CONGENITAL VIRAL INFECTION 2021.pptx

There are nearly 100 viruses of the herpes group that infect many different animal species.
Official name of herpesviruses that commonly infect human is Humans herpesvirus (HHV)
herpes simplex virus types 1 (HHV 1)
Herpes simplex virus type 2 (HHV 2)
Varicella-zoster virus (HHV 3)
Epstein-Barr virus, (HHV 4)
Cytomegalovirus (HHV 5)
Human herpesvirus 6 (HHV 6)
Human herpesvirus 7 (HHV 7)
Human herpesvirus 8 (HHV 8) (Kaposi's sarcoma-associated herpesvirus).
Herpes B virus of monkeys can also infect humans
hELMINTHS#corona virus#Aspergillosis#BUGANDO#CUHAS#CUHAS#CUHAS

1. CONGENITAL VIRAL INFECTION S DR.HAMISI MKINDI,MD . TO DOWNLOAD CONTACT: [email protected]

2. Congenital babies Congenital defects

3. INTRODUCTION Congenital viral infections are those infection of the new born which are either transmitted via placenta (utero) during pregnancy or acquired from the birth canal at the time of labor. M ostly cause are viral infection although can arise from other spectrum of organisms. Congenital infections account for 2% to 3% of birth defects.

4. List of congenital viral infection Rubella Cytomegalovirus(CMV) Parvovirus B19 Varicella zoster Virus(VZV) Hepatitis B&C Zika virus HIV.

5. RUBELLA Rubella virus is a member of the genus rubivirus and togavirus family . It is composed of one piece of single-stranded RNA, The virus has a single antigenic type. Its surface spikes contain hemagglutinin . Antibody against hemagglutinin neutralizes infectivity Humans are the natural host Vaccine are the preventable disease Mild, self-limiting illness(resolve without treatment) Infection earlier in pregnancy has a higher probability of affected infant

6. Rubella virus 6

7. EPIDEMIOLOGY Before introduction of rubella vaccination, epidemics of rubella have resulted in rates of CRS of 0.8–4.0 per 1,000 live births (1). Rubella vaccine has been highly effective at reducing the burden of CRS, and vaccination has led to elimination of rubella and CRS from several European and Western Pacific countries and the Pan American Health Organization Region. However , insufficient population vaccination coverage can result in a median age shift of rubella cases to young adults, which may result in more CRS cases.

8. EPIDEMIOLOGY The risk of congenital infection after maternal rubella virus infection depends on the stage of pregnancy when maternal infection occurs; multiple severe defects are inevitable when infection occurs during the first 12 weeks of pregnancy. Thereafter, the risk of fetal damage decreases from 17% at 13–16 weeks gestation to nil at 20 weeks.

9. S eropositivity The IgM seropositive pregnant women had significantly higher adverse pregnancy outcomes than those in second and third trimesters. And younger the Age the higher the risk for acute Rubella virus infection .(M.M. Mirambo et al 2019) Conclusion :There is one case of Congenital Rubella syndrome in every100 pregnancies, necessitating additional strategies to reach a goal of elimination of congenital Rubella syndrome.( M.M.Mirambo et al 2019)

10. TRANSIMISSION AND PATHOGENESIS Transmission Respiratory droplets and across the placenta from mother to fetus. Pathogenesis The initial site of infection is the nasopharynx , from which it spreads to local lymph nodes. It then disseminates to the skin via the bloodstream.

11. Cont … The rash is attributed to both viral replication and immune injury. During maternal infection, the virus replicates in the placenta and then spreads to fetal tissue. If infection occurs during the first trimester, a high frequency of congenital malformations occurs. Maternal antibody protects against fetal infection.

12. COMPLICATION Sensorineural hearing loss (50-75%) Cataracts and glaucoma (20-50%) Cardiac malformations (20-50%) Neurologic (10-20%) Others to include growth retardation, bone disease, thrombocytopenia, “blueberry muffin” lesions. Other eye defects (retinopathy, microophthalmos ), Also deafness, microcephaly, hepatosplenomegaly

13. Laboratory diagnosis Infection in the neonate diagnosed by detection of virus in urine, blood or respiratory samples. Serologic testing ELISA to detect specific IgM Detection of IgG is evidence of immunity, Maternal infection diagnosed by detection of rubella-specific IgM antibodies By detection of rubella specific IgM antibodies in neonatal blood. The HI test is a standard serologic test for rubella.A rise in antibody titer 13

14. TREATEMENT AND PREVENTION No specific treatment exists for rubella . Surgical correction of CHD ( Patent ductus arteriosus ) IMMUNIZATION...IMMUNIZATION………. Rubella is included in the MMR/MR vaccine that is part of the routine childhood immunization schedule. AT 9month and 18 month of age.

15. Cytomegalovirus (CMV) Enveloped virus with linear dsDNA. Member of herpesvirus family Humans are the natural hosts Animal CMV strains do not infect humans. Giant cells are formed Most common congenital viral infection Mild, self limiting illness 15

16. Epidemiology By Marin et al in Brazil 2016 CMV is the most common cause of congenital viral infection world wide(0.2%-2%) 85%-90% of cases are asymptomatic at birth. 90% of symptoms neurological impairment and sensorineural deafness. A study involved 2100 newborn between(Feb 2010-Dec 2012), Viral DNA was detected in saliva swab of 25 new borns,showing prevalence of 1.19%(25/2100). 16

17. Epidemiology Prevalence and determinants of congenital cytomegalovirus infection at a rural South African central hospital in the Eastern Cape by Donald et al 2018. Results: A total of 302 births were assessed. Congenital CMV was prevalent in 18 births (5.96%). In resource-limited settings with very high CMV seroimmunity , congenital CMV rates of 1%–5% have been reported compared with rates of under 1% in industrialised nations. The most commonly observed physical findings are petechial rash, jaundice and hepatosplenomegaly with neurological abnormalities like microcephaly and lethargy. 17

18. Epidemiology Cytomegalovirus, Parvovirus B19 and Rubella Co-infection among Pregnant Women Attending Antenatal Clinics in Mwanza City: The Need to be considered in Tanzanian Antenatal Care Package by M. Mirambo etal-2016 . 214 women involved, Result-Previous co-infections of rubella, cytomegalovirus and B19 was detected in 78 (36.5%) of pregnant women tested. A total of 20 (9.4%) pregnant women had acute co-infection of rubella and parvovirus B19 while 1(0.5%) had acute co-infection of cytomegalovirus and parvovirus B19. Conclusion: Considerable proportion of pregnant women in Mwanza is co-infected with rubella, Cytomegalovirus and parvovirus B19.Routine screening for these infections during antenatal visits was recommended so as to reduce the possibility of congenital infection . 18

19. Transmission and clinical presentation 19

20. Pathogenesis Incubation period 4-8weeks CNS,T and B lymphocytes, Monocytes,kidney,lungs,coloc, liver and others organs involved. CMV enter latent state in leukocytes Activated in cell mediated immunesuppression Persistent in kidneys for years 20

21. LABORATORY DIAGNOSIS Maternal infection is diagnosed by detection of CMV-specific IgM antibodies. Fetal infection is diagnosed prenatally by detection of CMV in amniotic fluid (usually by PCR) or of IgM antibodies in fetal blood. Infection in the neonate is diagnosed by detection of CMV-specific IgM or detection of the virus (by culture or PCR) in throat swabs , blood or urine . Congenital infection can only be diagnosed with certainty on samples collected within the first three weeks of life.

22. TREATMENT AND PREVENTION Ganciclovir or valganciclovir should be considered for treatment of congenitally infected babies:this may alleviate sensorineural hearing loss . Supportive care There are no specific preventative measures . However, babies with congenital CMV infection in hospital should be isolated while in hospital, because large amounts of virus are excreted in urine and respiratory secretions for months or years.

23. HUMAN PARVOVIRUS (B19 ) Nonenveloped virus with ssDNA genome . Belongs to the family parvoviridae and genus erythrovirus. There is one serotype. Replication restricted to erythroid progenitor cells -Adult bone marrow -Fetal liver 23

24. Replication of Parvovirus B19 24

25. Epidemiology Around 40% of adults in the UK are non-immune to parvovirus B19. Upto15% of maternal infections in the first 20 weeks of pregnancy result in fetal infection infections after 20 weeks do not cause serious morbidity 25

26. Epidemiology The magnitude and correlates of Parvovirus B19 infection among pregnant women attending antenatal clinics in Mwanza, Tanzania by Mirambo MM et al 2017. A cross-sectional study involved 258 pregnant women attending two antenatal clinics representing rural and urban areas in the city of Mwanza. 26

27. Epidemiology….. A total of 50/258(19.4%) women were positive for both IgG and IgM indicating true IgM positive. Seroprevalence of IgM among pregnant women has been found to range between 3.3% in South Africa and 13.2% in Nigeria [16] while that of IgG was found to range from 24.9% in South Africa to 58.4% in Malawi [17]. 27

28. Transmission B19 virus is transmitted primarily by the respiratory route; transplacental transmission also occurs. 28

29. Pathogenesis Incubation 7-10 days Lasts 5-7 days. First phase peak level of virus in RBCs(erythroblast) destruction causing aplastic anaemia - infect endothelial cells in the blood vessels, rash associated with erythema infectiosum - Fever,chills,malaise and bright red “slap cheek” rash present 29

30. Pathogenesis….. Second phase -rash&arthralgia -Viral disappear,no longer infectious following parvovirus IgM Third phase -Frequent clearing and recurrences for weeks due stimuli like exercise,irritation,sulight overheating. 30

31. COMPLICATION Maternal When maternal infection occurs in the first 20 weeks of pregnancy, there is a 10% risk of spontaneous abortion.( Shairahm et al 2013) Fetus fetus including A nemia , H ydrops fetalis (congenital heart failure and edema) I ntrauterine fetal death C ongenital anomalie

32. Clinical features 32

33. Skin rashes

34. Laboratory diagnosis Maternal infection diagnosed by detection of specific anti-parvovirus IgM antibodies. Where necessary, fetal infection diagnosed prenatally by detection of parvovirus in amniotic fluid or fetal blood by PCR or by detection of IgM antibodies in fetal blood. Diagnosis of infection in the neonatal period not usually relevant. 34

35. Treatment and prevention Supportive care -acetaminophen or Ibuprofen for fever -Intravenous immunoglobulin(IVGV) in chronic parvovirus 400mg/kg/day 5days. -Aplastic crisis with severe anaemia give packed RBCs. -Vaccine is in trials No specific antiviral therapy ; where parvovirus infection has been diagnosed, enhanced monitoring of the pregnancy . Pregnant women should avoid contact with children with parvovirus infection. 35

36. Cont. Most of infants with hydrops fetalis will require Endotrachial intubation so as to correct respiratory depression Thoracosynthesis , paracentesis and cardiocentesis are perfomed if the neonate presents with pleural effusion, ascites and pericardial infusion. 36

37. VARICELLA ZOSTER Enveloped virus with linear double-stranded DNA. Found in herpesvirus family. It is extremely rare congenital viral infection. Epidemiology Around 90% of UK-born adults are immune to chickenpox, but the proportion of immune adults who were brought up in other countries may be lower. In Tanzania ?? Transmission -The virus is transmitted by respiratory droplets and by direct contact with the lesions

38. PATHOGENESIS VZV infects the mucosa of the upper respiratory tract, then spreads via the blood to the skin, where the typical vesicular rash occurs. After the host has recovered, the virus becomes latent, probably in the dorsal root ganglia.

39. Clinical features Small risk (<3%) of fetal malformation (congenital varicella syndrome) where maternal chickenpox occurs in the first trimester. Recognised congenital varicella syndrome; -Hypoplasia of limbs -CNS and eye defects -Death in infancy normal

40. Cont . The other period of high risk is where maternal chickenpox occurs between 7 days before and 7 days after delivery: the baby is at risk of severe systemic neonatal infection, because it will not acquire passive immunity from its mother

41. DIAGNOSIS Chickenpox is usually diagnosed clinically. Where necessary, the diagnosis can be confirmed by direct detection of the virus in blood, CSF by PCR or ELISA. Serology has no part in diagnosis of acute chickenpox, but is needed to assess the immunity of persons who have been exposed to chickenpox

42. TREATMENT AND PREVENTION High dose acyclovir for neonatal varicella infection. Non-immune pregnant women should avoid contact with chickenpox. Contacts should be treated with varicella zoster immune globulin (VZIG). There are two vaccines against VZV: one designed to prevent varicella , called Varivax , and the other designed to prevent zoster, called Zostavax . The varicella vaccine is recommended for children between the ages of 1-12 years(not given to pregnant women or immunocompromised )

43. HERPEX SIMPLEX VIRUS HSV-1 and HSV-2,more HSV-2 causing congenital infection Epidemiology Herpes simplex virus type 2 (HSV-2) is the main causative agent of genital ulcer diseases worldwide It can be transmitted vertically from mother to the fetus and it is highly prevalent in the sub-Saharan Africa whereby it has been found to cause severe illness to the neonates .( Mirambo et.al 2019) Rarely cause transplacental spread, which almost always leads to loss of the pregnancy.

44. PATHOGENESIS Entry by skin or mucosa membrane Viral multiplication in blood. Sensory nerve involvement Dorsal root ganglia where there is latency period until another infection occurs.

45. Cont. Transmission - HSV-1 is transmitted primarily in saliva, whereas HSV-2 is transmitted by sexual contact. Oral-genital sex changes the course(mixed up). Clinical features Encephalitis or meningoencephalitis , generalized infection with hepatitis and mucocutaneous lesions.

46. Laboratory investigation Isolation and identification( culture) Detection of virus in clinical material by PCR. Treatment and prevention Treatment of herpes encephalitis with high doses of acyclovir has reduced the mortality rate to under 25%.

47. HEPATITIS VIRUS Is a DNA virus, member of hepadnaviridae family. Enveloped virus with incomplete circular double-stranded DNA Consisting of: core antigen ( HBcAg ), derived from the core gene, encapsidates the viral genome ‘e’ antigen ( HBeAg ), also derived from the core gene surface antigen ( HBsAg ), derived from the surface gene, surrounds the nucleoprotein core of the virus

48. Cont. Epidemiology Vertical transmission is the most important route of infection of HBV. Acquisition rates vary according to hepatitis B e antigen status of the mother (70–90% if the mother is HBeAg -positive and 10–40% if HBeAg -negative). Transmission -can occur in utero(across the placenta) and during delivery. Clinical features Neonatal infection is often sub-clinical disease in later childhood or adulthood Symptomatic infection causes jaundice, lethargy, failure to thrive, abdominal distention, and clay-colored stools.

49. Laboratory diagnosis Diagnosis is by ELISA/PCR /rapid test Detection of seromarkers of hepatitis B (especially surface antigen (HBsAg)) in neonatal blood. Other tests include complete blood count (CBC) with platelets, LFT (alanine aminotransferase (ALT) and alpha-fetoprotein levels. L iver ultrasonography.

50. Treatment and prevention Rarely, severe illness may cause acute liver failure requiring liver transplantation. Less severe illness is treated supportively. Active and passive immunization of the mother helps to prevent vertical transmission Pregnant women should be routinely screened for HBsAg .

51. Zika virus(ZKV ) Single stranded RNA virus Genus Flavivirus , family Flaviviridae Closely related to dengue, yellow fever, Japanese encephalitis, and West Nile viruses 51

52. Epidemiology The very first known case of Zika fever was in a rhesus monkey in the Zika Forest in Uganda in 1947. It was later identified in humans in 1952 in Uganda and Tanzania. The first human cases were reported in Nigeria in 1954. A few outbreaks have been reported in tropical Africa and in some areas in Southeast Asia. The first major outbreak, with 185 confirmed cases, was reported in 2007 in the Yap Islands of the Federated States of Micronesia. In 2013 another large outbreak was reported in French Polynesia that was thought to be from an independent introduction of the virus from Asia than the Yap Island outbreak. 52

53. Epidemiology 53

54. Epidemiology ….. By Guamaraes C et al 2017 A retrospective study involved 233 children with microcephaly born(2015-2017). 69/233(29.6%) were found to have Zika infection by serology IgM and/or PCR. Neuralogical,musculoskeletal malformation,eye damage,and hearing impairment. 54

55. Epidemiology Congenital Zika Virus Infection Paradigm:What is the Wardrobe?A Narrative Review.By Mirambo M et al 2019. articles (11 case series, 9 case reports, and 4 others). These articles reported 919 cases,presumed to have Zika infection, Of these cases, 884 (96.2%) had microcephaly. Of the 884 cases of microcephaly, 783 (88.6%) were tested for Zika virus infection, and 216 ( 27.6%; 95% CI)were confirmed to be Zika virus-positive. 55

56. Epidemiology In addition to microcephaly, other common abnormalities reported – out of 442 cases investigated – were calcifications of brain tissue (n=240, 54.3%), ventriculomegaly (n=93, 20.8%), cerebellar hypoplasia (n=52, 11.7%), and ocular manifestations (n=46, 10.4%). Conclusion: Based on the available literature, Zika virus infection during pregnancy might lead to a wide array of outcomes other than microcephaly. 56

57. Epidemiology There is a need for more epidemiological studies in Zika-endemic areas, particularly in Africa, to ascertain the role of Zika virus in causing congenital neurologicaldefects 57

58. Transmission of zika virus Zika virus is transmitted to people primarily through the bite of an infected Aedes species mosquito ( A. aegypti and A. albopictus ). These mosquitoes typically lay eggs in and near standing water in things like buckets, bowls,animal dishes, flower pots and vases. They prefer to bite people, and live indoors and outdoors near people. Mosquitoes that spread chikungunya, dengue, and Zika are aggressive day time biters. They can also bite at night. Mosquitoes become infected when they feed on a person already infected with the virus. Infected mosquitoes can then spread the virus to other people through bites 58

59. Transmision cont … Sexually Blood transfusion From mother to child: -Zika virus can pass from a pregnant woman to her fetus during pregnancy or around the time of birth. Zika infection in pregnancy is a cause of microcephaly and other severe brain defects. Other problems include Eye defects, hearing loss, impaired growth, and fetal loss. 59

60. Pathogenesis Symptoms appear 2-12 days post infection Fully recovery,with symptoms resolving in about a week( headache,fever,rash Joint&muscle,myalgia,ache,pruritus , non-purulent conjuctivitis 60

61. Clinical symptoms Infants with confirmed or possible Zika infection Microcephaly Miscarriage Stillbirth Absent or poorly developed brain structures Defects of the eye Hearing defects Impaired growth 62

62. Cont … 64

63. Diagnosis IgM , IgG and PCR for Zika virus. Acute serum (taken within 5 days of symptom onset) and convalescent serum (2–3 weeks later) should be taken. The two samples are important to rule out false positive tests due to cross reactivity with similar viruses such as Dengue . Amniocentesis to screen for Zika virus. 65

64. Treating patients who test positive There are no vaccine or medicine for Zika virus. Treat the symptoms of Zika Plenty of rest Drink fluids to prevent dehydration Take acetaminophen to reduce fever and pain Do not take aspirin or other non-steroidal anti-inflammatory drugs (NSAIDS) until dengue can be ruled out to reduce the risk of bleeding. 66

65. Prevention Prevention involves reducing mosquito populations and avoiding bites, which occur mainly during the day. Eliminating and controlling Aedes aegypti mosquito breeding sites reduces the chances that Zika will be transmitted. To prevent mosquito bites, it is recommended for people who live in areas where there are cases of the disease, as well as travelers and, especially, pregnant women to use mosquito nets,repellants,long sleeves, windows with mosquito wires etc. 67

66. HIV/AIDS INFECTION Human immunodeficiency virus(HIV) is a virus that attacks the bodies immune system. Human immunodeficiency virus is the etiological of AIDS. It is belong to lentivirus subgroup of retroviridae family. The family of viruses is known for latency, persistency viraemia ,infection of the nervous system, and weak host immune .

67. HIV Epidemiology Human immunodeficiency virus (HIV) is one of the most important global health problems. More than one and half million of children are living with HIV in the world, and majority of them are found in sub-Saharan Africa.( Belachew et.al. 2020) HIV transmission from infected mothers to their babies can occur in utero (<1% of cases ), during delivery or via breast milk . Without preventative measures, the risk of vertical transmission is 15–40%, but with careful management the risk falls to almost zero.

68. HIV

69. Pathogenesis

70. Clinical features Infected neonates are usually asymptomatic at birth, but the illness can progress rapidly in infancy. Poor weight gain, lymphadenopathy, hepatosplenomegaly and recurrent infections are early signs of infection. Intrauterine growth retardation, IUFD,abortion .

71. Treatment and prevention   ARV Prophylaxis :  The administration of one or more ARV drugs to a newborn without documented HIV infection to reduce the risk of perinatal acquisition of HIV. Presumptive HIV Therapy :  The administration of a three-drug ARV regimen to newborns who are at highest risk of perinatal acquisition of HIV. Presumptive HIV therapy is intended to be preliminary treatment for a newborn who is later documented to have HIV, but it also serves as prophylaxis against HIV acquisition for those newborns who are exposed to HIV  in utero , during the birthing process, or during breastfeeding and who do not acquire HIV .

72. HIV Therapy :  The administration of a three-drug ARV regimen at treatment doses (called antiretroviral therapy [ART]) to newborns with documented HIV infection

73. D iagnosis Detection of HIV RNA or proviral DNA in neonatal blood by PCR Prevention Pregnant women should be routinely screened for HIV. Infected cases have to be treated with antiretroviral drug TIMELY. Newborns are also treated with antiretroviral drugs.

74. References Rosenthal, P., & Alrabadi , L. (2021). Neonatal Hepatitis and Congenital Infections. ,   Liver Disease in Children  (pp. 147-161). Cambridge: Cambridge University Press. doi:10.1017/9781108918978.010 Belachew , A., Tewabe , T. & Malede , G.A. Prevalence of vertical HIV infection and its risk factors among HIV exposed infants in East Africa: a systematic review and meta-analysis.  Trop Med Health   48,  85 (2020). https://doi.org/10.1186/s41182-020-00273-0

75. Cont.. Viennet E, Montgomery BL, et al. (2020) Estimation of mosquito-borne and sexual transmission of Zika virus in Australia: Risks to blood transfusion safety. PLoS Negl Trop Dis 14(7): e0008438. https:// doi.org/10.1371/journal.pntd.0008438   Chengula , D.  et al.   Treponema pallidum  infection predicts sexually transmitted viral infections (hepatitis B virus, herpes simplex virus-2, and human immunodeficiency virus) among pregnant women from rural areas of Mwanza region, Tanzania.  BMC Pregnancy Childbirth   19,  392 (2019). https://doi.org/10.1186/s12884-019-2567-1

76. Cont. Mirambo , M., et al. "Cytomegalovirus, parvovirus B19 and rubella co-infection among pregnant women attending antenatal clinics in Mwanza City: The need to be considered in Tanzanian Antenatal Care Package."  Epidemiology (Sunnyvale)  6.230 (2016): 2161-1165 . Mirambo MM, Mshana SE, Groß U. Rubella virus,  Toxoplasma gondii  and  Treponema pallidum  congenital infections among full term delivered women in an urban area of Tanzania: a call for improved antenatal care. Afr Health Sci. 2019 Jun;19(2):1858-1865. doi : 10.4314/ahs.v19i2.8. PMID: 31656468; PMCID: PMC6794536.

77. Cont. Mandell,Douglas and Benett’s principles of infectious diseases Eighty Edition . Medical microbiology 19 th ed by Jawetz et al . WHO Regional Committee for Africa Measles Elimination by 2020: A Strategy for the African Region. AFR/RC61/R1.