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Title: Vector-borne%20diseases


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

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

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 lt 4 weeks illness - IgM and IgG tested
  • If gt 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
  • lt 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

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

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 (gt 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 lt 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

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

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

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 gt 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 gt 10
  • Or MSOF
  • Transfusion
  • Removes parasitized red blood cells
  • Parasitic toxins
  • Cytokines
  • Replaces with fresh plasma

44
Prognosis
  • Mortality
  • Untreated-100
  • Treated -10-40
  • Indicators of poor prognosis
  • Age lt 3 years
  • Deep coma
  • Convulsions
  • Papilledema
  • Absent corneal reflexes,decorticate/decerebrate
    rigidity
  • Organ dysfunction,ARDS,shock
  • Parasitemia gt 5
  • Peripheral mature pigmented parasites
  • Hematocrit lt15 , hemoglobin lt 5 g/dL
  • Peripheral WBC gt 12,000
  • Blood glucose lt 40 g/dL
  • BUN gt 60 mg/dL or creatinine gt 3mg/dL
  • Lactate gt 5 mmol/L
  • Increased liver function test 3 times normal
  • High CSF lactate gt6 mmol/L

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 lt100, 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
  • lt 4 years
  • 3-4
  • gt 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

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
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