Q Fever in Pregnancy—Case Presentation and Literature Review

doi:10.4236/ijcm.2013.48065

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International Journal of Clinical Medicine, 2013, 4, 364-368

http://dx.doi.org/10.4236/ijcm.2013.48065 Published Online August 2013 (http://www.scirp.org/journal/ijcm)

Q Fever in Pregnancy—Case Presentation and Literature

Review

Kugler Eitan1*, Amital Howard2, Alon Danny3

1Rabin Medical Center, Beilinson Hospital, Department of Medicine F, Petah Tikva, Israel; 2Sheba Medical Center, Department of

Medicine B, Tel Hashomer, Israel; 3Rabin Medical Center, Beilinson Hospital, Department of Medicine B, Petah Tikva, Israel.

Email: *[email protected]

Received August 2nd, 2012; revised August 10th, 2012; accepted September 3rd, 2012

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Q fever is a widespread zoonotic infection caused by Coxiella burnetii. During acute infection, three clinical patterns

are commonly encountered—self limited, flu like disease, atypical pneumonia or hepatits. Chronic infection almost al-

ways implies endocarditis. Acute infection during pr egnancy may result in obstetrical complications, and predispose to

chronic transformation. Treatment during pregnancy is more complex, and the duration of treatment was debatable up

until recently. We describe a 31 years old patient with acute Q fever infection during pregnancy. We review the medical

treatment, complications and follow up of acute and chronic Q fever during pregnancy.

Keywords: Q Fever; Coxiella burnetii; Pregnancy

1. Introduction

A 31 years old female with no sign ifican t medical h istor y,

presented to our department at 15 weeks of gestation,

with a 10 days history of headaches, general muscle

weakness, malaise with fever reaching 39 degrees.

As a tourist guide she reported frequent visits of caves

and drinking unpasteurized milk, the last occurrence was

two weeks prior to this hospitalizatio n. It should be noted

that her husband who shared the same occupation suf-

fered from the similar symptoms.

On admission, her clinical and gynecological exami-

nation was unrevealing apart from a 2/6 systolic murmur

over the aortic valve. Her laboratory results demonstrated

normal white blood cell count with mild atypical lym-

phocytes and band forms appearing in her peripheral

blood smear. The platelet count was normal. In addition,

hepatocelluler liver enzymes were elevated up to 7 - 10

times the normal levels.

Due to the patients’ medical history, a high suspicion

of a zoonotic infection was taken. Sero logical testin g was

consistent with acute Q fever infection. Transthoracic

echocardiography (TTE) revealed normal valvular mor-

phology and function. Treatment with Cotrimoxazole

was initiated.

During treatment, a wid espread skin eruption app eared,

and treatment with azythromycin was initiated in place of

cotrimoxazole.

Despite appropriate antibiotic treat ment, serologic pro-

file was consistent with ch ronic Q fever infection—phase

1 IgG titer was over 25,000 at week 37 of gestation. La-

bor was induced in order to start standard combination

antibiotic treatment. A healthy baby girl was born, and

Treatment with doxyciline and plaquenil was initiated

immediately.

Figures 1-3 present the pathological findings of the

patient s’ p lacenta.



Figure 1. Gross view of placenta. Multiple foci of firm white

tissue, flat or wedge shape (infract-like), involving maternal

floor of placenta (yellow arrows).

*Corresponding a uthor.

Q Fever in Pregnancy—Case Presentation and Li t erature Rev i ew 365

Figure 2. Histologic section of a wedge shaped focus: necrosis with abundant nuclear debris, surrounded with uninvolved

placental villi (H&E, ×100).

Figure 3. Details of involved maternal floor: (I) Necrosis intermixed with numerous disintegrating inflammatory cells in de-

cidua (×100); (II) Polymorphonuclear leukocites in decidua (×100); (III) Plasma cells in decidua (×100); (IV) Necrotizing vil-

litis and perivillitis (H&E, ×50).

2. Discussion

Q fever is a widespread zoonotic infection caused by

Coxiella burnetii (C. burnetii). While previously classi-

fied as a Rickettsia, C. burnetii has been placed into a

subdivision of the Proteobacteria.

C. burnetii is a strict intracellular bacterium which can

survive efficiently for a long period of time in highly

acidic conditions such as the phagolysosomes of macro-

phages, or in the external environment. Sources of hu-

man infection are mainly cattle, sheep and goats. Infec-

tion follows inhalatio n of aerosolized organisms from in-

fected parturient fluids. Occupational exposure is the

most common form of acquisition. Consumption of raw

milk is another source of infection.

C. burnetii was first described by Derrick in 1937 as a

cause of both acute and chronic manifestations [1].

The majority of acute Q fever cases remain asympto-

matic. Only 2% of patients with acute Q fever are hospi-

talized [2].

During acute infection, three clinical patterns are com-

monly encountered—a self-limitedshort “flu like” illness

associated with headaches, atypical pneumonia and/or

hepatits.

Pulmonary involvement is usually atypical in nature

Q Fever in Pregnancy—Case Presentation and Li t erature Rev i ew

366

and most cases are mild, presenting with a non-produc-

tive cough, fever, and minimal auscultatory abnormali-

ties. However, some patients present with acute respira-

tory distress. Pleural effusion can occur. Radiographic

findings are usually non-specific, and resemble viral pneu-

monia. Symptoms can last from 10 to 90 days [2,3].

During acute Q fever hepatitis, serum transaminases

are usually mildly elevated. Abdominal pain and jaun-

dice are uncommon. Extensive destruction of the liver

and hepatic failure was described [2]. Liver histology ty-

pically reveals a granulomatous hepatitis, even in asymp-

tomatic patients. The hepatic lesion is very specific, in

which some of the granulomas appear to be “doughnut-

like” because they contain a lipidic vacuole surrounded

by a fibrinoid ring. Moreover, patients with hepatits may

exhibit autoantibodies directed to smooth muscle, anti-

cardiolipin, anticoagulant and antinuclear antibodies [2].

The clinical presentation may vary, depending on the

geographic location. Pneumonia is the major clinical pre-

sentation in Nova Scotia, Canada, in the Basque region in

Spain and in Switzerland. Hepatits is more common in

Ontario, Canada, in Andalusia, Spain, and in California,

USA [2]. Animal models suggested that the route of in-

oculation, aerosol or ingestion of contaminated food

(mostly raw milk) might be a proposed pathophysiologic

mechanism for this phenomenon. Different strain of the

pathogen may also be an explanation [2]. Raoult et al.,

described the clinical and epidemiologic feature of 1383

Q fever infections during 1985-1998, and has suggested

that in any given geographic area, mostly host factors

contribute to the clinical presentation during acute infec-

tion and not the route of inoculation. Patients with heap-

titis were younger, less frequently immunocompromised,

had more febrile episodes, more headache and myalgia,

more thrombocytopenia and more elevated erythrocyte

sedimentation rates. Patients who presented mainly with

pulmonary involvement had the opposite epidemiologic

and clinical characteristic. They were older, more immu-

nocompromised, had less febrile episodes, suffered less

headaches and myalgia, had more electrocardiogrphic ab-

normalities, and were less likely to develop thrombocy-

topenia. In additio n, patients without pu lmonary involve-

ment or hepatitis were more frequently female [2].

Although acute Q fever infection is usually a mild and

self limited disease, severe and rare complication can oc-

cur in approximately 1% of cases, and include myocardi-

tis, pericarditis and meningoencephalitis. The pathogene-

sis is unknown, and patients from all age groups with no

remarkable medical history may be involved. Myocardi-

tis is probably underestimated, and is considered to be

the most serious complication of acute Q fever infection

[2].

Chronic infection is defined as infection lasting more

than six months and it almost always implies endocardi-

tis, though ostemyelitis and infection of vascular graft

and aneurysms may occur. Occasionally, chronic hepatits

in association with endocarditis or as an isolated condi-

tion may develop. Seldom, chronic infection can develop

insidiously, months or years after the acute disease. Host

factors play a role in the clinical expression of the dis-

ease and existence of an immunocompromised state, pre-

existing valvular heart disease or pregnancy predispose

to chronic infection [2].

Treatment of acute Q fever is warranted only for

symptomatic patients. Doxycycline 100 mg twice daily

for 2 weeks is the recommended regimen. Fluoroquinol-

ones are useful as well, but are contraindicated in chil-

dren and pregnant women. Prolonged treatment for a mi-

nimum of 18 months with doxycycline in combination

with hydroxychloroquine is necessary in chronic infec-

tion.

All patients with acute Q fever should undergo trans-

thoracic echocardiography to exclude the possibility of

valvular heart disease, which mandates a longer treat-

ment in order to prevent the progression to Q fever en-

docarditis. Therapy with doxycycline and hydroxychlo-

roquine for a minimum of 12 months is warranted in this

case [4].

Acute or chronic infection during pregnancy may re-

sult in obstetrical complication such as spontaneous abor-

tion, intrauterine growth retardation, intrauterine fetal

death, oligoamnios, and premature delivery. It appears

that the risk is higher during the first trimester and that

the majority of infected patients were asymptomatic [5,6].

Obstetrical adverse outcomes are frequent, occurring in

up to 81% of infected patient s [7].

Treating Q fever during pregnancy is more complex

since doxycycline, fluoroqu inollones and hydroxychloro-

quine are contraindicated. Cotrimoxazole (trimethoprim

320 mg/sulphamethoxazole 1600 mg daily) has been

found to be safe and effective. Up until recently, the du-

ration of treatment was debatable. In 2007, a retrospec-

tive study of 53 pregnant patients with Q fever concluded

that a long-term duration of cotrimoxazole protects ag ainst

maternal transformation into chronic Q fever infection,

placental infection, and obstetric complications regard-

less of gestational age. Therefore it is recommended from

diagnosis until term [7].

In non-pregnant patients, the chance developing chro-

nic Q fever if a valvular abnormality exists is approxi-

mately 40% [4]. The chance to progress to chronic Q

fever in pregnancy may reach 50% even if no valvular

abnormality is present [7]. This may be due to high de-

gree of bacterial colonization and replication in the ma-

ternal uterus and placenta, and to lack of appropriate im-

mune response during pregnancy [5]. As mentioned ear-

lier, those infected during the first trimester are at greater

risk [7].

Q Fever in Pregnancy—Case Presentation and Li t erature Rev i ew 367

In addition, it should be noted that cotrimoxazole ex-

erts a bacteriostatic effect on C. burnetii. As a result, it is

recommended that all Q fever pregnant patients should

be monitored serologically for a minimum of 24 months.

Those with persisting Phase 1 IgG titers > 800 on indi-

rect fluorescent antibody assay should undergo transoe-

sophageal echocardiography to detect early endocarditis.

Treatment with doxycycline and hydroxychloroquine for

a minimum of 18 months is indicated if endocarditis is

confirmed [5].

Following delivery, a few precautions should be taken

into account. C. burnetii may colonize breast milk, thus

nursing should be avoided [8,9]. Furthermore, intrauter-

ine transmission of C. burnetii has been documented in

the past and in addition, an infected mother can poten-

tially transmit the pathogen during deliv ery through aero-

solized amniotic fluid thus it may be prudent to follow

infants closely [10-12].

During treatment in this case, a wide spread skin erup-

tion appeared, and treatment with azythromycin was ini-

tiated in place of cotrimoxazole.

Macrolides may represent a potential alternative for

treatment of Q fever infection in children and pregnant

women.

Erythromycin is now rar ely used due to a small risk of

sudden cardiac death due to QT interval prolongation in

susceptible patients (acquired long QT syndrome or pa-

tient receiving other drugs concurrently which are meta-

bolized by CYP3A4) [13].

Newer macrolides are more potent in vitro than eryth-

romycin[14] and Preliminary clinical studies showed that

they might be of clinical use [15].

In addition, skin rash may appear in Q fever infection

in up to 10% - 21% of cases. The eruption is not specific

and may consist of maculopapular or purpuric rash of the

trunk [2]. In the case presented here, it seemed likely to

be due to drug allergy owing to a resolution upon drug

replacement.

3. Conclusions

We presented a case of Q fever infection in a 31 years

old patient during her second trimester of pregnancy.

TTE was normal and treatment with cotrimoxazole was

initiated. Later on it was switched to azythromycin du e to

skin eruption most probab ly related to drug allergy. Nev-

ertheless, progression to chronic in fection was eviden t by

serology. Eventually labor was induced at week 37 due

to rising titres, and treatment with doxyciline and plaque-

nil was initiated after delivery with decreasing antibody

titres on follow up.

Q fever infection during pregnancy is a serious condi-

tion due to high rate of obstetrical complications and

transformation to a chronic state of infection. Cotrimoxa-

zole for the entire length of pregnancy, regardless of ge-

stational age, shou ld be administrated, while close follow

up for serologic conversion should be mandatory for at

least 24 months after delivery. In case of transformation

to a chronic state, treatment with doxyciline and plaqe-

unil should be initiated i mmediately after delivery for 18

months. A strict gynecological observation must be made

to rule out obstetrical complications. During labor, pre-

cautions must be carried out to prevent healthcare work-

ers infection. Nursing should be avoided and serologic

monitoring of the infant is required due to concern about

aerosol or transplacental transmission.

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