By: Dr.JEEJA.S, M.D.Hom (Repertory), M.D.Hom (HOMOEOPATHIC PHYLOSOPHY)
Tutor, Department of Organon of Medicine, Govt.Homoeopathic Medical College, Thiruvananthapuram, Kerala.
DEFENITION:- Defined as disabling or life threatening illness caused by HIV, characterized by encephalopathy, a wasting syndrome, or disease caused by immunodeficiency , with demonstrable evidence for HIV infection and without other causes of immunodeficiency.
EPIDEMOLOGY: – HIV was first reported early 1980s. HIV was identified as the causative organism of AIDS in 1983. In 1984 the association between infection with human immunodeficiency virus and the development of AIDS was established. Recent serological test have demonstrated HIV sero positivity in an African male in a blood sample taken in 1947. First confirmed incident in India April 1986 in Tamil Nadu. It is estimated that 10%of normal population are now infected. Worldwide between 5 and 10 million (about 13 million) people are now thought to be now infected with HIV in which 2.5 million have died. The HIV epidemic continues on a global scale. Alarming increases being reported in Central Africa, South America, the Indian sub continent and South East Asia. By the year 2000 WHO estimated that there will be up to 80 million infections worldwide.
MODES OF TRANSMISSION
Infection with HIV essentially requires exchange of semen or other body secretions, milk or blood or blood products infected by the virus.
- Sexual Inter course: – Vaginal and Anal.
Transmitted via semen, cervical secretions and blood.
- Mother to child: – (Prenatally, perinatally and breast feeding)
Neonates of infected women have 13-52 % chances
of acquiring HIV from the mother .
During parturition on contact with HIV containing fluids in the vagina accounts for around 80% of vertical transmission. The risk is increased if the mother has advanced HIV disease with high viral titers. In utero may infect the foetus by crossing the placenta. Breast fed babies have an additional risk of between 10-20%.
PARENTERAL (contaminated blood, blood products and organ donation.)
IVDUs are at risk of infection as a result of the practice needle sharing. There is no evidence that HIV is spread by social or household contact or by blood sucking insects such as mosquitoes and bed bugs.
Transmission to health care workers:-
In these cases major risk factor is needle stick injuries with HIV contaminated blood from an infected patient. The risk of transmission following needle stick injury has been calculated to be 0.3%.
Transmission of HIV has also been postulated through the conjunctiva and open lesions on the skin when in contact with HIV containing body fluid.
% Of risk factors for HIV infection: –
Hetero & Homo sexual intercourse: – 75%
IVDA: – 12%
Contaminated blood and blood products or tissue transfer: -7%
Others: – 4%.
HIV belongs to the Lenti virinae sub family of retrovirus.
Retrovirus has RNA genome and the unique property of transcribing DNA copy of the RNA genome following penetration of the host cell. The DNA is then used as a template to transcribe new RNA viral copies-thus the term retro virus. Lenti viruses generally evade host immune responses and cause persistent infections in several species. HIV has a core consisting of the RNA genome and core protein surrounded by an envelope with high lipid content rendering it sensitive to organic solvent. The unique feature of the virus is that it gains entry to host cell by binding to the CD4 receptor using the viral surface membrane glycoprotien 120. This allows viral attachment and penetration of the host cell. The CD4 receptor is present predominantly on T helper lymphocytes, which are therefore a major target of the virus. But in addition other cell surface molecules act as receptors and core receptors for the virus. Many of these are chemokine receptors, e.g.: – CCR 5 receptor. Following penetration of the host cell the viral RNA is transcribed by the viral enzyme reverse transcriptase into a DNA copy, which becomes incorporated into the host, cell genomic DNA. This viral DNA may then lie dormant within the cell or undergo replication (particularly if that cell is simulated) resulting in transcription of RNA and translation of peptides which joined together with the help of proteinase enzyme to form viral proteins resulting in new virus formation and assembly viruses then bud from the cell surface. New virus is then available to infect other cell and repeat the process.
Two main types of virus-HIV1 & HIV2.
Disease caused by HIV2 is similar to disease caused by HIV1, but is generally milder, slower to progress and poorly transmitted vertically. Until recently HIV2 was confined to West Africa but it is now being detected in India. HIV1 is responsible for most of the disease seen worldwide. HIV2 has 5 sub types. In India HIV1 sub types A, B, C & E have been identified along with HIV2.
The exact mechanism of immunopathology however remained undetermined, since direct infection and damage by HIV to TH cell is not a sufficient explanation as it is frequently found that only 1:10000. TH cells are actually infected by HIV .In addition to lymphocytes HIV can infect and impair the function of many other cell types, in particular cells of the monocyte/macrophage lineage, dentric cells and B lymphocytes.
The over whelming abnormality of immune function caused by HIV is in cell meditated immunity which particularly protected against intra cellular parasites [e.g.: – viruses, protozoa and mycobacteria), where as failure of appropriate antibody responses, which also occurs with HIV infection, results in infection with capsulated bacteria.
HIV also infected cells in the central nervous system. This may be due to migration of HIV infected monocytes to the brain where they become microglial cells.
Immunological abnormalities in AIDS:-
HIV principally affects CD4 helper T lymphocytes. TH cells are responsible for initiation of nearly all immunological responses to pathogens, and following infection with HIV there is attrition of the CD4 population resulting in gradual and increasing failure of most aspect immune function but particularly cell meditated immunity.
T-Helper (CD4) Lymphocytes: –
Decreased in number (low CD$ count in peripheral blood)
Abnormal function: –
Reduced response to antigen
Reduced response to interleukin
Reduced production of interleukin 2 and interferon gamma.
B Lymphocytes: –
Abnormal function: –
Reduced response to specific antigen or mitogen.
Polyclonal activation leading to increased in immunoglobulins.
Monocytes/Macrophages and Dendritic cells: –
Defective antigen presentation.
Defective cytokine secretion
|Sero conversion illness (Fever,rash,splenomegaly diarrhea)||Generalised Lymphadenopathy Fever, Wt: loss||Opportunistic infn: Malignancy|
|Asymtomatic||Pre AIDS syndrome||Acquired immuno deficiency|
|Acquisition of virus||Death CDC|
Following infection with HIV there is a latent period of a few weeks (8-10) during which there is intense viraemia. This period is followed by sero conversion when detectable antibodies to HIV and HIV specific cytotoxic lymphocytes appear in serum. At this time there is a rapid fall in viraemia suggesting that the immunological response has contained the infection. At this stage approximately one third of individual have a brief illness lasting about two weeks.
Symptoms include fever, malaise, and headache, fleeting anthralgia, maculo popular rash, tender lymphadenopathy and occasionally encephalitis, diarrhea and mouth ulcer.
This follows an asymptomatic phase of variable duration. Some may symptomatic y one or two but some remains asymptomatic for many years.
Some but not all HIV infected patients develop progressive generalized lymphadenopathy.
Definition:- Presence of enlarged lymph nodes greater than 1 cm in diameter in two anatomically distinct sites for more than three months in the absence other detectable cause of lymphadenopathy.
They may asymptomatic or have fever and weight loss. Biopsy of lymph node shows reactive hypherplasia. The prognosis of patient develops PGL is the same as for those who do not.
FNACof lymphnode help to exclude other causes such as TB, Lymphoma.
CLASSIFICATION OF HIV ASSOCIATED CONDITIONS
|Absolute CD4 count (cumm)||A||B||C|
|1) > 500||A1||B1||C1|
|2) 200 – 400||A2||B2||C2|
|3) < 200||A3||B3||C3|
Group A: – A/C HIV infection
Group-B: – AIDS related complex
Clinical features of Symptomatic HIV disease
|General symptoms||General Signs|
||3. Oral candidia|
||4. Oral hairy leucoplakia|
||5. Peri anal herpes|
|7. Ideopathic thrombocytopenic purpura|
|8. Herpes zoster involving more than one dermatone|
Group B, characterized by conditions not exclusively confined to immuno-compromised individuals, but are relatively immuno suppressed, are prone to develop ordinary infections such as herpes zoster and bacterial pneumonia.
Group-C: – AIDS
The lower the CD4 count and the higher the viral load, the greater the likely hood of opportunistic infection and secondary neoplasm. Survival for patients once AIDS is established is used to be poor, with only 50% of patients still alive by 18 months.
Opportunistic infections: –
- Cytomegalo viral infection
- C/C (> 1 mounth) mucocutaneous disseminated herpes simplex.
- Progressive multifocal leucoencephalopathy (Papavovirus).
- Extra pulmonary TB or pubnonary TB with CD4 count < 200/mm
- Disseminated mycobacterium avium intra cellular or mycobacterium kanasasii infection.
- Pneumocystis carinii pneumonia.
- Candidiasis of oesophagus bronchi or pulmonary tree.
- C/C (> 1 mth) Cryptosporidiosis.
- Taxoplamosis of brain.
10. Disseminated histoplasmosis or coccidiodomycosis.
- Extra intestinal strongyloidiasis.
SECONDARY NEOPLASMS: –
- 1. Karposis sarcoma.
- 2. Primary lymphoma of brain.
- Non hodgkin’s(immunoblastic) lymphoma.
Lymphocytic interstitial pneumonia (mainly in children).
Disseminated disease in AIDS: –
- CMV infection
- 2. Bacterial septicemia
- 3. M.Tuberculosis
- 4. M.Avium intercellular infections
- 5. Toxoplasmosis
- 6. Cryptococcosis
- 7. Histoplasmosis
CYTOMEGALO VIRUS INFECTION
CD4 count is normally below 50/cumm when clinical disease appears.
Organs involved – eyes, CNS, liver, gut adrenals, mouth and lung.
Most common problem – CMV chorodoretinitis leads to blindness and is characterized by fundal perivascular haemorrage and exudates.
Adrenal involvement – Lassitude, postural hypotension, dehydration and hyponatraemia.
CMV – Encephalitis: – Sub a/c, personality change, poor concentration, headache, insomnia, myelitis, polyradiculopathy.
Colitis:- diarrhoea, weight loss, anorexia, fever (on sigmoidoscopy: diffuse sub mucosal haemorrage and ulceration.
Oesophagitis Rarely causes pneumonia.
Herpes virus: –
Herpes zoster: – Usually in the form of multi dermatomal shingles.
Herpes simplex: – C/C mucocutaneous infection.
Bacterial Infection: –
Due to defective cell mediated immunity intra cellular bacterial infections such as TB. Due to defective antibody mediated protection and neutrophil function infection with capsulated bacteria.
Mycobacterial Infection: –
Mycobacterium tuberculosis: – Tuberculosis may occur at any stage of HIV infection when immunity is still preserved pulmonary disease alone is seen, when CD4 count is low extra pulmonary disease involving lymphnodes, bones pericardium, peritoneum, CNS, liver and bone marrow may occur in addition to military TB.
Non-specific feature such as fever, weight loss and fatigue. Tuberculin test may be unhelpful as it is frequently negative because of immune defect. As disease may be disseminated pulmonary disease may be minimal and there may be no sputum for examination. The chest radiograph appearance is not always typical. The diagnosis relies on suspicion.
A typical mycobacteria: –
Mycobacterium avium intracellular (MAI)
MAI causes disease when the CD4 count is very low <50 cmm towards the end of natural history of AIDS.
Portal of entry: – Through gut.
Clinical features: – Persistant high grade fever, night sweats, anaemia and weght loss, malaise, anorexia, diarrohea, myalgia, occasionally painful lymphadenopathy, hepatomegaly. Chest radiograph or CT scan shows intrathoracic and abdominal lymphadenpathy. Affected organ contain numerous AF bacilli.
Fungal infection: –
- Candidosis: – When candida dpreads beyond the mouth to the cesophagus or more rarely lung it becomes an AIDS defining diagnosis. With oesophagial involvement painful dysphagia is frequent and barium swallow may reveal a very ragged looking mucoscal surface.
- Cryptococcal infection: – Cryptococcal neoformans is the commonest cause of meningitis in AIDS patients and may also cause pulmonary involvement. The organism may be cultured from blood urine, gut or bone marrow involvement.
Initial symptoms of cryptococcal meningitis are fever fatigue weight followed by nausea, vomiting and photophobia.diagnosis is made by Indian ink staining of CSF to identify the organism. CSF culture and measurement of cryptococcal antigen both in serum and CSF. CSF examination shows monocytosis and raised protein.
- Endemic fungal infection in AIDS: – Disseminated infection with histoplasma capstulatum and coccidiomycosis are seen in AIDS patient who have been exposed to these fungi in endemically restricted areas.
Toxoplasma gondii :- is very common in man and following immunosuppression in AIDS . Clinical disease with fever headache and lymphadenopathy. The brain is the most common site for lesions with focal neurological symptoms, convulsions, cognitive impairment, confusion, lethargy or coma.
Retina may be involved.
Cranial CT scan shows a characterized ring surrounded enhancing lesions surrounded by cereberal oedema.
Nematode infections: –
SECONDARY NEOPLASMS OF AIDS
It is an unusual neoplastic condition, rare before AIDS. The aetology remains undetermined although noval herpes virus like DNA has been Is the most common non infectious AIDS defining diagnosis in HIV disease. Identified AIDS associated karposis sarcoma. Karposis sarcoma is most common in homosexual male AIDS patients (about 25%) and sexually transmitted HIV infection whereas it is comparatively rare in AIDS patients with hemophilia. This suggests that a co- factor transmitted by sexual route is required for tits development. Histologically the tumour consists of spindle cells and blood vessels. Most common site of involvement – skin. The mouth the hard palate, the penis, the tip of nose and lower legs are also favorite sites. Lesions are red or volaceous, well circumscribed flat or raised. In dark skinned individuals lesions may appear brown or even black. As CD4 counts falls, Kaposis sarcoma indicates a poor prognosis. Stomach or rectal involvement may present with pain, bleeding or obstruction, hepatospleenomegaly. Cough and breathlessness from pulmonary involvement, May with large pleural effusion.
Non-Hodgkin’s Lymphoma: – this group of lymphoma arises from B lymphocytes (80%) and remains from T lymphocytes. B cell lymphoma including immunoloblastic lymphoma and Burkit type lymphoma. The development of NHL in AIDS patients is an AIDS defining diagnosis. Extra nodal sites are more frequently involved such as CNS, bone marrow, GIT and liver.
Diagnosis: – Tissue biopsy and histological examination. Primary lymphoma of brain however difficult to treat. Short-term responses have been reported following cranial irradiation.
Carcinoma:- There is an increase of cervical dysplasia and neoplasia in HIV infected women and anal carcinoma particularly in HIV infected homosexual men. It is thought to be due to a greater incidence of infection by the human papilloma virus.
Common skin disease in HIV infection: –
- 1. Serborrhoeic dermatitis
- 2. Follicultis / Impetigo/ Cellutitis.
- 3. Secondarysyphilis
- 4. Herpes simplex / Herpeszoster
- 5. Molluscum contagiosum.
- 6. Fungal infections
- 7. Kaposi’s Sarcoma
- 8. Drug eruption
Oral disease in HIV: –
- 1. Candidosis
- 2. Angularstomatitis
- 3. Hairy leukoplakia: – Serrated while area adhered along the sides of tongue. Painless caused by EB virus.
- 4. Gingivitis
- 5. CMV / Herpes simplex
- 6. Stomatitis
- 7. Warts
- 8. Kaposi’s sarcoma
- 9. Aphthous creation
Gastrointestinal disease: –
The oesophagus: – Oesophagus caused by candida Herpes simplex and CMV. Primary lymphoma, Kaposi’s sarcoma and squamous cell ca:
Aphthous ulceration, Gastro oesophageal reflux.
Small bowel disease: – Wt loss, high volume diarrhoea colicky para umbilical pain.
- Entamoeba hystolitica
- Giardia lamblia
- Clostridium difficile
- Strongyloids stercoralis
11. Kaposi’s sarcoma
Colorectal disease: – Frequent small volume stool, left lower quadrant and supra pubic colicky pain, tenesmus and pain on defecation. Number of infections can be among them. Important are CMV and Cryptospridium.
Hepato biliary disease: –
Hepatitis A, B or C.
CMV and MAI infections.
Acalculous cholangitis : – CMV, Candidia, Cryptosporidium.
Respiratory diseases: –
Spectrum of lung disease in AIDS:
|Pneumocystis pneumonia||Herpes simplex/Varicella zoster|
|Haemophilus influenza||Candida/ Aspergillus|
|Moraxella catarrhalis||Strongyloids stercoralis|
|Gram negative bacteria||Toxoplasma gondi|
|Kaposi’s sarcoma||Non specific interstitial pneumonitis|
Pneumocystic carnii pneumonia.
The chest radiograph shows diffuse bilateral interstitialperihilar shadowing. 10% normal chest X-ray. 10% atypical features such as focal consolidation, nodular shadows or cavities. Mediastinal lymphodenopathy and pleural effusion are rare. As sputum production is rare diagnosis requires bronchoscopy and bronchoalvaeolar lavage. The lung washings reveal the cyst of pneumocystis carinii with silver stain.
HIV infects the central nervous system at an earlier stage in the disease. HIV infects direct damage on the central nervous system unlike other organs. HIV can be readily isolated from brain tissue and CSF in a high proportion of patients with neurological conditions and at postmortem pathological changes are present in the brain in about three quarter of patients with AIDS, CT scan, MRI, Lumbar puncture electrophysiological studies help in diagnosis.
Disease of the nervous system in HIV infection and their presentation: –
Seroconvertion illness: – Encephelitis [mood change, altered consciousness, convulsion], aseptic meningitis.
C/C disease: – AIDS dementia complex,
Encephalopathy, Meningitis, myelopathy, Peripheral neuropathy.
Other infections: –
Toxoplasmosis: – Brain abscess
Cryptococcosis: – Meningitis
Papavo virus infection: – progressive multi focal leucoencephalpathy
CMV: – Retinitis, Encephalitis
Herpes zoster: – Meningitis
Tuberculosis: – Brain abcess, Meningitis
Syphilis: – Neurosyphilis
Tumours :- Secondary neoplasms, primary lymphoma, Space occupying lesion.
HIV associated cognitive motor complex [HCMC]
AIDS related organicbrain disease
HIV associated demeniia
AIDS dementia complex [Sub cortical dementia]
Neuropathology and pathogenesis: –
Leucoencephalopathy : – Characterized by diffuse pallor with myelin loss phagocytosis and reactive astrocytosis. Atrophy and diffuse gliosis
HIV encephalopathy: – unique to HIV infection characterized by multinucleate giant cells with multifocal perivascular macrophage infiltration and macrophage containing HIV1. These are most commonly seen in white matter, brain stem and basal ganglia. Neuronal loss in frontal cortex.
Subcortical pattern of impairment. Slowness of thought, social withdrawal, indifference. General loss of interest, bradyphrenia, poor concentration, attention deficit, impairment of visuomotor task and poor impairment.
Signs: – Abnormal eye movement, spasticity, ataxia and movement disorders, myoclonus, hyper reflexia, loss of fine co-ordination pyramidal tract signs.
HIV-1 Related Myelopathy
Three distinct types of myelopathies
- Vascular myelopathy: – Neuropathological feature are similar to those of sub a/c combined degeneration of cord with posterior and lateral column white matter vacuolation.
CF sub a/c, progressive, spastic, ataxicparaparesis.
An abnormal CSF methylation ratio as Vitamin B12 deficiency.
- Degeneration restricted to the gracile tracts with a consequent de afferenting gait atxia may follow dorsal root ganglion necrosis. It may link with cytomegalo virus infection.
- Multnuclleate giant cell changes may extend from brain to spinal cord, more often in children.
HIV related peripheral nerve disease
Diffuse axonal sensorimotor neuropathy.
Distal axonopathy with proximal macrophage infiltration of the peripheral nerve.
Peripheral neuropathies of various types in addition to those caused by HIV may occur, including ascending polyneuritis (Guillen Barre Syndrome) automatic neuropathy or may be caused to Herpes Zoster or CMV infection or drug induced
A positive HIV test result can result in a variety of reaction ranging from anger, guilt, and anxiety with panic attacks through to depression. The patient may have symptoms of organic mental disorders. The stress of HIV and AIDS in terms of relationships, work and social life is likely to result in wide range of affective disorders with depression also common. Episodes of psychosis like Schizophrenia or paranoid illness in AIDS Dementia complex.
Idiopathic Thrombocytopenic Purpura (ITP) : – It is thought to be related to HIV itself and is associated with antiplatelet antibodies. It is usually relatively mild and tends to resolve with the onset of AIDS.
Lymphopenia: – Progressive lymphopenia in particularly CD4 count.
Anaemia : – HIV itself has suppressive effect on bone marrow. Results from wide variety of infection and neoplastic complication of AIDS, marrow infiltration due to MAI, M.Tuberculosis or Lymphoma, C/C blood loss from Kaposi’s sarcoma of stomach, B12 deficiency due to malabsorption following C/C gastrointestinal infection, Drug induced.
Renal involvement: –
Nephropathy: – HIV induced, IVDA, Drug induced with intrinsic renal disease
Cardiac involvement: –
Myocarditis, congestive cardiomyopathy, Pericardial effusion
Endocrine disease: – Adrenalitis(C.M.V Infection)
Therapeutics: – According to Murphi’s Repertory,
3 marks: – Ars, Med, Merc, Thuja
2 marks: – Carc, Echi, Fer-P, Gels, Phos, Syph, Tub
1 mark: – Acon, Arsiod, Bapt, Lyco, Phos acid, Puls, Pyrog, Sil, Sulph, X- ray