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Vector-borne diseases S. Sears, MD. Lyme disease Multisystem inflammatory disease Causes by spirochetes –Borrelia burgdorferi Spread by Ixodes ticks –I.

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Presentation on theme: "Vector-borne diseases S. Sears, MD. Lyme disease Multisystem inflammatory disease Causes by spirochetes –Borrelia burgdorferi Spread by Ixodes ticks –I."— Presentation transcript:

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 youve 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

51 Petechial rash

52 Diagnosis Laboratory Thrombocytopenia Hyponatremia Increased liver function tests Azotemia CSF-WBC <100, increased protein, normal glucose Skin biopsy Direct immunofluorescence Serologic Indirect fluorescent antibody

53 Serum-indirect fluorescent antibody

54 Treatment Orally or IV Doxycycline 100mg bid Continued for at least three days after patient afebrile Usual length 5-7 days

55 Outcome Severe RMSF sequelae Peripheral neuropathy Hemiparesis Deafness Mortality < 4 years 3-4 % > 60 years 4-9 % Host factors associated with severe disease Male gender Black race Chronic alcohol abuse Glucose-6-phosphate dehydrogenase deficiency

56 Tularemia Caused by a gram-negative coccobacilli Francisella tularensis Predominantly in the Northern hemisphere Can persist in water,mud or animal carcasses for weeks Replicates in macrophages/leukocytes Natural infections found in Ticks,mosquitoes,horse flies,fleas,lice Human infections Vectors (ticks,biting flies,mosquito) Handling of infected animals (cleaning rabbits) Undercooked meat Drinking contaminated water Cat scratches or bites Splashing infected material in the eye

57 Francisella tularensis

58 Clinical manifestations Abrupt onset Fever Chills Headache Malaise Incubation period 2-10 days Six clinical syndromes Ulceroglandular Glandular Thyphoidal Pneumonia Oropharyngeal Oculoglandular

59 Syndromes Ulceroglandular –Single erythematous papuloulcerative lesion –Central eschar –Tender regional lymph nodes Glandular –Enlargement of single of multiple lymph nodes Typhoidal –Febrile septic illness –Lack of exposure history Pneumonic –Pulmonary infection –Airborne or hematogenous spread –Unilateral of bilateral infiltrates –Infiltrates are nodular –Hilar adenopathy,pleural effusions Oropharyngeal –Ingestion of poorly cooked meat –Severe painful pharyngitis –Cervical lymphadenopathy Oculoglandular –Conjunctival erythema –Periorbital edema

60 Ulceroglandular

61 Pneumonic

62 Oropharyngeal

63 Tularemia Diagnosis Serologic –Tube agglutination –ELISA –PCR Treatment Streptomycin-drug of choice –10mg/kg IM q 12hrs for 7-10 days –Recommended for meningitis –Severe disease Other options –Gentamicin : 3-5mg/kg IM/IV q8hrs for 7-10days –Tetracycline: 500mg po qid for 14 days –Doxycycline : 100mg po bid for 14 days –Chloramphenicol : 25-60mg/kg per day in 4 doses for 14 days Mortality 2-4 percent Complications –Drainage of lymph nodes –Pericarditis –Meningitis –ARDS –Rhabdomyolysis/renal failure

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