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. 2022 Apr 4;16(4):e0010331.
doi: 10.1371/journal.pntd.0010331. eCollection 2022 Apr.

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

Janith Warnasekara  1 , Shalka Srimantha  1 , Chamila Kappagoda  1 , Dinesha Jayasundara  1   2 , Indika Senevirathna  1   3 , Michael Matthias  4 , Suneth Agampodi  1   4 , Joseph M Vinetz  4
Affiliations

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

Janith Warnasekara et al. PLoS Negl Trop Dis. .

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Distribution of study settings in relation to climate zones of Sri Lanka.
Black: Blood, urine, and culture were collected from undifferentiated febrile patients throughout the period; Green: Blood, urine, and culture were collected from undifferentiated febrile patients during 2016, 2017; Red: Blood, urine, and culture were collected from probable leptospirosis patients during 2018, 2019; Blue: Blood, urine, and culture were collected from undifferentiated febrile patients during the flood season of 2017; Yellow: Only cultures were received.
Fig 2
Fig 2. Study flow chart, inclusion-exclusion criteria, and diagnostic tests.
Fig 3
Fig 3. Heat map showing the percentage of positive cases by patient-reported day of illness, until day 15 of patient-reported symptoms.
Fig 4
Fig 4. Comparison of the distribution of confirmed cases of leptospirosis with the general population age structure in Sri Lanka.
Fig 5
Fig 5. Diagnostic method-based underestimation of leptospirosis in clinical settings.
The total number of tests done to calculate proportions is indicated in the inner circle. Figure legend: The inner circle shows the number of samples tested using each test (denominator) and the number of confirmed cases included in that sample (numerator). The outer circle indicates the percentage of confirmed cases detected or missed by each test (from the numerator of the inner circle). For example, 1455 samples were tested using whole blood qPCR. Of these 1455 patients, 540 were finally confirmed as leptospirosis. However, only 322 were tested positive using qPCR, and it missed approximately 40% of confirmed cases.
See this image and copyright information in PMC

References

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