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SUMMARIZED! Hepatitis, HIV, Dengue, Malaria, Infectious Mononucleosis, Study notes of Immunology

Information on three infectious diseases: Hepatitis, Dengue, and Malaria. It describes the causes, symptoms, and laboratory tests for each disease. Hepatitis is caused by viruses and noninfectious agents, and the most common type is Hepatitis B. Dengue is a viral disease transmitted by mosquitoes, and severe dengue can be fatal. Malaria is caused by Plasmodium parasites and is spread through mosquito bites. The document also provides information on laboratory tests for each disease, including serological tests and rapid diagnostic tests.

Typology: Study notes

2020/2021

Available from 11/04/2022

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HEPATITIS
Inflammation of the liver caused by viruses
and by noninfectious agents such as
ionizing radiation, chemicals and
autoimmune process Viral hepatitis is the
most common liver disease world wide
2 major groups
(1) Primary hepatitis viruses: A,B, C, D,
E and GB virus C- 95% cases of
hepatitis
(2) Secondary hepatitis viruses:
Epstein-Barr virus(EBV),
Cytomegalovirus,
Herpes virus - involve the liver secondarily
to infection
Hepatitis B
Hepatitis B virus is a complex DNA
virus from the family of Hepadnaviridae.
Long incubation hepatitis
Major cause of morbidity and mortality
throughout the world
Highly endemic in the Far East, parts of
the Middle East, sub-Saharan Africa, and
the Amazon areas.
Mode of transmission
◦Parenteral by intimate contact with HBV
contaminated blood, semen, vaginal fluid
◦Mother-fetus transmission
Laboratory Assay
Hepatitis B surface Antigen (HBsAg)-
general marker of infection.
Hepatitis B e Antigen (HBeAg)- active
replication of virus, infectious
Hepatitis B core antibody, total or IgM
(anti-HBc)- marker of acute infection
Hepatitis B core antibody, IgG- past
infection or chronic infection
Hepatitis B e antibody (anti-HBe)- virus
not replicating but still positive for HBsAg
Hepatitis B surface antibody (anti-HBs)-
document recovery/ immunity to HBV
Hepatitis B viral DNA by PCR
HBsAg- Hepatitis B surface antigen
General marker of infection of
Hepatitis B.
- Serum HBsAg- marker for HBV
infection (active, acute, chronic)
- The initial detectable marker found
in serum during incubation period of
HBV infection
- Detectable within 2 weeks to 2
months before clinical sign and
symptoms appear or 2 weeks after
infection
- Present 2-3 months, undetectable
after 4-6 months in acute hepatitis
Chronic hepatitis present 6 months or
more.
- Screens the presence of major
coat-protein of the HBV envelope
protein
- Most reliable method of choice to
prevent transmission of HBV via
blood
pf3
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pf9

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HEPATITIS

Inflammation of the liver caused by viruses and by noninfectious agents such as ionizing radiation, chemicals and autoimmune process Viral hepatitis is the most common liver disease world wide ◼ 2 major groups (1) Primary hepatitis viruses: A,B, C, D, E and GB virus C- 95% cases of hepatitis (2) Secondary hepatitis viruses: Epstein-Barr virus(EBV), Cytomegalovirus, Herpes virus - involve the liver secondarily to infection Hepatitis B Hepatitis B virus is a complex DNA virus from the family of Hepadnaviridae. ◼ Long incubation hepatitis ◼ Major cause of morbidity and mortality throughout the world ◼ Highly endemic in the Far East, parts of the Middle East, sub-Saharan Africa, and the Amazon areas. Mode of transmission ◦Parenteral by intimate contact with HBV contaminated blood, semen, vaginal fluid ◦Mother-fetus transmission Laboratory Assay ◼ Hepatitis B surface Antigen (HBsAg)- general marker of infection. ◼ Hepatitis B e Antigen (HBeAg)- active replication of virus, infectious ◼ Hepatitis B core antibody, total or IgM (anti-HBc)- marker of acute infection ◼ Hepatitis B core antibody, IgG- past infection or chronic infection ◼ Hepatitis B e antibody (anti-HBe)- virus not replicating but still positive for HBsAg ◼ Hepatitis B surface antibody (anti-HBs)- document recovery/ immunity to HBV ◼ Hepatitis B viral DNA by PCR HBsAg- Hepatitis B surface antigen General marker of infection of Hepatitis B.

  • Serum HBsAg- marker for HBV infection (active, acute, chronic)
  • The initial detectable marker found in serum during incubation period of HBV infection
  • Detectable within 2 weeks to 2 months before clinical sign and symptoms appear or 2 weeks after infection
  • Present 2-3 months, undetectable after 4-6 months in acute hepatitis Chronic hepatitis – present 6 months or more.
  • Screens the presence of major coat-protein of the HBV – envelope protein
  • Most reliable method of choice to prevent transmission of HBV via blood

Principle Lateral flow immunochromatographic assay- screening only - HBsAg conjugate + serum

  • If present: purple line in T band and C Band
  • Reactive; needs confirmatory testing
  • If not detected: purple line in C band only
  • Non-reactive ◦Can give false negative if mutants HBV is present SD BIOLINE In vitro immunochromatographic, rapid assay designed for the qualitative detection of Hepatitis B surface antigen, in human serum, plasma (heparin, EDTA and sodium citrate) or venous whole blood (heparin, EDTA and sodium citrate). The membrane is pre-coated with mouse monoclonal anti-HBsAg pool on the test line region and Mouse monoclonal anti-chicken IgY on the control line region. Confirmatory Testing Serum testing may be performed by
  • EIA (ELISA)
  • Chemiluminescent immunoassay
  • real-time PCR
  • Quantitative
  • PCR-nucleic acid

HIV 1/

Human Immunodeficiency Virus (HIV)

- etiologic agent of AIDS HIV-1 - Epidemic HIV-2 - West Africa HIV member of the family Retroviridae, a type D retrovirus belongs to the lentivirus subfamily. Included are oncoviruses HTLV- I and HTLV-2, which induce proliferation of infected cells and formation of tumors. Retrovirus is an RNA virus with a unique enzyme reverse transcriptase that can

Confirmatory Testing Western blot, IFA HIV RNA by NAAT (Nucleic acid amplification testing)

DENGUE

Viral infection transmitted to humans through the bite of infected mosquitoes.

- Primary vectors - Aedes aegypti and, to a lesser extent, Ae. albopictus. Vector of chikungunya, yellow fever and Zika virus

  • The virus responsible for causing dengue, is called dengue virus (DENV).
  • There are four DENV serotypes and it is possible to be infected four times. ❑ Single stranded RNA virusBelong to family of FlaviviridaeFour serotypes of the virus that cause dengue (DENV-1, DENV-2, DENV-3 and DENV-4)Recovery from infection is believed to provide lifelong immunity against that serotypeCross-immunity to the other serotypes after recovery is only partial, and temporary.Subsequent infections (secondary infection) by other serotypes increase the risk of developing severe dengue. EPIDEMIOLOGY Dengue is widespread throughout the tropics, with local variations in risk influenced by climate parameters as well as social and environmental factors.
  • Dengue causes a wide spectrum of disease. This can range from subclinical disease (people may not know they are even infected) to severe flu-like symptoms in those infected. SEVERE DENGUE Although less common, some people develop severe dengue, which can be any number of complications associated with severe bleeding, organ impairment and/or plasma leakage
  • Severe dengue has a higher risk of death when not managed appropriately.
  • Severe dengue was first recognized in the 1950s during dengue epidemics in the Philippines and Thailand.
  • Today, severe dengue affects most Asian and Latin American countries and has become a leading cause of hospitalization and death among children and adults in these regions SEVERE DENGUE SIGN AND SYMPTOMS A patient enters what is called the critical phase normally about 3-7 days after illness onset. During the 24-48 hours of critical phase, a small portion of patients may manifest sudden deterioration of symptoms. It is at this time, when the fever is dropping (below 38°C/100°F) in the patient, that warning signs associated with severe dengue can manifest. Severe dengue is a potentially fatal complication, due to plasma leaking, fluid accumulation, respiratory distress, severe bleeding, or organ impairment. SEVERE DENGUE SIGN AND SYMPTOMS Warning signs that doctors should look for include: (1) severe abdominal pain (2) persistent vomiting (3) rapid breathing (4) bleeding gums or nose (5) fatigue (6) restlessness (7) liver enlargement (8) blood in vomit or stool. MODE OF TRANSMISSION
  • Mosquito bite
  • Human to mosquito
  • Maternal transmission- low When a mother does have a DENV infection when she is pregnant, babies may suffer from preterm birth, low birthweight, and fetal distress. Rare cases of transmission via blood products, organ donation and transfusions have been recorded SIGN AND SYMPTOMS
  • High fever- 40°C
  • severe headache
  • pain behind the eyes
  • muscle and joint pains
  • nausea
  • vomiting
  • swollen glands
  • rash LABORATORY TEST (1) Viral isolation- PCR (2) NS1-Highly conserve glycoprotein present in high concentration in dengue-infected patient during the early clinical phase of the disease (3) Present from the first day up to 9 days after the onset of fever from the primary or secondary infected person Serological Test, Detection of specific antibodies
  • IgM – 1 week after infection till 3 months detectable
  • IgG- 14 weeks and persist for life DENGUE DUO Principle
  • LFA
  • Detects the NS1 protein and the antibodies either IgM or IgG

LABORATORY TEST

❑Microscopy- blood film ❑Serological test ❑LFA ❑Pf/Pan Antigen Test ❑Rapid self-performing qualitative, two site sandwich immunoassay ❑Utilizes whole blood for the detection of P.falciparum specific histidine rich protein 2 (Pf HRP-2) and pan specific pLDH ❑Differentiation of P.falciparum and other malarial species ❑Follow-up of anti-malarial therapy PRINCIPLE ❑Test Line Pan - for P. falciparum, P. vivax, P. malariae, and P. ovale ❑Test line Pf - for P. falciparum

INFECTIOUS

MONONUCLEOSIS

Primary infection caused by EBV in adolescents and adults. If in infants, asymptomatic or mild. Incubation period is 10 to 50 days. Sign and symptoms Classic symptoms: are fever, lymphadenopathy and sore throat

  • Other symptoms are splenomegaly, hepatomegaly and periorbital edema
  • Last for 1 to 4 weeks EPSTEIN-BARR VIRUS Human herpes DNA virus Discovered by Dr. M. Anthony Epstein and Dr. Yvonne Barr in 1964
  • Causes a wide spectrum of diseases, including infectious mononucleosis, lymphoproliferative disease, and several malignancies
  • Human cancer virus
  • Burkitts’s Lymphoma : malignant B-cell neoplasm
  • Presents as a rapidly growing tumors of the jaw, face or eye grows very quickly, and without treatment most children die within a few months. MODE OF TRANSMISSION Intimate contact with salivary secretions, Blood transfusions, Bone marrow and solid organ transplants, Sexual contact, and perinatal transmission, these routes appear to be much less frequent EPIDEMIOLOGY Developing countries and lower socioeconomic groups living under poor hygiene conditions infections usually occur during early childhood
  • Industrialized nations with higher standards of hygiene, infections are typically delayed until adolescence or adulthood.
  • More than 90 percent of individuals have been infected, as evidenced by the presence of EBV antibodies in their serum LABORATORY TEST (1) Detection of heterophile antibodies- not sensitive (2) Detection of IM specific antibodies (3) ELISA (4) Latex Agglutination Test HETEROPHILE ANTIBODIES Antibodies that are capable of reacting with similar antigens from two or more unrelated species Broad class of antibodies Stimulated by one antigen (EBV), and react with an entirely unrelated surface antigen present on cells of different mammalian cells.
  • Horse, sheep and ox erythrocytes IgM is the immunoglobulin during acute phase of IM CHARACTERISTICS
  • Reacts with horse, ox and sheep erythrocytes
  • Absorbed by beef erythrocytes
  • Not absorbed by guinea pig kidney cells
  • Does not react with Epstein-Barr virus –specific antigens DETECTION OF HETEROPHILE ANTIBODIES Paull-Bunnell Screening test
  • Classic hemagglutination test to detect heterophile antibodies using antigen-bearing sheep erythrocyte Davidsohn Differential Test
  • Differentiate heterophile type of antibody
  • IM and serum sickness
  • Using guinea pig kidney cell and beef erythrocyte PAUL-BUNNELL The original Paul-Bunnell test was a simple titration of sheep cell agglutinins - But this procedure was subsequently modified in order to distinguish between sheep cell agglutinins formed in IM and the Forssman-type antibodies found in normal serum, serum sickness and in certain other conditions. DAVIDSOHN DIFFERENTIAL The principle behind the Paul-Bunnell -Davidsohn test is that the two types of sheep agglutinins are distinguished by titrating them before and after absorption with guinea pig kidney and ox cells.
  • Patients' serum containing antibodies due to IM is added to guinea pig kidney cells. These antibodies are not absorbed by the kidney cells. These antibodies then react with Beef (Ox) red blood cells which causes agglutination and is a positive test for IM.
  • Patients' serum containing Forssman antibodies are added to guinea pig kidney cells. Antibodies are absorbed by the kidney cells. These antibodies are then allowed to react with Beef red blood cells which do not cause agglutination. This is a positive test for Forssman antigens.