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

Yamamoto, Aparecida Yulie; Mussi-Pinhata, Marisa Márcia; Boppana, Suresh B.; Novák, Zdeněk; Wagatsuma, Virginia Mara De Deus; Oliveira, Patricia de Frizzo; Duarte, Geraldo; Britt, William J.

doi:10.1016/j.ajog.2009.11.018

Cited by 181 publications

(163 citation statements)

References 53 publications

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“…Namely, not only CMV-naive but also CMV-immune women can acquire CMV infection during pregnancy with subsequent transmission to the fetus. 3,4 Although primary maternal infection carries a greater risk of CMV transmission and severe sequelae for the neonate than do recurrent infections, the burden associated with nonprimary infection is nonetheless substantial. Development of a vaccine able to induce immunity that is more effective than the natural infection or able to ameliorate the preexisting immune response is a highly challenging concept.…”

Section: Future Prospects For the Prevention And Therapy Of Congenitamentioning

confidence: 99%

Immunobiology of congenital cytomegalovirus infection of the central nervous system—the murine cytomegalovirus model

et al. 2014

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Congenital human cytomegalovirus infection is a leading infectious cause of long-term neurodevelopmental sequelae, including mental retardation and hearing defects. Strict species specificity of cytomegaloviruses has restricted the scope of studies of cytomegalovirus infection in animal models. To investigate the pathogenesis of congenital human cytomegalovirus infection, we developed a mouse cytomegalovirus model that recapitulates the major characteristics of central nervous system infection in human infants, including the route of neuroinvasion and neuropathological findings. Following intraperitoneal inoculation of newborn animals with mouse cytomegalovirus, the virus disseminates to the central nervous system during high-level viremia and replicates in the brain parenchyma, resulting in a focal but widespread, non-necrotizing encephalitis. Central nervous system infection is coupled with the recruitment of resident and peripheral immune cells as well as the expression of a large number of pro-inflammatory cytokines. Although infiltration of cellular constituents of the innate immune response characterizes the early immune response in the central nervous system, resolution of productive infection requires virus-specific CD8 1 T cells. Perinatal mouse cytomegalovirus infection results in profoundly altered postnatal development of the mouse central nervous system and long-term motor and sensory disabilities. Based on an enhanced understanding of the pathogenesis of this infection, prospects for novel intervention strategies aimed to improve the outcome of congenital human cytomegalovirus infection are proposed.

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Section: Future Prospects For the Prevention And Therapy Of Congenitamentioning

confidence: 99%

Immunobiology of congenital cytomegalovirus infection of the central nervous system—the murine cytomegalovirus model

et al. 2014

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“…While protective, this natural immunity is incomplete. [27][28][29] Recent studies in Brazil, where almost all congenital infections occur in infants born to CMV-experienced women, 30 are consistent with a significant worldwide burden of CMV congenital disease due to recurrent infections. 13,14 Recurrent infections are the result of reactivation of resident viruses as well as the acquisition of new virus strains (re-infection or super-infection).…”

mentioning

confidence: 73%

“…30,49,50 Clearly, hand washing would not be expected to prevent congenital diseases that follow a pattern of reactivation or long-term infections with multiple virus strains that reactivate independently during pregnancy. Antiviral chemotherapy with ganciclovir in newborns provides a benefit in severe cytomegalic inclusion disease; however, it does not reverse damage or impact progressive diseases, such as hearing loss.…”

Section: Infection and Disease Preventionmentioning

confidence: 99%

The immunological underpinnings of vaccinations to prevent cytomegalovirus disease

McCormick

Mocarski

2014

Cell Mol Immunol

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A universal cytomegalovirus (CMV) vaccination promises to reduce the burden of the developmental damage that afflicts up to 0.5% of live births worldwide. An effective vaccination that prevents transplacental transmission would reduce CMV congenital disease and CMV-associated still births and leave populations less susceptible to opportunistic CMV disease. Thus, a vaccination against this virus has long been recognized for the potential of enormous health-care savings because congenital damage is life-long and existing anti-viral options are limited. Vaccine researchers, industry leaders, and regulatory representatives have discussed the challenges posed by clinical efficacy trials that would lead to a universal CMV vaccine, reviewing the links between infection and disease, and identifying settings where disrupting viral transmission might provide a surrogate endpoint for disease prevention. Reducing the complexity of such trials would facilitate vaccine development. Children and adolescents are the targets for universal vaccination, with the expectation of protecting the offspring of immunized women. Given that a majority of females worldwide experience CMV infection during childhood, a universal vaccine must boost natural immunity and reduce transmission due to reactivation and re-infection as well as primary infection during pregnancy. Although current vaccine strategies recognize the value of humoral and cellular immunity, the precise mechanisms that act at the placental interface remain elusive. Immunity resulting from natural infection appears to limit rather than prevent reactivation of latent viruses and susceptibility to re-infection, leaving a challenge for universal vaccination to improve upon natural immunity levels. Despite these hurdles, early phase clinical trials have achieved primary end points in CMV seronegative subjects. Efficacy studies must be expanded to mixed populations of CMV-naive and naturally infected subjects to understand the overall efficacy and potential. Together with CMV vaccine candidates currently in clinical development, additional promising preclinical strategies continue to come forward; however, these face limitations due to the insufficient understanding of host defense mechanisms that prevent transmission, as well as the age-old challenges of reaching the appropriate threshold of immunogenicity, efficacy, durability and potency. This review focuses on the current understanding of natural and CMV vaccine-induced protective immunity.

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“…По современным представлениям, диагностика врожденной цитомегаловирусной инфекции у но-ворожденного ребенка основывается на обнаруже-нии ДНК цитомегаловируса методом полимеразной цепной реакции (ПЦР) в первые 3 нед жизни [1,5,8,13,15,28,29], однако ряд авторов ограничивают сроки диагностики первыми двумя неделями жизни [6,11,16,25,27,30,31]. При выделении вируса после 2-3 нед жизни уже нельзя исключить интранаталь-ное или постнатальное заражение.…”

Section: клиническая картина и диагностика врожденной цитомегаловирусunclassified

“…Частота реактивации/реинфекции цито-мегаловирусом во время беременности не определе-на, в связи с чем риск инфицирования плода в этих случаях остается неясным [6]. Кроме того, показано, что риск трансмиссии цитомегаловируса плоду от се-ропозитивных женщин может зависеть от некоторых факторов, в частности, он повышается при реинфек-ции несколькими штаммами вируса во время бере-менности [13].…”

unclassified

Congenital cytomegalovirus infection: Diagnosis, treatment, and prevention

Karpova¹,

Narogan²,

Karpov³

2017

Ross. vestn. perinatol. pediatr.

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

Abstract: Maternal reinfection by new strains of cytomegalovirus is a major source of congenital infection in this population.

Cited by 181 publications

References 53 publications

Immunobiology of congenital cytomegalovirus infection of the central nervous system—the murine cytomegalovirus model

Immunobiology of congenital cytomegalovirus infection of the central nervous system—the murine cytomegalovirus model

The immunological underpinnings of vaccinations to prevent cytomegalovirus disease

Congenital cytomegalovirus infection: Diagnosis, treatment, and prevention

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