Chest radiography patterns in 75 adolescents with vertically-acquired human immunodeficiency virus (HIV) infection.

AIM: To evaluate lung disease on chest radiography (CR), the relative frequency of CR abnormalities, and their clinical correlates in adolescents with vertically-acquired human immunodeficiency virus (HIV) infection. MATERIALS AND METHODS: CRs of 75 patients [59 inpatients (33 males; mean age 13.7±2.3 years) and 16 outpatients (eight males; mean age 14.1±2.1 years)] were retrospectively reviewed by three independent observers. The overall extent of disease (to the nearest 5%), its distribution, and the proportional extents (totalling 100%) of different radiographic patterns (including ring/tramline opacities and consolidation) were quantified. CR features and clinical data were compared. RESULTS: CRs were abnormal in 51/75 (68%) with "extensive" disease in 38/51 (74%). Ring/tramline opacities and consolidation predominated (i.e., proportional extent >50%) in 26 and 21 patients, respectively. Consolidation was significantly more common in patients hospitalized primarily for a respiratory illness than patients hospitalized for a non-respiratory illness or in outpatients (p<0.005, χ(2) for trend); by contrast, ring/tramline opacities did not differ in prevalence across the groups. On stepwise logistic regression, predominant consolidation was associated with progressive dyspnoea [odds ratio (OR) 5.60; 95% confidence intervals (CI): 1.60, 20.1; p<0.01] and was associated with a primary respiratory cause for hospital admission (OR: 22.0; CI: 2.7, 181.1; p<0.005). Ring/tramline opacities were equally prevalent in patients with and without chronic symptoms and in those admitted to hospital with respiratory and non-respiratory illness. CONCLUSION: In HIV-infected adolescents, evaluated in secondary practice, CR abnormalities are prevalent. The presence of ring/tramline opacities, believed to reflect chronic airway disease, is not linked chronic respiratory symptoms.

Risk factors for recurrent tuberculosis in England and Wales, 1998-2005.

BACKGROUND: Information on recurrent tuberculosis can provide an indication of the effectiveness of tuberculosis services and identify patients who are most vulnerable. The objective of this study was to estimate the incidence of, and investigate risk factors for, recurrent episodes of tuberculosis in England and Wales. METHODS: Episodes of recurrent tuberculosis were identified among prospectively collected records of tuberculosis cases reported to the Health Protection Agency between 1998 and 2005. An episode of recurrent tuberculosis was defined as a re-notified case in the same patient after at least 12 months from the date of the initial notification. To estimate incidence, follow-up time was calculated for all cases until re-notification or censure. Multivariable Cox proportionate hazard models were used to determine hazard ratios (HR) for recurrence of tuberculosis and investigate the risk associated with clinical, demographic and microbiological factors. RESULTS: Five hundred and eighty-eight recurrent tuberculosis events were identified among 53 214 cases reported between 1998 and 2005, a rate of 4.1 (95% CI 3.8 to 4.5) episodes per 1000 person years of follow-up. Factors independently associated with a greater risk of recurrent tuberculosis were HIV co-infection (HR 1.64, 95% CI 1.13 to 2.38) and belonging to a South Asian ethnic group (HR 1.54, 95% CI 1.23 to 1.93). CONCLUSION: Tuberculosis recurrence is uncommon in England and Wales despite the absence of a universal directly observed treatment policy. The identification of HIV co-infection as a risk factor for recurrent tuberculosis is consistent with findings elsewhere. The higher risk among South Asians, however, requires further investigation.

Traditional healers, treatment delay, performance status and death from TB in rural South Africa.

BACKGROUND: People in sub-Saharan Africa frequently consult traditional healers before reaching the government health services (GHS). This can lead to delays in starting effective anti-tuberculosis chemotherapy. To our knowledge, no studies have shown a direct relationship between visiting traditional healers, increased morbidity and death from TB. METHODS: All patients starting on anti-tuberculosis chemotherapy at a rural hospital in South Africa in 2003 were included in the study. TB nurses interviewed the patients and established how long they had had symptoms before treatment was started, whether they had visited traditional healers before coming to the hospital, their performance status and, later, whether they had died. RESULTS: Of 133 patients, those who attended a traditional healer took longer to access anti-tuberculosis chemotherapy (median 90 days, range 0-210) than those who went directly to the GHS (median 21, range 0-120). Patients who visited a traditional healer had worse performance status (P < 0.001), and were more likely to die (24/77 [31%] vs. 4/33 [12%], P = 0.04). CONCLUSION: Treatment delay due to visiting traditional healers can have dire consequences for patients with TB. Efforts are required to engage with health care practitioners outside the government sector to improve the prospects for patients with TB.

Poor performance status is associated with early death in patients with pulmonary tuberculosis.

The objective of this study was to determine whether poor performance status at the start of anti-tuberculous (anti-TB) treatment is associated with early death in patients admitted to hospital with pulmonary tuberculosis (PTB). During 3 months in 2001, all adult patients admitted to eight hospitals in Limpopo Province, South Africa, and diagnosed with PTB were eligible for inclusion. At initiation of anti-TB treatment, a performance status between 0 and 4 was estimated for each patient using a modified version of the Eastern Cooperative Oncology Group scoring system. Hospital records and local TB registers were reviewed to identify patients who had died during the first 2 months of treatment. In addition, it was ascertained whether a death notification had been received by the provincial administration. Fifty-three of 295 (18%) patients died within 2 months. Mortality increased from 6% in patients with the best performance status to 51% in patients with the poorest performance status. Univariate and multivariate Cox regression analysis showed that the hazard ratio for dying was significantly higher for patients with a performance status of 3 or 4. Poor performance status shows a strong association with early death in patients with PTB and has the potential to be a useful clinical, epidemiological and research tool.

Residual lung damage after completion of treatment for multidrug-resistant tuberculosis.

SETTING: Limpopo Province, South Africa. OBJECTIVE: To assess the residual lung damage of patients who completed treatment for multidrug-resistant tuberculosis (MDR-TB). DESIGN: Chest radiograph and lung function tests were performed at the end of treatment. The radiographs were read by two independent observers who attributed a zonal score of between 0 and 18, depending on the extent of radiographic abnormalities (opacification or cavitation), counted the number of visible cavities and measured the diameter of the largest cavity. RESULTS: The mean zonal score was 6.5. Cavitation was present in more than half of the patients. Of 33 patients, 31 (94%) had abnormal lung function tests. The median FEV1 was 63% and FVC was 57% of the predicted value. Restrictive and combined restrictive-obstructive lung function patterns were the predominant abnormalities. CONCLUSIONS: Residual lung damage in MDR-TB patients who completed treatment is common and extensive. This may increase the risk of relapse of tuberculosis and reduce the quality of life and life expectancy of these patients. Additional efforts are warranted to diagnose MDR-TB early to reduce the extent of residual lung damage. Close follow-up of MDR-TB patients completing treatment will have to be ensured to detect relapses.

Is the distance a patient lives from hospital a risk factor for death from tuberculosis in rural South Africa?

SETTING: Tuberculosis programmes that rely on district hospitals for diagnosis and initiation of treatment may disadvantage those living furthest away. We present an analysis of such a programme in rural South Africa to see whether those living furthest from the hospital were at greatest risk of dying from tuberculosis. METHODS: All patients diagnosed and treated for tuberculosis in three health districts in 1997 and 1998 were included. An estimate of the distance each patient travelled to get to the hospital was obtained. The distances the patients travelled were categorised into four groups. The furthest distance patients could reasonably be expected to travel to get to their nearest hospital was estimated as 60 km. Outcomes of treatment were recorded using standard definitions. The mortality of patients in each of the four groups was compared. RESULTS: Of 1187 patients started on treatment for tuberculosis in the hospitals, 877 (74%) were known to be alive at the end of treatment, whereas 158 (13%) had died. Distance travelled was a risk factor for death, but only amongst those travelling more than 60 km to get to the hospital (0-20 km: n = 313, odds ratio [OR] 1; >20-40 km: n = 436, OR 1.09, 95% confidence interval [CI] 0.71-1.67; >40-60 km: n = 205, OR 0.97, 95%CI 0.57-1.65; >60 km: n = 79, OR 2.87, 95%CI 1.59-5.17). CONCLUSION: The mortality from tuberculosis was high, even amongst those living closest to the hospital, and did not rise significantly within 60 km. The situation may be different for the relatively small number of patients who come from further away. The distance travelled to hospital for initial diagnosis does not account for the relatively high mortality amongst tuberculosis patients in this area.

Aminohexyl-sepharose affinity chromatography : purification of an auxin receptor.

Affinity chromatography is a widely used technique that is based on specific binding, usually between proteins and low-molecular weight ligands. It is often found that the presence of a spacer arm between the supporting matrix and the affinity ligand is beneficial to binding capacity. A convenient starting material for affinity chromatography involving carboxyl-containing ligands is aminohexyl-Sepharose, which is commercially available and contains a spacer arm; any carboxyl-containing ligand can easily be coupled to the amino group of the resin. As an example of the use of aminohexyl-Sepharose, this chapter describes the purification of a soluble auxin receptor using an affinity resin produced by derivatization of aminohexyl-Sepharose.

Tuberculosis and HIV seroprevalence in Lambeth, Southwark and Lewisham, an area of South London.

Since the mid-1980s the number of cases of TB notified within the U.K. has continued to rise although the contribution of HIV to this rise remains unclear. A 12-month prospective cohort study was conducted at chest and HIV clinics in four hospitals in Lambeth, Southwark and Lewisham (LSL), an area of South London, to determine the proportion of patients with culture-proven TB infected with HIV. Secondary aims were to determine the proportion of patients with TB and undiagnosed HIV at first presentation to chest clinics, to determine the proportion of patients presenting with TB as an AIDS defining illness (ADI) and to identify risk factors for co-infection with TB and HIV. In chest clinics, demographic data and left-over blood from patients aged 16 or over with culture-proven TB was collected, anonymised and HIV tested. In HIV clinics, demographic data on patients with TB already known to be HIV seropositive were also obtained. Twenty-one patients (13%, 95% CI-8-19%) of 159 with culture-proven TB were infected with HIV Four (3%) of 133 patients at first presentation to chest clinics had undiagnosed HIV; two were subsequently diagnosed. Of the 21 patients withTB and HIV, nine (43%) presented with TB as an ADI. Patients with TB and HIV were significantly more likely to be aged between 35 and 55 years compared to HIV seronegative patients [12/21 (57%) vs. 38/138 (28%), P=0.006]. None of the patients from the Indian Subcontinent were HIV seropositive [0/21 vs. 25/138 (18%), P=0.047]. At the present time, universal HIV testing of patients with culture-provenTB in chest clinics within the U.K. is unlikely to significantly reduce the number of patients with undiagnosed HIV.

Increased incidence of tuberculosis in zimbabwe, in association with food insecurity, and economic collapse: an ecological analysis.

BACKGROUND: Zimbabwe underwent a socioeconomic crisis and resultant increase in food insecurity in 2008-9. The impact of the crisis on Tuberculosis (TB) incidence is unknown. METHODS: Prospective databases from two mission hospitals, which were geographically widely separated, and remained open during the crisis, were reviewed. RESULTS: At the Howard Hospital (HH) in northern Zimbabwe, TB incidence increased 35% in 2008 from baseline rates in 2003-2007 (p<0.01) and remained at that level in 2009. Murambinda Hospital (MH) in Eastern Zimbabwe also demonstrated a 29% rise in TB incidence from 2007 to 2008 (p<0.01) and remained at that level in 2009. Data collected post-crisis at HH showed a decrease of 33% in TB incidence between 2009 to 2010 (p<0.001) and 2010/2011 TB incidence remained below that of the crisis years of 2008/2009 (p<0.01). Antenatal clinic HIV seroprevalence at HH decreased between 2001(23%) to 2011(11%) (p<0.001). Seasonality of TB incidence was analyzed at both MH and HH. There was a higher TB incidence in the dry season when food is least available (September-November) compared to post harvest (April-June) (p<0.001). CONCLUSION: This study suggests that an epidemic of TB mirrored socioeconomic collapse and recovery in Zimbabwe. The seasonal data suggests that food security may have been associated with TB incidence both annually and during the crisis in this high HIV prevalence country.

Airway emergency in tuberculosis.

We report a case of acute fatal stridor in a patient newly diagnosed with pulmonary tuberculosis and human immunodeficiency virus (HIV) infection. No evidence of direct airway encroachment was identified at autopsy. We review mechanisms by which tuberculosis may cause stridor and discuss the implications of co-existent HIV infection with reference to the recent literature. The report highlights the need for recognition of acute or evolving airway compromise as an uncommon manifestation of tuberculosis.

Unpaid community volunteers--effective providers of directly observed therapy (DOT) in rural South Africa.

OBJECTIVE: To illustrate successes and difficulties for the South African National Tuberculosis Programme in a rural area. DESIGN: Prospective cohort study. SETTING: Sekhukhuneland, Provincial Health Service Southern Region, Northern Province, South Africa. SUBJECTS: All patients diagnosed with tuberculosis (TB) in the catchment area of four rural hospitals between January 1997 and June 1999. MAIN OUTCOME MEASURES: Standard outcomes for TB treatment as defined by the World Health Organisation. Treatment failure, treatment interruption and death were grouped as poor outcomes. RESULTS: One thousand four hundred and seventy-six people were diagnosed with TB. The majority (76%) had smear-positive pulmonary disease. Treatment was given by directly observed therapy (DOT) throughout in all but 15 instances. Excluding 10 subjects with known multidrug-resistant TB (MDRTB), 723 (66%) were cured, 68 (6%) completed treatment, 73 (7%) interrupted treatment, 37 (3%) failed treatment, 66 (6%) transferred out, and 134 (12%) died. Of the 920 initially smear-positive patients who survived the first 2 months to receive DOT in the community, 693 (75%) were supervised by unpaid community volunteers. Poor outcomes were no more common among patients supervised by these volunteers than among patients supervised by professional health care workers. Male gender (odds ratio 1.38, 95% confidence interval 1.02, 1.87) was significantly associated with a poor outcome. CONCLUSION: Although there were difficulties, the national programme was successfully applied with no additional funds or facilities. Explanations for the high death rate and poor outcomes for men need to be found. Great efforts will be required to preserve the quality of the TB programme if it is devolved to primary care level.

The association of HLA-DR3 with specific IgE to inhaled acid anhydrides.

We have undertaken a case referent study of the association between HLA allele frequency and specific IgE antibody to acid anhydride-human serum albumin (AA-HSA) conjugates among acid anhydride workers. Thirty cases with radio-allergosorbent test score versus AA-HSA conjugates > 2 were compared with 30 referents without specific IgE selected from the same factory sites as the cases and matched for age, sex, duration of exposure, atopic status, and smoking habit. We found a significant excess of HLA-DR3 in the cases with specific IgE to acid anhydrides when compared with the referents (50% versus 14%, Fisher's statistic = 8.4; odds ratio = 6, p = 0.05 corrected). The excess of HLA-DR3 was particularly associated with IgE versus trimellitic anhydride, with HLA-DR3 present in eight of 11 workers with and in two of 14 referents without IgE (Fisher's statistic = 8.5, odds ratio = 16, p = 0.004). The proportion of HLA-DR3 among the phthalic anhydride workers was not different in those with IgE (two of 12) from their referents (two of 14). These findings suggest MHC II proteins are an important determinant of the specificity of the IgE response to an inhaled hapten.

An unusual case of pneumonia.

A previously healthy 37-year-old man was admitted with a two-month history of increasing shortness of breath and high temperature. A chest X-ray demonstrated bibasal shadowing and small bilateral pleural effusions; arterial blood gases demonstrated low pO2. Despite intravenous antibiotics no significant improvement was observed. A high-resolution chest computed tomography showed diffuse ground-glass opacification with segmental and subsegmental airways opacification, indicating fine fibrosis. Subsequently, open lung biopsy showed diffuse alveolar damage and a histopathological diagnosis of acute interstitial pneumonia (Hamman-Rich syndrome) was made. Antibiotics were stopped and high intravenous doses of steroids were given with a dramatic improvement in the patient's breathing and radiographic findings. The pathophysiological mechanisms of acute interstitial pneumonia and current therapeutic options are discussed.

Exposure to acid anhydrides in three resin and one cushioned flooring manufacturing plants.

Acid anhydrides are reactive organic chemicals of low molecular weight which cause occupational asthma. No previous research on the relationship between exposure to these chemicals and respiratory sensitization and development of occupational asthma has been reported. A retrospective cohort study was carried out in four factories (three alkyd resin factories and one cushioned flooring factory) to investigate the nature of exposure-response relationships for sensitization to phthalic anhydride (PA), trimellitic anhydride (TMA) and maleic anhydride (MA). This paper describes the results of full-shift and task-specific exposure measurements. Exposure to PA was low in relation to the Occupational Exposure Standard (OES). The highest full-shift PA exposures occurred among resin operators in the resin factory that used solid PA as compared to other resin factories where liquid PA was used. Arithmetic mean exposure levels to TMA and MA in the resin factories were well below their respective OESs. Short-term high exposures occurred during loading of acid anhydrides into the reactors and sampling and testing of the resin. Relatively high full-shift exposure to TMA occurred in the cushioned flooring factory, although no high peak exposures were detected.

Risk factors for sensitisation and respiratory symptoms among workers exposed to acid anhydrides: a cohort study.

OBJECTIVES: To examine the relation between exposure to acid anhydrides and the risk of developing immediate skin prick test responses to acid anhydride human serum albumin (AA-HSA) conjugates or work related respiratory symptoms; to assess whether these relations are modified by atopy or smoking. METHODS: A cohort of 506 workers exposed to phthalic (PA), maleic (MA), and trimellitic anhydride (TMA) was defined. Workers completed questionnaires relating to employment history, respiratory symptoms, and smoking habits. Skin prick tests were done with AA-HSA conjugates and common inhalant allergens. Exposure to acid anhydrides was measured at the time of the survey and a retrospective exposure assessment was done. RESULTS: Information was obtained from 401 (79%) workers. Thirty four (8.8%) had new work related respiratory symptoms that occurred for the first time while working with acid anhydrides and 12 (3.2%) were sensitised, with an immediate skin prick test reaction to AA-HSA conjugates. Sensitisation to acid anhydrides was associated with work related respiratory symptoms and with smoking at the time of exposure to acid anhydride. When all subjects were included and all three acid anhydrides were taken into account there was no consistent evidence for an exposure-response relation, but with the analysis restricted to a factory where only TMA was in use there was an increased prevalence of sensitisation to acid anhydrides and work related respiratory symptoms with increasing full shift exposure. This relation was apparent within the current occupational exposure standard of 40 micrograms.m-3 and was not modified significantly by smoking or atopy. CONCLUSIONS: Intensity of exposure and cigarette smoking may be risk factors for sensitisation to acid anhydrides. Exposure is also a risk factor for respiratory symptoms. As there was evidence for sensitisation to TMA at full shift exposures within the occupational exposure standard this standard should be reviewed.

Retrospective exposure assessment for a cohort study into respiratory effects of acid anhydrides.

OBJECTIVES: To estimate past exposure to phthalic (PA), trimellitic (TMA) and maleic anhydride (MA) in three alkyd resin and one cushioned flooring factory to estimate exposure-response relations in a retrospective cohort study. METHODS: Personal exposure measurements were carried out in 1992 and quantitative and qualitative information on past exposure and production processes were collected. Job titles were ranked by decreasing exposure and amalgamated into job categories and exposure groups. Multiplication factors for back calculating past exposure levels were estimated with past exposure data, or if no such data were available these factors were estimated by a panel of occupational hygienists. Exposure levels were back calculated starting with the exposure levels in 1992. RESULTS: High exposures to PA were estimated to have occurred among workers operating the PA melting pots in factory 1 (estimated exposure in 1960-9 was 2480 micrograms.m-3). Highest concentrations of TMA were estimated to have occurred among the ink mixers in factory 2 from 1979 to 1986 (554 micrograms.m-3). Exposure in most other job titles was thought to be fairly constant over time for PA, TMA, and MA. CONCLUSIONS: Exposure to acid anhydride at these factories has fallen during the period covered by the study. However, it is estimated that in only one job in factory 2 did past exposure to acid anhydride exceed the current occupational exposure standard. Accuracy of the estimated exposure is limited by a paucity of reliable past exposure data.