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MATERIALS AND METHODS penicillin G, every 6 hours. l* The antibiotic was switched
to 500 mg of oral amoxycillin thrice daily when the
Subjects patients were free of fever and clinically improved for at
least 24 hours. For mild cases of leptospirosis, 100 mg of
This study was conducted in Khon Kaen General oral doxycycline twice daily was given for seven days.19
Hospital, a tertiary care hospital in the northeastern part Intravenous third generation cephalosporin were given
of Thailand, between June 1999 and December 1999. initially in 16 patients before severe bacterial infection
Diagnosis of leptospirosis was based on the World
could be excluded. The antibiotic was then switched to
Health Organization (WHO) criteria for leptospirosis
sodium penicillin G when the diagnosis of leptospirosis
diagnosis12 and serologically proven leptospirosis using
was confirmed. Fifty-nine patients (48.7%) had received
an IgM-specific LEPTO dipstick assay (titer >1:100).13
at least one dose of antibiotics, including sodium penicillin
Serovars of leptospirosis were identified by a micro- G, ampicillin, doxycycline, amoxycillin, or third gener-
scopic agglutination test. 14,15Patients who had concurrent ation cephalosporin before admission. Supportive care,
systemic infection, such as respiratory tract infection,
including intravenous fluid infusion, respirator support,
bacterial septicemia, malaria, and rickettsial infection,
blood component transfusions, vasopressors, dialysis,
were excluded from this study. Children, who contri-
and other medications were provided as needed. All
buted less than 5% of the total leptospirosis patients in
patients were requested to return for follow up at 2
this hospital, were also excluded. Two hundred and
weeks after discharge.
seventy six patients were admitted to the hospital because
of acute febrile illness and suspicion of leptospirosis.
However, only 121 cases met the study criteria and Statistical analysis
formed the cohort. They were then followed until they
Continuous data were presented as mean *SD.
died or for two weeks after discharge from the hospital.
Unpaired t-test was used to test for the difference of the
means between two studied groups, survivors and
nonsurvivors. Categorical data were presented as
Data collection
proportions. Chi square test and Fisher’s exact test were
Patients’ characteristics, presenting symptoms, previous used to test the difference of the proportion between the
antibiotic use, and physical findings were recorded on two groups as appropriate. The Kaplan-Meier survival
admission. Blood samples were obtained on admission method was used to estimate survival probability. Onset
for determination of the following parameters: hemo- was the date when the first symptom presented, and the
globin, hematocrit, complete blood count, blood urea end of study was the date when the patient died or was
nitrogen, serum creatinine, serum electrolyte, creatine still alive at two weeks after discharge. The event of
phosphokinase (CPK), albumin, aspartate transaminase interest was death from leptospirosis. Patients were
(AST), total bilirubin, and alkaline phosphatase; a co- discounted if they still were alive at two weeks after
agulogram was performed for prothrombin time and discharge. Patient survival was related to multiple
partial thromboplastin time. Blood samples for hemo- potential risk factors, including age (>29,29-48 or ~48
culture, thick and thin film for malaria, IgM-specific years), interval between the first symptoms and admis-
LEPTO dipstick assay, and dot blot immunoassay for sion (> or 14 days), previous antibiotic use, the presence
the rapid diagnosis of rickettsial infection were also of hemorrhagic symptoms, neurological symptoms,
obtained.16 The WHO criteria for leptospirosis diagnosis
was recorded. The severity of the disease in the first 24
hours of admission was also assessed using a modified
APACHE II scoring system. The modified APACHE II Table 1. Percentage of presenting symptoms of survivors, non-
score was basically the same as the original APACHE II survivors, and total patients
except that the information on oxygenation was not Non-
included as this was not performed routinely on admis- survivors Survivors Overall
sion unless there was an indication.17 The modified Presenting symptoms (n=17) (n=104) (n=721)
APACHE II score was assessed and recorded by a well- Fever 100.0 100.0 100.0
trained nurse. The identification of organ involvement Myalgia 100.0 95.2 95.9
by leptospirosis was performed on admission by two Headache 88.2 89.4 89.3
Chill 82.4 77.0 77.7
internists. If there were discrepancies between the two Hemoptysis 29.4 22.5 23.5
internists, a third internist would be consulted for a final Jaundice 88.2 49.0* 54.5
decision. Definitions of organ involvement and indi- Conjunctival suffusion 52.9 52.9 52.9
Hypotension 94.1 44.2* 51.2
cations for treatment were presented in the appendix. Tachypnea
Severe cases of leptospirosis, defined by the presence (RR z 28/min) 70.6 18.3” 25.6
of acute renal failure (serum creatinine >2 mg/dl), Oliguria
(urine<400cdday) 76.5 12.5* 21.5
unstable vital signs, or multiple organ failure were
treated with 1.5 million unit of intravenous sodium *P<O.O5 when compared to non-survivors.
54 International Journal of Infectious Diseases I Volume 6, Number 1,2002
hemoptysis, bilateral pulmonary rales, hypotension that Most of them experienced prolonged water contact in
required vassopressor infusion, oliguria, respiratory rate rice fields. The WHO criteria for leptospirosis diagnosis
(> or 528 times/min), hematocrit (< or ?32%), leuko- was 22.2k3.1. The presenting symptoms and laboratory
cyte counts (> or <13,000/mm3), platelet counts (< or findings on admission are shown in Tables 1 and 2,
2 100,000/mm3), creatinine (> or 55 mg/dl), potassium respectively. Mean *SD duration between the date of
(> or 55 mg/dl), total bilirubin (> or 19 mg/dl), the first symptom related to leptospirosis and the date
aspartate transaminase (> or 580 IU/L), albumin level at admission was 5+2.2 days. Based on organ involve-
(< or 22.9 g/dl), creatine phosphokinase (> or 1440 ment, the clinical presentations of leptospirosis could be
IU/L), and modified APACHE II score (> or 515). categorized into four clinical syndromes: a) fever with
Univariate analysis of the potential risk factors was jaundice and renal failure, Weil’s syndrome, (60.3%); b)
done by univariate Cox regression analysis and log rank fever with renal failure (14.9%); c) fever with jaundice
test. Each factor was presented as incidence rate (per (4.1%); and d) f ever alone, without either jaundice and
100 patient-days), relative risk (hazard ratio) and renal failure (20.7%). Almost all patients were healthy
its 95% CL Multivariable Cox regression model was prior to the infection. Only two (1.6 %) patients had
performed to determine factors affecting patient’s diabetes mellitus.
survival, taking into account effects of several potential
factors simultaneously. Input variables for the multi-
Serovars of leptospira species
variable analysis were selected from significant variables
obtained from the univariate analysis. Linearity of Information on the serovars was available in only 35
continuous variables were explored and dichotomized, patients (28.9%). The serovars were L. sejroe in 21
using mean as the cutoff point, before the model fitting. patients (60%), L. brutisluva in eight patients (22.8%)
The linear variables included respiratory rate, L. bangkoki in three patients (8.4%), L. pyrogenese
hematocrit, leukocyte counts, serum creatinine, total in two patients (5.8%), and L. copenhageni and L.
bilirubin, aspartate aminotransferase, albumin level and icterohaemorrhagia in one patient each (2.9%). There
serum creatine transaminase. Age was the only non- were also combined infections with two serovas, L.
linear variable and was then categorized into three sejroe and L. bratislava in two patients (5.8%), and
groups based on the reverse U-shaped curve of the L. sejroe and L. pyrogenese in one patient (2.9%).
relationship between age and log hazard. The model was
fitted using backward elimination method. The signifi- Organ dysfunctions
cance of each variable in the model was determined
using partial likelihood ratio test. Model assumption and Thrombocytopenia, platelet count < 100,000 cells/mm3,
adequacy was assessed for the final model. was the most frequent organ dysfunction found in this
study (78.6%). Other organ involvement included acute
renal failure (74.2%), hepatitis (65.3 %), hypotension
requiring dopamine therapy (51.6%) congestive heart
RESULTS
failure (28.2%) pulmonary hemorrhage (9.1%) and
acute respiratory distress syndrome or ARDS (3.4%).
Baseline characteristics
Most patients with acute renal failure were nonoliguric
Among the 121 definite cases of leptospirosis (114 males type (80.4% of all patients with renal failure). Volume
and 7 females), 74.4% were farmers, aged 38t13.4 years. depletion was found to be the major contributing factor
Table 2. Laboratory findinqs on admission for survivors, non-survivors, and all patients
Non-
survivors Survivors Overall
Laboratory values (n=17) (n= 104) (f-t= 121)
Age (year)
~28 289 0.7 1 - -
29-48 601 1.8 2.7 0.6, 12.2 0.201
>48 316 1.3 1.9 0.3, 10.2 0.476
Delay time >4 days 678 1.4 1.0 0.4. 2.7 0.983
Previous antibiotic use 875 1.6 1.7 0516.1 0.378
Hemoptysis 292 1.7 1.4 0.5, 3.8 0.571
Hemorrhagic symptoms 402 1.4 1.0 0.4, 2.9 0.910
Neurological symptoms 222 0.9 0.6 0.1, 2.6 0.470
Tachypnea (resp. rate z28/min) 313 3.8 6.9 2.4, 9.7 <O.OOl
Bilateral pulmonary rales 447 3.1 7.9 2.3, 27.6 <O.OOl
Hypotension (dopamine use) 644 2.5 13.5 1.8,.101.9 0.001
Oliguria (urine ~400 cc/day) 247 5.3 14.5 4.7, 44.6 <O.OOl
Hematocrit ~32% 533 2.3 3.0 1.1, 8.6 0.028
WBC counts >13,000/mm3 613 2.1 3.2 1, 9.9 0.031
Platlet counts < 1 00,000/mm3 969 1.4 1.0 0.3, 3.6 0.958
Creatinine >5 mg/dl 656 2.3 6.0 1.4, 26.6 0.006
Hvperkalemia (K>5 mmolll) 67 10.4 14.2 5.2, 38.6 <O.OOl
Tdial bilirubin >9 mg/dl 488 2.0 2.1 0.8, 5.6 0.123
AST <8OIlJ/L 538 2.0 2.3 0.8, 6.2 0.093
Albumin c2.9 q/dl 494 2.4 3.5 1.2. 9.9 0.012
CPK>440lU/L - 499 2.6 5.1 1.6;15.8 0.005
Modified APACHE II score >I5 243 4.9 1.4 1.2, 1.6 -c0.001
Table 4. Unadjusted and adjusted relative risk of death for each selected factor using Cox-regression
model. Only significant risk factors in Table 3 were selected for the analysis
Unadjusted Adjusted
Factors RR RR 95% Q P*
Several risk factors for death from leptospirosis found to be a contributing factor to the development of
have been identified in previous studies.3,6-11 In our renal failure.lO In this study, there was a correlation
present study, a prospective, multivariable analysis to between creatine phosphokinase level and the maxi-
identify independent risk factors of death was done. mum serum creatinine level. However, the correlation
Factors that were included in the analysis based on between serum creatinine and degree of rhabdomyolysis
initial clinical and biochemical parameters were may be misleading. Serum creatinine is a metabolite of
obtained routinely on admission in order to develop an muscle creatine. Elevation in serum creatinine could
initial guideline for physicians to assess the severity of result from both rhabdomyolysis and the impaired renal
the disease. Subjective symptoms and biochemical function. The presence of renal failure in leptospirosis
parameters that were occasionally obtained in medical patients should receive special attention when it is
wards were excluded from our analysis. Additional organ accompanied by jaundice (Weil’s syndrome) because it
involvement or biochemical changes that developed is the clinical syndrome most associated with risk of
subsequently after the first day of admission were also death. In the absence of jaundice, the risk of death in
excluded. Cox regression model revealed that the renal failure patients was much lower, but it still
presence of hypotension, oliguria, hyperkalemia, and existed.30.31 There was no mortality in patients who had
bilateral pulmonary rales were the four risk factors no renal failure in our study. Hyperkalemia, the third
associated with death in leptospirosis. The presence of independent risk factor in our study, may reflect exten-
one or more of these risk factors should alert physicians sive cellular damage, resulting in massive potassium
to provide close monitoring and proactive management leakage into the systemic circulation, in addition to the
for all potential complications of leptospirosis. These presence of renal failure.
four parameters are simple and can be obtained in most The presence of bilateral diffuse pulmonary rales,
hospital settings.The biochemical markers that indicated the last independent risk factor in our study, may be
the severity of hepatitis, including bilirubin and serum associated with congestive heart failure, pulmonary
aspartate transaminase, were not independent risk hemorrhage, ARDS, or interstitial pneumonitis caused
factors of death in our analysis by leptospirosis. 32,33 Pulmonary manifestations are
Our findings are comparable to the findings from frequently observed in patients with leptospirosis. The
the DuPont et al. study in many aspects7 In their study, incidence varies from 20 to 70%, depending on the
a retrospective analysis of 56 leptospirosis patients over studies.3k36 Pulmonary hemorrhage and ARDS are two
a period of five years, five factors were independently of the most severe complications of leptospirosis. This
associated with mortality: dyspnea, oliguria, elevated association has been recognized in the last 20 years.37,38
white blood cell, abnormal ECG, and alveolar infil- Pulmonary hemorrhage and ARDS were the predomin-
tration on chest radiograph. By contrast, cardiovascular ant complications associated with death, involving 60%
collapse and hyperkalemia were not associated with of all mortality in our study, followed by complicated
higher mortality in their study. renal failure and multiple organ failure.
Hypotension or cardiovascular collapse on admis- The modified APACHE scoring system, which
sion, which was associated with the highest relative risk included multiple clinical and laboratory parameters
of death in our study, might reflect the presence of that were also used for the relative risk analysis, were
hypovolemia, increased vascular permeability, or poor not considered as another independent risk factor in our
myocardial function. 25,26Oliguria reflected the presence model. However, the scoring system is simple and
of severe renal failure, severe volume depletion, or very familiar to most physicians. It also provides a graded
poor renal perfusion. Renal failure, a common compli- assessment of the risk of death from leptospirosis. We,
cation of leptospirosis, affected one third of the cases in therefore, suggest that the modified APACHE II scoring
our study.6,27-29 The majority of cases were nonoliguric system may be an alternative indicator for the assess-
type and had spontaneous recovery without the need of ment of severity in leptospirosis. For patients with high
dialysis. Judicious fluid replacement in the early stage of modified APACHE II score, intensive care and early
disease is mandatory, as volume depletion is a common management to prevent complications should be
contributing factor to the development of acute renal provided.
failure.
The clinical picture and outcome of renal failure in
CONCLUSIONS
our study were similar to that reported by Seguro et a1.6
In our study, however, more than 10% of renal failure Leptospirosis is a re-emerging infectious disease in
patients still needed a short period of dialysis. There was Thailand, with rapidly increasing incidence . The disease
no relationship between the severity of rhabdomyolysis affects predominantly adult male farmers, who have
and the severity of renal failure, suggested by the lack of history of prolonged water contact, and is associated
difference in the initial serum creatine phosphokinase in with more severe clinical manifestations and higher
patients who needed and those who did not needed mortality than in the past. Pulmonary hemorrhage and
dialysis. The latter finding contradicts the findings from ARDS are the most common complications associated
the Marotto et al. study where rhabdomyolysis was with death nowadays. The presence of hypotension,
58 International Journal of Infectious Diseases I Volume 6, Number 1,2002
oliguria, hyperkalemia, or bilateral diffuse pulmonary gum bleeding, gross hematuria, or upper gastro-
rales on admission indicates a poor prognosis for the intestinal hemorrhage.
patients and the need for intensive care.
Indication for treatment
ACKNOWLEDGMENTS
Dialysis therapy was initiated when one of the following
This study was supported by The Khon Kaen Hospital conditions was present:
Research Fund. The study would not have been possible l intractable hyperkalemia ([K+] >6.5 mmol/l);
without the substantial contribution of time and talent from . intractable acidemia;
W Susaengrat, MD, K Tomnakan, MSc, W Saenhome, RN, and .
W Piyasawatkul, RN. The critical review of this manuscript by clinically significant pulmonary edema;
. uremic encephalopathy;
Professor B Sathapatayawong and the service for serological
. uremic pericarditis;
diagnosis of rickettsial infection by Dr. G Watt are highly
appreciated. . oliguria (urine output ~200 ml/12 h) and BUN
> 100 mg/dl.
APPENDIX Ventilatory support was started when one of the
following criteria was present:
Clinical definition . respiratory rate >35 breaths/min when a patient
was ventilated with facemask 8-10 L/min of 100%
1. Acute renal failure was defined by the presence of
oxygen;
serum creatinine of >2 mg/dl.
l hypoxemia was defined by the presence of arterial
2. Oliguria was defined by the presence of first 24
oxygen saturation ~95% even FiO2BO.6;
hours urine volume of ~400 ml. . cyanosis;
3. Pulmonary hemorrhage was defined as frank
l deterioration of consciousness with respiratory rate
hemoptysis or frank blood from an endotracheal
>30 breaths/min.
tube with at least two of the following:
decreased hematocrit over 3% without other Dopamine infision was started when a patient had
explainable source of bleeding; hypotension (BP<90/60 mmHg) after fluid resuscitation
no clinical signs of volume overload (‘jugular venous as needed for maintain vital signs.
pulsation <5 cm above sternal angle, or central
venous pressure < 12 cm;
chest x-ray showing unilateral or bilateral alveolar REFERENCES
infiltration with normal cardiothoracic ratio. 1. Jordan WT, David AA, Bradley AP. Leptospira species
4. Congestive heart failure was defined by the presence (Leptospirosis). In: Mandell GL, Bennett JE, Dolin R, eds.
of at least two of the following: Principles and practice of infectious diseases.5th ed. New
clinical signs of left ventricular dysfunction (JVP > 6 York: Churchill Livingstone, 2000; pp. 2495-2501.
cm above sternal angle, pulmonary rales, hepatic 2. Sasaki DM, Pang L, Minette HP, et al. Active surveillance
pulsation, or S3 galloping); and risk factors for leptospirosis in Hawaii. Am J Trop Med
central venous pressure > 15 cm (if indicated) Hyg 1993; 48:35-43.
chest x-ray showing diffuse alveolar pattern and 3. Everard CO, Edwards CN, Webb GB, White HS, Nicholson
increased cardiothoracic ratio. GD.The prevalence of severe leptospirosis among humans
on Barbados. Trans R Sot Trop Med Hyg 1984; 78:596-603.
5. Acute respiratory distress syndrome (ARDS) was
4. Everard CO, Fraser-Chanpong GM, Everard JD. The
defined by the presence of the following criteria: incidence of severe leptospirosis in Trinidad. Trop Geogr
no clinical signs of congestive heart failure as Med 1987; 39:126-132.
defined above; 5. Park SK, Lee SH, Rhee YK, et al. Leptospirosis in
arterial gas exchange index of PO2/FiO2 ~200; Chonbuk Province of Korea in 1987: a study of 93 patients.
chest x-ray showing diffuse alveolar process with Am J Trop Med Hyg 1989; 41:345-351.
normal cardiothoracic ratio; 6. Seguro AC, Lomar AV, Rocha AS. Acute renal failure of
pulmonary capillary wedge pressure of ~18 mmHg. leptospirosis: nonoliguric and hypokalemic forms.
6. Jaundice was defined as frank icteric sclera or serum Nephron 1990; 55:146-151.
total bilirubin of >3 mg/dl. 7. DuPont H, DuPont-Perdrizet D, Perie JL, Zehner-Hansen
7. Cardiovascular collapse was defined as systolic BP S,Jarrige B, Daijardin JB. Leptospirosis: prognostic factors
associated with mortality. Clin Infect Dis 1997; 25:720-724.
~90 mmHg and needing vasopressors to maintain
8. Ramachandran S,Rajapakse CN, Perera MV, Yoganathan
blood pressure. M. Patterns of acute renal failure in leptospirosis. J Trop
8. Neurological symptoms were defined by the Med Hyg 1976; 79:158-160.
presence of either alteration of consciousness 9. Daher E, Zanetta DM, Cavalcante MB, Abdulkader RC.
(Glasgow Coma Score ~13) or seizure. Risk factors for death and changing patterns in
9. Hemorrhagic symptoms were defined by the leptospirosis acute renal failure. Am JTrop Med Hyg 1999;
presence of at least one of the following: epistaxis, 61:630-634.
Prognostic factors of death in leptospirosis I Panaphut et al 59
10. Marotto PC, Nascimento CM, Eluf-Neto J, et al. Acute 25. de Brito T, Morais CF, Yasuda PH, et al. Cardiovascular
lung injury in leptospirosis: clinical and laboratory involvement in human and experimental leptospirosis:
features, outcome, and factors associated with mortality. pathologic findings and immunohistochemical detection
Clin Infect Dis 1999; 29:1561-1563. of leptospiral antigen. Ann Trop Med Parasitol 1987;
11. Ko AI, Galvao Reis M, Ribeiro Dourado CM, Johnson 81:207-214.
WD, Jr. Riley LW. Urban epidemic of severe leptospirosis 26. Ramachandran S, Perera MV Cardiac and pulmonary
in Brazil. Salvador Leptospirosis Study Group [see involvement in leptospirosis. Trans R Sot Trop Med Hyg
comments]. Lancet 1999; 354820-825. 1977; 71:56-59.
12. Faine S. Guidelines for the control of leptospirosis. World 27. Farr RW. Leptospirosis. Clin Infect Dis 1995; 21%8.
Health Organization 1982:50-51. 28. Abdulkader RC, Seguro AC, Malheiro PS,Burdmann EA,
13. Gussenhoven GC, van der Hoorn MA, Goris MG,Terpstra Marcondes M. Peculiar electrolytic and hormonal
WJ, Hartskeerl RA, Mol BW. LEPTO dipstick, a dipstick abnormalities in acute renal failure due to leptospirosis.
assayfor detection of Leptospira-specific immunoglobulin Am J Trop Med Hyg 1996; 54:1-6.
M antibodies in human sera. J Clin Microbial 1997; 29. Sitprija V, Pipatanagul V, Mertowidjojo K, Boonpucknavig
35:92-97. V, Boonpucknavig S. Pathogenesis of renal disease in
14. Weyant RS, Bragg SL, Kaufman AF. Leptospira and leptospirosis: clinical and experimental studies. Kidney Int
Leptonema. In: Murray PR, Baron EJ, Pfaller MA et al, 1980;17:827-836.
eds. Manual of clinical microbiology. 7th ed. Washington, 30. Per&elan A, Pruzanski JC. Leptospira canicola infection:
DC: American Society for Microbiology. 1999:739-745. report of 81 casesand review of literature. Am J Trop Med
15. Sulzer CR, Jones WL. Leptospirosis: methods in Hyg 1963; 12:75-81.
laboratory diagnosis (revised ed.). HEW Publication 31. Berman SJ,Tsai CC, Holmes K, Fresh JW, Watten RH.
(CDC) 80-8275. Washington, DC: US Department of Sporadic anicteric leptospirosis in South Vietnam. A study
Health, Education, and Welfare, 1978. in 150 patients. Ann Intern Med 1973; 79:167-173.
16. Watt G, Kantipong P,Jongsakul K, Paxton H. Performance 32. Nicodemo AC, Duarte MI, Alves VA,Takakura CF, Santos
of a dot blot immunoassay for the rapid diagnosis of Scrub RT, Nicodemo EL. Lung lesions in human leptospirosis:
Typhus in a longitudinal case series. J Infect Dis 1998; microscopic, immunohistochemical, and ultrastructural
178:1457-1463. features related to thrombocytopenia. Am J Trop Med Hyg
17. William AK, Elizabeth AD, Douglas PW, Jack EZ. 1997; 56:181-187.
APACHE II: A severity of disease classification system. 33. O’Neil KM, Rickman LS, Lazarus AA. Pulmonary
Crit Care Med 1985; 13:818-829. manifestations of leptospirosis. Rev Infect Dis 1991;
18. Watt G, Padre LP, Tuazon ML, et al. Placebo-controlled 13:705-709.
trial of intravenous penicillin for severe and late lepto- 34. Ercolani MG, Papa M. Clinico-radiological observations
spirosis.Lancet 1988;1:4333435. on pulmonary manifestations of leptospirosis during the
19. McClain JB, Ballou WR, Harrison SM, Steinweg DL. Montefeltro epidemic. Radio1 Med (Torino) 1988; 76:64-67.
Doxycycline therapy for leptospirosis. Ann Intern Med 35. Carre P,Arvin-Berod C, Duval G, Michault A. Predomin-
1984; 100:696-698. ant pulmonary manifestations in leptospirosis ictero-
20. Ministry of Public Health, Thailand. Anna1 report of hemorrhagica. Rev Ma1 Respir 1985; 2:343-349.
infectious disease; 1996-1999. 36. Goncalves AJ, de Carvalho JE, Guedes e Silva JB,
21. Sundharagiati B, Harinasuta C. Studies on leptospirosis in Rozembaum R, Vieira AR. Hemoptysis and the adult
Thailand, a review. J Med Assoc Thai 1964; 47:662-679. respiratory distress syndrome as the causes of death in
22. Edwards CN, Nicholson GD, Hassell TA, Everard CO, leptospirosis. Changes in the clinical and anatomicopatho-
Callender J. Leptospirosis in Barbados. A clinical study. logical patterns. Rev Sot Bras Med Trop 1992; 25:261-270.
West Indian Med J 1990; 39:27-34. 37. Berendsen HH, Rommes JH, Hylkema BS, Meinesz AF,
23. Heath CW, Jr., Alexander AD, Galton MM. Leptospirosis Sluiter HJ. Adult respiratory failure with leptospirosis. Ann
in the United States. Analysis of 483 cases in man, 1949, Intern Med 1984; 101:402.
1961. N Engl J Med 1965; 273:915-922. 38. Perdrix C, Clement C, Druart I?.Acute respiratory distress
24. Bethlem NL, Pereira N. Leptospirosis. Sem Respir Med disclosing leptospirosis. Ann Fr Anesth Reanim 1986;
1991; 12:58-67. 5:599-600.