Viral infections during pregnancy.

Viral infections during pregnancy have long been considered benign conditions with a few notable exceptions, such as herpes virus. The recent Ebola outbreak and other viral epidemics and pandemics show how pregnant women suffer worse outcomes (such as preterm labor and adverse fetal outcomes) than the general population and non-pregnant women. New knowledge about the ways the maternal-fetal interface and placenta interact with the maternal immune system may explain these findings. Once thought to be 'immunosuppressed', the pregnant woman actually undergoes an immunological transformation, where the immune system is necessary to promote and support the pregnancy and growing fetus. When this protection is breached, as in a viral infection, this security is weakened and infection with other microorganisms can then propagate and lead to outcomes, such as preterm labor. In this manuscript, we review the major viral infections relevant to pregnancy and offer potential mechanisms for the associated adverse pregnancy outcomes.

Zidovudine exposure in HIV-1 infected Tanzanian women increases mitochondrial DNA levels in placenta and umbilical cords.

BACKGROUND: Zidovudine (AZT) constitutes part of the recommended regimens for prevention and treatment of HIV-1 infection. At the same time, AZT as well as HIV-1 infection itself may induce mitochondrial damage. In this study, we analyzed the impact of prenatal AZT-exposure on mitochondrial alterations in HIV-infected women and their infants. METHODS: Mitochondrial DNA (mtDNA) levels in placentas of HIV-1 infected Tanzanian women with and without prenatal AZT exposure, and in the umbilical cords of their AZT-exposed/unexposed infants were quantified using real-time PCR. Furthermore, we checked for the most common mitochondrial deletion in humans, the 4977 base pair deletion (dmtDNA4977) as a marker for mitochondrial stress. RESULTS: 83 women fulfilled the inclusion criteria. 30 women had been treated with AZT (median duration 56 days; IQR 43-70 days) while 53 women had not taken AZT during pregnancy. Baseline maternal characteristics in the two groups were similar. The median mtDNA levels in placentas and umbilical cords of women (311 copies/cell) and infants (190 copies/cell) exposed to AZT were significantly higher than in AZT-unexposed women (187 copies/cell; p = 0.021) and infants (127 copies/cell; p = 0.037). The dmtDNA4977 was found in placentas of one woman of each group and in 3 umbilical cords of AZT-unexposed infants but not in umbilical cords of AZT-exposed infants. CONCLUSIONS: Antenatal AZT intake did not increase the risk for the common mitochondrial deletion dmtDNA4977. Our data suggests that AZT exposure elevates mtDNA levels in placentas and umbilical cords possibly by positively influencing the course of maternal HIV-1 infection.

Renal disease in HIV infected patients at University of Benin Teaching Hospital in Nigeria.

BACKGROUND: HIV related renal disease is a common occurrence in patients with HIV infection. It is the third leading cause of end stage renal disease among African-American males between the ages of 20 and 64 years in USA. Renal function impairment has been reported at all stages of HIV infection. The aim of this study is to determine the relationship between severity of renal function impairment and CD4 cell count in HIV infected patients. METHOD: HIV patients presenting at University of Benin Teaching Hospital Benin, City Nigeria from 1(st) January to 30(th) June 2007 were randomly selected and screened for renal functional impairment (RFI). Those with RFI detected by glomerular filtration rate < 60 ml/min/1.73 m(2) or urine protein creatinine ratio 3 200 were stratified into mild, moderate and severe RFI. Forty patients from each stratum and forty HIV infected patients with normal renal functions were recruited as subjects and control respectively. Their clinical and laboratory parameters were evaluated. The data obtained were analysed using SPSS vs 15.0. RESULTS: Of the HIV patients screened, 53.3% had renal functional impairment. of these, 40.2% had mild, 37.7% had moderate and 22.2% had severe impairment in their renal functions respectively Their mean age was 36.0 ± 8.8 years. The CD4 cell count was found to be 309.75 ± 268.71/ul, 188.45 ± 173.12/ul, and 141.10 ± 126.01/ul among subjects with mild, moderate and severe RFI respectively. The CD4 cell count in control group was 319.05 ± 248.41/ul. The difference was statistically significant. (p = <0.001). CD4 cell count had a significant positive correlation with GFR (r = 0.32, p = 0.042). However, there was a negative correlation between CD4 cell count and proteinuria but this was not statistically significant (r = 0.09, p = 0.173). CONCLUSION: Severity of RFI has a positive correlation with degree of immunosuppression in HIV infected patients.

Are we going to close social gaps in HIV? Likely effects of behavioral HIV-prevention interventions on health disparities.

Although experimental behavioral interventions to prevent HIV are generally designed to correct undesirable epidemiological trends, it is presently unknown whether the resulting body of behavioral interventions is adequate to correct the social disparities in HIV-prevalence and incidence present in the United States. Two large, diverse-population meta-analytic databases were reanalyzed to estimate potential perpetuation and change in demographic and behavioral gaps as a result of introducing the available behavioral interventions advocating condom use. This review suggested that, if uniformly applied across populations, the analyzed set of experimental (i.e. under testing) interventions is well poised to correct the higher prevalence and incidence among males (vs. females) and African-Americans and Latinos (vs. other groups), but ill poised to correct the higher prevalence and incidence among younger (vs. older) people, as well as men who have sex with men, injection-drug users, and multiple partner heterosexuals (vs. other behavioral groups). Importantly, when the characteristics of the interventions most efficacious for each population were included in the analyses of behavior change, results replicated with three exceptions. Specifically, after accounting for interactions of intervention and facilitator features with characteristics of the recipient population (e.g. gender), there was no behavior change bias for men who have sex with men, younger individuals changed their behavior more than older individuals, and African-Americans changed their behavior less than other groups.

[Antenatal transmission of hepatitis B virus in an area of HIV moderate prevalence, Burkina Faso]. / Transmission anténatale du virus de l'hépatite B en zone de prévalence modérée du VIH, Ouagadougou, Burkina Faso.

The aim of this study was to assess antenatal transmission of hepatitis B virus in a context of moderate prevalence of HIV in Burkina Faso. Among 360 counselled pregnant women for HIV and HBV testing, 307 were voluntarily enrolled at their last antenatal clinic at the university hospital, in Ouagadougou. Blood samples were collected from all the 307 mothers and tested for HBsAg, HBeAg and antibodies to HIV Blood samples were collected from 313 newborns in the 24 hours after birth and screened for HBV Data from mothers and newborns were collected and analysed using the EPI Info 2002 software. Values for p < 0.05 were considered statistically significant. HBsAg were found in 35 (11.4%) mothers, including 7 with HBeAg and 6 co-infected by both HIV and HBV. Seven babies born to 13 carrier mothers for HBsAg and HBeAg had HBsAg versus 6 born to 22 HBsAg carrier mothers HBeAg-negative. HBsAg was detected in 4 babies born to 6 HIV/HBV co-infected mothers versus 9 born to 29 mothers with HBsAg and HIV-negative. HIV infection, HBeAg and mothers excision were significantly associated with mother-to-child transmission (MTCT) of HBV (p < 0.02). HBV antenatal transmission was important in Ouagadougou and it occurred 2.5 folds more from HIV coinfected mothers than in HIV-negative mothers to newborns. These results showed the need of the implementation of national programme for HBV screening and immunisation in Burkina Faso.

[HIV prevalence in sub-Saharan Africa: background of an estimation]. / Prévalences du VIH en Afrique sub-saharienne: historique d'une estimation.

In 2008 UNAIDS global report on AIDS, the number of people living with HIV in sub-Saharan Africa was estimated at 22 millions in 2007 and 20.4 millions in 2001, while in the 2002 report, the same estimation for 2001 was 28.5 millions. Changes in UNAIDS reflects evolutions of data sources and methods used for the estimates. Sentinel surveillance of pregnant women attending antenatal clinics (ANC) was developed in 1980's with the WHO recommendation of unlinked anonymous testing approach. The objective was not to be representative but to monitor trends. In the 1990's, as ANC data were available, they were used by EpiModel, a model developed by WHO for HIV prevalence estimates from 1992 to 2000. In 2002, a new epidemiological model called EPP (Estimation and Projection Package) was developed by the UNAIDS Reference Group on Estimates, Modelling and Projections, which, in countries with a generalised epidemic, is still based on ANC data collected over time. Since 2001, many countries have conducted national population-based surveys (NPS). Their results have often diverged from estimates based on ANC data. This was explained by the under-representation of rural clinics in sentinel surveillance and relative small participation rate in NPS. Since, several studies have shown that the impact of several biases (participation rate, non-household members, serological window of tests...) in NPS remains relatively low. NPS constitute a good indicator of HIV prevalence level. If pregnant women can be locally representative of the general population, at the national scale, it depends of the localization of selected clinics. But ANC provides data over time, which is not the case for NPS. The current approach of UNAIDS consists in estimating HIV prevalence trends from ANC and the level of the epidemics from NPS. But the hypothesis that ANC data are representative of trends still needs to be verified when several NPS will be available for a same country.

[Antiretroviral therapy and pregnancy]. / Antiretrovirale Medikamente und Schwangerschaft.

Whereas the perinatal transmission rate with untreated HIV positive women is around 30%, the results of Pediatric AIDS Clinical Trials Group in 1994 showed a reduction by nearly 70% with Zidovudin chemoprophylaxis. The transmission rate can even be reduced to under 2%, if a cesarean section before onset of labour and before premature rupture of membranes is done in addition. An individualized, optimal antiretroviral combination therapy, ideally introduced in the second trimenon (in special cases even already in the first trimenon), is of great importance. As a further strategy of prevention of perinatal transmission, intravenous Zidovudin chemoprophylaxis should be given in addition to the mother during labour and to the newborn during the first six weeks of life. Besides very few exceptions, long-term data after intrauterine administration of antiretroviral therapy do not show any teratogen or other long term consequences to date. The situation in developing countries is very critical with still high transmission rates because of the lack of antiretroviral therapy due to logistical reasons and costs and the need of breastfeeding. For these reasons, more and more feasible short protocols are developed with at least fifty percent reduction of neonatal transmission rates.

Embryonic immune development and risks of HIV infection.

The importance of the maternal immune system, during both gestation and breastfeeding, for the health of future generations is discussed.

Maternal antibodies to HIV-1 envelope domains: No correlation with HIV-1 vertical transmission in patients from Argentina.

The role of the maternal antibody response in relation to vertical human immunodeficiency virus type 1 (HIV-1) transmission was investigated in HIV-1-infected mothers from Argentina. Sera from 23 transmitting and 18 nontransmitting HIV-1-infected mothers were tested for the presence of antibodies to V3 loop gp120 peptides representing both Argentinian sequences and several well-characterized viral isolates from different geographic areas. Argentinian sera from transmitting mothers had significantly higher capacity to react with four of 14 V3 loop peptides tested than sera from nontransmitting mothers. Frequency of reactivity against the other peptides did not differ between the two maternal groups. Furthermore, no differences in antibody affinity were found between transmitting and nontransmitting mothers. Sera were also tested against overlapping peptides covering a neutralizing epitope of the HIV-1 MN gp41 (amino acids 648-677). Statistical analysis indicated that no correlation between anti-gp41 antibodies and vertical transmission exists. Although we used V3 loop peptides based on local HIV-1 sequences, our data showed that maternal antibodies to these peptides, as well as to gp41 peptides, are not correlated with protection against HIV-1 vertical transmission.

Development of a chronically catheterized maternal-fetal macaque model to study in utero mother-to-fetus HIV transmission: a preliminary report.

The lack of a representative animal model that permits frequent in utero fetal blood sampling is a major limiting factor for the study of maternal-fetal HIV transmission. Therefore, we have developed a maternal-fetal virus infection model using chronically catheterized macaques to simultaneously study the time-course of viral infection in the mother and the response of the fetus to maternal HIV infection. Pregnant macaques were infected with 10(3) infectious units of HIV-2(287); every 3 days blood samples from both the mother and the fetus as well as amniotic fluid samples were collected. We found a varying degree of peak and time-to-peak virus load, virus-infected PBMCs, and free virus (determined by QC-RNA-PCR method) in maternal blood. Two of the three mothers with more than 10(8) copies of viral RNA/ml of plasma at peak viremia transmitted the virus to their fetuses at about 14 days post-infection. As observed with HIV-2(287) infected mothers, virus-infected fetuses also produced a rapid rate of CD4+ cell decline in utero.

Drug abuse and reproduction.

The spreading of drugs in the western world has increased dramatically, especially among young people. Over 10% of the population of the USA in reproductive age uses cannabinoids, cocaine, heroin or other drugs. Data related to Italy indicates a progressive increase in cocaine abuse, that adds up to the already dramatic rise in heroin and alcohol abuse. Although the research work on the reproductive effects of drugs has started recently and is still limited, the damages that they can cause to endocrine system, pregnancy and conceptus are clear.

Laboratory diagnosis of fetal infections.

In utero infections of the fetus can lead to significant morbidity and mortality in the newborn child. The signs and symptoms of clinical disease, however, do not always suggest a given pathogen. The laboratory must be able to provide an early and accurate diagnosis of the causative agent so that prompt and appropriate antimicrobial therapy and medical care can be initiated. The scope of this article includes the methods employed by the laboratory to assist in the diagnosis of bacterial, fungal, parasitic, and viral infections of the fetus. Where appropriate, detection methods were addressed for the diagnosis of the major pathogens responsible for infection during the birth process.

Fetal human immunodeficiency virus type 1 infection of different organs in the second trimester.

Human immunodeficiency virus type 1 (HIV-1) infection in utero was examined by isolating the virus and detecting the HIV-1 DNA sequence from different fetal tissues. The brain, thymus, lung, liver, spleen, and placenta tissues from fetuses (10-23 weeks of gestation) born to HIV-1-infected asymptomatic mothers were examined. HIV-1 was isolated from 2 of 7, 1 of 7, and 1 of 7 cocultures of splenic, thymic, and trypsin-resistant cells from the liver and placenta, respectively, with peripheral blood mononuclear cells; 20-30% and 40-60% of splenic and of thymic cells were CD4+ lymphoid cells and 40-80% of trypsin-resistant cells were mononuclear phagocytes. The HIV-1 DNA sequence was detected in 4 of 7, 3 of 7, 1 of 7, 1 of 7, 2 of 7, and 2 of 6 samples from the spleen, thymus, brain, lung, liver, and placenta, respectively, using the polymerase chain reaction. In one case, the intensity of the HIV-1 DNA sequence appeared to be correlated with the success of viral isolation. We indicate that fetal HIV-1 infection may frequently occur in the second trimester and the cells responsible for the infection may be CD4+ lymphoid cells and mononuclear phagocytes.