Asynchronous Video Directly Observed Therapy to Monitor Short-Course Latent Tuberculosis Infection Treatment: Results of a Randomized Controlled Trial.

Background: Observing medication ingestion through self-recorded videos (video directly observed therapy [VDOT]) has been shown to be a cost-effective alternative to in-person directly observed therapy (DOT) for monitoring adherence to treatment for tuberculosis disease. VDOT could be a useful tool to monitor short-course latent tuberculosis infection (LTBI) treatment. Methods: We conducted a prospective randomized controlled trial comparing VDOT (intervention) and clinic-based DOT (control) among patients newly diagnosed with LTBI who agreed to a once-weekly 3-month treatment regimen of isoniazid and rifapentine. Study outcomes were treatment completion and patient satisfaction. We also assessed costs. Pre- and posttreatment interviews were conducted. Results: Between March 2016 and December 2019, 130 participants were assigned to VDOT (n = 68) or DOT (n = 62). Treatment completion (73.5% vs 69.4%, P = .70) and satisfaction with treatment monitoring (92.1% vs 86.7%, P = .39) were slightly higher in the intervention group than the control group, but neither was statistically significant. VDOT cost less per patient (median, $230; range, $182-$393) vs DOT (median, $312; range, $246-$592) if participants used their own smartphone. Conclusions: While both groups reported high treatment satisfaction, VDOT was not associated with higher LTBI treatment completion. However, VDOT cost less than DOT. Volunteer bias might have reduced the observed effect since patients opposed to any treatment monitoring could have opted for alternative unobserved regimens. Given similar outcomes and lower cost, VDOT may be useful for treatment monitoring when in-person observation is prohibited or unavailable (eg, during a respiratory disease outbreak). The trial was registered at the National Institutes of Health (ClinicalTrials.gov NTC02641106). Clinical Trials Registration: ClinicalTrials.gov NTC02641106; registered 24 October 2016.

Uniting for Ukraine Tuberculosis Screening Experience, San Francisco, California, USA.

Ukraine surveillance data suggest high tuberculosis (TB) incidence, including multidrug resistance. Of 299 newcomers from Ukraine screened in San Francisco, California, USA, by using an interferon-γ-release-assay (IGRA) and chest radiograph, 7.4% were IGRA positive and 1 had laboratory-confirmed pansusceptible TB. Screening with IGRA and chest radiograph can help characterize TB risk.

Adverse Events Associated With Treatment for Pan-Susceptible Tuberculosis in San Francisco.

Of 373 patients treated for drug-susceptible tuberculosis, 35.4% (46.2% aged ≥65 years) developed moderate/severe adverse events that required treatment interruption (34.8%), first-line drug discontinuation (26.2%, primarily pyrazinamide), second-line drug initiation (30.0%), and treatment duration up to 3.8 months longer. More safe and effective options are needed, including for the elderly.

Pre-treatment chest X-ray stability duration and tuberculosis disease in San Diego, California, 2012-2017.

Background: Overseas screening for tuberculosis (TB) has sought to reduce the burden of active TB in the United States. The duration of time between two unchanged, or stable, chest X-rays (CXRs) taken four to six months apart has been considered clinically useful in the evaluation of suspected pulmonary TB disease, but this relationship has not been previously quantified. Objective: To investigate the association between pre-treatment CXR stability duration and future clinical or culture-confirmed (Class 3) diagnosis of pulmonary TB in San Diego, California, USA. Methods: This retrospective record review included County of San Diego TB clinic patients with abnormal CXR results who were started on treatment between 2012 and 2017; multivariable logistic regression was used to analyze the clinical data. Results: Pre-treatment CXR stability duration of at least four months was not significantly associated with a Class 3 pulmonary TB diagnosis (adjusted odds ratio [AOR], 0.83; 95 % confidence interval [CI], 0.20-3.48), nor was pre-treatment CXR stability duration of at least six months (AOR, 0.97; 95 % CI, 0.30-3.10). Similar results were obtained when four-to-six-month stability was considered (AOR, 0.78; 95 % CI, 0.16-3.89). Patients screened overseas (B1 notification) were less likely to develop Class 3 TB (unadjusted OR, 0.15; 95 % CI 0.05-0.44). Conclusion: Pre-treatment chest X-ray stability duration was not associated with excluding Class 3 pulmonary TB in this setting, and CXR stability duration cut points may not be as clinically informative as previously understood, but overseas screening is likely an important step in reducing active TB disease burden in the U.S.

Tuberculosis-Associated Hospitalizations and Deaths after COVID-19 Shelter-In-Place, San Francisco, California, USA.

A mandated shelter-in-place and other restrictions associated with the coronavirus disease pandemic precipitated a decline in tuberculosis diagnoses in San Francisco, California, USA. Several months into the pandemic, severe illness resulting in hospitalization or death increased compared with prepandemic levels, warranting heightened vigilance for tuberculosis in at-risk populations.

Genetic Network Analysis to Assess the Risk of Human Immunodeficiency Virus Transmission Among Men Who Have Sex With Men Seeking Partners on the Internet.

BACKGROUND: Online partner seeking (OPS) among men who have sex with men (MSM) is associated with increased risk behavior including frequency of unprotected anal intercourse, number of partners, and incidence of sexually transmitted infections (STIs). However, the impact on transmission of human immunodeficiency virus (HIV) is uncertain. METHODS: MSM diagnosed with acute and early HIV infection were recruited from the Primary Infection Resource Consortium. HIV transmission events in the year following infection were inferred using estimated date of infection combined with genetic network analysis with linked sequences defined as ≤0.015 sequences/site difference in the HIV type 1 (HIV-1) pol coding region. Participants completed a detailed baseline questionnaire including reported methods of meeting sexual partners, including OPS, in the prior 3 months, and regression was performed with inferred transmission as the outcome. RESULTS: From 147 MSM who completed the questionnaire, there were an associated 20 inferred HIV transmissions. No association with OPS was found (odds ratio, 0.64 [95% confidence interval, .24-1.69]; P = .37), though individuals who reported OPS were more likely to have reported a greater number of partners (P = .003) and prior STIs (P = .002). Geospatial analysis did not indicate that OPS was associated with increased geographical reach of the user (P = .68). CONCLUSIONS: Individuals reporting OPS did not have increased odds of inferred HIV-1 transmission in the year following infection using genetic linkage analysis despite apparently increased risk behavior. OPS also did not increase the geographic distance between genetically clustered HIV infections, suggesting that individuals mainly use the internet to meet partners in their local region.

Tuberculosis infection risk, preventive therapy care cascade and incidence of tuberculosis disease in healthcare workers at Maputo Central Hospital.

BACKGROUND: Mozambican healthcare workers have high rates of latent and active tuberculosis, but occupational screening for tuberculosis is not routine in this setting. Furthermore, the specificity of tuberculin skin testing in this population compared with interferon gamma release assay testing has not been established. METHODS: This study was conducted among healthcare workers at Maputo Central Hospital, a public teaching quaternary care hospital in Mozambique. With a cross sectional study design, risk factors for tuberculosis were assessed using multivariable logistic regression. The care cascade is reported for participants who were prescribed six months of isoniazid preventive therapy for HIV or highly reactive testing for latent tuberculosis infection. The agreement of interferon-gamma release assay results with positive tuberculin skin testing was calculated. RESULTS: Of 690 screened healthcare workers, three (0.4%) had active tuberculosis and 426 (61.7%) had latent tuberculosis infection. Less education, age 35-49, longer hospital service, and work in the surgery department were associated with increased likelihood of being tuberculosis infected at baseline (p < 0.05). Sex, Bacillus Calmette-Guerin vaccination, HIV, outside tuberculosis contacts, and professional category were not. Three new cases of active tuberculosis developed during the follow-up period, two while on preventive therapy. Among 333 participants offered isoniazid preventive therapy, five stopped due to gastrointestinal side effects and 181 completed treatment. For HIV seropositive individuals, the agreement of interferon gamma release assay positivity with positive tuberculin skin testing was 50% among those with a quantitative skin test result of 5-10 mm, and among those with a skin test result ≥10 mm it was 87.5%. For HIV seronegative individuals, the agreement of interferon gamma release assay positivity with a tuberculin skin test result of 10-14 mm was 63.6%, and for those with a quantitative skin test result ≥15 mm it was 82.2%. CONCLUSIONS: There is a high prevalence of tuberculosis infected healthcare workers at Maputo Central Hospital. The surgery department was most heavily affected, suggesting occupational risk. Isoniazid preventive therapy initiation was high and just over half completed therapy. An interferon gamma release assay was useful to discern LTBI from false positives among those with lower quantitative tuberculin skin test results.

Attitudes and Preferences Regarding the Use of Rapid Self-Testing for Sexually Transmitted Infections and HIV in San Diego Area Men Who Have Sex With Men.

BACKGROUND: Sexually transmitted infections (STIs) increase the risk of HIV transmission and are present at high rates among men who have sex with men (MSM). Adherence to HIV/STI testing guidelines is low in the United States. Testing programs that utilize rapid self-administered HIV/STI tests improve testing rates, though multiple factors influence their uptake. METHODS: MSM were recruited at an HIV/STI testing and treatment program in 2014 and provided consent, demographics, risk behaviors, HIV/STI test preferences, and perceived testing barriers via an online questionnaire. Comparisons of testing preferences and barriers were made based on age, risk group, and HIV serostatus using the Fisher exact test. RESULTS: HIV testing preferences included rapid oral test (71.1%), home test location (78.5%), electronic delivery of HIV-negative test results (76.4%), and direct provider notification for HIV-positive test results (70%), with respondents age >45 years being significantly more likely to prefer home testing (P = .033). STI testing preferences included self-collection of specimens (73.2%), home test location (61%), electronic delivery of negative STI test results (76.4%), and direct provider notification for positive STI test results (56.6%) with no significant differences between age, HIV serostatus, or risk groups. The most frequently reported HIV and STI testing barrier was lack of known prior HIV/STI exposure (57.3% for HIV, 62.9% for STI) with respondents age <45 years more frequently citing inconvenience as a barrier to testing (HIV: 50.9% vs 17.4%, P = .010; STI: 58.3% vs 31.8%, P = .070). CONCLUSIONS: Although additional research is needed, increasing resources directed specifically toward home testing has the potential to translate into improved uptake of rapid HIV/STI testing. Efforts to improve convenience in testing programs must be balanced with the need for continued educational outreach.

Pleurodesis: a comparison of two sclerosing agents for pleural effusions in Mozambique.

BACKGROUND: Pleural effusions constitute one of the most frequent pathologies encountered in the pulmonary service of Maputo Central Hospital (MCH) in Mozambique. Bleomycin and talc are commonly used for pleurodesis, but cost prohibitive, therefore we aimed to retrospectively compare the efficacy and safety of sodium hydroxide (NaOH) with bleomycin for pleurodesis. METHODS: Case records of pleurodesis using bleomycin and NaOH from 2002 to 2013 were reviewed. Standard of care for pleurodesis for recurrent pleural effusions at MCH was developed using the materials available. NaOH remained the agent of choice until 2006 when bleomycin became available. Clinical data regarding general complications, rate of success and lung expansion were noted for every patient who underwent pleurodesis at MCH during this time frame. RESULTS: Review of pleurodesis at MCH revealed 24 cases using bleomycin and 23 cases using NaOH as the sclerosing agent. Patient characteristics were balanced between the two groups with majority of pleural effusions malignant in etiology. CONCLUSIONS: There was no statistically significant difference between the use of bleomycin and NaOH as defined by lung expansion. General complications were observed less frequently in 2 (10%) of patients treated with NaOH compared with 8 (38%) of patients using bleomycin. Only three patients presented with recurrent pleural effusion after pleurodesis with NaOH. NaOH may offer a low cost alternative sclerosing agent for resource limited areas.

Risk profile and HIV testing outcomes of women undergoing community-based testing in San Diego 2008-2014.

Women comprised 19% of new HIV diagnoses in the United States in 2014, with significant racial and ethnic disparities in infection rates. This cross-sectional analysis of women enrolled in a cohort study compares demographics, risk behaviour, and sexually transmitted infections (STI) in those undergoing HIV testing in San Diego County. Data from the most recent screening visit of women undergoing voluntary HIV screening April 2008 -July 2014 was used. HIV diagnosis, risk behaviour and self-reported STIs were compared among women aged ≤24, 25-49, and ≥50, as well as between HIV-infected and uninfected women and between Hispanic and non-Hispanic women. Among the 2535 women included, Hispanic women were less likely than other women to report unprotected vaginal intercourse (p = 0.026) or stimulant drug use (p = 0.026), and more likely to report one or fewer partners (p < 0.0001), but also more likely to report sex with an HIV-infected individual (p = 0.027). New HIV infection was significantly more prevalent among Hispanic women (1.6% vs. 0.2%; p < 0.001). Hispanic women were more likely than other women to be diagnosed with HIV despite significantly lower rates of risk behaviour. Culturally specific risk reduction interventions for Hispanic women should focus on awareness of partner risk and appropriate testing.

An innovative system for 3D clinical photography in the resource-limited settings.

BACKGROUND: Kaposi's sarcoma (KS) is the most frequently occurring cancer in Mozambique among men and the second most frequently occurring cancer among women. Effective therapeutic treatments for KS are poorly understood in this area. There is an unmet need to develop a simple but accurate tool for improved monitoring and diagnosis in a resource-limited setting. Standardized clinical photographs have been considered to be an essential part of the evaluation. METHODS: When a therapeutic response is achieved, nodular KS often exhibits a reduction of the thickness without a change in the base area of the lesion. To evaluate the vertical space along with other characters of a KS lesion, we have created an innovative imaging system with a consumer light-field camera attached to a miniature "photography studio" adaptor. The image file can be further processed by computational methods for quantification. RESULTS: With this novel imaging system, each high-quality 3D image was consistently obtained with a single camera shot at bedside by minimally trained personnel. After computational processing, all-focused photos and measurable 3D parameters were obtained. More than 80 KS image sets were processed in a semi-automated fashion. CONCLUSIONS: In this proof-of-concept study, the feasibility to use a simple, low-cost and user-friendly system has been established for future clinical study to monitor KS therapeutic response. This 3D imaging system can be also applied to obtain standardized clinical photographs for other diseases.

Simultaneous presentation of Kaposi sarcoma and HHV8-associated large B-cell lymphoma in the same lymph node: A rare diagnosis in an HIV-negative patient.

PATIENT: Female, 18 FINAL DIAGNOSIS: Simultanous presentation of Kaposi Sarcoma and Lymphoma Symptoms: - MEDICATION: - Clinical Procedure: - Specialty: Oncology. OBJECTIVE: Rare disease. BACKGROUND: KSHV/HHV-8 is associated with Kaposi's sarcoma (KS) as well as with a few categories of lymphoproliferative diseases, mostly occurring in patients with HIV infection/AIDS. Although the association between lymphomas and Kaposi's sarcoma has been described, the simultaneous presence of the 2 entities within the same organ is rare and mainly associated with HIV/ AIDS. CASE REPORT: We report a case of simultaneous occurrence of Kaposi's sarcoma and large B-cell lymphoma in the same lymph node in a 18-year-old African woman who was HIV-negative. We found concurrent infection with Kaposi's sarcoma herpes virus (KSHV) and Epstein-Barr virus (EBV), confirmed by PCR amplification of DNA obtained from distinct tumor areas selected in the paraffin block. CONCLUSIONS: The possibility of occurrence of 2 lesions with distinct features in the same organ may be unexpected for pathologists performing fine-needle aspiration cytology (FNAC) evaluation but must be considered, even in HIV-negative individuals, despite its rare occurrence, as was demonstrated by this case.

NOD-scid IL2rgamma(null) mouse model of human skin transplantation and allograft rejection.

BACKGROUND: Transplantation of human skin on immunodeficient mice that support engraftment with functional human immune systems would be an invaluable tool for investigating mechanisms involved in wound healing and transplantation. Nonobese diabetic (NOD)-scid interleukin-2 gamma chain receptor (NSG) readily engraft with human immune systems, but human skin graft integrity is poor. In contrast, human skin graft integrity is excellent on CB17-scid bg (SCID.bg) mice, but they engraft poorly with human immune systems. METHODS: Human skin grafts transplanted onto immunodeficient NSG, SCID.bg, and other immunodeficient strains were evaluated for graft integrity, preservation of graft endothelium, and their ability to be rejected after engraftment of allogeneic peripheral blood mononuclear cells. RESULTS: Human skin transplanted onto NSG mice develops an inflammatory infiltrate, consisting predominately of host Gr1(+) cells, that is detrimental to the survival of human endothelium in the graft. Treatment of graft recipients with anti-Gr1 antibody reduces this cellular infiltrate, preserves graft endothelium, and promotes wound healing, tissue development, and graft remodeling. Excellent graft integrity of the transplanted skin includes multilayered stratified human epidermis, well-developed human vasculature, human fibroblasts, and passenger leukocytes. Injection of unfractionated, CD4 or CD8 allogeneic human peripheral blood mononuclear cell induces a rapid destruction of the transplanted skin graft. CONCLUSIONS: NSG mice treated with anti-Gr1 antibody provide a model optimized for both human skin graft integrity and engraftment of a functional human immune system. This model provides the opportunity to investigate mechanisms orchestrating inflammation, wound healing, revascularization, tissue remodeling, and allograft rejection and can provide guidance for improving outcomes after clinical transplantation.