Listeriosis in pregnancy: a challenge in diagnosis

Abstract

Listeriosis is a rare foodborne infection caused by Listeria monocytogenes. It has been reported to be commonly found among the obstetric population, immunocompromised group and elderly, presumably due to the lower immunity status in these populations. Presentation in pregnancy is usually non-specific like fever, diarrhoea, respiratory tract symptoms and preterm rupture of membrane. These make the diagnosis challenging and may delay the correct management. We present a case of a female in her early 40s, gravida 4 para 0+3 at 27 weeks who presented with fever. She later developed preterm rupture of membrane 24 hours after admission. The leaking of liquor later changed from clear to meconium stained raising the suspicion of listeria chorioamnionitis, necessitating an emergency preterm delivery via caesarean section. The newborn acquired listeria infection and required ventilation support. He subsequently was discharged from neonatal unit after nearly 3 months of life.

Background

Listeria monocytogenes (LM) is a facultative, anaerobic gram positive rod causing listeriosis.¹ Listeriosis is divided into invasive and non-invasive types. The non-invasive listeriosis causes mild symptoms with a shorter incubation period. In contrast, the invasive type affects high-risk groups which include pregnant women, the elderly, neonates, immunocompromised populations such as those undergoing chemotherapy and organ transplant recipients.

Listeriosis is caused by ingestion of food contaminated with LM. LM can be found in water and soil. Vegetables or fruits became contaminated through the soil or fertiliser. Raw vegetables, fruits and food stored long enough in the fridge such as ready-to-eat meat, dairy products and prepared salad could be contaminated by LM. Hence, it is crucial to ensure these raw foods are cleaned thoroughly and cooked as necessary to kill the LM. Pregnant women are advised to avoid consuming raw food to reduce their risk of contracting listeriosis. The infection if acquired by a pregnant woman, can be transmitted to the fetus causing serious complications. In early pregnancy, it can result in miscarriage while in late pregnancy, it can cause stillbirth.

Due to the rarity of listeriosis, clinicians may not suspect this as it commonly presents with vague symptoms similar to other infections. Clinicians should have high suspicion when managing pregnant women with non-obvious causes of fever. Empirical treatment with suitable antibiotics (ampicillin or penicillin) should be considered while waiting for the culture result. LM is generally resistant to cephalosporin antibiotics.^{1 2} Other differential diagnosis that should be considered in febrile-like illness includes Staphylococcus and Group B streptococcus infection, which are also commonly sensitive to the penicillin group of antibiotics.

Case presentation

A female in her early 40s, gravida 4 para 0+3 was referred from a private hospital for preterm prelabour rupture of membrane at 27 weeks. This pregnancy was achieved through in vitro fertilisation. There is no significant medical or surgical history except for unexplained recurrent first trimester miscarriages. She gave a history of fever for one day where she initially presented to a private hospital and was treated for fever of unknown origin. She denies respiratory tract infection or urinary tract symptoms, no abdominal pain or leaking of liquor at the time of presentation. She was febrile with a temperature of 38.8°C, but not tachycardic nor hypotensive. She was initially managed by the physician and commenced on intravenous ceftriaxone 1 g daily and antipyretic for fever of unknown origin. Test for influenza, COVID-19 and dengue were negative. After 24 hours of admission, she complained leaking of liquor. At that time, her fever has subsided.

On assessment by the obstetrician, she was clinically alert, not pale and afebrile with pulse rate between 100 and 110 beats per minute (bpm), and blood pressure of 124/84 mm Hg. She gave a history of eating outside food including raw salads and 1-day history of diarrhoea one week before the admission. Her abdomen was soft and not tender. The uterus was not irritable with the presence of a singleton fetus in longitudinal lie and cephalic presentation. The estimated fetal weight was 1 kg and fetal heart rate was between 140 and 145 bpm. Her lungs were clear and renal punch was negative. Sterile speculum examination confirmed the presence of minimal non-foul-smelling clear liquor. Her cervix was long and tubular with closed cervical os. Vaginal swab was obtained for culture and sensitivity.

A diagnosis of preterm prelabour rupture of the membrane was made with the possibility of chorioamnionitis in mind. Due to her extreme premature gestation, intramuscular corticosteroid was given in anticipation of preterm delivery together with intravenous magnesium sulphate for cerebral neuroprotection. The neonatologist was alerted of the possibility of preterm delivery and the couple was counselled for the risk of a preterm baby. Considering the most common organisms causing chorioamnionitis in preterm gestation responded to the penicillin group of antibiotics, her antibiotic was changed to intravenous ampicillin and sulbactam (unasyn). This was also in accordance with the local hospital guideline which recommended intravenous ampicillin or unasyn for women presented with preterm prelabour rupture of membrane with unknown Group B streptococcus (GBS) status as in this case.

Investigations

Her blood investigation at presentation showed haemoglobin of 10.6 g/dL, normocytic normochromic, white cell count of 11×10^∧9/L and C reactive protein (CRP) of 88 mg/L. Her platelet count, renal and liver function test were normal. Urinalysis was negative for infection. Ultrasound abdomen showed normal liver and kidneys. Blood culture and urine culture results were pending on transfer to the care of an obstetrician.

Repeat full blood count after 24 hours showed white cell count increased to 15.7×10^∧9/L and CRP increased to 217 mg/L. Fetal ultrasound showed a viable singleton fetus with parameters at 27–28 weeks, estimated fetal weight of 1.2 kg, deep vertical pole of 4 cm and placenta located at anterior upper segment.

Differential diagnosis

Possible differential diagnosis at this moment was GBS infection given this is a common organism causing preterm rupture of membrane and fever. The vaginal swab culture and blood culture taken will be able to rule in or exclude this. Probable foodborne infections such Salmonella and LM were kept in mind given her history of gastrointestinal symptoms prior to the admission.

Treatment

Her antibiotic treatment was changed to intravenous ampicillin/sulbactam (unasyn 3 g stat followed by 1.5 g 6 hourly). She was hydrated with intravenous fluids and managed as sepsis. She was monitored closely in the high dependency unit for any changes in vital signs, presence of fever and colour of liquor observed on her pad. After 8 hours of admission, meconium-stained liquor was noted on her sanitary pad. Her temperature was 37.7°C, pulse rate was 105 bpm with normal blood pressure. At this moment, the possibility of listeria chorioamnionitis was suspected, and hence the decision for delivery via caesarean section was made.

During the surgery, the baby was delivered via cephalic and the liquor was noted to be meconium stained. Placenta swab culture and sensitivity as well as for histopathological examination were sent. The baby was intubated at delivery by the neonatologist on standby. The surgery was complicated with uterine atony in which she responded to intramuscular carboprost 250 µg and Hayman compressive suture. The estimated blood loss was 1 L. Postoperatively, she was monitored in the high dependency unit and continued on the intravenous ampicillin/sulbactam (unasyn) 1.5 g 6 hourly for another 48 hours.

Outcome and follow-up

She delivered a male baby weighing 1.1 kg with Apgar score of 5 at 1 min and intubated immediately. The baby was given intravenous ampicillin 50 mg every 8 hours and gentamicin 2.7 mg every 12 hours covering for listeriosis while waiting for the culture result. At delivery, the baby required fluid bolus for resuscitation and stable with ventilator support at medium setting. He required sodium bicarbonate in view of persistent metabolic acidosis during the first 24 hours of life. Fortunately, he did not require any inotropic support. Surfactant was given two times at 1 hour and 13 hours of life.

After 48 hours of admission, her high vaginal swab culture came back positive for LM, so as the baby’s blood culture, both were sensitive to ampicillin and gentamicin. She was discharged home 36 hours postdelivery with oral unasyn 750 mg two times a day for 1 week.

She was seen 2 weeks later at our postnatal clinic where she had recovered clinically. Her placenta histopathological examination confirmed chorioamnionitis with the presence of micro abscess and necrosis of the surrounding villi. There was dense subchorionic neutrophilic infiltration and the umbilical cord showed phlebitis and funisitis.

Her baby was intubated and monitored in neonatal intensive care unit. He required ventilation support and was unable to wean off oxygen due bronchopulmonary dysplasia. He did not have any signs to suggest nervous system involvement. His condition subsequently improved with antibiotics and ventilatory support. He was discharged with home oxygen therapy after 12 weeks of life. At that time, he was able to tolerate oral feeding and his weight was 3.2 kg.

Discussion

The incidence of listeriosis in pregnancy has been described as between 0.7 and 12 cases in 100 000 pregnancies.^{3 4} Evidence also suggests that ethnicity is a significant risk factor with Asian and Afro-Caribbean pregnant women found to have a higher incidence of listeriosis compared with Caucasians.² However, these data remain scarce due to the low number of reported cases. The incidence rate was reported to be high in China whereas it showed a decline in Europe and USA.⁵ This could be due to better preventive measures such as a strict requirement on food manufacture and better maternal care in such countries.⁵

Listeriosis is caused by the ingestion of raw foods, unpasteurised milk or processed food such as cheese and sausages.⁴ On consumption of food infested with LM, the intracellular bacteria reach the small intestinal mucosa and subsequently enter the blood stream and lymphatic circulation. The bacteria will then enter the cells and release toxins to dissolve the vacuole membrane to survive within the cells. It then penetrates the cytoplasm, proliferates and accesses the plasma membrane. Then, there will be protrusions of the plasma membrane followed by intercellular diffusion to infect their adjacent cells and other organs.

Diagnosing listeriosis in pregnant women is challenging due to the vague symptoms which may be similar to other illnesses. Definitive diagnosis involves laboratory testing which includes blood culture, vaginal swab culture, placental culture or cerebrospinal fluid analysis.^{6 7} Commonly, LM infection is least suspected until blood as well as swab cultures isolate the organism, which usually will take at least 36–48 hours from the initial presentation. Thus, this will result in delay of treatment and the fetal condition may have been compromised by the time the laboratory results become available.

Fever remains the most common manifestation of listeriosis making the diagnosis challenging. Other symptoms are respiratory symptoms, abdominal pain, nausea, diarrhoea, reduced fetal movement and premature rupture of the membrane. Although listeriosis infrequently results in maternal morbidity or mortality, the infection can be transmitted to the fetus through the placenta and bloodstream. The risk of miscarriage, preterm delivery, stillbirth and other serious health problems to the newborn including pneumonia, sepsis and meningitis is high.

In the case described above, the patient was initially treated with the standard treatment of preterm prelabour rupture of membrane with probable subclinical chorioamnionitis. Meconium-stained liquor, which manifests later is an indicator of listeria chorioamnionitis and is seen in up to 70% of listeriosis.² It is a distressing sign of fetal compromise and often associated with poor neonatal outcome. The woman may have tachycardia with leucocytosis and raised CRP as demonstrated in our case. Thus, closed monitoring is extremely important to ensure timely decisions for intervention and delivery. Recognising changes in maternal pulse rate, increase in temperature, abdominal pain and change in liquor colour are critical signs to look for to point towards the correct diagnosis.

Evidence suggests that early antibiotic treatment to the mother can prevent transplacental infection to the fetus. However, due to the difficulty in recognising listeria infection in pregnancy, most fetus may have been infected in-utero by the time of suspected diagnosis or delivery. The reported incidence of neonatal listeriosis was nearly 8 in 100 000 live births with a mortality rate up to 20%–30%.⁸ Early administration of penicillin or aminopenicillin to the neonate may improve the neonatal outcome. Use of cephalosporin or fosfomycin is not recommended as LM are resistant to these antibiotics due to the reduced affinity of the enzyme in the development of the last step of the cell wall synthesis.²

Conclusion

Diagnosis of listeriosis in pregnancy remains a challenge. The presentation may be vague and can be mistaken with other infections. As most listeria infections is sensitive to the penicillin group of antibiotics, early administration of penicillin may improve both the maternal and neonatal outcome.

Patient’s perspective.

It was so heartbreaking to know the diagnosis. I blamed myself for not being careful and looking after the food that I ate. It took me lots of effort to conceive as it was an in vitro fertilisation pregnancy. I wish I could turn the time around and that this event never happened. Nevertheless, I am grateful to all the staff who looked after me and observed me thoroughly that they managed to detect and deliver my baby as soon as the change in liquor colour was identified. I would be very depressed if anything happened to my baby, luckily, he managed to go through the obstacle and survived.

Learning points.

• Listeriosis in pregnancy is rare, however, it may lead to serious complications to both mother and fetus if undetected and untreated.

• History taking should include food consumption (raw food, unpasteurised milk, cheese, ready-to-eat daily product) to help point towards the possible diagnosis.

• High index of suspicion of listeriosis infection in pregnant women presenting with unknown source of fever and treatment should be initiated immediately.

• Early delivery despite the gestation being far from term may reduce the infection related complications of the newborn.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).