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Vector-borne diseases

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Presentation on theme: "Vector-borne diseases"— Presentation transcript:

1 Vector-borne diseases
S. Sears, MD Know what vectors are, environments (ticks – suburban environments)

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 3 phase disease Late or chronic - arthritis

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 EM – bulls eye rash

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 Most common is neurologic and carditits

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 Encephalomyelitis Ataxia Dementia Psychiatric disturbances Cutaneous involvement Acrodermatitis chronica atrophicans Morphea (localized scleroderma-like lesions) Mostly arthralgias and arthritis, with neurologic disease

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 Headache Fatigue paresthesias Usually a musculoskeletal, joint disease, neurologic. Need to think about it. EM is pathognomonic

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 days Amoxicillin 500mg po tid for days Cefuroxime 500mg po bid for days Disseminated disease Cardiac First degree AV block Doxycycline 100mg po bid for days Late disease Ceftriaxone 2g IV daily for days

14 Treatment Disseminated disease Neurologic disease Early
Isolated facial nerve palsy Doxycycline 100mg po bid for days Amoxicillin 500mg po tid for days Cefuroxime 500mg po bid for days More serious disease Early or late Meningitis Radiculopathy Encephalitis Ceftriaxone 2 g IV daily for 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 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 After tx for Lyme still had fever and such. Co-infection. These infect WBC – get flu etc, WBC ct goes down. Sicker than with Lyme

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 CSF lymphocytic pleocytosis
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 Need to think about it as a coinfection- fever and low white count

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 Can have triple infection.

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 Dosing Severe disease
Clindamycin-quinine Or atovaquone-azithromycin Dosing Atovaquone mg po q 12 hrs Azithromycin mg po x1 then 250 mg po daily Clindamycin mg po tid or 300 mg IV qid Quinine 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 Predominates
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 Liver and spleen enlarge over time
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 Very common cause of infant mortality

33 Cycle of malaria Vivax and ovale can live a while in liver.

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 Sick for a while, quiet period, then get sick again

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 Tx has changed. Artemisinin are DOC

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 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 Malaria – know it is prevetable. Travelers with a fever need to RO malaria.

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 Mostly in maryland

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 Spreads peripherally to central

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 Can be severe and still causes deaths in people that have other issues.

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 Mostly causes ulcer, dis in lungs and lymph nodes. Someone with ulcerative disease, and get fevers.

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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