TB preventive therapy preferences among children and adolescents.

BACKGROUND: TB preventive therapy (TPT) is critical for ending TB, yet implementation remains poor. With new global guidelines expanding TPT eligibility and regimens, we aimed to understand TPT preferences among children, adolescents and caregivers.METHODS: We undertook a discrete choice experiment among 131 children, 170 adolescents and 173 caregivers, and conducted 17 in-depth interviews in 25 clinics in Cape Town, South Africa. The design included attributes for location, waiting time, treatment duration, dosing frequency, formulation/size, side effects, packaging and taste. Mixed-effects logistic regression models were used for analysis.RESULTS: Among children and caregivers, the number and size of pills, taste and side effects were important drivers of preferences. Among adolescents and caregivers, clinic waiting times and side effects were significant drivers of preferences. Adolescents expressed concerns about being stigmatised, and preferred services from local clinics to services delivered in the community. Dosing frequency and treatment duration were only significant drivers of choice among adolescents, and only if linked to fewer clinic visits.CONCLUSIONS: Introducing shorter TPT regimens in isolation without consideration of preferences and health services may not have the desired effect on uptake and completion. Developing TPT delivery models and formulations that align with preferences must be prioritised.

Health system barriers to implementation of collaborative TB and HIV activities including prevention of mother to child transmission in South Africa.

In South Africa, the control of TB and HIV co-infection remains a major challenge despite the availability of international and national guidelines for integration of TB and HIV services. This study was undertaken in KwaZulu-Natal, one of the provinces most affected by both TB and HIV, to identify and understand managers' and community care workers' (CCWs) perceptions of health systems barriers related to the implementation of collaborative TB/HIV activities, including prevention of mother to child transmission of HIV (PMTCT). We conducted 29 in-depth interviews with health managers at provincial, district and facility level and with managers of NGOs involved in TB and HIV care, as well as six focus group discussions with CCWs. Thematic analysis of transcripts revealed a convergence of perspectives on the process and the level of the implementation of policy directives on collaborative TB and HIV activities across all categories of respondents (i.e. province-, district-, facility- and community-based organizations). The majority of participants felt that the implementation of the policy was insufficiently consultative and that leadership and political will were lacking. The predominant themes related to health systems barriers include challenges related to structure and organisational culture; management, planning and power issues; unequal financing; and human resource capacity and regulatory problems notably relating to scope of practice of nurses and CCWs. Accelerated implementation of collaborative TB/HIV activities including PMTCT will require political will and leadership to address these health systems barriers.

Training community care workers to provide comprehensive TB/HIV/PMTCT integrated care in KwaZulu-Natal: lessons learnt.

OBJECTIVE: To describe a participatory approach to implement and evaluate ways to integrate and train community care workers (CCWs) to enhance collaborative TB/HIV/PMTCT activities, and home-based HIV counseling and testing (HCT) at community level. METHODS: The intervention study was conducted in Sisonke, a rural district of KwaZulu Natal, South Africa. A baseline household (HH) survey was conducted in 11 villages. Six villages were randomly selected into intervention and control clusters. Training was provided first to CCWs from the intervention cluster (IC) followed by the control cluster (CC). Routine monthly data from CCWs were collected from March-December 2010. The data was subjected to bivariate tests. RESULTS: The baseline HH survey revealed that of 3012 HH members visited by CCWs in 2008, 21% were screened for TB symptoms, 7% were visited for TB adherence support and 2% for ART adherence, and 1.5% were counselled on infant feeding options. A total of 89 CCWs were trained. Data show that during the study period in IC, 684 adults were offered HCT by CCWs, 92% accepted HCT and tested and 7% tested HIV-positive and were referred to the clinic for further care. Of 3556 adults served in IC, 44% were screened for TB symptoms and 32% for symptoms of sexually transmitted infections (STIs) and 37% of children were traced as TB contact. Out of 6226 adults served in CC, 10% were screened for TB symptoms and 7% for STI symptoms. The differences in uptake of services between IC and CC were statistically significant (p<0.05). CONCLUSION: The findings of this study suggest higher uptake of TB and STI symptoms screening, TB contact tracing and home based HCT in the intervention clusters. This study suggests that up-skilling CCWs could be one avenue to enhance TB/HIV case finding, TB contact tracing and linkages to care.

Stabilisation of cardiopulmonary function in newborns with congenital diaphragmatic hernia using lung function parameters and hemodynamic management.

OBJECTIVE: Evaluation of lung function parameters and additional use of prostaglandin E1 (PGE1) for the stabilisation of cardiopulmonary function in patients with congenital diaphragmatic hernia (CDH) and pulmonary hypertension (PHT). DESIGN: Observational study. PATIENTS: Between 2007 and 2009 8 patients with CDH have been treated in our pediatric intensive care unit (gestational age 34 + 0 - 40 + 4 weeks, birth weight 2 160-3 840 g). All patients required respiratory support. Gentle mechanical ventilation adapted to the degree of pulmonary hypoplasia based on serially measurements of lung function parameters to find appropriate ventilator settings has been performed. MAIN RESULTS: Functional residual capacity (FRC) and compliance of the respiratory system in all patients were markedly reduced. A FRC between 9.3-10.6 ml/kg and compliance between 1.1-1.8 ml/kPa/kg indicated pronounced hypoplasia of the lungs. Doppler flow patterns through the arterial duct were classified into left-to-right, right-to-left and bidirectional shunting and correlated to the degree of PHT. The additional use of PGE1 to reopen the arterial duct and to stabilize right ventricular function led to an amelioration of severe PHT and preoperative stabilisation in 2 newborns with pronounced pulmonary hypoplasia. All patients underwent successful surgery, and did not show any complications after 2 years follow-up. CONCLUSION: Measurements of lung function parameters and adaptation of mechanical ventilation to the degree of pulmonary hypoplasia and additional therapy with PGE1 may help to improve the outcome in CDH patients.

Reasons for poor uptake of TB preventive therapy in South Africa.

BACKGROUND: South Africa has one the highest TB and HIV burdens globally. TB preventive therapy (TPT) reduces the risk of TB disease and TB-related mortality in adults and children living with HIV and is indicated for use in TB-exposed HIV-negative individuals and children. TPT implementation in South Africa remains suboptimal. METHODS: We conducted a pragmatic review of TPT implementation using multiple data sources, including informant interviews (n = 134), semi-structured observations (n = 93) and TB patient folder reviews in 31 health facilities purposively selected across three high TB burden provinces. We used case descriptive analysis and thematic coding to identify barriers and facilitators to TPT implementation. RESULTS: TPT programme implementation was suboptimal, with inadequate monitoring even in health districts with well-functioning TB services. Health workers reported scepticism about TPT effectiveness, deprioritised TPT in practice and expressed divergent opinions about the cadres of staff responsible for implementation. Service- and facility-level barriers included ineffective contact tracing, resource shortages, lack of standardised reporting mechanisms and insufficient patient education on TPT. Patient-level barriers included socio-economic factors. CONCLUSIONS: Improving TPT implementation will require radically simplified and more feasible systems and training for all cadres of health workers. Partnership with communities to stimulate demand driven service uptake can potentially facilitate implementation.

CONTEXTE: L'Afrique du Sud a l'une des charges de TB et de VIH les plus élevées au monde. La thérapie préventive contre la TB (TPT) réduit le risque de TB maladie et de mortalité liée à la TB chez les adultes et les enfants vivant avec le VIH et est indiquée chez les personnes et les enfants séronégatifs exposés à la TB. La mise en œuvre du TPT en Afrique du Sud reste sous-optimale. MÉTHODES: Nous avons procédé à un examen pragmatique de la mise en œuvre du TPT à l'aide de plusieurs sources de données, notamment des entretiens avec des informateurs (n = 134), des observations semi-structurées (n = 93) et des examens de dossiers de patients atteints de TB dans 31 établissements de santé sélectionnés à dessein dans trois provinces fortement touchées par la TB. Nous avons utilisé une analyse descriptive des cas et un codage thématique pour identifier les obstacles et les facilitateurs de la mise en œuvre du programme TPT. RÉSULTATS: La mise en œuvre du programme TPT était sousoptimale, avec un suivi inadéquat, y compris dans les districts sanitaires où les services de lutte contre la TB fonctionnaient correctement. Les agents de santé ont fait part de leur scepticisme quant à l'efficacité de la TPT, n'ont pas accordé la priorité à la TPT dans la pratique et ont exprimé des opinions divergentes sur les cadres du personnel responsables de la mise en œuvre. Les obstacles au niveau des services et des établissements comprennent l'inefficacité de la recherche des contacts, la pénurie de ressources, l'absence de mécanismes de déclaration standardisés et l'insuffisance de l'éducation des patients sur la TPT. Les obstacles au niveau des patients comprenaient des facteurs socio-économiques. CONCLUSIONS: L'amélioration de la mise en œuvre des TPT nécessitera des systèmes radicalement simplifiés et plus réalisables ainsi qu'une formation pour tous les cadres du personnel de santé. Un partenariat avec les communautés pour stimuler l'adoption de services axés sur la demande peut potentiellement faciliter la mise en œuvre.

Delivery of TB preventive therapy to incarcerated people living with HIV in southern African correctional facilities.

TB preventive treatment (TPT) is recommended for high-risk and hard-to-reach populations such as incarcerated people living with HIV (PLHIV). To assess implementation of TPT delivery in correctional settings, we conducted an exploratory analysis of data from a multisite cohort study in South Africa and Zambia. From 975 participants, 648 were screened for TB, and 409 initiated TPT mostly within a month after initiation of antiretroviral therapy (190/409, 46.5%). We observed a median gap of one month (IQR 0.6-4.7) in TPT delivery to incarcerated PLHIV. Future research should examine standardised quality improvement tools and new strategies such as short-course regimens to improve TPT initiation in this population.

Le traitement préventif antituberculeux (TPT) est recommandé pour les populations à haut risque et difficiles à atteindre, telles que les personnes vivant avec le VIH (PLHIV) qui sont incarcérées. Afin d'évaluer la mise en place du TPT en centres correctionnels, nous avons réalisé une analyse exploratoire des données d'une étude de cohorte multisites en Afrique du Sud et en Zambie. Sur 975 participants, 648 ont subi un test de dépistage de la TB et 409 ont été mis sous TPT, dans le mois ayant suivi l'instauration du traitement antirétroviral pour la plupart (190/409 ; 46,5%). Nous avons observé un écart médian d'un mois (IQR 0,6­4,7) en matière de dispense du TPT aux PLHIV incarcérées. Les études futures devraient analyser l'utilisation d'outils standardisés d'amélioration de la qualité ainsi que de nouvelles stratégies, telles que les schémas thérapeutiques de courte durée, afin d'améliorer l'instauration du TPT dans cette population.

A position statement and practical guide to the use of particulate filtering facepiece respirators (N95, FFP2, or equivalent) for South African health workers exposed to respiratory pathogens including Mycobacterium tuberculosis and SARS-CoV-2.

SUMMARY: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is transmitted mainly by aerosol in particles <10 µm that can remain suspended for hours before being inhaled. Because particulate filtering facepiece respirators ('respirators'; e.g. N95 masks) are more effective than surgical masks against bio-aerosols, many international organisations now recommend that health workers (HWs) wear a respirator when caring for individuals who may have COVID-19. In South Africa (SA), however, surgical masks are still recommended for the routine care of individuals with possible or confirmed COVID-19, with respirators reserved for so-called aerosol-generating procedures. In contrast, SA guidelines do recommend respirators for routine care of individuals with possible or confirmed tuberculosis (TB), which is also transmitted via aerosol. In health facilities in SA, distinguishing between TB and COVID-19 is challenging without examination and investigation, both of which may expose HWs to potentially infectious individuals. Symptom-based triage has limited utility in defining risk. Indeed, significant proportions of individuals with COVID-19 and/or pulmonary TB may not have symptoms and/or test negative. The prevalence of undiagnosed respiratory disease is therefore likely significant in many general clinical areas (e.g. waiting areas). Moreover, a proportion of HWs are HIV-positive and are at increased risk of severe COVID-19 and death. RECOMMENDATIONS: Sustained improvements in infection prevention and control (IPC) require reorganisation of systems to prioritise HW and patient safety. While this will take time, it is unacceptable to leave HWs exposed until such changes are made. We propose that the SA health system adopts a target of 'zero harm', aiming to eliminate transmission of respiratory pathogens to all individuals in every healthcare setting. Accordingly, we recommend: the use of respirators by all staff (clinical and non-clinical) during activities that involve contact or sharing air in indoor spaces with individuals who: (i) have not yet been clinically evaluated; or (ii) are thought or known to have TB and/or COVID-19 or other potentially harmful respiratory infections;the use of respirators that meet national and international manufacturing standards;evaluation of all respirators, at the least, by qualitative fit testing; andthe use of respirators as part of a 'package of care' in line with international IPC recommendations. We recognise that this will be challenging, not least due to global and national shortages of personal protective equipment (PPE). SA national policy around respiratory protective equipment enables a robust framework for manufacture and quality control and has been supported by local manufacturers and the Department of Trade, Industry and Competition. Respirator manufacturers should explore adaptations to improve comfort and reduce barriers to communication. Structural changes are needed urgently to improve the safety of health facilities: persistent advocacy and research around potential systems change remain essential.

Factors Associated with Prevalent Tuberculosis Among Patients Receiving Highly Active Antiretroviral Therapy in a Nigerian Tertiary Hospital.

BACKGROUND: Tuberculosis (TB) causes significant morbidity/mortality among human immunodeficiency virus-infected individuals in Africa. Reducing TB burden in the era of highly active antiretroviral therapy (HAART) is a public health priority. AIM: We determined the factors associated with prevalent TB among patients receiving HAART. SUBJECTS AND METHODS: We conducted a cross-sectional study of adult patients who had received HAART for ≥12 weeks in a Nigerian tertiary hospital. Patients whose TB diagnosis predated HAART were excluded from the study. Pre-HAART data were collected from the clinic records, whereas post-HAART data were obtained through medical history, physical examination, and laboratory investigations. Standard TB screening/diagnostic algorithms as applicable in Nigeria were used. Logistic regression analysis was used to determine factors independently associated with prevalent TB. RESULTS: about 65.8% (222/339) were women. The mean age was 41.1 (10.0) years and 23.6% (73/339) had past history of TB. The prevalence of active TB was 7.7% (26/339). Among these patients, 42.3% (11/26) had pulmonary TB, 34.6% (9/26) had disseminated TB, whereas 23.1% (6/26) had only extra-pulmonary disease. Only 45% (9/20) of patients with pulmonary involvement had positive sputum smear. Factors independently associated with prevalent TB were lower social class (adjusted odds ratio [aOR]: 31.7; 95% confidence interval [CI]: 1.1-1417.3), HAART non-adherence (aOR125.5; 95% CI: 9.6-1636.3), baseline CD4 <200cells/µl (aOR31.0; 95%CI: 1.6-590.6), previous TB (aOR13.8; 95% CI: 2.0-94.1), and current hemoglobin <10 g/dl (aOR10.3; 95% CI: 1.1-99.2). CONCLUSION: Factors associated with prevalent TB were a lower social class, HAART non-adherence, severe immunosuppression before HAART initiation, previous TB, and anemia post-HAART. TB case finding should be intensified in these high-risk groups.

Adherence to TB preventive therapy for HIV-positive patients in rural South Africa: implications for antiretroviral delivery in resource-poor settings?

OBJECTIVES: To explore patient and health worker perspectives on adherence to tuberculosis preventive therapy (TBPT), and to derive lessons for improving access to care amongst human immunodeficiency virus (HIV) infected individuals in resource-poor settings. DESIGN: Both quantitative and qualitative methods were employed. Patient records were reviewed for HIV-positive individuals attending a hospital-based HIV clinic between January 2000 and March 2002. Eighteen patients and two health care workers underwent in-depth interviews exploring perspectives around adherence. RESULTS: Of 229 HIV-positive clinic attendees, 94 (41.0%) were eligible for TBPT. Of 87 patients initiating a 6-month TBPT course of isoniazid 300 mg daily, 41 (47.1%) completed TBPT. Of the 46 interrupters, 16 (34.7%) did not return to the clinic after receiving their first dose of TBPT. Barriers to adherence included fear of stigmatization, lack of money for food and transport, the belief that HIV is incurable, competition between Western and traditional medicine, and a reluctance to take medication in the absence of symptoms. Disclosure of HIV status, social and family support, and a supportive clinic environment positively influenced adherence. CONCLUSION: Interventions to improve the accessibility and quality of the care delivery system have the potential to support adherence to TBPT and other HIV care regimens, including antiretroviral therapy.

A review of sex differences in the epidemiology of tuberculosis.

Globally, the prevalence of infection with Mycobacterium tuberculosis is similar in males and females until adolescence, after which it is higher in males. In industrialized countries in the middle of this century (1930s to 1950s), females aged 15 to 34 years had higher tuberculosis notification rates than males of the same age. However, as notification rates in these countries decreased over time, rates in males became higher than those of females for all ages over 15. Present notification rates of both sexes combined in many developing countries are similar to those of industrialized countries in the middle of the century, although the sex and age pattern is similar to that in industrialized countries at present, with men's disease rates exceeding women's after the age of 15. These findings raise the possibility that cases of tuberculosis among women are being under-reported in developing regions. This is supported by the results of a study comparing active and passive case-finding in which women with tuberculosis were under-notified to public health authorities when relying on passive case-finding. In addition, epidemiological evidence from the pre-human immunodeficiency virus (HIV) era shows that young to early-middle-aged women progress from infection to disease with greater frequency than do men. This elevated frequency of progression among women now coincides with a peak in HIV prevalence among women of the same age. National Tuberculosis Programmes must assess possible sex differences that exist in their countries. In addition, information about the risks of tuberculosis in younger women should be incorporated into maternal and child health, and HIV/AIDS programmes. Further research comparing sex differences in tuberculosis rates, preferably using active as well as passive case-finding, would be necessary to determine whether young women are undernotified in developing countries.

Tuberculosis care in community care organizations in sub-Saharan Africa: practice and potential.

SETTING: Community care organizations in sub-Saharan Africa. OBJECTIVES: To evaluate current tuberculosis (TB) care in community health care organizations in sub-Saharan Africa, to assess their potential contribution to tuberculosis care, and to develop a model for expanded community participation in effective TB control. DESIGN: Quantitative assessment of tuberculosis care and cross-sectional assessment of qualitative measures in 14 community care organizations in Uganda, Zambia, South Africa and Malawi. RESULTS: The community care organizations assessed mainly provided care for human immunodeficiency virus (HIV) and aquired immune deficiency syndrome (AIDS) patients, and received funding from non-governmental organizations. Shortcomings in tuberculosis care included delays in diagnosis (which was often not based on sputum examination), drug shortages, low completion rates, high default rates, inadequate recording, little interaction with government tuberculosis programmes, and inadequate training of staff. However, one organization that provided primarily tuberculosis care and collaborated closely with the district tuberculosis programme and hospital attained a high treatment completion rate. The strong points of the community care organizations that favour a potential role of community participation in tuberculosis care were accessibility and staff motivation. CONCLUSION: Despite most community care organizations' shortcomings in tuberculosis care, they do have the potential to improve the care of tuberculosis patients, thus reducing the load on overstretched health facilities. Their potential impact on tuberculosis control depends on their population coverage and sustainability. HIV/AIDS community care organizations with strengthened management of tuberculosis care could serve as a model for expanded community participation in tuberculosis control. Operational research is needed to assess the feasibility and cost-effectiveness of community-based TB care.

Assessing health seeking behaviour among tuberculosis patients in rural South Africa.

SETTING: South Africa's rural Northern Province. OBJECTIVES: To examine patterns of health seeking behaviour among hospitalised tuberculosis patients. DESIGN: Information on personal characteristics, health seeking behaviour and delays to presentation and hospitalisation was collected from hospitalised TB patients. Analysis of rates was used to investigate factors associated with delay. RESULTS: Among 298 patients, median total delay to hospitalisation was 10 weeks, with patient delay contributing a greater proportion than service provider delay. Patients more often presented initially to public hospitals (41%) or clinics (31 %) than to spiritual/traditional healers (15%) or private GPs (13%). Total delay was shorter amongst those presenting to hospitals than those presenting to clinics (rate ratio 1.33, 95%CI 1.13-1.85), with a significantly smaller proportion of the total delay attributable to the health service provider (18% vs. 42%). Those exhibiting a conventional risk profile for TB (migrants, alcohol drinkers, history of TB) were diagnosed most quickly by health services, while women remained undiagnosed for longer. CONCLUSION: Considerable delay exists between symptom onset and treatment initiation among pulmonary tuberculosis patients. While a substantial delay was attributable to late patient presentation, an important, preventable period of infectiousness was caused by the failure of recognised clinical services to diagnose tuberculosis among symptomatic individuals.

Undiagnosed pulmonary tuberculosis deaths in rural South Africa.

This research explores death from pulmonary tuberculosis (PTB) using a verbal autopsy (VA) tool within the established Agincourt Health and Demographic Surveillance System site in South Africa's rural northeast. Previous work on active case finding in the area highlighted a modest burden of undiagnosed PTB in the community. This VA research confirms the existence of undiagnosed PTB deaths, with 13 (46%) of 28 PTB deaths among the permanent adult population (n = 38,251) going undetected by the health service. There was a median duration of coughing in the community of 16 weeks among these undiagnosed PTB deaths. As most undiagnosed cases present to the health service at some point during their illness, intervention strategies to support early diagnosis at this level can only be re-emphasised by this work.

Active case finding: understanding the burden of tuberculosis in rural South Africa.

SETTING: The Agincourt demographic and health surveillance site in South Africa's rural Northern Province. OBJECTIVES: To accurately assess the true burden of tuberculosis in a rural sub-district with a known high prevalence of human immunodeficiency virus. DESIGN: Data on hospital registrations of tuberculosis were combined with data from an ongoing demographic health and surveillance system to accurately describe the burden of tuberculosis in a well-defined community. Undiagnosed active cases of sputum-positive disease in the community were detected among chronic coughers identified by heads of household during a single-pass census interview. RESULTS: The incidence of hospitalised tuberculosis among the permanently resident population (n = 56 566) was 212/100,000 person-years during 1999. The average point prevalence of detected tuberculosis (all forms) among patients aged over 10 years was 133/100,000, and 81/100,000 for sputum-positive pulmonary disease. This compares with a point prevalence of 16/100,000 cases of sputum-positive disease detected through active case finding. CONCLUSION: For every nine cases of sputum positive pulmonary tuberculosis being treated at any one time, there are two cases of undiagnosed disease in the community. This study demonstrates a modest burden of undiagnosed tuberculosis among residents in a rural sub-district in South Africa.

Sphenoid sinusitis.

We review our clinical experience with infectious sphenoid sinusitis in an effort to characterize the clinical presentation, bacteriology and associated severe complications of this frequently misdiagnosed infection.

Cultural feasibility studies in preparation for clinical trials to reduce maternal-infant HIV transmission in Haiti.

A cultural feasibility study is defined as one that investigates scientific as well as ethical, behavioral, and social issues in the design of clinical trials. The value of such a broadly defined assessment is illustrated through the presentation of two case studies conducted to prepare for clinical trials to reduce maternal-infant HIV transmission on Cité Soleil, Haiti. The first study addressed issues surrounding a trial of breast-feeding and exclusive bottle-feeding among HIV seropositive mothers. The second study focused on the implementation of a double-blind trial of HIV immune globulin and standard immune globulin to be administered to infants of seropositive mothers shortly after birth. Both cases used focus group interviews with mothers and in-depth interviews with key informants to investigate AIDS-related beliefs, acceptability of trial participation, risks to subjects, and community reactions and repercussions to the trial. Findings point to the difficulties posed by attempts to conduct trial involving complex research designs in socially disadvantaged populations. Recommendations highlight the need to consider the community-wide impact of a trial, and the need to undertake extensive educational preparation of participants to ensure informed consent and adherence to protocols.

PIP: Cultural feasibility studies use ethnographic methods to explore ethical, behavioral, and social issues inherent in the design of proposed clinical trials. This approach was applied in advance of clinical trials aimed at reducing maternal-infant HIV transmission in Cite Soleil, Haiti. The first focused on conditions that would be necessary to conduct a trial of breast feeding versus exclusive bottle feeding by HIV-positive mothers; the second investigated the feasibility of a double-blind trial of administration of a high- titer antibody preparation--HIV immune globulin (HIVIG)--to infants of seropositive mothers shortly after birth. Study methods included focus group discussions with mothers and in-depth interviews with key informants about AIDS-related beliefs, acceptability of trial participation, risks to subjects, and community repercussions. Concerns identified included the potential negative effect on breast feeding promotion efforts in Haiti, the scarcity of economic means to sustain safe bottle feeding, the risk of being labeled HIV-positive by virtue of study participation, the potential for the HIVIG trial to reinforce the misconception that a vaccine effective against AIDS exists, and problems explaining the concept of a double-blind study and accepting random assignment to treatment and control groups. As a result of these studies, it was decided to conduct the infant feeding study in a community with higher rates of exclusive bottle feeding and lower infant mortality than exist in Cite Soleil. The HIVIG trial could be conducted, but only after extensive community education to ensure informed consent. An objective assessment of subject comprehension was developed for this purpose.

Development of a sterilizing in-place application for a production machine using Vaporized Hydrogen Peroxide.

The use of steam in sterilization processes is limited by the implementation of heat-sensitive components inside the machines to be sterilized. Alternative low-temperature sterilization methods need to be found and their suitability evaluated. Vaporized Hydrogen Peroxide (VHP) technology was adapted for a production machine consisting of highly sensitive pressure sensors and thermo-labile air tube systems. This new kind of "cold" surface sterilization, known from the Barrier Isolator Technology, is based on the controlled release of hydrogen peroxide vapour into sealed enclosures. A mobile VHP generator was used to generate the hydrogen peroxide vapour. The unit was combined with the air conduction system of the production machine. Terminal vacuum pumps were installed to distribute the gas within the production machine and for its elimination. In order to control the sterilization process, different physical process monitors were incorporated. The validation of the process was based on biological indicators (Geobacillus stearothermophilus). The Limited Spearman Karber Method (LSKM) was used to statistically evaluate the sterilization process. The results show that it is possible to sterilize surfaces in a complex tube system with the use of gaseous hydrogen peroxide. A total microbial reduction of 6 log units was reached.

A report on pathological changes of the dipole moment in children suffering from anthracycline cardiomyopathy.

Cardiomyopathy is a severe complication of the tomour therapy with anthracyclines. Since even minor disturbances of myocardial cell membranes could influence the dipole moment of the heart the noninvasive measurements of this parameter might be useful, particularly in the paediatric population. 17 children aged 2-15 years treated clinically for various malign blood diseases were examined repeatedly with a modified Nelson lead-system up to 3 years. The dipole moment was evaluated by visual comparison of the calculated horizontal and frontal VCGs, evaluation of 3 distinctive vectors, as well as of the magnitude curves and the velocity curves, all of them compared with the normal age dependent percentiles of each respective child. Conventional 12-lead ECGs were used to confirm rhythm disturbances and alterations of P-, PQ-, QRS-, and QT-durations. Our results show that damages of the heart are different during the time of the drug administration, then consisting of acute toxic reactions such as sudden dilatation and/or rhythm disturbances, and of long-term disturbances leading to growth retardation of the heart with the danger of chronic congestive heart failure months or years after the end of the anthracycline treatment. Morphological and biochemical damages of myofibrils caused by the toxicity of anthracyclines precede functional restraints of the heart. A noninvasive method for an early and reliable diagnosis of these damages is urgently needed, particularly for children. Measurements of the dipole moment with the Nelson-lead system seem to offer this diagnostic tool which aims possible changes of the drug administration protocol. (Fig. 3, Ref. 15.)

Community-based intervention to enhance provision of integrated TB-HIV and PMTCT services in South Africa.

OBJECTIVE: To conduct an impact assessment of an intervention to enhance the provision of community-based integrated services for tuberculosis (TB), human immunodeficiency virus (HIV) and prevention of mother-to-child transmission (PMTCT). METHODS: The intervention consisted of a combination of training of community care workers (CCWs), structural adjustments, harmonisation of scope of practice and stipend of CCWs and enhanced supervision of CCWs to provide comprehensive TB-HIV/PMTCT services in a rural South African district. A before and after study design was used with a household survey to assess the operational effectiveness of the intervention. Six clusters were randomised into intervention and control arms. Quantitative data were analysed using logistic regression, adjusting for cluster design. RESULTS: Logistic regression analyses of the survey data show that CCWs from the intervention arm performed better in the provision of TB-HIV/PMTCT services, such as screening for TB and sexually transmitted infections, adherence to anti-tuberculosis treatment and antiretroviral therapy and counselling on infant feeding compared to the control CCWs (P < 0.05). However, intervention CCWs performed worse in the integrated management of childhood illnesses education and social welfare referrals (P < 0.05). The uptake of HIV testing increased significantly in the intervention arm, from 55% to 78% (P < 0.001). CONCLUSION: The intervention was effective in enhancing the provision of community-based TB-HIV and PMTCT services. However, attention to other primary health care services is required to ensure that all key services are provided.