Common Tropical Infections
Siriluck Anunnatsiri, MD
Infectious Disease & Tropical Medicine
Department of Medicine
Khon Kaen University
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.
Tropical and Subtropical Regions
350
230
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
Leptospirosis
• The most widespread zoonosis in the world
• Situation in Thailand
สำนักระบำดวิทยำ กรมควบคุมโรค กระทรวงสำธำรณสุ ข
Pathogenic Leptospira spp.
1% each
7.5%
88%
2.5%
Lancet Infect Dis 2003; 3: 758
Saprophytic Leptospira species
Species
Serovar
Reference
strain
Serogroup
Genomospecies 3 holland
Waz Holland Holland
(P438)
L. biflexa
patoc
Patoc I
L. wolbachii
codice
CDC
Semaranga
Lancet Infect Dis 2003; 3: 758
Reservoir hosts of common leptospiral serovar
Lancet Infect Dis 2003; 3: 758
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
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 Immune complex
mediated inflammation:
protein:
Interstitial nephritis Interstitial nephritis
Vasculitis
Clinical manifestations
Anicteric leptospirosis
Icteric leptospirosis
Weil’s syndrome
Leptospiremic
phase
3-7 days
Immune phase Leptospiremic
phase
0-30 days
3-7 days
Associated
symptoms
Myalgia
Headache
Nausea, Vomiting
Abdominal pain
Conjunctival
suffusion
Meningitis
Uveitis
Rash
Leptospires
present in
Blood
(Incubation
period 2-20
days)
Immune phase
0-30 days
Fever
Jaundice
Hemorrhage
Acute renal failure
Myocarditis
Hemorrhagic pneumonitis
Meningoencephalitis
Hypotension
Blood
CSF
CSF
Urine
Urine
Clinical manifestations
Lancet Infect Dis 2003; 3: 758
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
Treatment
• Supportive & Symptomatic Treatment
• Antimicrobial therapy
Mild form
• Doxycycline
• Amoxicillin
• Erythromycin
Moderate-to-severe form
• Penicillin G
• Doxycycline
• Ceftriaxone
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
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
Distribution of scrub typhus in Asia
Redrawn from Harwood and James (1979)
Life cycle of murine typhus
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 via the
microcirculation and invade
all organ systems
• Vasculitis resulting in local
thrombus formation and end
organ damage.
• Spread to contiguous
endothelial cells, smooth
muscle cells, and
phagocytes
http://pathmicro.med.sc.edu/mayer/ricketsia.htm
Clinical presentations
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Fever
Myalgia
Headache
Nausea/vomiting
Abdominal pain
Diarrhea
Conjunctival suffusion
/ subconjunctival
hemorrhage
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Lymphadenopathy
Rash
Hepatomegaly
Splenomegaly
Jaundice
Altered
consciousness
• Seizure
• Hypotension
Clinical presentations
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
Treatment
Scrub typhus
• Doxycycline
• Chloramphenicol
• Rifampicin
• Azithromycin
Murine typhus
• Doxycycline
• Chloramphenicol
Melioidosis
• Burkholderia pseudomallei
• Risk factors
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Diabetes mellitus
Thalassemia
Preexisting renal diseases
Chronic liver diseases
Immunosuppressive use
• Transmission
• Direct inoculation
• Inhalation
• Ingestion, sexual contact (rare)
Worldwide distribution of melioidosis
Melioidosis: Clinical classification
• Disseminated septicemic melioidosis
• Non-disseminated septicemic
melioidosis
• Multifocal localized melioidosis
• Localized melioidosis
• Probable melioidosis
• Subclinical melioidosis
Clinical presentations of melioidosis
% of patients in:
Clinical
presentations
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 presentations
Lancet 2003; 361: 1720
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
Treatment
• Acute phase
• Ceftazidime + cotrimoxazole
• Cefoperazone/sulbactam
+ co-trimoxazole
• Imipenem/Meropenem
• Co-amoxiclav
At least 10-14 days
• Maintenance phase
• Co-trimoxazole +
doxycycline
• Co-amoxiclav
• Ciprofloxacin +
azithromycin
At least 20 weeks
Enteric fever
• Typhoid fever
Salmonella Typhi
• Paratyphoid fever
Salmonella Paratyphi A, B, and C
สำนักระบำดวิทยำ กรมควบคุมโรค กระทรวงสำธำรณสุ ข
Pathogenesis
www.netterimages.com
Symptoms of enteric fever
Symptoms
Fever
Headache
Nausea
Vomiting
Abdominal
cramp
Diarrhea
Constipation
Cough
Typhoid fever (%)
89-100
43-90
23-36
24-35
8-52
Paratyphoid fever (%)
92-100
60-100
33-58
22-45
29-92
30-57
10-79
11-36
17-68
2-29
10-68
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
Laboratory 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. Typhi 1990-2004
Lancet 2005; 366: 752
Treatment
Lancet 2005; 366: 755
Prevention
• Safe water & food, personal hygiene, appropriate sanitation
• Vaccination
Vi polysaccharide vaccine, Ty21a vaccine, Vi conjugate
vaccine
Lancet 2005; 366: 757
Malaria
• 4 human Plasmodium sp. pathogens
P. falciparum
P. vivax
P. ovale
P. malariae
• Vector: Anopheles sp.
สำนักระบำดวิทยำ กรมควบคุมโรค กระทรวงสำธำรณสุ ข
Malaria: Life Cycle
http://www.cdc.gov
Clinical outcome of malarial infection
Nature 2002; 415: 673-679.
Pathogenesis of P. falciparum
Nature 2002; 415: 673-679.
Uncomplicated malaria
Signs and symptoms of malaria: non-specific
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Fever
Chills
Headache
Myalgia
Sore throat
Anorexia
Anemia
Hepatosplenomegaly
WHO criteria for severe malaria
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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 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 falciparum
Plasmodium vivax
Plasmodium malariae
Plasmodium ovale
Antimalarial treatment: Uncomplicated
falciparum malaria or mixed infection
Drugs
Doses
Duration (days)
Artemether (20) –
lumefantrine (120)
<15 kg: 1 tab BID
16-25 kg: 2 tabs BID
26-35 kg: 3 tabs BID
>35 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
7
Artesunate +
Mefloquine
4 mg/kg/day
4 mg/kg QID
2 mg/kg BID
5 mg/kg TID
15 mg/kg
10 mg/kg
3
2nd day of Rx
3rd day of Rx
Antimalarial treatment: Severe malaria or
Uncomplicated malaria with parasitemia >4% 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.
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
Prevention
• Vector control
• Insecticide spraying
• Larva control
• Personal protection
• Insecticide-treated bednets
• Insect repellents
• Wearing appropriate clothing
• Antimalarial chemoprophylaxis
• “Stand-by” emergency treatment