Common Tropical Infections

1. Common Tropical Infections Siriluck Anunnatsiri, MD Infectious Disease & Tropical Medicine Department of Medicine Khon Kaen University

2. 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.

3. Tropical and Subtropical Regions 350 230

4. Leptospirosis Rickettsioses: Scrub typhus Murine typhus Melioidosis Enteric fever Typhoid fever Paratyphoid fever Nontyphoidal salmonellosis Tuberculosis Malaria Dengue infection Helminthic infection Infective diarrhea Common Tropical Infectious Diseases in Thailand

5. Leptospirosis • The most widespread zoonosis in the world • Situation in Thailand สำนักระบาดวิทยา กรมควบคุมโรค กระทรวงสาธารณสุข

6. Pathogenic Leptospira spp. 1% each 7.5% 88% 2.5% Lancet Infect Dis 2003; 3: 758

7. Lancet Infect Dis 2003; 3: 758

8. Reservoir hosts of common leptospiral serovar Lancet Infect Dis 2003; 3: 758

9. 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

10. 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 Immune complex mediated inflammation: Interstitial nephritis Vasculitis Outer membrane protein: Interstitial nephritis

11. Clinical manifestations

12. Clinical manifestations Lancet Infect Dis 2003; 3: 758

13. 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

14. Mild form Doxycycline Amoxicillin Erythromycin Moderate-to-severe form Penicillin G Doxycycline Ceftriaxone Treatment • Supportive & Symptomatic Treatment • Antimicrobial therapy

15. 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

16. 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

17. Distribution of scrub typhus in Asia Redrawn from Harwood and James (1979)

19. Life cycle of murine typhus

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

21. Fever Myalgia Headache Nausea/vomiting Abdominal pain Diarrhea Conjunctival suffusion / subconjunctival hemorrhage Lymphadenopathy Rash Hepatomegaly Splenomegaly Jaundice Altered consciousness Seizure Hypotension Clinical presentations

22. Clinical presentations

23. 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

24. Scrub typhus Doxycycline Chloramphenicol Rifampicin Azithromycin Murine typhus Doxycycline Chloramphenicol Treatment

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

26. Worldwide distribution of melioidosis

27. Melioidosis: Clinical classification • Disseminated septicemic melioidosis • Non-disseminated septicemic melioidosis • Multifocal localized melioidosis • Localized melioidosis • Probable melioidosis • Subclinical melioidosis

28. Clinical presentations of melioidosis

29. Clinical presentations Lancet 2003; 361: 1720

30. 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

31. Acute phase Ceftazidime + co-trimoxazole Cefoperazone/sulbactam+ co-trimoxazole Imipenem/Meropenem Co-amoxiclav Maintenance phase Co-trimoxazole + doxycycline Co-amoxiclav Ciprofloxacin + azithromycin Treatment At least 10-14 days At least 20 weeks

32. Enteric fever • Typhoid fever Salmonella Typhi • Paratyphoid fever Salmonella Paratyphi A, B, and C สำนักระบาดวิทยา กรมควบคุมโรค กระทรวงสาธารณสุข

33. Pathogenesis www.netterimages.com

34. Symptoms of enteric fever

35. Signs of enteric fever

37. 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

38. Drug resistance S. Typhi 1990-2004 Lancet 2005; 366: 752

39. Treatment Lancet 2005; 366: 755

40. Prevention • Safe water & food, personal hygiene, appropriate sanitation • Vaccination • Vi polysaccharide vaccine, Ty21a vaccine, Vi conjugate • vaccine Lancet 2005; 366: 757

41. Malaria • 4 human Plasmodium sp. pathogens P. falciparum P. vivax P. ovale P. malariae • Vector: Anopheles sp. สำนักระบาดวิทยา กรมควบคุมโรค กระทรวงสาธารณสุข

43. Malaria: Life Cycle http://www.cdc.gov

44. Clinical outcome of malarial infection Nature 2002; 415: 673-679.

45. Pathogenesis of P. falciparum Nature 2002; 415: 673-679.

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

47. WHO 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).

48. 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

49. Plasmodium falciparum

50. Plasmodium vivax