Concomitant leptospirosis-hantavirus co-infection in acute patients hospitalized in Sri Lanka: implications for a potentially worldwide underestimated problem

Abstract

Two global (re-)emerging zoonoses, leptospirosis and hantavirus infections, are clinically indistinguishable. Thirty-one patients, hospitalized in Sri Lanka for acute severe leptospirosis, were after exclusion of other potentially involved pathogens, prospectively screened with IgM ELISA for both pathogens. Of these, nine (29·0%) were positive for leptospirosis only, one (3·2%) for hantavirus only, seven (22·5%) for both pathogens concomitantly, whereas 13 (41·9%) remained negative for both. Moreover, in a retrospective study of 23 former patients, serologically confirmed for past leptospirosis, six (26·0%) were also positive in two different IgG ELISA hantavirus formats. Surprisingly, European Puumala hantavirus (PUUV) results were constantly higher, although statistically not significantly different, than Asian Hantaan virus (HTNV), suggesting an unexplained cross-reaction, since PUUV is considered absent throughout Asia. Moreover, RT-PCR on all hantavirus IgM ELISA positives was negative. Concomitant leptospirosis-hantavirus infections are probably heavily underestimated worldwide, compromising epidemiological data, therapeutical decisions, and clinical outcome.

Keywords: Acute kidney injury (AKI); Sri Lanka; co-infections; hantavirus; leptospirosis; rodents; scrub typhus.

Fig. 1.

Prospective study. ELISA IgM results in acute and convalescent sampling for Puumala virus (PUUV) in eight cases of seroconfirmed (ELISA IgM positive) leptospirosis; and one leptospirosis-negative case (case 7). Results are expressed as Q values (observed OD/control cut-off OD), where Q values ⩾2 (- - - -) are considered as positives. Case 1 (red line) remained just under the positivity level, whereas case 2 (■) and case 5 (*) remained PUUV-negative. Five other cases are clearly PUUV-positive in at least one sampling.

Fig. 2.

Prospective study. ELISA IgM results in acute and convalescent sampling for Hantaan virus (HTNV) in eight cases of seroconfirmed (ELISA IgM positive) leptospirosis and one leptospirosis-negative case (case 7). Results are expressed as Q values (observed OD/control cut-off OD), where Q values ⩾2 (- - - -) are considered as positives. Case 1 (red line) is confirmed as hantavirus-negative, whereas case 9 (◊) and case 6 (○) are confirmed as PUUV-positive. Case 2 (■) and case 5 (*) are confirmed as borderline HTNV-positive, and consequently as only PUUV positive.

Fig. 3.

Prospective study. ELISA IgM in acute and convalescent sampling for leptospirosis in nine cases with equivocal or confirmed hantavirus infection. An OD of 0·3 (- - - -) is the cut-off for positivity. Case 1 (red line) is the only case with a seroconversion within 25 days, thus very likely an acute leptospirosis case. All other cases have more stable titres, suggesting recent but not acute leptospirosis. Case 7 (□) is confirmed as leptospirosis-negative, thus as an exclusive hantavirus (PUUV)-only infection.

Fig. 4.

Retrospective study. (a) ELISA Ig G results for leptosirosis. The solid line (––) is the mean optical density (OD), the dotted line (- - - -) the cut-off level for positivity. Only one patient was completely IgG-negative (OD = 0·0), shown as an open symbol on the baseline of OD = 0. (b) ELISA IgG results for hantaviruses, Hantaan virus (HTNV) and Puumala virus (PUUV). Results are expressed as Q values (observed OD/control cut-off OD), where Q values >1 (- - - -) are considered as positives. Six patients had IgG levels positive for PUUV, where two cross-reacted also with HTNV. No case had exclusive HTNV seroreactivity. The only patient seronegative for leptospirosis is shown in red.

Fig. 5.

Map of Sri Lanka with the localization of habitats of the different categories of patients described.