Dengue fever and leptospirosis are important causes of acute febrile illness whose clinical signs overlap. Clinical diagnosis and confirmation remain a challenge mainly because of the lack of affordable and practical diagnostic tests for both [22, 25]. Other common differential diagnosis of systemic leptospirosis includes hemorrhagic yellow fever, influenza, hantavirus infection, viral hepatitis, malaria, typhoid, Rickettsial relapsing fever, meningitis, and encephalitis.

Complete blood count may reveal neutrophilia, elevated erythrocyte sedimentation rate, thrombocytopenia, and anemia. Renal function tests reveal azotemia and hyponatremia. Urine examination may reveal microscopic hematuria, proteinuria, pyuria, and granular casts.

Diagnosis of systemic leptospirosis is confirmed only by isolation of the organisms which is possible during the first week of infection, before the appearance of antibodies. Alive motile leptospires can be seen under dark-field microscopy in the blood, urine, or cerebrospinal fluid. Leptospira can be grown in special media such as Ellinghausen-McCullough-Johnson-Harris (EMJH) medium. Beyond 10 days, the microscopic agglutination test (MAT) is commonly used as a diagnostic gold standard. Motile bacteria in liquid medium are added with titrated amounts of patient’s serum. When the serum contains antibodies, agglutination is observed under dark-field microscopy. This test relies on detecting an increase in antibody titer between two serum samples obtained at least 2 weeks apart. Seroconversion or a fourfold rise in paired serum samples or a titer above 1:400 dilution in the presence of a compatible clinical illness is considered diagnostic for systemic leptospirosis. In chronic immunological reactions like uveitis where fourfold raise cannot be demonstrated, a titer of 1:100 dilutions is usually considered significant. MAT requires live organisms and considerable expertise, and it is performed only by reference laboratories. It is not available in primary ophthalmic setup [6, 26].

Other serological tests include ELISA, macroscopic agglutination, indirect hemagglutination, LEPTO dipstick, immunofluorescence assay, microcapsule agglutination tests, microsphere immunoassay, and lateral flow assays. Molecular diagnostics include conventional polymerase chain reaction (PCR) and real-time PCR [27, 28]. In one of the studies, commercial serodiagnostic kits showed varying sensitivity and specificities, and they did not correspond with each other [29]. It is mandatory for the practitioner to check the reliability of the locally available diagnostic kits.

Next-generation sequencing is a very recent technology for determining DNA sequence by analyzing multiple DNA fragments in parallel. It allows sequencing of an exponentially greater number of genes than conventional DNA sequencing. Molecular diagnostics will prove its potential use in future [22]. But these advanced procedures are not available in health centers in tropical countries where the disease is more common.

Leptospires are sensitive in vitro to most antimicrobial agents, including penicillin, amoxicillin, doxycycline, and ceftriaxone. Treatment details are given in Table 8.2. In addition to antimicrobial agents, supportive therapy is mandatory in severe cases. Depending upon the organ involved, patient may need management of electrolyte imbalance, renal dialysis, mechanical ventilation, airway protection, and cardiac monitoring and administration of vitamin K in patients with hypoprothrombinemia [30].

The spectrum of ocular manifestation leptospirosis can be seen both in septicemic phase and in immune phase. In a febrile patient, conjunctival chemosis and congestion are pathognomonic signs for the diagnosis of systemic leptospirosis, but they are frequently overlooked. In one case series, chemosis and congestion occurred in 55 % of patients with systemic leptospirosis [31].

Uveitis is an important late complication of leptospirosis [26, 32]. The precise incidence of uveitis in patients with systemic leptospirosis is not known, but it is estimated to be about 10–45 % [33]. Uveitis manifests within 2 months after infection or may be delayed for up to 1 year. The onset and severity of leptospiral uveitis is quite variable, and the severity of ocular inflammation does not correlate with the severity of systemic infection. Leptospiral uveitis more commonly occurs as single episode than recurrent episodes. The primary anatomical location of inflammation tends to be either anterior or panuveitis. Nongranulomatous uveitis is the most common presentation.

Ocular signs of leptospirosis are given in Table 8.3. Anterior uveitis is usually mild in contrast to severe course characteristic of panuveitis. Leptospiral uveitis is one of the most common causes of hypopyon uveitis in leptospiral endemic areas. Early onset, rapid progression, and spontaneous absorption of cataractous lens are unique features in this uveitis; however it is seen only in 10 % of leptospiral uveitis [34] (Fig. 8.1).

Dense vitreous inflammation with the formation of veil-like vitreous membranes is a pathognomonic sign seen in posterior segment. Although these membranes persist for several months, most patients regain good vision. Exudative retinal vasculitis with perivascular sheathing of the vein is frequently seen in leptospiral uveitis; however occlusion and neovascularization are uncommon. Disc hyperemia and edema are seen in 40 % of leptospiral uveitis patients. Retinitis and choroiditis are never seen in leptospiral uveitis. Although leptospiral uveitis is a common entity, it remains underdiagnosed mainly because of the lack of laboratory support in ophthalmic setup (Figs. 8.2 and 8.3).

Differential diagnosis of leptospiral uveitis includes Behcet’s disease, HLA-B27-associated anterior uveitis, syphilis, Lyme disease, endogenous endophthalmitis, sarcoidosis, and early stage of acute retinal necrosis.