Question 32: A positive IgM antibody cannot be considered a recent infection, either before or during the second trimester?
A positive IgM antibody result cannot be considered as a recent infection. IgM antibodies in acute infections can be present for more than a year, and most pregnant women with positive IgM antibodies have had the infection for a long time, beyond the time when it affects the fetus. These patients had chronic infections, and Jose tested 100 consecutive serum samples from other laboratories that were positive for IgM antibodies and sent to the PAMF-TSL reference laboratory, and confirmatory tests at the PAMF-TSL reference laboratory confirmed that 62% of these serum samples were negative for IgM antibodies. Additional tests confirmed that these infections were distant rather than recent. the greatest value of a positive IgM test result is that it emphasizes the possibility of a recent infection and therefore requires further confirmation at the reference laboratory.
Q33: How many possibilities are there for the final interpretation of the Toxoplasma gondii antibody test results in the reference laboratory?
There are 3 possibilities for the final interpretation of the serologic test results at the reference laboratory.
1. The test result is consistent with recent infection, suggesting that the patient acquired the infection after pregnancy, but infection at the time of imminent conception cannot be excluded.
2. The test results are consistent with a distant infection prior to conception.
3. The test result is inconclusive and further serological tests are needed in parallel.
Q34: What is the clinical significance of the Toxoplasma IgG affinity test?
The Toxoplasma IgG affinity test is generally applied in reference laboratories. High affinity IgG antibodies do not appear until at least 12-16 weeks of gestation after infection (depending on the test method applied). The presence of high-affinity antibodies suggests that the infection appears at least before 16 weeks. Therefore, the results of high-affinity IgG tests in pregnant women in the first trimester, regardless of the results of IgM antibody tests, suggest that the fetus is essentially free of congenital toxoplasma infection. For pregnant women >16 weeks gestation, high affinity test results are useful to determine infection until at least 12-16 weeks of early gestation, in which case the rate of Toxoplasma transmission to the fetus is low compared to late gestation infection, but the potential for fatal fetal damage is high, see Table 5, and the negative predictive value of amniotic fluid PCR would be high, see Table 7. Table 7 Maternal weeks of gestation for infection Relationship with fetal infection and amniotic fluid PCR
Note: Positive predictive value is 100% regardless of the weeks of gestation, data from the literature. NA: Not applicable. a: 270 pregnant women were tested by seroconversion to identify maternal infection, of which 261 (97%) were treated with acetylspiramycin. b: 1 year later, congenital infection was diagnosed by the presence of Toxoplasma IgG antibodies
Special attention needs to be paid to the fact that low affinity or inconclusive test results may be present for several months or more than 1 year after the initial infection, and for this reason, the Toxoplasma IgG affinity test alone cannot be used to determine whether the infection is recent. In fact, if a serum sample, with low-affinity or critical-value affinity antibodies, has a negative IgM antibody test result, suggesting a distant infection. If used alone, the IgG affinity test is not useful and may even be misleading.
Question 35: How to perform the diagnosis of fetal infection when Toxoplasma gondii is suspected for the first time during pregnancy?
PCR amplification of amniotic fluid Toxoplasma DNA at 18 weeks of gestation (optimal time) or slightly later has been successfully used for the prenatal diagnosis of congenital toxoplasmosis. Performing amniotic fluid testing early in pregnancy carries a high risk to the fetus and is unnecessary. Data show that testing at 17-21 weeks of gestation has the highest sensitivity and the best negative predictive value (100% positive predictive value regardless of the number of weeks of gestation).
Ultrasound is mainly used when a pregnant woman is suspected or diagnosed with an acute infection within a short period of time (3 months) before conception. Ultrasound can show fetal malformations including hydrocephalus, calcification of the brain or liver, splenomegaly and ascites.
Question 36: When should the treatment of Toxoplasma gondii infection in pregnancy be started with acetylspiramycin? Once an acute infection is suspected and the infection occurs within 18 weeks of gestation or a short time before pregnancy, to stop vertical transmission of the parasite, acetyl spiramycin is considered by some authors in the United States and Europe to be the drug of choice.
Question 37: When is acetaminophen, sulfadiazine, and formyltetrahydrofolate used in combination to treat Toxoplasma gondii infection?
If a positive result of PCR in amniotic fluid confirms fetal infection, at or after 18 weeks of gestation, the use of etanercept, sulfadiazine, and formyltetrahydrofolate is recommended (if the patient is already on acetyl spiramycin, a change to a combination is recommended). Ethamiprazine is teratogenic and therefore should not be co-administered before 18 weeks of gestation (in some centers in Europe, co-administration can be as early as 14-16 weeks of gestation). Due to the high rate of vertical transmission after 18 weeks of gestation, etanercept, sulfadiazine, and formyltetrahydrofolate are also recommended to stop fetal infection if Toxoplasma gondii infection occurs after 18 weeks of gestation.
If vertical transmission has already occurred, treatment of the fetus is prepared. At this point acetaminophen should not be applied early because of the potential teratogenic effects of this drug. Acetospiramycin, a macrolide antibiotic, can reduce the probability of vertical transmission. However, well-designed studies have not been performed. This protection has been reported to be more effective for infections in early pregnancy. In this study, the probability of congenital infection was reduced by about 60% with reference to historical controls. Acetospiramycin does not pass rapidly through the placenta and therefore would not be very effective in treating fetal infections. There is no evidence of teratogenic effects of acetylchloramphenicol, see Table 8.
Because infection in early pregnancy can theoretically be transmitted to the fetus in late pregnancy, acetylspiramycin should be used until delivery, even if the amniotic fluid PCR result is negative. In pregnant women with a high risk of fetal infection, or with proven fetal infection, the regimen of acetylchlorothiazide alone after 18 weeks of pregnancy should be changed to a combination of acetaminophen, sulfadiazine, and formyltetrahydrofolate. The medication must be applied under the guidance of a medical specialist.
Table 8 Medications for pregnant women suspected or identified with Toxoplasma gondii infection during pregnancy
Note: FDA: U.S. Food and Drug Administration.
a: PaloAltoMedicalFoundationToxoplasmaSerologyLaboratory,telephonenumber(650)853-4828,orUS(Chicago,IL) NationalCollaborativeTreatmentTrialStudy, telephonenumber(773)834-4152,.
b: Folic acid cannot be used as a substitute for formyltetrahydrofolate
Q38: Do I still need prenatal diagnosis and anti-Toxoplasma treatment if I had Toxoplasma infection (IgG antibody positive) before pregnancy?
The probability of a child with congenital toxoplasmosis is very small (close to 0) when toxoplasma infection was clearly established before pregnancy or when serologic testing shows a long-ago (pre-pregnancy) toxoplasma infection, so treatment with acetylchlorothiazide or ethidiazine, sulfadiazine, formyltetrahydrofolate, and prenatal diagnosis of fetal infection are not necessary unless the mother is immunocompromised.
Q39: What information is available for each suspected case of Toxoplasma gondii infection (women of childbearing age, pregnant women and primary care physicians) in consultation and discussion with specialists?
1. Choice of Toxoplasma testing method.
2. The correct interpretation of the test results.
3.Prenatal diagnosis for pregnant women and fetuses.
4. Giving individualized treatment plans.
Q40: What is the treatment of patients with immunodeficiency who had Toxoplasma infection before pregnancy?
Pregnant women co-infected with HIV and Toxoplasma are at risk for reactivation of Toxoplasma and development of toxoplasmosis, such as Toxoplasma encephalitis, pneumonia, etc., and/or transmission of parasites to offspring.
HIV-infected pregnant women are not candidates for amniotic fluid PCR because of the risk of HIV transmission to the fetus during amniocentesis. Amniotic fluid PCR testing may be considered in pregnant women with chronic Toxoplasma gondii infection (also during pregnancy) who are not HIV-infected and have immunodeficiency. For all pregnant women with chronic Toxoplasma infection who are also immunodeficient, an ultrasound should be performed every month.
Question 41: What is a safe time to get pregnant if I have recently been infected with Toxoplasma gondii?
Women of childbearing age who are clearly infected with Toxoplasma gondii are often asked when it is safe to become pregnant given the risk of transmission to offspring. There is no definitive information on this issue. Conservative advice is for such women to wait 6 months (from the time the acute infection is confirmed or documented) before becoming pregnant. It is advisable to have a specialist consultation for each patient.
V. Herpes simplex virus (HSV) screening
Q42: What is the purpose of herpes simplex virus (HSV) screening before and during pregnancy?
Serologic screening for HSV during pregnancy can clarify whether a pregnant woman is infected with the virus. In contrast, comparative pre-pregnancy and gestational HSV screening is performed to determine whether the infection is initial or recurrent in order to provide a basis for treatment and intervention, with the goal of preventing infection in the newborn. The process of management after laboratory screening in pregnancy is shown in Figure 7, the
Q43: What are the characteristics of HSV infection during pregnancy?
1. Once infected for life, the virus is latent in the ganglion and is a neuroherpesophilic virus.
The probability of fetal infection due to initial infection in early and mid-pregnancy is very low, and screening in early pregnancy is of little significance; HSV causes rare fetal malformations via blood-placenta, such as microcephaly, hepatosplenomegaly, intrauterine fetal death (IUFD), and intrauterine growth retardation (IUGR).
3, HSV infection mainly infects newborns through the birth canal.
4, HSV infection during pregnancy is mainly initial infection. Prior IgG positivity has a weak protective effect against HSV infection in the newborn.
5, Neonatal infection rate: initial infection in pregnant women > recurrent infection.
6. 60%-80% of infants who become infected with HSV during delivery have no prior history of genital herpes infection or no history of genital herpes in their sexual partners.
7. 70% of mothers do not know they are infected until after they find out their newborn is infected.
8. Both HSV-1 and HSV-2 types can cause genital herpes infection (up to 50% of initial genital herpes infections are caused by HSV-1, but viral shedding in recurrent and subclinical infections is mainly due to HSV-2). The risk of infection to the newborn in late pregnancy is 30% to 50%, regardless of whether the initial infection is HSV-1 or HSV-2.
Question 44: HSV infection in newborns? Congenital HSV?
Neonatal HSV infection is an infection acquired by the newborn through exposure to the maternal genital tract virus close to or during labor and delivery. In rare cases, infection of medical origin or postpartum infection through the baby’s mouth or broken skin may also occur. A definitive diagnosis of HSV infection needs to be made 48 hours after the end of labor, which is important to distinguish a newborn from a congenital HSV infection. Congenital HSV infection is rare, and in utero HSV infects the fetus through the placenta.
Question 45: How many types of genital herpes infections are there?
First-time infections, where the patient is first exposed to HSV-1 or HSV-2 viruses, has not been previously exposed to either or both viruses, and is not immune (no antibodies to HSV-1 or HSV-2).
First episode of non-first infection, where the patient has a first clinically confirmed episode of HSV infection, but the appropriate antibodies have been produced in the patient’s body during prior infection with HSV-1 or HSV-2 viruses.
Symptomatic relapse, where there is a clear clinical presentation and the patient is diagnosed with HSV infection and antibody production, followed by a relapse.
Q46: What should I pay attention to in HSV serologic testing?
The following issues should be noted when performing serologic testing.
1. It is recommended that direct testing for the virus (I-A) be used for all pregnant women suspected of having HSV infection. However, the results of the direct virus testing method can be negative for those with a history of recurrent infection or a history of atypical reproductive tract disease (III, B).
2, HSV-2 antibodies can diagnose genital herpes; HSV-1 antibodies cannot distinguish between genital tract or oropharyngeal infections.
3, HSV-2 IgG negative and HSV-1 IgG positive should be considered as an uncommon recurrent genital tract infection.
4, First genital herpes, a distinction should be made between initial infection and previous infection (III, B). Evidence of seroconversion of the primary infection should be found at the time of symptom onset, as no IgG against HSV of that virus has been produced (consistent with the type detected in genital lesions), and at follow-up.
5. Initial infection type-specific HSV antibodies can be detected 2 weeks to 3 months after the onset of symptoms. Anyone with clinical symptoms should be followed up with a sample assay to confirm serologic conversion (IIa-B).
6. Since patients with early infection lack IgG antibodies, detection of herpes simplex virus IgM antibodies can improve the detection rate of early infection (IIb-B). However, because HSVIgM can be positive in recurrent infections and may be negative in initial infections, it is a non-viral specific antibody.
7. There is no FDA-approved HSVIgM typing kit, and a truly credible typing test for identifying acute HSV infection should be a molecular biology method using PCR technology.
Q47: What is the management of primary HSV infection in late pregnancy?
In late pregnancy, primary HSV infection in pregnant women has the most serious impact on the newborn. In this case, the infant lacks passive immune protection from maternal IgG because the mother cannot produce sufficient IgG antibodies prior to delivery. At this time, 30% to 50% of newborns will be infected with HSV.
Question 48: What should I do if HSV infection recurs during delivery?
When a recurrent HSV infection is detected during delivery, with prodromal symptoms or lesions, the physician should recommend a cesarean delivery, even if the lesions are located away from the vulva (e.g., buttocks or thighs), as both the cervix and vagina may secrete the virus. Ideally, cesarean delivery should be performed within 4 hours of rupture of membranes in order to prevent infection. If labor has already been initiated, the choice of cesarean delivery will most likely not help to reduce the infection rate. In another case, the protective effect of cesarean delivery has not been demonstrated in cases of active vaginal HSV replication combined with delayed rupture of membranes.
Question 49: Is there a clinical significance of HSV serological typing during pregnancy?
Both HSV-1 and HSV-2 types can produce herpes in the genital area, and both can cause neonatal infection. The current clinical treatment strategy does not differ according to the typing, nor does it change according to the site of HSV infection or the tissues and organs, and HSV-1 accounts for a high proportion of genital herpes, up to 1/3 of the cases, so typing is not necessary. The most reliable.
Question 50: What is the management of recurrent HSV infection during pregnancy?
When a recurrent HSV infection occurs in a pregnant woman at <36 weeks of gestation, antiviral therapy should not be used even if the clinical symptoms are severe. However, when the clinical symptoms are so severe that antiviral therapy cannot be avoided, individualized regimens should also be considered for treatment. The use of antiviral therapy after >36 weeks of gestation may reduce its infectivity, alleviate clinical symptoms, and reduce the rate of cesarean delivery. In the absence of extensive data from clinical safety studies, acyclovir and valacyclovir should be used in pregnant women only if they present with an indication for antiviral therapy.
Question 51: Is serologic testing required even in women without a history of HSV infection?
HSV infection is acquired during delivery and 60%-80% of infants have no prior history of HSV infection or sexual partners with no history of genital herpes. 70% of mothers do not know they are infected until they find out their newborn is infected.
Question 52: What happens to the newborn after the first episode of genital herpes in pregnancy?
The postpartum neonate of a pregnant woman with the first outbreak of genital herpes during pregnancy should be treated as follows.
1. The pediatrician should be notified first.
2. HSV cultures of urine, stool, oropharynx, eyes and skin should be done for early detection of infection in the newborn.
3. When culture results are not available, the pros and cons should be weighed to investigate whether to initiate acyclovir therapy.
4. If acyclovir therapy is not initiated immediately, the newborn should be monitored closely for signs of lethargy, fever, refusal to eat, or lesions.
Question 53: What is the management of the newborn after delivery of recurrent genital herpes in pregnancy?
Although some physicians believe that a group of specimens should be obtained for viral culture after delivery in pregnant women with recurrent genital herpes in pregnancy to help detect neonatal infection early, there is no evidence to support this practice. However, physicians and parents should be advised to consider the differential diagnosis of HSV infection if the infant has any lesions of the skin, eyes, or mucous membranes, especially within 2 weeks of birth.