Placental Listeriosis: Case Report and Literature Review

ABSTRACT.

Listeria monocytogenes, a foodborne, facultative, intracellular gram-positive bacillus, is one of 17 species of the Listeria genus and was responsible for the world’s largest outbreak of listeriosis in 2017–2018 in South Africa. Listeria monocytogenes tends to cause mild gastrointestinal symptoms in healthy individuals. However, pregnancy-associated listeriosis can be fatal to the fetus and can lead to serious adverse effects in the neonate. Listeria monocytogenes has an affinity for the placenta, as opposed to other nonreproductive organs. Herein, we present a case of placental listeriosis diagnosed in a 33-year-old female, parity 4, with unknown gestational age during the listeriosis outbreak in South Africa in 2017–2018. The patient presented with pregnancy-related complications and underwent a caesarean section. Morphological features demonstrated acute suppurative villitis and intervillositis with a heavy load of gram-positive bacilli, which is highly suggestive of placental listeriosis. Multiplex polymerase chain reaction confirmed the presence of L. monocytogenes.

The Listeria genus, first described in 1926, comprises facultative, intracellular, gram-positive bacteria that are morphologically identified as single rods or chains (bacilli) and possess flagella.^1–3 Only two of the 17 Listeria species are known to cause disease in humans. Listeria monocytogenes is responsible mainly for a foodborne disease known as listeriosis. Listeria monocytogenes was responsible for the world’s largest outbreak of listeriosis, which occurred from January 2017 to July 2018 in South Africa.¹ During the outbreak, approximately 1,000 cases of listeriosis were confirmed, and 42% of these cases affected fetuses and neonates.^4–6

In healthy individuals, infection with L. monocytogenes is often limited to mild gastrointestinal symptoms.⁷ However, L. monocytogenes can cause severe disease and fatality in individuals at risk, including pregnant women, patients at the extremes of age, patients with underlying malignant conditions and chronic diseases, and immunocompromised individuals.^1,8,9

Pregnant women have an 18 times greater likelihood of becoming infected with L. monocytogenes than healthy individuals in the general population.^9,10

Although pregnancy-associated listeriosis is rare, there are high mortality and morbidity rates in fetuses and neonates of mothers with listeriosis, such that listeriosis is considered to be one of the worst-known maternal–neonatal infections.^4,9

It is postulated that L. monocytogenes has an affinity for infecting the placenta as opposed to nonreproductive tissues such as the liver and spleen. Pregnancy-associated listeriosis spreads transplacentally or as an ascending infection. Infection during pregnancy is notoriously associated with premature birth, miscarriage, or stillbirth, especially during the second and third trimesters. Furthermore, neonates can be affected by disseminated diseases such as granulomatosis infantiseptica of the newborn and meningitis.^1,11,12

In this report, we describe a case of placental listeriosis that was confirmed by histopathologic and molecular findings during the aforementioned listeriosis outbreak in South Africa. A 33-year-old female patient, parity 4, presented at a tertiary academic hospital in Johannesburg with a gestation of unspecified duration. Placenta previa and fetal distress were present. A caesarean section was performed for severe preeclampsia, and intrauterine growth retardation was evident. After the delivery, the placenta was submitted for histopathologic assessment. Macroscopic examination of the placenta confirmed a weight of 234 g and dimensions of 145 × 90 mm. Meconium staining was absent, and there was evidence of hypocoiling. Microscopic examination revealed acute suppurative villitis of patchy and high-grade extent (Figure 1). There was also acute suppurative intervillositis with micro-abscesses (Figure 2). Gram stain (Figure 3) highlighted the presence of numerous gram-positive bacilli within the areas of inflammation. Immunohistochemical tests were performed to assess for other possible infective etiological agents, including Cytomegalovirus and Treponema pallidum, which yielded negative results. Multiplex polymerase chain reaction (PCR) performed on placental tissue for L. monocytogenes subsequently confirmed the diagnosis of listeriosis. As part of the laboratory-specific multiplex PCR, tests for the following infective etiological agents had negative results: Group B Streptococcus, Escherichia coli, Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. During multiplex PCR, more than one pair of primers was used to target the genes of the organisms being investigated. The primers, together with extracted DNA from the organisms, master mix, magnesium chloride, Taq polymerase enzyme, deoxyribonucleotide triphosphate, and reaction buffer, undergo the three stages of PCR. These stages include initial denaturation of the DNA double helix to form single-stranded DNA molecules, followed by annealing of the primers to the target sequence on the single-stranded DNA at a lowered temperature, and lastly elongation/extension at a higher temperature. The results of the three stages of PCR are multiple DNA copies, which can be analyzed using techniques such as electrophoresis on agarose gel.¹³

Figure 1.

Microscopy of the placenta showing acute suppurative villitis (hematoxylin and eosin–stained section at ×400 magnification).

Figure 2.

Placental acute intervillositis and micro-abscess formation (hematoxylin and eosin, ×400 magnification).

Figure 3.

Numerous gram-positive bacilli are highlighted in the areas of inflammation (Gram-stained section of the placenta at ×400 magnification).

Listeria monocytogenes is more common in pregnant women and may be associated with severe effects on the fetus and neonate. The incubation period for L. monocytogenes in pregnant women is approximately 2–4 weeks. However, the onset of symptoms can occur between 3 and 70 days after exposure. Listeria monocytogenes infection most often occurs during the second or third trimester. If the fetus is infected during the first trimester, there is a higher chance for stillbirth as opposed to infection during the second or third trimester.^9,10

A pregnant patient who is infected with L. monocytogenes may be asymptomatic. Symptoms may vary from mild respiratory to mild gastrointestinal manifestations.^9,10 The most common symptom is fever, with a temperature ranging between 38°C and 39°C, usually without any identifiable source.^10,14 Other clinical manifestations include chorioamnionitis and rarely maternal sepsis and meningitis.^10,14 Routine laboratory investigations may prove to be nonspecific, much like the clinical presentation. Based on the fact that pregnant women may be asymptomatic or may present with nonspecific symptoms, the diagnosis of L. monocytogenes is challenging.¹⁰ A heightened index of clinical suspicion for pregnancy-associated listeriosis should be present if a pregnant woman presents with unexplained fever and a history of consuming potentially contaminated food.^6,10

Although L. monocytogenes infection rarely causes maternal death, it can lead to serious adverse effects on the fetus and neonate. Fetal infection may occur by means of vertical transmission or ascending infection. Listeria monocytogenes infection is dependent on its ability to invade cells, reproduce within the cell, and spread from cell to cell. Initially, L. monocytogenes binds to the host’s epithelial cells or macrophages via receptors and is phagocytosed. The bacteria use listeriolysin O and two phospholipases to escape the phagolysosome and are subsequently propelled to the neighboring uninfected cell. An effective host cell response can eradicate the pathogen with interferon gamma in acute infection or type 1 T helper and CD8⁺ T cells in chronic infection. In the case of transplacental infection, the bacteria will travel through the umbilical vein, allowing entry into the fetal circulation, which can then affect all fetal organs. Furthermore, the bacteria can be excreted by the fetal kidneys, leading to contamination of amniotic fluid, and may be ingested by the fetus. Should aspiration occur at this point, the gastrointestinal tract and respiratory system may be infected. Listeria monocytogenes can also reside in the placenta and lead to repeated infections.^{7,9,10,12,15,16}

After an infection has been established, the pregnant patient may experience premature birth, reduced fetal movement, abdominal pain, premature rupture of membranes, and vaginal bleeding. Only 5% of pregnancies associated with L. monocytogenes have favorable outcomes, whereas 20–30% of the remaining cases lead to severe consequences and fetal death.^10,14

Because pregnancy-associated listeriosis is rare, confirming an infection of L. monocytogenes usually requires blood culture or PCR.^3,8,14 Additional diagnostic modalities include placental tissue culture, a continuous rise in white blood cell count, serological testing of anti-listeriolysin O, testing of amniotic fluid for gram-positive bacilli, and vaginal smear.⁹

An invaluable diagnostic tool in suspected cases of listeriosis is the histopathologic evaluation of the placenta, which confirms the presence of distinctive findings. Unfortunately, only 50% of cases undergo histopathologic examination.^9,17,18 Macroscopic findings often include yellow-colored nodules that are irregularly spread over the placental surface, membranes, and/or umbilical cord. Macro-abscess formation occurs less frequently. Microscopic findings include intervillous and/or intravillous micro-abscesses containing necrotic foci with histiocytic palisading, necrotic villi, neutrophilic intervillositis, hemorrhage, and karyorrhexis with gram-positive bacilli. In larger and chronic lesions, granulomas may form. Ancillary histochemical tests such as the Gram stain will highlight gram-positive bacilli. Grocott and Warthin-Starry stains will also highlight the bacilli. Histopathologic evaluation can be complemented by a confirmatory PCR test.^6,9,17

When L. monocytogenes infection is confirmed, treatment may include intravenous ampicillin or oral amoxicillin. In cases of penicillin allergy, erythromycin, trimethoprim/sulfamethoxazole, vancomycin, and fluoroquinolones can be considered. A neonate born to a mother with listeriosis should continue with follow-up for 2–3 months after delivery.⁹

Pregnancy-associated listeriosis is a rare entity, and the declining prevalence rate may be attributed to stricter food production requirements, improved health education, improved health care, and access to health care during pregnancy.¹⁰