Tuberculosis in sub-Saharan Africa: a regional assessment of the impact of the human immunodeficiency virus and National Tuberculosis Control Program quality

BACKGROUND: The effect of the human immunodeficiency virus (HIV) epidemic on tuberculosis (TB) has been evaluated for certain countries in sub-Saharan Africa. However, no multi-country comparisons have been performed of the magnitude of the changes in TB case rates and the roles of the HIV epidemic and national TB control program (NTP) quality in these changes. METHODS: We examined trends in TB case rates after 1985 for 20 sub-Saharan African countries, and also from 1975-1984 for 10 of these countries (core countries). Average annual changes in TB case rates after 1985 were stratified by 1992 urban low-risk HIV seroprevalence and by NTP quality, as determined by a survey of international TB experts. RESULTS: Case rates in the core countries decreased by an average of -1.6% per year prior to 1985, but increased by an average of +7.0% per year after 1985 (+7.7% per year after 1985 in all 20 countries). Average annual case rates after 1985 increased approximately twice as fast in countries with high vs low or intermediate HIV seroprevalence ratings. In both the core countries and all 20 countries, the average annual rate of rise in case rates after 1985 decreased as NTP quality rating increased. This relationship persisted even after stratification by HIV seroprevalence rating. CONCLUSIONS: TB case rates have increased in sub-Saharan Africa since 1985. These increases were relatively greater as HIV seroprevalence increased, and relatively lower as NTP quality increased. Improving NTP quality is essential to mitigate the resurgence of TB in the HIV era.     

Tuberculosis in drug users

The rise in tuberculosis (TB) has disproportionately affected specific populations. Historically, many patients with TB became iatrogenic opiate addicts through therapeutic use of these drugs for symptom control. Demographic trends reshaped the relationship between drug use and TB into one in which drug use became a risk factor for tuberculosis as a result of the overlap of epidemiological and social factors associated with both drug use and TB. The spread of human immunodeficiency virus infection has amplified the spread of TB among drug users. We review the epidemiology of TB in drug users as well as the factors relevant to screening and compliance in drug-using populations. Drug users constitute a high-risk group for whom screening, prevention of infection, diagnosis, and treatment pose particular challenges. The development of TB services capable of engaging drug users (those both in and out of drug treatment programs) has potential for disrupting a significant chain of rapid TB transmission.     

Cosmocerca parva Travassos, 1925 (Nematoda: Cosmocercidae) in toads from Argentina

PURPOSE: To report a case of acute viral disease accompanied by bilateral optic neuritis with substantial paraclinical evidence that human immunodeficiency virus was the causative agent. METHODS: Clinical and paraclinical examination. Magnetic resonance imaging. RESULTS: Virus and antibody titers as well as reverse lymphocytosis were consistent with acute infection by the human immunodeficiency virus-1. CONCLUSIONS: Human immunodeficiency virus infection should be considered in the differential diagnosis of acute optic neuritis.     

Surrogate marker of preclinical tuberculosis in human immunodeficiency virus infection: antibodies to an 88-kDa secreted antigen of Mycobacterium tuberculosis

Antibodies to purified, size-fractionated secreted proteins of Mycobacterium tuberculosis in sera from patients with human immunodeficiency virus (HIV) infection and active tuberculosis (HIV/TB patients), and in stored sera obtained from the same patients prior to clinical manifestation of TB, were evaluated by ELISA, and the repertoire of antigens recognized was analyzed by immunoblotting. Compared with non-HIV/TB patients, HIV/TB patients had lower levels of anti-mycobacterial antibodies, and these were directed toward a restricted set of antigens. Antibodies to an 88-kDa secreted antigen were present in the sera of 74% of HIV/TB patients during the years (1.5-6) prior to manifestation of active, clinical tuberculosis, although only 66% were positive by the time tuberculosis was diagnosed. The presence of antibodies to the 88-kDa antigen can serve as a surrogate marker for identifying HIV-infected persons with active, subclinical disease who are at a high risk of developing clinical tuberculosis.     

Factors related to in-hospital deaths in patients with tuberculosis

BACKGROUND: Deaths from tuberculosis (TB) continue to occur despite the availability of effective antimicrobial agents. Multidrug resistance, human immunodeficiency virus (HIV) infection, and delayed therapy have been implicated. OBJECTIVE: To examine clinical factors associated with in-hospital death in patients with active TB. METHODS: A retrospective case-control study was performed on patients admitted to a government hospital in Johannesburg, South Africa, used as a referral center for patients with TB. Eighty patients admitted with TB who died during hospitalization were matched with 80 similar patients with TB who survived hospitalization. Clinical, demographic, and radiological characteristics of each group were compared. RESULTS: In-hospital fatalities were associated with female sex (P=.01), lower admission hemoglobin level (P<.01), and weight (P<.01), and a trend to more extensive infiltrative patterns on chest radiographs. Multidrug resistance, extrapulmonary disease, and HIV infection were unexpectedly not related to in-hospital mortality. High mortality in the first weeks of admission suggested that late presentation was a major factor for in-hospital death. The HIV-infected participants in the study showed less drug resistance than HIV-negative patients (P=.07), equivalent extents of infiltrative patterns on chest radiographs, but much less cavitation and fibrosis (P<.01). CONCLUSIONS: Clinical predictors of early mortality from TB included anemia, low body weight, and extensive infiltrates, while multidrug resistance and HIV infection were not significant factors. Previous exposure to TB and delayed presentation may have influenced our findings. Since patients present late in their illness, aggressive case finding would be important in controlling TB in this population.     

Nucleic acid components of mycobacteria: recent studies on secreted protein genes

Among the nucleic acid components of mycobacteria, secreted protein genes have been attractive targets in relation to the role in the bacteria-host cell interaction. The alpha antigen gene family is of particular interest from its evolutional constitution process and as a candidate of protective antigen for tuberculosis (TB). Recent studies on DNA vaccination revealed that the antigen 85A, a member of the alpha antigen family, could induce protective immunity against TB. The other studies on the development of recombinant BCG vaccines demonstrated that alpha antigen gene is applicable to a foreign antigen carrier which could obtain protective immunity against human immunodeficiency virus and malaria parasite infections. In this paper, advanced applications of such mycobacterial secreted protein genes are reviewed.     

Acquired drug resistance in Mycobacterium tuberculosis isolates recovered from compliant patients with human immunodeficiency virus-associated tuberculosis

We describe five compliant patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB) that relapsed, with acquisition of resistance by the original Mycobacterium tuberculosis strains. Both the first and second isolates from each patient had the same IS (insertion sequence) 6110-based DNA fingerprint patterns. Three of the five patients developed TB that was resistant to rifampin alone; no mutation in the region of the rpoB gene was detected by a line probe assay in two of the isolates from these patients. We discuss several factors presumably associated with acquired drug resistance in HIV-infected patients, including exogenous reinfection, drug interactions, malabsorption of drugs, and the presence of a large organism burden.     

Transitional cell carcinoma of the bladder in an HIV-infected patient

A case of transitional cell carcinoma of the urinary bladder in a patient infected with the human immunodeficiency virus is reported. The tumour was very large, occupying most of the bladder, however cystoscopic removal of the tumour was successful with no recurrence after one year. This association has never reported before. The possible contribution of human immunodeficiency virus infection to its occurrence is discussed.     

Induction of interleukin-1 and glucocorticoid hormones by HIV promotes viral replication and links human chromosome 2 to AIDS pathogenesis: genetic mechanisms and therapeutic implications

Human immunodeficiency virus may regulate its replication by stimulating the synthesis of interleukin-1. Interleukin-1, in turn, has the ability to stimulate the human immunodeficiency virus enhancer region. The human genes responsible for interleukin-1 and interleukin-1 receptor antagonist synthesis are located on the long arm of chromosome 2. Coincidentally, the trans-activation responsive ribonucleic acid element in the R region of the long terminal repeat of human immunodeficiency virus-1 has been found to interact directly with a factor present on the long arm of chromosome 2 to facilitate transactivation by the human immunodeficiency virus Tat protein. The human CD26 gene is also located on the long arm of chromosome 2. CD26 is a lymphocyte cell surface antigen that is stimulated by interleukin-1 and serves with CD4 as a coreceptor that interacts with the V3 loop in gp120 of human immunodeficiency virus. The human immunodeficiency virus-induced interleukin-1 excess, thus, serves human immunodeficiency virus by enhancing replication, and by increasing human immunodeficiency virus infectivity via activation of CD26. IL-1 also adversely affects acquired immune deficiency syndrome-related Kaposi's sarcoma. Several genetic treatments for human immunodeficiency virus infection are proposed.     

The regurgitation of large vitreous injections

The increasing prevalence of tuberculosis (TB) and human immunodeficiency virus (HIV), particularly in Africa and Asia, led us to investigate the prevalence of HIV infection in immigrants with pulmonary TB at the time of arrival in the UK. We performed anonymous HIV testing of stored sera from 39/65 immigrants referred to our unit between January 1991 and December 1994, who had culture-positive pulmonary TB. None of the 39 patients tested was positive for either HIV-1 or HIV-2, and the characteristics of the 26 patients for whom no serum was available were similar to those of the tested group. Despite the need to consider concomitant HIV infection in any patient with TB, particularly those from an area of HIV endemnicity, the present data do not suggest that recently arrived refugees, asylum seekers, immigrants or long-term visitors to the UK constitute a group in whom dual infection of HIV and Mycobacterium tuberculosis is common.     

Childhood human immunodeficiency virus and tuberculosis co-infections: reconciling conflicting data

The impact of the human immunodeficiency virus (HIV) pandemic on childhood tuberculosis (TB) is unclear because of inconsistent and often contradictory findings in different types of studies. We review the evidence which supports or refutes the likelihood that HIV infection in children predisposes them to TB, and conclude that, on balance, HIV during infancy increases the risk of developing TB. Surveillance shows an association between rising TB rates among children and the HIV epidemic in some parts of the world. A number of cross-sectional studies which have taken children with TB as their starting population, have yielded high rates of association with HIV (11%-64% HIV prevalence). Similarly, cross-sectional studies of hospitalised children with HIV show that many also have TB. These rates of association are all over-estimated because of the uncertainty of diagnosis of TB. Birth cohorts of perinatally HIV-infected infants and children prospectively followed up for a few years have generally failed to detect a higher incidence of TB than anticipated. The few TB cases identified in these cohorts were usually over 15-18 months of age. In acute progressive lung disease there is no excess of TB in HIV-infected over non HIV-infected children. These inconsistencies are discussed and attributed mainly to study design and statistical artefact. However, maternal factors in HIV-positive women which might affect transmission of TB to their babies are assessed, and infant immunoparesis due to HIV which may adversely influence resistance to TB is considered.     

Comparison of genotype and intellectual phenotype in untreated phenylketonuric children

Plasmocytic variants of Castleman's disease are uncommon. We report a new case of abdominal location with a rapidly fatal outcome. Another particularity of that case was the negativity of Kaposi's sarcoma associated herpesvirus, a virus recently implicated in human immunodeficiency virus associated Castleman's disease.     

Molecular dynamics of oligopeptides. 1. The use of long trajectory and high temperature data for determination of statistical weight of conformational substates

The purpose of this study was to assess the accuracy of chest x-ray (CXR) interpretation in the diagnosis of pneumocystis carinii pneumonia (PCP), bacterial pneumonia (BP), and pulmonary tuberculosis (TB) in human immunodeficiency virus (HIV)-positive patients and to identify the frequency with which these infections mimic one another radiographically. The admitting CXRs of 153 HIV-positive patients with laboratory proven BP (n = 71), PCP (n = 73), and TB (n = 9) and those of 10 HIV-positive patients with no active disease were reviewed retrospectively and independently by three radiologists who were blinded to clinical and laboratory data. Median percent accuracies were as follows: TB, 84%; PCP, 75%; BP, 64%; and no active disease, 100%. Fifteen of 153 cases (9.8%) were shown to mimic other infections radiographically. A confident and accurate diagnosis can be made radiographically in the majority of cases of PCP, BP, and TB in HIV-positive patients at the time of hospitalization. In approximately 10% of cases, these infections may mimic one another radiographically.     

Clinical features of tuberculosis associated with HIV infection in Taiwan

To understand the clinical characteristics and outcome of tuberculosis (TB) in patients with acquired immunodeficiency syndrome (AIDS) in Taiwan, we reviewed the medical records of 118 adult AIDS patients who were hospitalized at National Taiwan University Hospital between January 1988 and September 1995. Among them, 29 (24.6%) had TB. The mean age of the AIDS patients with TB was 37 years (range, 25-66 yr). Most patients were in the advanced stages of AIDS when human immunodeficiency virus (HIV) infection and/or TB were first diagnosed. The mean CD4+ lymphocyte count was 0.037 x 10(9)/L (range, 0-0.152 x 10(9)/L) at the time TB was diagnosed. There was no statistically significant difference in the mean CD4+ lymphocyte count between patients with isolated pulmonary TB and those with extrapulmonary involvement. Twenty-two patients (75.8%) had extrapulmonary TB with the most common site being the lymph nodes (72.7%). Clinical symptoms were nonspecific, and the chest physical examination was not helpful in the diagnosis. Acid-fast bacilli were detected in sputum smears from eight patients (36.4%). A primary tuberculosis pattern (hilar adenopathy, pleural effusion, middle or lower lobe infiltrates) in the chest radiographs was the most common radiologic finding (36.4%) in patients with pulmonary TB. The reactivation pattern (predominant upper-lobe infiltrates with or without cavitation) could only be found in cases of pulmonary TB without extrapulmonary involvement. Atypical patterns (diffuse interstitial infiltrates mimicking Pneumocystis carinii pneumonia or other patterns) and normal chest radiographs were noted in nearly one-third of the patients with pulmonary TB. A good response to antituberculosis drugs and a favorable outcome were demonstrated in the patients, except for two with drug-resistant Mycobacterium tuberculosis infection. Early identification of TB in HIV-infected patients requires clinical awareness of the unusual clinical presentations, especially among patients in the advanced stages of AIDS.     

Does extended pancreaticoduodenectomy increase operative morbidity and mortality vs. standard pancreaticoduodenectomy?

SETTING: A study conducted by the Uganda-Case Western Reserve University Research Collaboration in Kampala, Uganda, a country with high incidence rates of tuberculosis (TB) and human immunodeficiency virus type 1 (HIV-1) infection. OBJECTIVE: To assess clinical, microbiologic and radiographic factors associated with risk for relapse in HIV-infected adults treated for initial episodes of pulmonary TB. DESIGN: Nested case-control study within a randomized prospective clinical trial comparing the safety and efficacy of thiacetazone- and rifampicin-containing regimens for TB treatment in HIV-infected adults. RESULTS: The analysis was based on 119 patients who completed therapy. Median follow-up for all subjects was 22.3 months. Ten patients relapsed a median of 12.7 months after the end of therapy; seven of these were initially treated with the thiacetazone (T)-containing regimen. Each relapse case was matched to four controls by length of follow-up after initial TB treatment. In a univariate analysis risk for relapse was associated with treatment with the T-containing regimen (OR = 4.2, P = 0.08), age > or = 30 yrs (OR = 2.9, P = 0.16), and irregular compliance (OR = 3.6, P = 0.1). Baseline anergy on Mantoux tuberculin skin testing, cavitary disease, radiographic extent of disease and sputum bacillary burden, two month culture negativity, and residual cavitary disease at the end of treatment did not differ between relapses and controls. CONCLUSION: Older HIV-1 infected patients, those with poor treatment compliance, and those being treated with T-containing regimens, may be at increased risk for relapse after TB treatment and require closer post-treatment surveillance. Risk for relapse in HIV-infected adults with pulmonary TB after treatment with a nine month rifampicin-containing regimen was low (3.1 per 100 person-years observation) compared with those treated with a thiacetazone-containing regimen (10.1 per 100 person-years observation).     

Carcinoma of the lung in three brothers and two sisters

SETTING: Patients were recruited from Siriraj, Bamrasnaradura, and Central Chest Hospitals, the three major hospitals responsible for tuberculosis patients in Bangkok, Thailand, and vicinity. OBJECTIVE: To evaluate a new rapid serologic test, the MycoDot test, for diagnosis of tuberculosis (TB). DESIGN: The study was conducted as a cross-sectional survey. A total of 594 patients were tested with the MycoDot test. This included 142 human immunodeficiency virus (HIV) seropositive patients with active TB, 144 HIV seronegative patients with active TB, 153 HIV seropositive controls, and 155 HIV seronegative controls. RESULTS: The sensitivity of the MycoDot test for detection of TB was 40.1% in HIV seropositive patients, compared with 63.2% in HIV seronegative patients (P < 0.001). If only patients with laboratory proven TB were evaluated, the sensitivity was 40.6% in seropositive and in 70.8% seronegative patients. The sensitivity of the MycoDot test was similar in TB patients with pulmonary and extra-pulmonary disease. The sensitivity of the test in patients with CD4 counts > or = 200 cells/mm3 was significantly higher than in those with CD4 counts < 200 cells/mm3. The specificity of the test was 97.4%, and was identical in HIV seropositive and seronegative individuals. CONCLUSION: The MycoDot test had a higher sensitivity for the diagnosis of TB among HIV seronegative than HIV seropositive patients. Although the MycoDot test has a less than optimal sensitivity, the test specificity approaches 100%. It may be useful in patients with suspected TB and negative smears and in extra-pulmonary TB.     

Value of dacryocystography in localization diagnosis of lacrimal duct stenosis

SETTING: Department of internal medicine in a general hospital in Rio de Janeiro, Brazil, which provides secondary care to the poor population. OBJECTIVE: The aim of this study was to evaluate the prevalence of human immunodeficiency virus (HIV) infection in patients with pleural tuberculosis (TB) and to compare its manifestations in HIV-negative and HIV-infected patients. DESIGN: Cross-sectional study. METHODS: Forty-three patients with a final diagnosis of pleural TB were submitted to HIV testing (ELISA), chest X-ray, and thoracentesis for biochemical, cytological and bacteriological analysis. Pleural tissue was obtained in 36 patients for histopathological examination. PPD testing was performed in 29 patients. Whenever productive cough was present, sputum acid-fast smears and culture for Mycobacterium tuberculosis were performed. RESULTS: The HIV prevalence was high (30%). TB symptoms were similar in both groups. Atypical radiological aspects were observed in HIV-infected patients with concurrent pulmonary TB (P = 0.03). Pleural fluid, tissue aspects and PPD testing were comparable in both groups. CONCLUSION: Only atypical radiographic patterns in patients with concurrent pulmonary TB were indicative of HIV infection. Therefore, a high index of suspicion is necessary for the early recognition of HIV/TB co-infection. We suggest that all patients presenting with pleural TB should be screened for anti-HIV antibodies.     

Multidrug-resistant tuberculosis. 5. Human immunodeficiency virus infection and multidrug-resistant tuberculosis

Outbreaks of multidrug-resistant tuberculosis (MDR-TB) among human immunodeficiency virus (HIV)-infected persons reported in the United States were very serious and the risks were increased by the delay of diagnosis, rapid progression from infection to active disease, inadequate therapy and poor tuberculosis (TB) control. Prevalence of drug-resistant TB among HIV-infected patients in Japan was studied. The results of drug susceptibility were collected through the nationwide working group for a survey of HIV-infected TB. Data of susceptibility for 39 cases were obtained. The isolates of two cases were resistant to isoniazid and rifampicin (including clinical failure of response), although no outbreak of MDR-TB was found in Japan. Case study of a patient who developed MDR-TB revealed that drug resistance might be selected by insufficient anti-TB therapy. The rate of resistance to any of the anti-TB drugs in HIV-infected patients seemed to be high, although strictly evaluation was difficult due to no standardization for drug susceptibility testing. Of 9 cases with resistance to any of the anti-TB drugs, 8 had extrapulmonary TB including 5 cases of disseminated TB. In contrast thirteen of 30 cases without drug resistance had extrapulmonary TB. Since it has been reported that HIV infection is related to increased rates of drug resistance of TB bacilli, treatment with four-drug regimen should be started and sufficient courses of therapy are needed in HIV-infected TB patients.     

A complete congenital heart block in twins

Ofuji papuloerythroderma (OPE) is a distinctive clinical entity of unknown etiology which occasionally may be associated with B-cell and T-cell lymphomas and visceral malignancy. We describe a case of OPE in a male with the acquired immunodeficiency syndrome. To our knowledge, this is the first report of OPE in a patient infected by the human immunodeficiency virus.     

Detection of HIV infection in pulmonary tuberculosis patients

Well documented 112 pulmonary tuberculosis patients were studied for the prevalence of human immunodeficiency virus (HIV) seropositivity by using two antibody screening tests along with western blot test. Nineteen of the pulmonary tuberculosis patients were HIV seropositive, 12 were acid-fast bacillus smear positive; 12 patients were tuberculin skin test positive and 15 patients were culture positive. As the incidence of HIV infection is increasing in India, it is observed that patients co-infected with HIV and TB are also on the rise. Recognition of the dual infection and taking adequate steps to deal with this epidemic are needed.