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Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus-immune maternal population.

OBJECTIVE To determine contribution of reinfection with new strains of cytomegalovirus in cytomegalovirus seromimmune women to incidence of congenital cytomegalovirus infection. STUDY DESIGN In 7848 women studied prospectively for congenital cytomegalovirus infection from a population with near universal cytomegalovirus seroimmunity, sera from 40 mothers of congenitally infected infants and 109 mothers of uninfected newborns were analyzed for strain-specific anticytomegalovirus antibodies. RESULTS All women were cytomegalovirus seroimmune at first prenatal visit. Reactivity for 2 cytomegalovirus strains was found in 14 of 40 study mothers and in 17 of 109 control mothers at first prenatal visit (P = .009). Seven of 40 (17.5%) study women and 5 of 109 (4.6%) controls (P = .002) acquired antibodies reactive with new cytomegalovirus strains during pregnancy. Evidence of infection with more than 1 strain of cytomegalovirus before or during current pregnancy occurred in 21 of 40 study mothers and 22 of 109 controls (P < .0001). CONCLUSION Maternal reinfection by new strains of cytomegalovirus is a major source of congenital infection in this population.

Maternal antiretroviral drugs during pregnancy and infant low birth weight and preterm birth

Objective:To determine the relationship between maternal antiretroviral regimens during pregnancy and adverse infant outcomes [low birth weight (LBW) and preterm birth]. The a priori hypothesis was that protease inhibitor (PI)-containing regimens are associated with an increased risk of LBW and preterm birth. Design:Prospective cohort study of HIV-1-infected women and their infants (NISDI Perinatal Study). Methods:Data were analysed from 681 women receiving at least one antiretroviral drug [in order of increasing complexity: one or two nucleoside reverse transcriptase inhibitors (1–2 NRTI), two NRTI plus one non-nucleoside reverse transcriptase inhibitor (NNRTI) (HAART/NNRTI), or two NRTI plus one PI (HAART/PI)] for at least 28 days during pregnancy, and who delivered live born, singleton infants with known birth weight and gestational age by 1 March 2005. Multivariable logistic regression modeling was used to assess the relationship of maternal ART with LBW and with preterm birth, adjusting for covariates. Results:The incidence of LBW and preterm birth, respectively, was 9.6% and 7.4% (1–2 NRTI), 7.4% and 5.8% (HAART/NNRTI), and 16.7% and 10.6% (HAART/PI). There was no statistically significant increased risk of LBW [adjusted odds ratio (AOR), 1.5; 95% confidence interval (95% CI), 0.7–3.2] or preterm birth (AOR, 1.1; 95% CI, 0.5–2.8) among women who received HAART/PI compared with women receiving 1–2 NRTI. Conclusions:Among a population of HIV-1-infected women in Latin America and the Caribbean, maternal receipt of PI-containing ART regimens during pregnancy was not associated with a statistically significant increase in risk of LBW or preterm birth.

Toxoplasmose aguda: estudo da freqüência, taxa de transmissão vertical e relação entre os testes diagnósticos materno - fetais em gestantes em estado da Região Centro - Oeste do Brasil

PURPOSE: to establish the frequency of acute toxoplasmosis in pregnant women, vertical transmission rate and the perinatal results of the infected fetuses and also to evaluate the relationship between the most used maternal-fetal diagnostic tests for toxoplasmosis during pregnancy and the relationship between age and acute toxoplasmosis infection during pregnancy. METHODS: longitudinal prospective study of 32,512 pregnant women attended by The Pregnancy Protection Program of the State of Mato Grosso do Sul - Brazil, from November 2002 to October 2003. ELISA (IgG and IgM) and IgG avidity test were performed for maternal diagnosis and amniotic fluid PCR for fetal investigation of the infection. The relationship between data was analyzed statistically by the c2 or two-sided Fishers exact test in contingency tables. RESULTS: a 0.42% frequency of acute Toxoplasma gondii infection among pregnant population was found, where 92% were previously exposed and 8% were susceptible. Among IgM-positive pregnant women, the age ranged from 14 to 39 years, with a mean of 23±5.9 years. There was no statistically significant relationship between age and maternal acute T. gondii infection (p=0.73). The vertical transmission rate was 3.9%. A statistically significant relationship was shown (p=0.001) between a lower avidity IgG test ( 60%) and the absence of fetal infection. There was a statistically significant association (p=0.001) between fetal infection (amniotic fluid PCR) and neonatal infection. CONCLUSIONS: maternal acute toxoplasmosis frequency was lower than the Brazilian national parameters, whereas vertical transmission rate did not differ from the rates found in other studies. The IgG avidity test, when associated with gestational age and the examination date, was useful to evaluate the therapeutical options and to consider the risk of vertical transmission when performed before 12 weeks. Positive PCR in amniotic fluid showed a positive relationship with the worst neonatal prognosis, being a specific method in diagnosing intrauterine fetal infection.

Congenital and perinatal cytomegalovirus infection in infants born to mothers infected with human immunodeficiency virus

OBJECTIVES To determine the rates of congenital and perinatal cytomegalovirus (CMV) infection among infants born to mothers infected with HIV compared with infants born to mothers not infected with HIV from a CMV-immune, low-income population. STUDY DESIGN A total of 325 newborns from CMV-seropositive mothers were enrolled and evaluated for congenital CMV infection (150 infants from HIV+ mothers and 175 infants from HIV- mothers. A total of 101 infants from HIV+ mothers and 33 infants from HIV- mothers were evaluated for perinatal CMV infection. The virus was isolated from urine by culture in human fibroblasts and was detected by polymerase chain reaction at birth and at 15 days and 12 weeks of age. RESULTS Only 13 of 150 HIV+ mothers (8.7%) had an AIDS-defining condition, and none had a late-stage HIV infection. Congenital CMV infection was detected in 4 of 150 (2.7%) infants from HIV+ mothers and in 5 of 175 (2.9%) infants from HIV- mothers (p = 1.00). Perinatal CMV infection was diagnosed in 8 of 101 (7.9%) infants from HIV+ mothers and in 13 of 33 (39.4%) infants from HIV- mothers (p < 0.00001). Most infants (93.9%) from HIV- mothers and only 5.9% of infants from HIV+ mothers were breastfed. CONCLUSIONS CMV coinfection in mothers without advanced HIV disease from a CMV-immune population does not enhance the likelihood of congenital CMV infection. Perinatal CMV transmission from HIV-infected mothers may be decreased by avoiding breastfeeding. Further studies on mothers with late-stage HIV infection are needed.

Visceral leishmaniasis (kala-azar) and pregnancy

OBJECTIVE: The aim of the present review was to close the gap in the approach to pregnant women with visceral leishmaniasis (kala-azar) by providing up-to-date information to obstetricians about physiopathology, epidemiology, vertical transmission, drugs and treatment during pregnancy. BACKGROUND: Infection with Leishmania chagasi during pregnancy is rare and deserves special attention since little information is available regarding the occurrence of visceral leishmaniasis during gestational period and the real possibility of vertical transmission of this disease. Because specific areas in the world are endemic for the disease and considering the continuous growth of the population, cases of pregnant women with visceral leishmaniasis are becoming more frequent. Unfortunately, textbooks on infectious diseases do not include this specific group of patients, and studies in the literature on aspects related to pregnancy and visceral leishmaniasis are scarce. CONCLUSIONS: Vertical transmission of leishmaniasis is possible and the institution of treatment is imperative in cases of pregnant women with kala-azar. Amphotericin B is strongly recommended as the first choice drug due to its fewer maternal-fetal adverse effects.

Matrix metalloproteinase (MMP)-9 genotypes and haplotypes in preeclampsia and gestational hypertension

BACKGROUND Abnormal production of matrix metalloproteinases (MMPs), especially MMP-9, may play a role in hypertensive disorders of pregnancy. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 gene, which are known to change MMP-9 expression. We examined whether 2 MMP-9 polymorphisms (C(-1562)T and (CA)n) and haplotypes are associated with preeclampsia and/or gestational hypertension. METHODS We studied 476 pregnant women: 176 healthy pregnant (HP), 146 pregnant with gestational hypertension (GH), and 154 pregnant with preeclampsia (PE). Genomic DNA was extracted from whole blood and genotypes for C(-1562)T and (CA)n polymorphisms were determined by PCR-RFLP. Haplotype frequencies were inferred using the PHASE ver. 2.1 program. RESULTS For the g.-90(CA)13-25 polymorphism, no significant differences were found in genotype and allele distributions when PE or GH groups were compared with HP group. However, the CT genotype and T allele for g.-1562C>T polymorphism were more commonly found in GH subjects compared with the HP group (both P<0.05). Conversely, we found no differences in genotypes or allele distributions for the g.-1562C>T polymorphism when the PE and the HP groups were compared. No significant differences were found in overall distributions of haplotype frequencies when the GH or the PE group was compared with the HP group. CONCLUSIONS The C(-1562)T polymorphism in MMP-9 gene is associated with gestational hypertension, but not with preeclampsia. These findings may help to explain the higher plasma MMP-9 levels previously reported in GH compared with HP.

HLA-G polymorphisms in women with squamous intraepithelial lesions harboring human papillomavirus

Human papillomavirus (HPV) infection is etiologically associated with low- (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and with cervical cancer. The progression or regression of the lesions may depend, among other factors, on the host heritable immune response. Because human leukocyte antigen (HLA)-G molecules are involved in the modulation of innate and adaptive immune responses, and because no previous studies have evaluated HLA-G polymorphism in patients with SIL, we conducted a study to assess the association between HLA-G polymorphisms and cervical lesions harboring HPV infection. Cervico-vaginal scrapings and blood samples were collected from 125 women with SIL (68 LSIL and 57 HSIL) and from 94 healthy women without HPV infection and cytological abnormalities. HPV type and HLA-G polymorphisms in exons 2, 3 and 8 (14 bp insertion/deletion) were evaluated by PCR methodology, and digested with restriction endonucleases. The Genepop software and the EM and PHASE algorithms were used for statistical analysis. A significant protective association was observed between the presence of the G*0103 allele and SIL and between the G0101/G0104 genotype and HSIL in the group of patients compared to control. The presence of the G0104/+14 bp and G0104/−14 bp haplotypes conferred susceptibility to SIL compared to control. In addition, patients possessing the G0104/+14 bp haplotype and harboring HPV-16 and -18 co-infections were particularly associated with HSIL. These findings suggest that HLA-G polymorphisms may be associated with HPV infection and SIL, consequently representing a profile of predisposition to cervical cancer.

Management of human immunodeficiency virus-infected pregnant women at Latin American and Caribbean sites.

OBJECTIVE: To describe the management of a population of human immunodeficiency virus (HIV)–infected pregnant women in Latin America and the Caribbean, and to assess factors associated with maternal viral load of 1,000 copies/mL or more and with infant HIV-1 infection. METHODS: Eligibility criteria were enrollment in the prospective cohort study as of March 2006; delivery of a liveborn, singleton infant; and completion of the 6-month postpartum or postnatal visit. RESULTS: Of 955 women enrolled in Argentina, the Bahamas, Brazil, and Mexico, 770 mother-infant pairs were eligible. At enrollment, most women were relatively healthy (87% asymptomatic, 59% with viral load less than 1,000 copies/mL, 62% with CD4+% of 25% or more). Most (99%) received antiretrovirals during pregnancy (56% prophylaxis, 44% treatment), and 38% delivered by cesarean before labor and before ruptured membranes. Only 18% of women had a viral load of 1,000 copies/mL or more after delivery (associated in adjusted analyses with receipt of antiretrovirals at conception, CD4+% [lower], viral load [higher], and country at enrollment, enrollment late in pregnancy, and inversely related to antiretroviral regimen [two nucleoside or nucleotide analogue reverse transcriptase inhibitors plus one nonnucleoside reverse transcriptase inhibitor] during pregnancy). None of the infants breastfed, and all received antiretroviral prophylaxis. Seven infants became infected (0.91%; 95% confidence interval 0.37–1.86). Low birth weight infants and those whose mothers had a low CD4+% at hospital discharge after delivery and were not receiving antiretrovirals at enrollment were at higher risk of HIV infection. CONCLUSION: Only a minority of women had a viral load of 1,000 copies/mL or more around delivery, and mother-to-child transmission of HIV occurred rarely (1%). LEVEL OF EVIDENCE: II

Matrix metalloproteinase-9 polymorphisms affect plasma MMP-9 levels and antihypertensive therapy responsiveness in hypertensive disorders of pregnancy.

Abnormal matrix metalloproteinase (MMP)-9 levels may have a role in hypertensive disorders of pregnancy. We examined whether MMP-9 genetic polymorphisms (g.−1562C>T and g.−90(CA)13−25) modify plasma MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels and the responses to antihypertensive therapy in 214 patients with preeclampsia (PE), 185 patients with gestational hypertension (GH) and a control group of 214 healthy pregnant (HP). Alleles for the g.−90(CA)13−25 polymorphism were grouped L (low) (<21 CA repeats) or H (high) (⩾21 CA repeats). Plasma MMP-9 and TIMP-1 concentrations were measured by enzyme-linked immunosorbent assay. Plasma MMP-9 concentrations were not affected by genotypes or haplotypes in HP and PE groups, except for the g.−90(CA)13−25 polymorphism: GH patients with the LH genotype for this polymorphism have higher MMP-9 levels than those with other genotypes. The T allele for the g.−1562C>T polymorphism and the H4 haplotype (combining T and H alleles) are associated with GH and lack of responsiveness to antihypertensive therapy in GH. The H2 haplotype (combining C and H alleles) was associated with lack of responsiveness to antihypertensive therapy in PE, but not in GH. In conclusion, our results show that MMP-9 genetic variants are associated with GH and suggest that MMP-9 haplotypes affect the responsiveness to antihypertensive therapy in hypertensive disorders of pregnancy.

Association between matrix metalloproteinase (MMP)-2 polymorphisms and MMP-2 levels in hypertensive disorders of pregnancy

We examined whether two functional polymorphisms (g.-1306C>T and g.-735C>T) in matrix metalloproteinase (MMP)-2 gene are associated with preeclampsia (PE) or gestational hypertension (GH), and whether they modify MMP-2 or tissue inhibitor of metalloproteinase (TIMP)-2 plasma concentrations in these hypertensive disorders of pregnancy. We studied 130 healthy pregnant (HP), 130 pregnant with GH, and 133 pregnant with PE. Genomic DNA was extracted from whole blood and genotypes for g.-1306C>T and g.-735C>T polymorphisms were determined by Real Time-PCR, using Taqman allele discrimination assays. Haplotypes were inferred using the PHASE program. Plasma MMP-2 and TIMP-2 concentrations were measured by ELISA. The main findings were that pregnant with PE have higher plasma MMP-2 and TIMP-2 concentrations than HP (P<0.05), although the MMP-2/TIMP-2 ratios were similar (P>0.05). Moreover, pregnant with GH have elevated plasma MMP-2 levels and MMP-2/TIMP-2 ratios compared to HP (P<0.05). While MMP-2 genotypes and haplotypes are not linked with hypertensive disorders of pregnancy, MMP-2 genotypes and haplotypes are associated with significant alterations in plasma MMP-2 and TIMP-2 concentrations in preeclampsia (P<0.05). Our findings may help to understand the relevance of MMP-2 and its genetic polymorphisms to the pathophysiology of hypertensive disorders of pregnancy. It is possible that patients with PE and the MMP-2 haplotype combining the C and T alleles for the g.-1306C>T and g.-735C>T polymorphisms may benefit from the use of MMPs inhibitors such as doxycycline. However, this possibility remains to be determined.