K. M. De Cock

Contribution of tuberculosis to slim disease in Africa.

Abstract Objectives: To assess the contribution of tuberculosis to the aetiology of the HIV wasting syndrome (slim) in Africa, a condition usually considered an enteropathy. Methods: Clinical examination and representative necropsy study of adult patients positive for HIV. Setting: Hospital medical wards in Abidjan, Ivory Coast. Subjects: Adults positive for HIV. Main outcome measures: CD4 T lymphocyte counts before death, clinical and anthropometric data, and gross and microscopic pathology. Results - Necropsy was done on 212 HIV positive adults. Tuberculosis was found in 41 of 93 with the clinical HIV wasting syndrome and in 32 of 119 without (odds ratio 2.1, 95% confidence interval 1.2 to 4.0). A significant association existed between the prevalence of tuberculosis at necropsy and the degree of cadaveric wasting (no wasting 25% (15/59); moderate wasting 40% (23/58); skeletal wasting 44% (42/95); P=0.02). Wasting was also associated with a history of chronic diarrhoea, but no association existed between diarrhoea and tuberculosis. Median CD4 T lymphocyte counts were lowest in wasted patients irrespective of findings at necropsy and in those with chronic diarrhoea (<60x106/l). Conclusion: Wasting and chronic diarrhoea are late stage manifestations of HIV disease in Africa. The importance of tuberculosis as a contributing factor in the pathogenesis of the slim syndrome has been underestimated. In nearly half of patients dying with severe wasting, tuberculosis was the dominant pathological finding.

From exceptionalism to normalisation: a reappraisal of attitudes and practice around HIV testing.

Since recognition of the first cases in 1981, AIDS has been handled differently from other infectious diseases. Recently, therapeutic interventions that influence the clinical course and perinatal transmission of human immunodeficiency virus have become available.1 2 3 In this paper we argue that earlier and more widespread diagnosis of HIV infection will be required for these interventions to fulfil their potential. At the start of the epidemics in the United States and the United Kingdom, men who have sex with men argued when HIV/AIDS was first recognised—with the support of civil liberties groups, physicians, public health officials and others—for policies that differed from a traditional infectious disease control approach.3 4 5 6 This strategy has previously been termed “HIV/AIDS exceptionalism.”3 Clinical confidentiality and anonymised surveillance systems were emphasised, and informed consent was strengthened. The use of HIV antibody tests, when they became available, was restricted in a way not seen previously for other diagnostic investigations. This initial response, based on concerns about abuses of civil rights, was influenced by the vocal involvement of members of affected communities in the science and politics of HIV/AIDS (AIDS activism). Exceptionalism initially had a limited effect on clinical care because treatment had only a modest influence on prognosis. The issue of generalised antenatal testing in women retained a low profile because women accounted for a minority of people in industrialised countries infected with HIV. Concerns about discrimination and compulsory testing dominated debate at a time when the only measures to prevent transmission to infants were termination of pregnancy or avoidance of breast feeding. Normalisation then refers to treating HIV/AIDS more like other infectious diseases for which early diagnosis is essential for appropriate therapeutic and preventive measures, within the requirements of informed consent and respect for confidentiality. A number of recent scientific …

Disease progression and survival in HIV-1-infected Africans in London

Objective:To examine differences in progression to AIDS and death between HIV-1-positive Africans (most infected in sub-Saharan Africa and therefore with non-B subtypes) and HIV-1-positive non-Africans in London. Design:Retrospective cohort study of 2048 HIV-1-positive individuals. Setting:HIV-1-infected individuals attending 11 of the largest HIV/AIDS units in London. Patients:Subjects were 1056 Africans and 992 non-Africans seen between 1982–1995. Results:There were no differences in crude survival from presentation to death between Africans and non-Africans (median 82 and 78 months, respectively; P = 0.22). Africans progressed more rapidly to AIDS [hazard ratio (HR), 1.21; 95% confidence interval (CI), 1.02–1.45] but after adjustment for age, sex, Centers for Disease Control and Prevention category B symptoms and CD4+ lymphocyte count at presentation, year of HIV diagnosis and hospital attended, this difference was no longer significant (adjusted HR, 1.15; 95% CI, 0.93–1.43). Africans with AIDS had a reduced risk of death compared with non-Africans (HR, 0.78; 95% CI, 0.63–0.96) but not after adjustment for age, CD4+ lymphocyte count at AIDS, initial AIDS-defining conditions (ADC) and hospital attended (HR, 0.98; 95% CI, 0.76–1.27). Tuberculosis as the first ADC was associated with a 64% reduction in the risk of death. CD4+ lymphocyte decline was not significantly different between Africans and non-Africans (P = 0.18). Conclusions:Differences in progression to AIDS and death and CD4+ lymphocyte decline between HIV-1-infected Africans and non-Africans in London could not be attributed to ethnicity or different viral subtypes. Age and the clinical and immunological stage at presentation, or AIDS, were the major determinants of outcome. Compared with other diagnoses, tuberculosis as the initial ADC was associated with increased survival. Lack of access to health care and exposure to environmental pathogens are the most likely causes of reduced survival with AIDS in Africa, rather than inherently different rates of progression of immune deficiency due to racial differences or viral subtypes.

Disease progression and survival following specific AIDS-defining conditions: a retrospective cohort study of 2048 HIV-infected persons in London.

Objective: To assess the impact of specific AIDS‐defining conditions on survival in HIV‐infected persons, with emphasis on the effect of tuberculosis. Methods: A retrospective cohort analysis of HIV‐infected Africans and non‐Africans attending 11 specialist HIV/AIDS units in London enrolled for a comparison of the natural history of HIV/AIDS in different ethnic groups. Results: A total of 2048 patients were studied of whom 627 (31%) developed 1306 different AIDS indicator diseases. Pneumocystis carinii pneumonia accounted for 159 (25%) of initial AIDS episodes and tuberculosis for 103 (16%). In patients with HIV disease, tuberculosis had the lowest risk [relative risk (RR), 1.11; 95% confidence interval (CI), 0.75–1.63], and high‐grade lymphoma had the highest risk (RR, 20.56; 95% CI, 2.70–156.54) for death. For patients with a prior AIDS‐defining illness, the development of subsequent AIDS indicator diseases such as Pneumocystis carinii pneumonia (RR, 1.18; 95% CI, 0.77–1.83) and tuberculosis (RR, 1.36; 95% CI, 0.76–2.47) had the best survival, and non‐Hodgkins lymphoma had the worst survival (RR, 9.67; 95% CI, 1.26–74.33). Patients with tuberculosis had a lower incidence of subsequent AIDS‐defining conditions than persons with other initial AIDS diagnoses (rate ratio, 0.47; 95% CI, 0.37–0.59). Conclusions: Considerable variation exists in the relative risk of death following different AIDS‐defining conditions. The development of any subsequent AIDS‐defining condition is associated with an increased risk of death that differs between diseases, and this risk should be considered when evaluating the impact of specific conditions. Like other AIDS‐defining conditions, incident tuberculosis was associated with adverse outcome compared with the absence of an AIDS‐defining event, but we found no evidence of major acceleration of HIV disease attributable to tuberculosis.

Risk of tuberculosis in patients with HIV-I and HIV-II infections in Abidjan, Ivory Coast.

OBJECTIVE--To examine the association between HIV-II infection and tuberculosis. DESIGN--Cross sectional study comparing the prevalence of HIV-I and HIV-II infections in patients with tuberculosis and in blood donors. SETTING--Abidjan, Ivory Coast, west Africa. PATIENTS--2043 consecutive ambulant patients with tuberculosis (confirmed pulmonary, presumed pulmonary, or extrapulmonary) and 2127 volunteer blood donors. MAIN OUTCOME MEASURE--Prevalence of HIV-I and HIV-II infections as assessed by presence of serum antibodies. RESULTS--Overall rates of HIV infection were 40.2% in patients with tuberculosis (26.4% positive for HIV-I, 4.7% for HIV-II, and 9.0% for both); and 10.4% in blood donors (7.2% positive for HIV-I, 1.9% for HIV-II, and 1.3% for both). HIV-II infection was significantly more common in patients with all types of tuberculosis than in blood donors (97/2043, 4.7% v 40/2127, 1.9%; odds ratio 3.8%, 95% confidence interval 2.6 to 5.6). CONCLUSION--Both HIV-I and HIV-II infections are associated with tuberculosis in Abidjan. 35% of adult tuberculosis in Abidjan is attributable to HIV infection and 4% specifically to HIV-II.

HIV/AIDS among African Americans: progress or progression?

ObjectivesTo review data on the extent of HIV infection and associated risk behaviors, the occurrence of AIDS, and HIV-related mortality in African Americans and to suggest what can be done to reduce HIV exposure and infection in this population. Design/methodsReview of epidemiologic, published, multisite data on HIV infection in, and related behaviors of, African Americans. ResultsOn every epidemiologic measure in common use, African Americans, compared with the four other federally recognized racial/ethnic groups, have the most severe epidemic. The trend data show continuing growth in the African American epidemic despite the availability of effective behavioral interventions and biomedical treatments. Few published intervention studies with African American populations have been adequately evaluated; nor have they focused proportionately on men who have sex with men, a group in the African American community with continuing high rates of infection. ConclusionsRates of HIV transmission and disease among African Americans are high, disproportionate, and are not declining as significantly in response to effective interventions as they are among whites. Attention is urgently needed to increase our understanding of risk behaviors, social networks, and specific factors in the African American community that can be altered to reduce HIV infection. Macroenvironmental factors – poverty, social class, racism – need to be studied to suggest possible intervention components to reduce rates of HIV transmission and to increase the use of therapies that are more effectively slowing disease progression and lowering death rates among whites.

Preventive therapy for tuberculosis in HIV-infected persons: international recommendations, research, and practice

The World Health Organization estimates that more than four million people worldwide are infected with both Mycobacterium tuberculosis and HIV. HIV infection is the strongest known risk factor for the development of tuberculosis (TB). Mechanisms for the development of active TB include the reactivation of latent infection, rapid progression in primary infection, and/or reinfection with Mycobacterium tuberculosis. Indeed, HIV-infected people with a positive tuberculin skin test have a 5-8% annual risk and a 30% or greater lifetime risk of developing TB. Case-finding and treatment, preventive therapy, the use of BCG, and environmental measures can, however, control TB. Emphasis in developing countries has been upon case-finding and treatment, and providing infants with BCG. Preventive therapy has not been recommended except for breastfeeding infants of mothers with pulmonary TB or other children under five years old living with infectious persons. The high incidence of TB in HIV-infected people in developing countries has, however, led to reconsideration of the role of preventive therapy as a public health strategy. The authors briefly discuss preventive therapy for TB in HIV-infected persons, research issues, and the international role of preventive therapy.

Tuberculosis control in resource-poor countries: alternative approaches in the era of HIV

WHO projections suggest that the annual number of tuberculosis (TB) cases worldwide will reach 10.2 million by the year 2000. HIV plays a dominant role in this increase in many resource-poor countries. The internationally recommended treatment regimens for TB combine some of the six major antituberculosis drugs: isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin, and thiacetazone. WHO treatment guidelines give priority to patients according to the nature of their disease and recommend two regimens of 6-8 months duration, the longer regimen incorporating thiacetazone. Recently, WHO has favored a 6-month treatment regimen given as directly observed therapy (DOT). The disadvantages of the standard approach are the heavy workload of smear examinations, the complexity of some drug regimens, and the low rates of therapy completion. With the increasing TB case load in areas of high HIV infection prevalence, laboratories cannot do initial as well as follow-up smear examinations. In Botswana the proportion of smear-positive TB cases declined to 40% in 1992, but the overall proportion of patients who had smears performed had declined (52% in 1992). The multiple regimens in use cause confusion and nonadherence to guidelines. Nonadherence is the major risk factor for the emergence of drug resistance, and low completion rates are the most obvious signs of inadequate control programs. Alternative approaches mean ensuring high completion rates and using the most effective drugs. Regarding diagnosis, research might show that the number of smears could be reduced depending on the initial reading. There is no reason why a rifampicin-based short-course regimen could not replace the multiple regimens now in use. Rifampicin-containing regimens of 62-78 doses given intermittently have been effective and are suitable for use within a DOT program. For prevention of drug resistance, only pills combining different drugs should be used and rifampicin should be limited to the treatment of TB and leprosy.

HIV and AIDS, other sexually transmitted diseases, and tuberculosis in ethnic minorities in United Kingdom: Is surveillance serving its purpose?

Experience of disease differs across ethnic groups, and ethnicity is a relevant personal characteristic for descriptive epidemiology. Information about ethnicity and country of birth is omitted from the routine notification of many diseases. HIV infection and AIDS, other sexually transmitted diseases, and tuberculosis have different incidence rates in different ethnic groups in the United Kingdom. Omission of ethnic data from surveillance activities allows such differences in incidence to go undetected and unaddressed. Surveillance data that included ethnic details could guide interventions to reduce inequalities in health between different subpopulations.

Tropical medicine for the 21st century

The specialty of tropical medicine originated from the needs of the colonial era and is removed from many of the health care requirements of tropical countries today. Tropical medicine concentrates on parasitic diseases of warm climates, although other infections and diseases related to poverty rather than climate dominate medicine in developing countries challenged by population pressure, civil strife, and migration. In the new century, tropical medicine would best be absorbed into the specialty of infectious diseases, which should incorporate parasitic diseases, travel medicine, and sexually transmitted diseases. Pressing questions for health care and research in developing countries concern the provision of appropriate services for problems such as HIV/AIDS, tuberculosis, sexually transmitted diseases, and injuries. The question of how to provide appropriate clinical care in resource poor settings for the major causes of morbidity and premature mortality has been neglected by donors, academic institutions, and traditional tropical medicine.