|
Journal of Postgraduate Medicine
Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India
ISSN: 0022-3859 EISSN: 0972-2823
Vol. 51, Num. 3, 2005, pp. 201-204
|
Journal of Postgraduate Medicine, Vol. 51, No. 3, July-September, 2005, pp. 201-204
Symposium
Human leptospirosis: Management and prognosis
Kobayashi Y
First Department of Internal Medicine, School of Medicine, Ehime University, Ehime 791-0295
Correspondence Address:First Department of Internal Medicine, School
of Medicine, Ehime University, Ehime 791-0295, yu-eins@fc4.so-net.ne.jp
Code Number: jp05074
Abstract As leptospirosis is a treatable disease, early diagnosis and prompt treatment are important for better prognosis. Early diagnosis depends on the knowledge of epidemiological factors, presenting features and use of appropriate laboratory tests. Early institution of appropriate antimicrobial therapy in combination with supportive therapy reduces the mortality from this disease. Leptospires are sensitive to a variety of antimicrobial agents, including penicillin, cephems, aminoglycosides, tetracyclines and macrolides. Of these antimicrobial agents, short-term treatment with streptomycin exterminates, leptospires. When penicillin, cephems, tetracylines and macrolides are used, long-term therapy with large doses may be required from the early stage of the disease until the appearance of antibodies.
Keywords: Antimicrobial agen, Chemotherapy, Leptospirosis, Management, Prognosis, Weil′s disease
Human leptospirosis, an acute febrile illness that presents with a wide variety of clinical manifestations, is encountered throughout the world, especially in tropical and subtropical areas with high rainfall. [1],[2],[3],[4],[5],[6],[7]The epidemics tend to follow natural disasters such as cyclones and floods. [8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23] Leptospirosis is a treatable disease, and hence early diagnosis and prompt treatment are important for the improvement of prognosis. Although, efforts to reach a definitive diagnosis should always be undertaken, prompt institution of pertinent therapy should take precedence, as patients with leptospirosis are known to demonstrate a rapid deterioration in their clinical course. This is especially so as the serological tests do not yield a positive result for about a week after the onset of illness, and cultures may not become positive for several weeks. Under such circumstances, therapy could be initiated on the basis of clinical manifestations under appropriate epidemiological situations.
Collecting evidence for diagnosing leptospirosis In the medical examination, medical professionals must always keep leptospirosis in mind to allow for early suitable treatment. The clinical manifestations of leptospirosis are variable, ranging from mild febrile illness to icteric-haemorrhagic illness with dysfunction of several organ-systems. The diagnosis is suspected on the basis of a combination of evidences generated by clinical manifestations, laboratory findings, clinical course and above all, epidemiological features (location, season, habits, occupation, contact with animals, travel to endemic areas, leisure activities, etc.). The most characteristic clinical signs for early diagnosis are acute febrile illness of sudden onset, severe general malaise, lumbago, muscular pains and conjunctival suffusion. Proteinuria, raised erythrocyte sedimentation rate, and leucocytosis with neutrophilia are the most indicative clinical laboratory findings for early diagnosis.[24],[25] Serum aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and lactic dehydrogenase (LDH) levels are slightly elevated even in severe patients with jaundice. These findings are very important in differentiating between leptospirosis and viral hepatitis.[25] Although, jaundice and haemorrhage are the most important signs of the severe form of leptospirosis, they are rarely useful in early diagnosis.
Management
Appropriate chemotherapy and supportive therapy help reduce the mortality of severe cases. Early treatment is very important. If the disease is not treated appropriately within the first 2-3 days, it may progress in severity. In the olden days, immune horse serum or specific immunoglobulin were used, and proved to be effective when given early.[24],[26] However, availability of effective antimicrobial therapy has supplanted the use of these remedies. Effective antimicrobial therapy should also be initiated before the fifth day after the onset of illness.[25]
General management and supportive therapy
General management of leptospirosis includes providing symptomatic and supportive therapy, as indicated by the nature and severity of the symptoms and signs. Bed rest is required for 1-2 weeks in the mild forms, and for 2-4 weeks in the severe forms. Return to work should be gradual. The progress is monitored with routine measurement of temperature, pulse rate and blood pressure, monitoring of the urinary output and fluid balance, and review of tests such as complete blood count, erythrocyte sedimentation rate, liver function tests, urinalysis, blood urea nitrogen (BUN), creatinine and electrolyte analysis.
Chest radiograph, electrocardiogram, determination of bleeding, clotting
and prothrombin time, and analysis of cerebrospinal fluid are also important
and are done to determine the severity of illness and for detection of
complications.
Restriction of fluid intake and provision of a high carbonate, low
protein diet are desirable in subjects with renal involvement. Headache
and muscular
pains are treated with analgesic agents, and fever is managed with antipyretic
agents. Intravenous injection of diazepam is very effective in controlling
convulsions. Role of appropriate fluid management strategy titrated to
clinical manifestations, state of illness and presence or otherwise of
renal involvement cannot be over-emphasized. Oliguria due to dehydration
or hypotension should be corrected and urine output maintained through
fluid supplementation and restitution of blood pressure. After hydration
and correction of blood pressure, furosemide (with doses up to 1000 mg/day)
may be used to ensure adequate diuresis. Severe and worsening renal failure
is treated with dialysis. It is advisable to institute dialysis early,
as soon as BUN level reaches 200 mg/dl. Peritoneal dialysis is preferred
to haemodialysis, as it is technically simpler. Plasmapheresis with dialysis
may be effective for serious case with disturbance of consciousness.[27]
Myocarditis requires pertinent cardiological treatment. Management of
bleeding and thrombocytopenia may require packed cell transfusion, or
platelet transfusion, respectively. Some authorities believe in prudent
use of steroids in subjects with severe manifestations. However, association
of remarkable haemorrhage, and macroscopic and histological changes with
steroid therapy in experimentally infected guinea pigs cast doubts over
its use.[28]
Chemotherapy
Leptospires are sensitive to a variety of antimicrobial agents, including
penicillin, cephems, aminoglycosides, tetracyclines and macrolides. [29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45],[46],[47] Of
these antimicrobial agents, penicillin and cephems have the lowest minimal
inhibitory concentrations (MIC) against leptospires in vitro .[25],[29],[41] The
results of several studies have shown that penicillin kills leptospires
in the logarithmic growth phase, but not in the stationary phase.[29],[36],[41] The
same is true of cephaloridine, cefazolin and erythromycin.[37],[41],[44] Streptomycin
has been shown to kill leptospires in both the logarithmic growth phase
and the stationary phase.[29],[36],[41] High
concentrations of tetracycline were associated with a leptospirocidal
effect, which could not be attained with low concentrations of the drug.[36],[39],[41] Gentamicin,
tobramycin and isepamicin showed reliable bactericidal effects on leptospires
in both the logarithmic growth phase and the stationary phase. [45],[46],[47]
Several in vivo studies done in lower animals (experimental leptospirosis)
have shown that streptomycin was more effective than others in completely
removing leptospires from all tissues.[29],[34],[41] Although,
penicillin, cephems, tetracyclines and macrolides were also effective
in experimental leptospirosis, small numbers of leptospires sometimes
remained in the liver and kidney.[29],[31],[32],[34],[35],[38],[41] Recently,
Truccolo et al. evaluated the susceptibility of leptospies to selected
antimicrobial agents (ampicillin, doxycycline and ofloxacin) in a hamster
model.[48] Their results
demonstrated the ability of ampicillin at a high dose to clear leptospires
from the host, except from kidneys and heart, where leptospires remained
at day 6. Ofloxacin was unable to clear leptospires from blood or kidneys.
With doxycycline, the clearance of leptospires occurred in 2 days in
all the target organs studied, with the exception of liver, which required
3 days. The standard treatment for carrier animals has been chemotherapy
by injection of streptomycin; it is an effective cure for excretion of
leptospires by carriers.[1],[3] A
single dose of streptomycin will usually remove the chronic renal carrier
state caused by pomona or other serovars. [49],[50],[51]Streptomycin
has also been effectively used for acutely ill domestic animals.[1],[3]
Studies on chemotherapy of leptospirosis carried out as early as 1950s
through 1990s in human beings indicated a role for streptomycin and other
aminoglycosides.[25],[30],[42] Short-term
treatment with streptomycin exterminates leptospires. It has been also
shown to be effective for chemoprophylaxis and is used to treat subjects
who are likely to have been infected in laboratory accidents or other
high-risk exposure, except in circumstances where it is contraindicated.[25],[42] Gentamicin,
tobramycin and isepamicin may be effective as alternatives to streptomycin. [45],[46],[47]
[Figure - 1] shows
the clinical course of Weil′s disease in a patient treated with
streptomycin beginning on the first day after onset of the illness. In
this patient, the fever dropped precipitously and the causative leptospires
were removed. Although the patient recovered quickly, jaundice and haemorrhage
appeared after the fever subsided.[25]
Although, penicillin was effective for treating leptospirosis, the causative
organism has sometimes been isolated from the blood of patients after
treatment with penicillin in the febrile stage. [Figure - 2] shows
the clinical course of a patient with leptospirosis treated with penicillin
and streptomycin in the early stage. The causative organism was isolated
from the blood of the patient during the time of treatment with penicillin,
and afterward the patient recovered quickly, with streptomycin treatment.[25] Recently,
a sequential therapy of penicillin and doxycycline on a case of severe
leptospirosis was reported.[52] In
this case, the patient progressed to pancytopenia despite initial penicillin
therapy. The patient needed a second course of antimicrobial agent with
doxycycline to improve his persistent symptoms and cytopenia.
Penicillin, cephems, tetracyclines and macrolides have been widely
used in the treatment of human leptospirosis. However, when these antimicrobial
agents are used for the treatment of leptospirosis, long-term therapy
with large doses may be required from the early stage of the disease
until the appearance of antibodies.[42] [Table
- 1] shows
the clinical application of principal drugs for treatment of leptospirosis.
Prognosis
The mortality due to leptospirosis varies from less than 1% to more than 20%.[53] The mortality is dependent on many factors including the incriminated serovar with serovars icterohaemorrhagiae and copenhageni having the propensity to produce severe disease. The clinical spectrum of human leptospirosis ranges from mild anicteric illness to a severe illness characterized by multiple organ failure. The mild forms of leptospirosis may be much more common than the severe forms and most patients with the mild form tend to recover within 1-2 weeks. In addition to the serovar and severity of clinical spectrum, the types of clinical manifestations and complications also have a bearing on the fatality rate. Fatal outcome is mainly related to renal failure although other features such as hyperkalaemia, thrombocytopenia, cardiovascular failure with hypotension and arrhythmia, and respiratory failure with massive haemoptysis are known to contribute to the mortality rate. Neurological manifestations (e.g. disturbance of consciousness, delirium and stiffness of the neck) and digestive system symptoms (e.g. gastrointestinal bleeding, repeated nausea and vomiting, abdominal pain, meteorism and hiccups) are also associated with high mortality rate.[24],[25] Patient factors such as old age [Figure - 3], nutritional status and presence of concomitant health problems are often associated with more severe clinical illness and increased mortality.[25]
Most deaths occur between the 10th and 15th days of illness, although death can occur as early as the fifth day of illness in fulminant severe cases [Figure - 4].[25]
If the patient is not treated for the severe form within 2-3 days after the onset of illness, it may progress in severity and sometimes be fatal. Medical professionals, especially primary care physicians, who are primarily responsible for the diagnosis and treatment, need to know about the early symptoms and signs, and early clinical laboratory findings. The beginning of early pertinent antimicrobial therapy within 4-5 days after the onset of illness and proper supportive therapy and use of dialysis to treat renal failure have reduced the leptospirosis-related mortality.
References
1. | In : Faine S, editor. Guidelines for the control of leptospirosis. Geneva:World Health Organization; 1982. Back to cited text no. 1 |
2. | In : Kobayashi Y, editor. Leptosirosis. Proceedings of the Leptospirosis Conference 1990. Tokyo:University of Tokyo Press; 1991. Back to cited text no. 2 |
3. | In : Faine S, Adler B, Bolin C, Perolat P. Leptospira and Leptospirosis. 2nd edn. Melbourne:Med Sci; 1999. Back to cited text no. 3 |
4. | Levett PN. Leptospirosis. Clin Microbiol Rev 2001;14:296-326. Back to cited text no. 4 [PUBMED] [FULLTEXT] |
5. | Vinez JM. Leptospirosis. Curr Opin Infect Dis 2001;14:527-38. Back to cited text no. 5 |
6. | Bharti AR, Nally JE, Ricaldi JN, Matthias MA, Diaz MM, Lovett MA, et al . Leptospirosis:a zoonotic disease of global importance. Lancet Infect Dis 2003;3:757-71. Back to cited text no. 6 |
7. | International Leptospirosis Society (principal author Terpstra WJ). Human Leptospirosis:Guidance for diagnosis, surveillance and control. Geneva: World Health Organization; 2003. Back to cited text no. 7 |
8. | Venkataraman KS, Nedunchelliyan S. Epidemiology of an outbreak of leptospirosis in man and dog. Comp Immunol Microbiol Dis 1992;15:243-7. Back to cited text no. 8 [PUBMED] |
9. | Sehgal SC, Murhekar MV, Sugunan AP. Outbreak of leptospirosis with pulmonary involvement in north Andaman. Indian J Med Res 1995;102:9-12. Back to cited text no. 9 [PUBMED] |
10. | Muthusethupathi MA, Shivakumar S, Suguna R, Jayakumar M, Vijayakumar R, Everard CO, et al . Leptospirosis in Madras a clinical and serological study. J Assoc Physic India 1995;43:456-8. Back to cited text no. 10 |
11. | Kuriakose M, Eapen CK, Paul R. Leptospirosis in Kolenchery, Kerala, India;eidemiology, prevalent local serogroups and serovars and a new serovar. Eur J Epidemiol 1997;13:691-7. Back to cited text no. 11 [PUBMED] [FULLTEXT] |
12. | Sehgal SC, Sugunan AP, Vijayachari P. Outbreak of leptospirosis after the cyclone in Orissa. Natl Med J India 2002;15:22-3. Back to cited text no. 12 [PUBMED] |
13. | Clerke AM, Leuva AC, Joshi C, Trivedi SV. Clinical profile of leptospirosis in South Gujarat. J Postgrad Med 2002;48:117-8. Back to cited text no. 13 |
14. | Karande S, Kulkarni H, Kulkarni M, De A, Varaiya A. Leptospirosis in children in Mumbai slums. Indian J Pediatr 2002;69:855-8. Back to cited text no. 14 [PUBMED] [FULLTEXT] |
15. | Natarajaseenivasan K, Boopalan M, Selvanayaki K, Suresh SR, Ratnam S. Leptospirosis among rice mill workers of Salem, South India. Jpn J Infect Dis 2002;55:170-3. Back to cited text no. 15 [PUBMED] [FULLTEXT] |
16. | Bharadwaj R, Bal AM, Joshi SA, Kagal A, Pol SS, Garad G, et al . An urban outbreak of leptospirosis in Mumbai, India. Jpn J Infect Dis 2002;55:194-6. Back to cited text no. 16 |
17. | Karande S, Bhatt M, Kelkar A, Kulkarni M, De A, Varaiya A. An observational study to detect leptospirosis in Mumbai, India, 2000. Arch Dis Child 2003;88:1070-5. Back to cited text no. 17 [PUBMED] [FULLTEXT] |
18. | Sethi S, Sood A, Pooja, Sharma S, Sengupta C, Sharma M. Leptospirosis in northern India:a clinical and serological study. Southeast Asian J Trop Med Pub Health 2003;34:822-5. Back to cited text no. 18 |
19. | Basu D, Sarkar P, Chakraborty N, Chanda PR, Biswas S, Bera AB, et al. Leptospirosis and Weil's disease in eastern India. J Indian Med Assoc 2003;101:532-6. Back to cited text no. 19 [PUBMED] |
20. | Ramakrishnan R, Patel MS, Gupte MD, Manickam P, Venkataraghavan S. An institutional outbreak of leptospirosis in Chennai, South India. J Commun Dis 2003;35:1-8. Back to cited text no. 20 |
21. | Vijayachari P, Ahmed N, Sugunan AP, Ghousunnissa S, Rao KR, Hasnain SE, et al . Use of fluorescent amplified fragment length polymorphism for molecular epidemiology of leptospirosis in India. J Clin Microbiol 2004;42:3575-80. Back to cited text no. 21 |
22. | Jena AB, Mohanty KC, Devadasan N. An outbreak of leptospirosis in Orissa, India:the importance of surveillance. Trop Med Int Health 2004;9:1016-21. Back to cited text no. 22 |
23. | Pappachan MJ, Mathew S, Aravindan KP, Khader A, Bharghaven PV, Kareem MM, et al . Risk factors for mortality in patients with leptospirosis during an epidemic in northern Kerala. Natl Med J India 2004;17:240-2. Back to cited text no. 23 |
24. | Misao T, Kobayashi Y, Kuwashima K, Yano T. Statistical observation on leptospirosis icterohaemorrhagica and canicola fever in the First Medical Clinic of Kyushu University Hospital for recent 16 years (in Japanese). Jpn J Clin Exp Med 1957;34:856-66. Back to cited text no. 24 |
25. | Kobayashi Y. Clinical observation and treatment of leptospirosis. J Infect Chemother 2001;7:59-68. Back to cited text no. 25 |
26. | Inada R, Ido Y, Kaneko R, Hoki R, Ito H, Wani H. Mitteilung über die Aetiologie, Immunitδt, Prophylaxis und Serumbehandlung der Weilschen Krankheit (Spirochaetosis icterohaemorrhagica Inada). Fukuoka:Mitteilungen aus der Medizinischen Fakultδt der Kaiserlichen Universitδt Kyushu, Fukuoka, Japan 1917;3:1-143. Back to cited text no. 26 |
27. | Sanai T, Motomura K, Fujio N, Kumagai H, Hirakata H, Okuda S, et al . An urgent case of Weil's disease with fulminant renal failure and unconsciousness (In Japanese). Jpn J Clin Exp Med 1988;65:3853-6. Back to cited text no. 27 |
28. | Aso M. The effects of antihistamic drug, rutin and cortisone on hemorrhage of leptospirosis icterohaemorrhagica (In Japanese). Fukuoka Med Acta 1955;46:188-201. Back to cited text no. 28 |
29. | Misao T, Yamada H, Hiroyoshi S, Katsuta K, Nishihara Y, Tanaka H, et al . Chemothrapy of leptospirosis icterohaemorrhagica. 1. Basic experiments (in Japanese). Jpn J Clin Exp Med 1950;27:822-8. Back to cited text no. 29 |
30. | Misao T, Yamada H, Hiroyoshi S, Katsuta K, Nishihara Y, Tanaka H, et al . Chemotherapy of leptospirosis icterohaemorrhagica. 2. Clinical application of penicillin and streptomycin (in Japanese). Jpn J Clin Exp Med 1951;28:424-31. Back to cited text no. 30 |
31. | Misao T, Yamada H, Hiroyoshi Y, Katsuta K, Nishihara Y, Nagai S, et al . Chemotherapy of leptospirosis icterohaemorrhagica. 3.1. Experimental therapy of guinea pigs infected with Leptosira icterohaemorragiae using aureomycin and chloromycetin (in Japanese). Jpn J Clin Exp Med 1952;29:405-11. Back to cited text no. 31 |
32. | Misao T, Yamada H, Hiroyoshi S, Katsuta K, Nishihara Y, Nagai S, et al . Chemotherapy of leptospirosis icterohaemorrhagica. Therapeutic effects of aureomycin on infected guinea pigs and patients with Leptospira icterohaemorrhagiae (in Japanese). Nippon Rinsho (Jpn J Clin Med) 1952;10:141-7. Back to cited text no. 32 |
33. | Misao T, Hiroyoshi S, Katsuta K, Nishihara Y, Kuwashima K, Kobayashi Y. Terramycin therapy of leptospirosis icterohaemorrhagica (in Japanese). Jpn Med J 1952;1455:843-5. Back to cited text no. 33 |
34. | Nishihara Y. An experimental study on the working mechanism of penicillin and streptomycin against Leptospira icterohaemorrhagiae (in Japanese). Fukuoka Acta Med 1952;43:935-51. Back to cited text no. 34 |
35. | Misao T, Yamada H, Hiroyoshi S, Katsuta K, Nishihara Y, Nagai S, et al . Chemotherapy of leptospirosis icterohaemorrhagica. 3.2. Experimental therapy of hamsters infected with Leptospira icterohaemorrhagiae using Terramycin (in Japanese). Jpn J Clin Exp Med 1953;30:408-10. Back to cited text no. 35 |
36. | Misao T, Yamada H, Hiroyoshi S, Katsuta K, Nishihara Y, Nagai S, et al . Chemotherapy of leptospirosis icterohaemorrhagica. Mode of action of various antibiotics against Leptospira icterohaemorrhagiae (in Japanese). Jpn J Clin Exp Med 1953;30:515-21. Back to cited text no. 36 |
37. | Misao T, Hiroyoshi S, Katsuta K, Nishihara Y, Kuwashima K, Kobayashi Y. Ilotycin therapy. 2. Studies on the anti-leptospiral action of Ilotycin (in Japanese). J Jpn Soc Intern Med 1953;42:708-10. Back to cited text no. 37 |
38. | Misao T, Hiroyoshi S, Katsuta K, Nishihara Y, Kuwashima K, Kobayashi Y. Therapeutic effects of Ilotycin on hamsters infected with Leptospira icterohaemorrhagiae (In Japanese). J Jpn Soc Intern Med 1954;42:880-3. Back to cited text no. 38 |
39. | Kuwashima K. The influence of various antibiotics on Leptospira itcerohaemorrhagiae. II. Studies on the resistance of leptospira against antibiotics and the anti-leptospira action of tetracycline (in Japanese). Nisshin Igaku (Jpn J Med Prog) 1955;42:296-302. Back to cited text no. 39 |
40. | Misao T, Kuwashima K, Kobayashi Y. Ilotycin therapy of leptospirosis (in Japanese). Saishin Igaku (Latest J Med Prog) 1955;10:1319-23. Back to cited text no. 40 |
41. | Misao T, Hiroyoshi S, Katsuta K, Nishihara Y, Kuwashima K, Kobayashi Y. Antibiotics therapy of leptospirosis. 1. Basic section (in Japanese). Rinsho no Nippon (Clinics) 1955;1:199-207. Back to cited text no. 41 |
42. | Misao T, Hiroyoshi S, Katsuta K, Nishihara Y, Kuwashima K, Kobayashi Y. Antibiotics therapy of leptospirosis. 2. Clinical section (in Japanese). Rinsho no Nippon (Clinics) 1955;1:274-85. Back to cited text no. 42 |
43. | Kobayashi Y, Tachibana N. Chemotherapy of leptospirosis. Effects of leucomycin, Kanamycin, neomycin and novobiocin (in Japanese). J Jpn Assoc Infect Dis 1963;37:302. Back to cited text no. 43 |
44. | Kobayashi Y, Ichiki T. Chemotherapy of leptospirosis. Effect of cephaloridine (in Japanese). J Jpn Assoc Infect Dis 1966;39:411. Back to cited text no. 44 |
45. | Kobayashi Y, Tachibana N, Ichiki T, Kusaba T, Matsumoto I. Chemotherapy of leptospirosis. Effects of aminodeoxykanamycin, vistamycin and gentamicin (in Japanese). Media Circle 1971;16:335-40. Back to cited text no. 45 |
46. | Kobayashi Y, Oyama T, Ninomiya T. Chemotherapy of leptospirosis. Effects of tobramycin, debekacin and amikacin on the leptospira (in Japanese). J Jpn Assoc Infect Dis 1984;58:197-202. Back to cited text no. 46 |
47. | Kobayashi Y, Sada E, Tamai T, Shinozaki F. Activities of isepamicin and imipenem against leptospira. In : Kobayashi Y, editor. Leptospirosis. Proceedings of the Leptospirosis Research Conference 1990. Tokyo:University of Tokyo Press; 1991. p. 202-12. Back to cited text no. 47 |
48. | Truccolo J, Charavay F, Merlen F, Perolat P. Quantitative PCR assay to evaluate ampicillin, ofloxacin, and doxycycline for treatment of experimental leptospirosis. Antimicrob Agents Chemother 2002;46:848-53. Back to cited text no. 48 |
49. | Doherty P. Streptomycin treatment of bovine carriers of Leptospira pomona . Aust Vet J 1967;43:138-9. Back to cited text no. 49 |
50. | Gerritsen MJ, Koopmans MJ, Olyhoek T. Effect of streptomycin treatment on the shedding of and the serologic responses to Leptospira interrogans serovar hardjo subtype hardjobovis in experimentally infected cows. Vet Microbiol 1993;38:129-35. Back to cited text no. 50 |
51. | Gerritsen MJ, Koopmans MJ, Dekker TC, De Jong MC, Moerman A, Olyhoek T. Effective treatment with dihydrostreptomycin of naturally infected cows shedding Leptospira interrogans serovar hardjo subtype hardjobovis. Am J Vet Res 1994;55:339-43. Back to cited text no. 51 |
52. | Bee PC, Chow SK, Tan LH. A cases of severe leptospirosis with pancytopaenia. Med J Malaysia 2003;58:777-9. Back to cited text no. 52 |
53. | World Health Organization. Leptospirosis worldwide. Wkly Epidemiol Rec 1999;74:237-42. Back to cited text no. 53 |
Copyright 2005 - Journal of Postgraduate Medicine
The following images related to this document are available:
Photo images
[jp05074f3.jpg]
[jp05074f2.jpg]
[jp05074t1.jpg]
[jp05074f4.jpg]
[jp05074f1.jpg]
|