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Tuberculosis retreatment category predicts resistance in hospitalized retreatment patients in a high HIV prevalence area.
International Journal of Tuberculosis and Lung Disease. 2009 Oct; 13(10):1274-80.SETTING: Rates of multidrug-resistant tuberculosis (MDR-TB) are currently as high as 7.7% in retreatment cases in KwaZulu-Natal, South Africa. MDR-TB prevalence is known to be high in patients categorized as treatment failures. Recent reports have questioned the effectiveness of the World Health Organization (WHO) Category II regimen in retreatment TB cases. OBJECTIVE: To determine whether treatment category predicts susceptibility patterns and outcomes in a hospitalized population of retreatment TB cases. DESIGN: Retrospective cohort of 197 pulmonary retreatment cases. RESULTS: Retreatment cases treated with the standard retreatment regimen had a high in-hospital mortality (19.8%), or poor outcome (26.4%) and a high rate of MDR-TB (16.2%). The 'treatment failure' category predicted resistance, with 57.1% of patients exhibiting any resistance compared to other treatment categories (P = 0.02); 53.8% of patients with any resistance experienced poor outcomes, compared to 16.6% of pan-susceptible cases (P = 0.02). There was a trend towards poor outcome in the treatment failure category (42.9%, P = 0.13). CONCLUSION: The retreatment category 'treatment failure' is associated with a high prevalence of resistance in an area of high human immunodeficiency virus (HIV) prevalence. The 'treatment failure' category should be used to identify patients who may benefit from alternative regimens using directed, intensified therapy or second-line agents instead of the current standard retreatment regimen.
BMJ. British Medical Journal. 1991 Nov 9; 303(6811):1189-90.The article proposes that the clinical case definition for Acquired Immunodeficiency Syndrome in Africa is an unworkable concept, with the wrong definition, incorrect validation, improper use, and consequently is a poor surveillance tool. The definition was proposed by the World Health Organization in 1986 to satisfy the use in countries with limited diagnostic resources, and resources for serological testing. Critical review until now of this procedure was lacking. Currently serological testing is available and of high quality. It does not seem justifiable to continue using a provisional surveillance definition. Abandoning this classification procedure may also lead to the focus on problems other than opportunistic infections and AIDs. Clinical surveillance is important, but as well morbidity and mortality need monitoring. It is argued that the definition is an unworkable concept because patients with underlying immunosuppression disorders such as AIDs can not be easily distinguished from chronic disease patients; i.e., pulmonary tuberculosis, renal failure, uncontrolled diabetes, or diarrhea with weight loss. Clinical accuracy is insufficient. It is the wrong definition because pulmonary tuberculosis with a persistent cough cannot be distinguished for those HIV positive and those not. There is inconsistency in the WHO clinical definition and the Centers for Disease Control definitions of AIDs. The incidence of tuberculosis in countries with unmodified clinical case definitions may contribute to an inflated number of AIDs cases. The wrong standards were used to validate the WHO definition in evaluative studies. The reference sensitivity ranges indicate that the definition is insensitive to identifying seropositive patients. Also, the HIV status of patients does not equate with AIDs. Although designed for surveillance, the clinical case definition is used by doctors for individual patient management. Labeling a patient as having AIDs, when he is HIV negative, leads to negative consequences. Researchers compare African AIDs data with North American data with imprecise and noncomparable definitions. As a surveillance tool in countries with a fragmentary or without a vital registration system, it is an inaccurate tool. Alternatives to obtaining data about the spread and impact of HIV are cluster sampling, hospital surveillance of selected populations, anonymous testing of pregnant women or patients in sexually transmitted disease clinics. In Nairobi, a necropsy survey found that 16% had AIDs but 38% were HIV positive.
BMJ. British Medical Journal. 1991 Nov 9; 303(6811):1185-8.Surveillance of Acquired Immunodeficiency Syndrome (AIDS) provides a measure of severe morbidity and mortality caused by the human immunodeficiency virus (HIV); these cases represent severe symptomatic illness within the health care system. AIDs reporting in the US is considered complete with 70-90% of deaths related to HIV. In Africa, WHO estimates that 10% of AIDs cases are reported. This article suggests modifications in the WHO clinical definition of AIDs and discusses problems in the surveillance system. It is noted that clinical work required a simple staging system of HIV infection and disease, rather than epidemiological monitoring. The WHO definition requires 2 major symptoms with at least 1 minor sign in the absence of known causes of immunosuppression such as cancer or severe malnutrition or other recognized etiologies. The major signs are weight loss >10% of body weight, chronic diarrhea >1 month, and prolonged fever >1 month (intermittent or constant). Minor signs are persistent cough >1 month, generalized pruritic dermatitis, recurrent herpes zoster, oropharyngeal candidiasis, chronic progressive and disseminated herpes simplex infection, and generalized lymphadenopathy. The present of generalized Karposi's sarcoma or cryptococcal meningitis are sufficient alone for an AIDs diagnosis. Inadequacies of the WHO definition are its lack of sensitivity, moderate predictive value, and failure to include common symptoms of HIV infection. There is evidence of HIV associated disease not recognized as AIDs. The common symptoms of AIDs in Africa are profound weight loss, chronic diarrhea, and chronic fever (slim disease). The WHO definition was modified in 1987 to include the manifestation of the wasting syndrome. This increased sensitivity was shown in a hospital study in Abidjan in 1988/9. The WHO clinical case definition based on tuberculosis patients in Abidjan. HIV infection and case definitions for AIDs in patients with neurological disease and Kaposi's sarcoma is also discussed. Recommendations for future action are proposed including surveillance of severe HIV associated disease based on clinical presentation combined with serologic tests of HIV--I or II. The WHO definition with modifications is suggested and the need for strong political and medical commitment to complete and timely reported of AIDs and interventions to control the spread of HIV infection.
NEW ENGLAND JOURNAL OF MEDICINE. 1991 Mar 21; 324(12):848.Dr. Goodgame pleads for more openness in discussing the diagnosis of AIDS with the patient. On the other hand, he believes testing for HIV antibodies is largely unnecessary for diagnosis in Uganda, which has 1 of the highest prevalences in the world. Given, however, that the WHO clinical AIDS definition has a positive predictive value of 73% in Ugandan patients (or 83% if cough due to tuberculosis is excluded), 27% of patients in whom there is a clinical suspicion will be erroneously told they have AIDS--"dreadful and at times almost unbearable" news. In other parts of Africa with a lower prevalence this may be even less acceptable. In Gemena, northern Zaire, we evaluated the WHO clinical Aids definition, as modified by Colebunders et al., in 166 patients in 1988-1989. The positive predictive value was 61% (67% if patients with tuberculosis were excluded). This means a wrong diagnosis of AIDS in 1 of every 3 patients. The HIV seroprevalence in this population was 7.9%, as measured in a group of 340 healthy pregnant women. Another problem is the lack of sensitivity of the clinical case definition of AIDS, leading to the possible exclusion of 30-46% of African patients with HIV-related disease in the absence of testing for HIV antibodies. Many patients with AIDS would thus escape detection until they were ill enough to meet the diagnostic criteria. If a standard of care for patients with AIDS is to be achieved in Africa, as Dr. Goodgame proposes, correctly identifying the patients early in the course of the disease is necessary, and we do not believe this is possible without laboratory confirmation. We are aware of the problems that may arise when anti-HIV testing is introduced, and the questions raised (e.g. Who will be tested? What will be done when a positive result is found?) should be thoroughly discussed with the local health team before the test is introduced. In addition, screening of blood donors should have absolute priority over diagnostic testing if a choice has to be made because of the dearth of reagents. (full text)