Vertical Infection Research Articles

Case report: vertical dengue infection

To report a case of vertical dengue infection in a newborn from Rio de Janeiro, Brazil, and to review the literature concerning this problem. We report a case of vertical dengue infection. Female neonate, birth weight 3,940 g, term, was admitted to a neonatal intensive care unit on the fifth day of life with fever and erythematous rash. Her mother had had dengue fever 3 days before delivery. Her platelet count was 38,000, dropping to 15,000. She did not have any hemorrhagic episodes, including cerebral hemorrhages. Anti-dengue antibodies (IgM) were positive in the mother and infant. Dengue type 2 was detected in the infant using polymerase chain reaction. This report emphasizes that pediatricians should be aware of the possibility of vertical dengue infection so that early management can be instituted.

High and low temperatures differently affect infection density and vertical transmission of male-killing Spiroplasma symbionts in Drosophila hosts.

We investigated the vertical transmission, reproductive phenotype, and infection density of a male-killing Spiroplasma symbiont in two Drosophila species under physiological high and low temperatures through successive host generations. In both the native host Drosophila nebulosa and the nonnative host Drosophila melanogaster, the symbiont infection and the male-killing phenotype were stably maintained at 25 degrees C, rapidly lost at 18 degrees C, and gradually lost at 28 degrees C. In the nonnative host, both the high and low temperatures significantly suppressed the infection density of the spiroplasma. In the native host, by contrast, the low temperature suppressed the infection density of the spiroplasma whereas the high temperature had little effect on the infection density. These results suggested that the low temperature suppresses both the infection density and the vertical transmission of the spiroplasma whereas the high temperature suppresses the vertical transmission preferentially. The spiroplasma density was consistently higher in the native host than in the nonnative host, suggesting that the host genotype may affect the infection density of the symbiont. The temperature- and genotype-dependent instability of the symbiont infection highlights a complex genotype-by-genotype-by-environment interaction and may be relevant to the low infection frequencies of the male-killing spiroplasmas in natural Drosophila populations.

In pregnant mice, the infection of Toxoplasma gondii causes the decrease of CD4+CD25+‐regulatory T cells

Acute maternal infection with Toxoplasma gondii during pregnancy is associated with adverse pregnancy outcomes. Although previous reports have indicated that T. gondii may result in abortion without direct transmission of the parasite to the foetus, the molecular mechanism remains unclear. CD4+CD25+-regulatory T cells are known to be involved in maternal tolerance toward the foetus-bearing alloantigens. With a model of pregnant mice infected with T. gondii, we found that Foxp3 mRNA expression levels in both splenocytes and placenta were reduced markedly during the process of infection. Furthermore, the numbers of splenic CD4+CD25+-regulatory T cells and placental Foxp3+ cells decreased synchronously in the infected mice, and the reduction of splenic CD4+CD25+-regulatory T cells were associated with apoptosis induced by the infection. Additionally, injection of pregnant mice with excretory-secretory antigens (ESA) of T. gondii also resulted in foetal loss, which could be partly prevented by adoptive transfer of CD4+CD25+-regulatory T cells from normal pregnant mice. These data suggest that foetal loss caused by T. gondii can be independent of vertical infection and that the decrease of CD4+CD25+-regulatory T cells during infection may represent a previously unrecognized mechanism for the pathogenesis of abortion caused by this parasite.

Negative Effects of Low Temperatures on the Vertical Transmission and Infection Density of a Spiroplasma Endosymbiont in Drosophila hydei

Maternally transmitted endosymbionts of the genus Spiroplasma infecting several species of Drosophila are known to cause selective death of male offspring (male killing). The male-killing trait is considered to be advantageous for maternally transmitted endosymbionts. However, a non-male-killing spiroplasma is present in Japanese populations of Drosophila hydei at high frequencies (23-66%). This spiroplasma is phylogenetically closely related to the male-killing spiroplasma infecting other Drosophila species. It is unknown why this spiroplasma is maintained in its host populations despite its inability to cause male killing. We examined the susceptibilities of the spiroplasma in D. hydei to four different temperatures (28, 25, 18, and 15 degrees C). Diagnostic PCR revealed that vertical transmission of the spiroplasma was nearly perfect at 28 and 25 degrees C, partially suppressed at 18 degrees C, and completely blocked at 15 degrees C. Furthermore, quantitative PCR demonstrated that offspring treated at 18 degrees C exhibited dramatically lower densities of spiroplasma (i.e., approximately one-tenth) compared to offspring treated at 28 and 25 degrees C. Considering the low temperatures during winter in Japan, some unknown advantageous effects of the spiroplasma that compensate for the failure of vertical transmission are suggested to act in natural populations of D. hydei.

Effect of HIV vertical transmission on the ontogeny of T cell antigens involved in the regulation of humoral immune response.

HIV infection causes progressive impairment of humoral immunity, including defective specific antibody production. To evaluate whether vertical HIV infection interferes with the expression on CD4+ lymphocytes of developmentally regulated molecules, that play a crucial role in the generation of immunological memory (CD45 isoforms) and in attainment of antibody responses (CD40L), 22 HIV-infected children and 36 seroreverted children born to HIV+ mothers were studied. The percentage of CD40L+ PBMC after activation in vitro with phorbol myristate acetate (PMA) plus ionomycin was lower in HIV-infected children than in controls (P < 0.004). This correlated with the depletion of CD4+ lymphocytes (r = 0.75; P < 0.001). CD40L expression rose progressively with age (r = 0.36; P = 0.03) in seroreverted children, but not in HIV-infected children, suggesting that while in normal children in vivo antigen stimulation results in progressive attainment of CD40L expression (and thus to effective T-B cell cooperation), this process is largely defective in HIV-infected children, contributing to the genesis of humoral immune deficiency. The proportion of CD4+ cells bearing the CD45RO isoform was increased among HIV-infected infants during the first years of life. However, the percentage of CD4+ CD45RO+ peripheral blood mononuclear cells (PBMC) progressively increased with age in controls (r = 0.69; P = 0.03), but not in HIV-infected children, showing that while vertical transmission of HIV does not prevent CD45RO expression early in life, it is associated with a disturbance of the physiological process of antigen priming, contributing to poor immunological memory to T cell-dependent antigens.

Dengue Virus Infection in Late Pregnancy and Transmission to the Infants

Vertical dengue virus transmissions have been infrequently described. To date there are no published data on long-term outcome and antibody kinetics of infants who were infected in utero. This is the first report of vertical dengue transmission with 12 months follow-up evolution of antibody and the clinical outcome. Three mother-infant pairs were confirmed to have perinatally dengue infection by serology, viral isolation, or reverse transcription polymerase chain reaction (RT-PCR). The infants were followed clinically at 1, 2, 4, 6, 9, and 12 months. Sera were collected at 1, 6, and 12 months of age for serologic testing. Three mothers developed symptomatic dengue infection 1 day, 12 days, and 5 weeks before delivery of their infants. The first infant developed presumed bacterial illness on day 6 of life. Dengue virus serotype 1 was detected by RT-PCR and viral isolation. The second infant developed fever, petechiae, and hepatomegaly 9 hours after birth. Dengue virus serotype 2 was detected by RT-PCR. The third infant was asymptomatic. All mothers and infants had uneventful recoveries. One year follow-up revealed normal growth and development in all infants. The pattern of antibody kinetics suggested primary infection in the first and second infants, and the transferred antibody without infection in the third infant. In endemic areas, dengue infection can cause an acute febrile illness in pregnant women and sepsis-like illness in neonates. Vertical infection did not result in long-term sequelae.

Managing primary CMV infection in pregnancy

Vertical infection can occur antenatally throughthe placenta, during delivery through cervical secretions andblood and postnatally through breast milk. CMV is endemicand most adults will be infected during their lifetime. Adultseroprevalence in developed countries is around 50%, but indeveloping countries it may be as high as 90–100%. Primaryinfection in immunocompetent adults is usually asymptom-atic, and viral shedding continues for some months before theinfection is brought to its latent phase. In children, viral shed-ding may persist for years after a primary infection and tod-dlers in day care constitute an important infectious source. Incommon with other herpesviruses, CMV remains lifelong atspecific sites (mainly the salivary glands) and the viral repli-cation cycle can be reactivated. Secondary infection can occurdue to such reactivation of the residing virus or due to infec-tion with a different strain (reinfection).

Extrinsic Incubation Periods for Horizontal and Vertical Transmission of West Nile Virus by &lt;I&gt;Culex pipiens pipiens&lt;/I&gt; (Diptera: Culicidae)

Culex pipiens pipiens L. (Diptera: Culicidae), infected per os from a membrane feeder, transmitted West Nile virus (family Flaviviridae, genus Flavivirus, WNV) at 26 degrees C horizontally during feeding to hamsters and suckling mice and vertically to F1 progeny during egg deposition. Horizontal transmission rates increased with extrinsic incubation, with 75-100% of the females transmitting on days 16 through 25 postinfection (pi). No females deposited eggs infected with WNV after the first bloodmeal on 3-8 d pi. Females vertically transmitted WNV during egg laying after their second, third, and fourth bloodmeals on days 13-33 pi. The vertical transmission rate was 4.7%. The vertical minimal infection rate was 0.52 infected F1 specimens/1,000 specimens tested from females feeding during their second and later bloodmeals on hamsters or suckling mice. The sequence of horizontal and vertical transmission is reported. A female may transmit WNV 1) horizontally to a host during feeding and subsequently vertically to her offspring during egg laying, 2) vertically to her offspring during oviposition without prior horizontal transmission to a host, and 3) horizontally to a host without vertically transmitting the virus. These two means of transmission by Cx. p. pipiens contribute to the relatively high minimum infection rates that are reached in late summer and to the survival of virus during winter and initiation of amplification in the spring in the northeastern United States.

Atypical manifestations of congenital parvovirus B19 infection

Parvovirus B19 infection in pregnancy is associated with fetal anemia, hydrops and fetal death. We report two unusual manifestations of vertical parvovirus B19 infection. The first patient developed hydrops as consequence of myocarditis with involvement of sino-atrial node. The other had pleural effusion reactive to the hepatic localization of the virus.

Effects of vertical HIV infection on the persistence of anti-HBs after a schedule of three doses of recombinant hepatitis B vaccine

Anti-HBs persistence following HBV vaccination among HIV-positive children has never been systematically studied in central Brazil. An historical cohort study was performed aiming to evaluate persistence of anti-HBs in HIV-positive children in comparison with an HIV-negative child group. Fifty-eight HIV-positive and 116 HIV-negative individuals were enrolled. Birth weight, breast-feeding duration, and the time elapsed since the last hepatitis B vaccine doses were similar between the groups. Fourteen (24%) out of 58 HIV-positive participants were anti-HBs positive and 101 (87%) out of 116 were HIV-negative (p<0.001). Among anti-HBs-positive individuals, the geometric mean titres were 118 and 298 mIU/mL, respectively to HIV-positive and HIV-negative groups (p=0.04). These results disclose a worrying picture regarding the failure of standard HBV vaccination among Brazilian HIV-infected children.

The natural history of vertically acquired HCV infection

Little information is available on the epidemiology, natural history and responsiveness to antiviral therapy of HCV infection in children. The epidemiology has changed substantially in recent years. In Italy, for example, in the 90's most children were affected by post-transfusional hepatitis. In contrast, in the new millennium most have been due to mother-to-child transmission. The total number of vertically infected children has also been decreasing, because the screening of blood donors has reduced the spread of the virus to women of child-bearing age. However, in the USA approximately 7000 new cases of vertical infection are estimated to occur over the next decade. The screening of blood donors has also changed the relative prevalence of different genotypes in infected children, with a decrease in transfusion-associated type 1b genotype and an increased percentage of genotypes 3 and 4; this has relevant therapeutic implications since the latter are more sensitive to specific treatment. Newer population-based studies on the epidemiology of paediatric infection in different parts of the world are needed.

Characteristics of a group of pregnant women voluntarily tested for hiv antibodies in the Facatativa’s San Rafael hospital

A nivel mundial, el principal factor de riesgo de contagio en la mujer en la adquisición del VIH son las relaciones sexuales. Prevenir la trasmisión vertical madre-hijo es el objetivo del programa y, con este estudio, se deseaba conocer la prevalencia de VIH en mujeres embarazadas, en el municipio de Facatativá. En la consulta externa de control prenatal, se buscaron las madres con factores de riesgo para VIH y SIDA, quienes recibieron una asesoría y una evaluación pre-test. Se registraron 620 mujeres embarazadas que se sometieron voluntariamente a la prueba de VIH; el 65% eran menores de 24 años. De los 620 casos registrados, el 84,35% tenía seguridad social. Solo dos de ellas salieron positivas, una en la contra muestra negativa. A los casos positivos, se les aplicó la prueba confirmatoria de Western Blot. Se ejecutó el protocolo propuesto de AZT por cuatro semanas antes del parto. Después de éste la madre recibió nueva asesoría, se suprimió la lactancia y se le ofreció lactancia artificial por doce meses. Con una prevalencia del 0,06%, las principales características de la población mostraron: el promedio de la menarquia fue de 12,9 años, el inicio de las relaciones sexuales estaba por debajo de los 16 años (44%), el 50% no tuvo orientación sexual y solo fue obtenida en el colegio (36%). Su primer embarazo ocurrió por debajo de los 22 años. Este programa permite confirmar que la prueba durante control prenatal detecta madres VIH positivas y su manejo adecuado previene la infección vertical madre-feto.

HEPATITIS B MARKERS

Objective: To determine the transmission of Hepatitis B virus from infectedmother to their newborns. Design: Cross-sectional descriptive study. Setting: Pediatrics Ward-2 and Gynecology &amp;Obstetric Department Bahawal Victoria Hospital/Quaid-e-Azam Medical College Bahawalpur. Period: From August2004 to December 2005 Material and Methods: A total of 300 pregnant ladies admitted in the gynecological andobstetric department for delivery were screened for HBsAG, HBeAG, HBcAB, HBsAB, and HBeAB. The newborns ofthe mothers with HBsAG and HBeAG were tested for the same antigens at the time of birth and the ones who werepositives for the antigens were labeled as having “vertical infection” through placenta. Results were tabulated; incidenceof hepatitis was calculated. RESULTS: HBsAG was positive in 37(12.3%) out of the 300 enrolled mothers. Out of the37 babies born to 37 hepatitis B positive mothers, 4(21%) newborns were positive for HBsAG.In the mothers of theseinfected newborns, HBeAG was present in 3 while one mother did not have HBeAG. CONCLUSION: Universal prenatalscreening for hepatitis B in all the pregnant women and protection of their off springs should be provided both by activeand passive prophylaxis immediately after birth depending upon their serological status.

The Role of Vertical Transmission and Health Care-Related Factors in HIV Infection of Children

To determine the probable route of transmission of HIV to children aged 12 years or younger in a rural area of Uganda from 1999 through 2000 and to examine associations between HIV infection and health care-related variables. The HIV infections status for 6991 children was determined from 1 round of an ongoing population surveillance system, and the reported numbers of injections in the past year and blood transfusions were determined for 5922 of these children based on a medical questionnaire. Data from the surveillance system and from an additional survey were used to assess the potential for vertical infection from a mother to her child. The HIV prevalence among children was 0.4%. Of 23 definite and 4 probable cases of HIV infection in children, vertical transmission was not possible for 1 case, not likely for another case, and possibly not vertical for another case. The population-attributable fraction for vertical transmission was between 90% and 94%. Large numbers of injections in the past year and ever having a blood transfusion were only associated with HIV infection in children exposed to vertical transmission. Up to 10% of HIV infections in children in the study area were not attributable to vertical transmission, and thus were possibly attributable to iatrogenic transmission. Associations seen between health care-related variables and HIV were likely to be attributable to treatment for AIDS-related illness in children infected vertically.

Immune activation and normal levels of endogenous antivirals are seen in healthy adolescents born of HIV-infected mothers

Immunological analyses performed in healthy adolescents born of HIV-infected (seroreverters) or healthy mothers (healthy controls; HC) showed that immune activation and a skewing of postthymic differentiation are present in adolescent seroreverters. In-utero HIV exposure results in long-lasting imprinting on the immune system. Alternatively, an immune response naturally more prone to activation could prevent vertical infection. Endogenous antivirals (APOBEC, TRIM5alpha) were comparable in seroreverters and HC, and might not play a role in resistance to vertical HIV infection.

Transplacental murine cytomegalovirus infection in the brain of SCID mice.

BackgroundCongenital cytomegalovirus (CMV) infection is the most common congenital viral infection in humans and the major nonhereditary cause of central nervous system (CNS) developmental disorders. Previous attempts to develop a murine CMV (MCMV) model of natural congenital human CMV (HCMV) infection have failed because MCMV does not cross the placenta in immunocompetent mice.ResultsIn marked contrast with immunocompetent mice, C.B-17 SCID (severe combined immunodeficient) mice were found to be highly susceptible to natural MCMV transplacental transmission and congenital infection. Timed-pregnant SCID mice were intraperitoneally (IP) injected with MCMV at embryonic (E) stages E0-E7, and vertical MCMV transmission was evaluated using nested polymerase chain reaction (nPCR), in situ hybridization (ISH) and immunohistochemical (IHC) assays. SCID mouse dams IP injected at E0 with 102 PFU of MCMV died or resorbed their fetuses by E18. Viable fetuses collected at E18 from SCID mice IP injected with 102–104 PFU of MCMV at E7 did not demonstrate vertical MCMV transmission. Notably, transplacental MCMV transmission was confirmed in E18 fetuses from SCID mice IP injected with 103 PFU of MCMV at stages E3-E5. The maximum rate of transplacental MCMV transmission (53%) at E18 occurred when SCID mouse dams were IP injected with 103 PFU of MCMV at E4. Congenital infection was confirmed by IHC immunostaining of MCMV antigens in 26% of the MCMV nPCR positive E18 fetuses. Transplacental MCMV transmission was associated with intrauterine growth retardation and microcephaly. Additionally, E18 fetuses with MCMV nPCR positive brains had cerebral interleukin-1α (IL-1α) expression significantly upregulated and cerebral IL-1 receptor II (IL-1RII) transcription significantly downregulated. However, MCMV-induced changes in cerebral cytokine expression were not associated with any histological signs of MCMV infection or inflammation in the brain.ConclusionSevere T- and B-cell immunodeficiencies in SCID mice significantly enhance the rate of natural MCMV transplacental transmission and congenital infection. During gestation MCMV exhibits a tissue tropism for the developing brain, and vertical MCMV transmission is correlated with fetal growth retardation and abnormal cerebral proinflammatory cytokine expression. These data confirm that natural vertical MCMV infection in SCID mice constitutes a useful new experimental rodent model of congenital HCMV infection.

Toxoplasmosis in captive Bennett's wallabies ( Macropus rufogriseus) in Argentina

Wallabies and other Australian marsupials are among the most susceptible species to Toxoplasma gondii. Fatal generalized toxoplasmosis was diagnosed in two captive 3 year-old female Bennett's wallabies ( Macropus rufogriseus) from Argentina (w 1 and w 2) with a history of sudden death. Both animals had internal joeys which died 2 days after their mothers. Serologically, both females and one adult male without clinical signs from the same enclosure (w 3) had antibody titers for T. gondii ≥ 800 by the modified agglutination test (MAT); another adult male (w 4) was negative (MAT titer < 25). Microscopically, tachyzoites were observed associated to non-suppurative meningoencephalitis, hepatitis, myositis, myocarditis and severe enteritis in hematoxylin and eosin stained sections from both w 1 and w 2. Immunohistochemically, parasites in heart, brain and liver sections of both female wallabies reacted with T. gondii antiserum. T. gondii was isolated from brain tissues of w 1 and w 2 by bioassay in mice and by culture in bovine monocytes and both isolates were cryopreserved. Genomic DNA was isolated from tachyzoites grown in cultures derived from both animals. The primer pair B22/B23 specific for T. gondii produced 115 bp amplicons on poliacrylamide electrophoretic gels. Stray cats were suspected as the possible source of infection. Not all infected macropods were ill, showing that the infection may be asymptomatic and is not always fatal. A vertical infection could not be proved in the joey from w 2. As far as we know, this is the first confirmed report of toxoplasmosis in Bennet's wallabies in Argentina.

Absence of detectable viremia in a perinatally HIV-1–infected teenager after discontinuation of antiretroviral therapy

A 15-year-old girl with perinatal HIV-1 infection has remained asymptomatic with undetectable plasma HIV-1 viremia for more than 5 years after discontinuing all antiretroviral therapy. Viral sequence analysis of proviral HIV-1 DNA revealed no evident fitness-attenuating deletions or mutations. This subject exhibited an unusually robust HIV-specific T-cell response, with an intact CD4+ T cell-proliferative response to HIV-1 antigens. In addition, the subject was found to be heterozygous for the 32-bp deletion in the CCR5 gene, which encodes the primary coreceptor for HIV-1 entry into cells. This mutation mediates profound resistance to HIV infection in homozygotes and has been associated with delayed disease progression in heterozygotes after both horizontal and vertical HIV-1 infection. Although adults with long-term nonprogressive HIV disease have been studied at length, there is no prior description in the literature of a perinatally HIV-infected child whose plasma HIV-1 viremia is controlled to undetectable levels in the absence of antiretroviral therapy.

Clinical Outcomes Improve with Highly Active Antiretroviral Therapy in Vertically HIV Type‐1–Infected Children

Background. Use of antiretroviral therapy has resulted in a decrease in morbidity and mortality rates in human immunodeficiency virus type 1 (HIV-1)-infected children.Methods. We performed a retrospective study involving 427 children to determine the effectiveness of different antiretroviral therapy protocols on clinical outcome. The follow-up period was divided into 5 calendar periods (CPs): CP1 (1980-1989), before antiretroviral therapy was administered; CP2 (1990-1993), when monotherapy was administered; CP3 (1994-1996), when combined therapy was administered; CP4 (1997-1998), when </=50% of children were receiving highly active antiretroviral therapy (HAART); and CP5 (1999-2003), when >/=60% of children were receiving HAART.Results. Children experienced a progressive increase in the CD4(+) cell count and decrease in the viral load from 1997 onwards. A lower number of AIDS cases and deaths occurred during CP5 than during the other CPs (P<.01), with a relative risk of an absence of AIDS of >20 and a relative risk of survival of >30. The AIDS rate was >50% in CP1; we observed a very strong decrease to 14% in CP2, to 16% in CP3, to 7% in CP4, and to 2% in CP5. The mortality rates in CP2 and CP3 were >6% and thereafter decreased to 0.5% in CP5. The relative risks for no hospital admission in CP4 and CP5 were >3.5. The total rates of hospital admission in CP1, CP2, and CP3 were >30%; we observed a decrease in CP4 and CP5. The duration of hospitalization decreased during the follow-up period, and it was higher in CP1 (~30 days) than in the other periods.Conclusions. We observed that HAART produces a decrease in adverse clinical outcomes (i.e., hospital admission, AIDS, and death) in children with vertical HIV-1 infection in Madrid, Spain.

Self-Extending Symbiosis: A Mechanism for Increasing Robustness Through Evolution

Robustness is a fundamental property of biological systems, observed ubiquitously across species and at different levels of organization from gene regulation to ecosystem. The theory of biological robustness argues that robustness fosters evolv-ability and that together they entail various tradeoffs as well as characteristic architectures and mechanisms. We argue that classes of biological systems have evolved to enhance their robustness by extending their system boundary through a series of symbioses with foreign biological entities (“self-extending symbiosis”). A series of major biological innovations has been achieved by events consistent with this framework: horizontal gene transfer, serial endosymbiosis, oocytes-mediated vertical infection, and host-symbiont mutualism for bacterial flora. Self-extending symbiosis contributes to robustness because symbiotic foreign biological entities can enhance the adaptative capacity of the system against environmental perturbations as well as contribute novel functions. In addition, evolutionary history indicates that the degree of symbiosis achieved has substantially changed from tight integration into the genome (which is less adaptive) to loose integration as bacterial flora (which can be highly adaptive). The most dramatic example can be seen in the symbiosis of host immune system and bacterial flora in which substantial function of host defense depends on the proper maintenance of bacterial flora and its adaptive capability. Biological systems following this type of evolutionary path might have attained high levels of functionality, robustness, and evolvability. Thus, robustness, evolution, and self-extending symbiosis may form essential system principles for biology.