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Vector-borne diseases

Vector-borne diseases. S. Sears, MD. Lyme disease. Multisystem inflammatory disease Causes by spirochetes Borrelia burgdorferi Spread by Ixodes ticks I. scapularis Eastern,North central and Southern United States I. pacificus Western United States I. ricinus Europe I. persulcatus

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Vector-borne diseases

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  1. Vector-borne diseases S. Sears, MD

  2. Lyme disease • Multisystem inflammatory disease • Causes by spirochetes • Borrelia burgdorferi • Spread by Ixodes ticks • I. scapularis • Eastern,North central and Southern United States • I. pacificus • Western United States • I. ricinus • Europe • I. persulcatus • Asia • Transmission • Bite of an infected nymph in the spring-really small, barely even know you’ve been bitten • Preferred host • White-tailed deer

  3. Borrelia burgdorferi

  4. Ixodes scapularis

  5. Clinical manifestations • Early localized disease • Occurring few days to one month after the tick bite • Early disseminated disease • Occurring days to 10 months after the tick bite • Late or chronic disease • Occurring months to years after the tick bite

  6. Early localized disease • Erythema migrans • 50-70% of patients • Found • Near axilla • Inguinal region • Behind the knees • Belt line • Asymptomatic • May burn or itch • Expands over the course a few days with central clearing • Associated symptoms • Fatigue • Malaise • Lethargy • Headache • Stiff neck • Myalgias • Arthralgias • Lymphadenopathy

  7. Erythema migrans

  8. Early disseminated disease • Carditis : 8 -10% of patients • Conduction defects • Cardiomyopathy or myopericarditis • Neurologic disease :10% of patients • Lymphocytic meningitis • Encephalitis • Cranial neuropathy (often bilateral facial) • Peripheral neuropathy • Radiculoneuropathy • Myelitis • Musculoskeletal involvement : 50% of patients • Migratory polyarthritis • Skin involvement • Erythema nodosum • Lymphadenopathy • Eye involvement • Conjunctivitis • Iritis • Retinitis • Vitritis • Choroiditis • Hepatitis • Microhematuria with proteinuria

  9. Late or chronic disease • Musculoskeletal symptoms • 50% : migratory polyarthritis • 10% : chronic monoarthritis (knee) • Neurologic disease (incidence not established) • Neuroborrelosis • Encephalopathy • Neurocognitive dysfunction • Peripheral neuropathy • Encephalopathy • Encephalomyelitis • Peripheral neuropathy • Ataxia • Dementia • Psychiatric disturbances • Cutaneous involvement • Acrodermatitis chronica atrophicans • Morphea (localized scleroderma-like lesions)

  10. Acrodermatitis chronica atrophicans

  11. Diagnosis Centers of Disease Control and Prevention criteria • Presence of erythema migrans • OR • At least one late manifestation • Plus laboratory confirmation • Late manifestations can include if not explained by another disease • Musculoskeletal system • Chronic arthritis • Not • Chronic progressive arthritis • Chronic symmetrical arthritis • Fibromyalgia • Nervous system • Lymphocytic meningitis • Cranial neuritis • Encephalomyelitis • CSF confirmation of antibody against B. burgdorferi • Not • Headache • Fatigue • paresthesias

  12. Diagnosis • Serologic tests • Used to confirm the diagnosis • Diagnosis make on clinical grounds • Two-rest step approach • Sensitive enyzme-linked immunosorbent assay (ELISA) • Followed by Western immunoblot • If ELISA positive-test Western blot • If ELISA negative-no Western blot • Same sample tested by each test • If < 4 weeks illness - IgM and IgG tested • If > 4 weeks illness - IgG tested • Synovial fluid or CSF • Tested for the antibodies to B.burgdorferi • Antibiotics in early disease may prevent seroconversion • Prior vaccine interferes with the test (vaccine no longer available)

  13. Treatment Early disease • Erythema migrans • < 10% do not respond • Do not use macrolides • For areas also endemic for human ehrlichiosis use doxycycline • Doxycycline 100mg po bid for 10-21 days • Amoxicillin 500mg po tid for 14-21 days • Cefuroxime 500mg po bid for 14-21 days Disseminated disease • Cardiac • First degree AV block • Doxycycline 100mg po bid for 14-21 days • Amoxicillin 500mg po tid for 14-21 days • Cefuroxime 500mg po bid for 14-21 days • Late disease • Ceftriaxone 2g IV daily for 14-21 days

  14. Treatment Disseminated disease • Neurologic disease • Early • Isolated facial nerve palsy • Doxycycline 100mg po bid for 14-21 days • Amoxicillin 500mg po tid for 14-21 days • Cefuroxime 500mg po bid for 14-21 days • More serious disease • Early or late • Meningitis • Radiculopathy • Encephalitis • Ceftriaxone 2 g IV daily for 14-28 days • Arthritis • No evidence of neurologic disease • Doxycycline 100mg po bid for 28 days • Amoxicillin 500mg po tid for 28 days • Cefuroxime 500mg po bid for 28 days • With neurologic disease • Ceftriaxone 2g IV daily for 14-28 days

  15. Outcome • Treatment with standard antibiotics generally successful • 10 % experience treatment failure • Non-specific symptoms may linger • Asymptomatic seropositive patients • Recommendation not to treat

  16. Human ehrlichiosis Ehrlichiae • Obligate intracellular bacteria • Grow in membrane bound vacuoles • Human and animal leukocytes • Diseases • Human monocytic ehrlichiosis (HME) • Caused by Ehrlichia chaffeensis • Human granulocytic anaplasmosis (HGA) • Caused by Anaplasma phagocytophilum • Occurs in spring and summer • In southeastern, southcentral,mid-Atlantic United States • Tick vector • E.chaffeensis - Lone star tick (Amblyomma americanum) • A.phagocytophilum - Ixodes scapularis • Animal reservoir • HME - white tail deer • HGA - deer and white-footed mouse

  17. Ehrlichia chaffeensis

  18. Lone star tick

  19. Clinical manifestations • Incubation period 1-2 weeks prior to presentation of symptoms • Fever can persist for 2 months • Nonspecific • Malaise • Myalgia • Headache • Chills • Nausea • Vomiting • Arthralgias • Cough • Maculopapular or petechial rash • Neurologic • Mental status changes • Stiff neck • Clonus • Complications • Seizures • Coma • Congestive heart failure • Pericardial effusion

  20. Rash

  21. Investigations • Laboratory findings • Leukopenia • Thrombocytopenia • Anemia • Increased liver function tests • CSF lymphocytic pleocytosis • Diagnosis • Indirect fluorescent antibody (IFA) test • Examination of peripheral blood or buffy coat • PCR for HME and HGA • Immunochemical staining of ehrlichial/anaplasmal antigens in tissue

  22. Treatment • Drug of choice • Doxycycline IV or oral • 100 mg bid for 10 days • Intolerance to doxycycline • Use rifampin 300mg po bid for 7-10 days

  23. Outcome Mortality rates • HME - 2 to 5 percent • HGA - 7 to 10 percent Life-threatening disease • In patients co-infected with HIV • Solid organ transplant recipients Prevention • Tick repellants • Tick removal

  24. Babesiosis • Tick borne illness • Protozoa of the family Babesiidae • Animal reservoir • Rodents and cattle • Human disease • Due to Babesia microti • Enters the red blood cells and causes hemolysis • Vector • Ixodid tick • Occurs northeast coast of the United States

  25. Clinical manifestations • Incubation period • Following a tick bite • 1-3 weeks • After blood transfusion • 6-9 weeks • Symptoms • Fever • Chills • Sweats • Myalgia • Arthralgia • Nausea • Vomiting • Fatigue • Physical exam • Splenomegaly • Hepatomegaly • Jaundice

  26. Severe disease • High-level parasitemia (> 10 percent) • Significant hemolysis ( plus DIC) • Renal ,hepatic, pulmonary compromise Risk factors • Age over 50 years • Asplenia • Underlying malignancy • Immunosuppressive therapy • HIV/AIDS

  27. Diagnosis Laboratory • Anemia • Thrombocytopenia • Conjugated hyperbilirubinemia Confirmation • Blood smear • Intraerythrocytic parasites • PCR • Serology • Indirect immunofluorescent antibody test

  28. Babesia microti

  29. Treatment • First-line treatment • 7-10 days • Clindamycin-quinine • Or atovaquone-azithromycin • Dosing • Atovaquone - 750 mg po q 12 hrs • Azithromycin - 500-1000 mg po x1 then 250 mg po daily • Clindamycin - 600 mg po tid or 300 mg IV qid • Quinine - 650 mg po q6hrs • Severe disease • Antibiotics • Plus exchange transfusion • Until parasitemia is < 5 percent • Outcome is variable with level of disease

  30. Malaria • Human malaria caused by species Plasmodia • P. falciparum • P. vivax • P. ovale • P. malariae • Predominates • Tropical Africa • Southeast Asia • Haiti • South America • Dominican Republic • Central America • Middle East • India • Transmission • Bite of Anopheles mosquito • Congenital • Blood transfusion • Contaminated needles • Transplantation

  31. Anopheles mosquito

  32. Malaria All four malaria parasites • Digest red blood cell proteins and hemoglobin • Results in hemolysis and increased splenic clearance Liver and spleen enlarge over time • Thrombocytopenia from increased splenic clearance P. Falciparum • Forms stick knobs • Forms rosettes • Results in obstruction of blood flow Protection against malaria • Sickle cell genetic alterations • Alpha thalassemia • Beta thalassemia • Ovalocytes Immunity • Partial immunity may occur in those in endemic areas

  33. Cycle of malaria

  34. Clinical manifestations Incubation period • 1-4 weeks Symptoms • Chills • Sweats • Headache • Myalgias • Fatigue • Nausea • Abdominal pain • Vomiting • Diarrhea • Cough • Signs • Anemia • Thrombocytopenia • Splenomegaly • Hepatomegaly • Jaundice • Splenic rupture

  35. Clinical manifestations P. falciparum • Associated with transient increases in HIV viral load • Cerebral malaria • Impaired state of consciousness • Seizures Risk factors • Age • Pregnancy • Poor nutritional status • HIV infection • Prior splenectomy Complications • Renal failure • ARDS • Hypoglycemia • Anemia • Bleeding • Gastroenteritis P. vivax and ovale • Liver forms-late relapses P. malariae • GN from chronic immune complex formation and deposition

  36. Diagnosis Light microscopy • Stained thick and thin blood smear • Thick smear • Malaria • Thin smear • Morphologic features • Parasite density estimation • Fluorescent microscopy • Antigen detection • PCR- DNA / RNA

  37. Blood smear

  38. Treatment Supportive measures Antimalarial medications Mechanisms of antimalarial drugs • Quinoline derivatives • Chloroquine,quinine,quinidine,mefloquine • Inhibit heme polymerase activity • Accumulation of free heme is toxic to parasites • Antifolates • Pyrimethamine,sulfonamides,dapsone • Kill intrahepatic forms of the parasite • Artemisinin derivatives • Artemisinin,artemether,artesunate • Produce free radical that damage parasite proteins • Antimicrobials • Clindamycin,atovaquone,tetracyclines • Kill blood parasites

  39. Treatment Chloroquine-sensitive • P.vivax • P.ovale • P. malariae • Chloroquine 10mg base/kg (max 600mg base) • Followed by 5mg/kg base (max 300mg base) • At 6, 24,and 48 hours • Cure rates 95% Chloroquine resistant • P. vivax • Mefloquine or quinine PLUS doxycycline Prevention of relapse • Liver forms of malaria • P. vivax and P. ovale • Primaquine 30mg/day for 14 days • Start immediately after completing chloroquine • Screen for glucose-6-phosphate-dehydrogenase to prevent hemolysis

  40. P. Falciparum malaria Chloroquine-sensitive • Treat like other forms of malaria for the chloroquine Most cases are chloroquine-resistant • Uncomplicated disease • One of the following: • Quinine-based • Atovaquone-proquanil • Mefloquine • Artemisinin derivative combinations Quinine-based • Quinine sulfate 10mg/kg salt (max 650 mg) q8hrs for 3-7days • Combined with • 3 tabs of pyrmethamine-sulfadoxine(25/500mg) on day three • Or doxycycline 100mg po bid for seven days • Quinine causes reversible tinnitus and reversible high-tone hearing loss

  41. P. Falciparum malaria Atovaquone-proquanil • 250mg atovaquone plus 100mg proguanil • Four tablets for 3 days • Common side-effects gastrointestinal Mefloquine • 25 mg/kg base as a single dose • Side-effects • Vomiting,nightmares,ataxia,delirium,seizures Artemisinin derivatives • IV ,IM or oral • Given for 5-7 days • 4mg/kg on day 1 • 2mg/kg on days 2,3 • 1mg/kg on days 4-7 • Combined with • Mefloquine-750mg then in 12 hrs 500mg • Or doxycycline 100mg po bid for 7 days • No serious toxicities from artenisinin derivatives have been observed in humans

  42. Severe Falciparum malaria Definition • Parasitemia of > 5 percent • Altered consciousness • Oliguria • Jaundice • Severe normocytic anemia • Hypoglycemia • Organ failure Additional features • Seizures • Acute renal failure • Electrolyte abnormalities • Metabolic acidosis • ARDS • Shock • Hemoglobinuria • bleeding

  43. Treatment-severe disease Use intravenous medications • Quinine-based • IV quinidine gluconate 10mg/kg over 2 hrs the 0.02mg/kg/min • Artemisinin-based • Artesunate 2.4 mg/kg IV followed by 1.2mg/kg at 12 and 24 hrs the 1.2mg/kg daily for 6 days • Quinine-resistant • Artenisinin-based • Plus tetracycline or mefloquine • Artenisinin not in the United states • Need to use quinine plus tetracycline/doxycycline • Supportive measures • Exchange transfusion • For parasitemia > 10% • Or MSOF • Transfusion • Removes parasitized red blood cells • Parasitic toxins • Cytokines • Replaces with fresh plasma • Continue until parasitemia < 5 %

  44. Prognosis Mortality • Untreated-100% • Treated -10-40 % Indicators of poor prognosis • Age < 3 years • Deep coma • Convulsions • Papilledema • Absent corneal reflexes,decorticate/decerebrate rigidity • Organ dysfunction,ARDS,shock • Parasitemia > 5% • Peripheral mature pigmented parasites • Hematocrit <15 %, hemoglobin < 5 g/dL • Peripheral WBC > 12,000 • Blood glucose < 40 g/dL • BUN > 60 mg/dL or creatinine > 3mg/dL • Lactate > 5 mmol/L • Increased liver function test 3 times normal • High CSF lactate >6 mmol/L • Low antithrombin III levels • High plasma TNF concentration

  45. Rocky Mountain Spotted Fever Causative agent rickettsia • Gram-negative bacteria-coccobacillus • Intracellular parasite • Grows in the nucleus and cytoplasm of host cells Vector • Dermacentor variabilis-American dog tick • Eastern and south central United States • Dermacentor andersonii-Rocky Mountain wood tick • Mountain states west of Mississippi • Brown dog tick (Rhipicephalus sanguineus) • Arizona • Ricksettsia • Induces cell death and necrosis • Leads to vasculitis • Hemorrhage • Increased vascular permeability • Edema • Activation of humoral immunity

  46. Rickettsia rickettsii

  47. American dog tick

  48. Brown dog tick

  49. Clinical manifestations Occurs in spring and summer • Fever-common • Severe headache • Malaise • Arthralgias • Nausea • Between 3-5 days • Rash • Begins on the ankles and wrists • Spreads to hands and feet • Spreads centrally • Maculopapular and becomes petechial • Abnormal mentation • Seizures • Focal neurologic deficits

  50. Rash

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