Bacterial and Protozoan Infections during Pregnancy

The Impact of Infections During Pregnancy

Infections during pregnancy pose significant risks to maternal, fetal, and neonatal health. These infections can lead to serious complications, affecting morbidity and mortality rates across the spectrum of pregnancy. To effectively mitigate these risks, it is vital to understand the various transmission routes and implement robust prevention strategies.

Routes of Transmission

Infections during pregnancy can follow different transmission pathways:

1. Prenatal Transmission: Also known as vertical transmission, this occurs when pathogens are passed from the mother to the fetus via the placenta. This route can result in congenital infections, affecting the developing fetus directly.
2. Perinatal Transmission: This transmission occurs during labor or delivery, primarily through exposure to blood or vaginal secretions. It is crucial to manage this risk to protect the newborn during the birthing process.
3. Postnatal Transmission: After birth, infections can spread through breastfeeding. This route poses a risk to the newborn if the mother is infected with certain pathogens.

Factors Influencing Transmission and Impact

Several factors determine how infections during pregnancy affect the fetus or newborn:

• Infectious Agent: The specific pathogen involved plays a crucial role in the severity of the infection. Bacteria, viruses, and protozoa each have unique impacts.
• Gestational Age: The timing of infection during pregnancy greatly influences its severity. Early infections might cause different outcomes compared to those acquired later in gestation.
• Type of Infection: Primary infections are generally more severe than reactivations or re-infections. Understanding this helps in predicting potential complications.
• Maternal Immune Status: The health and function of the mother’s immune system can affect how both she and the fetus respond to the infection.

Many maternal infections can be asymptomatic or present with mild symptoms, making early diagnosis challenging. Thus, timely intervention is crucial for better outcomes.

Infections during pregnancy: Prevention Strategies

Effective prevention strategies can significantly reduce the incidence of infections during pregnancy:

• Education Programs: Educating prospective and expectant mothers about preventive measures during pre-conception counseling or early obstetric visits is vital. Knowledge about risk factors and prevention techniques can greatly reduce infection rates.
• Systematic Screening Programs: Routine screenings for seroprevalence and seroconversions help in early detection and management of infections.
• Immunization: Vaccinations are a powerful tool in preventing certain infections, protecting both mother and fetus from potential threats.

Scope of Discussion

This chapter explores common bacterial and protozoan infections transmitted from mother to baby during pregnancy, childbirth, or breastfeeding. It focuses on preventive measures, diagnostic techniques, and treatments. Viral infections will be addressed in separate sections for clarity and comprehensive understanding.

Understanding Toxoplasmosis

Cause and Nature

Toxoplasmosis is caused by the protozoan parasite Toxoplasma gondii. This zoonotic disease affects all warm-blooded animals, including humans, and is found worldwide.

Congenital Toxoplasmosis

The incidence of congenital toxoplasmosis varies between 1 in 1000 to 1 in 10,000 births. The risk of transmission from mother to fetus depends on the timing of infection:

• First Trimester: The risk ranges from 5% to 15%.
• Second Trimester: The risk increases to 20% to 40%.
• Third Trimester: The risk peaks at 50% to 60%.

The maturity of the placenta affects the likelihood of transmission, with more mature placentas facilitating the parasite’s passage.

Modes of Transmission

The primary modes of transmission for toxoplasmosis include:

• Ingestion of Raw Meat: Consuming undercooked meat containing tissue cysts.
• Contaminated Food: Eating fruits or vegetables contaminated with Toxoplasma oocysts from infected cat feces.

Clinical Presentation

In adults, including pregnant women, toxoplasmosis is often asymptomatic in about 80% of cases. When symptoms are present, they are nonspecific and may resemble a common viral syndrome, often mistaken for mononucleosis. Common signs include:

• Enlarged Cervical Lymph Node: Particularly notable in women when mononucleosis tests are negative.

Genetic Diversity

Tozoplasma gondii exhibits considerable genetic diversity, affecting its virulence and the disease’s clinical and epidemiological profiles. This variability means that the public health impact of congenital toxoplasmosis can vary by region, requiring localized evaluations.

Placental Transmission and Early Treatment

Transmission Through the Placenta

During parasitemia, Toxoplasma gondii can cross the placenta, potentially infecting the fetus. Early treatment is essential to minimize severe outcomes.

Gestational Age and Risk

The impact of congenital toxoplasmosis varies with gestational age:

• Early Infection (First and Second Trimesters): The likelihood of fetal infection is lower, but if it occurs, it can lead to severe outcomes such as spontaneous abortion or fetal death.
• Late Infection (Third Trimester): The probability of fetal infection is higher, up to 60%, but the severity of outcomes is generally less severe compared to earlier infections.

Polymorphic Manifestations

Congenital toxoplasmosis can present in various ways:

• Fetal Death: A severe outcome.
• Neurological and Ocular Damage: Significant conditions that may arise.
• Asymptomatic Cases: Some newborns may show no clinical signs, complicating diagnosis if maternal infection is undiagnosed.

Prevention

Prevention primarily involves educating pregnant women about the risks and preventive measures to reduce the likelihood of contracting toxoplasmosis.

Diagnostic Methods

Direct Tests

• PCR Testing: Detects Toxoplasma gondii DNA in amniotic fluid, offering a definitive diagnosis.

Indirect Tests

• Serological Tests: Including toxotests, these help diagnose infections during pregnancy.

Serological Interpretation

• Anti-Toxoplasma IgM: Indicates acute infection, peaking between 4 to 8 weeks post-exposure and becoming undetectable after 3–4 months.
• Anti-Toxoplasma IgG: Reflects past infection and remains long-term in circulation.

Avidity Testing

• Low Avidity IgG: Suggests recent infection.
• High Avidity IgG: Indicates past or latent infection.

Prenatal Diagnosis

• Amniocentesis: Performed after 18 weeks of gestation or 4 weeks post-infection to test for toxoplasmosis DNA. The PCR test is highly sensitive and specific.

Prenatal Follow-Up

• Ultrasound: Recommended monthly to monitor for abnormalities, with increased frequency if amniocentesis is positive. Fetal brain MRI is used only if necessary.

Management After Positive Amniocentesis

A positive result necessitates appropriate care and management rather than considering medical termination of pregnancy.

Treatment of Ongoing Infection with Toxoplasmosis During Pregnancy

When acute toxoplasmosis is diagnosed during pregnancy, the primary objective of treatment is to prevent the parasite Toxoplasma gondii from crossing the placenta and infecting the fetus. Treatment strategies vary based on the stage of infection and whether the fetus is already infected.

Antibiotic Treatment Options

1. Spiramycin: This antibiotic is commonly used in many European countries due to its safety profile during pregnancy. Spiramycin helps reduce the risk of transmission from mother to fetus. It is typically administered until 21 weeks of gestation or even longer if no signs of congenital infection are present. The standard dosage is 3 grams per day or 1.5 grams twice a day. Despite its efficacy in reducing transmission risk by up to 60%, spiramycin does not address existing fetal infections.
2. Pyrimethamine and Sulfadiazine: When fetal infection is confirmed after 18 weeks of gestation or if congenital toxoplasmosis is diagnosed postnatally, this combination therapy is more effective. The regimen includes:
   • Pyrimethamine: 50 mg per day
   • Sulfadiazine: 1 gram orally three times a day
   • Folinic acid (10-20 mg/day) to counteract the folic acid deficiency caused by pyrimethamine. Note that pyrimethamine is generally avoided during the first trimester due to potential teratogenic effects.

Effectiveness of Treatments

Spiramycin has been shown to reduce the risk of transmission to the fetus by about 60%. However, it is ineffective once the fetus is already infected. Conversely, pyrimethamine and sulfadiazine therapy can resolve active congenital toxoplasmosis symptoms, typically within the first week of treatment.

Monitoring Newborns

Newborns diagnosed with congenital toxoplasmosis should undergo continuous monitoring throughout their early years. This follow-up is essential to detect and manage any late-emerging complications that may arise from the infection.

Prevention Strategies

Preventing toxoplasmosis primarily involves behavioral modifications to avoid initial maternal infection:

• Avoid Handling Raw Meat: Prevent contact with undercooked or raw meat to reduce infection risk.
• Prevent Contact with Contaminated Soil: Avoid exposure to soil or surfaces that may be contaminated with infected cat feces.
• Practice Good Hygiene: Regular handwashing after gardening or handling raw meat further decreases infection risk.

Education plays a crucial role, especially during pre-conception counseling or early pregnancy. Since many pregnancies are unplanned, early education on prevention methods is vital for reducing infection rates.

Global Efforts and Progress in Malaria Management

Reduction in Malaria Burden

Over the past decade, global initiatives have significantly reduced malaria-related morbidity and mortality. In some regions, malaria has been eliminated as an endemic disease. Despite these advancements, malaria remains a major public health challenge, particularly in sub-Saharan Africa.

Endemic Regions

Malaria continues to be endemic in various parts of the world, with sub-Saharan Africa and India bearing a substantial portion of the global burden. In 2018, these regions accounted for 85% of global malaria cases and 94% of malaria-related deaths. This highlights the ongoing challenge malaria presents in these areas.

Impact on Pregnant Women

Malaria, especially that caused by Plasmodium falciparum, poses severe risks to both maternal and fetal health:

• Maternal Mortality: Malaria is a leading cause of death among pregnant women in endemic areas, accounting for approximately 10% of maternal deaths.
• Adverse Pregnancy Outcomes: These include maternal anemia, miscarriage, stillbirth, low birth weight, and preterm birth.

Placental Malaria

Placental malaria occurs when parasite-infected red blood cells accumulate in the placenta. This condition contributes to adverse pregnancy outcomes through increased pro-inflammatory cytokines, oxidative stress, and apoptosis, which impair the placenta’s ability to exchange nutrients with the fetus. Key effects include:

• Fetal Growth Restriction: Limited nutrient exchange results in poor fetal growth and low birth weight.
• Altered Vascular Structure: Early pregnancy placental malaria disrupts vascular development, impacting birth weight and gestational length.

Associated Risks

Placental malaria is linked to several complications:

• Pre-eclampsia: Increased risk, especially in first-time mothers, due to histopathological changes in the placenta.
• Preterm Birth: Infections occurring in mid-pregnancy are associated with preterm birth, likely due to disruptions in angiogenic, metabolic, and inflammatory pathways.

Risk Factors

Several factors heighten the risk of malaria in pregnancy:

• Parity: First and second pregnancies (primigravidas and secundigravidas) face higher risks compared to women with multiple pregnancies (multigravidas).
• Maternal HIV Infection: HIV exacerbates susceptibility to placental malaria by impairing antibody development, cytokine regulation, and interferon-gamma responses. Antiretroviral treatments, particularly protease inhibitors, may reduce malaria incidence, though further research is needed.
• Socioeconomic Status: Poor housing conditions, lack of access to insecticide-treated bed nets, and limited availability of antimalarial drugs contribute to increased risk.
• Antenatal Stress and Mental Health: Stress and mental health issues also play a role in heightened vulnerability to malaria.

Congenital Malaria

Although rare, congenital malaria has been associated with placental malaria. Studies suggest increased odds of congenital malaria in neonates born to mothers with placental malaria, though evidence on vertical transmission remains inconclusive.

Diagnostic Challenges and Advances

Difficulty in Diagnosis

• Peripheral Blood Smears: Often ineffective for diagnosing placental malaria due to sequestration of infected red blood cells in the placenta.
• PCR (Polymerase Chain Reaction): More reliable for diagnosing placental malaria but often inaccessible in low-resource settings.
• LAMP (Loop-mediated Isothermal Amplification): Offers a quick and practical alternative for diagnosing placental malaria outside reference laboratories, providing accuracy comparable to nested PCR.

Gold Standard

• Placental Histology: Considered the gold standard but applicable only post-delivery, making it impractical for managing ongoing pregnancies.
• Rogerson Criteria: Categorizes placentas into four groups based on infection status for histological examination. While it offers insight into infection stage and extent, it does not resolve the challenge of diagnosing placental malaria during pregnancy.

Prevention and Treatment of Malaria in Pregnancy

Current Strategies

• Artemisinin-based Combination Therapies (ACTs): Effective and safe even in the first trimester, though the World Health Organization (WHO) does not recommend their use during this period.
• Intermittent Preventive Treatment (IPT) with Sulfadoxine-Pyrimethamine: Not advised during the first trimester due to potential risks. IPT faces challenges such as inadequate dosing, poor antenatal attendance, rising drug resistance, and decreased maternal immunity.

Need for Alternative Strategies

Current prevention and treatment methods do not fully eliminate the risk of adverse outcomes related to malaria in pregnancy. Therefore, exploring alternative strategies is essential to enhance both prevention and treatment efforts.

Global Efforts

• Epidemiological Data Analysis: Accurate data analysis helps tailor public health interventions to address malaria effectively in endemic regions, aiming to mitigate its impact on pregnancy and improve health outcomes for mothers and infants.

Bacterial and Protozoan Infections in Pregnancy

Tuberculosis (TB)

Epidemiology and Pathogenesis

• Global Impact: Annually, 3.2 million women are diagnosed with TB. In low- and middle-income countries (LMICs), TB, HIV/AIDS, and maternal conditions collectively contribute to nearly 50% of deaths among women of reproductive age.
• Pregnant Women Affected: In 2011, about 216,500 pregnant women had TB. Data on drug-resistant TB (DR-TB) prevalence among pregnant women is limited.

Maternal Presentation and Obstetric Outcome

• Risks: TB during pregnancy can lead to increased morbidity for both mother and fetus, potentially causing adverse birth outcomes such as preterm birth, low birth weight, and fetal growth restriction.
• Diagnosis: TB symptoms can mimic pregnancy-related symptoms, complicating diagnosis. A comprehensive evaluation includes assessing TB risk, medical history, physical examination, symptom screening, and TB testing. Active TB must be confirmed or excluded using chest radiography and other diagnostics before delivery.

Prevention and Management

• Active TB Disease: Requires treatment. Most pregnant women do not need treatment for latent TB infection during pregnancy but require close monitoring.
• Treatment Guidelines:
  • First-line Drugs: Isoniazid, rifampicin, pyrazinamide, and ethambutol are safe throughout pregnancy.
  • Second-line Drugs: Limited safety evidence. Aminoglycosides (e.g., kanamycin, amikacin) are avoided early in pregnancy due to risks of ototoxicity and fetal malformation. Ethionamide and prothionamide may cause increased nausea and vomiting, thus used after delivery if necessary.
• Coordination of Care: A multidisciplinary team, including specialists in infectious disease, gynecology, and neonatology, should manage treatment.

Conclusion: High-quality evidence and detailed guidelines are needed to enhance TB management in pregnant women and inform TB control programs.

Syphilis

Epidemiology and Pathogenesis

• Re-emergence: Syphilis has re-emerged as a modern epidemic in some regions.
• Transmission: Caused by Treponema pallidum, transmitted sexually or, less commonly, through skin contact or transplacental passage, leading to congenital syphilis.
• Disease Stages:
  • Primary Stage: Chancre (sore) at the infection site.
  • Secondary Stage: Skin rashes and mucous membrane lesions.
  • Tertiary Stage: Affects internal organs if untreated.

Prevention and Treatment

• Early Detection: Syphilis is treatable with antibiotics, especially if detected early. Early diagnosis and treatment are crucial to prevent complications and transmission to the fetus.

Diagnosis of Syphilis

• Diagnostic Tests:
  • Screening Tests:
    • Reaginic (Non-Treponemal) Tests: Examples include VDRL and RPR. They are sensitive but not highly specific, potentially yielding false positives.
  • Confirmation Tests:
    • Treponemal Tests: Example includes TPHA. Detects antitreponemal antibodies and is highly specific for syphilis.
    • Darkfield Microscopy: Sensitive and specific for early primary syphilis but not always available.
    • Growth of T. pallidum: Cannot be grown in vitro; initial testing involves reaginic tests confirmed by treponemal tests.

Congenital Syphilis

• Risk of Transmission: Approximately 60–80% risk of transplacental infection, higher in the latter half of pregnancy. Untreated primary or secondary syphilis in the mother typically leads to transmission; latent or tertiary syphilis transmits in about 20% of cases.
• Fetal Outcomes: Untreated syphilis increases the risk of fetal and neonatal death.
• Early Congenital Syphilis: Manifests within the first 3 months of life with symptoms like vesiculo-bullous rash, copper-colored macular rash on palms and soles, papular lesions, and systemic involvement.
• Late Congenital Syphilis: Appears after 2 years, with symptoms including gummy ulcers, saber tibias, and dental abnormalities. Diagnosis is based on history, physical signs, and positive serological tests.

Screening, Prevention, and Treatment

• Screening: All pregnant women should be screened serologically. Testing should be done in high-prevalence areas during the third trimester and at delivery. Infants should have maternal serological status assessed.
• Diagnosis: Use both non-treponemal and treponemal tests to avoid false positives. Penicillin G is the preferred treatment throughout pregnancy.
• Prevention: Public health efforts should focus on education, pre-conceptional and antenatal screening, and awareness in high-risk populations.

Listeriosis

Epidemiology and Pathogenesis

• Cause: Listeriosis is a rare foodborne infection caused by Listeria monocytogenes, a Gram-positive bacillus.
• Manifestations: Can cause septicemia, neurolisteriosis, and severe maternal-fetal infections. In pregnancy, it leads to maternal fever, premature delivery, fetal loss, and neonatal systemic and central nervous system infections.
• Incidence: Estimated at 4–10 cases per 100,000 pregnant women/year in Europe and North America. Incidence is higher in areas with less surveillance.

Maternal Presentation

• Patterns: Includes nonspecific obstetric signs such as uterine contractions, labor, and abnormal fetal heart rate.

Obstetric Outcome

• Complications: 82% of pregnant women with listeriosis experience major complications, including fetal loss, premature delivery, and birth of infants with early or late-onset listeriosis. Despite preventive measures, fetal loss rates remain high.

Prevention and Management

• Prevention: Educate on avoiding risky foods like unpasteurized dairy products and ready-to-eat meats. Ensure clean food preparation and avoid cross-contamination.
• Treatment: Requires collaboration with infectious disease specialists and neonatologists. Treatment includes ampicillin or gentamicin for 14 days. Early recognition and intervention improve outcomes.

Group B Streptococcus (GBS) Infections

Prevalence and Impact

• GBS: A major global cause of severe neonatal disease, affecting 0.5–3 newborns per 1000 live births.

Clinical Syndromes

• Early-onset Disease (EOD): Occurs within the first week of life, primarily presenting as sepsis.
• Late-onset Disease (LOD): Affects infants aged over 1 week to 3 months, with symptoms such as bacteremia and/or meningitis.

Screening and Prevention

• Screening Methods: Antenatal GBS screening and intrapartum antibiotic prophylaxis (IAP) have reduced early-onset neonatal disease by over 80%. Screening is usually done at 35–37 weeks or via rapid real-time PCR tests during labor.
• Current Strategies: Recommendations vary; some countries use antenatal screening, others rely on risk-based strategies. Intrapartum tests could be a cost-effective alternative to antepartum screening.

Treatment

• Intrapartum Antibiotic Prophylaxis: Recommended for specific situations per CDC guidelines. Administering beta-lactam antibiotics for at least 4 hours before delivery effectively prevents vertical transmission of GBS.
• Additional Strategies: Vaginal chlorhexidine application could reduce maternal GBS colonization and neonatal infection, but results are mixed and depend on application methods.

Conclusion

Infections during pregnancy present a multifaceted challenge that demands careful management and preventive strategies. The diverse range of bacterial and protozoan infections, from tuberculosis and syphilis to listeriosis and Group B Streptococcus, underscores the critical need for ongoing research and improved clinical practices. Addressing these infections during pregnancy effectively requires a thorough understanding of their epidemiology, clinical presentation, and treatment options. As we continue to advance our knowledge and refine our approaches, it is essential to emphasize the importance of early detection and proactive management to minimize adverse outcomes. By focusing on infections during pregnancy with a comprehensive and informed strategy, we can better protect maternal and fetal health and ensure healthier pregnancies and births.