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In: International Conference on the Implications of AIDS for Mothers and Children: technical statements and selected presentations jointly organized by the Government of France and the World Health Organization, Paris, 27-30 November 1989. Geneva, Switzerland, WHO, Global Programme on AIDS, 1989. 23-4. (WHO/GPA/DIR/89.12)Large gaps exist in knowledge of the clinical, immunologic, and virologic correlates of human immunodeficiency virus (HIV) transmission from infected mothers to their infants. Physiological changes in the immune system of pregnant women as well as maternal antibodies to certain virus-encoded proteins may affect the natural history of HIV infection. Also relevant may be the stage of the mother's infection and the time of HIV transmission to the fetus. There is some evidence that maternal antibodies to the immunodominant hypervariable loop in gag protein 120 may reduce the risk of transmission to the fetus. More basic research in virology and immunology is needed for the development of prophylactic and therapeutic approaches to maternal-infant HIV infection. Research priorities include the following: the impact of pregnancy on clinical outcome and virological and immunologic markers in HIV-infected women; correlates of perinatal transmission such as virus characteristics and load, neutralizing antibodies, and cell-mediated immunity; possible immunologic or chemotherapeutic interventions to decrease perinatal transmission; and the standardization of virologic and immunologic markers for pediatric HIV infection.
BULLETIN OF THE WORLD HEALTH ORGANIZATION. 1993; 71(5):641.Oral fluids are a mixture of saliva and oral mucosal transudates (OMT). Saliva is a product of the salivary glands and contains mostly IgA, while OMT is mostly fluid in the subgingival space derived from the passive transport of plasma and contains mostly IgG. The IgG concentration, however, is much lower than that in serum. Testing for antibodies to HIV in oral fluids has been proposed as an alternative to antibody testing in blood. The fluids may be collected directly by dribbling into a receptacle and via absorption onto pads using specially designed collection devices. Only one commercially available HIV antibody test is, however, specifically designed for use with oral fluid samples. Some existing commercial tests designed to detect antibody to HIV in blood samples have been modified for use with oral fluids, but only limited information is available on their performance. Several studies suggest that using tests to detect HIV antibodies in oral fluids may be adequate for some situations, but a number of issues remain to be addressed. WHO therefore recommends that a full evaluation of the detection of HIV antibody in oral fluids be undertaken to address the issues before recommendations on HIV antibody testing using oral fluids are made. Such evaluation would gather information on the accuracy and cost-effectiveness of testing oral fluids. Ethical considerations when performing HIV testing using oral fluids would be the same as those for blood: non-coercion, informed consent, counseling, and confidentiality.
WHO international quality assessment scheme for HIV antibody testing: results from the second distribution of sera.
BULLETIN OF THE WORLD HEALTH ORGANIZATION. 1992; 70(5):605-13.The WHO international quality assessment scheme for human immunodeficiency virus (HIV) antibody testing has been established to monitor the quality of laboratory performance in testing for antibodies to HIV. Following a small trial distribution of specimens early in 1989, the second distribution was made in February 1990. A total of 20 specimens of sera, 10 of which contained antibodies to HIV-1, were sent to 103 laboratories located in the 6 WHO Regions. Participants were asked to report to WHO their findings on each specimen for each diagnostic assay used and their interpretation of the HIV antibody status of each specimen. For the antibody-positive specimens; 98.2% of the results were interpreted as positive and 1.8% as indeterminate; no false-negative interpretations were reported. For their antibody-negative specimens, 90.3% of the results were interpreted as negative, 1.3% as positive, and 8.4% as indeterminate. Most of the indeterminate reports were associated with one particular specimen. A wide variety of diagnostic assays and combinations of assays were used. In terms of the technical results obtained rather than their interpretation, the assays appeared extremely reliable for the positive specimens, with 99.5% of assay results being recorded as positive, 0.17% as negative, and 0/34% as indeterminate. There were more errors associated with the negative specimens: 93.5% of assay results were recorded as negative, 3.5% as positive, and 3% as indeterminate. However, ;61% of the false-positive and indeterminate assay results obtained with the negative specimens were associated with only 2 specimens. There were considerable variations in the Western blot patterns reported and a variety of different interpretative criteria were applied to them. (author's)
ANNALS OF TROPICAL PAEDIATRICS. 1989 Mar; 9(1):1-5.A total of 177 children seen at 2 hospitals in Kampala are described who were strongly suspected of having acquired immunodeficiency syndrome (AIDS), either on clinical grounds or because they fulfilled WHO case- definition criteria for diagnosis of pediatric AIDS. Blood was taken from the 177 children and 154 of their mothers and tested for antibody to human immunodeficiency virus (HIV) by an enzyme-linked immunoassay (ELISA). Altogether, 119 (67%) children were seropositive, but only 85 (71%) fulfilled the WHO case-definition criteria, and they were significantly older than the 34 who did not fulfill the criteria. A further 58 children were seronegative but fulfilled the WHO criteria. Of the 119 seropositive children, only 3 had a history of previous blood transfusion, but 103 (98%) of 105 mothers were HIV seropositive: consequently, their children were considered to have been infected in utero or perinatally. 13 (26%) of 49 mothers of seronegative children were seropositive. 80% of HIV-infected children were under 2 years of age at diagnosis and 23% died within 3 months of diagnosis. None of the parents was known to be an intravenous drug user, a prostitute, or bisexual. The difficulty of accurate diagnosis of AIDS presents a major problem in Africa, as the WHO clinical case-definition criteria alone are clearly not adequate. (author's)
JAMA. 1988 Dec 9; 260(22):3286-9.In Africa, as in many developing countries where AIDS has been documented, the specific serologic test for antibody to the human immunodeficiency virus is not feasible, and the case definition of the Centers for Disease Control is impracticable because facilities for diagnosing the opportunistic infections are inadequate and the clinical spectrum of AIDS is different in tropical countries. The World Health Organization developed a clinical case definition at a 1985 AIDS workshop in the Central African Republic. It was tested to determine its generalizability in Zaire, and the present paper is a report on experience using the definition to identify AIDS in Uganda. A clinical case of AIDS is defined by the presence of at least 2 major signs and 1 minor sign. The major signs are fever for more than 1 month, weight loss greater than 10%, and chronic diarrhea for more than 1 month. The minor signs are persistent cough for more than 1 month, pruritic dermatitis, herpes zoster, oropharyngeal candidiasis, ulcerated herpes simplex, and general lymphadenopathy. The presence of disseminated Kaposi's sarcoma or disseminated cryptococcosis is sufficient by itself to diagnose AIDS. The Uganda study included 1328 patients at 15 hospitals. 562 patients (42%) tested positive by enzyme-linked immunosorbent assay, and 776 (58%) tested negative. 424 patients (32%) met the world Health Organization clinical case definition for AIDS. The World Health Organization definition had a sensitivity of 55%, a specificity of 85%, and a positive predictive value of 73%. However, so many of the patients in this sample had active tuberculosis that it was decided to substitute "persistent cough for more than 1 month without concurrent tuberculosis" as a minor sign in place of "cough for longer than 1 month." With this modification 350 patients met the clinical case definition for AIDS. Sensitivity dropped to 52%, but specificity rose to 92%, and positive predictive value rose to 83%. Moreover, 26% of the seropositive females indicated amenorrhea as a symptom. Addition of amenorrhea to the modified case definition gave it a sensitivity of 56%, a specificity of 93%, and a positive predictive value of 86%. However, this is the 1st report of amenorrhea as a symptom of AIDS, and it may only be a symptom of severe weight loss in women of childbearing age. The findings in the Ugandan experience support the generalizability of the modified World Health Organization clinical case definition of AIDS and its use for surveillance purposes in Africa.
Washington, D.C., National Academy Press, 1988. x, 239 p.The Committee for the Oversight of AIDS Activities presents an update to and review of the progress made since the publication 1 1/2 years ago of Confronting Aids. Chapter 1 discusses the special nature of AIDS (Acquired Immunodeficiency Syndrome) as an incurable fatal infection, striking mainly young adults (particularly homosexuals and intravenous drug users), and clustering in geographic areas, e.g., New York and San Francisco. Chapter 2 states conclusively that HIV (Human Immunodeficiency Virus) causes AIDS and that HIV infection leads inevitably to AIDS, that sexual contact and contaminated needles are the main vehicles of transmission, and that the future composition of AIDS patients (62,000 in the US) will be among poor, urban minorities. Chapter 3 discusses the utility of mathematical models in predicting the future course of the epidemic. Chapter 4 discusses the negative impact of discrimination, the importance of education (especially of intravenous drug users), and the need for improved diagnostic tests. It maintains that screening should generally be confidential and voluntary, and mandatory only in the case of blood, tissue, and organ donors. It also suggests that sterile needles be made available to drug addicts. Chapter 5 stresses the special care needs of drug users, children, and the neurologically impaired; discusses the needs and responsibilities of health care providers; and suggests ways of distributing the financial burden of AIDS among private and government facilities. Chapter 6 discusses the nomenclature and reproductive strategy of the virus and the needs for basic research, facilities and funding to develop new drugs and possibly vaccines. Chapter 7 discusses the global nature of the epidemic, the responsibilities of the World Health Organization (WHO) Global Program on AIDS, the need for the US to pay for its share of the WHO program, and the special responsibility that the US should assume in view of its resources in scientific personnel and facilities. Chapter 8 recommends the establishment of a national commission on AIDS with advisory responsibility for all aspects of AIDS. There are 4 appendices: Appendix A summarizes the 1986 publication Confronting Aids; Appendix B reprints the Centers for Disease Control (CDC) classification scheme for HIV infections; Appendix C is a list of the 60 correspondents who prepared papers for the AIDS Activities Oversight Committee; and Appendix D gives biographical sketches of the Committee members.