Diagnostic method-based underestimation of leptospirosis in clinical and research settings; an experience from a large prospective study in a high endemic setting

Abstract

Background Leptospirosis has globally significant human mortality and morbidity, yet estimating the clinical and public health burden of leptospirosis is challenging because timely diagnosis remains limited. The goal of the present study was to evaluate leptospirosis undercounting by current standard methods in both clinical and epidemiological study settings. Methodology/Principal findings A prospective hospital-based study was conducted in multiple hospitals in Sri Lanka from 2016 to 2019. Culture, whole blood, and urine samples were collected from clinically suspected leptospirosis cases and patients with undifferentiated fever. Analysis of biological samples from 1,734 subjects confirmed 591 (34.1%) cases as leptospirosis and 297 (17.1%) were classified as “probable” leptospirosis cases. Whole blood quantitative PCR (qPCR) did identify the most cases (322/540(60%)) but missed 40%. Cases missed by each method include; urine qPCR, 70% (153/220); acute sample microscopic agglutination test (MAT), 80% (409/510); paired serum sample MAT, 58% (98/170); and surveillance clinical case definition, 53% (265/496). qPCR of negative culture samples after six months of observation was of diagnostic value retrospectively with but missed 58% of positives (109/353). Conclusion Leptospirosis disease burden estimates should consider the limitations of standard diagnostic tests. qPCR of multiple sample types should be used as a leading standard test for diagnosing acute leptospirosis.

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

“…Leptospirosis has globally significant mortality and morbidity, yet the diagnosis is challenging because of the lack of ‘the diagnostic test’ which has high sensitivity and specificity [1 ▪▪ ,47 ▪▪ ].…”

“…Cases missed by each method include; acute sample MAT, 80% (409/510); paired serum sample MAT, 58% (98/170); urine qPCR, 70% (153/220); and surveillance clinical case definition, 53% (265/496). Whole blood quantitative PCR (qPCR) missed 40% of cases [47 ▪▪ ]. Authors conclude that qPCR of multiple sample types should be used as a leading standard test for diagnosing acute leptospirosis [47 ▪▪ ] which is indeed not possible in primary care settings.…”

“…Whole blood quantitative PCR (qPCR) missed 40% of cases [47 ▪▪ ]. Authors conclude that qPCR of multiple sample types should be used as a leading standard test for diagnosing acute leptospirosis [47 ▪▪ ] which is indeed not possible in primary care settings.…”

Remember Leptospirosis: two cases report

“…Leptospirosis is one of the most common but potentially fatal zoonoses, caused by Leptospira species. As the clinical manifestations can be very diverse, the occurrence of this disease is underestimated [1,2], and is often misinterpreted as other causes of the febrile syndrome. Ninety percent of patients are asymptomatic or have mild symptoms, with sudden-onset fever being the most reported symptom [2].…”

“…As the clinical manifestations can be very diverse, the occurrence of this disease is underestimated [1,2], and is often misinterpreted as other causes of the febrile syndrome. Ninety percent of patients are asymptomatic or have mild symptoms, with sudden-onset fever being the most reported symptom [2]. Anicteric leptospirosis can also present with other manifestations, such as headache, myalgias, chills, abdominal pain, vomiting, diarrhea, conjunctival suffusion, and skin rash [3].…”