Common Tropical Infections

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Common Tropical Infections

• Siriluck Anunnatsiri, MD
• Infectious Disease Tropical Medicine
• Department of Medicine
• Khon Kaen University

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Tropical 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.

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Tropical and Subtropical Regions

350
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Common Tropical Infectious Diseases in Thailand

• Leptospirosis
• Rickettsioses
• Scrub typhus
• Murine typhus
• Melioidosis
• Enteric fever
• Typhoid fever
• Paratyphoid fever

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

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Leptospirosis

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

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Pathogenic Leptospira spp.
1 each
7.5
88
2.5
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Saprophytic Leptospira species Saprophytic Leptospira species Saprophytic Leptospira species 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
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Reservoir hosts of common leptospiral serovar
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Risk factors for exposure to leptospires

• Occupational groups
• Farmers, ranchers, abattoir workers, trappers,
  veterinarians, loggers, sewer workers, rice-field
  workers, military personnel
• Recreational activities
• Freshwater swimming, canoeing, kayaking, trail
  biking, hunting
• Household environment
• Pet dogs, domesticated livestock, rainwater
  catchment systems, rodent infestation

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Pathogenesis
Route of transmission Abrasion cuts in
skin Mucous membrane/Conjunctiva Intact skin
after prolong immersion in water Inhalation of
aerosol/water Ingestion
Toxin production LPS Hemolysin Cytotoxin
Outer envelope Antiphagocytic component
Outer membrane protein Interstitial
nephritis
Immune complex mediated inflammation Interstitial
nephritis Vasculitis
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Clinical manifestations
Anicteric leptospirosis Anicteric leptospirosis Icteric leptospirosis Weils syndrome Icteric leptospirosis Weils syndrome
(Incubation period 2-20 days) Fever Leptospiremic phase 3-7 days Immune phase 0-30 days Leptospiremic phase 3-7 days Immune phase 0-30 days
(Incubation period 2-20 days) Fever
Associated symptoms Myalgia Headache Nausea, Vomiting Abdominal pain Conjunctival suffusion Meningitis Uveitis Rash Jaundice Hemorrhage Acute renal failure Myocarditis Hemorrhagic pneumonitis Meningoencephalitis Hypotension Jaundice Hemorrhage Acute renal failure Myocarditis Hemorrhagic pneumonitis Meningoencephalitis Hypotension
Leptospires present in Blood Blood
Leptospires present in CSF CSF
Leptospires present in Urine Urine
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Clinical manifestations
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Laboratory diagnosis

• Culture
• Antibody detection
• Screening test
• MSAT, IHA, IFA, LA, ELISA, LEPTO dipstick
• Confirmation test
• Microscopic agglutination test
• Antigen detection
• Polymerase chain reaction (PCR)
• Pathology

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Treatment

• Supportive Symptomatic Treatment
• Antimicrobial therapy

• Mild form
• Doxycycline
• Amoxicillin
• Erythromycin

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

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Prevention

• 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

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Rickettsioses

• 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
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Distribution of scrub typhus in Asia
Redrawn from Harwood and James (1979)
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Life cycle of murine typhus
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Pathogenesis 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

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

http//pathmicro.med.sc.edu/mayer/ricketsia.htm
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Clinical presentations

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

• Lymphadenopathy
• Rash
• Hepatomegaly
• Splenomegaly
• Jaundice
• Altered consciousness
• Seizure
• Hypotension

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Clinical presentations
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Laboratory 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

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Treatment

• Scrub typhus
• Doxycycline
• Chloramphenicol
• Rifampicin
• Azithromycin

• Murine typhus
• Doxycycline
• Chloramphenicol

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Melioidosis

• Burkholderia pseudomallei
• Risk factors
• Diabetes mellitus
• Thalassemia
• Preexisting renal diseases
• Chronic liver diseases
• Immunosuppressive use
• Transmission
• Direct inoculation
• Inhalation
• Ingestion, sexual contact (rare)

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Worldwide distribution of melioidosis
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Melioidosis Clinical classification

• Disseminated septicemic melioidosis
• Non-disseminated septicemic melioidosis
• Multifocal localized melioidosis
• Localized melioidosis
• Probable melioidosis
• Subclinical melioidosis

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Clinical presentations of melioidosis
Clinical presentations of patients in of patients in of patients in
Clinical presentations Royal Darwin Hospital n252 Infectious Diseases Association of Thailand n686 Srinagarind Hospital n100
Pneumonia 58 45 49
Bacteremia 46 57 59
Hepatosplenic abscess 6 9 52
Skinsoft tissue infection 17 16 23
Genitourinary tract infection 19 7 13
Bonejoint infection 4 5 27
Neurological melioidosis 4 3 NR
Pericardial effusion 1 3 NR
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Clinical presentations
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Laboratory diagnosis

• Culture Gold standard
• Antibody detection
• IHA,ELISA, immunochromatographic test, dot
  immunoassay, Gold-blot immunoassay
• Antigen detection
• ELISA, latex agglutination, IFA
• Polymerase chain reaction

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Treatment

• 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
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Enteric fever

• Typhoid fever
• Salmonella Typhi
• Paratyphoid fever
• Salmonella Paratyphi A, B, and C

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Pathogenesis
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Symptoms of enteric fever
Symptoms Typhoid fever () Paratyphoid fever ()
Fever 89-100 92-100
Headache 43-90 60-100
Nausea 23-36 33-58
Vomiting 24-35 22-45
Abdominal cramp 8-52 29-92
Diarrhea 30-57 17-68
Constipation 10-79 2-29
Cough 11-36 10-68
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Signs of enteric fever
Symptoms Typhoid fever () Paratyphoid fever ()
Abdominal tenderness 33-84 6-29
Splenomegaly 23-65 0-74
Hepatomegaly 15-52 16-32
Relative bradycardia 17-50 11-100
Rose spots 2-46 0-3
Rales rhonchi 8-84 2-87
Epitaxis 1-21 2-13
Meningism 1-12 0-3
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Laboratory diagnosis

• Culture Gold standard Blood, BM, duodenal
  string test
• Antibody detection
• Widal test poor sensitivity specificity
• Rapid serological diagnostic test

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Drug resistance S. Typhi 1990-2004
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Treatment
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Prevention

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

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Malaria

• 4 human Plasmodium sp. pathogens
• P. falciparum P. vivax
• P. ovale P. malariae
• Vector Anopheles sp.

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Malaria Life Cycle
http//www.cdc.gov
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Clinical outcome of malarial infection
Nature 2002 415 673-679.
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Pathogenesis of P. falciparum
Nature 2002 415 673-679.
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Uncomplicated malaria

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

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WHO criteria for severe malaria

• Cerebral malaria
• Impaired of consciousness (GCS lt11)
• Severe anemia (Hct lt20 or Hb lt7 g/dl)
• Hypoglycemia (BS lt40 mg/dl)
• Metabolic acidosis (HCO3 lt15 mmol/L)
• Acute renal failure (Cr gt3 mg/dl and urine output
  lt400 ml/day)
• Acute pulmonary edema and ARDS
• Shock
• Abnormal bleeding
• Jaundice (TB gt2.5 mg/dl)
• Hemoglobinuria
• Hyperparasitemia ( infection rate gt5)

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

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Plasmodium falciparum
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Plasmodium vivax
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Plasmodium malariae
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Plasmodium ovale
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Antimalarial treatment Uncomplicated falciparum
malaria or mixed infection
Drugs Doses Duration (days)
Artemether (20) lumefantrine (120) lt15 kg 1 tab BID 16-25 kg 2 tabs BID 26-35 kg 3 tabs BID gt35 kg 4 tabs BID 3
Atovaquone (250) proguanil (100) 20 mg/kg/day 8 mg/kg/day 3
Quinine SO4 Tetracycline or Doxycycline Clindamycin 10 mg/kg TID 4 mg/kg QID 2 mg/kg BID 5 mg/kg TID 7
Artesunate Mefloquine 4 mg/kg/day 15 mg/kg 10 mg/kg 3 2nd day of Rx 3rd day of Rx
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Antimalarial treatment Severe malaria or
Uncomplicated malaria with parasitemia gt4 IRBC
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. 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.
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Antimalarial 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
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Prevention

• Vector control
• Insecticide spraying
• Larva control
• Personal protection
• Insecticide-treated bednets
• Insect repellents
• Wearing appropriate clothing
• Antimalarial chemoprophylaxis
• Stand-by emergency treatment

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