Impact of interventions for tuberculosis prevention and care in South Africa - a systematic review of mathematical modelling studies.

BACKGROUND: Substantial additional efforts are needed to prevent, find and successfully treat tuberculosis (TB) in South Africa (SA). In thepast decade, an increasing body of mathematical modelling research has investigated the population-level impact of TB prevention and careinterventions. To date, this evidence has not been assessed in the SA context. OBJECTIVE: To systematically review mathematical modelling studies that estimated the impact of interventions towards the World HealthOrganization's End TB Strategy targets for TB incidence, TB deaths and catastrophic costs due to TB in SA. METHODS: We searched the PubMed, Web of Science and Scopus databases for studies that used transmission-dynamic models of TB in SAand reported on at least one of the End TB Strategy targets at population level. We described study populations, type of interventions andtheir target groups, and estimates of impact and other key findings. For studies of country-level interventions, we estimated average annualpercentage declines (AAPDs) in TB incidence and mortality attributable to the intervention. RESULTS: We identified 29 studies that met our inclusion criteria, of which 7 modelled TB preventive interventions (vaccination,antiretroviral treatment (ART) for HIV, TB preventive treatment (TPT)), 12 considered interventions along the care cascade for TB(screening/case finding, reducing initial loss to follow-up, diagnostic and treatment interventions), and 10 modelled combinationsof preventive and care-cascade interventions. Only one study focused on reducing catastrophic costs due to TB. The highest impactof a single intervention was estimated in studies of TB vaccination, TPT among people living with HIV, and scale-up of ART. Forpreventive interventions, AAPDs for TB incidence varied between 0.06% and 7.07%, and for care-cascade interventions between 0.05%and 3.27%. CONCLUSION: We describe a body of mathematical modelling research with a focus on TB prevention and care in SA. We found higherestimates of impact reported in studies of preventive interventions, highlighting the need to invest in TB prevention in SA. However, studyheterogeneity and inconsistent baseline scenarios limit the ability to compare impact estimates between studies. Combinations, rather thansingle interventions, are likely needed to reach the End TB Strategy targets in SA.

Use of interactive messaging to reduce pre-diagnosis loss to follow-up for TB care.

OBJECTIVE: To investigate the uptake and usage of a WhatsApp-based interactive communication strategy to avert pre-diagnosis loss to follow-up (LTFU) from TB care in a high-incidence setting.METHODS: We enrolled adults (≥18 years) who underwent routine sputum TB testing in two primary healthcare clinics in Khayelitsha, Cape Town, South Africa. The intervention consisted of structured WhatsApp-based reminders (prompts) sent prior to a routine clinic appointment scheduled 2-3 days after the diagnostic visit. Pre-diagnosis LTFU was defined as failure to return for the scheduled appointment and within 10 days.RESULTS: We approached 332 adults with presumptive TB, of whom 103 (31%) were successfully enrolled; 213 (64%) did not own a WhatsApp-compatible phone. Of 103 participants, 74 (72%) actively responded to WhatsApp prompts; 69 (67%) opted to include a close contact in group communication to co-receive reminders. Pre-diagnosis LTFU was low overall (n = 7, 6.8%) and was not associated with failure to respond to WhatsApp prompts.CONCLUSION: In this high-incidence setting, enrolment in a WhatsApp-based communication intervention among adults with presumptive TB was low, mainly due to low availability of WhatsApp-compatible phones. Among participants, we observed high message response rates and low LTFU, suggesting potential for interactive messaging services to support pre-diagnosis TB care.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Effects of autoclaving on compressive strength of bovine bones and their use as chewing agents for dogs.

This study aimed to evaluate the effect of autoclave processing on compressive stress of spongy and cortical bones, and the effect of autoclaved bones as chewing agents to reduce dental calculus in adult dogs. Spongy and cortical bones were autoclaved (1 ATM, 30 min, and 120°C) and compressive strength was evaluated in autoclaved and raw bone specimens. Autoclaved bones were offered to ten Beagle dogs divided into two groups of 5 dogs each: Group 1 - received a portion of the autoclaved bovine cortical bone (ACB) and Group 2 - received a portion of the autoclaved bovine spongy bone (ASB). Prior to the experimental period (1-d) and every two days thereafter, oral photographs were taken on both sides of the dental arch to evaluate dental calculus reduction over time. The vestibular surface of the canines, premolars, and molars teeth was evaluated using integration software to measure the proportion between the area covered by calculus and the total teeth area. The effect of bone type, treatment (raw vs. autoclaved), and their interaction were evaluated using the PROC GLIMMIX procedure of SAS (version 9.4). Linear equations were generated to estimate calculus reduction over time for ACB and ASB. Compressive strength was higher (P < 0.05) in cortical bones compared to spongy bones. However, the autoclaving procedure did not affect (P > 0.05) compressive strength, regardless of the bone type. The teeth area covered by calculus of dogs that were offered ACB reduced from 41% to 32% in 5 days, and at the end of 15 days a reduction of 62.2% was observed, resulting in a remaining of 15.5% of teeth area covered by calculus. In this group, the dental calculus area reduced by 57.7% after 5 days, and at the end of the trial, only 5.4% of teeth were still covered by calculus, which represents a reduction of 81%. The linear regression analysis revealed no significant difference between the slopes for the ACB and ASB equations (P > 0.05). No health complications such as tooth fracture, intestinal obstructions, and oral lesions were observed throughout the study. Our results demonstrated that the autoclave processing did not impair compressive strength of spongy and cortical bones. This corroborates with the results observed in vivo, which suggests that autoclaved bones are chewing agents for adult dogs with additional benefits of lower risk of bacterial contamination.

Persistent chronic respiratory symptoms despite TB cure is poorly correlated with lung function.

BACKGROUND: Persistent respiratory symptoms and lung function deficits are common after patients with TB. We aimed to define the burden of post-TB lung disease (PTLD) and assess associations between symptoms and impairment in two high TB incidence communities.METHODS: This was a cross-sectional survey of adults in Cape Town, South Africa who completed TB treatment 1-5 years previously. Questionnaires, spirometry and 6-minute walking distance (6MWD) were used to assess relationships between outcome measures and associated factors.RESULTS: Of the 145 participants recruited (mean age: 42 years, range: 18-75; 55 [38%] women), 55 (38%) had airflow obstruction and 84 (58%) had low forced vital capacity (FVC); the mean 6MWD was 463 m (range: 240-723). Respiratory symptoms were common: chronic cough (n = 27, 19%), wheeze (n = 61, 42%) and dyspnoea (modified MRC dyspnoea score 3 or 4: n = 36, 25%). There was poor correlation between FVC or obstruction and 6MWD. Only low body mass index showed consistent association with outcomes on multivariable analyses. Only 19 (13%) participants had a diagnosis of respiratory disease, and 16 (11%) currently received inhalers.CONCLUSION: There was substantial burden of symptoms and physiological impairment in this "cured" population, but poor correlation between objective outcome measures, highlighting deficits in our understanding of PTLD.

Post-tuberculosis lung health: perspectives from the First International Symposium.

ALTHOUGH CURABLE, TB frequently leaves the individual with chronic physical and psycho-social impairment, but these consequences have been largely neglected. The 1st International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to discuss priorities and gaps in addressing this issue. A barrier to progress has been the varied terminology and nomenclature, so the Delphi process was used to achieve consensus on definitions. Lack of sufficient evidence hampered definitive recommendations in most domains, including prevention and treatment of post-TB lung disease (PTLD), but the discussions clarified the research needed. A consensus was reached on a toolkit for future PTLD measurement and on PTLD patterns to be considered. The importance of extra-pulmonary consequences and progressive impairment throughout the life-course was identified, including TB recurrence and increased mortality. Patient advocates emphasised the need to address the psychological and social impacts post TB and called for clinical guidance. More generally, there is an urgent need for increased awareness and research into post-TB complications.

Inferring diet, feeding behaviour and causes of mortality from prey-induced injuries in a New Zealand fur seal.

New Zealand fur seals Arctocephalus forsteri are the most abundant of the 4 otariid (eared seal) species distributed across Australasia. Analyses of stomach contents, scats and regurgitates suggest a diet dominated by bony fish and squid, with cartilaginous species (e.g. sharks and rays) either absent or underrepresented because of a lack of preservable hard parts. Here we report on a subadult specimen from south-eastern Australia, which was found ashore emaciated and with numerous puncture wounds across its lips, cheeks, throat and the inside of its oral cavity. Fish spines embedded in the carcass revealed that these injuries were inflicted by chimaeras and myliobatiform rays (stingrays and relatives), which matches reports on the diet of A. forsteri from New Zealand, but not South Australia. Shaking and tearing of prey at the surface may help to avoid ingestion of the venomous spines, perhaps contributing to their absence from scats and regurgitates. Nevertheless, the number and severity of the facial stab wounds, some of which led to local necrosis, likely affected the animal's ability to feed, and may account for its death. Despite their detrimental effects, fish spine-related injuries are difficult to spot, and may be a common, albeit cryptic, type of trauma. We therefore recommend that stranded seals be systematically examined for this potentially life-threatening pathology.

Two small, cysteine-rich and cationic antifungal proteins from Penicillium chrysogenum: A comparative study of PAF and PAFB.

The filamentous fungus Penicillium chrysogenum Q176 secretes the antimicrobial proteins (AMPs) PAF and PAFB, which share a compact disulfide-bond mediated, ß-fold structure rendering them highly stable. These two AMPs effectively inhibit the growth of human pathogenic fungi in micromolar concentrations and exhibit antiviral potential without causing cytotoxic effects on mammalian cells in vitro and in vivo. The antifungal mechanism of action of both AMPs is closely linked to - but not solely dependent on - the lipid composition of the fungal cell membrane and requires a strictly regulated protein uptake into the cell, indicating that PAF and PAFB are not canonical membrane active proteins. Variations in their antifungal spectrum and their killing dynamics point towards a divergent mode of action related to their physicochemical properties and surface charge distribution. In this review, we relate characteristic features of PAF and PAFB to the current knowledge about other AMPs of different sources. In addition, we present original data that have never been published before to substantiate our assumptions and provide evidences that help to explain and understand better the mechanistic function of PAF and PAFB. Finally, we underline the promising potential of PAF and PAFB as future antifungal therapeutics.

Notification of relapse and other previously treated tuberculosis in the 52 health districts of South Africa.

OBJECTIVE: To investigate the extent to which relapse and other previously treated tuberculosis (TB) contribute to the notified TB burden in South Africa.DESIGN: We conducted an ecological analysis at the level of the 52 South African health districts using national electronic TB register data. We included all bacteriologically confirmed TB cases treated for presumed drug-susceptible TB in 2011. Treatment history information was based on recorded patient categories (new vs. retreatment).RESULTS: Relapse and other previously treated TB cases constituted between 7.6% and 40% (median 17%, interquartile range 12-22) of all bacteriologically confirmed TB cases in the 52 South African districts. Multivariable analysis suggested that districts with higher proportions of previously treated TB cases had higher TB case notification rates (P < 0.001), lower estimates of antenatal human immunodeficiency virus (HIV) prevalence in the district population (P < 0.001) as well as lower HIV co-infection rates (P < 0.001) among new TB cases.CONCLUSION: Relapse and other previously treated TB cases contributed substantially to the notified TB burden in several South African health districts, particularly those with high case notification rates and lower antenatal HIV prevalence. Additional efforts to prevent TB among previously treated people, such as strengthening treatment monitoring and/or secondary preventive therapy, should be considered.

Recurrent tuberculosis in the pre-elimination era.

Recurrent tuberculosis (TB), defined as TB that recurs after a patient has been considered cured, constitutes a challenge to TB control. In low TB burden countries, the underlying causes and consequences of recurrent TB are poorly understood. We conducted a literature review to summarise the evidence of recurrent TB in low-burden settings and to address current gaps in knowledge. We included peer-reviewed publications on studies conducted in countries with an estimated TB incidence of <100 cases per 100 000 population. The Newcastle-Ottawa scale was used to assess study quality. The review yielded 44 manuscripts, 39 of which were reports of observational studies and 5 of clinical trials. The median percentage of TB patients experiencing an episode of recurrent TB after treatment completion was 3.4% (interquartile range [IQR] 1.6-6.0, range 0.4-16.7) in studies with a median follow-up of 7.8 years (IQR 5-12, range 2-33). The median percentage of recurrences attributable to endogenous reactivation (rather than exogenous reinfection) was 81% (IQR 73.1-85.5, range 49-100). Commonly identified risk factors for recurrence in low-burden settings included infection by the human immunodeficiency virus, low socio-economic status, foreign birth and infection with drug-resistant TB. Current understanding of recurrence in low-burden settings is limited, in part due to substantial methodological differences between studies. Further research is required to delineate the mechanisms of TB recurrence, its health and clinical impact, as well as the implications for TB elimination efforts in low-burden countries.

Endogenous fat loss and true total tract digestibility of poultry fat in adult dogs.

Fat plays an important role in the carnivore diet. It has high digestibility and high energy content and likely improves digestibility of the diet when present in greater amounts, suggesting that endogenous fat adversely affects the apparent digestibility of fat in low-fat diets. This study aimed to determine the endogenous fat loss (EFL) and true total tract digestibility (TTTD) of fat in dogs by using diets having different fat:carbohydrate ratios. Furthermore, the apparent total tract digestibility (ATTD) of macronutrients and energy, food intake, fecal output, and stool quality were evaluated. Twelve adult Beagle dogs were stratified into three 10-d periods in a 6 × 3 balanced incomplete Latin square design. Dietary treatments included a low-fat basal diet (3.4% fat) supplemented with 6 poultry fat levels (1, 4, 10, 12, 16, or 20%). The dogs were individually housed in metabolic cages and fed to meet the maintenance energy requirements. The ME intake was similar across the diets, despite the clearly low palatability of the 1 and 4% fat diets. Dietary ATTD of DM, OM, fat, and GE were improved after fat inclusion ( < 0.001). The ATTD of CP was not affected by dietary fat increase ( > 0.05). The amount of fecal output decreased with increasing level of fat in the diet, but the fecal score was not affected. The stool quality was close to ideal (2.4-2.8) and no different among diets. The EFL was estimated using 2 regression methods and was expressed as 155 mg∙kg BW∙d or 7.9 g/kg of DMI. The TTTD of poultry fat was the same irrespective of the dietary fat level. Poultry fat was 99.3% digestible for the dogs. The relation between EFL and fat intake was higher for the lower-fat diets, explaining the ATTD of fat increase according to the dietary fat inclusion. In conclusion, dietary fat is well digested by dogs irrespective of the level included, close to 100%. The ATTD of fat in low-fat diets is underestimated because the endogenous content is proportionally greater than that in high-fat diets.

Palatability, digestibility, and metabolizable energy of dietary glycerol in adult cats.

Glycerol is a humectant, which reduces water activity when added to the diet. This property seems to offer dietary benefits, specifically in high-moisture diets for cats, where some humectants cannot be used. According to the U.S. Food and Drug Administration, glycerol is generally recognized as sustenance safe (GRAS). It is suggested that cats are able to metabolize glycerol and use it as an energy source without compromising health. Three experiments were conducted to evaluate the following characteristics of glycerol in the diet for cats: 1) a preference test, 2) digestibility, ME, and fecal and urinary characteristics, and 3) postprandial plasma glycemia. Twelve healthy adult female cats were randomly distributed among 4 treatments consisting of a basal diet (4,090 kcal ME/kg DM, 32% CP, 11% fat, 2.3% crude fiber, and 7.0% ash) and 3 diets with varying percentages of glycerol, made by replacing the basal diet with 2.5, 5.0, and 10.0% purified glycerol (99.5%). The inclusion of glycerol proportionally reduced ( < 0.05) water activity in the diets. The preference test was conducted by observing the contrast between the basal diet and the 5.0% and 10% glycerol diets. Cats did not show a preference for any diet in particular ( > 0.05). The digestibility assays showed that increasing dietary glycerol levels did not affect food intake or the apparent total tract digestibility of macronutrients and energy ( > 0.05). The inclusion of glycerol in the diets did not alter the stool moisture, fecal score, or urine volume. However, glycerol was detected in urine when it was incorporated into the diet at 10%. Glycemia increased up to 900 min following the first meal after the fasting period with no difference between treatments, even when the means were adjusted for food intake. The blood glucose area under the curve also showed no significant difference between treatments ( > 0.05). Cats accepted glycerol under the conditions of the study, and its nutritional value was determined as it has been done for other species. The ME of glycerol for adult cats was estimated to be 3,185 kcal/kg DM. Supplementing the diets of the cats with 10% glycerol may exceed their capacity to metabolize glycerol, possibly leading to urinary excretions.

Multiple cytokines for the detection of Mycobacterium tuberculosis infection in children with tuberculosis.

SETTING: Interferon-gamma (IFN-γ) release assays (IGRAs) play an important role in the diagnosis of Mycobacterium tuberculosis infection. However, in children with tuberculosis (TB), some studies have shown increased frequencies of false-negative or indeterminate IGRA results. OBJECTIVE: To analyse the spectrum of different cytokines to improve the diagnostic accuracy of IGRAs in latent tuberculous infection (LTBI) and active TB. DESIGN: We performed multiplex cytokine expression analysis of QuantiFERON® Gold In-Tube supernatants in children with active TB (n = 21) and disease-free contacts with (n = 15) and without LTBI (n = 12), to determine the sensitivity and specificity of the modified tests. RESULTS: Of 21 initial cytokines analysed, IFN-γ and six other candidates (interleukin [IL] 2, inducible protein 10 [IP-10], IL-13, IL-1α, tumour necrosis factor alpha [TNF-α] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) were significantly more elevated in children with TB and those with LTBI than in the non-infected controls. Sensitivity and specificity were similar for IFN-γ and IL-2, but lower for the remaining candidates. Notably, a subset of candidates, including IP-10, showed M. tuberculosis antigen-induced specific expression in non-infected children. None of the candidates showed differences in expression between children with TB and those with LTBI. CONCLUSIONS: Our results did not suggest that alternative IGRA cytokines can distinguish between children with active TB and those with LTBI. IFN-γ and IL-2 showed comparable capacity in diagnosing M. tuberculosis infection in our study groups.

Raw beef bones as chewing items to reduce dental calculus in Beagle dogs.

OBJECTIVE: Evaluate the effect of raw bovine cortical bone (CB) (medullary bone cross-sectioned) and marrow or epiphyseal 'spongy' bone (SB) as chew items to reduce dental calculus in adult dogs. METHODS: Eight 3-year-old Beagle dogs were observed in two study periods. In the first study, the dogs each received a piece of bovine femur CB (122 ± 17 g) daily and in the second study, a piece of bovine femur SB (235 ± 27 g). The first study lasted 12 days and the second 20 days. Dental calculus was evaluated using image integration software. RESULTS: At the start of the studies, dental calculus covered 42.0% and 38.6% of the dental arcade areas, respectively. In study one, the chewing reduced the established dental calculus area to 27.1% (35.5% reduction) after 3 days and after 12 days the dental calculus covering was reduced to 12.3% (70.6% reduction). In study two, the dental calculus covered 16.8% (56.5% reduction) after 3 days, 7.1% (81.6% reduction) after 12 days and 4.7% (87.8% reduction) after 20 days. The CB remained largely intact after 24 h, but SB was reduced to smaller pieces and in some cases totally consumed after 24 h. No complications such as tooth fractures, pieces of bone stuck between teeth or intestinal obstructions were observed during the studies. CONCLUSIONS: Chewing raw bovine bones was an effective method of removing dental calculus in dogs. The SB bones removed dental calculus more efficiently in the short term.

[Michel de Montaigne (1533-1592). Writer philosopher, kidney stone patient and medical critic]. / Michel de Montaigne (1533-1592). "Écrivain philosophe", Nierensteinpatient und Medizinkritiker.

Michel de Montaigne (1533-1592) was the most important representative of French Humanism in the sixteenth century. Fragmentarily scattered throughout his "essais" and in chronological order in the diary of his spa journeys to Italy, he extensively describes his suffering from kidney stones, which accompanied him from the age of 45 years up to his death. This urological self-report achieves additional weight due to the extraordinary personality of the patient, who reflects on his urolithiasis and the effect on his own life not only from a subjective viewpoint but also makes his disease experience a starting point for critical thoughts on the value and limitations of the medical possibilities in his epoch. With a clear knowledge of the difficulty of medical practice, he postulates a rational approach supported by experience. Particularly interesting is Montaigne's stance towards contemporary physicians. He sees the benefits of physician consultations for himself and for patients generally, as being rarely substantiated but, despite sometimes strong antimedical invectives, accuses the doctors themselves less than the, although rationally structured but still mostly speculative, medical teaching structure influenced by Hippocrates and Galenism.

[Medical operations at the 2010 love parade in Duisburg]. / Medizinischer Einsatz bei der Loveparade 2010 in Duisburg.

On 24 July 2010 the love parade, a large scale open air concert was held in the city of Duisburg to which more than 500,000 guests were expected. During the course of the early evening a major tragic incident occurred in which 21 people were crushed to death and several hundred others were injured. In this article the preparation of the emergency and rescue services prior to the event is described and their operations entailing more than 1,600 staff members from all over Germany are illustrated. The article focuses on the mass casualty incident which took place in the tunnel in the early evening of that day.

[Galen of Pergamum (129-216/217 AD) and his contribution to urology: part I: life, work and medical system]. / Galen von Pergamon (129-216/217) und seine Beiträge zur Urologie: Teil I: Leben, Werk und medizinisches System.

Galen of Pergamum was, along with Hippocrates, the most influential physician and undoubtedly the most important medical scholar of classical antiquity. His anatomy and his concept of humoral pathology dominated western medicine until the sixteenth century and influenced all fields of medicine until after the seventeenth century. After referring to some biographical data the philosophical and epistemic fundamentals of Galen's"medical system" are outlined and brought into relation with the prevailing medical sects of the second century AD. The very treatises of his enormous work which are the most relevant with reference to the issue are briefly characterized.In the second part of the paper to be published in one of the next issues of this journal, Galen's significant contributions to the speciality we today define as urology are presented and analyzed. In addition pertinent case reports based on the Greek original texts will illustrate and substantiate his theoretical and clinical approach to the urology patient. Finally the significance of Galen's thinking for the present day physician will be evaluated.

[Galen of Pergamum (129-216/217 AD) and his contribution to urology: part II: urological treatment in theory and practice]. / Galen von Pergamon (129-216/217) und seine Beiträge zur Urologie : Teil II: Urologika in Theorie und Praxis.

Galen's significant and original contributions to the field we today define as urology are presented and discussed. In addition his case reports connected to urological organs or symptoms, based on the Greek original texts, illustrate and substantiate his theoretical and clinical approach to the urology patient. This way of proceeding to a certain extent comes close to today's understanding of medical practice. Furthermore, some aspects of his self-image as a physician, his ethical positions and relationship to his patients are analyzed. Finally an attempt is made to evaluate whether Galen's ideas still bear a meaning for the physician of today. Dealing with this leading figure of medical history and his many clinical, scientific and philosophical abilities may give us a better understanding of the technical as well as the ideational roots of our profession.

Increased risk of default among previously treated tuberculosis cases in the Western Cape Province, South Africa.

OBJECTIVE: To investigate, in two urban communities with high tuberculosis (TB) incidence and high rates of TB recurrence, whether a history of previous TB treatment is associated with treatment default. METHODS: Retrospective cohort study of TB cases with an episode of treatment recorded in the clinic-based treatment registers between 2002 and 2007. Probabilistic record linkage was used to ascertain treatment history of TB cases back to 1996. Based on the outcome of their most recent previous treatment episode, previously treated cases were compared to new cases regarding their risk of treatment default. RESULTS: Previous treatment success (adjusted odds ratio [aOR] 1.79; 95%CI 1.17-2.73), previous default (aOR 6.18, 95%CI 3.68-10.36) and previous failure (aOR 9.72, 95%CI 3.07-30.78) were each independently associated with treatment default (P < 0.001). Other factors independently associated with default were male sex (P = 0.003) and age 19-39 years (P < 0.001). CONCLUSIONS: Previously treated TB cases are at increased risk of treatment default, even after previous successful treatment. This finding is of particular importance in a setting where recurrent TB is very common. Adherence to treatment should be ensured in new and retreatment cases to increase cure rates and reduce transmission of TB in the community.

Wilhelm Fabry's 1614 report on a giant condyloma of the penis.

For many years it has been the work of Buschke and Löwenstein that has justified calling the exophytic, locally destructive tumour of the anogenital mucosal surface 'giant condyloma of Buschke and Löwenstein' or GCBL. In order to investigate the early history of this rare disease we examined the writings of the barber-surgeon Wilhelm Fabry (1560-1634) who had a serious interest in dermatological disorders and their treatment. We analysed Fabry's 600 Latin case reports and identified the case of a 'monstrous penile tumour'. We then translated this text into English and compared it point by point with later publications. This was followed by a cursory review of surgical treatises from the 16th to the 18th centuries. In 1614 Fabry described and depicted a tumour of the penis; the clinical characteristics (gradual formation of a warty lesion, considerable size, invasive growth, absence of metastases) indicated it was a giant condyloma. His mention of the urethral fistulization enables discrimination from 'common' condylomata acuminata, and the survival period of 10 years after amputation allows exclusion of a 'true' carcinoma. This report is singular among 17th-century case histories. The neoplasias described 300 years later are most probably biologically identical. Thus, Fabry's is the first clinical report; the histological classification, however, belongs to Buschke and Löwenstein. From now on the disease should be designated with the eponym giant condyloma of Fabry-Buschke-Löwenstein or GCFBL.