article_wmc002772.pdf

13

Click here to load reader

Upload: munawirsyam91

Post on 14-May-2017

213 views

Category:

Documents


1 download

TRANSCRIPT

Page 1: Article_WMC002772.pdf

Article ID: WMC002772 2046-1690

LeptospirosisCorresponding Author:Prof. Syed Azhar Syed Sulaiman,Professor , School of Pharmaceutical Sciences, University of Sciences Malaysia. - Malaysia

Submitting Author:Ms. Hui Yi Leow,Undergraduate student, School of Pharmaceutical Sciences, USM Penang. - Malaysia

Previous Article Reference: http://www.webmedcentral.com/article_view/2757

Article ID: WMC002772

Article Type: Review articles

Submitted on:21-Dec-2011, 03:16:00 PM GMT Published on: 22-Dec-2011, 05:52:53 PM GMT

Article URL: http://www.webmedcentral.com/article_view/2772

Subject Categories:INFECTIOUS DISEASES

Keywords:Leptospirosis, Leptospires, Floods, Rodents, Urine, Antibiotics, Traditional medicines, Supportivecare, Contaminated, Prevent

How to cite the article:Hui Yi L , Sing Hwa N , Chia Ying T , Abdullah A , Azmi F , Samsuki N , Syed SulaimanS . Leptospirosis . WebmedCentral INFECTIOUS DISEASES 2011;2(12):WMC002772

Copyright: This is an open-access article distributed under the terms of the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the originalauthor and source are credited.

Source(s) of Funding:

None

Competing Interests:

None

WebmedCentral > Review articles Page 1 of 13

Page 2: Article_WMC002772.pdf

WMC002772 Downloaded from http://www.webmedcentral.com on 28-Dec-2011, 11:12:20 AM

LeptospirosisAuthor(s): Hui Yi L , Sing Hwa N , Chia Ying T , Abdullah A , Azmi F , Samsuki N , Syed Sulaiman S

Abstract

Background: Leptospirosis disease has beenrecognized for decades, particularly in resource-poor,developing countries.Outbreaks have been associatedwith flooding and natural disasters. Leptospirosis istransmitted by direct or indirect contact with urine ofinfected animals. Other sources of exposure includeblood, fluids, or tissues of parturition of infectedanimals. Diagnosis requires a high manifestation ofsuspicion based on clinical presentation associatedwith epidemiological exposure. Affected individualscan present with an extensive spectrum of clinicalmanifestations ranging from subclinical illness to renaland hepatic failure and pulmonary haemorrhages.Disease can be presented in two phases, the initialphase and the immune phase. Treatment of diseaseincludes usage of antibiotics such as penicillin-G andDoxycycline along with supportive therapy. Alternativetherapeutic agents include Cephalosporins andtraditional medicines. Prevention and controls ofLeptospirosis should be targeted at the source ofinfection, the route of transmission between infectionsources and the human host; or infection of disease inthe human host. Personal and environmental hygieneshould be emphasised by the high risk groups wherepreventive measures should be taken.Conclusion: The studies of etiology and epidemiologyof Leptospirosis has led to the development ofeffective preventive strategies. Recent advances in themolecular biology of Leptospires offer the prospect ofmore rapid progress in the future.

Introduction

Leptospirosis is recognized as an emerging andre-emerging disease of public health problem in anumber of countries of South-East Asia (SEA) regionand it occurs regularly in tropical and subtropical areaswith high rainfall.[1][2][6][12] Flash flooding is reportedfrequently from these countries which is responsiblefor Leptospirosis epidemics in past two decades. Forinstance, outbreaks of Leptospirosis have often beenreported from coastal areas of India, Sri Lanka,Indonesia and Thailand. [6][7]As in Malaysia,Leptospirosis had been discovered in the year 1925 bya scientist named Fletcher W. Later on, numerous andcontinuous researches have been conducted in

Malaysia as to investigate the causes of infection andalso to figure out the ways of treatments. [14]

The first description of Leptospiral infection in humanwas made by Landouzy' in 1883 but it remains until1886 where Adolf Weil was to clearly separateLeptospiral jaundice from a heterogeneous group ofinfections associated with icterus. [4]Adolf Weil’s nameis still attached to a severe form of Leptospirosis calledWeil's disease, conventionally attributed to rattransmitted infection caused by the serovarsicterohaemorrhagiae and copenhageni. At present, itis preferable to refer to all Leptospires infections asLeptospirosis regardless of clinical symptoms andsigns. [2][4]

Leptospirosis, commonly known as “rat-urine fever” incertain countries, is caused by infection withpathogenic spirochetes of the genus Leptospira and itis transmitted directly or indirectly from animals tohumans.[1][2] The disease is found mainly whenhuman come into contact with carrier animals orenvironment contaminated with Leptospires. Althoughrats and other rodents are the primary hosts, a widerange of other mammals including dogs, cattle, sheep,and pigs also carry and transmit the disease assecondary hosts. [3][6][7]

Humans get infected through skin contact with wateror soil containing urine from infected animals or byconsuming contaminated food or water .Human-to-human transmission is rare to occur.[3][7][12][14] Leptospirosis is usually a biphasic illnesswhere the first phase is called the acute orsepticaemia phase and the second phase as immunephase. [5][6]

Etiology And Microbiology

The classification of Leptospires is based onserological analysis of the antigens of Leptospires.[9][10] Each serovar has a characteristic antigenicmake-up. Serovars having antigenic similarities areformed into serogroups, and over 200 pathogenicserovars divided into 25 serogroups have beenverified. [2][7][8] Pathogenic serovars are now found inthe species such as Leptospira interrogans, L.noguchii, L. weilii, L. fainei and L. alexanderi. The twoclassification systems based on the serovar andspecies can be confusing as a serogoup can havestrains belongs to different species. [9]

WebmedCentral > Review articles Page 2 of 13

Page 3: Article_WMC002772.pdf

WMC002772 Downloaded from http://www.webmedcentral.com on 28-Dec-2011, 11:12:20 AM

Leptospirosis is caused by various species ofLeptospira (genus). Leptospires are aerobicspirochetes whose cells are flexuous, motile, tightlycoiled and have axial flagella. [8][9][10] They differfrom other spirochetes by the presence of end hooks.[2] In general, the bacteria are about 0.1µm indiameter and 10-20µm in length. They are gramnegative and there is no visual difference betweenserovars. They appear as a chain of dots instead of acontinual structure with their rapid rotation undervisible light. They are propelled by two flagella as well.The capability of Leptospires to move fast throughwater is vital to their life cycle, as they need to spreadout in extend to maximise the chance of infecting anew host. [7][8][10] Several Leptospires arepathogenic, although others are harmless freshwatersaprophytes. Pathogenic Leptospires are found innature in the renal tubules of certain animals whereasSaprophytic Leptospires are found in settings of wet orhumid environments. [2][7][8][12]

Mode Of Transmission

Leptospirosis is an infectious disease caused bypathogenic bacteria called Leptospires. [2]Bothhumans and animals can get infected withLeptospirosis. [12]Leptospirosis can be transmittedboth directly between hosts and indirectly in theenvironment. Humans can be infected withLeptospirosis when they come into contact with theurine of infected animals or a urine-contaminatedenvironment, such as soil and water. [12][2] Animalsthat can cause or transmit the disease are such asrodents, cattle, dogs and pigs. [12] There are alsoother possible modes of transmission of infection suchas managing infected animal tissues and ingestion ofcontaminated food or water. [10][15][16]

Leptospires can invade into humans through cuts andabrasions in the skin, intact mucous membranes (nose,mouth, eyes) and conceivably through waterloggedskin. [2][7][8][9]Besides, for special cases, they mayenter the human body via the inhalation of droplets ofurine. [14][15][16] 30-50% of the cases are due to theoccupational exposure.

Infection In Humans

In order to cause an infection, Leptospires have togain entry into the bloodstream. [2][7][8] After enteringthe bloodstream, systemic infection can develop veryrapidly. However, Leptospires grow very slow. [8] Theincubation period can be between 2-30 days, typically

ranging between 5 and 14 days. [2]

Incidences of human- to- human transmission areseldom to occur. They can be transmitted from humanto human by sexual intercourse, the mother to thefoetus through placenta and via breast milk to a child.There are also examples of human cases wheretransmission occurred as a result from rodent bites orafter laboratory accidents. [2][7][9][16]

Clinical manifestationsLeptospirosis in human is a biphasic infection,meaning that the disease develops in two phases.[2][5][6] The first phase is known as the acute orsepticaemia phase. This phase usually startsunexpectedly and lasts around a week. This phase isfeatured by nonspecific signs such as fever, chills,conjunctiva suffusion and headache. Besides, patientswill also experience myalgia. Other symptoms such asmental confusion, nausea, abdominal pain, temporaryskin rash, cough and minor haemoptysis may beobserved as well. In some severe infections, evensymptom like jaundice can be diagnosed. [5][6] Allthese symptoms last for around 4 to 9 days. Then,drop in temperature and fading away of the symptomsare typically observed in the following 1 to 3 days.[2][9][10][18]

The second phase of Leptospirosis is known as theimmune phase. This phase is featured by thedevelopment of antibodies for Leptospires and theexcretion of the bacteria in the urine. [5][6] This phasedoes not occur in all patients and can last up to 30days. The patient becomes sick again during thisphase. Those symptoms in the first phase, such asfever and myalgia, reoccur but with less severity.[9][10]

Leptospirosis is seen in two forms, icteric and anicteric.[9]To make it simple, it means Leptospirosis withjaundice (icteric) and without jaundice (anicteric). Mostof the infections are of the anicteric form and theicteric form is more serious than the anicteric form. Ingeneral, deaths are rare in the anicteric form. Theicteric form of disease occurs in 5-10% of all patients.This form progresses rapidly and is related withmulti-organ failure (liver, kidneys and central nervoussystem). Kidney failure, cardiac involvement(congestive heart failure, myocarditis and pericarditis),pulmonary haemorrhage and other serious organdysfunction can cause deaths. [2][8][9]

Infection In AnimalsAll mammals are subjected to Leptospirosis. [9]Rodents are the main reservoir hosts for mostserovars while domestic animals such as cattle, dogs,pigs and sheep are known to be the secondary hosts.

WebmedCentral > Review articles Page 3 of 13

Page 4: Article_WMC002772.pdf

WMC002772 Downloaded from http://www.webmedcentral.com on 28-Dec-2011, 11:12:20 AM

The infections of Leptospires in animals areasymptomatic in most of the time. [2][7][9] Theyusually show unobvious effects after the infection witha particular serovar. However, disease may developafter infection with another serovar. [2] The clinicalsigns are usually associated to kidney disease, liverdisease or reproductive dysfunction. Most dogsrecover after two weeks if treatments are given.However, severe damage of kidney or liver can befatal. [9]

Epidemiology

Internationally, there are up to 80% of individuals intropical areas est imated to have posit iveseroconversion rates, indicating either past or presentinfection. [10] While in Malaysia, statistical data hadshown that there are large numbers of cases ofLeptospirosis infection during 1925. Table 1 showingthe number of cases of Leptospirosis in Malaysia fromyear 2006 to 2009 was constructed as according tothe investigations conducted by Ministry of Health ofMalaysia.

Yet, morbidity of Leptospirosis is not clear asLeptospirosis is thought to be under-diagnosed andunderreported. This is because many cases are mildor asymptomatic. [9] Besides, Leptospirosis is easilyconfused with other diseases as its symptoms arenonspecific and diverse. [2] On the other hand, fromall cases that have been reported, the mortality rate ofLeptospirosis is observed to range from [2] In addition,the mortality rate varies with the form (icteric oranicteric), and elderly has higher mortality rate. [9][18]

Risk groups are certain groups of humans in apopulation that are more likely to be exposed as aresult of either occupational or recreationalactivities.[16] Since there are a large number ofpotential sources of infection and many differentopportunities for transmission, risk groups may differfrom one area to another. Occupations with a high riskof infection include sewer workers, coal miners,plumbers, farm workers, veterinarians, pet shopowners, abattoir workers, meat handlers,slaughterhouse workers, workers in the fishingindustry, and the military.[2][9] Recreational activitiesthat increase the risk of Leptospirosis includegardening and water sports such as canoeing,swimming and white-water rafting. Residents of someurban areas are exposed to Leptospirosis via rat urine.[2][8][9][16] The epidemiology of Leptospirosis isdynamic. [2] New risk groups may be formed as aresult of changes in agricultural and social practices,or in reservoir animal populations in an area. [2][9]

Studies also revealed that males are having highertendency to suffer from Leptospirosis than femalesbecause of greater occupational exposure to infectedanimals and contaminated environment. [18] Genderdifference in susceptibility is not obvious underconditions where both men and women are at equalrisk.[18] People in 20-30 years of age group are proneto Leptospires infections as compared to youngchildren and infants, most probably, because ofminimal exposure. [10][18]

Diagnosis Test

Generally, in most cases of human infection, diagnosisbased on clinical symptoms is complicated andimprecise, thus the only assured diagnoses can bethose based on serology tests such as MAT, ELISAand PCR. [1][2][8] Early diagnosis of Leptospirosis iscrucial since antibiotic therapy provides greatestbenefit when initiated early in the course of illness. Inhumans, the diagnosis of Leptospirosis starts byculturing the Leptospires from infected blood, spinalfluid, or urine and the detection of antigens or nucleicacids. Culture can be complicated and may require upto 13 to 26 weeks. [7][9][15]Identification to the species’ serogroup and serovarlevel is accomplished by reference laboratories, usinggenetic (DNA probes and polymerase chain reaction(PCR) techniques) and immunologic techniques.[2][7][8][9] Darkfield microscopy can be used but it isnot specific. MAT is only performed in reference labsand requires acute and convalescent samples fordiagnostic confirmation. [8][9] The test is serogroupbut not serovar specific, and can be convoluted bycross-reactions. [9] Conversely, tests such ascomplement f ixat ion, radioimmunoassay,immunofluorescence, counterimmunoelectrophoresisand thin layer immunoassay are less frequently used.[2][7]

Treatments

Modern medicinal treatmentBasically, treatments for acute or severe illness inhumans can be categorized into two fractions- with theapplication of antibiotic to control the bacteria andgeneral support of the patient's internal organs withclose monitoring of serology, renal, hepatic andcardiac function in order to maintain their ability torecover whi le the bacter ia are removed.[2][15]Leptospirosis can be treated by a broad rangeof antibiotics consist of Doxycycline, Ampicillin,

WebmedCentral > Review articles Page 4 of 13

Page 5: Article_WMC002772.pdf

WMC002772 Downloaded from http://www.webmedcentral.com on 28-Dec-2011, 11:12:20 AM

Amoxicillin, Penicillin and Erythromycin, thereforepractitioners will decide on the most appropriateantibiotics based on availability, the patient's age andany other medications they might be consuming. [8] Inmild cases, the medication will be given orally to thepatient, however for severe infections; the antibioticsare administered intravenously and thus requirepatients to be hospitalized. [8][10][5] This is essentialto monitor their health status as the infectionprogresses. [10][14][15][16]

AntibioticsTreatment with proper antibiotics should be initiated assoon as the diagnosis of Leptospirosis is suspectedand preferably before the fifth day after the onset ofillness. Nevertheless, most clinicians treat the patientswith antibiotics despite of the date of onset of theillness. [2][7] In most of the cases, penicillin is used.However, several alternatives are still accessible if thepatient is allergic to it. [8] It is vital to take antibiotics asprescribed by finishing the full course of medication.Stopping a course of antibiotics before it ends canlead to arising of resistant bacteria and causing verysevere illness. [8] Early antibiotic intervention is themajor factor in recovery, and any delays while pendingtest results can be critical. [1][8][10]

In mild to moderate cases, oral antibiotics such asAmoxycillin, Ampicillin, Doxycycline or Erythromycincan be used, with consideration of contraindicationsand age limits. [2][7][9]Oral Doxycycline has shown todecrease duration of fever and most symptoms ofLeptospirosis. [10]Besides, a recent clinical trialreviewed that third-generation Cephalosporins such asCeftriaxone and Cefotaxime are as effective asDoxycycline and penicil l in in the treatment.[10]Cephalosporins are known to be rather effectivebut the primary drug of choice is always penicillin.[13][18]

Severe cases of Leptospirosis should be treated withhigh doses of intravenous penicillin G therapy. [7]Severe liver and kidney manifestations of the infectionmay occasionally involve intensive medical care anddialysis treatment. Adult dose is 5MU to 8MU per dayfor five days. In patients with penicillin allergy, acourse of erythromycin can be used at 250mg QID forfive days. [8] A Jarisch-Herxheimer reaction cansometimes triggered by penicillin therapy; but the riskbalance is acceptable and should not provokediscontinuance. [8] Leptospires are usually resistant toVancomycin, Chloramphenicol, Rifampicin andMetronidazole. [2][8][9][18]Below is a Table 2 showing the summarization oftreatment and prevention of Leptospirosis bydrugs.[6][17][18]

Traditional TreatmentThe early stage of Leptospirosis follows a patterndescribed in the ancient text Shang Han Lun. Thesymptoms of Leptospirosis such as muscle ache, fever,chills, and headache match the Shang Han diseasedescribed in the ancient text. In the advanced stage ofLeptospirosis, it can cause symptoms like meningitisand jaundice. These symptoms are similar to somecases of advanced Shang Han disease stated inShang Han Lun. [24] The effectiveness of this5000-year old medicinal system is proven when theprognosis according to Traditional Oriental Medicine(TOM) shows a much convincing outcome. Theefficiency of TOM herbal approaches in treatingLeptospirosis is ascertained by an immense amount ofproofs. [25]

There is a list of herbs that have been found to bemedically effective in preventing and treatingLeptospirosis. Basically, the herbs have two types ofaction in preventing and treating the disease. Theirability to inhibit the growth of Leptospira has beenvalidated through laboratory testing where the culturedbacteria are dead when the herb extract is applied.The other action of the herbs is that they result in theclearance of symptoms when administered to infectedpatients. This action is observed in clinical evaluation.[24] Examples of Leptospira-inhibiting herbs are Isatisleaf (da qing ye), Isatis root (ban lan gen), SmilaxGlabra (tu fu ling), Gardenia, Hu-chang, Coptis (huanglian), Scute (huang qin), Verbena. [24][25]

The herb, Smilax Glabra is said to be the best amongall the herbs listed above. This is because Smilaxcauses least damages to the body due to its gentleand neutral action. [26] Smilax is a popular Chinesetraditional medicine which has potent effect inpreventing and treating Leptospirosis. This profoundeffect of Smilax is seen in large clinical trials. [27][28]Apparently, Smilax is not really appreciated as amedical agent as there are only a few of SmilaxGlabra in the market in spite of its profound efficacy.[24]

According to the book “Thousand Formulas andThousand Herbs of Traditional Chinese Medicine”, it isstated that there are five traditional formulassuggested for treating Leptospirosis. These formulaswere formulated and divided based on the syndromesof the disease. [24] Table 3 below shows the traditional formulassuggested for treating Leptospirosis. [24]If the patient encounters a severe condition where thedisease has already proceeded to the advanced stage,the traditional treatment is probably the bestapproaches. [25]

WebmedCentral > Review articles Page 5 of 13

Page 6: Article_WMC002772.pdf

WMC002772 Downloaded from http://www.webmedcentral.com on 28-Dec-2011, 11:12:20 AM

Non-pharmacology treatmentsSupportive treatment and haemodialysis

As severe cases of Leptospirosis can distress any ofthe organ system and subsequently lead tomulti-organ failure, thus, admission to hospital for afew weeks is necessary. [2][18]Excellent supportivecare and dialysis have reduced the mortality of thisillness in recent years. [7] Immediate supportive careswith strict attention to fluid, electrolyte, painkillers andhelp with their breathing balance is therefore essential.[2][7]Patients should be managed in a monitoredsetting because their condition can rapidly progress tocardiovascular collapse and shock. [10][15] ECGmonitoring is important as cardiac arrhythmias caneventually develop into fatal instabilities as theinfection progresses. [8][9]

Liver function should be carefully evaluated anddialysis is indicated to patients in cases of renal failure.[7][15] In most of the conditions, the renal damage isreversible if the patient survives the acute illness. [10]Access to mechanical ventilation and airway protectionshould be available in the event of respiratorycompromise. [7][10] In very rare cases patients canbecome psychologically disturbed and may needsedation for their own safety. [8][9] The infection is notparticularly contagious where these symptoms aretemporary and would not require specific treatment.Yet, symptoms such as longer-term depression andfatigue are to be expected, often lasting for severalyears. [8][18]

Other medications, Activities, Diets and Consultations

Regularly, patients will experience severe headaches,fever and nausea during the first or two week, andthese can be overcome by usual non-prescriptionmedicines. In some cases medical staff may prescribeadditional programs of medication to help with liver orkidney function, or to support deficiencies in diet. Afew cases have reviewed that plasma exchange,corticosteroids, and intravenous immunoglobulin maybe beneficial in selected patients in whomconventional therapy does not elicit a response. [8][10]

Maintaining a healthy diet with all the proper vitaminsand minerals is vital during recovery and patients thatfeel fatigued should rest as much as they need to. [10]In mild cases, patients are encouraged to maintainadequate fluid intake as to avoid volume depletion.Patients with hypotension or clinical shock should notbe fed enterally until adequate perfusion is restored.[8][10]

In severe cases of Leptospirosis, several specialtyconsultations may aid in proper patient management.[10] An infectious disease specialist may assist in

differentiating Leptospirosis from diseases with similarpresentations but with significantly different treatments.Nephrologists should be prepared early in the courseas the need for dialysis may present rapidly. [10]Besides, critical care specialists might be needed tomanage patients with affected multiple systems. Lastbut not least, the CDC or the World HealthOrganization (WHO) can assist the clinician withlaboratory diagnosis. [9][10][18]

PrognosesImmediate therapy or treatment can reduce themortality rate to a very low level. Most of the patientsrecover within one or two months. If the infection ispersistent, there is a considerable number that showsmedium-term health issues. Patients who undergoacute or subclinical infection will not suffer from anysignificant deficiency. Patients usually will besubjected to supervision and management for severalyears after the infection as long-term issues are verycommon in Leptospirosis. Symptoms such asheadaches and depression are expected to occuragain. [7]

Prevention And Controls

The control of Leptospirosis is complicated and ishighly depend on the local conditions. This is due tothe presence of large number of serovars and infectionsources plus the wide differences in transmissionconditions. [2][7] Hence, preventive measures must beconducted based on knowledge of the risk groups andthe local epidemiological factors. [2][7] Prevention andcontrol should be targeted at the infection source, theroute of transmission between the infection source andthe human host; or infection of disease in the humanhost. [2][6][8] There are several ways that can beimplemented to prevent Leptospirosis.

Control of infection sourceAs we know, human can be infected if they are incontact with the animal urine or faces. Therefore,public should avoid themselves from consumingcontaminated food or water. [2][6] It must be ensuredthat all the food and drinking water to be consumedare cleaned. All drinking water should also be boiledunless it is known to be absolutely safe as physicalfiltration through ceramic or charcoal filters is notadequate for preventing Leptospirosis. [7][8][9][11]Thefood must be covered from the rat. In addition, freshvegetables and fruit should be washed using cleanwater and then cooked or peeled before eating. [9][19]

Another approach to prevent Leptospirosis is topractice personal hygiene. At home, one should wash

WebmedCentral > Review articles Page 6 of 13

Page 7: Article_WMC002772.pdf

WMC002772 Downloaded from http://www.webmedcentral.com on 28-Dec-2011, 11:12:20 AM

their hands with soap before and after eating or usehand sanitizer after using the toilet. [19]If anyone hadany cuts on their body, one should clean and coveredit properly so that the germs cannot enter the wounds.[18]

Rodent controlThis can be achieved by controlling or reducinginfection in animal reservoir populations such as dogsor livestock. [9][18] Domestic animals should not beallowed to urinate in water as most of the residents inthe rural area routinely depend on river as their mainwater sources. Thus, animal reservoirs should beseparated from human habitations by means of fencesand screens. [7] Besides, dogs and livestock shouldalso be brought for immunization. [18][19][20][22]

Interruption of transmissionWorkers from agriculture field like rice and canefarming area, construction workers, pest controller andwater or sewer engineers have a higher tendency tobe affected. [8] If working with materials that couldpotentially be contaminated, one should wearprotective clothing that covers the skin, includingwaterproof boots or waders. [2][6][8][9]Farmer workersshould habitually clean their hand after completingtheir work. By doing so, they can avoid or reduce theirexposures to Leptospirosis infection.

On top of that, public should avoid visiting recreationareas or having vacation at the place where thedisease is spreading especially the one that havetropical and subtropical climate with the high rainfall.[2][6][8][23] During flood season, workers in floodedfields should be cautioned against direct contact withcontaminated water or mud. [11] Anyone that works inflood area is advised to put on waterproof dressingswhich include rubber shoes and gloves. [2][6][8][9][19]People should also avoid activities such as swimmingor canoeing at the contaminated area as the diseasecan be easily transmitted from the water sources.[19][20][22]

The mapping of water bodies and human activities inwater logged areas should be implemented. This willhelp to identify the high risk population. Farmers maybe educated to drain out the urine from the cattle shedinto a pit, instead of letting it flow and mix with waterbodies (rivers, ponds etc.) [8][18]

Human Protection The key preventive measure for Leptospirosis is tobuild awareness regarding the disease and itsprevention. [2] This has to be carried out continuouslyby various intensive educational campaigns so as torise cautious among people against Leptospirosisdisease, especially to the high-risk groups. [18] With

these efforts, people can understand better and get toknow well on every aspects of Leptospirosis. Inaddition, the disclosure of the risks and dangers ofLeptospirosis can also motivate people to sustain ournatural environment. Therefore, latest and updatednews or information about Leptosprirosis should beconveyed to the public through print and electronicmedia. [23]

One should not be hesitate to consult a physician forearly medication if he or she experiences any of thesigns and symptoms. [7] Children and pregnantwomen need to be aware of this disease as they aremore susceptible to be affected by Leptospirosis. It isalways advisable for pregnant mothers to stay awayfrom the animal and its environment. Meanwhile,parents are advised to pay more attentions on theiryounger children’ personal hygiene. [23]

In addition, Leptospirosis should be made a reportabledisease in all endemic states. [2][7][18] During thepeak transmission season, Doxycycline 200 mg maybe prescribed to agricultural workers (eg paddy fieldworkers, canal cleaning workers in endemic areas)once a week. [20][23]The chemoprophylaxis shouldnot be extended for more than six weeks. [2][7][18]Health impact assessment should also be made obligefor al l developmental projects along withenvironmental assessment. [2][8][9][18][19][20]

Vaccination of animalsLeptospires vaccines offer a limited period of immunity.[8] Boosters are needed every one to two years.[2][8][9][11] Vaccination should yet be very selectiveand used only in endemic situations having highincidence of Leptospirosis. [23] The vaccine mustcontain the dominant local serovars. Although this willhelp in preventing illness, however, it does notguarantee immunization from infection and renalshedding. [18][19][20][22]

Conclusion

Leptospirosis is an emerging infectious diseases witha much greater incidence in tropical regions and. Theetiology and epidemiology of Leptospirosis have beenstudied for many years where this knowledge haseventually led to the development of effectivepreventive strategies. Recent outbreaks ofLeptospirosis have drawn public’s attention to thepotential effects of climate change and human activityon the incidence of the disease. At a morefundamental level, understanding of the mechanismsof pathogenesis remains incomplete, but recentadvances in the molecular biology of Leptospires offer

WebmedCentral > Review articles Page 7 of 13

Page 8: Article_WMC002772.pdf

WMC002772 Downloaded from http://www.webmedcentral.com on 28-Dec-2011, 11:12:20 AM

the prospect of more rapid progress in the future.

As in Malaysia, it is crucial for each party in thecountry including both the government and publicbodies to have awareness towards proper precautionsof Leptospirosis. The Ministry of Health had stressedthat the situation of Leptospirosis is under control inour country where various precautions have beentaken to provide intensive care to patients. Yet,nations need to be alert and responsible on theirpersonal and environmental hygiene. As the sayinggoes "Prevention is better than cure", one must beprepared with the latest knowledge of Leptospirosis.

Acknowledgement

First and foremost I would like to acknowledge andoffer my heartfelt gratitude to our supervisor, Prof.Syed Azhar Syed Sulaiman, where his encouragement,guidance and support from the initial to the final levelenabled us to develop an understanding of the subject.One simply could not wish for a better or friendliersupervisor.I appreciate the efforts shown by our coursecoordinator; Dr. Amin Malik Shah Bin Abdul Majid inconducting this assignment. I would also like toacknowledge him for the precious advices andguidance. Next, a special thanks my group members incompleting this review article. I appreciate their hardworks and efforts all these time; as without them, Iwould never be able to make this review article asuccess.I would also like to thank my family members andfriends for supporting and encouraging me to completethis review article. Lastly, I offer my regards and blessings to all of thosewho supported me in any respect during thecompletion of the review article. And especially to God,who made all things possible.

References

1. Yupin Suputtamangkol, W.P., Yoel Lubell, ChuanpitSuttinont, Siriwan Hoontrakul, Kriangsak Phimda, KittiLosuwanaluk, Duangjai Suwancharoen, SaowalukSilpasakorn, and N.D. Wirongrong Chierakul,Strategies for Diagnosis and Treatment of SuspectedLeptospirosis: A Cost-Benefit Analysis. Plos Negl TropDis, 2010. 4(2): p. 1-6.2 . D r W . J . T e r p s t r a , P . B . A . , H U M A NLEPTOSPIROSIS: GUIDANCE FOR DIAGNOSIS,SURVEILLANCE AND CONTROL. World Health

Organization,2003:p.1-1223. Vijayachari P, Sugunan A. P. & Shriram A. N.Leptospirosis: an emerging global public healthproblem. J. Biosci. 2008.33:557–569.4. Victor M. A. The Pathologic Anatomy andPathogenesis Of Fatal Human Leptospirosis (Weil'sDisease). National Center for BiotechnologyInformation, 1962.40(4):393-4145. Glenda D., Anna R. S. & James A. R Handbook forzoonotic diseases of companion animals. CFSPHIowa State University. 20086. Dr. Hartskeel R, Dr. Sehgal S et al. Informal Expertconsultation on Surveillance, Diagnosis and RiskReduct ion of Leptospirosis. World HealthOrganization- Regional Office for South- East Asia,2009. SEA-CD-217:p. 1-177. Dr. Hartskeel R, Dr. Vijayachari P. Fact Sheet ofLeptospirosis. [Pamplet] World Health Organization-Regional Office for South- East Asia, 2009.p. 2-128. Leptospirosis: Medical Information for healthprofessionals. Leptospirosis Information CentreOrganization. [Internet] 2004-2009 [cited 2011Oct 30]Available from: http://www.leptospirosis.org/.9. Leptospirosis. Center for Food Security and PublicHealth, College of Veterinary Medicine. Institute forInternational Cooperation in Animal Biologics An OIECollaborating Center Iowa State University College ofVeterinary Medicine. 2005.p: 1-710. Sandra G.G. Ana Paula Velez. Leptospirosis.Drugs, Disease & Procedures. Medscape.[Internet]2011[updated 2011 Mar 8; cited 2011 Oct 30]A v a i l a b l e :http://emedicine.medscape.com/article/220563.11. Apa itu Leptospirosis. Info Penyakit. Laman WebRasmi Hospital Bukit Mertajam. 2009.p: 1-212. Water-related Diseases: Leptospirosis. Watersanitation and Health (WSH). World HealthOrganization. [Internet] 2011 [cited 2011 Oct 30].A v a i l a b l e f r o m :http://www.who.int/water_sanitation_health/diseases/leptospirosis/en/13. Penyakit Leptospirosis. Pusat Maklumat Rakyat.Jabatan Penerangan Malaysia. [ Internet]2011[updated 2011Nov 17; cited 2011 Oct 30].http://pmr.penerangan.gov.my/index.php/component/content/article/200-jenis-jenis-penyakit/3585-penyakit-leptospirosis-.html14. Leptospirosis. My health for life. [Internet]. 2008Apr 28 [ c i ted 2009 Ju ly 29 ] ; Ava i lab lefrom:http://www.myhealth.gov.my.15. John P., Cunha, DO, FACOEP. Leptospirosis.[Internet]. 2011[cited 2011 Oct 29]. Available from:http://www.medicinenet.com/leptospirosis/article.htm#1whatis

WebmedCentral > Review articles Page 8 of 13

Page 9: Article_WMC002772.pdf

WMC002772 Downloaded from http://www.webmedcentral.com on 28-Dec-2011, 11:12:20 AM

16. Leptospirosis. [Internet]. NSW Health DepartmentIndonesian.2003 Dis [cited 2009 Jul 27] Available from:http://www.mhcs.health.nsw.gov.au17. Anthony S.F, Eugene B, Dennis L.K, Stephen L.H,et al. Harrison's Principles of Internal Medicine 17thedition. McGraw-Hill Companies, Inc; 2008.18. Guidelines for Prevention and Control ofLeptospirosis. National Institute of CommunicableDiseases; Directorate General of Heal thServices.World Health Organization. 2006.5-2819. Dr. Ahmad Mahir HM. Situasi SemasaLeptospirosis & Melioidosis Serta Langkah Kawalan &Pencegahan. [Slide shows] Seminar KesihatanPersekitaran PBT 2010. Bahagian Kawalan Penyakit:Kementerian Kesihatan Malaysia. 201020. Adnan S A. Bahaya Penyakit Leptospirosis(Kencing Tikus). Gabungan Persatuan- persatuanPengguna- pengguna Malaysia (FOMCA). 201021. Jalii El, M. L., Bahaman A. R. A Review Of HumanLeptospirosis In Malaysia. Department of PreventiveMedicine and Public Health. Faculty of VeterinaryMedicine of University of Khartoum Medicine andUniversiti Putra Malaysia. 2002; 2-1222. John TJ. The prevention and control of humanLeptospirosis. J Postgrad Med [Internet].2005 [cited2011 Oct 21]; 51(3):205-9. Available from:http://www.jpgmonline.com/text.asp?2005/51/3/205/1902223. Fitri Indrawati. Laptospirosis (Aspek Biomedis DanEpidemiologis). KEMAS. Unnes2009 June. 4(2):2-7.24. Subhuti Dharmananda. LYME DISEASE:Treatment with Chinese Herbs. Institute for TraditionalMedicine, Portland, Oregon.[Internet] 1999 June [cited2 0 1 1 N o v 1 0 ] . A v a i l a b l e f r o m :http://www.itmonline.org/arts/lyme.htm25. Luke J. Terry. Treat Lyme disease withover-the-counter Chinese herbal medicines. NaturalNews [Internet] 2011[updated 2008 Mar 12; cited 2011N o v 1 2 ] . A v a i l a b l e f r o m :http://www.naturalnews.com/022820.html26. Dr. Ray Sahelian. Sarsaparilla root benefit andside effects. www.rayshelian.com [Internet] 2011 [cited2 0 1 1 N o v 1 3 ] . A v a i l a b l e f r o m :http://www.raysahelian.com/sarsaparilla.html

WebmedCentral > Review articles Page 9 of 13

Page 10: Article_WMC002772.pdf

WMC002772 Downloaded from http://www.webmedcentral.com on 28-Dec-2011, 11:12:20 AM

Years No of cases

2006 527

2007 949

2008 1,263

2009 1,418

Illustrations

Illustration 1

Table 1: Number of cases of Leptospirosis

WebmedCentral > Review articles Page 10 of 13

Page 11: Article_WMC002772.pdf

WMC002772 Downloaded from http://www.webmedcentral.com on 28-Dec-2011, 11:12:20 AM

Purposes of Medications Methods of medication

Indications

Mild illness (suspect case) Doxycycline, 100 mg orally administered twice daily for 7 days OR

Ampicillin, 500- 750 mg orally 4 times daily OR

Amoxicillin, 500 mg orally 4 times daily

Mild illness (Probable case)/

Severe case

Penicillin G, 1.5 thousand units intravenously 4 times daily OR

Ampicillin, 1 g intravenously 4 times daily OR

Amoxicillin, 1 g intravenously 4 times daily OR

Ceftriaxone, 1 g intravenously 4 times daily OR

Cefotaxime, 1 g intravenously 4 times daily OR

Erythromycin, 500 mg intravenously 4 times daily

Prevention by drugs Doxycycline, 200 mg orally administered once a week

]

Illustration 2

Table 2: Summarization of Treatment and Prevention of Leptospirosis by drugs [6][17][18]

WebmedCentral > Review articles Page 11 of 13

Page 12: Article_WMC002772.pdf

WMC002772 Downloaded from http://www.webmedcentral.com on 28-Dec-2011, 11:12:20 AM

Formula Treatment of / Syndrome

Yin Qiao San Initial symptoms (flu-like pattern)

Sanshi San Skin manifestations of the disease (rashes) (applied tropically)

Ermiao San Manifestations of the disease as liver disease (acute jaundice)

Xin Jia Xiangru Yin Summer heat injuring the lung

Zhengan Xifeng Tang plus

Angong Niuhuang Wan

Manifestations of the disease such as meningitis

Illustration 3

Table 3: Traditional formulas suggested for treating Leptospirosis[24]

WebmedCentral > Review articles Page 12 of 13

Page 13: Article_WMC002772.pdf

WMC002772 Downloaded from http://www.webmedcentral.com on 28-Dec-2011, 11:12:20 AM

DisclaimerThis article has been downloaded from WebmedCentral. With our unique author driven post publication peerreview, contents posted on this web portal do not undergo any prepublication peer or editorial review. It iscompletely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscriptbut also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions beforesubmitting any information that requires obtaining a consent or approval from a third party. Authors should alsoensure not to submit any information which they do not have the copyright of or of which they have transferredthe copyrights to a third party.

Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater tothe needs of an individual patient. The web portal or any content(s) therein is neither designed to support, norreplace, the relationship that exists between a patient/site visitor and his/her physician. Your use of theWebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harmthat you may suffer or inflict on a third person by following the contents of this website.

WebmedCentral > Review articles Page 13 of 13