Isoniazid or rifampicin preventive therapy with and without screening for subclinical TB: a modeling analysis

Background Short-course, rifamycin-based regimens could facilitate scale-up of tuberculosis preventive therapy (TPT), but it is unclear how stringently tuberculosis (TB) disease should be ruled out before TPT use. Methods We developed a state-transition model of a TPT intervention among two TPT-eligible cohorts: adults newly diagnosed with HIV in South Africa (PWH) and TB household contacts in Pakistan (HHCs). We modeled two TPT regimens—4 months of rifampicin [4R] or 6 months of isoniazid [6H]—comparing each to a reference of no intervention. Before initiating TPT, TB disease was excluded either through symptom-only screening or with additional radiographic screening that could detect subclinical TB but might limit access to the TPT intervention. TPT’s potential curative effects on both latent and subclinical TB were modeled, as were both acquisitions of resistance and prevention of drug-resistant disease. Although all eligible individuals received the screening and/or TPT interventions, the modeled TB outcomes comprised only those with latent or subclinical TB that would have progressed to symptomatic disease if untreated. Results When prescribed after only symptom-based TB screening (such that individuals with subclinical TB were included among TPT recipients), 4R averted 45 active (i.e., symptomatic) TB cases (95% uncertainty range 24–79 cases or 40–89% of progressions to active TB) per 1000 PWH [17 (9–29, 43–94%) per 1000 HHCs]; 6H averted 37 (19–66, 52–73%) active TB cases among PWH [13 (7–23, 53–75%) among HHCs]. With this symptom-only screening, for each net rifampicin resistance case added by 4R, 12 (3–102) active TB cases were averted among PWH (37 [9–580] among HHCs); isoniazid-resistant TB was also reduced. Similarly, 6H after symptom-only screening increased isoniazid resistance while reducing overall and rifampicin-resistant active TB. Screening for subclinical TB before TPT eliminated this net increase in resistance to the TPT drug; however, if the screening requirement reduced TPT access by more than 10% (the estimated threshold for 4R among HHCs) to 30% (for 6H among PWH), it was likely to reduce the intervention’s overall TB prevention impact. Conclusions All modeled TPT strategies prevent TB relative to no intervention, and differences between TPT regimens or between screening approaches are small relative to uncertainty in the outcomes of any given strategy. If most TPT-eligible individuals can be screened for subclinical TB, then pairing such screening with rifamycin-based TPT maximizes active TB prevention and does not increase rifampicin resistance. Where subclinical TB cannot be routinely excluded without substantially reducing TPT access, the choice of TPT regimen requires weighing 4R’s efficacy advantages (as well as its greater safety and shorter duration that we did not directly model) against the consequences of rifampicin resistance in a small fraction of recipients.

Phenotypic status of elbow dysplasia in Boerboel dogs in Nigeria

Elbow dysplasia (ED) is a developmental, multifactorial, polygenic disease of rapidly growing, large breed of dogs. ED can be a significant health concern for affected dogs because treatments are largely ineffective, making selectively breeding of normal dogs the best option for disease control. Despite the relative availability of data on ED prevalence in other breeds, there is dearth of information on ED prevalence in Boerboel dogs. This study evaluated ED prevalence and relative percentages of different ED grades in Boerboel dogs using radiographs of dogs presented for screening between April 2016 and September 2020. Extended latero-medial, flexed latero-medial and cranio-lateral-caudo-medial oblique radiographs from 64 dogs were reviewed. Radiographs were graded using international elbow working group (IEWG) criteria and grades 0-3 assigned to each joint. ED prevalence expressed as percentages were obtained by dividing the number of dogs with grades 1, 2 and 3 by total number of dogs. Age and sex difference in ED prevalence were compared using chi-square test. Differences were considered significant at P ≤ 0.05. Mean age of the dogs was 2.3 ± 0.6 years. Thirty-six (56.3%) dogs were graded as non-dysplastic, while 28(43.7%) were graded as dysplastic, with grade 3 (46.4%) accounting for majority of ED cases. There were no significant (p > 0.05) difference in sex and age prevalence of ED in the breed. In conclusion, ED prevalence in Boerboel dog is high with majority of dogs having severe grade. Widespread phenotypic screening and strict breeding restrictions are recommended| to control the disease in the breed. Keywords: Boerboel, Dog, Elbow dysplasia, Prevalence, Radiographic screening

Incidentally identified ductus arteriosus aneurysm in eight adults: a case series

Ductus arteriosus aneurysm (DAA) in adulthood is a rare entity. We retrospectively reviewed our medical records from the past ten years and identified eight cases of adult DAA (six males and two females aged between 69 and 89 years; mean, 76 years), using multi planar reconstruction and three-dimensional reconstruction computed tomography (CT) images. The aneurysm was suspected incidentally in all cases based on the results of chest radiographic screening or postoperative follow-up CT for lung or colon cancer. All eight patients were asymptomatic but had a history of or concurrent hypertension (n = 5, 62.5%), diabetes mellitus (n = 3, 37.5%), cerebrovascular disease (n = 3, 37.5%), ischemic heart disease (n = 1, 12.5%), and cardiac failure (n = 1). All patients had no history of trauma (n = 8, 100%). Six had a history of cigarette smoking. The aneurysm size ranged from 2.0 × 4.0 to 6.3 × 5.3 cm (mean, 3 × 5 cm). The surgical procedures used were four cases of total arch replacement and two cases of thoracic endovascular aortic repair. Two patients were not surgically treated. The median follow-up was 14.5 months (range, 2 months to 9 years). In the two patients who were not surgically treated, the aneurysm enlarged in one, and remained unchanged in the other. Of the six cases surgically-managed cases, one was lost to follow-up, and another patient died of an unrelated cause. The remaining four cases had no enlargement of the aneurysm. No ruptures were reported in any of the cases. DAA should be considered when a saccular aneurysm is located in the minor curvature of the aortic arch and extending toward the left pulmonary trunk in adult patients. Differentiating adult DAA is important, because it is associated with a high risk of rupture due to the fragile nature of true aneurysms.

Management and control of tuberculosis control in socially complex groups: a research programme including three RCTs

Background Socially complex groups, including people experiencing homelessness, prisoners and drug users, have very high levels of tuberculosis, often complicated by late diagnosis and difficulty in adhering to treatment. Objective To assess a series of interventions to improve tuberculosis control in socially complex groups. Design A series of observational surveys, evaluations and trials of interventions. Setting The pan-London Find&Treat service, which supports tuberculosis screening and case management in socially complex groups across London. Participants Socially complex groups with tuberculosis or at risk of tuberculosis, including people experiencing homelessness, prisoners, drug users and those at high risk of poor adherence to tuberculosis treatment. Interventions and main outcome measures We screened 491 people in homeless hostels and 511 people in prison for latent tuberculosis infection, human immunodeficiency virus, hepatitis B and hepatitis C. We evaluated an NHS-led prison radiographic screening programme. We conducted a cluster randomised controlled trial (2348 eligible people experiencing homelessness in 46 hostels) of the effectiveness of peer educators (22 hostels) compared with NHS staff (24 hostels) at encouraging the uptake of mobile radiographic screening. We initiated a trial of the use of point-of-care polymerase chain reaction diagnostics to rapidly confirm tuberculosis alongside mobile radiographic screening. We undertook a randomised controlled trial to improve treatment adherence, comparing face-to-face, directly observed treatment with video-observed treatment using a smartphone application. The primary outcome was completion of ≥ 80% of scheduled treatment observations over the first 2 months following enrolment. We assessed the cost-effectiveness of latent tuberculosis screening alongside radiographic screening of people experiencing homelessness. The costs of video-observed treatment and directly observed treatment were compared. Results In the homeless hostels, 16.5% of people experiencing homelessness had latent tuberculosis infection, 1.4% had current hepatitis B infection, 10.4% had hepatitis C infection and 1.0% had human immunodeficiency virus infection. When a quality-adjusted life-year is valued at £30,000, the latent tuberculosis screening of people experiencing homelessness was cost-effective provided treatment uptake was ≥ 25% (for a £20,000 quality-adjusted life-year threshold, treatment uptake would need to be > 50%). In prison, 12.6% of prisoners had latent tuberculosis infection, 1.9% had current hepatitis B infection, 4.2% had hepatitis C infection and 0.0% had human immunodeficiency virus infection. In both settings, levels of latent tuberculosis infection and blood-borne viruses were higher among injecting drug users. A total of 1484 prisoners were screened using chest radiography over a total of 112 screening days (new prisoner screening coverage was 43%). Twenty-nine radiographs were reported as potentially indicating tuberculosis. One prisoner began, and completed, antituberculosis treatment in prison. In the cluster randomised controlled trial of peer educators to increase screening uptake, the median uptake was 45% in the control arm and 40% in the intervention arm (adjusted risk ratio 0.98, 95% confidence interval 0.80 to 1.20). A rapid diagnostic service was established on the mobile radiographic unit but the trial of rapid diagnostics was abandoned because of recruitment and follow-up difficulties. We randomly assigned 112 patients to video-observed treatment and 114 patients to directly observed treatment. Fifty-eight per cent of those recruited had a history of homelessness, addiction, imprisonment or severe mental health problems. Seventy-eight (70%) of 112 patients on video-observed treatment achieved the primary outcome, compared with 35 (31%) of 114 patients on directly observed treatment (adjusted odds ratio 5.48, 95% confidence interval 3.10 to 9.68; p < 0.0001). Video-observed treatment was superior to directly observed treatment in all demographic and social risk factor subgroups. The cost for 6 months of treatment observation was £1645 for daily video-observed treatment, £3420 for directly observed treatment three times per week and £5700 for directly observed treatment five times per week. Limitations Recruitment was lower than anticipated for most of the studies. The peer advocate study may have been contaminated by the fact that the service was already using peer educators to support its work. Conclusions There are very high levels of latent tuberculosis infection among prisoners, people experiencing homelessness and drug users. Screening for latent infection in people experiencing homelessness alongside mobile radiographic screening would be cost-effective, providing the uptake of treatment was 25–50%. Despite ring-fenced funding, the NHS was unable to establish static radiographic screening programmes. Although we found no evidence that peer educators were more effective than health-care workers in encouraging the uptake of mobile radiographic screening, there may be wider benefits of including peer educators as part of the Find&Treat team. Utilising polymerase chain reaction-based rapid diagnostic testing on a mobile radiographic unit is feasible. Smartphone-enabled video-observed treatment is more effective and cheaper than directly observed treatment for ensuring that treatment is observed. Future work Trials of video-observed treatment in high-incidence settings are needed. Trial registration Current Controlled Trials ISRCTN17270334 and ISRCTN26184967. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 8, No. 9. See the NIHR Journals Library website for further project information.