ABSTRACT.
Leptospirosis affects numerous animal species, including domestic dogs, but documented transmission to humans is rare. Here, we describe epidemiologically linked cases in a 12-year-old Minnesota boy and his pet dog. While human leptospirosis is often thought of as a disease of tropical locations, this case report describes a rare documented example of local transmission in the northern United States, a region historically not perceived to be at high risk of Leptospira species transmission to humans. This case highlights an unusual presentation, with facial nerve palsy, underappreciated epidemiological risks, and diagnostic challenges of this reemerging infection.
A 12-year-old previously healthy child presented to a primary care clinic with 3–4 weeks of fatigue and two brief episodes of right-upper-quadrant abdominal pain (Figure 1, day 0). The physical exam, comprehensive metabolic panel, and complete blood count were normal. Urinalysis revealed mild proteinuria.
Figure 1.
Timeline of significant clinical events, including symptoms, encounters with health care providers, laboratory investigations, and administered treatments. d = days; ED = emergency department; LMAT = Leptospira microscopic agglutination test; PCP = primary care physician; PCR = polymerase chain reaction.
Nine days later, the child was reevaluated for persistent fatigue and two additional episodes of abdominal pain. Conjunctival injection was present, and urinalysis showed ongoing proteinuria with a normal renal ultrasound. During this time period, the patient’s dog, a 6-pound Maltese-Yorkshire hybrid, also received care for severe fatigue and decreased oral intake. Evaluation by a local veterinarian demonstrated acute kidney injury. Point-of-care testing with the IDEXX SNAP® Lepto Test, a rapid enzyme-linked immunosorbent assay that detects both IgM and IgG antibodies targeting the LipL32 Leptospira protein,1,2 was positive. In the absence of prior administration of canine leptospirosis vaccine, this finding suggested natural infection. However, no additional diagnostic testing was recommended for the child by public health authorities since he was afebrile.
At day 26, the child presented to the emergency department with a 1-day history of right-sided facial palsy (Figure 2). Lyme serologies and an anti-Leptospira IgM were negative. He received prednisolone, doxycycline, and acyclovir.
Figure 2.
Photograph of child with right-sided facial nerve palsy taken by a parent at the time of emergency department presentation, shared with the clinical care team, and approved for publication.
At day 35, he was evaluated in an infectious diseases clinic, at which time his facial nerve palsy had nearly resolved and a repeat anti-Leptospira IgM test remained negative. A serum Leptospira microscopic agglutination test (LMAT) showed no seroconversion, but whole blood and serum were positive for pathogenic Leptospira DNA by a LipL32 polymerase chain reaction (PCR) (CDC).3,4 A species-specific PCR on both samples identified the species as Leptospira interrogans.5 An investigation by the Minnesota Department of Health revealed that the pet dog developed transaminase elevation and hyperbilirubinemia after the initial veterinary exam. Testing of the dog’s serum yielded a positive LMAT with a peak titer of 1:6,400 for antibodies to L. interrogans serogroup Autumnalis, with lower titers against serogroups Djasiman, Grippotyphosa, Cynopteri, and Pomona, suggesting cross-reactivity.
At day 53, the child tested positive by PCR on urine for Leptospira spp. but negative on whole blood. Serum remained negative by LMAT. The child completed 14 additional days of doxycycline. Results of repeat testing of urine by PCR and serum by LMAT after the second course of antibiotics (day 123) were negative. Facial nerve palsy remained completely resolved, but the child continued to have fatigue and mild proteinuria.
This case highlights multiple diagnostic and management challenges with leptospirosis. Published cases describe highly variable presentations, ranging from asymptomatic to life-threatening disease due to renal and hepatic failure. Leptospira-associated unilateral6 and bilateral7 facial nerve palsies have been reported but are uncommon in adults and, to our knowledge, have not been previously described in children. The pathogenesis is incompletely understood but hypothesized to be caused by immune-mediated vasculitis,7 as cranial nerve palsies typically occur later in the course of illness, when most patients have a detectable antibody response. More typically, symptomatic individuals present with fevers and nonspecific associated symptoms, including headache and myalgias,8 making a diagnosis difficult on clinical grounds. Although some renal abnormalities were documented here, this finding was subtle (unexplained proteinuria), and other classic leptospirosis manifestations such as fever or liver abnormalities were notably absent. The patient did not fulfill the clinical criteria of the 2013 Council of State and Territorial Epidemiologists’ leptospirosis case definition9 but nevertheless met the laboratory criteria for a confirmed case based on the positive PCR test. Because fever is likely a key sign to prompt diagnostic evaluation, we speculate that there may be underdiagnosis of leptospirosis that occurs without fever if clinicians rely primarily on clinical criteria to establish the diagnosis.
Testing limitations presented an additional challenge. Rapid diagnostic tests are approved for veterinary use1,2 but are not widely available for humans. The only diagnostic testing available in the treating hospital was anti-Leptospira IgM, which was negative, but this result does not rule out leptospirosis, especially in early illness. The presence of anti-Leptospira IgM, by itself, is considered to be a supportive laboratory finding but is not confirmatory of a case of leptospirosis.9 The organism can be cultured, but this requires specialized media, bedside inoculation, and > 8 weeks of incubation. Polymerase chain reaction and LMAT were available only as send-out testing at the CDC. The Clinical Laboratory Improvement Amendments-approved PCR offers greater convenience than culture, and published data suggest high sensitivity for detection of Leptospira spp. in early illness. Identification of DNA in the blood is usually observed in the first days to a week after symptom onset.10 In contrast, urine PCR typically has a longer window for detection, and shedding can be intermittent and delayed for days to weeks from symptom onset. Nevertheless, comparative studies have shown improved sensitivity of leptospiral urine PCR, even early in disease.11 Consistent with this literature, Leptospira species was detectable in the patient’s urine nearly 8 weeks after initial presentation, at a time when blood testing had become negative. Interestingly, despite multiple positive PCR tests for Leptospira species, all serologic testing remained persistently negative, a discordance that has been previously described.10,12 For unclear reasons, some patients exhibit delayed seroconversion or no seroconversion at all, perhaps due to the ability of Leptospira species to evade the immune system.13 Titers can also be affected by antibiotic treatment initiated early in the illness, thereby blunting a robust antibody response. Thus, reliance on only serological testing may lead to a missed diagnosis.
Without a characteristic clinical illness, the epidemiologic risk factors are of paramount diagnostic importance. Leptospirosis is common worldwide, and many documented US cases occur among international travelers. Domestically acquired cases are also reported throughout the United States, with the majority of cases in tropical areas such as Hawaii and Puerto Rico.14 This patient had no international travel history and only potential exposures in Minnesota and Wisconsin. The co-occurrence of leptospirosis in the patient’s Minnesota-resident dog suggests that this was the likely location of exposure. Since 2005, 13 human cases of leptospirosis have been reported in Minnesota—seven associated with travel to international destinations or Hawaii and three linked to water exposure from triathlons in Florida and Texas. However, serological studies from Wisconsin children describe 7% seroprevalence,15 suggesting a substantial rate of potential undetected exposure and infection.
The lack of classic risk activities was also notable in this case. The majority of reported US-acquired cases are associated with recreational water exposure or occupational animal exposures. In this case, dog-to-child transmission seems possible, as a retrospective epidemiological investigation revealed that the boy reported cleaning up urine from the incontinent, ill-appearing dog without protective equipment prior to his own symptom onset. Clusters of dog infections have been well documented across the United States,16 but a recent serosurvey of pet owners, veterinarians, and veterinary technicians during an outbreak of canine leptospirosis in Arizona showed no evidence of seroconversion in adult persons exposed to infected dogs.17 Notably, the study did not include children, who may be at increased risk for transmission from pets due to factors such as poor hygiene and the close nature of contacts.18 In this case, we cannot rule out infection of both the child and the dog from a common environmental source nor prove that they were infected by the same Leptospira species or serovar, since isolates could not obtained and the dog had no PCR-positive sample available. Although dogs may be infected via traditional water activities such as hunting or swimming, more modest outdoor exposure to environments frequented by urban and suburban domestic animals and wildlife (e.g., raccoons) may also pose significant transmission risk.19,20 Although a canine vaccine against some serogroups has been licensed since the 1970s, the vaccine is not universally recommended, and published data indicate geographically heterogeneous coverage at the state level ranging from 20.3% to 97.5%, with a median rate of 57.4% in Minnesota.21 2022 AAHA Canine Vaccination Guidelines from the American Animal Hospital Association recommend Leptospira species vaccination “for some dogs based on lifestyle, geographic location, and risk of exposure.”22 Thus, there is a risk that vaccination may be administered preferentially in larger dogs with higher perceived environmental risk factors than smaller, primarily indoor, breeds. Although smaller dogs may be perceived to be at lower risk, the rates of leptospirosis have actually increased disproportionately among these dogs, particularly those < 15 pounds.23 Thus, small-breed dogs should also be regarded as at risk for infection and a potential risk of transmission to their owners. Vaccination efforts among these companion animals may provide an opportunity to prevent zoonotic transmission.
In summary, this case highlighted several unusual features of leptospirosis, including the rare clinical manifestation of facial nerve palsy, absence of traditional exposures, prolonged PCR detection after initial treatment, and lack of seroconversion. Clinicians should be aware of the specialized testing needed to confirm the diagnosis and epidemiological trends of leptospirosis in the US canine and other animal populations, as increased animal cases may indicate increased risk of this disease in US-based human populations due to both animal and environmental exposures.
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