First report of multi-drug resistant tuberculosis in a systemic lupus erythematosus patient.

BackgroundTreatment of a multi-drug resistant tuberculosis (MDR-TB) patient is clinically challenging, requiring a minimum of 18 months of therapy. Its occurrence in a systemic lupus erythromatosus (SLE) patient may complicate management of both MDR-TB and SLE. This is the first descriptive report of MDR-TB in an SLE patient.Case presentationA 19-year old female receiving long-term prednisolone for SLE was diagnosed with MDR-TB. She was started on MDR-TB treatment regimen and prednisolone was replaced with azathioprine. After an initial response to therapy, patient experienced a flare of lupus symptoms. Imaging studies revealed avascular necrosis of right femoral head. She was then treated with intravenous methyl-prednisolone, followed by maintenance corticosteroid. Azathioprine was discontinued due to hematological toxicity and failure to control SLE. Her symptoms of lupus regressed and did not re-occur for the duration of her MDR-TB treatment. Patient was declared cured of MDR-TB after 18 months of ATT. She is currently scheduled for a total hip replacement surgery.ConclusionsThis case highlights the challenges of simultaneously managing MDR-TB and SLE in a patient due to their over-lapping signs and symptoms, drug-drug interactions, and the need for use of immunomodulatory agents in the absence of standard guidelines and documented previous experiences. Our experience underscores the importance of appropriate selection of treatment regimens for both MDR-TB and SLE

Integrating quantitative and qualitative methodologies for the assessment of health care systems: emergency medicine in post-conflict Serbia

BACKGROUND: Due to the complexity of health system reform in the post-conflict, post-disaster, and development settings, attempts to restructure health services are fraught with pitfalls that are often unanticipated because of inadequate preliminary assessments. Our proposed Integrated Multimodal Assessment – combining quantitative and qualitative methodologies – may provide a more robust mechanism for identifying programmatic priorities and critical barriers for appropriate and sustainable health system interventions. The purpose of this study is to describe this novel multimodal assessment using emergency medicine in post-conflict Serbia as a model. METHODS: Integrated quantitative and qualitative methodologies – system characterization and observation, focus group discussions, free-response questionnaires, and by-person factor analysis – were used to identify needs, problems, and potential barriers to the development of emergency medicine in Serbia. Participants included emergency and pre-hospital personnel from all emergency medical institutions in Belgrade. RESULTS: Demographic data indicate a loosely ordered network of part-time emergency departments supported by 24-hour pre-hospital services and an academic emergency center. Focus groups and questionnaires reveal significant impediments to delivery of care and suggest development priorities. By-person factor analysis subsequently divides respondents into distinctive attitudinal types, compares participant opinions, and identifies programmatic priorities. CONCLUSIONS: By combining quantitative and qualitative methodologies, our Integrated Multimodal Assessment identified critical needs and barriers to emergency medicine development in Serbia and may serve as a model for future health system assessments in post-conflict, post-disaster, and development settings

Lymph node hemophagocytosis in rickettsial diseases: a pathogenetic role for CD8 T lymphocytes in human monocytic ehrlichiosis (HME)?

BACKGROUND: Human monocytic ehrlichiosis (HME) and Rocky Mountain spotted fever (RMSF) are caused by Ehrlichia chaffeensis and Rickettsia rickettsii, respectively. The pathogenesis of RMSF relates to rickettsia-mediated vascular injury, but it is unclear in HME. METHODS: To study histopathologic responses in the lymphatic system for correlates of immune injury, lymph nodes from patients with HME (n = 6) and RMSF (n = 5) were examined. H&E-stained lymph node tissues were examined for five histopathologic features, including hemophagocytosis, cellularity, necrosis, and vascular congestion and edema. The relative proportions of CD68 macrophages, CD8 and CD4 T lymphocytes, and CD20 B lymphocytes were evaluated by immunohistochemical staining. RESULTS: Hemophagocytosis was similar in HME and RMSF, and was greater than in control cases (p = .015). Cellularity in HME was not different from controls, whereas RMSF lymph nodes were markedly less cellular (p < 0.002). E. chaffeensis-infected mononuclear phagocytes were infrequent compared to R. rickettsii-infected endothelial cells. More CD8 cells in lymph nodes were observed with HME (p < .001), but no quantitative differences in CD4 lymphocytes, macrophages, or B lymphocytes were identified. CONCLUSION: Hemophagocytosis, CD8 T cell expansion, and the paucity of infected cells in HME, suggest that E. chaffeensis infection leads to macrophage activation and immune-mediated injury

Minimally Symptomatic Infection in an Ebola ‘Hotspot’: A Cross-Sectional Serosurvey

Introduction: Evidence for minimally symptomatic Ebola virus (EBOV) infection is limited. During the 2013–16 outbreak in West Africa, it was not considered epidemiologically relevant to published models or projections of intervention effects. In order to improve our understanding of the transmission dynamics of EBOV in humans, we investigated the occurrence of minimally symptomatic EBOV infection in quarantined contacts of reported Ebola virus disease cases in a recognized ‘hotspot.’ Methodology/Principal Findings We conducted a cross-sectional serosurvey in Sukudu, Kono District, Sierra Leone, from October 2015 to January 2016. A blood sample was collected from 187 study participants, 132 negative controls (individuals with a low likelihood of previous exposure to Ebola virus), and 30 positive controls (Ebola virus disease survivors). IgG responses to Ebola glycoprotein and nucleoprotein were measured using Alpha Diagnostic International ELISA kits with plasma diluted at 1:200. Optical density was read at 450 nm (subtracting OD at 630nm to normalize well background) on a ChroMate 4300 microplate reader. A cutoff of 4.7 U/mL for the anti-GP ELISA yielded 96.7% sensitivity and 97.7% specificity in distinguishing positive and negative controls. We identified 14 seropositive individuals not known to have had Ebola virus disease. Two of the 14 seropositive individuals reported only fever during quarantine while the remaining 12 denied any signs or symptoms during quarantine. Conclusions/Significance: By using ELISA to measure Zaire Ebola virus antibody concentrations, we identified a significant number of individuals with previously undetected EBOV infection in a ‘hotspot’ village in Sierra Leone, approximately one year after the village outbreak. The findings provide further evidence that Ebola, like many other viral infections, presents with a spectrum of clinical manifestations, including minimally symptomatic infection. These data also suggest that a significant portion of Ebola transmission events may have gone undetected during the outbreak. Further studies are needed to understand the potential risk of transmission and clinical sequelae in individuals with previously undetected EBOV infection

Improved Detection of Tuberculosis and Multidrug-Resistant Tuberculosis among Tibetan Refugees, India

The incidence of tuberculosis (TB) among Tibetan refugees in India is 431 cases/100,000 persons, compared with 181 cases/100,000 persons overall in India in 2010. More than half of TB cases in these refugees occur among students, monks, and nuns in congregate settings. We sought to increase TB case detection rates for this population through active case finding and rapid molecular diagnostics. We screened 27,714 persons for symptoms of TB and tested 3,830 symptomatic persons by using an algorithm incorporating chest radiography, sputum smear microscopy, culture, and a rapid diagnostic test; 96 (2.5%) cases of TB were detected (prevalence 346 cases/100,000 persons). Of these cases, 5% were multidrug-resistant TB. Use of the rapid diagnostic test and active case finding enabled rapid detection of undiagnosed TB cases in congregate living settings, which would not have otherwise been identified. The burden of TB in the Tibetan exile population in India is extremely high and requires urgent attention

Strengthening the Free Healthcare Initiative through a pharmacy and supply chain intervention: Partners in Health's experience in rural Sierra Leone

Background: To improve high maternal and under-5 mortality—among the worst globally—Sierra Leone's Ministry of Health and Sanitation (MOHS) enacted the Free Healthcare Initiative in 2010. Under this initiative, pregnant and lactating women and children aged younger than 5 years receive medical treatment and essential medicines free of charge at public facilities. However, the availability of medicines remains inconsistent, which results in patients paying for medicines and an undermining of the quality of care and trust in the health-care system. These gaps between services and medicines promised under the Free Healthcare Initiative and actual resources delivered worsened during the 2013–15 Ebola epidemic, which strained an already weak health-care system. Here, we describe an approach to strengthen pharmacy and supply chain systems to improve access to essential medicines at a district hospital in Sierra Leone. Methods: In 2015, Partners In Health undertook a gap analysis to understand the barriers to drug availability for patients eligible for the Free Healthcare Initiative at Koidu Government Hospital (KGH). A multidisciplinary task force identified priorities and created a partnership with the MOHS. Partners In Health's Director of Pharmacy led meetings with hospital management, shadowed clinical staff, and performed an inventory of drugs and medical supplies. Findings: The gap analysis revealed challenges in the areas of human resources, infrastructure, storage, and information systems. The results led to the following interventions: decentralisation of medication distribution from hospital to ward level; the hiring of four pharmacy technicians; expansion of central warehousing; and implementation of electronic reporting tools to improve consumption data. MOHS pharmacy staff were mentored to improve feedback mechanisms between central and district levels. Between November, 2015, and August, 2016, these changes resulted in nearly 100% availability of essential drugs—with 80% provided via the strengthened MOHS system—and elimination of out-of-pocket expenses for patients. Additionally, trust in the public health-care system has improved: compared with a 2012 and 2013 pre-Ebola baseline at KGH, paediatric and maternity admissions have increased by 47%, with a 95% increase in hospital-based deliveries. Interpretation: The success of the Free Healthcare Initiative is rooted in its shared ownership with the MOHS and the integration of central-level and district-level information systems. The approach described here could be used to guide new interventions to strengthen pharmacy supply chains elsewhere in Sierra Leone and other low-resource settings. Funding: Partners In Health, Sierra Leone

Remdesivir for the Treatment of Covid-19 - Final Report.

BackgroundAlthough several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.MethodsWe conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.ResultsA total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P&lt;0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%).ConclusionsOur data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)

Remdesivir for the Treatment of Covid-19-Final Report

BackgroundAlthough several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. MethodsWe conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. ResultsA total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). ConclusionsOur data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.) In this randomized, double-blind trial in 1062 adults hospitalized with Covid-19, remdesivir was superior to placebo in shortening the time to recovery (10 days, vs. 15 days with placebo). The estimates of mortality by day 29 were 11.4% with remdesivir and 15.2% with placebo. The benefit of remdesivir was most apparent in patients who were receiving low-flow oxygen at baseline