Visceral Leishmaniasis is a deadly disease caused by Leishmania infantum, endemic in more than 98 countries across the globe. Although the most common means of transmission is via a sand fly vector, there is growing evidence that vertical transmission may be critical for maintaining L. infantum infection within the reservoir, canine, population. Vertical transmission is also an important cause of infant morbidity and mortality particularly in sub-Saharan Africa. While vertical transmission of visceralizing species of Leishmania has been reported around the globe, risk factors associated with this unique means of Leishmania transmission have not been identified therefore interventions regarding this means of transmission have been virtually non-existent. Furthermore, the basic reproductive number, (R0), or number of new L. infantum infections that one infected mother or dam can cause has not been established for vertical transmission, also hampering the ability to assess the impact of this means of transmission within reservoir of human hosts. Canine Leishmaniosis (CanL) is enzootic within a U.S. hunting dog population. CanL is transmitted within this population via transplacental transmission with no reported vector transmission, despite many repeated attempts to find infected sand flies associated with these dogs and kennels. This population with predominantly, if not solely, vertical transmission of L. infantum was used to evaluate the critical risk factors for vertical transmission of Leishmania and establish the R0 of vertical L. infantum infection. Evaluation of 124 animals born to eighteen dams diagnostically positive for infection with L. infantum showed that there was a 13.84x greater chance of being positive for L. infantum within their lifetime if the mother was also positive within her lifetime (RR: 13.84, 95% CI: 3.54-54.20, p-value: <0.0001). The basic reproductive number for vertically transmitted L. infantum within this cohort was 4.12. These results underscore that there is a high risk of L. infantum infection to transmit from mother to offspring. Targeted public health interventions and control efforts that address vertical transmission of L. infantum are necessary in endemic countries to eliminate visceral leishmaniasis.

Certain professionals have more exposure to animals and therefore an increased risk of zoonoses. Professional hunting dog caretakers work with upwards of 50 dogs and are exposed to zoonoses through exposure to multiple potentially infectious canine secretions or excretions, as well as to the ticks that dogs carry. Dog caretakers reported having found embedded ticks on their bodies 5.83 times more than environment-only controls. Zoonotic Lyme disease, first in the United States for morbidity due to a vector-borne infection, has dramatically expanded its geographic range over the last two decades. This finding emphasizes the increased risk of tick-borne diseases, including Lyme disease, based on dog exposure and in areas of disease emergence.

Leishmania is the causative agent of leishmaniasis, a deadly protozoan disease which affects over 1 million people each year. Autochthonous cases of canine leishmaniasis are generally associated with tropical and subtropical climatic zones. However, in 1999, U.S. hunting dogs were found to have leishmaniasis with no history of travel outside the country. Transmission of this disease was found to be primarily vertical. In endemic areas, dogs are a dominant domestic reservoir host for Leishmania infantum. This study evaluated L. infantum infection prevalence and incidence within US dogs tested over a nine-year span (2007–2015). This investigation used both passive and active surveillance, following an initial outbreak investigation by the Centers for Disease Control. L. infantum infection incidence and prevalence over time and across regions were examined to evaluate whether transmission was sufficient to maintain ongoing infection within this population. These studies also established whether this disease is becoming more or less prominent within this reservoir host, dogs. There was no significant difference between prevalence and incidence rates via as measured by passive vs. active surveillance. Although due to fluctuations in sample submission there were significant changes in both incidence and prevalence of L. infantum in US hunting dogs over this nine year span, these differences were not outside of the interquartile range and therefore there is likely to be a steady-state of transmission within U.S. dogs. Based on these findings, if vertical transmission is the primary means of L. infantum spread in U.S. dogs, with appropriate husbandry and infection control procedures, elimination of L. infantum from US dogs could be possible.

Infection with Leishmania causes diseases with variable presentation. The most severe form is visceral leishmaniasis (VL), caused by either L. donovani or L. infantum. Despite efforts to eliminate VL, to date, molecular detection in resource-poor settings have lacked the accuracy and rapidity that would enable widespread field use and the need for accurate, sensitive assays to detect asymptomatic Leishmania infection has become apparent. The domestic dog serves as the primary reservoir host of L. infantum. Study of this reservoir population provides an opportunity to evaluate the sensitivity and specificity of diagnostics for well-defined, symptomatic, canine visceral leishmaniasis (CVL) and asymptomatic L. infantum infection. Blood samples from an L. infantum-endemic population of US hunting dogs were evaluated with Dual-Path Platform (DPP®) CVL compared to those obtained via direct detection methods (culture- and Leishmania-specific quantitative polymerase chain reaction, qPCR) and immunofluorescence anti-Leishmania antibody test (IFAT). Statistically significant correlations were found between DPP® CVL development time and clinical status, culture status, circulating DNA levels, and IFAT titer. DPP® CVL results correlated with both clinical severity of disease and serological evidence of asymptomatic L. infantum infection. By precisely documenting the minimum time required for the development of a clear positive result in DPP® CVL, this test could be used in a rapid, semi-quantitative manner for the evaluation of asymptomatic and symptomatic CVL. Our results also indicate that a similar test could be used to improve our understanding of human VL.

During visceral leishmaniasis (VL), Th1-based inflammation is induced to control intracellular parasites. Inflammation-based pathology was shown to be dampened by IL-10 and eventual programmed death 1-mediated T cell exhaustion. Cell type(s) responsible for the initiation of T cell-produced IL-10 during VL are unknown. CD19(+), CD5(-), CD1d(-), IgD(hi) regulatory B cells from healthy controls produced IL-10 in the absence of infection or stimulation, in contrast to IgD(lo/neg) B cells. IgD(hi) B cells may have a de novo versus induced regulatory program. The population of IgD(hi) B cells increased 3-fold as VL progressed. B cells from VL dogs were necessary and sufficient to suppress Th1 cell effector function. IgD(hi) B cells induced IL-10 production by T cells and IgD(lo) B cells. Blockage of B cell-specific PD-L1 restored Th1 responses. IgD(hi) regulatory B cells represent a novel regulatory B cell that may precipitate T cell exhaustion during VL.

Are Kinetoplastids Transmitted Vertically?Kinetoplastids Leishmania infantum and Trypanosoma cruzi, the causative agents of zoonotic visceral leishmaniasis (ZVL) and Chagas' disease (CD), respectively, can both be transmitted vertically in utero from mother to infant [1].Congenital infection can be either asymptomatic infection or overt, symptomatic infection [2].Dogs are a primary domestic reservoir associated with human CD in certain endemic areas and with human ZVL where L. infantum infection predominates.CD, or American Trypanosomiasis, is endemic in 21 countries within the Americas, where classical transmission is via reduviid bugs.Dogs can present with clinical CD.Although rarer, vertical transmission of CD has been reported in dogs.L. infantum (syn.L. chagasi) is one of the Leishmania species causing visceral leishmaniasis (VL).L. donovani, another causative agent of VL and predominantly a human pathogen, has not demonstrated vertical transmission, but this is an understudied area.L. infantum is endemic in the Americas and the Mediterranean region, with primary transmission by sand fly.Although both Lutzomyia shannoni and Lu.anthophora, present in North America, are potential vectors for Leishmania spp.[3], sand fly transmission of L. infantum in North America has not been confirmed.VL is not endemic in North American human populations, but it is endemic in hunting dogs due to vertical transmission of L. infantum [4,5].What Is the Scope of Vertically Transmitted Kinetoplastid Disease and How Is It Detected?