Exploring HIV disease indicators at MDR-TB treatment initiation in South Africa.

BACKGROUND: Understanding relationships between HIV and multidrug-resistant TB (MDR-TB) is crucial for ensuring successful MDR-TB outcomes.METHODS: We used a cross-sectional analysis to evaluate sociodemographic and clinical characteristics as correlates of antiretroviral therapy (ART) use, having an HIV viral load (VL) result, and HIV viral suppression in a cross-sectional sample of people with HIV (PWH) and MDR-TB enrolled in a cluster-randomized trial of nurse case management to improve MDR-TB outcomes.RESULTS: Among 1,479 PWH, the mean age was 37.1 years; 809 (54.7%) were male, and 881 (59.6%) were taking ART. Housing location, employment status, and CD4 count differed significantly between those taking vs. those not taking ART. Among the 881 taking ART, 681 (77.3%) had available HIV VL results. Housing location, CD4 count, and prior history of TB differed significantly between those with and without a VL result. Among the 681 with a VL result, 418 (61.4%) were virally suppressed. Age, education level, CD4 count, TB history, housing location, and ART type differed significantly between those with and without viral suppression.CONCLUSION: PWH presenting for MDR-TB treatment with a history of TB, taking a protease inhibitor, or living in a township may risk poor MDR-TB outcomes.

Determining the prevalence of tuberculosis in emergency departments in the Eastern Cape region of South Africa and the utility of the World Health Organization tuberculosis screening tool.

BACKGROUND: South Africa (SA) faces a significant tuberculosis (TB) burden complicated by high rates of HIV-TB co-infection. In SA, emergency departments (EDs) play an important role in screening for TB. OBJECTIVES: To determine the prevalence of TB in the ED and the effectiveness of the World Health Organization (WHO) TB screening tool. METHODS: This was a cross-sectional observational study, conducted in the ED at Livingstone Hospital, Port Elizabeth, from 4 June to 15 July 2018. All patients aged >18 years and able to consent were administered the WHO TB screening questions and underwent a point-of-care HIV test and demographic data collection. Patients were followed up for 1 year and tracked in the National Health Laboratory Service database to determine TB status using laboratory testing. RESULTS: Over the study period, 790 patients were enrolled. Overall, 121 patients (15.3%) were TB-positive, with 46 (38.0%) diagnosed after presenting to the ED and 75 (62.0%) with a previous TB history determined by self-report or confirmed laboratory testing. A greater proportion of the TB-positive patients were HIV-positive (49.6%) compared with the TB-negative population (24.8%). TB-positive individuals were more likely to present to the ED with a chief complaint of shortness of breath (SoB) (18.2%) compared with the TB-negative population (10.5%). Overall, the WHO TB screening tool had poor sensitivity (46.5%) and specificity (62.5%) for identifying TB-positive patients in the ED. A multiple logistic regression analysis, controlled for age and sex, showed HIV status (odds ratio (OR) 2.81; p<0.001) and SoB (OR 2.19; p<0.05) to be significant predictors of TB positivity. Adding positive HIV status and a presenting complaint of SoB increased sensitivity to 78.3%. CONCLUSIONS: EDs in SA face a high burden of TB. While WHO screening guidelines identify some of these patients, including routine HIV testing in the ED could significantly affect the number of TB diagnoses made.

Risk factors for poor engagement in drug-resistant TB care in South Africa: a systematic review.

BACKGROUND: Metrics of poor patient engagement, including missed appointments, treatment interruption, sub-optimal medication adherence, and loss to follow-up, have been linked to poor clinical multidrug-resistant TB (MDR-TB) outcomes. Understanding the risk factors for poor patient engagement is necessary to improve outcomes and control TB. This review synthesizes the risk factors for poor patient engagement in MDR-TB treatment across South Africa. DESIGN: A systematic review of five databases (PubMed, Embase, CINAHL, Cochrane, and Web of Science) was conducted, covering articles published between 2010 and 2020. Articles were included if they provided information about risk factors associated with poor engagement among adults (⩾15 years) in treatment for MDR-TB in South Africa. Reviews, editorials, abstracts, and case studies were excluded. RESULTS: Six studies met the inclusion criteria. Male sex and younger age were the most consistently identified risk factors for poor engagement; however, there was a lack of consistency in the choice of covariates, measurement of the variables, analytic methods, and significant factors associated with poor engagement between studies. Alcohol use, substance use, living with HIV, pulmonary TB site, and ethnicity were all identified as risk factors in at least one included study, while formal housing and steady employment were found to be protective. CONCLUSION: The available literature offers little cohesive data to address poor patient engagement in this population. Further research needs to focus on identifying and addressing risk factors for poor patient engagement. This is particularly salient within the context of newer all-oral and short-course MDR-TB treatment regimens.

CONTEXTE: Les indicateurs d'une faible coopération des patients, tels que les rendez-vous manqués, les arrêts de traitement, une observance thérapeutique sous-optimale et une perte de vue du patient, ont été associés à de mauvais résultats cliniques dans le cadre de la TB multirésistante (MDR-TB). Il convient de comprendre les facteurs de risque d'une faible coopération des patients pour améliorer les résultats et contrôler la TB. Cette revue synthétise les facteurs de risque d'une faible coopération des patients dans le cadre du traitement de la MDR-TB en Afrique du Sud. MÉTHODE: Une revue systématique de cinq bases de données (PubMed, Embase, CINAHL, Cochrane et Web of Science) a été réalisée, englobant les articles publiés entre 2010 et 2020. Les articles ont été inclus s'ils apportaient des informations sur les facteurs de risque associés à la faible coopération des patients adultes (⩾15 ans) sous traitement pour MDR-TB en Afrique du Sud. Les revues, les éditoriaux, les résumés et les études de cas ont été exclus. RÉSULTATS: Six études satisfaisaient les critères d'inclusion. Les facteurs de risque d'une faible coopération les plus fréquents étaient le genre masculin et le jeune âge. Cependant, un manque de cohérence a été observé entre les études dans le choix des covariables, la mesure des variables, les méthodes analytiques et les facteurs significatifs associés à une faible coopération. La consommation d'alcool et de drogues, la séropositivité au VIH, une TB pulmonaire et l'origine ethnique ont tous été identifiés comme facteurs de risque dans au moins une étude incluse, alors que des facteurs tels que « logement formel ¼ et « emploi stable ¼ étaient des facteurs protecteurs. CONCLUSION: La littérature disponible offre peu de données cohérentes permettant d'examiner la faible coopération des patients dans cette population. Les recherches à venir doivent identifier et analyser les facteurs de risque de la faible coopération des patients. Ceci est particulièrement important au vu des nouveaux schémas thérapeutiques courts et entièrement par voie orale de la MDR-TB.

Leveraging nurse practitioner capacities to achieve global health for all: COVID-19 and beyond.

AIM: To argue that nurse practitioners have been under-utilized generally in the current global health environment, creating barriers to achieving universal health coverage and the Sustainable Development Goals. BACKGROUND: Nurse practitioners are advanced practice nurses possessing expert knowledge and leadership skills that can be optimized to narrow disparities and ensure access to high-quality health care globally. Nurses worldwide have been challenged to meet global public health needs in the context of COVID-19 (SARS-CoV-2 virus), and there are early indications that nurse practitioners are being called upon to the full extent of their capabilities in the current pandemic. SOURCES OF EVIDENCE: PubMed; Google Scholar; the International Council of Nurses; World Health Organization; United Nations; and the experiences of the authors. DISCUSSION: Several international reports, nursing and health organizations have called for continued investment in and development of nursing to improve mechanisms that promote cost-effective and universally accessible care. Expanding nurse practitioner scopes of practice across nations will leverage their clinical capacities, policy and advocacy skills, and talents to lead at all levels. CONCLUSION: Ongoing empirical data and policy change is needed to enable the full scope and strategic utilization of nurse practitioners across healthcare systems and contexts. IMPLICATIONS FOR NURSING PRACTICE, AND NURSING AND HEALTH POLICY: Widespread education regarding nurse practitioner capacities for interdisciplinary partners, policymakers and the public is needed. Policies that safely expand their roles are critical. Role titles and remuneration reflective of their scope and service are required to lead, sustain and grow the workforce internationally.

Risk of hearing loss among multidrug-resistant tuberculosis patients according to cumulative aminoglycoside dose.

SETTING: The ototoxic effects of aminoglycosides (AGs) lead to permanent hearing loss, which is one of the devastating consequences of multidrug-resistant tuberculosis (MDR-TB) treatment. As AG ototoxicity is dose-dependent, the impact of a surrogate measure of AG exposure on AG-induced hearing loss warrants close attention for settings with limited therapeutic drug monitoring.OBJECTIVE: To explore the prognostic impact of cumulative AG dose on AG ototoxicity in patients following initiation of AG-containing treatment for MDR-TB.DESIGN: This prospective cohort study was nested within an ongoing cluster-randomized trial of nurse case management intervention across 10 MDR-TB hospitals in South Africa.RESULTS: The adjusted hazard of AG regimen modification due to ototoxicity in the high-dose group (≥75 mg/kg/week) was 1.33 times higher than in the low-dose group (<75 mg/kg/week, 95%CI 1.09-1.64). The adjusted hazard of developing audiometric hearing loss was 1.34 times higher than in the low-dose group (95%CI 1.01-1.77). Pre-existing hearing loss (adjusted hazard ratio [aHR] 1.71, 95%CI 1.29-2.26) and age (aHR 1.16 per 10 years of age, 95%CI 1.01-1.33) were also associated with an increased risk of hearing loss.CONCLUSION: MDR-TB patients with high AG dose, advanced age and pre-existing hearing loss have a significantly higher risk of AG-induced hearing loss. Those at high risk may be candidates for more frequent monitoring or AG-sparing regimens.

Evaluation of miLINC to shorten time to treatment for rifampicin-resistant Mycobacterium tuberculosis.

BACKGROUND: Achieving the 90-90-90 targets for tuberculosis (TB) will require interventions that enhance diagnosis, linkage, treatment and adherence to care. As a first step in the process, our team designed a suite of smartphone applications known as miLINC to improve time from diagnosis to treatment initiation in drug-resistant TB patients.SETTING: Three clinical locations in a large, peri-urban district in KwaZulu-Natal, South Africa.OBJECTIVE: To assess the acceptability, feasibility and impact of the miLINC mobile health applications as a solution to reducing the time from presentation to treatment initiation of rifampicin-resistant (RR) TB patients.METHODS: We used a prospective, observational quality improvement evaluation of miLINC's impact among newly diagnosed patients with RR-TB.RESULTS: A convenience sample comprising details of 6341 patients with presumptive TB were entered into miLINC. Of the 631 TB-positive sputum specimens, 41 (6.5%) were found to be RR-TB. The mean time from clinical presentation to RR-TB treatment initiation was 3 days, 21 h, 17 min.CONCLUSION: This is the first study to suggest that the time from presentation to diagnosis and to treatment initiation for patients with RR-TB can be significantly improved using an integrated approach combining technology with appropriate human resources.

Cardiovascular risk prevalence in South Africans with drug-resistant tuberculosis: a cross-sectional study.

In South Africa, the risk factors for cardiovascular disease (CVD) are increasing, thereby impacting patients with drug-resistant tuberculosis (DR-TB). To determine the prevalence of traditional CVD risk factors (diabetes mellitus [DM], smoking, hypertension, increased body mass index [BMI]) and a total risk score for CVD among patients with DR-TB. This cross-sectional study was nested within an ongoing cluster-randomized trial in 10 DR-TB hospitals in South Africa. The data for the present study were collected between November 2014 and July 2016. Of 900 participants aged 18 years, 75.1% were co-infected with the human immunodeficiency virus (HIV), and 52.3% had one or more CVD risk factors. The prevalence of CVD risk factors was hypertension (16.7%), increased BMI (16.6%), DM (5.2%), and smoking (31.4%). Among patients with DM or hypertension, 58.8-95.5% had additional comorbid CVD risk factors. Of 398 participants eligible for the CVD risk score (age 35 years), 23.4% had a moderate or high CVD risk score. Patients with multiple diseases, including DR-TB and HIV, with traditional CVD risk factors, may have higher risks for negative outcomes during treatment for DR-TB. TB providers should identify people at risk to initiate primary and secondary prevention to improve outcomes. .

A systematic review of the effectiveness of smoking cessation interventions among patients with tuberculosis.

Smoking is a significant risk factor for morbidity and mortality, particularly among patients with tuberculosis (TB). Although smoking cessation is recommended by the World Health Organization and the International Union Against Tuberculosis and Lung Disease, there has been no published evaluation of smoking cessation interventions among people with TB. The purpose of this review was to synthesize the evidence on interventions and suggest practice, research and policy implications. A systematic review of the literature identified 14 peer-reviewed studies describing 13 smoking cessation interventions between 2007 and 2017. There were five randomized controlled trials, three non-randomized interventions, and five prospective cohort studies. The primary types of interventions were brief advice (n = 9), behavioral counseling (n = 4), medication (n = 3), and community-based care (n = 3). A variety of health care workers (HCWs) implemented interventions, from physicians, nurses, clinic staff, community health workers (CHWs), as did family members. There was significant heterogeneity of design, definition of smoking and smoking abstinence, and implementation, making comparison across studies difficult. Although all smoking interventions increased smoking cessation between 15% and 82%, many studies had a high risk for bias, including six without a control group. The implementing personnel did not make a large difference in cessation results, suggesting that national TB programs may customize according to their needs and limitations. Family members may be important supporters/advocates for cessation. Future research should standardize definitions of smoking and cessation to allow comparisons across studies. Policy makers should encourage collaboration between tobacco and TB initiatives and develop smoking cessation measures to maximize results in low-resource settings.

Le tabac constitue un facteur de risque significatif en termes de morbidité et de mortalité, particulièrement pour les patients atteints de tuberculose (TB). L'arrêt du tabac a été recommandé par l'Organisation Mondiale de la Santé et l'Union Internationale contre la Tuberculose et les Maladies Respiratoires ; aucune évaluation n'a cependant été publiée à propos des interventions de sevrage du tabac parmi les personnes atteintes de TB. Le but de cette revue a été de synthétiser les données probantes relatives à ces interventions et de suggérer les implications en matière de pratique, de recherche et de politique. Une revue systématique de la littérature a identifié 14 études revues par des pairs, décrivant 13 interventions d'arrêt du tabac entre 2007 et 2017 : 5 essais randomisés contrôlés, 3 interventions non randomisées et 5 études prospectives de cohorte. Les types principaux d'intervention ont consisté en brefs conseils (n = 9), en conseil comportemental (n = 4), en médicaments (n = 3) et en prise en charge communautaire (n = 3). Les interventions ont été mises en œuvre par toute une gamme de personnel de santé­médecins, infirmiers, personnel des dispensaires, travailleurs de santé communautaire­et par des membres de la famille. Ces interventions ont été significativement hétérogènes en matière de schéma, de définition du tabagisme et de l'abstinence et de mise en œuvre, ce qui a rendu difficiles les comparaisons entres les études. Dans l'ensemble, toutes les interventions ont accru le taux d'arrêt du tabac de 15% à 82%, mais de nombreuses études sont très sujettes aux biais, notamment les six études dépourvues de groupe témoin. Le type de personnel de mise en œuvre n'a pas entrainé de modifications majeures en termes de résultats, ce qui suggère que les programmes nationaux TB peuvent adapter la mise en œuvre de ces interventions à leurs besoins et à leurs limites. Les membres de la famille semblent jouer un rôle important en matière de soutien et de plaidoyer. Des recherches ultérieures devraient standardiser les définitions de la consommation et de l'arrêt du tabac afin de permettre des comparaisons entre les études. Les décideurs politiques devraient encourager la collaboration entre les initiatives liées au tabac et celles liées à la TB et élaborer des mesures d'arrêt du tabac pour maximiser les résultats dans les contextes de faibles ressources.

El tabaquismo representa un importante factor de riesgo de morbilidad y mortalidad, sobre todo para los pacientes con tuberculosis (TB). La Organización Mundial de la Salud y la Unión Internacional contra la Tuberculosis y las Enfermedades Respiratorias han recomendado que se promueva la deshabituación tabáquica, pero aún no se ha publicado una evaluación de las intervenciones que favorecen el abandono del tabaquismo en las personas con diagnóstico de TB. La finalidad de la presente revisión consistió en reunir la evidencia existente sobre estas intervenciones y proponer los corolarios que se podrían aplicar en la práctica, la investigación y la formulación de políticas. En una revisión sistemática de artículos científicos se encontraron 14 estudios publicados del 2007 al 2017 en revistas con comité de lectura que describían 13 intervenciones de deshabituación tabáquica. Los artículos abordaban 5 ensayos aleatorizados, 3 intervenciones no aleatorizadas y 5 estudios de cohortes prospectivos. Los principales tipos de intervenciones consistieron en asesoramiento breve (n = 9), orientación conductual (n = 4), tratamiento médico (n = 3) y atención al nivel comunitario (n = 3). Diversos profesionales de salud participaron en la ejecución de las intervenciones como miembros del personal médico, de enfermería, auxiliares clínicos, agentes de salud comunitarios y miembros de la familia. Se observó una gran heterogeneidad con respecto al diseño de los estudios, la definición de tabaquismo y de la abstinencia de tabaco y a la ejecución, que dificultó las comparaciones entre los estudios. En general, todas las intervenciones de deshabituación tabáquica aumentaron el abandono del tabaco de 15% a 82%, pero en muchos de los artículos existía la probabilidad de sesgo como en seis estudios que no contaban con un grupo testigo. El tipo de personal que ejecutaba la intervención no tuvo un efecto notorio en los resultados de abandono, lo cual indica que los programas nacionales contra la TB pueden adaptar las iniciativas a sus necesidades y limitaciones. Los miembros de la familia pueden cumplir una función importante de apoyo o promoción del abandono del tabaco. En las investigaciones futuras es preciso normalizar las definiciones de tabaquismo y de abandono del tabaco con el fin de facilitar las comparaciones entre los estudios. Las instancias normativas deben fomentar la colaboración entre las iniciativas contra el tabaquismo y contra la TB y formular medidas encaminadas a la deshabituación tabáquica que optimicen sus resultados en los entornos con bajos recursos.

Increased risk of aminoglycoside-induced hearing loss in MDR-TB patients with HIV coinfection.

SETTING: A high proportion of individuals with multidrug-resistant tuberculosis (MDR-TB) develop permanent hearing loss due to ototoxicity caused by injectable aminoglycosides (AGs). The prevalence of AG-induced hearing loss is greatest in tuberculosis (TB) and human immunodeficiency virus (HIV) endemic countries in sub-Saharan Africa. However, whether HIV coinfection is associated with a higher incidence of AG-induced hearing loss during MDR-TB treatment is controversial. OBJECTIVE: To evaluate the impact of HIV coinfection on AG-induced hearing loss among individuals with MDR-TB in sub-Saharan Africa. DESIGN: This was a meta-analysis of articles published in PubMed, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Cochrane Review, and reference lists using search terms 'hearing loss', 'aminoglycoside', and 'sub-Saharan Africa'. RESULTS: Eight studies conducted in South Africa, Botswana and Namibia and published between 2012 and 2016 were included. As the included studies were homogeneous (χ2 = 8.84, df = 7), a fixed-effects model was used. Individuals with MDR-TB and HIV coinfection had a 22% higher risk of developing AG-induced hearing loss than non-HIV-infected individuals (pooled relative risk 1.22, 95%CI 1.10-1.36) during MDR-TB treatment. CONCLUSION: This finding is critical for TB programs with regard to the expansion of injectable-sparing regimens. Our findings lend credibility to using injectable-sparing regimens and more frequent hearing monitoring, particularly in resource-limited settings for HIV-coinfected individuals.

Discordance between patient and clinician reports of adverse reactions to MDR-TB treatment.

SETTING: An urban out-patient clinic in Durban, South Africa, providing community-based treatment for drug-resistant tuberculosis (TB). OBJECTIVE: To describe concordance between patient report and clinician documentation of adverse drug reactions (ADRs) to treatment for multidrug-resistant TB (MDR-TB). DESIGN: ADRs were documented by interview using an 18-item symptom checklist and medical record data abstraction during a cross-sectional parent study with 121 MDR-TB patients, 75% of whom were co-infected with the human immunodeficiency virus. Concordance was analyzed using Cohen's κ statistic, Gwet's agreement coefficient (AC) 1, and McNemar's test. RESULTS: ADRs were reported much more frequently in patient interviews (µ = 8.6) than in medical records (µ = 1.4). Insomnia was most common (67% vs. 2%), followed by peripheral neuropathy (65% vs. 18%), and confusion (61 vs. 4%). κ scores were very low, with the highest degree of concordance found in hearing loss (κ = 0.23), which was the only ADR not found to be significantly different between the two data sources (P = 0.34). CONCLUSIONS: Our study showed a lack of concordance between patient report and clinician documentation of ADRs. These findings indicate the need for improved documentation of ADRs to better reflect patients' experiences during MDR-TB treatment. These data have important implications for country-level pharmacovigilance programs that rely on clinician documentation of ADRs for MDR-TB policy formation.

Health care workers' fears associated with working in multidrug- and or extensively-resistant tuberculosis wards in South Africa.

SETTING: Twenty-four drug-resistant tuberculosis (TB) hospitals and wards across all nine provinces of South Africa. OBJECTIVE: To assess health care workers' (HCWs') fears of working in multidrug-resistant TB (MDR-TB) or extensively drug-resistant TB (XDR-TB) wards. DESIGN: A cross-sectional descriptive study was conducted from June to September 2009 in 24 drug-resistant TB hospitals across South Africa. HCWs completed a self-administered questionnaire, including one open-ended question regarding personal concerns about their fear of contracting MDR- or XDR-TB. Responses were analysed by content analysis. RESULTS: Among the 24 hospitals, 499 HCWs were surveyed, of whom 363 (73%) responded to the open-ended question: 286 (86%) were nurses, 38 (11%) medical officers and 10 (3%) others. Six major themes regarding fears associated with the personal risk of acquiring drug-resistant TB emerged. These included the fear of 1) developing MDR- and XDR-TB, 2) the treatment course, 3) the financial implications, 4) family concerns, 5) working environment and 6) psychosocial issues. CONCLUSIONS: These data suggest that the greatest fear of HCWs working in drug-resistant TB wards is contracting MDR- or XDR-TB and infecting others. This fear may negatively impact the provision of quality patient-centred care, and highlights the need for training of HCWs in infection control measures, and specifically on how HCWs can protect themselves and others from developing TB.

Occupational health policies and practices related to tuberculosis in health care workers in KwaZulu-Natal, South Africa.

SETTING: Three district hospitals in KwaZulu-Natal, South Africa, with specialized drug-resistant tuberculosis (TB) wards. OBJECTIVE: To increase understanding of the implementation of occupational health (OH) and infection control (IC) guidelines for the prevention and control of TB among health care workers (HCWs). DESIGN: An operational cross-sectional study conducted between July and September 2011, consisting of interviews with OH and IC nurses and chart review of OH medical records. RESULTS: Although general national and provincial OH policies are in place, no specific OH policies exist for hospital settings. Two of three hospitals had a full-time OH nurse and all had a full-time IC nurse. All hospitals offered TB symptom screening; however, only 19% of HCWs were screened in 2010. TB incidence among HCWs was 1958 per 100 000 population in 2010. All hospitals offered HIV counseling and testing; however, only 22% of staff were tested across sites. Two hospitals offered isoniazid preventive therapy to HIV-positive staff and reassigned these staff to low TB risk areas. CONCLUSIONS: While OH policies and procedures are in place, implementation of these policies and procedures is inconsistent. This potentially places HCWs at risk of acquiring TB. These findings support the need for strengthening OH and IC services to prevent TB.

A national infection control evaluation of drug-resistant tuberculosis hospitals in South Africa.

BACKGROUND: The importance of infection control (IC) in health care settings with tuberculosis (TB) patients has been highlighted by recent health care-associated outbreaks in South Africa. OBJECTIVE: To conduct operational evaluations of IC in drug-resistant TB settings at a national level. METHODS: A cross-sectional descriptive study was conducted from June to September 2009 in all multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB) facilities in South Africa. Structured interviews with key informants were completed, along with observation of IC practices. Health care workers (HCWs) were asked to complete an anonymous knowledge, attitudes and practices (KAP) questionnaire. Multilevel modeling was used to take into consideration the relationship between center and HCW level variables. RESULTS: Twenty-four M(X)DR-TB facilities (100%) were enrolled. Facility infrastructure and staff adherence to IC recommendations were highly varied between facilities. Key informant interviews were incongruent with direct observation of practices in all settings. A total of 499 HCWs were enrolled in the KAP evaluation. Higher level of clinical training was associated with greater IC knowledge (P < 0.001), more appropriate attitudes (P < 0.001) and less time spent with coughing patients (P < 0.001). IC practices were poor across all disciplines. CONCLUSION: These findings demonstrate a clear need to improve and standardize IC infrastructure in drug-resistant TB settings in South Africa.

Transitions in psychiatric inpatient clinical social work.

As a group, psychiatric inpatient clinical social workers have been dramatically affected by the economic crisis in mental health. As they have attempted to cope with a myriad of changes, they also have become leaders in bringing change about. This article described the transition process as experienced by 27 social workers who were interviewed in a descriptive exploratory study. The study showed that inpatient social workers are struggling to create ways to meet increased workload demands and are questioning the effectiveness of short-term hospital treatment. Respondents reported personal and professional losses as well as challenges. They expressed considerable concern about the future of their profession because of pressure to compromise standards.

The e (P4) outer membrane protein of Haemophilus influenzae: biologic activity of anti-e serum and cloning and sequencing of the structural gene.

Outer membrane proteins of nontypeable (NT) Haemophilus influenzae are among the major candidates for inclusion in vaccines against these organisms. This article reports the purification of the e (P4) lipoprotein of H. influenzae and the subsequent production of antiserum directed against this protein. The anti-e polyclonal serum cross-reacted with e protein in multiple clinical NT H. influenzae isolates. Monoclonal antibody analysis of e protein showed at least one surface-exposed epitope to be conserved among NT H. influenzae strains. Anti-e serum also had bactericidal activity against multiple clinical isolates of NT H. influenzae. These results are in contrast to previous reports in the literature that purified P4 protein did not elicit biologically active antibodies. Anti-e antibodies exhibited synergistic bactericidal activity directed against NT H. influenzae when mixed with antibodies directed against another Haemophilus lipoprotein, PCP. This bactericidal synergy was observed against a variety of NT clinical isolates. We also report the cloning of the Haemophilus e lipoprotein, or hel, gene encoding the e protein and its expression and processing in Escherichia coli. The nucleotide sequence of the gene and deduced amino acid sequence of the protein are given. These results demonstrate that e protein is a viable candidate to be a component of a vaccine against NT H. influenzae.

Responses of mental health professionals to lay-offs.

In this study, 39 laid-off mental health professionals responded to a questionnaire that focused on the emotional stress of being laid off and the respondents' efforts to cope with the stress. In the early weeks after lay-off, shock, disbelief, anger, and sadness gave way to depression, anxiety, and feelings of being betrayed and discounted. Most respondents coped with these feelings by talking to others who were being laid off or by focusing their energies on seeking a new job. Many respondents felt that mismanagement of the lay-off process was a major factor in their emotional distress. The author makes recommendations for managing lay-offs based on the responses of the laid-off workers and the principles of crisis management. She also speculates about why most of the lay-offs were poorly managed.

Deduced amino acid sequences of class 1 protein (PorA) from three strains of Neisseria meningitidis. Synthetic peptides define the epitopes responsible for serosubtype specificity.

The previously determined nucleotide sequence of the porA gene, encoding the class 1 outer membrane protein of meningococcal strain MC50, has been used to clone and sequence the porA gene from two further strains with differing serosubtype specificities. Comparison of the predicted amino acid sequences of the three class 1 proteins revealed considerable structural homology with major variation confined to two discrete regions (VR1 and VR2). The high degree of structural homology between the sequences gave predicted secondary structures that were almost identical, with the variable domains located in hydrophilic regions that are likely to be surface located and hence accessible to antibody binding. The predicted amino acid sequences have been used to define the epitopes recognized by mAbs with serosubtype specificity. A series of overlapping decapeptides spanning each of the class 1 protein sequences have been synthesized on solid-phase supports and probed with mAbs. Antibodies with P1.16 and P1.15 subtype specificity reacted with sequences in the VR2 domain, while antibodies with P1.7 subtype specificity reacted with sequences in the VR1 domain. Further peptides have been constructed to define the minimum epitopes recognized by each antibody. Thus we have been able to define linear peptides on each class 1 protein molecule that are responsible for subtype specificity and that represent targets for a protective immune response.

Cloning of genes encoding a 15,000-dalton peptidoglycan-associated outer membrane lipoprotein and an antigenically related 15,000-dalton protein from Haemophilus influenzae.

We have cloned and expressed in Escherichia coli a gene encoding a 15,000-apparent-molecular-weight peptidoglycan-associated outer membrane lipoprotein (PAL) of Haemophilus influenzae. The nucleotide sequence of this gene encodes an open reading frame of 153 codons with a predicted mature protein of 134 amino acids. The amino acid composition and sequence of the predicted mature protein agree with the chemically determined composition and partial amino acid sequence of PAL purified from H. influenzae outer membranes. We have also identified a second gene from H. influenzae that encodes a second 15,000-apparent-molecular-weight protein which is recognized by antiserum against PAL. This protein has been shown to be a lipoprotein. The nucleotide sequence of this gene encodes an open reading frame of 154 codons with a predicted mature protein of 136 amino acids and has limited sequence homology with that of the gene encoding PAL. Southern hybridization analysis indicates that both genes exist as single copies in H. influenzae chromosomal DNA. Both genes encode polypeptides which have amino-terminal sequences similar to those of reported membrane signal peptides and are associated primarily with the outer membrane when expressed in E. coli.