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Severe leptospirosis and pancreatitis; A case series from a leptospirosis outbreak in Anuradhapura district, Sri Lanka

BMC Infectious DiseasesBMC series – open, inclusive and trusted201616:644

https://doi.org/10.1186/s12879-016-2010-4

Received: 8 January 2016

Accepted: 2 November 2016

Published: 7 November 2016

Abstract

Background

Acute pancreatitis is identified as an atypical and rare presentation of leptospirosis. In this report, we discuss a case series of severe leptospirosis with pancreatitis as a main complication during an unusual outbreak of leptospirosis in Anuradhapura district, Sri Lanka.

Case presentation

We retrospectively reviewed clinical presentation, investigations, treatment and outcome of six confirmed cases of severe leptospirosis admitted to intensive care unit (ICU) of Teaching Hospital, Anuradhapura, within a three months period from November 2014 to January 2015.

All six patients were previously healthy paddy farmers presented with fever, myalgia and arthralgia. Four patients had abdominal pain, nausea and vomiting on admission. Hypotension, Neutrophilic leukocytosis and thrombocytopaenia was detected in all patients in the initial stage. Four patients had serum amylase more than 900 (range 941–2420). All patients had acute kidney injury and hepatitis. Significantly elevated amylase and low serum calcium were present in 4 cases. Five patients recovered without any evidence of residual organ damage, but one succumbed to the illness.

Conclusion

This case series emphasizes the importance of identification of acute pancreatitis as a common complication of Leptospirosis, in order to reduce mortality and morbidity.

Background

Leptospirosis is a poverty related, neglected tropical disease. Increased frequency of leptospirosis outbreaks were noted in Caribbean islands, Central and South Americas and South East Asia recently [1]. The disease is caused by a spirochete transmitted by direct or indirect contact with the urine of an infected animal through abrasions of the skin, or mucous membranes of mouth, nose, ear or conjunctiva. It is considered as the most widespread zoonotic disease [2] affecting all rodent, mammals, birds, marsupials and amphibians. Over 250 serovars, classified into more than 31 serogroups are reported from tropics and subtropics [3]. DNA hybridization based genetic classification shows at least 21 species of Leptospira.

Only a minor percentage of leptospirosis infections are symptomatic. Among symptomatic patients, initial leptospireamic phase is febrile with clinical features such as fever, arthralgia, myalgia, pharyngitis, cough, headache, chills, rigors, conjunctival suffusion and non pruritic rash [3]. Resolution of the febrile phase occurs with the clearance of Leptospira from bloodstream. The immune phase can occur in less than 10 % of patients, and was first described as Weil’s disease more than a century ago [4]. In this phase, fever, jaundice, hepatitis, acute kidney injury, myocarditis, hemorrhage and rarely pancreatitis can occur. Virtually any organ system can be involved during this phase [5]. Even though the classical Weil’s disease is considered “pathognomic” for leptospirosis by some clinicians, increasing number of atypical presentations are observed among leptospirosis recently. In Sri Lanka, differences of clinical presentations and sequale was described previously and attributed to micro geographic changes [6]. In this paper, we describe a series of patients with severe leptospirosis, presented to a single hospital within a period of three months, during an outbreak of leptospirosis.

Case presentation

We reviewed six cases of severe leptospirosis admitted to Intensive Care Unit (ICU) of Teaching Hospital, Anuradhapura, Sri Lanka within a three months period from November 2014 to January 2015. Data on socio-demographic factors, presenting clinical features, examination findings, investigations and management was collected through direct interviews during follow up clinic visits and from hospital records. Leptospirosis was confirmed in all patients with microscopic agglutination test (MAT) for acute sera, using a panel of 12 serovars in Medical Research Institute (MRI), Sri Lanka (National reference laboratory). Five patients were reviewed in outpatient clinics at two weeks after being discharged from the hospital. Informed written consent was taken from all the patients recruited for the study.

All six patients were previously healthy, male paddy farmers from Anuradhapura district. They all had fever, myalgia and arthralgia on presentation. Four patients (case 1–4) complained of abdominal pain radiating to back and nausea and vomiting on admission (Table 1).
Table 1

Presenting clinical symptoms of six confirmed cases of leptospirosis complicated with pancreatitis

Case number

Age

Fever

Myalgia

Chest pain

Abdominal pain

01

57

+

+

-

+

02

48

+

+

-

+

03

28

+

+

-

+

04

47

+

+

-

+

05

33

+

+

-

-

06

44

+

+

-

-

On examination, four patients had conjunctival suffusion and three were icteric (Table 2). None of the patients were edematous and only a single patient had bleeding manifestations. Epigastric tenderness and guarding (tensing of the abdominal wall muscles to guard inflamed organs within the abdomen from the pain of pressure upon them) was elicited with four patients who were having abdominal pain on admission. Hypotension (systolic blood pressure < 90 mm Hg) was detected in all cases.
Table 2

Clinical findings of six confirmed cases of leptospirosis

Case number

General examination

Cardiovascular System

Respiratory system

Abdomen

Conjunctival suffusion

Pallor

Icterus

Edema

Bleeding manifestations

Tachycardia (PR > 90/min)

Low BP (SBP < 90 mmHg)

Tachypnoea (RR > 20)

Crepitations

Tenderness

Hepatomegaly

01

+

-

+

-

-

+

+

-

+

+

-

02

-

+

+

-

-

-

+

-

+

+

+

03

+

-

-

-

-

+

+

+

+

+

-

04

+

-

-

-

-

+

+

+

+

+

-

05

-

-

-

-

-

-

+

-

+

-

+

06

+

-

+

-

+

+

+

+

+

-

+

PR Pulse rate, BP Blood pressure, SBP Systolic blood pressure, RR Respiratory rate

Neutrophilic leukocytosis (White Blood Cell count (WBC) > 11,000/ μl) and thrombocytopaenia (Platelet count <100,000/μl) was detected in all patients in the initial stage. All patients had acute kidney injury (AKI) with varying severity with proteinuria and microscopic haematuria. Liver enzymes (6/6), direct hyper-bilirubinemia (5/6) and high alkaline phosphatase (ALP) (in 6/6) had been present in all cases at the presentation. Significantly elevated amylase (> five times the upper normal value), and low serum calcium levels were present in cases 1-4 (Tables 3 and 4). There were marked epigastria tenderness and guarding in cases 1–4. Serial analysis of serum amylase showed initial rapid rise even before establishment of AKI. Thereafter, serum amylase level plateaued followed by declining to normal. Low serum calcium supported the diagnosis. We could not perform CT in view of AKI, but this would have been supportive evidence for diagnosis of acute pancreatitis.
Table 3

Blood and urine biochemistry of six confirmed cases of leptospirosis

Case

FBC

RFT

UFR

SE (mEq/L)

ABG

Number

WBC (x109/L)

N%

PCV (%)

Hb (g/dl)

Plt (x109/L)

Cr (mmol/l)

BUN (mmol/l)

Albumin

leucocytes/field

RBC/filed

Na

K

Ca

pH

HCO3-

1

13.5

87.4

34

10.9

23

177→379

16.1

2+

10–20

30–40

141

5

2.02

7.35

18.6

2

13.7

85.8

35.5

11.7

11

281→448

20.8

2+

15–20

20–30

129

5

1.50

7.32

12.8

3

18.2

86.2

36.9

11.6

13

429→464

37.5

2+

10–15

40–50

140

4

2.05

7.36

12.8

4

15.1

78

35.4

11.6

56

247→269

13

2+

10–15

20–30

140

2.9

2.00

7.38

14

5

14.4

82

36.5

12.6

27

144→167

13.3

2+

10–15

30–40

143

3.2

2.06

7.44

18.4

6

19

93

32

10.3

11

306→434

14

2+

15–20

40–50

139

4.5

1.76

7.4

18.4

FBC full blood count, WBC White blood cell count, PCV Packed cell volume, Hb Haemoglobin, Plt Platelet count, RFT Renal function tests, Cr Creatinine, BUN Blood uria nitrogen, UFR Urine full report, SE serum electrolytes, Na Sodium, K Potassium, Ca Calcium, ABG Arterial blood gasses

Table 4

Blood and urine biochemistry of six confirmed cases of leptospirosis

Case No

LFT

AST (units/l)

ALT (units/l)

Total Bilirubin (μmol/L)

Direst bilirubin (μmol/L)

INR

ALB (g/L)

Serum Amylase (units/l)

ALP units/l)

1

96

66

20.3

14.6

1.1

39

983→375

266

2

109

99

105

-

1.34

33

2162→ 2420

254

3

78

38

194

184

1.27

30

2365→204

292

4

148

148

53.5

29.1

1.15

32

941→285

270

5

85

77

54

32.8

NA

30

107

260

6

132

116

100

86.9

1.08

33

193

280

AST Aspartate aminotransferase, ALT Alanine aminotransferase, INR International normalized ratio, ALB Albumin, ALP Alkaline phosphatase

All patients had multiple complications (Table 5). They were treated in medical ICU and needed two or more inotropes. All of them were given IV C penicillin, cefotaxime and doxycycline for 10 days. Low dose IV hydrocortisone was given initially to all patients to improve blood pressure. Case number 2 and 6 needed dialysis and in others kidney functions improved without renal replacement therapy.
Table 5

Complications and clinical outcome among six confirmed cases of leptospirosis

Case No.

Complications

Outcome

01

Pancreatitis, AKI, hepatitis

Fully recovered

02

Pancreatitis, AKI, hepatitis,

Died

03

Pancreatitis, AKI, hepatitis, myocarditis

Fully recovered

04

Pancreatitis, AKI, hepatitis, myocarditis

Fully recovered

05

Myocarditis, AKI, hepatitis

Fully recovered

06

AKI, hepatitis, myocarditis

Fully recovered

Case number 2 died during acute illness (on day 7) due to refractory hypotension and multiorgan failure. Rests of the patients were reviewed after 2 to 4 weeks post discharge. They all had complete recovery, without any evidence of residual organ damage.

Discussion

Acute pancreatitis was previously reported as an uncommon complication of leptospirosis [79]. In Sri Lanka, pancreatitis was previously reported in one confirmed [10] and one probable [11] cases of leptospirosis.

The exact mechanism of acute pancreatitis in leptospirosis is not fully described. An immunological basis for pathogenesis of leptospirosis including Toll like receptor (TLR) 2 activation is described recently [12]. The most consistent pathologic finding in leptospirosis is vasculitis of capillaries manifested by endothelial oedema, necrosis and lymphocytic infiltration. Small vessel vasculitis and ischemic injury leading to activation of proteolytic enzymes and auto-digestion is a possible mechanism [12]. All the patients described in the current series, were hemodynamicaly unstable at presentation or within the first 24 h of hospital stay. Refractory hypotension can lead to multi-organ failure which could be another cause for acute pancreatitis in these patients.

Whatever the mechanism behind, finding of pancreatitis among four out of six confirmed cases admitted to ICU during a single epidemic of leptospirosis in a geographically defined region needs further investigation. In another study done during this same outbreak of leptospirosis in Anuradhapura district, but in a different hospital, clinical presentations were reported as different from 2011 outbreak [13]. This observation could be explained by previous observations of micro geographical changes of leptospirosis in Sri Lanka and the hypothesis on etiological differences of epidemic and endemic leptospirosis [6]. Alternatively, the observed outbreak of pancreatitis could be due to a new strain or a slight difference in the endemic strain of Leptospira as described previously [14]. We have not carried out molecular studies during this outbreak to evaluate latter hypothesis. However, we propose further studies to explain different clinical manifestations by different strains of Leptospira within the same localities during different outbreaks.

There are reports of co-infections of Leptospira and Hantavirus infections in Sri Lanka [15]. Similarly co-infections could occur in these patients with various other infectious causes of acute pancreatitis i.e. parasites (Ascaris, toxoplasma), viruses (hepatits B, Coxsackie, CMV, mumps), bacteria (Mycoplasma, Salmonella). We have not excluded other co-infections in the present case series, which could be a rare alternative explanation for the observation.

Conclusion

This case series highlight the importance of identification of acute pancreatitis as a complication of leptospirosis. Awareness regarding this important complication is important to decrease risk of lethal outcome.

Declarations

Funding

None.

Availability of data and materials

All data contained within the article.

Authors’ contributions

HNJ Perceived the study. HNJ and KCJ followed up the patients, provided patient care and collected and interpreted clinical data. ASB involved in design, analyzed and interpreted the data and prepared the first draft of manuscript. All authors contributed to the manuscript, and read and approved the final manuscript.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Written informed consent was obtained from all the patients, or next of kin, for publication of their individual details.

Ethics approval and consent to participate

Not applicable.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Teaching Hospital
(2)
Department of Community Medicine, Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka

References

  1. Hartskeerl RA, Collares-Pereira M, Ellis WA. Emergence, control and re-emerging leptospirosis: dynamics of infection in the changing world. Clin Microbiol Infect. 2011;17(4):494–501.View ArticlePubMedGoogle Scholar
  2. WER. Leptospirosis worldwide, 1999. Wkly Epidemiol Rec. 1999;74(29):237–42.Google Scholar
  3. Faine S, Adler B, Bolin C, Perolat P. Leptspira and Leptospirosis, 2 edn. Melbourne: MediSci; 1999.Google Scholar
  4. Inada R, Ido Y, Rokuro K, Kaneko R, Ito H. The etiology, mode of infection, and specific therapy of Weil's Disease (Spirochaetosis icterohaemorrhagica). J Exp Med. 1915;23:377–402.View ArticleGoogle Scholar
  5. Cachay ER, Vinetz JM. A global research agenda for leptospirosis. J Postgrad Med. 2005;51(3):174–8.PubMedPubMed CentralGoogle Scholar
  6. Agampodi SB, Dahanayaka NJ, Bandaranayaka AK, Perera M, Priyankara S, Weerawansa P, Matthias MA, Vinetz JM. Regional differences of leptospirosis in Sri Lanka: observations from a flood-associated outbreak in 2011. PLoS Negl Trop Dis. 2014;8(1):e2626.View ArticlePubMedPubMed CentralGoogle Scholar
  7. Daher Ede F, Brunetta DM, de Silva Junior GB, Puster RA, Patrocinio RM. Pancreatic involvement in fatal human leptospirosis: clinical and histopathological features. Rev Inst Med Trop Sao Paulo. 2003;45(6):307–13.View ArticlePubMedGoogle Scholar
  8. Panagopoulos P, Terzi I, Karanikas M, Galanopoulos N, Maltezos E. Myocarditis, pancreatitis, polyarthritis, mononeuritis multiplex and vasculitis with symmetrical peripheral gangrene of the lower extremities as a rare presentation of leptospirosis: a case report and review of the literature. J Med Case Rep. 2014;8:150.View ArticlePubMedPubMed CentralGoogle Scholar
  9. Silva AP, Burg LB, Locatelli JFS, Manes J, Crispim M. Leptospirosis presenting as ascending progressive leg weakness and complicating with acute pancreatitis. Braz J Infect Dis. 2011;15:493–7.View ArticlePubMedGoogle Scholar
  10. Ranawaka N, Jeevagan V, Karunanayake P, Jayasinghe S. Pancreatitis and myocarditis followed by pulmonary hemorrhage, a rare presentation of leptospirosis- a case report and literature survey. BMC Infect Dis. 2013;13:38.View ArticlePubMedPubMed CentralGoogle Scholar
  11. Prasanthie HMM, De Silva KHPUD. A rare complication of leptospirosis: acute pancreatitis. Galle Med J. 2008;13(1):69–70.Google Scholar
  12. Kaya E, Dervisoglu A, Eroglu C, Polat C, Sunbul M, Ozkan K. Acute pancreatitis caused by leptospirosis: report of two cases. World J Gastroenterol. 2005;11(28):4447–9.View ArticlePubMedPubMed CentralGoogle Scholar
  13. Ramsey A, Rubin-smith J, Norwich A, Katumuluwa S, Hettiarachchi A, Wimalage S, Danushka W, Madushanka T, Nadeeshani A, Thilakarathna C, et al. Outbreak Investigation of Leptospirosis in Padaviya, Sri Lanka. Anuradhapura Med J. 2015;09(2):23–6.View ArticleGoogle Scholar
  14. Thaipadungpanit J, Wuthiekanun V, Chierakul W, Smythe LD, Petkanchanapong W, Limpaiboon R, Apiwatanaporn A, Slack AT, Suputtamongkol Y, White NJ, et al. A Dominant Clone of Leptospira interrogans Associated with an Outbreak of Human Leptospirosis in Thailand. PLoS Negl Trop Dis. 2007;1(1):e56.View ArticlePubMedPubMed CentralGoogle Scholar
  15. Sunil-Chandra NP, Clement J, Maes P, Des HJ, Vane M, Vanr M. Concomitant leptospirosis-hantavirus co-infection in acute patients hospitalized in Sri Lanka: implications for a potentially worldwide underestimated problem. Epidemiol Infect. 2015;143(10):2081–93.View ArticlePubMedGoogle Scholar

Copyright

© The Author(s). 2016

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