Abnormal Development - Viral Infection

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 ICD-11 KA62 Viral infection in the foetus or newborn
Any condition affecting foetuses or newborns, caused by an infection with a virus.

KA62.0 Congenital Zika virus infection | KA62.1 Congenital Epstein-Barr virus infection | KA62.2 Congenital Varicella Zoster virus infection | KA62.3 Congenital cytomegalovirus infection | KA62.4 Congenital echovirus infection | KA62.5 Congenital enterovirus infection | KA62.6 Congenital human immunodeficiency virus infection | KA62.8 [Congenital rubella syndrome | KA62.9 Congenital viral hepatitis | KA62.A Perinatal Herpes simplex infection See also - Infections of the foetus or newborn

see full table

Introduction

Rubella virions

Below is a list of some known viral infections maternal, embryonic, fetal, and postnatal that impact upon development. Only a very brief overview is given for each virus for more specific details see the listed internal and external links.

Viruses cannot reproduce by themselves and therefore infect cells to use the cell machinery to produce more virus. Different viruses have genetic material as single- or double-stranded RNA or DNA. The infectious virus particle is called a "virion" and is the genetic material packed in a protein shell. Viruses come in many genetic sizes, as little as 4 proteins up to 200 proteins.


Viral infections can range in their effects from no discernable impact through to severe impacts on development. Furthermore this may occur either directly by the infection or indirectly by the associated maternal fever and other side-effects of the infection. (More? hyperthermia)


Rubella virus "German Measles" infection during pregnancy is one of the most serious causing congenital rubella syndrome with serious malformations of the developing fetus.


Viral infections have also recently been in the news with the 2009 novel influenza A (H1N1) "Swine Flu" pandemic.


Some early postnatal viral infections can also impact upon development and have been the target for worldwide immunization and eradication.


Human Immunodeficiency Virus (HIV) leads to AIDS and according to United Nations 2005 data about 38.6 million people had HIV. Of the 17.3 million women infected with HIV, 3.28 million gave birth each year (mostly in sub-Saharan Africa), leading to 700,000 new infections of HIV in children each year.


Note also that many cancers can be caused by viruses (papilloma viruses, hepatitis B and C viruses, Epstein-Barr virus and human T-cell lymphotropic virus). Virus-induced cancers account for about 20% of worldwide cancer incidence. In women, cervical cancer is caused by the human papillomavirus types (HPV16 and HPV18).

In a few developing countries, and mainly in Africa, at least 3 viruses induce a hemorrhagic fever: Ebola hemorrhagic fever, Marburg virus disease, and Lassa fever.


Viral Links: viral infection | TORCH | cytomegalovirus | hepatitis | HIV | parvovirus | polio | rubella virus | chickenpox | Lymphocytic Choriomeningitis Virus | Zika virus | human papillomavirus | rotavirus | vaccination | varicella virus | environment
Historic Embryology - Viral 
1941 Rubella Cataracts | 1944 Rubella Defects


Environmental Links: Introduction | low folic acid | iodine deficiency | Nutrition | Drugs | Australian Drug Categories | USA Drug Categories | thalidomide | herbal drugs | Illegal Drugs | smoking | Fetal Alcohol Syndrome | TORCH | viral infection | bacterial infection | fungal infection | zoonotic infection | toxoplasmosis | Malaria | maternal diabetes | maternal hypertension | maternal hyperthermia | Maternal Inflammation | Maternal Obesity | hypoxia | biological toxins | chemicals | heavy metals | air pollution | radiation | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Fetal Origins Hypothesis

Some Recent Findings

  • The impact of timing of maternal influenza immunization on infant antibody levels at birth[1] "Pregnant women and infants are at an increased risk of severe disease after influenza infection. Maternal immunization is a potent tool to protect both these at-risk groups. While the primary aim of maternal influenza vaccination is to protect the mother, a secondary benefit is the transfer of protective antibodies to the infant. A recent study using the tetanus, diphtheria and acellular pertussis (Tdap) vaccine indicated that children born to mothers immunized in the second trimester of pregnancy had the highest antibody titres compared to children immunized in the third trimester. The aim of the current study was to investigate how the timing of maternal influenza immunization impacts infant antibody levels at birth. Antibody titres were assessed in maternal and cord blood samples by both immunoglobulin (Ig)G-binding enzyme-linked immunosorbent assay (ELISA) and haemagglutination inhibition assay (HAI). Antibody titres to the H1N1 component were significantly higher in infants born to mothers vaccinated in either the second or third trimesters than infants born to unvaccinated mothers. HAI levels in the infant were significantly lower when maternal immunization was performed less than 4 weeks before birth. These studies confirm that immunization during pregnancy increases the antibody titre in infants. Importantly, antibody levels in cord blood were significantly higher when the mother was vaccinated in either trimesters 2 or 3, although titres were significantly lower if the mother was immunized less than 4 weeks before birth. Based on these data, seasonal influenza vaccination should continue to be given in pregnancy as soon as it becomes available."
  • Human papillomavirus infection and intrauterine growth restriction: a data-linkage study[2] "Using unbiased population data, to examine whether having a positive Pap smear, and thus a high probability of Human Papilloma Virus (HPV) infection, is a significant risk factor for intrauterine growth restriction (IUGR) in a subsequent pregnancy. Two independent population-based databases, namely the South Australian Perinatal Statistics Collection and the South Australian Cervical Screening Database, were deidentified and linked by the SANT Datalinkage Service. Analyses were performed on cases where Pap smear screening data was available for up to 2 years prior to a singleton live birth. ...Those having a positive Pap smear were more likely to have a baby with IUGR than those with negative smear results. For SGA, 5.8% babies were from mothers with positive Pap smears compared to 4.0% with negative smears indicating a 40% higher risk of having an SGA baby (95%CI 20-70%) among women with positive Pap smears. For VLBW, 7.6% mothers had positive Pap smears compared with 4.0% with negative smears (p < .001), which reflects a 90% increased risk (95%CI 40-150%). These associations reduced to 20% (95%CI 1-40%) and 50% (95%CI 10-100%) for SGA and VLBW, respectively, after adjusting for all other significant covariates including maternal age, ethnicity, marital status, occupation, smoking, pregnancy history, and maternal health during pregnancy. Mothers with a positive Pap smear have an increased risk of IUGR, especially for VLBW, which is independent of other risk factors. The results confirm previous findings in a small study and emphasise the need to consider the risks of both cancer and IUGR in all HPV vaccination programs."
  • The Association of H1N1 Pandemic Influenza with Congenital Anomaly Prevalence in Europe[3] "In the context of the European Surveillance of Congenital Anomalies (EUROCAT) surveillance response to the 2009 influenza pandemic, we sought to establish whether there was a detectable increase of congenital anomaly prevalence among pregnancies exposed to influenza seasons in general, and whether any increase was greater during the 2009 pandemic than during other seasons. We performed an ecologic time series analysis based on 26,967 pregnancies with nonchromosomal congenital anomaly conceived from January 2007 to March 2011, reported by 15 EUROCAT registries. Analysis was performed for EUROCAT-defined anomaly subgroups, divided by whether there was a prior hypothesis of association with influenza. Influenza season exposure was based on World Health Organization data. Prevalence rate ratios were calculated comparing pregnancies exposed to influenza season during the congenital anomaly-specific critical period for embryo-fetal development to nonexposed pregnancies. Our data do not suggest an overall association of pandemic or seasonal influenza with congenital anomaly prevalence. One interpretation is that apparent influenza effects found in previous individual-based studies were confounded by or interacting with other risk factors. The associations of heart anomalies with pandemic influenza could be strain specific."
  • Influenza A/H1N1 MF59 adjuvanted vaccine in pregnant women and adverse perinatal outcomes: multicentre study[3] "This large study using primary data collection found that MF59 adjuvanted A/H1N1 influenza vaccine did not result in an increased risk of adverse perinatal events and suggested a lower risk among vaccinated women. These findings should contribute to inform stakeholders and decision makers on the prescription of vaccination against influenza A/H1N1 in pregnant women."
More recent papers  
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This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.

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  • The displayed list of references do not reflect any editorial selection of material based on content or relevance.
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References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

More? References | Discussion Page | Journal Searches | 2019 References

Search term: Abnormal Development Viral Infection

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Update on childhood and adolescent immunizations: selected review of US recommendations and literature: part 2[4] "Vaccine coverage is relatively static or improving for the vaccines included in the 2010 annual harmonized immunization schedules. Providers should be reviewing patients' immunization records at each visit to take advantage of any opportunity to administer indicated, age-appropriate vaccines. There have been infectious disease outbreaks among highly immunized populations, although unvaccinated or undervaccinated individuals continue to play large roles in the spread of disease. Infants, many of whom are too young to be vaccinated, continue to bear a large disease burden, which underscores the importance of cocooning and, in some cases, vaccination of pregnant women. Influenza, measles, mumps, and rubella, varicella, hepatitis A, meningococcal conjugate, human papillomavirus, diphtheria and tetanus toxoids and acellular pertussis, and tetanus and diphtheria toxoids and acellular pertussis vaccines are reviewed in this second of two articles."
  • Fetal varicella - diagnosis, management, and outcome[5] "Fetal varicella syndrome (FVS) is due to transplacental infection by the Varicella zoster virus following maternal infection. The risks for the fetus and neonate depend on the timing. When varicella occurs around delivery, it often leads to disseminated neonatal varicella. When varicella occurs during pregnancy, transmission can occur, but is usually asymptomatic; some infants develop zoster postnatally and a few have FVS. Before 20 weeks' gestation, FVS can occur, with an incidence of about 1%. The lesions can affect the skin, limbs, central and autonomous nervous systems, eyes, cause calcifications, and growth retardation; mortality is high. Lesions typically follow one or several nerve territories, suggesting that damage results from in utero zoster following primary fetal infection."
  • ViralZone: a knowledge resource to understand virus diversity[6] "The molecular diversity of viruses complicates the interpretation of viral genomic and proteomic data. To make sense of viral gene functions, investigators must be familiar with the virus host range, replication cycle and virion structure. Our aim is to provide a comprehensive resource bridging together textbook knowledge with genomic and proteomic sequences. ViralZone web resource (www.expasy.org/viralzone/) provides fact sheets on all known virus families/genera with easy access to sequence data."
  • False-Positive Human Immunodeficiency Virus Enzyme Immunoassay Results in Pregnant Women [7] "False-positive HIV EIA results were rare and occurred less frequently among pregnant women than others."


  • Mother to child transmission of HIV among Zimbabwean women who seroconverted postnatally: prospective cohort study [8] "Breastfeeding associated transmission is high during primary maternal HIV infection and is mirrored by a high but transient peak in breast milk HIV load. Around two thirds of breastfeeding associated transmission by women who seroconvert postnatally may occur while the mother is still in the “window period” of an antibody based test, when she would test HIV negative using one of these tests."
  • Transplacental transmission of Human Papillomavirus.[9] "In conclusion the study suggests placental infection in 23.3% of the cases studied and transplacental transmission in 12.2%. It is suggested that in future HPV DNA be researched in the normal endometrium of women of reproductive age. The possible consequence of fetal exposure to HPV should be observed."
  • Infectious causes of stillbirth: a clinical perspective.[10]"In developed countries, up to 24% of stillbirths have been attributed to infection, although with increased availability of sophisticated diagnostics and rigorous screening, it appears likely that higher numbers may actually be associated with infection. In developed countries, ascending bacterial infection is usually the most common infectious cause of stillbirth, with a number of viral infections also an important factor. Screening, prevention, and treatment of maternal infections are important to reduce stillbirth risk."

International Classification of Diseases

 ICD-11 KA62 Viral infection in the foetus or newborn
Any condition affecting foetuses or newborns, caused by an infection with a virus.
  • KA62.0 Congenital Zika virus infection
  • KA62.1 Congenital Epstein-Barr virus infection - There are several forms of Epstein–Barr virus infection. Infectious mononucleosis, nasopharyngeal carcinoma, and Burkitt's lymphoma can all be caused by the Epstein–Barr virus.
  • KA62.2 Congenital Varicella Zoster virus infection - Transplacentally acquired Varicella zoster virus infection. Both the gestational age at the time of maternal infection and the time interval between maternal infection and birth have major influences on the clinical course.
  • KA62.3 Congenital cytomegalovirus infection - A condition affecting neonates, caused by an infection with cytomegalovirus in utero. This condition is characterized by jaundice, low birth weight, splenomegaly, hepatomegaly, or pneumonia if symptoms develop shortly after birth, or may be asymptomatic. This condition commonly present later in life with loss of hearing, loss of vision, or developmental disabilities. Transmission is by vertical transmission. Confirmation is by detection of cytomegalovirus in neonatal urine, saliva, blood, or other body tissues within 2-3 weeks of birth.
  • KA62.4 Congenital echovirus infection - A disease affecting neonates, caused by an infection with enteric cytopathic human orphan (ECHO) virus in utero. This disease presents with various symptoms depending on the site of the infection, or may be asymptomatic. Transmission is by vertical transmission. Confirmation is by identification of ECHO virus in the neonate.
  • KA62.5 Congenital enterovirus infection - Congenital viral infections with enteroviruses (including coxsackie viruses and ECHO viruses) is an infectious embriofetopathy that have been reported to cause fetal malformations, acute systemic illness in the newborn and long-term neurodevelopmental abnormalities.
  • KA62.6 Congenital human immunodeficiency virus infection - A disease affecting neonates, caused by an infection with human immunodeficiency virus in utero. Transmission is by vertical transmission. Confirmation is by identification of human immunodeficiency virus in the neonate.
  • KA62.7 Congenital parvovirus syndrome - Fetal parvovirus syndrome is a fetopathy likely to occur when a pregnant woman is infected by parvovirus B19. Fetal parvovirus infection results in aplastic crisis. Anaemia induces a risk of hydrops and fetal death by cardiac failure in 10 to 20% of cases.
  • KA62.8 Congenital rubella syndrome - A disease caused by an infection with the rubella virus in utero. This disease presents with symptoms depending on the timing of infection of the fetus and may present with birth defects (such as hearing loss), or intrauterine growth retardation. Transmission is by vertical transmission. Confirmation is by identification of rubella virus or detection of anti-rubella virus IgM antibodies in the neonate or infant.
  • KA62.9 Congenital viral hepatitis - A disease of the liver affecting the neonate, caused by an infection with either hepatitis A, B, C, D, or E virus in utero. This disease is characterized by lethargy, jaundice, abdominal distention, failure to thrive, or clay coloured stools. Transmission is by vertical transmission. Confirmation is by identification of the hepatitis A, B, C, D, or E virus in a blood sample from the neonate.
  • KA62.A Perinatal Herpes simplex infection - Herpes simplex infection acquired during the perinatal period, normally from active herpes infection of the mother's genital tract, but may also be transmitted in utero.
viral infection | environmental abnormalities |  ICD-11 | Infections of the foetus or newborn
International Classification of Diseases - Viral infection 
 ICD-11 KA62 Viral infection in the foetus or newborn
Any condition affecting foetuses or newborns, caused by an infection with a virus.
  • KA62.0 Congenital Zika virus infection
  • KA62.1 Congenital Epstein-Barr virus infection - There are several forms of Epstein–Barr virus infection. Infectious mononucleosis, nasopharyngeal carcinoma, and Burkitt's lymphoma can all be caused by the Epstein–Barr virus.
  • KA62.2 Congenital Varicella Zoster virus infection - Transplacentally acquired Varicella zoster virus infection. Both the gestational age at the time of maternal infection and the time interval between maternal infection and birth have major influences on the clinical course.
  • KA62.3 Congenital cytomegalovirus infection - A condition affecting neonates, caused by an infection with cytomegalovirus in utero. This condition is characterized by jaundice, low birth weight, splenomegaly, hepatomegaly, or pneumonia if symptoms develop shortly after birth, or may be asymptomatic. This condition commonly present later in life with loss of hearing, loss of vision, or developmental disabilities. Transmission is by vertical transmission. Confirmation is by detection of cytomegalovirus in neonatal urine, saliva, blood, or other body tissues within 2-3 weeks of birth.
  • KA62.4 Congenital echovirus infection - A disease affecting neonates, caused by an infection with enteric cytopathic human orphan (ECHO) virus in utero. This disease presents with various symptoms depending on the site of the infection, or may be asymptomatic. Transmission is by vertical transmission. Confirmation is by identification of ECHO virus in the neonate.
  • KA62.5 Congenital enterovirus infection - Congenital viral infections with enteroviruses (including coxsackie viruses and ECHO viruses) is an infectious embriofetopathy that have been reported to cause fetal malformations, acute systemic illness in the newborn and long-term neurodevelopmental abnormalities.
  • KA62.6 Congenital human immunodeficiency virus infection - A disease affecting neonates, caused by an infection with human immunodeficiency virus in utero. Transmission is by vertical transmission. Confirmation is by identification of human immunodeficiency virus in the neonate.
  • KA62.7 Congenital parvovirus syndrome - Fetal parvovirus syndrome is a fetopathy likely to occur when a pregnant woman is infected by parvovirus B19. Fetal parvovirus infection results in aplastic crisis. Anaemia induces a risk of hydrops and fetal death by cardiac failure in 10 to 20% of cases.
  • KA62.8 Congenital rubella syndrome - A disease caused by an infection with the rubella virus in utero. This disease presents with symptoms depending on the timing of infection of the fetus and may present with birth defects (such as hearing loss), or intrauterine growth retardation. Transmission is by vertical transmission. Confirmation is by identification of rubella virus or detection of anti-rubella virus IgM antibodies in the neonate or infant.
  • KA62.9 Congenital viral hepatitis - A disease of the liver affecting the neonate, caused by an infection with either hepatitis A, B, C, D, or E virus in utero. This disease is characterized by lethargy, jaundice, abdominal distention, failure to thrive, or clay coloured stools. Transmission is by vertical transmission. Confirmation is by identification of the hepatitis A, B, C, D, or E virus in a blood sample from the neonate.
  • KA62.A Perinatal Herpes simplex infection - Herpes simplex infection acquired during the perinatal period, normally from active herpes infection of the mother's genital tract, but may also be transmitted in utero.
viral infection | environmental abnormalities |  ICD-11 | Infections of the foetus or newborn

Rubella Virus

Rubella Virus visions budding from the host cell surface (Image: CDC USA)

Rubella virus (Latin, rubella = little red), also known as "German Measles" (due to early citation in German medical literature).

Infection during pregnancy can cause congenital rubella syndrome (CRS) with serious malformations of the developing fetus. The type and degree of abnormality relates to the time of maternal infection.


Links: rubella virus

Cytomegalovirus

Cytomegalovirus.jpg

Immunoflourescent detection of Cytomegalovirus

(Image: CDC USA)

Viral infection causes systemic infection and extensive brain damage and cell death by necrosis. Cytomegalovirus infection can also occur in the human placenta.[11]
Links: Cytomegalovirus | Medical Microbiology- Cytomegalovirus | Search Medical Microbiology "Cytomegalovirus"

Hendra Virus

Australia map - hendra virus outbreaks.jpg

Australia map - hendra virus outbreaks (1994-2008)

Hendra virus is a paramyxoviridae (ssRNA negative-strand virus) that mainly infects large fruit bats (flying foxes) which can be passed on to horses. The infection has occasionally been passed onto people who have been in close contact with an infected horse. There is evidence of fetal and placental infection in flying fox[12] and animal models.[13] There is currently insufficient information to determine whether there are developmental effects in humans.

Named after the Brisbane suburb where in 1994 the first outbreak was detected. Recently a vaccine for horses has been developed.


Links: NSW Public Health Sheet 2011 | Viralzone - Paramyxoviridae | Genome

Herpes Simplex Virus

Herpes virus.jpg

Herpes Virus, transmission electron micrograph

(Image: CDC USA)

Viral herpes simplex infection can cause a systemic infection and extensive brain damage and cell death by necrosis.

There is also some evidence which suggests that fetal exposure to herpesvirus infection is associated with pregnancy-induced hypertensive disorders and preterm birth.

NCBI Bookshelf (external link) Search Medical Microbiology "Herpes Simplex Virus"

Search PubMed: term = Herpes Simplex Virus teratology | embryo infection | fetal infection | neonatal infection

Human Papillomavirus

Human papilloma virus.jpg

Human papillomavirus

(HPV) A group of more that 118 identified viral strains about 40 infect the genital tract and 12 are known to be cancer-causing. Just eight HPV types 16, 18, 45, 33, 31, 52, 58, and 35 in descending order of frequency are responsible for more than 90 percent of cervical cancer cases. (Lancet 2010)

Infection can be detected by pap smear and at least 2 available vaccines, Cervarix (GSK) and Gardasil (Merck). Gardasil protects against HPV types 16 and 18, which cause 70% of cervical cancers in women and 90% of all HPV-related cancers in men. Also against two low-risk HPV types (types 6 and 11), which cause 90% of genital warts. through cross-protection also partially against HPV types 31 and 45.

Cervical Screening Program - HPV Vaccination Program 
National Cervical Screening Program

Clinical term for the detection of DNA from specific strains of human papillomavirus (HPV) from cervical samples. In Australia, this test will replace the "Pap Smear" test that identified pathological cells. Specific types of HPV infections are known precursors of cervical cancer and are also being preventively treated by the HPV vaccine. (More? Cervical Screening Program | human papillomavirus | National Cervical Screening Program The National HPV Vaccination Program is for girls and boys aged 12 to 13 years.

HPV Vaccination Program

In Australia, the National HPV Vaccination Program is for girls and boys aged 12 to 13 years. (More? HPV vaccine)

ICD-11 Cervical Cancer 
 ICD-11 2C77 Malignant neoplasms of cervix uteri - Primary or metastatic malignant neoplasm involving the cervix.
  • 2C77.0 Squamous cell carcinoma of cervix uteri - A squamous cell carcinoma arising from the cervical epithelium. It usually evolves from a precancerous cervical lesion. Increased numbers of sexual partners and human papillomavirus (HPV) infection are risk factors for cervical squamous cell carcinoma. The following histologic patterns have been described: Conventional squamous cell carcinoma, papillary squamous cell carcinoma, transitional cell carcinoma, lymphoepithelioma-like carcinoma, verrucous carcinoma, condylomatous carcinoma and spindle cell carcinoma. Survival is most closely related to the stage of disease at the time of diagnosis.
  • 2C77.1 Adenocarcinoma of cervix uteri - An adenocarcinoma arising from the cervical epithelium. It accounts for approximately 15% of invasive cervical carcinomas. Increased numbers of sexual partners and human papillomavirus (HPV) infection are risk factors. Grossly, advanced cervical adenocarcinoma may present as an exophytic mass, an ulcerated lesion, or diffuse cervical enlargement. Microscopically, the majority of cervical adenocarcinomas are of the endocervical (mucinous) type.
  • 2C77.2 Adenosquamous carcinoma of cervix uteri
  • 2C77.3 Neuroendocrine carcinoma of cervix uteri
Links: cervical cancer | human papillomavirus | viral infection | uterus
Links: human papillomavirus | cervical cancer | CDC STD Facts - Human papillomavirus | Medline Plus Human Papillomavirus | Cervical Screening Program)

Polio Virus

WHO - Polio Eradication Initiative

Poliomyelitis (polio) is a highly infectious viral disease, affecting only humans of any age, but mainly children under the age of 3 (> 50% cases) causing paralysis and death. There are three types (type 1, type 2, and type 3) of wild poliovirus which can invade the nervous system and can cause total paralysis in several hours. Polio cases have decreased by more than 99% since 1988.

  • 1988 - estimated 350,000 cases in more than 125 endemic countries
  • 2006 - 1997 reported cases
  • 2008 - only parts of four countries in the world remain endemic for the disease

A bivalent oral polio vaccine (BOPV) is presently being used in countries with high existing polio rates, India and Nigeria. A recent WHO release has shown the largest ever year-to-year drop in polio cases following the use of BOPV:

  • Nigeria - has seen a 98% drop in polio cases (2009 over 400 cases to 2010 just 9 so far)
  • India - has seen a 90% drop during the same period.


Links: Abnormal Development - Polio Virus | Polio Eradication Initiative | WHO - Africa seizes chance against polio

Human Immunodeficiency Virus

Human immunodeficiency virus.jpg

Human Immunodeficiency Virus, transmission electron micrograph (Image: CDC USA)

The human immunodeficiency virus (HIV) is a retrovirus that causes Acquired Immunodeficiency Syndrome (AIDS). Maternal transmission of HIV can occur perinatally in utero, during labour and delivery, or postnatally through breastfeeding and can be reduced by the use of antiretroviral treatment and avoidance of breastfeeding.

Neonatal infection diagnosis can be made by PCR from 6-12 week.

UNAIDS, the Joint United Nations Programme on HIV/AIDS, estimated that 38.6 million people had HIV (2005), 17.3 million were women. About 3.28 million pregnant women infected with HIV give birth each year (the majority in sub-Saharan Africa) leading to 700,000 new infections of HIV in children each year. (text modified from Gray and McIntyre, BMJ 2007;334:950-953)


Links: Human Immunodeficiency Virus

Hepatitis Virus

Hepatitis A virions (CDC)
Hepatitis B virions (CDC)

Hepatitis (inflammation of the liver) is caused in humans by one of 7 viruses (A, B, C, D, E) with the 2 additional F has not been confirmed as a distinct genotype; and G is a newly described flavivirus.

"All of these viruses can cause an acute disease with symptoms lasting several weeks including yellowing of the skin and eyes (jaundice); dark urine; extreme fatigue; nausea; vomiting and abdominal pain. It can take several months to a year to feel fit again." (CDC text).

Virus particles measure 42nm in overall diameter and contain a 27nm diameter DNA-based core.

Hepatitis Transmission Risk to the Fetus

Hepatitis A

  • Fetal transmission of virus occurs with extreme rarity.

Hepatitis B

  • Can occur as a consequence of intrapartum exposure, transplacental transmission, and breastfeeding.
  • 20% - 30% of HBsAg-positive/HbeAg-negative women will transmit virus to their infants.
  • 90% of HBsAg- and HBeAg-positive women will transmit virus to their infants.
  • Immunoprophylaxis at birth with both HBIG and Hepatitis B vaccine within 12 hours of birth decreases the risk of transmission.
  • Passive (HBIG) and active immunization is 85-95% effective in preventing neonatal HBV infection.

Hepatitis C

  • The overall risk of transmission is approximately 2-6% with unknown maternal viral titers.
  • All pregnant women with HCV should have viral titers performed.
  • The placenta appears to act as an immunological organ providing antiviral protection against hepatitis C viral transmission in the majority of cases.[14]

Data Sources[15][16][17]


Hepatitis E virus.jpg

Hepatitis E virions (CDC)

Search PubMed: term = Hepatitis Virus teratology | embryo infection | fetal infection | neonatal infection

Influenza Virus

1918 Influenza virus virions EM (CDC)

Flu is the general term and abbreviation of influenzaviral infections and the possible teratogenic effect of influenza viruses (orthomyxoviruses, "flu") is unclear, with very little evidence directly linking the two events. A relatively recent study was unable to identify any placental transmission of influenza virus during the second and third trimester. Severe maternal infection though may lead to hyperthermia, which has been demonstrated to be teratogenic, particularly in early neural development. (More? [hyperthermia.htm Maternal Hyperthermia])

Influenza virus infection in the second and third trimesters of pregnancy: a clinical and seroepidemiological study.[18] "We found no evidence for transplacental transmission of influenza virus or auto-antibody production in pregnancies complicated by influenza infections. There was an increase in the complications of pregnancy in our influenza cohort."

Postnatally, the suggested initial limited neonatal immune system makes postnatal infection dangerous.

See also: Transmission of influenza A in human beings.[19]

Links: Medline Plus - Flu | Search Medical Microbiology "orthomyxovirus"

Measles

Measles virus

Measles (rubeola) is a paramyxovirus appearing mainly as a respiratory viral infection, clinically different from Rubella. A single-stranded RNA virus which is highly contagious. Before measles vaccination (USA 1963) more than 90% of children had an infection before puberty and in developing countries it is still a common and often fatal childhood disease. Childhood immunisation and immunity persists in only about 80% of adults.

Pregnancy effects of measles results in a higher risk of premature labor, spontaneous abortion, low-birth-weight, and possibly rare cases of birth defects with no definable pattern of malformation.[20]

In terms of the immune response to post-natal infection, a monkey model has shown that the virus is initially regulated by T cells, but require an antibody response to eliminate the viral RNA.[21]


Links: Abnormal Development - Measles Virus

Rotavirus

Rotavirus (CDC)

A type of virus that is a common cause of diarrhoea and vomiting (viral gastroenteritis) in infants and young children. The live attenuated rotavirus vaccine is contraindicated in pregnancy, but can be safely administered to household contacts of pregnant women. There is only a very small risk of transmission of the rotavirus vaccine virus to a susceptible pregnant woman and there is no evidence of risk to the fetus if pregnant women are in contact with recently vaccinated individuals.

  • Non-enveloped, icosahedral virus of the Reoviridae family containing a genome of 11 segments of double stranded RNA (dsRNA).
  • Divided into seven serotypes (Rotavirus A–G).

(data based on: The Australian Immunisation Handbook 9th Edition 2008 2.3.2 Vaccination of women planning pregnancy, pregnant or breastfeeding women, and preterm infants - updated July 2009 )


Links: Abnormal Development - Rotavirus | Postnatal - Vaccination | The Australian Immunisation Handbook 9th Edition 2008 | Australian Immunisation Handbook - Rotavirus | 2.3.2 Vaccination of women planning pregnancy, pregnant or breastfeeding women, and preterm infants - updated July 2009 | Medical Microbiology - Rotaviruses

Varicella Zoster Virus (chickenpox)

Varicella zoster virus (CDC)

Fetal varicella syndrome (FVS) is caused by transplacental infection by the varicella zoster (chickenpox) virus following maternal infection.

Fetal and neonatal risks are dependent on infection timing.

  • before 20 weeks (GA) - FVS can occur with an incidence of about 1%. The lesions can affect the skin, limbs, central and autonomous nervous systems, eyes, cause calcifications, and growth retardation; mortality is high. Lesions typically follow one or several nerve territories, suggesting that damage results from in utero zoster following primary fetal infection.
  • during pregnancy - transmission can occur, but is usually asymptomatic; some infants develop zoster postnatally and a few have FVS.
  • around delivery - often leads to disseminated neonatal varicella.


Links: Abnormal Development - Varicella Zoster Virus

Swine Influenza Virus

Swine Influenza Virus (CDC)

In 2009 a global pandemic of the novel influenza A (H1N1) or Swine Flu has occurred. At this stage the possible teratogenic effect of this influenza virus should be considered the same as those described for the influenza virus above. The term "Pandemic" refers only to the spread of the virus, not the severity of the infection or potential developmental outcomes. This virus has also been spreading in an unseasonable pattern, that is in the northern hemisphere summer, when typically viral infections increase in the winter period.

H1 refers to one of the hemagglutinin subtypes (H1, H2 or H3) and N1 refers to one of the two neuraminidase subtypes (N1 or N2). Over the last century there have been at least three different human viral pandemic circulating strains H1N1 (1918, 1977), H2N2 (1957) and H3N2 (1968).

A study of the perinatal outcomes after maternal 2009/H1N1 infection: national cohort study.[22]

"Perinatal mortality was higher in infants born to infected women (10 deaths among 256 infants; rate 39 (95% confidence interval 19 to 71) per 1000 total births) than in infants of uninfected women (9 deaths among 1233 infants; rate 7 (3 to 13) per 1000 total births) (P < 0.001). This was principally explained by an increase in the rate of stillbirth (27 per 1000 total births v 6 per 1000 total births; P = 0.001). Infants of infected women were also more likely to be born prematurely than were infants of comparison women (adjusted odds ratio 4.0, 95% confidence interval 2.7 to 5.9). Infected women who delivered preterm were more likely to be infected in their third trimester (P = 0.046), to have been admitted to an intensive care unit (P < 0.001), and to have a secondary pneumonia (P = 0.001) than were those who delivered at term."


Region Number of Confirmed Cases(10 July 2009 based upon online data) Number of Confirmed Deaths
USA 37,246 211
Mexico 11,699 121
Canada 9,717 39
UK 9,718 14
Europe 13,667 16

(Table data source: BMJ 2009;339:b2840)

Confirmed infections per million population (July 2009)

  • Australia and New Zealand - 462
  • Britain - 158
  • USA - 118

Australia - H1N1 Influenza 09 (Human Swin Flu) Facts

  • Incubation period: maximum = 7 days (3 days would be more common)
  • Period of communicability: from 24 hours prior to the onset of symptoms until:
    • adults 12-64 yrs = 7 days
    • adults >65 yrs = 14 days
    • children <12 yrs = 14 days (or until resolution of fever, whichever is longer)
  • Means of virus transmission: most likely to be spread from person-to-person by inhalation of infectious droplets produced while talking, coughing and sneezing; transmission may also occur through direct and indirect (fomite) contact.

Australian State Information

(Facts from: Australian Commonwealth Department of Health and Ageing H1N1 Influenza 09 (Human Swine influenza) – Summary Sheet for General Practitioners Current as of 24 May 2009)

UK Information

20 July 2009: Chief Medical Officer's advice to pregnant women"Some pregnant women who catch the H1N1 (swine) ‘flu virus will develop complications of the infection (including pneumonia) that could put their own and their baby’s health at risk. The risks are greatest in the second and third trimesters of pregnancy. It is too early in the pandemic of influenza to be able to quantify these risks for the individual but most pregnant women who catch the disease are likely to make an uncomplicated recovery...."

Links: WHO - H1N1 Pandemic | USA CDC - H1N1 Flu | Medline Plus - H1N1 Flu (Swine Flu) | GenBank sequences from pandemic (H1N1) 2009 viruses

Avian Influenza Virus

Avian influenza virion.jpgAvian Influenza virion (Image: CDC USA)
In 1997 the first instance of direct bird-to-human spread of influenza A (H5N1) virus was documented during an outbreak of avian influenza among poultry in Hong Kong.

The virus caused severe respiratory illness in 18 people (6 died) and there have been subsequent instances of other H5N1 infection. The virus does not typically infect humans, and there is no evidence yet of a direct effect on development.

Lassa Virus

Lassa virus.jpgLassa virions (Image: CDC USA)
Lassa virus (LASV) of the arenaviridae family, a single-stranded RNA virus (see review[23]). First isolated in 1969 from a missionary nurse who worked in a clinic the small town of Lassa, Nigeria. The virus is the causative agent of a hemorrhagic fever and can be transmitted between species (zoonotic). Death rates are high for women in the third trimester of pregnancy. Fetal death (95%) occurs in uterus of infected pregnant mothers.


Links: Lassa Virus

Ebola Virus

Ebola virus disease (EVD, Ebola hemorrhagic fever, or EHF) is caused by three of the four species of “Ebola-like viruses” that appear to be maintained in a natural reservoir in the rain forests of Africa.


Ljungan virus

Zoonotic Ljungan virus associated with central nervous system malformations in terminated pregnancy.[24]

"LV was diagnosed in 9 of 10 cases with hydrocephalus and in 1 of 18 trisomy 21 controls by immunohistochemistry. Five of nine cases with anencephaly had a positive PCR result, whereas none of the 12 trisomy 21 available for PCR testing had a positive result. The 47 newborn mice exposed to LV all developed encephalitis, with eight having hydrocephalus. None of the 52 control animals had encephalitis or hydrocephalus."

Adenovirus

Adenovirus (CDC)

1953 - Human adenovirus was first isolated. This virus family is the causative agent of membrane infections in: respiratory tract, eyes, gastrointestinal tract, and urinary tract.

  • Adenovirus spherical virons are 70 - 90 nm in diameter.
  • Adenoviruses have a double-stranded linear DNA structure.
  • There are about 51 antigenically unique serotypes (species) grouped into six subgenera (A - F).


Modified adenovirus is currently used as a research tool to introduce genes into cells in vitro and in animal systems.[25]


Links: Medical Microbiology - Adenoviruses | Search Medical Microbiology "adenovirus"

Coxsackie

Coxsackie B4 virus.jpg Coxsackie B virus are 6 pathogenic enteroviruses with a range of adult illness from mild gastrointestinal to pericarditis and myocarditis. These viruses may cause an increase in early spontaneous abortions and rarely a fetal myocarditis.

Echoviruses

Echoviruses are RNA viruses found in the gastrointestinal tract that belongs to the genus Enterovirus of the Picornaviridae family. These viruses do not seem to damage the fetus.

Mumps

File:Mumps virus virion (CDC)
Mumps (epidemic parotitis) is a viral inflammation of the parotid glands, which are the major salivary glands in humans. This viral infection may cause increased early and late fetal death and neonatal mumps. Note that parotid inflammation can also occur during bacterial infections.

Marburg Virus

Marburg virus.jpgMarburg virions (Image: CDC USA)
Marburg RNA virus of the filovirus family, causes hemorrhagic fever in both humans and non-human primates and is a very rare. Virus has characteristic "Shepherd’s Crook" shape.

West Nile Virus

West Nile virus EM01.jpg

West Nile virus (WNV) activity reported by state, United States, 2012 (as of September 11, 2012)

"Since 1999, more than 30,000 people in the United States have been reported as getting sick with West Nile virus. Infected mosquitoes spread West Nile virus (WNV) that can cause serious, life altering disease."[26]

A 2006 study of 72 infected infants (2003 and 2004) "almost all seemed normal, and none had conclusive laboratory evidence of congenital WNV infection. ...Three infants had WNV infection that could have been congenitally acquired, seven infants had major malformations, but only 3 of these had defects that could have been caused by maternal WNV infection based on the timing of the infections and the sensitive developmental period for the specific malformations, and none had any conclusive evidence of WNV etiology."[27]


West Nile Links: Viral Infection | Zoonotic Infection | West Nile Virus

Zika Virus

Zika virus TEM02.jpg Zika virus (ZIKV) is a mosquito-borne flavivirus related to dengue virus first isolated from a rhesus monkey in Zika forest, Uganda (1947). Transmitted by mosquitoes (Aedes aegypti) it was then identified in humans in Nigeria in 1954 and subsequently in South America, Asia and Pacific regions. More recently in Australia from returning travellers.[28]

Virus particles are 40 nm in diameter, with an outer envelope, and an inner dense core. ZIKV is an RNA virus containing 10,794 nucleotides encoding 3,419 amino acids.[29]

Mosquito bites lead to an initial infection of skin cells.[30] The virus may also be transmitted transplacentally or during delivery.[31] Some limited evidence, from Brazil, for association with microcephaly.

Mosquito lifecycle Zika virus world map
Mosquito lifecycle Zika virus world map (CDC 2016)


Links: Abnormal Development - Zika Virus | Image - unlabelled virus EM | Image - labelled virus EM |WHO | PMID 26689277 | NCBI Taxonomy | Zika Genome

Prevention

Australia

The Australian Immunisation Handbook 10th edition (2015) Canberra: Australian Government Department of Health. ISBN: 978-1-74241-861-2 Online ISBN: 978-1-74241-862-9.

USA

CDC cover your cough.gif For some viral infections there are antiviral medicines and immunizations (vaccines), others have no current direct protection.

In general the following public health advice is given in preventing the spread of viruses:

  • Cover your nose and mouth with a tissue when you cough or sneeze and discard after you use it.
  • Wash your hands often with soap and water, or use alcohol-based hand cleaners, after you cough or sneeze.
  • Avoid touching your eyes, nose or mouth.
  • Avoid close contact with sick people.
  • Stay home from work or school if you are sick.


References

  1. Zhong Z, Haltalli M, Holder B, Rice T, Donaldson B, O'Driscoll M, Le-Doare K, Kampmann B & Tregoning JS. (2019). The impact of timing of maternal influenza immunization on infant antibody levels at birth. Clin. Exp. Immunol. , 195, 139-152. PMID: 30422307 DOI.
  2. Ford JH, Li M, Scheil W & Roder D. (2019). Human papillomavirus infection and intrauterine growth restriction: a data-linkage study. J. Matern. Fetal. Neonatal. Med. , 32, 279-285. PMID: 28889772 DOI.
  3. 3.0 3.1 Rubinstein F, Micone P, Bonotti A, Wainer V, Schwarcz A, Augustovski F, Pichon Riviere A & Karolinski A. (2013). Influenza A/H1N1 MF59 adjuvanted vaccine in pregnant women and adverse perinatal outcomes: multicentre study. BMJ , 346, f393. PMID: 23381200
  4. Lai J, Fay KE & Bocchini JA. (2011). Update on childhood and adolescent immunizations: selected review of US recommendations and literature: part 2. Curr. Opin. Pediatr. , 23, 470-81. PMID: 21743328 DOI.
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  7. False-Positive Human Immunodeficiency Virus Enzyme Immunoassay Results in Pregnant Women PMC3029371
  8. BMJ 2010; 341:c6580
  9. Rombaldi RL, Serafini EP, Mandelli J, Zimmermann E & Losquiavo KP. (2008). Transplacental transmission of Human Papillomavirus. Virol. J. , 5, 106. PMID: 18817577 DOI.
  10. McClure EM, Dudley DJ, Reddy UM & Goldenberg RL. (2010). Infectious causes of stillbirth: a clinical perspective. Clin Obstet Gynecol , 53, 635-45. PMID: 20661048 DOI.
  11. Pereira L & Maidji E. (2008). Cytomegalovirus infection in the human placenta: maternal immunity and developmentally regulated receptors on trophoblasts converge. Curr. Top. Microbiol. Immunol. , 325, 383-95. PMID: 18637517
  12. Plowright RK, Field HE, Smith C, Divljan A, Palmer C, Tabor G, Daszak P & Foley JE. (2008). Reproduction and nutritional stress are risk factors for Hendra virus infection in little red flying foxes (Pteropus scapulatus). Proc. Biol. Sci. , 275, 861-9. PMID: 18198149 DOI.
  13. Williamson MM, Hooper PT, Selleck PW, Westbury HA & Slocombe RF. (2000). Experimental hendra virus infectionin pregnant guinea-pigs and fruit Bats (Pteropus poliocephalus). J. Comp. Pathol. , 122, 201-7. PMID: 10684689 DOI.
  14. Hurtado CW, Golden-Mason L, Brocato M, Krull M, Narkewicz MR & Rosen HR. (2010). Innate immune function in placenta and cord blood of hepatitis C--seropositive mother-infant dyads. PLoS ONE , 5, e12232. PMID: 20814429 DOI.
  15. Practice Committee of American Society for Reproductive Medicine. (2008). Hepatitis and reproduction. Fertil. Steril. , 90, S226-35. PMID: 19007636 DOI.
  16. Ornoy A & Tenenbaum A. (2006). Pregnancy outcome following infections by coxsackie, echo, measles, mumps, hepatitis, polio and encephalitis viruses. Reprod. Toxicol. , 21, 446-57. PMID: 16480851 DOI.
  17. Lee C, Gong Y, Brok J, Boxall EH & Gluud C. (2006). Effect of hepatitis B immunisation in newborn infants of mothers positive for hepatitis B surface antigen: systematic review and meta-analysis. BMJ , 332, 328-36. PMID: 16443611 DOI.
  18. Irving WL, James DK, Stephenson T, Laing P, Jameson C, Oxford JS, Chakraverty P, Brown DW, Boon AC & Zambon MC. (2000). Influenza virus infection in the second and third trimesters of pregnancy: a clinical and seroepidemiological study. BJOG , 107, 1282-9. PMID: 11028582
  19. Brankston G, Gitterman L, Hirji Z, Lemieux C & Gardam M. (2007). Transmission of influenza A in human beings. Lancet Infect Dis , 7, 257-65. PMID: 17376383 DOI.
  20. Chiba ME, Saito M, Suzuki N, Honda Y & Yaegashi N. (2003). Measles infection in pregnancy. J. Infect. , 47, 40-4. PMID: 12850161
  21. Lin WH, Kouyos RD, Adams RJ, Grenfell BT & Griffin DE. (2012). Prolonged persistence of measles virus RNA is characteristic of primary infection dynamics. Proc. Natl. Acad. Sci. U.S.A. , 109, 14989-94. PMID: 22872860 DOI.
  22. . (). . , , . PMID: 221672992
  23. Yun NE & Walker DH. (2012). Pathogenesis of Lassa fever. Viruses , 4, 2031-48. PMID: 23202452 DOI.
  24. Niklasson B, Samsioe A, Papadogiannakis N, Gustafsson S & Klitz W. (2009). Zoonotic Ljungan virus associated with central nervous system malformations in terminated pregnancy. Birth Defects Res. Part A Clin. Mol. Teratol. , 85, 542-5. PMID: 19180651 DOI.
  25. Gordon JW. (2002). Adenovirus gene transfer vector toxicity to mouse embryos: implications for human IVF. Hum. Reprod. , 17, 2380-7. PMID: 12202428
  26. Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector-Borne Diseases (DVBD)West Nile information page viewed 11 September, 2012.
  27. O'Leary DR, Kuhn S, Kniss KL, Hinckley AF, Rasmussen SA, Pape WJ, Kightlinger LK, Beecham BD, Miller TK, Neitzel DF, Michaels SR, Campbell GL, Lanciotti RS & Hayes EB. (2006). Birth outcomes following West Nile Virus infection of pregnant women in the United States: 2003-2004. Pediatrics , 117, e537-45. PMID: 16510632 DOI.
  28. Pyke AT, Daly MT, Cameron JN, Moore PR, Taylor CT, Hewitson GR, Humphreys JL & Gair R. (2014). Imported zika virus infection from the cook islands into australia, 2014. PLoS Curr , 6, . PMID: 24944843 DOI.
  29. Kuno G & Chang GJ. (2005). Biological transmission of arboviruses: reexamination of and new insights into components, mechanisms, and unique traits as well as their evolutionary trends. Clin. Microbiol. Rev. , 18, 608-37. PMID: 16223950 DOI.
  30. Hamel R, Dejarnac O, Wichit S, Ekchariyawat P, Neyret A, Luplertlop N, Perera-Lecoin M, Surasombatpattana P, Talignani L, Thomas F, Cao-Lormeau VM, Choumet V, Briant L, Desprès P, Amara A, Yssel H & Missé D. (2015). Biology of Zika Virus Infection in Human Skin Cells. J. Virol. , 89, 8880-96. PMID: 26085147 DOI.
  31. Besnard M, Lastere S, Teissier A, Cao-Lormeau V & Musso D. (2014). Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014. Euro Surveill. , 19, . PMID: 24721538

Textbooks

Reviews

Fox KA & Theiler R. (2011). Vaccination in pregnancy. Curr Pharm Biotechnol , 12, 789-96. PMID: 21480828

Ornoy A & Tenenbaum A. (2006). Pregnancy outcome following infections by coxsackie, echo, measles, mumps, hepatitis, polio and encephalitis viruses. Reprod. Toxicol. , 21, 446-57. PMID: 16480851 DOI.

Best JM & Banatvala JE. (1990). Congenital virus infections. BMJ , 300, 1151-2. PMID: 2189514

Waterson AP. (1979). Virus infections (other than rubella) during pregnancy. Br Med J , 2, 564-6. PMID: 227524

Oberst RD. (1993). Viruses as teratogens. Vet. Clin. North Am. Food Anim. Pract. , 9, 23-31. PMID: 8384522

Articles

Pandolfi E, Chiaradia G, Moncada M, Rava L & Tozzi AE. (2009). Prevention of congenital rubella and congenital varicella in Europe. Euro Surveill. , 14, 16-20. PMID: 19317971

Horstmann DM. (1969). Viral infections in pregnancy. Yale J Biol Med , 42, 99-112. PMID: 4317516

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Cite this page: Hill, M.A. (2019, August 26) Embryology Abnormal Development - Viral Infection. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Abnormal_Development_-_Viral_Infection

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G