Актуальная Медицина - HIV/AIDS

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HIV/AIDS –With an Emphasis on Africa

For surveillance purposes AIDS is defined as an illness characterized by the presence of a reliably diagnosed disease at least moderately predictive of cellular immunodeficiency, and by the absence of an underlying cause for immunodeficiency or any defined cause for reduced resistance to the disease.
The major foci are in sub-Saharan Africa.
The second epidemic focus is around Ivory Coast in West Africa. In the major cities of East and Central Africa AIDS patients make up at least 50% of patients hospitalized in medical services. 
The mortality attributable to HIV infection was 44% for adult males, 50% for adult females, and as much as 89% for adults aged 25-34 years.
In general there are an equal number of men and women among AIDS cases and among people with HIV infection.
HIV seroprevalence rates among the general population in Africa vary widely, from well below 1% in many rural areas or in a country like Madagascar seroprevalence rates usually peak between 16 and 29 years.
(Table 12.1 p.306)

Diseases Moderately Predictive of Cellular Immunodeficiency
Another indication of the importance of sexual activity in the spread of HIV infection is the very high prevalence rates of HIV documented among female prostitutes and patients with other STD.
It is not unusual to find HIV seroprevalence rates over 80% in prostitutes and over 50% among patients with other sexually transmitted diseases in sub-Saharan Africa and even in areas where HIV infection is still uncommon infection rates exceeding 10% are often found.
There is now increasing evidence that, particularly in women, HIV infection is not confined any longer to people with high-risk sexual behaviour.
HIV incidence rates are usually below 1% per year, but may be as high as 5 % in the general population. In contrast, such annual incidence rates may reach a staggering 50% among female prostitutes. In some populations the HIV incidence appears to roughly equal the mortality from HIV infection, resulting in a stable or very slowly rising seroprevalence.
HIV-1 is far more common than HIV-2 in other West African countries, where HIV-1 is spreading fast, but prevalence levels of HIV-2 remain stable.
Both sexual and mother-to-child transmission of HIV-2 are less efficient than is the case for HIV-1.
Whereas homosexual and bisexual contacts have been the main mode of spread of HIV, heterosexual intercourse and injecting drug use become the main routes of transmission in many countries.
Epidemiology: 
HIV is transmitted by sexual contact (heterosexual or homosexual), administration of infected blood or blood products, contaminated injections and from infected mothers to their infants.
In the absence of amplifying factors, the efficiency of penile-vaginal intercourse is low for HIV transmission (well below 1%).
Factors which enhance the risk of heterosexual transmission of HIV include higher viraemia (during acute infection and more advanced stages of the disease) in the infecting partner, sex during menstruation, receptive anal intercourse, the presence of other sexually transmitted diseases, and possibly lack of circumcision in men, cervical ectopy and the use of desiccating vaginal agents.
In particular, genital ulcers such as chancroid syphilis, and genital herpes, and to a lesser extent, gonorrhoea and chlamydial infection, enhance the risk of sexual transmission of HIV.
Mother-to-child transmission of HIV during pregnancy, during delivery or through breast feeding is the second most common mode of spread of HIV-1 in the developing world. The observed rates of mother-to-child transmission of HIV-1 have been consistently higher in Africa than in Europe or North America (30-40% as compared with 15-20%, respectively). 
Factors:
• Transmission through breast feeding; 
• Frequent advanced immunodeficiency associated with higher HIV viraemia; 
• More common occurrence of chorioamnionitis as a result of genital infection;
• In several studies maternal HIV-1 infection was associated with adverse pregnancy outcome, including stillbirth, premature delivery and low birth weight.
• Blood transfusions continue to be a source of HIV infection in many parts of the developing world, particularly in sub-Saharan Africa. This clearly demonstrates that the existence of a fairly simple technology – HIV antibody tests – is not enough for assuring safe blood transfusions. 
There is much heterogeneity in the epidemiology of HIV throughout the world. The HIV/AIDS epidemic is still in an expanding phase in most parts of the world, with continuing geographical spread and changing epidemiological patterns.
Numerous variables may influence the spread of HIV, either directly (i.e. sexual behaviour) or indirectly (i.e. demography, poverty).
The health sector is directly affected by a growing demand for health care, as illustrated by the large numbers of men and women with AIDS occupying often over 50% of all medical beds in the hospitals of many African cities.
As a result of AIDS the incidence of tuberculosis is rising in many countries.
AIDS is already the leading cause of death in adults in many African cities, and is also increasing the under-5 child mortality, reversing the achievements of child survival programmes in high HIV prevalence areas. 

Aetiology and Pathogenesis: 
• AIDS is caused by HIV, which belongs to the lentiviruses, of which two distinct viruses have been identified in man: HIV-1 and HIV-2.
• HIV infection of helper T lymphocytes may result in cell destruction, but the virus may also remain in a state of latency in the lymphocytes or replicate without causing any obvious cell damage or clinical disease. HIV has been isolated from lymphocytes, cell-free blood, semen, cervical-vaginal secretions, brain tissue, cerebrospinal fluid, saliva, tears, breast milk, urine and bone marrow, and can be isolated from other tissues, body fluids, secretions and excretions.
• By nucleic acid analysis of the complete gag genes at least seven distinct HIV-1 genotypes can be identified.
• HIV isolates differ in their biological properties such as replication rate, syncytium inducing capacity and host range.
• African isolates generally exhibit more genetic heterogeneity 
• A second human lentivirus, occurring mostly in West Africa, shares approximately 40% nucleic acid homology.
• Simian immunodeficiency viruses (SIVs) are non-human primate lentiviruses which are more or less related to the HIVs. 
The pathogenesis of HIV infection and AIDS is not fully understood. An immune response to HIV ensues, with a decrease in detectable viraemia followed by prolonged period of clinical latency. 
The basic clinical features of AIDS originate from the critical injury of the immune system, due to the selective infection of helper T-lymphocytes. As a result of this, the host becomes susceptible to life-threatening opportunistic infections and malignancies
• Functional defects can be identified in almost every part of the immune system, including cellular and humoral immunity.
• The main immunological disorders include lymphopenia. 
• A decrease in helper T-lymphocytes.
• T-cell dysfunction. 
• Defective monocyte cytotoxic function. 
• Polyclonal β-cell activation. 
• Non-specific antilymphocyte antibodies.
• Increased levels of B2-microglobulin and defective delayed hypersensitivity. 
Clinical Features:
The clinical expression of HIV infection is very diverse, varying from a healthy carrier state to potentially fatal opportunistic diseases.
The clinical manifestations associated with HIV infection also vary in different populations, due to the relative frequency of endemic infections.
In Africa tuberculosis gastrointestinal and dermatological manifestations are more common than in Europeans and Americans with AIDS.
Acute illness:
Early in the infections with HIV an acute illness may occur, characterized by a mononucleosis-like syndrome, including fatigue, diarrhoea, fever, cough, pruritus, pallor, candidiasis, lymphadenopathy, hepatosplenomegaly and rhinorrhoea.
Occasionally patients may develop a transitory aseptic meningoencephalitis, mononeuritis or polyneuritis.

Asymptomatic HIV Infections 
Latent virus infection may last for at least 10 years after the acquisition of infection. Whereas the median time of progression to disease among individuals with HIV infection is 10-12 years in the industrialized world, this clinical evaluation may be more rapid in Africa.
Prophylaxis with isoniazid in patients with both HIV and Mycobacterium tuberculosis infections considerably prolonged life expectancy.
During this latent period, the patient is infective and HIV can be detected in various body fluids and in lymph nodes.
Antibody to HIV can be demonstrated in serum.
Symptomatic HIV Infection
Weight loss and weakness (asthenia) are the most common clinical manifestations in patients with HIV infection in Africa.
Symptoms and signs are often intermittent and can disappear spontaneously during variable periods.
• Lymphadenopathy involving two or more extra inguinal sites is found in majority of HIV-positive patients;
• Lymphadenopathy occurs most frequently in the cervical and auxiliary regions;
• Lymph nodes are firm, mobile, non-tender and generally do not exceed 6 cm in diameter;
• Lymph nodes larger than 6 cm in diameter in HIV-infected patients are often of tuberculous origin;
• Mucocutaneous manifestations are common in patients with HIV infection;
• A characteristic generalized popular pruritic eruption is found in approximately 20%-60% of African patients with HIV;
• Over 10 % of patients with HIV infection experience a varicella zoster infection, which is recurrent in one quarter of the cases;
• The initial episodes of varicella zoster infection are often the first manifestation of HIV-associated illness;
• Oral candidiasis in the absence of antimicrobial immunosuppressive therapy or an immunosuppressive illness is highly associated with HIV infection;
• Cutaneous hypersensitivity reactions occur with an increased frequency in individuals with HIV infection. They are particularly common during high-dose co-trimoxazole, sulphadiazine or thiacetazone treatment. 
• The predominant clinical presentations of AIDS in adults in the tropics is a diarrhoea-washing syndrome.
• Severe dehydration. 
• Cryptosporidium parvum, microsporidia and Isospora belli are found in variable proportions of patients with HIV /AIDS.
• Fever is a very common symptom in African patients with HIV infection. It may be due to endemic infections unrelated to underlying HIV infection, such as malaria.
• Non-opportunistic bacterial infections are an important cause of morbidity and mortality in adults with HIV infection in Africa.
• Salmonella typhimurium and Streptococcus pneumoniae are the major conventional pathogens in HIV infected patients.
• Staphylococcus aureus, Haemophilus influenzae, Escherichia coli and Shigella spp. also occur.
• Neurological syndromes such as chronic and acute meningitis, myelopathy, encephalopathy with dementia and Shigella spp. also occur.
• Neurological syndromes such as chronic and acute meningitis, myelopathy, encephalopathy with dementia and peripheral neuropathy complicate the clinical course of a majority of AIDS.
• The most common neurological disorder is a progressive change in behaviour associated with dementia which usually progress towards severe dementia.
• Cough in AIDS patients with Pneumocystis carinii pneumonia or with lymphoid intestitial pneumonitis is usually non-productive and frequently associated with dyspnoea.
• Haemoptysis and pleural effusion are mainly caused by tuberculosis or Kaposi’s sarcoma.

HIV Infection in Children 
Clinical disorders in infants and children with AIDS:
• Failure to thrive;
• Persistent oral candidiasis;
• Fever;
• Generalized lymphadenopathy;
• Persistent pulmonary infiltrates;
• Hepatosplenomegaly;
• Chronic parotitis; 
• Recurrent diarrhoea.
The rate of progression from HIV-1 infection to AIDS is faster in children than in adults. However, children with HIV–1 infection may remain asymptomatic for many years, though only 39% of perinatally infected children remain symptom free after 18 months of age.
Opportunistic Infections and Tumours:
An opportunistic infection is defined as an infection with an organism that usually does not cause disease in a healthy person, but that may cause a severe and life-threatening illness in the presence of immunodeficiency. 
• Tuberculosis; 
• Chronic diarrhoea; 
• Cerebral toxoplasmosis;
• Bacteraemia (Salmonella typhimurium, Streptococcus pneumoniae).
Lumbar puncture is therefore always indicated wherever an HIV-infected patient develops headache.
Extra pulmonary tuberculosis has been diagnosed in 10-20% of HIV-positive patients with tuberculosis in Africa.
Tuberculous lymph nodes in AIDS patients frequently show no granulomas, due to an inadequate cellular response.
Cutaneous allergy to tuberculin has been reported in a wide range of patients with both HIV infection and tuberculosis (20-93%).
Lesions may be surrounded by oedema, as in the classical type of Kaposi’s carcoma.
Patients with HIV-2 infection have severe cytomegalovirus infection and HIV-associated encephalitis more often than patients with HIV-1 infection. 
Diagnosis
The diagnosis of AIDS is initially a clinical one, and is based on the identification of an opportunistic infection or a malignancy.
• The presence of serum antibody to HIV should be demonstrated by a well-evaluated serological test; 
• TB represents one of the major problems in the differential diagnosis using this definition;
• The clinical definition for surveillance can be a useful tool in many areas;
• HIV antibody detection offers the most satisfactory approach to the laboratory diagnosis of HIV infection; 
• Serological tests are used for confirming a clinical diagnosis, for screening blood and for epidemiologic surveys; 
• An enzyme linked immunosorbent assay (ELISA) is most commonly used for confirming a clinical diagnosis, for the demonstration of HIV antibody; 
• Gelatine particle agglutination;
• Passive haemagglutination and dot immunoassays;
• Serum that is reactive is considered HIV antibody positive;
• Serum that is non-reactive is considered HIV antibody negative;  
• Serum that is reactive on both tests is considered HIV antibody positive;
• Any serum that is reactive on the first test but non-reactive on the second test is also considered antibody negative;
• Serum reactive at all three tests is considered HIV antibody positive;
• Serum that is reactive in the first and second tests but non-reactive in the third test is considered to be equivocal (Equivocal (Borderline) Test)).
• When diagnosis is the objective, an additional blood sample should be obtained and tested from all persons newly diagnosed as seropositive on the basis of the first sample;
• Any positive test results obtained with testing strategy (I) must not be used for purposes of diagnosis of HIV infection in an individual;
• If the serum produces equivocal results (neither clearly positive nor clearly negative) testing with Western blot may be considered, especially for persons from low-prevalence ( <1% ) populations.
• If the second serum sample also produces an equivocal result, the person is considered to be HIV antibody negative.
Management: 
• Assure psychological and social support; 
• Antiretroviral therapy with zidovudine; 
• Other nucleoside analogues; 
• Reduce suffering from conditions caused by HIV infection; 
• Primary chemoprophylaxis of tuberculosis;
• Avoid contact with mucosal surfaces, blood and other secretions and excretions; 
• Hospital personnel should be thoroughly informed on HIV infection and patient management; 
• Since no effective therapy or vaccine is available, control of AIDS is of necessity based on prevention; 
• Reduction in the number of sex partners;
• Disposable or properly sterilized needles and syringes should be used.

Vocabulary 

Surveillance [sə:`veǐləns] Нагляд
Behaviour [bǐ`heǐvјə] Поведінка
Staggering [`stægərǐŋ] Висип
Routes [`ru:ts] Шляхи передавання
Amplifying factors [əmplǐ`f a ǐ ǐŋ`fæktəz ] Фактори, які зростають
Receptive anal intercourse [rǐ`septǐv`ænəl`ǐntəko:s] Чуттєві анальні зносини
Circumcision [`sə:kəsǐзn] Обрізання, коловидне розсікання
Cervical ectopy [sə:`va ǐkl `e k t əpǐ ] Маткове зміщення
Desiccating vaginal agents 
[dǐsǐk`keǐtǐŋ və`dзa ǐnl`eǐdзǐnts] Вагінальні агенти, які втрачають вологу
Herpes [`hə:pǐs] Лишай
Delivery [dǐ`li:vǐrǐ] Пологи
Adverse pregnancy [əd`və:s`prægnənsǐ] Несприятлива вагітність
Heterogeneity [`hetərəυdзǐni:ǐtǐ] Гетерогенність, різнорідність
Poverty [`povətǐ] Бідність
To reverse [rǐ`və:s] Змінитися
Latency [`leǐtənsǐ] Прихованість
Pruritic eruption [prυə`ra ǐtǐk ǐ`rǎp∫n] Висип, що спричиняє зуд
Conventional [kən`ven∫nl] Традиційний
Dementia [dǐ`men∫ǐə] Недорозвинутість
Equivocal results [ǐ`kwǐvəkl] Сумнівні результати 
Saliva [sə`la ǐvə] Слина
Gag genes [`gæg`dзi:nǐs] Гени, що викликають рвоту
Primate [`pra ǐmeǐt] Первинний
HIV ensues [`eǐt∫ a ǐ v i: ǐn`sјu:z] ВІЛ, який з’являється у результаті
Response [rǐs`po:ns] Реакція на
Helper T-lymphocytes 
[`helpə`ti:lǐmfə`sa ǐts ] Допоміжні Т-лімфоцити 
To be diverse [bi: da ǐ`və:s] Відрізнятися
Pallor [`pælə] Блідність
Transitory aseptic meningoencephalitis 
[`trænzǐtərǐ ə`septǐk`menǐngəυǐnsǐfə`l a ǐtǐs] Перехідний асептичний менінгоенсефаліт
Median [`mi:dǐən] Посередній
Extra inguinal sites [`ekstrə`ǐngvǐnl`sa ǐts] Зовнішньопахові райони
Mucocutaneous manifestations [mјυkəυkјυ`tænǐəs mənǐfǐs`teǐ∫n] Слизовошкіряні прояви
Varicella zoster [`værǐsǐlə`zostə] Поясничний лишай вітряної віспи
To thrive [`θra ǐv] Зростати
Lumbar puncture [`lǎmbə`pǎnkt∫ə] Спинномозкова пункція

Questions:
1. What is the epidemiology of HIV and AIDS in Africa?
2. What are the main factors which influence the transmission of HIV in Africa?
3. How can we describe the etiology and pathogenesis of HIV in the tropics?
4. What are the basic clinical features of AIDS in the tropics?
5. How can we characterize the clinical expression of HIV infection in the tropics?
6. What are the peculiarities of asymptomatic HIV infection in the tropics? 
7. How can we define the symptomatic HIV infection?
8. What do you know about HIV infection in children?
9. Are there any opportunistic infections and tumours associated with HIV infection?
10. How can we diagnose and manage the HIV infection in the tropics?


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