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بسم الله الرحمن الرحيمبسم الله الرحمن الرحيمBiodefenseBiodefense

Epidemiology of Epidemiology of

Q feverQ feverShahid Beheshti University ofShahid Beheshti University of

medical sciences April 2005medical sciences April 2005

By: Hatami H. MD. MPHBy: Hatami H. MD. MPH

الف ـ مقدمه و معرفي الف ـ مقدمه و معرفي بيماريبيماري

- تعريف و اهميت بهداشتي- تعريف و اهميت بهداشتي11

– عامل يا عوامل اتيولوژيك – عامل يا عوامل اتيولوژيك22

ب ـ اپيدميولوژي توصيفي و ب ـ اپيدميولوژي توصيفي و ((OCCURRENCEOCCURRENCE))وقوعوقوع

ج ـ پيشگيري و كنترلج ـ پيشگيري و كنترل

• An An acuteacute (on occasion (on occasion chronicchronic) febrile illness that ) febrile illness that occurs occurs worldwideworldwide. .

• One of the important One of the important zoonoseszoonoses

- تعريف و اهميت بهداشتي- تعريف و اهميت بهداشتي11

Morbidity and MortalityMorbidity and MortalityMorbidity and MortalityMorbidity and Mortality

• Prevalence unknownPrevalence unknown–Endemic areasEndemic areas

• 18-55% of sheep with 18-55% of sheep with antibodiesantibodies

• 82% of dairy cattle82% of dairy cattle

• Morbidity in sheep: 5-50%Morbidity in sheep: 5-50%

Q Fever as a Biological WeaponQ Fever as a Biological WeaponQ Fever as a Biological WeaponQ Fever as a Biological Weapon

• AccessibilityAccessibility

• Low infectious doseLow infectious dose

• Stable in the environmentStable in the environment

• Aerosol transmissionAerosol transmission

• WHO estimateWHO estimate– 5 kg agent released on 5 million persons5 kg agent released on 5 million persons

• 125,000 ill - 150 deaths125,000 ill - 150 deaths• Could travel downwind for over 20 kmCould travel downwind for over 20 km

HistoryHistoryHistoryHistory

• 1935 1935 – 1st described in Queensland, Australia1st described in Queensland, Australia– Found in ticks in MontanaFound in ticks in Montana

• OutbreaksOutbreaks– Among military troopsAmong military troops

• When present in areas with infected When present in areas with infected animalsanimals

– Cities and townsCities and towns• Downwind from farmsDownwind from farms• By roads traveled by animalsBy roads traveled by animals

2 – Etiologic agent2 – Etiologic agent• CoxiellaCoxiella burnetii burnetii

– RickettsialRickettsial agent agent

– ObligateObligate intracellular parasite intracellular parasite

– StableStable and and resistantresistant

– Killed by Killed by pasteurizationpasteurization

– Two Two antigenic phasesantigenic phases• Phase 1: virulentPhase 1: virulent• Phase 2: less pathogenicPhase 2: less pathogenic

•One organism may cause diseaseOne organism may cause disease

ب ـ اپيدميولوژي توصيفي و ب ـ اپيدميولوژي توصيفي و QQتب تب وقوع وقوع

((Incubation periodIncubation period)) – دوره نهفتگي – دوره نهفتگي11( ( Natural courseNatural course)) – سير طبيعي – سير طبيعي22 Geographical Geographical)) – انتشار جغرافيائي – انتشار جغرافيائي33

distributiondistribution ) )((Timeline trendTimeline trend)) – روند زماني – روند زماني44 – تاثير سن، جنس، شغل و موقعيت – تاثير سن، جنس، شغل و موقعيت 55

اجتماعياجتماعي Predisposing Predisposing)) – تاثير عوامل مساعد كننده – تاثير عوامل مساعد كننده66

factorsfactors ) ) & Susceptibility & Susceptibility)) – حساسيت و مقاومت – حساسيت و مقاومت77

ResistanceResistance ) ) Secondary attack Secondary attack)) – ميزان حمله هاي ثانويه – ميزان حمله هاي ثانويه88

raterate ) ) – نحوه انتقال و دوره قابليت سرايت – نحوه انتقال و دوره قابليت سرايت99((Mode of transmission & period of communicabilityMode of transmission & period of communicability))

1 - Incubation Period1 - Incubation Period

• Incubation: 2-5 weeksIncubation: 2-5 weeks

• Depends on the size of the infecting Depends on the size of the infecting dosedose

2 - Natural course2 - Natural course

–Asymptomatic (50%)Asymptomatic (50%)

–AcuteAcute

–ChronicChronic

In contrast to other rickettsial In contrast to other rickettsial infections, rash rarely occurs in infections, rash rarely occurs in acute Q fever acute Q fever (ref: mandell)(ref: mandell)

Acute InfectionAcute InfectionAcute InfectionAcute Infection• Flu-likeFlu-like, self limiting , self limiting • Atypical Atypical pneumoniapneumonia (30-50%) (30-50%)

– Non-productive cough, chest painNon-productive cough, chest pain– Acute respiratory distress possible Acute respiratory distress possible

• HepatitisHepatitis• Skin rashSkin rash (rarely) (rarely)

– MyocarditisMyocarditis, pericarditis, meningoencephalitis, pericarditis, meningoencephalitis

• DeathDeath: 1-2%: 1-2%

Differences between Q fever Differences between Q fever and other rickettsiosisand other rickettsiosis

Differences between Q fever Differences between Q fever and other rickettsiosisand other rickettsiosis

• Rash rarely occurs in acute Q feverRash rarely occurs in acute Q fever• The rash in chronic Q fever (endocarditis) is The rash in chronic Q fever (endocarditis) is that of palpable purpura due to an immune that of palpable purpura due to an immune complex vasculitis. complex vasculitis. • The aerosol route of infectionThe aerosol route of infection• The lack of cross-reacting antibodies to The lack of cross-reacting antibodies to ProteusProteus X strain (the Weil-Felix reaction). X strain (the Weil-Felix reaction).

Ref: mandellRef: mandell

Chronic DiseaseChronic Disease• 1-5% of those infected

– Prior heart disease, pregnant women, immunocompromised

• Endocarditis• Other

– Osteomyelitis– Granulomatous hepatitis– Cirrhosis

• 50% relapse rate after antibiotic therapy

Risk to Pregnant WomenRisk to Pregnant WomenRisk to Pregnant WomenRisk to Pregnant Women

• Undergo reactivation during pregnancy in Undergo reactivation during pregnancy in animals other than humans ?? animals other than humans ??

• Most Most asymptomaticasymptomatic

• TransplacentalTransplacental transmission transmission

• Reported Reported complications :complications :– In-utero deathIn-utero death– Premature birthPremature birth– Low birth weightLow birth weight– PlacentitisPlacentitis– ThrombocytopeniaThrombocytopenia

–Immunity following recovery Immunity following recovery from clinical illness is probably from clinical illness is probably lifelong lifelong

–Cell mediated immunity lasting Cell mediated immunity lasting longer than humoral one longer than humoral one

ImmunityImmunityImmunityImmunity

PrognosisPrognosis

• Overall case-fatality rate <1 - 2.4%

• 50% cases self-limiting

• Only 2% develop severe disease

• Active chronic disease– Usually fatal if left untreated

– Fatality for endocarditis: 35-55%

– 50-60% need valve replacement

ـ سير طبيعي ـ سير طبيعي 22)مرور()مرور(

ميزان موارد بدون عالمت )ساب ميزان موارد بدون عالمت )ساب •كلينيكال(كلينيكال(

ميزان موارد حادميزان موارد حاد•ميزان موارد مزمن ميزان موارد مزمن •ميزان موارد بهبودي خودبخوديميزان موارد بهبودي خودبخودي•سير بعدي بيماري با درمان و بدون سير بعدي بيماري با درمان و بدون •

درماندرمانميزان مرتاليتي و مربيديتي ميزان مرتاليتي و مربيديتي •

• Reported from Reported from all continents all continents (at least (at least 51 countries)51 countries)

• The incidenceThe incidence is greater than that is greater than that reportedreported

• Is endemicIs endemic in areas where reservoir in areas where reservoir animals are present animals are present

Ref: control of communicable d.Ref: control of communicable d.

3 - Geographical distribution3 - Geographical distribution

44 - - Timeline trendTimeline trend

( ( PandemicsPandemics))پاندمي ها ؟پاندمي ها ؟• ( ( EpidemicsEpidemics)) اپيدمي ها ؟ اپيدمي ها ؟•( ( OutbreaksOutbreaks)) طغيان ها ؟ طغيان ها ؟ •( ( DurationDuration ) )تناوب زماني ؟تناوب زماني ؟•( ( SeasonalitySeasonality))الگوي فصلي ؟الگوي فصلي ؟•

Epidemics have occurred among:Epidemics have occurred among:• WorkersWorkers in stockyards, in stockyards,

• Meat packingMeat packing

• Rendering Rendering plantsplants

• LaboratoriesLaboratories

• MedicalMedical and and veterinaryveterinary centers that centers that use sheep in researchuse sheep in research

Ref: control of communicable d.Ref: control of communicable d.

Epidemics:Epidemics:Epidemics:Epidemics:

5 – impact of age, gender, occupation5 – impact of age, gender, occupationAnd social situationAnd social situation

، ، شيوعشيوع و و بروزبروز بر ميزان بر ميزان تاثير سنتاثير سن• و و بدون عالمتبدون عالمت و و با عالمتبا عالمتموارد موارد مزمنمزمن و احتمال و احتمال خفيفخفيف و و شديدشديد

و مير و ميرمرگمرگشدن و ميزان شدن و ميزان

بر عوامل مذكور بر عوامل مذكورتاثير جنستاثير جنس• ؟ ؟شغل و موقعيت اجتماعيشغل و موقعيت اجتماعي•

• An occupational disease An occupational disease affecting those with direct affecting those with direct contact with infected contact with infected animals, such as : animals, such as :

– Farmers, producersFarmers, producers

– Veterinarians and Veterinarians and technicianstechnicians

– Meat processors, abattoirMeat processors, abattoir

– Laboratory workersLaboratory workers

OccupationOccupation

66 – – predisposing factorspredisposing factors

عوامل فرهنگي و عقيدتيعوامل فرهنگي و عقيدتي•زمينه هائي نظير ضعف ايمني ، زمينه هائي نظير ضعف ايمني ، •

ابتالء به بيماريهاي سركوبگر ابتالء به بيماريهاي سركوبگر ايمني ، مصرف داروهاي مضعف ايمني ، مصرف داروهاي مضعف

سيستم ايمنيسيستم ايمنياسترس هاي مختلفاسترس هاي مختلف•فقر و بي خانمانيفقر و بي خانماني•

7 – Susceptibility and resistance7 – Susceptibility and resistance

–Susceptibility is general Susceptibility is general

–Immunity following recovery Immunity following recovery

Ref: control of communicable d.Ref: control of communicable d.

8 – Secondary attack rate8 – Secondary attack rate

•Humans are dead-end hostsHumans are dead-end hosts

ـ منابع و مخازن ، نحوه انتقال ـ منابع و مخازن ، نحوه انتقال 99

تب تب بيماري و دوره قابليت سرايتبيماري و دوره قابليت سرايتQQ

( ( SourceSource))تعريف منبع ؟تعريف منبع ؟•((ReservoirReservoir))تعريف مخزن ؟تعريف مخزن ؟•راه هاي انتقالراه هاي انتقال•

مستقيممستقيم–غير مستقيمغير مستقيم–

P. of P. of))دوره قابليت سرايت ؟دوره قابليت سرايت ؟–communicabilitycommunicability ) )

– Domestic animalsDomestic animals• Sheep, cattle, goatsSheep, cattle, goats• Dogs, catsDogs, cats

– BirdsBirds

– Ticks Ticks

– ReptilesReptiles

– WildlifeWildlife

The most common animal reservoirs for The most common animal reservoirs for this zoonosis are cattle, sheep, and goatsthis zoonosis are cattle, sheep, and goats

Reservoir :Reservoir :

– TicksTicks are natural reservoirs are natural reservoirs

– Transovarial & transstadial are common in Transovarial & transstadial are common in ticks ticks

– Infected animals are usually Infected animals are usually asymptomaticasymptomatic but but shedshed massive numbers of organisms in massive numbers of organisms in placental tissues at parturition placental tissues at parturition

– shed in urine, feces, milk, and especially in shed in urine, feces, milk, and especially in birth products of reservoirs birth products of reservoirs

Reservoir :Reservoir :

TransmissionTransmission• AerosolAerosol

– Parturient fluidsParturient fluids• 101099 bacteria per gram of placenta bacteria per gram of placenta

• Urine, feces, milkUrine, feces, milk

– Wind-borneWind-borne

• DirectDirect contact contact

• FomitesFomites

• IngestionIngestion

• ArthropodsArthropods (ticks) (ticks)

TransmissionTransmissionTransmissionTransmission• Person-to-personPerson-to-person (rare) (rare)

–Transplacental (congenital)Transplacental (congenital)

–Blood transfusionsBlood transfusions

–Bone marrow transplantsBone marrow transplants

–Intradermal inoculationIntradermal inoculation

–Possibly sexually transmittedPossibly sexually transmitted

TransmissionTransmissionTransmissionTransmission• Laboratory exposure Laboratory exposure

• Transport of infected sheep Transport of infected sheep through hospitals to research through hospitals to research laboratories laboratories

• Via blood transfusion.Via blood transfusion.3131

• Autopsy Autopsy

• One report of apparent human-to-One report of apparent human-to-human transmissionhuman transmission

Period of communicabilityPeriod of communicabilityPeriod of communicabilityPeriod of communicability

• Direct transmission occurs Direct transmission occurs rarelyrarely

• Contaminated clothing may be Contaminated clothing may be a sourcea source

ج ـ پيشگيري و كنترل تب ج ـ پيشگيري و كنترل تب QQ

• Primary Prevention:Primary Prevention: Prevention of disease in “well” Prevention of disease in “well”

individualsindividuals• Secondary Prevention:Secondary Prevention:

Identification and intervention Identification and intervention in early stages of diseasein early stages of disease

Tertiary Prevention:Tertiary Prevention: Prevention of further Prevention of further

deterioration, reduction in deterioration, reduction in complicationscomplications

ـ پيشگيري سطح اوzل ـ پيشگيري سطح اوzل 11

ـ ارتقــــاء آگاهي هــــاي 1بهداشتي مردم

ـ قطـع زنجـيره انتقـال2ــايل ــزن، وس ــع، مخ )منب

انتقال . . .ــا 3 ــ ــ ــي ب ــ ــ ـ پروفيالكس

ــال، ــ ــ ــازي )فع ــ ــ ايمنسانفعــــــــــــــــــــالي( و

كموپروفيالكسي

Prevention and ControlPrevention and Control

• Pasteurization

• Vaccination– Human and animal

– Not available in U.S.

• Eradication not practical– Too many reservoirs

– Constant exposure

– Stability of agent in environment

Prevention and ControlPrevention and ControlPrevention and ControlPrevention and Control

• EducationEducation– Sources of infectionSources of infection

• Good husbandryGood husbandry– Disposal of birth products (incinerate)Disposal of birth products (incinerate)

• Lamb indoors in separate facilities Lamb indoors in separate facilities

– DisinfectionDisinfection• 0.05% chlorine0.05% chlorine• 1:100 Lysol1:100 Lysol

• Isolate new animalsIsolate new animals

ـ پيشگيري سطح دوzم ـ پيشگيري سطح دوzم 22

ـ تشخيص زودرس1 ـ درمان به موقع2ــه 3 ــان ب ــه درم ــه ب ـ توج

عنــوان پيشــگيري ســطح اوzل و دوzم

DiagnosisDiagnosisDiagnosisDiagnosis

Serology (A fourfold rise in titer)Serology (A fourfold rise in titer)– IFA, CF, ELISA, microagglutinationIFA, CF, ELISA, microagglutination

• DNA detection methods DNA detection methods PCRPCR• No cross-reactions have been reported between antibodies No cross-reactions have been reported between antibodies

to other microorganisms and antibodies to to other microorganisms and antibodies to C. burnetiiC. burnetii

• Isolation of organismIsolation of organism– Risk to laboratory personnelRisk to laboratory personnel

– Rarely doneRarely done

•WBC usually normal, but WBC usually normal, but LFTs commonLFTs common

Low mortality, but Low mortality, but malaise may last monthsmalaise may last months

TreatmentTreatmentTreatmentTreatment–The treatment of choice for The treatment of choice for C. C.

burnetiiburnetii pneumonia is tetracycline pneumonia is tetracycline

–Chloramphenicol has been used to Chloramphenicol has been used to treat Q fevertreat Q fever

–The most effective agents are The most effective agents are quinolones (difloxacin, ciprofloxacin, quinolones (difloxacin, ciprofloxacin, oxolinic acid) and rifampin. oxolinic acid) and rifampin.

–Chronic disease – long courseChronic disease – long course• 2-3 years of medication2-3 years of medication

QQكنترل تب كنترل تب

ـ مـبارزه ـبا مـنابع و 1مخازن

ــيره 2 ــ ــع زنج ــ ـ قطانتقال

ـ حفظ افراد سالم3

QQكنترل تب كنترل تب

ـ مبارزه با مخازن1شناســــــــائي بيمــــــــاران و •

؟؟ ناقلينايزوله كردن بيماران ؟؟•تجويز آنتي توكسين ؟؟•تـجويز آـنتي بيوتـيك ـبه بيـماران • درمان حالت ناقلي ؟؟•

حيوانات بيمار و ناقل •منابع محيطي ؟؟•

QQكنترل تب كنترل تب

ـ قطع زنجيره انتقال2ــتقيم و • ــاي مسـ تماس هـ

غيرمستقيمآب، غذا و . . . •پوست، مخاط، هوا، . . .•

QQكنترل تب كنترل تب

ـ حفظ افراد سالم3مصونسازي اكتيو•مصونسازي پاسيو•كموپروفيالكسي•

Sources :Sources :

1 – Q fever, The center for food security and public health Iowa state University, Internet site.2 -control of communicable diseases . . . control of communicable diseases . . .