Computational investigation of α-SiO2 surfaces as a support for Pd.

The properties of a supported metal catalyst depend crucially on the interaction between the active metal and the support. A case in point is Pd supported on silica, Pd/SiO2, which is widely used in oxidation catalysis. There is a need for a broad range of computational models that describe the interaction of Pd with silica surfaces so that active site models can be proposed and tested. In this work, we create well-defined, reproducible, periodic models of SiO2 surfaces and investigate their interaction with Pd using dispersion-corrected DFT. We use crystalline α-SiO2 as a useful starting point for creating and estimating the adsorption properties of metals on SiO2 surfaces, which can represent the specific isolated functional groups present on more complex amorphous silica surfaces. We have modelled α-SiO2 (001), (100) and (101) surfaces containing isolated siloxane and silanol functional groups and estimated their affinity towards the adsorption of Pd atoms regarding an isolated gaseous Pd atom and the fcc Pd solid. This provides additional information on the ease with which Pd can be dispersed on the surfaces in question. From our model, we characterise the surface energies of the α-SiO2 (hkl) surfaces and calculate the geometries of the Pd1/α-SiO2 (hkl) adsorption site on each surface. We estimate that Pd1(g) will prefer to adsorb close to strained four-membered siloxane rings or on a vicinal silanol group of α-SiO2 (101).

Hypoxaemia during tracheal intubation in patients with hypertensive disorders of pregnancy: analysis of data from an obstetric airway management registry.

BACKGROUND: In South Africa, hypertensive disorders of pregnancy are the leading cause of maternal mortality. More than 50% of anaesthesia-related maternal deaths are attributed to complications of airway management. We compared the prevalence and risk factors for hypoxaemia during induction of general anaesthesia in parturients with and without hypertensive disorders of pregnancy. We hypothesised that hypertensive disorders of pregnancy are associated with desaturation during tracheal intubation. METHODS: Data from 402 cases in a multicentre obstetric airway management registry were analysed. The prevalence of peri-induction hypoxaemia (SpO2 <90%) was compared in patients with and without hypertensive disorders of pregnancy. Quantile regression of SpO2 nadir was performed to identify confounding variables associated with, and mediators of, hypoxaemia. RESULTS: In the cohort of 402 cases, hypoxaemia occurred in 19% with and 9% without hypertension (estimated risk difference, 10%; 95% CI 2% to 17%; P=0.005). Quantile regression demonstrated a lower SpO2 nadir associated with hypertensive disorders of pregnancy as body mass index increased. Room-air oxygen saturation, Mallampati grade, and number of intubation attempts were associated with the relationship. CONCLUSIONS: Clinically significant oxygen desaturation during airway management occurred twice as often in patients with hypertensive disorders of pregnancy, compounded by increasing body mass index. Intermediary factors in the pathway from hypertension to hypoxaemia were also identified.

The incidence of melanoma in South Africa: An exploratory analysis of National Cancer Registry data from 2005 to 2013 with a specific focus on melanoma in black Africans.

BACKGROUND: Melanoma is an aggressive skin cancer with poor survival when diagnosed late. There are important differences in clinical and histological features of melanoma and disease outcomes in people with darker skin types. METHODS: A retrospective review of data captured by the National Cancer Registry (NCR) of South Africa (SA) was performed for 2005 - 2013. Data on patient numbers, demography, location and biological features were analysed for all records. Closer analysis of melanoma of the limbs reported in black Africans was done after manually collecting this information from original reports. RESULTS: With 11 784 invasive melanomas reported to the NCR, the overall incidence of melanoma for SA was 2.7 per 100 000. Males (51%), individuals aged ≥60 years (48%) and the anatomical sites of lower limb (36%) and trunk (27%) were most commonly affected. Melanoma incidences in the white and black populations were 23.2 and 0.5 per 100 000, respectively. Most cases were diagnosed at private pathology laboratories (73%). Superficial spreading melanoma (47%) and nodular melanoma (20%) predominated. Among 878 black Africans diagnosed in the public sector with melanoma of the limbs, females (68%) and individuals aged ≥60 years (61%) were most commonly affected. Lower-limb lesions (91%) and acral lentiginous melanoma (65%) predominated, with 74% of cases affecting the foot and 62% of cases presenting with a Breslow depth >4 mm. CONCLUSIONS: This study provides up-to-date NCR incidence and demographic data on melanoma and highlights the neglected research gaps in relation to melanoma in black Africans to provide evidence needed to address health disparities in overlooked population groups.

A randomised comparison of bolus phenylephrine and ephedrine for the management of spinal hypotension in patients with severe preeclampsia and fetal compromise.

BACKGROUND: Studies in healthy patients undergoing elective caesarean delivery show that, compared with phenylephrine, ephedrine used to treat spinal hypotension is associated with increased fetal acidosis. This has not been investigated prospectively in women with severe preeclampsia. METHODS: Patients with preeclampsia requiring caesarean delivery for a non-reassuring fetal heart tracing were randomised to receive either bolus ephedrine (7.5-15mg) or phenylephrine (50-100µg), to treat spinal hypotension. The primary outcome was umbilical arterial base excess. Secondary outcomes were umbilical arterial and venous pH and lactate concentration, venous base excess, and Apgar scores. RESULTS: Among 133 women, 64 who required vasopressor treatment were randomised into groups of 32 with similar patient characteristics. Pre-delivery blood pressure changes were similar. There was no difference in mean [standard deviation] umbilical artery base excess (-4.9 [3.7] vs -6.0 [4.6] mmol/L for ephedrine and phenylephrine respectively; P=0.29). Mean umbilical arterial and venous pH and lactate concentrations did not significantly differ between groups (7.25 [0.08] vs 7.22 [0.10], 7.28 [0.07] vs 7.27 [0.10], and 3.41 [2.18] vs 3.28 [2.44] mmol/L respectively). Umbilical venous oxygen tension was higher in the ephedrine group (2.8 [0.7] vs 2.4 [0.62]) kPa, P=0.02). There was no difference in 1- or 5-min Apgar scores, numbers of neonates with 1-min Apgar scores <7 or with a pH <7.2. CONCLUSIONS: In patients with severe preeclampsia and fetal compromise, fetal acid-base status is independent of the use of bolus ephedrine versus phenylephrine to treat spinal hypotension.

Maternal cardiac output response to colloid preload and vasopressor therapy during spinal anaesthesia for caesarean section in patients with severe pre-eclampsia: a randomised, controlled trial.

We examined the haemodynamic effects of colloid preload, and phenylephrine and ephedrine administered for spinal hypotension, during caesarean section in 42 women with severe early onset pre-eclampsia. Twenty patients with pre-delivery spinal hypotension were randomly allocated to receive an initial dose of either 50 µg phenylephrine or 7.5 mg ephedrine; the primary outcome was percentage change in cardiac index. After a 300-ml colloid preload, mean (SD) cardiac index increased from 4.9 (1.1) to 5.6 (1.2) l.min-1 .m-2 (p < 0.01), resulting from an increase in both heart rate, from 81.3 (17.2) to 86.3 (16.5) beats.min-1 (p = 0.2), and stroke volume, from 111.8 (19.0) to 119.8 (17.9) ml (p = 0.049). Fourteen (33%) and 23 (54.8%) patients exhibited a stroke volume response > 10% and > 5%, respectively; a significant negative correlation was found between heart rate and stroke volume changes. Spinal hypotension in 20 patients was associated with an increase from baseline in cardiac index of 0.6 l.min-1 .m-2 (mean difference 11.5%; p < 0.0001). After a median [range] dose of 50 [50-150] µg phenylephrine or 15 [7.5-37.5] mg ephedrine, the percentage change in cardiac index during the measurement period of 150 s was greater, and negative, in patients receiving phenylephrine vs. ephedrine, at -12.0 (7.3)% vs. 2.6 (6.0)%, respectively (p = 0.0001). The percentage change in heart rate after vasopressor was higher in patients receiving phenylephrine, at -9.1 (3.4)% vs. 5.3 (12.6)% (p = 0.0027), as was the change in systemic vascular resistance, at 22.3 (7.5) vs. -1.9 (10.5)% (p < 0.0001). Phenylephrine effectively reverses spinal anaesthesia-induced haemodynamic changes in severe pre-eclampsia, if left ventricular systolic function is preserved.

Scanty smears associated with initial loss to follow-up in South African tuberculosis patients.

BACKGROUND: Smear-positive patients should be started on anti-tuberculosis treatment promptly. However, studies show that up to 38% of diagnosed patients are initial loss to follow-up (LTFU), meaning they do not start treatment after diagnosis. We investigated determinants of initial LTFU at primary health care facilities. DESIGN: In a facility-matched case-control study, health care facilities were visited from October 2010 to September 2012. After identification from registers, patients were traced and invited to complete a questionnaire. RESULTS: Of 973 participants, 233 (24%) were cases and 740 (74%) controls. Initial LTFU was associated with smear grade (pooled adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.64-0.90, scanty at baseline) for participants identified at facilities, but not with age (overall P = 0.80) or sex (aOR 0.83, 95%CI 0.58-1.20). Of the 233 cases, 197 (85%) were traced in the community, of whom 58 (29%) were found. Among the group found, initial LTFU was associated with age (aOR 3.38, 95%CI 1.15-9.95) and smear grade (aOR 0.08, 95%CI 0.02-0.34, scanty at baseline). CONCLUSION: Scanty smear positivity was associated with initial LTFU. Tuberculosis programmes should start scanty smear-positive patients on treatment early and develop alternative community tracing strategies. Health care worker training could address the first aspect, and the use of technology to improve treatment initiation, such as mobile phone applications, the second.

Structural Level Differences in the Mother-to-Child HIV Transmission Rate in South Africa: A Multilevel Assessment of Individual-, Health Facility-, and Provincial-Level Predictors of Infant HIV Transmission.

OBJECTIVES: In 2010, South Africa reported an early mother-to-child transmission (MTCT) rate of 3.5% at 4-8 weeks postpartum. Provincial early MTCT rates ranged from 1.4% [95% confidence interval (CI): 0.1 to 3.4] to 5.9% (95% CI: 3.8 to 8.0). We sought to determine reasons for these geographic differences in MTCT rates. METHODS: This study used multilevel modeling using 2010 South African prevention of mother-to-child transmission (PMTCT) evaluation (SAPMTCTE) data from 530 facilities. Interview data and blood samples of infants were collected from 3085 mother-infant pairs at 4-8 weeks postpartum. Facility-level data on human resources, referral systems, linkages to care, and record keeping were collected through facility staff interviews. Provincial level data were gathered from publicly available data (eg, health professionals per 10,000 population) or aggregated at province-level from the SAPMTCTE (PMTCT maternal-infant antiretroviral (ARV) coverage). Variance partition coefficients and odds ratios (for provincial facility- and individual-level factors influencing MTCT) from multilevel modeling are reported. RESULTS: The provincial- (5.0%) and facility-level (1.4%) variance partition coefficients showed no substantive geographic variation in early MTCT. In multivariable analysis accounting for the multilevel nature of the data, the following were associated with early MTCT: individual-level-low maternal-infant ARV uptake [adjusted odds ratio (AOR) = 2.5, 95% CI: 1.7 to 3.5], mixed breastfeeding (AOR = 1.9, 95% CI: 1.3 to 2.9) and maternal age <20 years (AOR 1.8, 95% CI: 1.1 to 3.0); facility-level-insufficient (≤2) health care-personnel for HIV-testing services (AOR = 1.8, 95% CI: 1.1 to 3.0); provincial-level PMTCT ARV (maternal-infant) coverage lower than 80% (AOR = 1.4, 95% CI: 1.1 to 1.9), and number of health professionals per 10,000 population (AOR = 0.99, 95% CI: 0.98 to 0.99). CONCLUSIONS: There was no substantial province-/facility-level MTCT difference. This could be due to good overall performance in reducing early MTCT. Disparities in human resource allocation (including allocation of insufficient health care personnel for testing and care at facility level) and PMTCT coverage influenced overall PMTCT programme performance. These are long-standing systemic problems that impact quality of care.

The use of phenylephrine to obtund oxytocin-induced hypotension and tachycardia during caesarean section.

BACKGROUND: Oxytocin causes clinically significant hypotension and tachycardia. This study examined whether prior administration of phenylephrine obtunds these unwanted haemodynamic effects. METHODS: Forty pregnant women undergoing elective caesarean section under spinal anaesthesia were randomised to receive either an intravenous 50 µg bolus of phenylephrine (Group P) or saline (Group S) immediately before oxytocin (3U over 15s). Systolic blood pressure, diastolic blood pressure, mean arterial pressure and heart rate were recorded using a continuous non-invasive arterial pressure device. Baseline values were averaged for 20s post-delivery. Between-group comparisons were made of the mean peak changes in blood pressure and heart rate, and the mean percentage changes from baseline, during the 150s after oxytocin administration. RESULTS: The mean ± SD peak percentage change in systolic blood pressure was -16.9 ± 2% in Group P, and -19.0 ± 1.9% in Group S and the estimated mean difference was 2.1% (95% CI -3.5% to 7.8%; P=0.44); corresponding changes in heart rate were 13.5 ± 2.3% and 14.0±1.5% and the mean estimated difference was 0.5% (95% CI -6.0% to 5%; P=0.87). The mean percentage change from the baseline measurements during the 150s period of measurement was greater for Group S than Group P: systolic blood pressure -5.9% vs -3.4% (P=0.149); diastolic blood pressure -7.2% vs -1.5% (P=0.014); mean arterial pressure -6.8% vs -1.5% (P=0.007); heart rate 2.1% vs -2.4% (P=0.033). CONCLUSION: Intravenous phenylephrine 50 µg immediately before 3U oxytocin during elective caesarean section does not prevent maternal hypotension and tachycardia.

Isoniazid preventive therapy in HIV-infected children on antiretroviral therapy: a pilot study.

SETTING: Tuberculosis (TB) is a common cause of mortality and morbidity in children infected with the human immunodeficiency virus (HIV). Data on isoniazid preventive therapy (IPT) efficacy in HIV-infected children receiving antiretroviral therapy (ART) are inconclusive. OBJECTIVE: To assess the efficacy, tolerability and safety of isoniazid (INH) in HIV-infected children on ART. DESIGN: A pilot randomised controlled study of INH was undertaken in HIV-infected children on ART. The primary outcome measure was TB disease or death. RESULTS: A total of 167 children were randomised to receive INH (n = 85) or placebo (n = 82), and followed for a median of 34 months (interquartile range [IQR] 24-52). The median age was 35 months (IQR 15-65). There was one death in a child on INH and none in the placebo group. Eleven (6.6%) cases of TB occurred, 4 (5%) in the INH and 7 (9%) in the placebo group. Among the TB cases, 5 were culture confirmed-2 in the INH group and 3 in the placebo group, all susceptible to INH. Severe adverse events occurred rarely (n = 6; 2%). CONCLUSION: IPT is safe and well tolerated in HIV-infected children on concomitant ART. This study supports the need for a larger study to assess efficacy in HIV-infected children living in TB-endemic areas.

Population structure analyses of Staphylococcus aureus at Tygerberg Hospital, South Africa, reveals a diverse population, a high prevalence of Panton-Valentine leukocidin genes, and unique local methicillin-resistant S. aureus clones.

Studies reporting on the population structure of Staphylococcus aureus in South Africa have focused only on methicillin-resistant S. aureus (MRSA). This study describes the population structure of S. aureus, including methicillin-susceptible S. aureus (MSSA) isolated from patients at Tygerberg Academic Hospital, Western Cape province. Pulsed-field gel electrophoresis (PFGE), detection of Panton-Valentine leukocidin (PVL), spa typing, multilocus sequence typing (MLST), agr typing and SCCmec typing were used to characterize strains. Of 367 non-repetitive S. aureus isolates collected over a period of 1 year, 56 (15.3%) were MRSA. Skin and soft tissue infections were the most frequent source (54.8%), followed by bone and joint (15.3%) and respiratory tract infections (7.7%). For strain typing, PFGE was the most discriminative method, and resulted in 31 pulsotypes (n = 345, 94.0%), as compared with 16 spa clonal complexes (CCs) (n = 344, 93.4%). Four MLST CCs were identified after eBURST of sequence types (STs) of selected isolates. One hundred and sixty isolates (MSSA, n = 155, 42.2%) were PVL-positive, and agr types I-IV and SCCmec types I-V were identified. Our S. aureus population consisted of genotypically diverse strains, with PVL being a common characteristic of MSSA. MSSA and MRSA isolates clustered in different clones. However, the dominant MRSA clone (ST612) also contained an MSSA isolate, and had a unique genotype. Common global epidemic MRSA clones, such as ST239-MRSA-III and ST36-MRSA-II, were identified. A local clone, ST612-MRSA-IV, was found to be the dominant MRSA clone.

Safety of long-term isoniazid preventive therapy in children with HIV: a comparison of two dosing schedules.

SETTING: Two paediatric hospitals in Cape Town, South Africa. OBJECTIVE: To investigate the incidence of and risk factors for severe liver injury in human immunodeficiency virus (HIV) infected children receiving long-term isoniazid preventive therapy (IPT). DESIGN: Randomised trial of IPT or placebo given daily or thrice weekly to HIV-infected children aged ≥8 weeks; placebo was discontinued early. Alanine transaminase (ALT) was measured at baseline, 6-monthly and during illness: an increase of ≥10 times the upper limit of normal defined severe liver injury. RESULTS: Of 324 children enrolled, 297 (91.6%) received IPT (559.1 person-years [py]). Baseline median age was 23 months (interquartile range [IQR] 9.5-48.6) and median CD4%, 20% (IQR 13.6-26.9). A total of 207 (63.9%) children received combination antiretroviral therapy: 19 developed severe liver injury, 16 while receiving IPT. Among these there were 8 cases of viral hepatitis (5 with hepatitis A), 2 antiretroviral-induced liver injuries and 1 case of abdominal tuberculosis. IPT-related severe liver injury occurred in 1.7% (5/297, 0.78/100 py). No child developed hepatic failure; one died of an unrelated cause. All surviving children subsequently tolerated IPT. CONCLUSIONS: This study suggests that long-term IPT has a low toxicity risk in HIV-infected children. In the absence of chronic viral hepatitis, IPT can be safely re-introduced following recovery from liver injury.

The impact of isoniazid preventive therapy and antiretroviral therapy on tuberculosis in children infected with HIV in a high tuberculosis incidence setting.

BACKGROUND: Tuberculosis (TB) is a major cause of morbidity and mortality among children infected with HIV. Strategies to prevent TB in children include isoniazid preventive therapy (IPT) and antiretroviral therapy (ART). IPT and ART have been reported to reduce TB incidence in adults but there are few studies in children. OBJECTIVE: To investigate the combined effect of IPT and ART on TB risk in children infected with HIV. METHODS: A cohort analysis was done within a prospective, double-blinded, placebo-controlled trial of isoniazid (INH) compared with placebo in children infected with HIV in Cape Town, South Africa, a high TB incidence setting. In May 2004 the placebo arm was terminated and all children were switched to INH. ART was not widely available at the start of the study, but children were started on ART following the establishment of the national ART program in 2004. Data were analysed using Cox proportional hazard regression. RESULTS: After adjusting for age, nutritional status and immunodeficiency at enrolment, INH alone, ART alone and INH combined with ART reduced the risk of TB disease by 0.22 (95% CI 0.09 to 0.53), 0.32 (95% CI 0.07 to 1.55) and 0.11 (95% CI 0.04 to 0.32) respectively. INH reduced the risk of TB disease in children on ART by 0.23 (95% CI 0.05 to 1.00). CONCLUSIONS: The finding that IPT may offer additional protection in children on ART has significant public health implications because this offers a possible strategy for reducing TB in children infected with HIV. Widespread use of this strategy will however require screening of children for active TB disease. Trial registration Trial registration-Clinical Trials NCT00330304.

Human immunodeficiency virus associated tuberculosis more often due to recent infection than reactivation of latent infection.

BACKGROUND: It is unclear whether human immunodeficiency virus (HIV) increases the risk of tuberculosis (TB) mainly through reactivation or following recent Mycobacterium tuberculosis (re)infection. Within a DNA fingerprint-defined cluster of TB cases, reactivation cases are assumed to be the source of infection for subsequent secondary cases. As HIV-positive TB cases are less likely to be source cases, equal or higher clustering in HIV-positives would suggest that HIV mainly increases the risk of TB following recent infection. METHODS: A systematic review was conducted to identify all studies on TB clustering and HIV infection in HIV-endemic populations. Available individual patient data from eligible studies were pooled to analyse the association between clustering and HIV. RESULTS: Of seven eligible studies, six contributed individual patient data on 2116 patients. Clustering was as, or more, likely in the HIV-positive population, both overall (summary OR 1.26, 95%CI 1.0-1.5), and within age groups (OR 1.50, 95%CI 0.9-2.3; OR 1.00, 95%CI 0.8-1.3 and OR 2.57, 95%CI 1.4-5.7) for ages 15-25, 26-50 and >50 years, respectively. CONCLUSIONS: Our results suggest that HIV infection mainly increases the risk of TB following recent M. tuberculosis transmission, and that TB control measures in HIV-endemic settings should therefore focus on controlling M. tuberculosis transmission rather than treating individuals with latent M. tuberculosis infection.

Comparison between pulse waveform analysis and thermodilution cardiac output determination in patients with severe pre-eclampsia.

BACKGROUND: This study compared cardiac output (CO) measurements derived from pulse waveform analysis with values obtained by thermodilution (TD), in patients with post-partum complications of severe pre-eclampsia. METHODS: Eighteen patients were recruited, 24-96 h post-delivery. After central venous calibration of the pulse waveform analysis monitor (LiDCOplus), CO readings were compared with those obtained by the TD method and repeated twice at 15 min intervals. The comparison was repeated after peripheral venous calibration. Further comparisons were made in eight patients at 120 and 240 min after peripheral venous calibration. RESULTS: Data were pooled for measurements at 0, 15, and 30 min after calibration. For the comparison between TD and LiDCOplus using central venous calibration, TD exhibited a significant positive bias of 0.58 litre min⁻¹ [95% confidence interval (CI): 0.77 to 0.39]. After peripheral venous calibration, there was no significant bias [0.16 litre min⁻¹ (95% CI: -0.37 to 0.06)]. The estimated limits of agreement for central and peripheral venous calibrations were -2.12 to 0.96 and -1.50 to 1.20 litre min⁻¹, respectively. When comparing LiDCOplus and TD, there was no time-based effect at 120 or 240 min post-peripheral calibration. CONCLUSIONS: Central and peripheral venous calibrations of the LiDCOplus monitor were associated with clinically insignificant bias when compared with TD. Limits of agreement were within the recommendation of 30% for acceptance of a new CO technique when compared with current reference methods. This form of minimally invasive CO monitoring may have a valuable role in obstetric critical care.

High prevalence of Mycobacterium tuberculosis infection and disease in children and adolescents with type 1 diabetes mellitus.

SETTING: Western Cape Province, South Africa. OBJECTIVES: To describe the prevalence of tuberculosis (TB) infection and disease in children with type 1 diabetes and to investigate the association between glycaemic control and prevalence of TB infection and disease. DESIGN: Cross-sectional hospital-based study conducted at two public referral hospitals. All children and adolescents (aged <21 years) with type 1 diabetes underwent a Mantoux tuberculin skin test (>or=10 mm classified as Mycobacterium tuberculosis infection), measurement of glycosylated haemoglobin and a chest radiograph. Patients with symptoms suggestive of TB were investigated using mycobacterial culture. Radiologically and/or bacteriologically confirmed disease was classified as TB disease. RESULTS: Of 291 eligible patients, 258 (88.7%) were included (58% female). The prevalence of M. tuberculosis infection was 29.8% (95%CI 24.2-35.4); nine patients were diagnosed with prevalent TB disease (point prevalence disease 3488 per 100,000 population). Poor glycaemic control (hazard ratio 1.39, 95%CI 1.18-1.63 per unit increase in glycated haemoglobin [HbA1c]) and contact with a TB source case (P = 0.0011) was associated with prevalent TB disease. CONCLUSIONS: There is a high prevalence of TB disease in diabetic children and adolescents in this setting. Routine TB screening of children with type 1 diabetes may be indicated in settings highly endemic for TB. Preventive treatment should be considered for diabetic children with proof of TB exposure and/or infection.

From suspect to patient: tuberculosis diagnosis and treatment initiation in health facilities in South Africa.

SETTING: Thirteen primary health care (PHC) facilities in the Stellenbosch District, South Africa. OBJECTIVE: To assess the use of a sputum register to evaluate the tuberculosis (TB) diagnostic process and the initiation of TB treatment in selected PHC facilities in a country with a centralised laboratory system. DESIGN: This prospective study was conducted between April 2004 and March 2005. The names of all individuals submitting sputum samples for TB testing were noted in a newly introduced sputum register. We classified all TB suspects with two positive smears as TB cases and consulted TB treatment registers until 3 months after sputum submission to determine how many had started treatment. RESULTS: A total of 4062 persons aged > or =15 years submitted sputum samples, of whom 2484 were TB suspects. There were 2037 suspects with at least two results, 367 (18%) had at least two positive smears and 64 (17%) of these did not start treatment (initial defaulters). Over the entire diagnostic process, up to 5% of TB cases were missed, and up to 26% did not start treatment and were not reported. CONCLUSION: By correcting diagnostic weaknesses identified in the sputum register, PHC facilities will be able to detect, treat and cure a higher percentage of TB patients.

Comparison of symptoms and treatment outcomes between actively and passively detected tuberculosis cases: the additional value of active case finding.

Passive detection of tuberculosis (TB) cases may lead to delay in treatment which may contribute to increased severity of disease and mortality. Active case finding may be an alternative. In a community survey in Cape Town, South Africa, we actively detected 27 bacteriologically positive TB cases and compared those with 473 passively detected TB cases. Seven of 27 (26%) actively detected TB cases did not start treatment within 2 months and were considered initial defaulters. Those who did start treatment had similar treatment success rates as passively detected TB cases (both 80%) (OR 1.01, CI 0.33-3.09). Passively detected cases reported the presence of the symptoms cough (OR 3.72, 95% CI 1.47-9.39), haemoptysis (OR 3.20, 95% CI 1.03-9.93), night sweats (OR 3.35, 95% CI 1.40-7.99), fever (OR 4.28, 95% CI 1.21-15.14), and weight loss (OR 11.14, 95% CI 4.17-29.74) more often than those detected actively. We conclude that although TB cases detected by a community survey are less symptomatic and are prone to a high initial default rate, active case finding can potentially identify a substantial portion of the existing caseload at an earlier stage of disease, thereby reducing the risk of transmission.

An evaluation of symptom and chest radiographic screening in tuberculosis prevalence surveys.

SETTING: A tuberculosis (TB) prevalence survey was performed in 2002 in two urban communities in Cape Town, South Africa. The population was 36,334 in 2001, and the TB notification rate was 341 per 100,000 population for new smear-positive TB in 2002. OBJECTIVE: To evaluate the relative contributions of symptom and chest radiographic (CXR) screening in the detection of subjects with smear- and/or culture-positive TB in prevalence surveys. DESIGN: Information on symptoms, CXR abnormalities, sputum smear and culture was gathered from a random cluster sample of 1170 adults (aged > or = 15 years). Smear and/or culture-positive TB was used as the gold standard. RESULTS: Of 1170 adults, 29 had bacteriologically positive TB (smear- and/or culture-positive). The presence of any abnormalities on CXR had the highest sensitivity for detecting subjects with bacteriologically positive TB (0.97, 95%CI 0.90-1.00). Specificity for any abnormalities on CXR was 0.67 (95%CI 0.64-0.70). The specificity of any of five TB-related symptoms was 0.68 (95%CI 0.65-0.71). Individual symptoms had low sensitivities, ranging from 0.10 for fever to 0.54 for cough of > or = 2 weeks. CONCLUSION: In this TB prevalence survey, CXR screening, but not symptom screening, was a sensitive alternative to sputum examination of all participants.

Respiratory atopic disease, Ascaris-immunoglobulin E and tuberculin testing in urban South African children.

BACKGROUND: Epidemiological relation of intestinal helminth infection and atopic disease, both associated with a T-helper (Th) 2 immune response, is controversial, as it has been reported that helminth infection may either suppress or pre-dispose to atopic disease. This relation has not been tested in an area with a high burden of Mycobacterium tuberculosis (MTB) infection, a known Th1-stimulating infection. OBJECTIVE: To study the association of intestinal helminth infection and atopic disease in a community where helminth infection is endemic and MTB infection is high. METHODS: Three-hundred and fifty-nine randomly selected children aged 6-14 years from a poor urban suburb were tested with allergy questionnaire, skin prick test (SPT) to common aeroallergens, Ascaris-specific IgE (Ascaris-sIgE), fecal examination for pathogenic intestinal helminths and tuberculin skin testing (TST). Histamine bronchoprovocation was tested in the group of children aged 10 years and older. RESULTS: were corrected for demographic variables, socioeconomic status, parental allergy, environmental tobacco smoke (ETS) exposure in the household, recent anthelminthic treatment and for clustering in the sampling unit. Results Ascaris-sIgE was elevated in 48% of children, Ascaris eggs were found in 15% and TST was positive in 53%. Children with elevated Ascaris-sIgE had significantly increased risk of positive SPT to aeroallergens, particularly house dust mite, atopic asthma (ever and recent), atopic rhinitis (ever and recent) and increased atopy-related bronchial hyper-responsiveness. In children with negative TST (<10 mm), elevated Ascaris-sIgE was associated with significantly increased risk of atopic symptoms (adjusted odds ratio (OR(adj)) 6.5; 95% confidence interval (CI) 1.9-22.4), whereas in those with positive TST (>/=10 mm) this association disappeared (OR(adj) 0.96; 95% CI 0.4-2.8). CONCLUSIONS: These results suggest that immune response to Ascaris (Ascaris-sIgE) may be a risk factor of atopic disease in populations exposed to mild Ascaris infection and that MTB infection may be protective against this risk, probably by stimulation of anti-inflammatory networks.