reservoir for L. donovani [77]. While it has been demonstrated that HVL and post kala-azar dermal leishmaniasis (PKDL) patients can be highly infectious 4, 78, the epidemiological significance of asymptomatic L. donovani infection in transmission remains unclear. Given that there appear to be between 4- and 17-fold

Concluding Remarks

CVL is an important veterinary complication that not only deserves attention in its own right but could potentially be highly informative for HVL control programs (see Outstanding Questions). Control of infection in dogs in L. infantum-endemic regions would likely create the additional benefit of limiting a critical reservoir that maintains the threat of human infection and disease. As discussed, many tools currently used to diagnose CVL are now being evolved to allow identification and

Disclaimer Statement

Malcolm Duthie is a coinventor on a patent for leishmaniasis vaccine development and IDRI supplies antigens to commercial partners for manufacture of diagnostic tests for VL. Orin Courtenay and Aurore Lison have stated no conflict of interest.

Acknowledgments

Diagnostic work at IDRI has been funded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01AI025038. Additional program support came from the Bill and Melinda Gates Foundation under grants #631 and #39129. Aurore Lison is funded by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 642609. Orin Courtenay acknowledges the continued support of the Wellcome Trust, UK.

Glossary

Asymptomatic
infection in the absence of clinical signs or symptoms.
DPP CVL
Dual-Path Platform technology (DPP®CVL rapid test) for the serodiagnosis of canine visceral. A lateral flow-based test that detects canine IgG antibodies against the rK28 antigen.
rK39
the gold standard recombinant, chimeric polyprotein rK39 used to confirm VL.
Super-spreaders
infected dogs, or humans, that make a disproportionally high contribution to ongoing parasite transmission to the intermediate sand fly host.
Visceral

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