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In this essay we will discuss about Human Immunodeficiency Virus (HIV). After reading this essay you will learn about: 1. Retro Virus 2. Human T-Cells Leukaemia Viruses 3. Pathogenesis of HIV 4. Laboratory Diagnosis of HIV 5. Human Foamy Virus 6. Antigenic Variation of HIV 7. Animal Lenti Virus 8. Tropism 9. Resistance of HIV 10. Transmission of HIV 11. Pathogenesis of HIV and Other Details.
Contents:
- Essay on Retro Virus
- Essay on the Human T-Cells Leukaemia Viruses
- Essay on the Pathogenesis of HIV
- Essay on the Laboratory Diagnosis of HIV
- Essay on Human Foamy Virus
- Essay on the Antigenic Variation of HIV
- Essay on the Animal Lenti Virus
- Essay on Tropism
- Essay on the Resistance of HIV
- Essay on the Transmission of HIV
- Essay on the Pathogenesis of HIV
- Essay on the Clinical Types of HIV
- Essay on the Complications of HIV
- Essay on Immuno-Pathology
- Essay on the Laboratory Diagnosis of HIV
- Essay on the Epidemiology of HIV
- Essay on the Prevention of HIV
- Essay on the Prophylaxis of HIV
- Essay on the Treatment of HIV
- Essay on the Arthropod Borne Rickettisal Infections
Essay # Retro Virus:
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Retrovirus (retro, L. backward) belong to the lenti virus subgroup of Retro viridiae family. They are RNA viruses. It was believed that RNA was the only source of genetic information during multiplication of host cells; later it was found that they reverse the process.
Retro viruses contain reverse transcriptase (RNA dependent DNA polymerase) which prepares a DNA copy of the RNA genome in host cell. The DNA copy is integrated with the chromosome of host cell.
Onco viruses include both strains of that cause tumour and that do not produce tumours though in man tumour producing strains are found in normal human placenta and tetra-carcinoma cell lines, they are not associated with the disease.
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So they, most probably, are endogenous human virus. Lenti viruses are so named because they give rise to slowly developing disease in man. HIV-1 and HIV-2 infections are exogenous in origin.
Essay # Human T-Cells Leukaemia Viruses:
Human T-cell leukemia/lymphoma virus (HTLV) first reported in Japan, has been isolated in 1980.
Essay # Pathogenesis of HIV:
Human T-cell leukaemia is an acute T-cell malignancy. This virus affects CD4+ T cells of adults—hence it is called as adult T cell leukaemia/lymphoma virus. Both HTLV-I and HTLV- II transform CD4+ T-cells in vitro.
HTLV-I is also responsible for a neurological disease, spastic para paresis or slowly progressive encephalopathy with spastic or ataxic features. There is a long latent period of many years. The T-cell proliferation may be due to protein coded by tart gene of virus. T-cell leukaemia in man is reported in Japan, tropical America and West Africa.
Essay # Laboratory Diagnosis of HIV:
(a) Serology:
Antibody to HTLV is detected by immunofluorescence, ELISA and confirmed by Western Blot test.
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(b) Antigen:
HTLV antigen is rarely detected in CSF.
(c) PCR:
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Gene amplification by polymerase chain reaction can be applied to lymphocytes of sero-positive patients.
Essay # Human Foamy Virus:
Human foamy virus (HFV) produces a characteristic foamy or vacuolated appearance of infected cell in human live cell culture, hence its name, HFV. Its pathogenic role in human disease is not yet established. In 1981, Virus was believed hypothetically to be responsible for Acquired Immunodeficiency Syndrome (AIDS).
AIDS was first detected in homosexuals at USA. All victims suffered a depletion of a specific subset of T-cells (T4 cells)—as a result they were susceptible to pathogens that will be controlled by a healthy immune system. In 1983, it was observed that Human T-Lymphotropic virus (HTLV) had affinity for T4 lymphocytes in vitro and in vivo.
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In USA, Gallo (Chief of the Laboratory of Tumour cell Biology at the National Cancer Institute, USA) hypothesized that AIDS is caused by HTLV virus or related virus. The two agents known in human pathology at that time (HTLV-I and II) induced leukemic lymphoid proliferation, while, in case of AIDS, lymphocytes depletion was observed.
Montagnier (Professor of Virology, Pasteur Institute, Paris) discovered a new retro virus known by him as Lymphadenopathy associated virus (LAV) from a patient affected with chronic lymphadenopathy. Later, LAV was found similar to HTLV-III. Gallo (1984) isolated HTLV-III similar to be morphologically and immunologically identical to LAV after molecular cloning.
In 1986, HIV (Fig. 55.1) was well-established as aetiological agent of AIDS. Montagnier has also isolated a new virus, HIV-II. The source for a new focus of AIDS in West Africa was HIV- II. In 1987, it was realised that HIV may be a mutant, dating to 20-40 years, of a human virus not much pathogenic or of a simian virus. Existence of vector of this disease was also demonstrated. HIV and HTLV-III are the same.
To eliminate the confusion, an international commission had changed its name to HIV. It is isolated from blood, semen, cerebrospinal fluid, urine, saliva, tears, vaginal secretions, milk, cerebral nervous tissue and spinal marrow. It has tropism for cells;
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(1) Tropism for T4 lymphocytes;
(2) For macrophages—hence it is isolated in CNS.
HIV is 110-120 nm particles. Its envelope is external part. It has small core (nucleotide) which contains viral RNA. HIV is a RNA retrovirus. It has 9,200 nucleotides in length.
Its genome contains 3 genes of retrovirus respectively coding for:
(a) Internal protein in core
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(b) Inverse transcriptase necessary for replication
(c) Glycoprotein on the envelope (Fig. 55.1).
HIV genome also contains:
(1) Gene coding for small protein, known as “tat” (for transactivation)
(2) Gene coding for small protein ‘art’ which has same role as ‘tat’;
(3) Gene coding for 2 proteins Q and F whose role is unknown.
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New virus—lymphadenopathy associated virus (LAV)—grew in T4 cells, not in related T8 cells. Later, LAV were identified as HTLV-III and were found to be the best cause of AIDS. LAV, HTLV-III, HIV are the same.
HIV is the cause of AIDS and is now firmly established. It could affect T4 cells and macrophages. HIV binds with marker for T4 cells, infects and kills T4 cells.
In the host blood cell (CD4 cells), HIV releases RNA which is transcribed by one of its enzymes, reverse transcriptase, first into single stranded DNA and then into double stranded DNA (pro virus) which becomes integrated into the cell’s chromosome by another enzyme.
The virus remains dormant for long period. When activated, virus reproduces itself and progeny virion buds out through the cell membrane and infects fresh cells. The virus acquires a lipoprotein envelope from the host cell membrane while budding out of the cell.
The envelope has got projecting spikes (peplomers) on the surface and anchoring trans-membrane pedicles. Genetic makeup of the virus (HIV) is highly variable from strain to strain, hence vaccine preparation is difficult.
HIV genome contains nine genes:
(a) Three structural genes (gag, pol, env) characteristic of all retro viruses. Both HIV-1 and HIV-2 have
(b) Five other small non-structural genes (tat, rev, nef, vif, vpr). Other than these, HIV-1 contains vpu and HIV-2 has vpx.
The products of these genes act as antigens and infected person’s serum contains antibodies to these antigens. The amount of circulating antibodies and antigens varies during the course of infection. HIV-2 has 40% genetic identity with HIV-1 and differs from HIV-1 in its envelope.
The core polypeptide displays some cross-reactivity. The major difference is that HIV-2 lacks the vpu gene; but it has vpx gene not contained in HIV-1, HIV-2 is much related to Simian Immuno- deficiency virus (SIV).
(I) Structural Genes:
(1) The gag gene encodes core and shell protein of the virus.
(2) The pol gene encodes the enzymes (reverse transcriptase, protease, endonuclease, and integrase).
(3) The env gene encodes glycoprotein 160 which is cleaved into:
gp 120 (surface spike); gp 41 (trans-membrane pedicle protein).
(II) Non-Structural, Regulatory Genes:
1. Tat (transactivation) gene. In collaboration with a cellular protein, it enhances expressions of all viral genes to increase the production of active messengers.
2. Rev (regulatory of virus) gene is required for expression of the gag, pol and env genes, but not for tat and rev.
3. Nef (negative factor) gene may be responsible for the regulation of latent state of virus.
4. Vif (viral infectivity factor) gene confers infectivity of the virus.
5. Vpv gene.
6. Vpu (in HIV-1) and vpx (in HIV-2). They code for small viral proteins of unknown function.
Essay # Antigenic Variation of HIV:
Most HIVs are considered to be variants of HIV-1 which was original isolate (LAV/HTLV- III). Pandemics of AIDS is due to HIV-1. HIV-2 is less virulent. Antigenic variation occurs within both HTV-1 and HIV-2. Strains of HIV differ from each other due to mutations, deletions and insertions. HIV-1 does not cause disease in animals whereas HIV-2 infects Rhesus monkey.
Essay # Animal Lenti Virus:
Simian AIDS virus (SN) is more closely related to HIV-2 than HIV-1, causes natural asymptomatic infection in the primates. Non-primates AIDS viruses are Feline T Lymphotropic virus (FTLV) causing AIDS-like syndrome in cats and bovine lenti virus (BTLV) causes degenerative wasting disease with defects in CNS in cattle.
Essay # Tropism:
The spikes (gp 120) of the viral envelope selectively binds to the 58 kd CD4 protein of T helper lymphocytes. Antibodies to CD4 protein block the viral binding site.
Mere attachment of virus to CD4 will not suffice for virus infection, but a second human receptor component is of great necessity for viral entry, mediated by gp 41. Any human cell with CD4 protein on its surface is susceptible to HIV infection. However, the principal target cells are CD4+/lymphocytes.
Two cleavage products of envelope glycoprotein (gp 160) i.e. gp 120 and gp 41 play a great role in the replication of virus. At first gp 120 binds to CD4 protein of host cell, then gp 41 terminus is exposed, thus helping the host cell membrane to fuse with the viral membrane. Hence, the viral core directly enters the cytoplasm of host cell.
The infected CD4 cells express a high level of gp 120 protein on their surface which ultimately fuses to CD4 protein of uninfected neighbouring cells, with formation of multi-nucleated syncitial cells. These fused cells die finally, thereby causing a depletion of large number of un-infected cells in the circulation.
Evolution usually virus remains hidden (latent) in host cell for a short period. Window period is the interval period between HIV infection and appearance of antibodies and lasts for 2 to 3 weeks; sometimes it may last for more than six months. During this window period the sero-negative person may transmit the virus.
After about 2 weeks of infection, free p 24 Ag and RT (reverse transcriptase) Ag circulate in the blood (anti-genaemia), which is difficult to identify—particularly in sexually contracted infection. But it is easier in infection acquired by blood transfusion as the blood contains free virus and large number of infected cells.
With the onset of acute infection or sero-conversion (about one month after infection), antibody titres becomes detectable and the level of antigens in the blood declines, disappears from the blood and remains absent throughout the asymptomatic phase.
With the formation of antibody, there is disappearance of the virus antigens in the blood. It indicates the immunological suppression of virus multiplication. Mostly serum p 24 antigen and viral replication remain suppressed during the first few years of infection.
The antigen appears again in the blood when the immune system is damaged. Hence p 24 anti-genaemia corresponds to the loss of anti p 24 antibody in patients with chronic HIV infection. Virus is easily cultured from a full-blown AIDS than from the asymptomatic person.
Essay # Resistance of HIV:
1. Temperature:
HIV is inactivated at 56°C in half an hour; at 100°C in less than a second. It withstands lyophilisation, hence, the virus in lyophilized blood products can be inactivated by heating at 68°C for 72 hrs.
2. Disinfectants:
50% ethanol, 35% isopropyl alcohol, 0.5% formalin, 3% hydrogen peroxide, 0.5% lysol, 0.5% iodine can inactivate HIV in 10 minutes.
Essay # Transmission of HIV:
1. Sexual Contact:
Sexual transmission occurs among homosexual and heterosexual individuals. There is exchange of body fluid during intercourse. HIV has been isolated from semen, vaginal secretion and breast milk. Genital ulcers may enhance transmission. HIV can also be transmitted by large quantity of saliva.
2. Transmission in Blood:
Infected blood transfusion, blood products, sharing needles as in drug abusers or accidental inoculation can transmit HIV.
3. Perinatal Transmission:
HIV can be transmitted from an infected mother to her foetus through placenta. At birth, an infant may be infected when infected placental blood or fluid cut animates abrasions of infant. Post-natal infection is acquired from breast milk.
Essay # Pathogenesis of HIV:
After entry into blood stream, HIV attaches itself to CD4 lymphocytes. Once in the host cell, the virus releases RNA which is transcribed by reverse transcriptase into DNA (provirus) which gets integrated into host cell chromosome causing latent infection.
HIV grows slowly in CD4 lymphocytes and monocytes. There will be depletion of T4 cells and macrophages. It results into impaired responses of T4 cells leading to recurrent life- threatening opportunistic infections characteristic of AIDS.
Group I: Acute HIV Infection:
The acute illness is characterised by malaise, fever, sore throat, rash and lymphadenopathy. Peripheral blood shows lymphocytosis. Acute HIV illness is mistaken for infectious mononucleosis. Some cases, are accompanied by transient signs of meningitis, encephalitis or neuropathy. Infection of CNS occurs early due to initial viraemia.
Group II:
Asymptomatic HIV infection in this group, all infected persons are well but HIV antibody positive.
Group III:
Persistent generalized lymphadenopathy.
In this group, lymph node is enlarged (more than 1 cm) at two or more extra-genital sites for three months.
Group IV:
AIDS or AIDS related conditions (ARC).
The immune system is overwhelmed by viruses. During this stage, the patients suffer from fever, night sweat, diarrhoea, muscle pain and weight loss. The T4 lymphocytes count decreased. In case of full blown AIDS, the ratio of CD4 (helper) to CD8 (suppressor) cell reversed from 2: 1 to 1: 1 or 0.5: 1. The total T cell count is less than 200/cu mm.
Essay # Clinical Types of HIV:
Incubation period varies from 1-14 years, average of 6 years.
(1) AIDS in Adults:
Anal and genital intercourse, intravenous drug abuse, haemophiliacs treated with blood or blood products, and blood transfusion are risk factors for transmission of AIDS in adults.
(2) AIDS in Pediatrics:
Infected mother can transmit HIV to babies. Children may be infected after transfusion of HIV infected blood or blood products. Symptoms develop within 2 years in paediatric AIDS. In human immunodeficiency in children, there is opportunistic infections (interstitial pneumonitis, candidiasis and recurrent bacterial sepsis) and death due to Kaposi’s sarcoma.
Essay # Complications of HIV:
A. Infections
1. Protozoal: Pneumocystis carinii, pneumonia, toxoplasmosis, cryptosporidiosis.
2. Fungal: Candidiasis, Cryptococcus’s, aspergillosis, histoplasmosis.
3. Bacterial: M. tuberculosis, M. avium, salmonellosis, nocardiasis.
4. Viral: Cytomegalovirus (CMV); Herpes simplex. B. Malignancies
They are common in about 40% homosexuals with AIDS:
1. Kaposi’s sarcoma 90%
2. Lymphoma 10%
Almost 90% of HIV infected individuals die due to supervening infections.
Essay # Immuno-Pathology:
1. Humoral Response:
Repeated infections result in massive antigenic stimulation of B cells. Depletion of regulatory T4 cells may result into the formation of polyclonal immunoglobulin’s. In-spite of adequate circulating Igs, an AIDS patient shows deficient immune response to new antigen.
2. Cellular Response:
In asymptomatic HIV infection, immune response does not recognise the latent provirus, Cell Mediated Immunity (CMI) is undisturbed and cytotoxic T-cells are capable of lysing cells that are producing HIV particles. As the disease progresses, there is destruction of T4 (helper) cells; as a result of which there is a decline in cell mediated response to all antigens.
Essay # Laboratory Diagnosis of HIV:
A. Specific Tests for HIV Infection:
1. Isolation of virus
2. Detection of HIV antigens: p 24 anti-genaemia, polymerase chain reaction
3. Detection of HIV specific antibodies ELISA (Screening test)
Western Blot (confirmatory test):
B. Non-Specific Tests:
1. Total and differential white cell count
2. Assay of T-lymphocyte subsets
3. Platelet count
4. Estimation of Ig G and Ig A levels
5. Skin test for CMI
C. Tests for opportunistic infections and tumors.
1. Isolation of Virus:
It can be done during window period and acute infection from CD4 lymphocytes of peripheral blood, bone marrow, serum or plasma.
2. HIV Antigen Detection:
Shortly after HIV infection (after about 2 weeks) free p 24 Ag and Reverse Transcriptase (RT) can be detected in sera. The serum level of p 24 Ag is an useful guide to monitor the virus suppression, when the patient is under Azidothymidine (AZT) therapy.
Polymerase Chain Reaction (PCR):
In HIV infection, PCR can detect viral gene (provirus) during window period.
3. Antibody Detection:
During “window period“, HIV infected person is sero-negative; in most laboratories, the diagnosis of HIV infection is made by detection of serum antibodies to viral protein both core (p 24) or envelope (gp 120, gp 41). There are two types of serological tests (screening and confirmatory). The screening test is easy to perform and are highly sensitive for a broad spectrum of antibodies.
Sera positive in screening (ELISA) test can be confirmed by confirmatory (Western Blot) test for HIV infection. ELISA kit contains both HIV-1 and HIV-2 and thus either detected in routine screening.
Western Blot Test:
There are three types of electro-blotting tests:
Southern blot, in human of Edward Southern who invented the process of analysing fragments of DNA and Northern blot (named factiously) employed to analyse transferred RNA. These two tests can detect antigen by known antibody.
The third electro-blot test is commonly termed Western blot to maintain the geographical contour and is used to detect unknown antibodies by known antigen. It is also known as “Immuno blot test.”
In Western blot test, HIV is broken down (speared) into protein fragments in a polyacrylamide gel. The separated proteins are blotted electrophoretically from the gel into a strip of nitro-cellulose sheet. These strips are incubated with test sera. Antibodies to HIV protein, present in test serum, combine with all or any fragment of HIV.
The strips are washed and treated with enzyme conjugated anti-human gamma globulin and allowed to react. Then a suitable substrate is added that produces colour bands. The position of colour bands on the strips indicates the fragment of antigen to which serum antibodies combined. In a typical case of HIV infection, usually bands with multiple proteins are formed.
B. Non-Specific Tests:
The following parameters can detect immuno deficiency arid monitor therapeutic response:
1. Blood Count:
In a full blown AIDS, there is leucopenia with a lymphocyte count of less than 400 per cu mm and thrown leucocytopenia.
2. T-cell Subset:
In AIDS, the count of CD4 lymphocytes fall below 200/cu mm. The count of CD4 lymphocytes rises with effective therapy.
3. Hyper-Gamma Globulinaemia:
Ig G and Ig A levels are raised in blood.
4. CMI is diminished as evident from tuberculin skin test.
Other Investigations:
1. Opportunistic infections are diagnosed by direct microscopy cultural or serological tests.
2. Malignancy is frequently associated with AIDS in homosexuals (4%); Kaposi’s sarcoma
(38%) is a malignant vascular tumour which appears pink on the skin and mucous membrane.
Essay # Epidemiology of HIV:
It is well-established that HIV is mainly a sexually transmitted disease, though it was originally observed in homosexuals. It may be transmitted through blood, semen, vaginal fluid, via breast milk, from infected mother to her child through placenta.
Because of the educational programme, homosexual contacts have fallen. Through routine screening test, HIV infection through blood transfusion is virtually eliminated. An infected person may transmit the virus unknowingly during latent period and asymptomatic phase.
Though AIDS has spread in 1970s or 1980s in America, Western Europe, East and central Africa, about 8 to 12 million individuals are infected with HIV and about 1.5 million AIDS cases may have occurred in adults worldwide (WHO, 1993). By August 1994, about 650 cases of AIDS have been reported from India; incidence is higher in males than females (2: 1).
On World AIDS Day—2000 it was reported on December 1, 2000 that about 3.5 lakh persons are already infected and most of them are in the prime of youth. 89% of the reported cases, are inactive and economically productive age group of 18-40 years, over 50% of new infection taking place among youth below 25 years.
HIV infection has reached over 1% among women attending antenatal clinic. 80% of all new infection, are through sexual transmission, 6% by injecting drugs, 4% through blood transfusion in India (National AIDS Control Organisation, NACO, New Delhi, India).
Further it was reported that there are mainly two types of HIV:
HIV type 1 and type 2. Within HIV-1 there are various subtypes.
In India, the most common type of HIV is HIV subtype 1 and subtype C which are more virulent. Subtype C spreads faster and—if not controlled—kills faster.
In much developed countries, HIV-1 and subtype B are more common (Northern America and Europe). Subtype O is also reported in India. However, HIV type 2 is generally less common and as well as less dangerous as it does not spread as fast as other subtypes. HIV type 1 is more common and consists of innumerable subtypes MNO.
As per NACO figures, in India about 80% cases are due to HIV type 1; 1.8% due to HIV type 2; 1.5% have HIV type 1 and 2 combined. HIV type C is more dangerous, spreads faster and kills faster.
Essay # Prevention of HIV:
Following preventive measures should be adopted through health education:
Sexual Contact:
Safer sex should be followed by avoiding exchange of body fluids (semen, vaginal discharge). The use of condoms should be encouraged to prevent the transmission of the virus.
Sharing Needles:
During drug abuse, needle and syringe should not be shared.
Blood and blood products should be screened before transfusion. The same procedure should also be practiced for donation of semen, cornea, bone marrow, kidney, since HIV can spread through any tissue.
Control of infection can be done by screening the individuals from risk group.
Isolation of AIDS patients is of great necessity to check the spread of infection. Then treatment against virus and other opportunistic infections is also essential.
Risk factors are female sex workers, intravenous drug abuse, men and women with multiple sex partners.
Essay # Prophylaxis of HIV:
No effective vaccine is available till date. Vaccine maker Yax Gen Ine President Dr. Donald Francis reported in February 24, 2003 that his first attempt to develop a vaccine to prevent AIDS has failed.
Essay # Treatment of HIV:
Azidothymidine (Zidovudine, AZI) is still a drug of choice. Alternative drugs (dideoxynosine, dideoxycytidine) are under evaluation.
HIV is diagnosed by IgG to viral protein not to virus of antigen:
(A) ELISA is an immuno-enzymatic technique, rapid, sensitive, reproducible, less specific, less costly. This test can detect antibody against viral protein.
(B) Western Blot or Immuno Blot. Denatured viral protein is the basis for this test. This technique can detect antibody against denatured viral protein or and body against fragments of gp 120 (glycoprotein of the envelope).
(C) RIPA test (Radio immunoprecipitation test) can detect antibody against glycoprotein and also native viral protein by radio-isotopic technique. This test is more specific, less sensitive, more costlier than ELISA test.
Seropositivity is observed between 1 to 4 months after contamination. Possible HIV transmission is through dental surgery.
Essay # Arthropod Borne Rickettisal Infections:
Rickettsiae occupy a biological position which is intermediate between the smallest bacteria and the largest virus. Rickettsiae are small prokaryotic cells that have an obligate intracellular existence. They resemble bacteria as they are visible under light microscope and are known to divide by binary fission. They have cell wall containing the amino sugar (muramic acid) and are susceptible to the action of antibiotics.
Like viruses, they are obligate intracellular parasites except Rickettsia Quintana which grows extracellularly in the louse gut and has been cultivated on modified blood agar medium. Under natural conditions, they are present in the alimentary canal of blood sucking arthropods (lice, ticks, flea, mite) but when they are transmitted to man they cause the disease “Typhus” characterised by fever and rash.
Diseases Arranged According to the Arthropod Vectors:
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1. Louse Borne Typhus:
(a) Epidemic typhus Rickettsia prowazekii
(b) Trench fever R. Quintana
2. Flea Borne Typhus:
Murine endemic typhus R. Mooseri
3. Tick Borne Typhus:
Rocky mountain spotted fever R. rickettsii
4. Mite Borne Typhus:
(a) Scrub typhus R. tsutsugamushi
Rickettsiae are Coccobacilli:
Though they are Gram negative, they can be stained with Castaneda or Giemsa stain. In general, they are easily destroyed by heat, drying and chemical disinfectants. Rocky mountain spotted fever, first recognised by Ricketts in America, is caused by R. rickettsii and is transmitted by a tick (Dermacentor andersoni). Fresh tick faeces are infectious.
Louse borne typhus fever (epidemic typhus fever) is caused by R. prowazekii and is spread by the human body louse (Pediculus corporis). Though it is worldwide in distribution, it is confined to Middle East, Asia, Africa, Mexico.
Lice become infected while biting infected patients or carriers, when the infected blood reaches the intestine of the louse, rickettsiae invade the epithelial cells until the host cells distend and rupture. As a result, the faeces of louse become heavily laden with the organisms and when they are discharged on the skin, they enter the blood stream through the abrasions or fresh bite wounds, causing rickettsiaemia.
Typhus is characterised by an onset about two days during which there are nausea, headache, dizziness and high fever, then appears a rash which may cover the whole body. The patient is lethargic and delirious. The blood of the patient is infectious to the louse.
The organism cannot be demonstrated microscopically in the blood, but it can be cultivated in yolk sac. However complement fixation test (CFT) is most accurate and specific as the antigen is derived from the rickettisae cultivated in yolk sac.
