Common Tropical InfectionsCommon Tropical Infections

Siriluck Anunnatsiri, MDInfectious Disease & Tropical MedicineDepartment of MedicineKhon Kaen University

Tropical Infections: DefinitionTropical Infections: Definition

Infectious diseases that either occur uniquely or more commonly in tropical and subtropical regions, are either more widespread in the tropics or more difficult to prevent or control.

Tropical and Subtropical RegionsTropical and Subtropical Regions

230

350

Common Tropical Infectious Diseases in Common Tropical Infectious Diseases in ThailandThailand

• Leptospirosis• Rickettsioses:

• Scrub typhus• Murine typhus

• Melioidosis • Enteric fever

• Typhoid fever• Paratyphoid fever

• Nontyphoidal salmonellosis

• Tuberculosis• Malaria• Dengue infection• Helminthic infection• Infective diarrhea

LeptospirosisLeptospirosis• The most widespread zoonosis in the world• Situation in Thailand

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Pathogenic Leptospira spp.

Lancet Infect Dis 2003; 3: 758

88%

7.5%

2.5%

1% each

Saprophytic Leptospira species

Species Serovar Reference strain

Serogroup

Genomospecies 3 holland Waz Holland (P438)

Holland

L. biflexa patoc Patoc I Semaranga

L. wolbachii codice CDC

Lancet Infect Dis 2003; 3: 758

Reservoir hosts of common leptospiral serovarReservoir hosts of common leptospiral serovar

Lancet Infect Dis 2003; 3: 758

Risk factors for exposure to leptospiresRisk factors for exposure to leptospires

• Occupational groupsFarmers, ranchers, abattoir workers, trappers, veterinarians, loggers, sewer workers, rice-field workers, military personnel

• Recreational activitiesFreshwater swimming, canoeing, kayaking, trail biking, hunting

• Household environmentPet dogs, domesticated livestock, rainwater catchment systems, rodent infestation

PathogenesisPathogenesisRoute of transmission:

Abrasion & cuts in skinMucous membrane/ConjunctivaIntact skin after prolong immersion in waterInhalation of aerosol/waterIngestion

Toxin production:LPSHemolysinCytotoxin

Outer envelope:Antiphagocytic component

Outer membrane protein:Interstitial nephritis

Immune complex mediated inflammation:Interstitial nephritisVasculitis

Clinical manifestationsClinical manifestationsAnicteric leptospirosis Icteric leptospirosis

Weil’s syndrome(Incubation period 2-20 days)

Fever

Leptospiremic phase3-7 days

Immune phase0-30 days

Leptospiremic phase3-7 days

Immune phase0-30 days

Associated symptoms

MyalgiaHeadacheNausea, VomitingAbdominal painConjunctival suffusion

MeningitisUveitisRash

JaundiceHemorrhage

Acute renal failureMyocarditis

Hemorrhagic pneumonitisMeningoencephalitis

Hypotension

Leptospires present in

Blood Blood

CSF CSF

Urine Urine

Clinical manifestationsClinical manifestations

Lancet Infect Dis 2003; 3: 758

Laboratory diagnosisLaboratory diagnosis• Culture• Antibody detection

• Screening testMSAT, IHA, IFA, LA, ELISA, LEPTO dipstick

• Confirmation testMicroscopic agglutination test

• Antigen detection• Polymerase chain reaction (PCR)• Pathology

TreatmentTreatment

Mild form• Doxycycline• Amoxicillin• Erythromycin

Moderate-to-severe form• Penicillin G• Doxycycline• Ceftriaxone

• Supportive & Symptomatic Treatment

• Antimicrobial therapy

PreventionPrevention

• Protective clothing, rodent control, preventing recreation exposure

• Chemoprophylaxis• Doxycycline 200 mg once a week

• Vaccine• Animal• Human – 2 developing vaccines but no

license vaccine approval in human use

RickettsiosesRickettsioses

Scrub typhus• Orientia tsutsugamushi• Vector: Trombiculid mite

(chigger): Leptothrombidium spp.Murine typhus

• Rickettsia typhi• Vector: Xenopsylla cheopsis

Spotted fever rickettsioses• R. helvetica, R. honei, R. felis, R.

conorii • Vectors: Ticks

www.eco-pestcontrol.com

Distribution of scrub typhus in Asia

1979Redrawn from Harwood and James ( )

Life cycle of murine typhus

Pathogenesis of rickettsiosesPathogenesis of rickettsioses• Vector bites and feeds

and regurgitate bacteria into skin bite site.

• Bacteria are carried via lymphatics/small blood vessels to general circulation where they invade endothelial cells (primary target)

• Spread to contiguous endothelial cells, smooth muscle cells, and phagocytes

http://pathmicro.med.sc.edu/mayer/ricketsia.htm

• Spread via the microcirculation and invade all organ systems • Vasculitis resulting in local thrombus formation and end organ damage.

Clinical presentationsClinical presentations

• Fever• Myalgia• Headache• Nausea/vomiting• Abdominal pain• Diarrhea• Conjunctival suffusion

/ subconjunctival hemorrhage

• Lymphadenopathy• Rash• Hepatomegaly• Splenomegaly• Jaundice• Altered

consciousness• Seizure• Hypotension

Clinical presentationsClinical presentations

Laboratory diagnosisLaboratory diagnosis

• Culture• Antibody detection

• Weil-Felix test: • OX-K for scrub typhus• OX-19 for murine typhus

• Latex agglutination test, dot-blot ELISA• Confirmation tests: IFA, IIP

• Polymerase chain reaction (PCR)• Pathology

Treatment Treatment

Scrub typhus• Doxycycline• Chloramphenicol• Rifampicin• Azithromycin

Murine typhus• Doxycycline• Chloramphenicol

MelioidosisMelioidosis• Burkholderia pseudomallei• Risk factors

• Diabetes mellitus• Thalassemia• Preexisting renal diseases• Chronic liver diseases• Immunosuppressive use

• Transmission• Direct inoculation• Inhalation• Ingestion, sexual contact (rare)

Worldwide distribution of melioidosisWorldwide distribution of melioidosis

Melioidosis: Clinical classificationMelioidosis: Clinical classification

• Disseminated septicemic melioidosis• Non-disseminated septicemic

melioidosis• Multifocal localized melioidosis• Localized melioidosis• Probable melioidosis• Subclinical melioidosis

Clinical presentations of melioidosisClinical presentations of melioidosisClinical presentations

% of patients in:

Royal Darwin Hospital; n=252

Infectious Diseases Association of

Thailand; n=686

Srinagarind Hospital; n=100

Pneumonia 58 45 49

Bacteremia 46 57 59

Hepatosplenic abscess

6 9 52

Skin&soft tissue infection

17 16 23

Genitourinary tract infection

19 7 13

Bone&joint infection

4 5 27

Neurological melioidosis

4 3 NR

Pericardial effusion

1 3 NR

Clinical presentationsClinical presentations

Lancet 2003; 361: 1720

Laboratory diagnosisLaboratory diagnosis

• Culture – Gold standard• Antibody detection

• IHA,ELISA, immunochromatographic test, dot immunoassay, Gold-blot immunoassay

• Antigen detection• ELISA, latex agglutination, IFA

• Polymerase chain reaction

TreatmentTreatment

• Acute phase• Ceftazidime + co-

trimoxazole• Cefoperazone/

sulbactam+ co-trimoxazole

• Imipenem/Meropenem • Co-amoxiclav

• Maintenance phase• Co-trimoxazole +

doxycycline• Co-amoxiclav• Ciprofloxacin +

azithromycin

At least 10-14 days At least 20 weeks

Enteric feverEnteric fever• Typhoid fever

Salmonella Typhi• Paratyphoid fever

Salmonella Paratyphi A, B, and C

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PathogenesisPathogenesiswww.netterimages.com

Symptoms of enteric feverSymptoms of enteric fever

Symptoms Typhoid fever (%) Paratyphoid fever (%)Fever 89-100 92-100Headache 43-90 60-100Nausea 23-36 33-58Vomiting 24-35 22-45Abdominal cramp

8-52 29-92

Diarrhea 30-57 17-68Constipation 10-79 2-29Cough 11-36 10-68

Signs of enteric feverSigns of enteric feverSymptoms Typhoid fever (%) Paratyphoid fever (%)

Abdominal tenderness

33-84 6-29

Splenomegaly 23-65 0-74Hepatomegaly 15-52 16-32Relative bradycardia

17-50 11-100

Rose spots 2-46 0-3Rales & rhonchi

8-84 2-87

Epitaxis 1-21 2-13Meningism 1-12 0-3

Laboratory diagnosisLaboratory diagnosis• Culture – Gold standard: Blood, BM, duodenal string test• Antibody detection

• Widal test – poor sensitivity & specificity• Rapid serological diagnostic test

Lancet 2005; 366: 754

Drug resistance S. Drug resistance S. Typhi 1990-2004Typhi 1990-2004

Lancet 2005; 366: 752

TreatmentTreatment

Lancet 2005; 366: 755

PreventionPrevention

Lancet 2005; 366: 757

• Safe water & food, personal hygiene, appropriate sanitation• Vaccination Vi polysaccharide vaccine, Ty21a vaccine, Vi conjugate vaccine

MalariaMalaria• 4 human Plasmodium sp. pathogens

P. falciparum P. vivaxP. ovale P. malariae

• Vector: Anopheles sp.

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Malaria: Life CycleMalaria: Life Cycle

http://www.cdc.gov

Clinical outcome of malarial infectionClinical outcome of malarial infection

Nature 2002; 415: 673-679.

Pathogenesis of P. falciparumPathogenesis of P. falciparum

Nature 2002; 415: 673-679.

Uncomplicated malaria Uncomplicated malaria

Signs and symptoms of malaria: non-specific• Fever• Chills• Headache• Myalgia• Sore throat• Anorexia• Anemia• Hepatosplenomegaly

WHO criteria for severe malariaWHO criteria for severe malaria• Cerebral malaria• Impaired of consciousness (GCS <11)• Severe anemia (Hct <20% or Hb <7 g/dl)• Hypoglycemia (BS <40 mg/dl)• Metabolic acidosis (HCO3 <15 mmol/L)• Acute renal failure (Cr >3 mg/dl and urine output <400 ml/day)• Acute pulmonary edema and ARDS• Shock• Abnormal bleeding• Jaundice (TB >2.5 mg/dl)• Hemoglobinuria• Hyperparasitemia ( infection rate >5%)

WHO. Trans R Soc Trop Med Hyg 2000; 94 (Suppl).

Laboratory diagnosisLaboratory diagnosis

• Thick and thin film blood smear – Gold standard

• Antigen detection by rapid dipstick immunochromatographic assays• Histidine-rich protein-2: P. falciparum• Parasite-specific LDH: All Plasmodium spp.

• PCR technique

Plasmodium falciparumPlasmodium falciparum

Plasmodium vivaxPlasmodium vivax

Plasmodium malariaePlasmodium malariae

Plasmodium ovalePlasmodium ovale

Antimalarial treatment: Uncomplicated Antimalarial treatment: Uncomplicated falciparum malaria or mixed infectionfalciparum malaria or mixed infection

Drugs Doses Duration (days)

Artemether (20) –lumefantrine (120)

<15 kg: 1 tab BID16-25 kg: 2 tabs BID26-35 kg: 3 tabs BID>35 kg: 4 tabs BID

3

Atovaquone (250) –proguanil (100)

20 mg/kg/day8 mg/kg/day

3

Quinine SO4 +Tetracycline orDoxycyclineClindamycin

10 mg/kg TID4 mg/kg QID2 mg/kg BID5 mg/kg TID

7

Artesunate +Mefloquine

4 mg/kg/day15 mg/kg10 mg/kg

32nd day of Rx3rd day of Rx

Antimalarial treatment: Severe malaria or Antimalarial treatment: Severe malaria or Uncomplicated malaria with parasitemia Uncomplicated malaria with parasitemia >>4% IRBC4% IRBC

Artesunate i.v.Artesunate i.v.2.4 mg/kg at hour 0 and 12 followed by 2.4 mg/kg daily until oral medication is tolerated. Continue oral drug 2 mg/kg daily until day 7, adding 2nd agent as for quinine (below)Quinine HCl i.v.Quinine HCl i.v.20 mg/kg given over 4 hours, then 10 mg/kg every 8 hours. A second drug, e.g. doxycycline, tetramycin, or clindamycin for 7 days; or atovaquone + proguanil for 3 days, should be added when the patient can tolerate oral medication.

Antimalarial treatment: Non-falciparum malariaAntimalarial treatment: Non-falciparum malaria

Chloroquine 600 mg base at hour 0 followed by 300 mg base at hour 6, 2nd day, and 3rd day of treatment +Primaquine (for P. vivax and P. ovale only) 0.3-0.6 mg base/kg daily for 14 days

PreventionPrevention• Vector control

• Insecticide spraying• Larva control• Personal protection

• Insecticide-treated bednets• Insect repellents• Wearing appropriate clothing

• Antimalarial chemoprophylaxis• “Stand-by” emergency treatment