Adrienne E Shapiro

Bio: Adrienne E Shapiro is an academic researcher from University of Washington. The author has contributed to research in topics: Medicine & Tuberculosis. The author has an hindex of 11, co-authored 33 publications receiving 626 citations. Previous affiliations of Adrienne E Shapiro include Johns Hopkins University & University of London.

Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Abstract: Importance Older patients and those with comorbidities who are infected with SARS-CoV-2 may be at increased risk of hospitalization and death. Sotrovimab is a neutralizing antibody for the treatment of high-risk patients to prevent COVID-19 progression. Objective To evaluate the efficacy and adverse events of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease. Design, Setting, and Participants Randomized clinical trial including 1057 nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for progression conducted at 57 sites in Brazil, Canada, Peru, Spain, and the US from August 27, 2020, through March 11, 2021; follow-up data were collected through April 8, 2021. Interventions Patients were randomized (1:1) to an intravenous infusion with 500 mg of sotrovimab (n = 528) or placebo (n = 529). Main Outcomes and Measures The primary outcome was the proportion of patients with COVID-19 progression through day 29 (all-cause hospitalization lasting >24 hours for acute illness management or death); 5 secondary outcomes were tested in hierarchal order, including a composite of all-cause emergency department (ED) visit, hospitalization of any duration for acute illness management, or death through day 29 and progression to severe or critical respiratory COVID-19 requiring supplemental oxygen or mechanical ventilation. Results Enrollment was stopped early for efficacy at the prespecified interim analysis. Among 1057 patients randomized (median age, 53 years [IQR, 42-62], 20% were ≥65 years of age, and 65% Latinx), the median duration of follow-up was 103 days for sotrovimab and 102 days for placebo. All-cause hospitalization lasting longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) (adjusted relative risk [RR], 0.21 [95% CI, 0.09 to 0.50]; absolute difference, -4.53% [95% CI, -6.70% to -2.37%]; P < .001). Four of the 5 secondary outcomes were statistically significant in favor of sotrovimab, including reduced ED visit, hospitalization, or death (13/528 [2%] for sotrovimab vs 39/529 [7%] for placebo; adjusted RR, 0.34 [95% CI, 0.19 to 0.63]; absolute difference, -4.91% [95% CI, -7.50% to -2.32%]; P < .001) and progression to severe or critical respiratory COVID-19 (7/528 [1%] for sotrovimab vs 28/529 [5%] for placebo; adjusted RR, 0.26 [95% CI, 0.12 to 0.59]; absolute difference, -3.97% [95% CI, -6.11% to -1.82%]; P = .002). Adverse events were infrequent and similar between treatment groups (22% for sotrovimab vs 23% for placebo); the most common events were diarrhea with sotrovimab (n = 8; 2%) and COVID-19 pneumonia with placebo (n = 22; 4%). Conclusions and Relevance Among nonhospitalized patients with mild to moderate COVID-19 and at risk of disease progression, a single intravenous dose of sotrovimab, compared with placebo, significantly reduced the risk of a composite end point of all-cause hospitalization or death through day 29. The findings support sotrovimab as a treatment option for nonhospitalized, high-risk patients with mild to moderate COVID-19, although efficacy against SARS-CoV-2 variants that have emerged since the study was completed is unknown. Trial Registration ClinicalTrials.gov Identifier: NCT04545060.

The benefits to communities and individuals of screening for active tuberculosis disease: a systematic review.

Abstract: BACKGROUND: Screening for tuberculosis (TB) disease aims to improve early TB case detection. The ultimate goal is to improve outcomes for people with TB and to reduce Mycobacterium tuberculosis transmission in the community through improved case detection, reduction in diagnostic delays and early treatment. Before screening programmes are recommended, evidence is needed of individual and/or community-level benefits. METHODS: We conducted a systematic review of the literature to assess the evidence that screening for TB disease 1) initially increases the number of TB cases initiated on anti-tuberculosis treatment, 2) identifies cases earlier in the course of disease, 3) reduces mortality and morbidity, and 4) impacts on TB epidemiology. RESULTS: A total of 28 798 publications were identified by the search strategy: 27 087 were excluded on initial screening and 1749 on full text review, leaving 62 publications that addressed at least one of the study questions. Screening increases the number of cases found in the short term. In many settings, more than half of the prevalent TB cases in the community remain undiagnosed. Screening tends to find cases earlier and with less severe disease, but this may be attributed to case-finding studies using more sensitive diagnostic methods than routine programmes. Treatment outcomes among people identified through screening are similar to outcomes among those identified through passive case finding. Current studies provide insufficient evidence to show that active screening for TB disease impacts on TB epidemiology. CONCLUSION: Individual and community-level benefits from active screening for TB disease remain uncertain. So far, the benefits of earlier diagnosis on patient outcomes and transmission have not been established.

Epidemiology of helminth infections and their relationship to clinical malaria in southwest Uganda

Abstract: It has recently been suggested that helminth infections may adversely influence susceptibility to other infections, including malaria. To investigate this hypothesis in a sub-Saharan African setting, surveys of helminth infections were conducted in 2003 among individuals who had been under weekly active case detection for clinical malaria during the preceding 18 months in four villages in Kabale District, southwest Uganda. Overall, 47.3% of individuals had at least one intestinal nematode species infection: hookworm, Ascaris lumbricoides and Trichuris trichiura were detected in 32.1, 17.4 and 8.1% of individuals, respectively. We found evidence of significant household clustering of A. lumbricoides, T. trichiura and hookworm, and clustering of heavy infection of each species. The association between helminth infection and clinical malaria was investigated in two villages and no evidence for an association was observed between the presence of infection or heavy infection and risk of malaria.

Community-based Targeted Case Finding for Tuberculosis and HIV in Household Contacts of Patients with Tuberculosis in South Africa

Abstract: Rationale:SouthAfricahasahighprevalenceoftuberculosis(TB)and HIV-coinfected adults in whom TB is often diagnosed late in the course of disease. Objectives: Improved case-finding approaches for TB and HIV are needed to reduce mortality and prevent transmission. Methods: We identified newly diagnosed index TB cases in a rural district and enrolled their households in a TB-HIV contact-tracing study. A group of randomly selected control households were enrolled to determine community prevalence of undetected TB and HIV. Field teams screened participants for TB symptoms, collected sputum specimens for smear microscopy and culture, provided HIV counselingandtesting,andcollectedbloodforCD4testing.Participantswere referred to public clinics for TB treatment and antiretroviral therapy. Measurements and Main Results: We evaluated 2,843 household contacts of 727 index patients with TB and 983 randomly selected controlhouseholdmembers.TheprevalenceofTBinhouseholdcontacts was 6,075 per 100,000 (95% confidence interval, 5,789‐6,360 per100,000),whereastheprevalencedetectedinrandomlyselected households was 407 per 100,000 (95% confidence interval, 0‐912 per 100,000; prevalence difference, 5,668 per 100,000; P , 0.001). TBdetectedamongcontactswaslesslikelytobesmear-positivethan in the index patients (6% vs. 22%; P , 0.001). Most contacts with culture-confirmed TB were asymptomatic. At least one case of undiagnosed TB was found in 141 (19%) of 727 contact versus 4 (1%) of 312 control households. HIV testing was positive in 166 (11%) of 1,568 contacts tested versus 76 (14%) of 521 control participants tested (odds ratio, 1.48; P ¼ 0.02). Conclusions: Active case finding in TB contact households should be consideredtoimproveTBandHIVcasedetectioninhigh-prevalence settings, but sensitive diagnostic tools are necessary.

Clinical, laboratory, and temporal predictors of neutralizing antibodies against SARS-CoV-2 among COVID-19 convalescent plasma donor candidates.

Abstract: BACKGROUNDSARS-CoV-2-specific antibodies may protect from reinfection and disease, providing rationale for administration of plasma containing SARS-CoV-2-neutralizing antibodies (nAbs) as a treatment for COVID-19. Clinical factors and laboratory assays to streamline plasma donor selection, and the durability of nAb responses, are incompletely understood.METHODSPotential convalescent plasma donors with virologically documented SARS-CoV-2 infection were tested for serum IgG against SARS-CoV-2 spike protein S1 domain and against nucleoprotein (NP), and for nAb.RESULTSAmong 250 consecutive persons, including 27 (11%) requiring hospitalization, who were studied a median of 67 days since symptom onset, 97% were seropositive on 1 or more assays. Sixty percent of donors had nAb titers ≥1:80. Correlates of higher nAb titers included older age (adjusted OR [AOR] 1.03 per year of age, 95% CI 1.00-1.06), male sex (AOR 2.08, 95% CI 1.13-3.82), fever during illness (AOR 2.73, 95% CI 1.25-5.97), and disease severity represented by hospitalization (AOR 6.59, 95% CI 1.32-32.96). Receiver operating characteristic analyses of anti-S1 and anti-NP antibody results yielded cutoffs that corresponded well with nAb titers, with the anti-S1 assay being slightly more predictive. nAb titers declined in 37 of 41 paired specimens collected a median of 98 days (range 77-120) apart (P < 0.001). Seven individuals (2.8%) were persistently seronegative and lacked T cell responses.CONCLUSIONnAb titers correlated with COVID-19 severity, age, and sex. SARS-CoV-2 IgG results can serve as useful surrogates for nAb testing. Functional nAb levels declined, and a small proportion of convalescent individuals lacked adaptive immune responses.FUNDINGThe project was supported by the Frederick National Laboratory for Cancer Research with support from the NIAID under contract number 75N91019D00024, and was supported by the Fred Hutchinson Joel Meyers Endowment, Fast-Grants, a New Investigator award from the American Society for Transplantation and Cellular Therapy, and NIH contracts 75N93019C0063, 75N91019D00024, and HHSN272201800013C, and NIH grants T32-AI118690, T32-AI007044, K08-AI119142, and K23-AI140918.

Incorporating a Rapid-Impact Package for Neglected Tropical Diseases with Programs for HIV/AIDS, Tuberculosis, and Malaria

Abstract: Hotez et al. argue that achieving success in the global fight against HIV/AIDS, tuberculosis, and malaria may well require a concurrent attack on the neglected tropical diseases.

Towards tuberculosis elimination: an action framework for low-incidence countries

Abstract: This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

Earlier versus Later Start of Antiretroviral Therapy in HIV-Infected Adults with Tuberculosis

Abstract: Background Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy. Methods We tested the hypothesis that the timing of ART initiation would significantly affect mortality among adults not previously exposed to antiretroviral drugs who had newly diagnosed tuberculosis and CD4+ T-cell counts of 200 per cubic millimeter or lower. After beginning the standard, 6-month treatment for tuberculosis, patients were randomly assigned to either earlier treatment (2 weeks after beginning tuberculosis treatment) or later treatment (8 weeks after) with stavudine, lamivudine, and efavirenz. The primary end point was survival. Results A total of 661 patients were enrolled and were followed for a median of 25 months. The median CD4+ T-cell count was 25 per cubic millimeter, and the median viral load was 5.64 l...

Measuring socio-economic position for epidemiological studies in low- and middle-income countries: a methods of measurement in epidemiology paper

Abstract: Much has been written about the measurement of socio-economic position (SEP) in high-income countries (HIC). Less has been written for an epidemiology, health systems and public health audience about the measurement of SEP in low- and middle-income countries (LMIC). The social stratification processes in many LMIC-and therefore the appropriate measurement tools-differ considerably from those in HIC. Many measures of SEP have been utilized in epidemiological studies; the aspects of SEP captured by these measures and the pathways through which they may affect health are likely to be slightly different but overlapping. No single measure of SEP will be ideal for all studies and contexts; the strengths and limitations of a given indicator are likely to vary according to the specific research question. Understanding the general properties of different indicators, however, is essential for all those involved in the design or interpretation of epidemiological studies. In this article, we describe the measures of SEP used in LMIC. We concentrate on measures of individual or household-level SEP rather than area-based or ecological measures such as gross domestic product. We describe each indicator in terms of its theoretical basis, interpretation, measurement, strengths and limitations. We also provide brief comparisons between LMIC and HIC for each measure.

Systematic review and meta-analysis of community and facility-based HIV testing to address linkage to care gaps in sub-Saharan Africa

Abstract: HIV testing and counselling is the first crucial step for linkage to HIV treatment and prevention. However, despite high HIV burden in sub-Saharan Africa, testing coverage is low, particularly among young adults and men. Community-based HIV testing and counselling (testing outside of health facilities) has the potential to reduce coverage gaps, but the relative impact of different modalities is not well assessed. We conducted a systematic review of HIV testing modalities, characterizing community (home, mobile, index, key populations, campaign, workplace and self-testing) and facility approaches by population reached, HIV positivity, CD4 count at diagnosis and linkage. Of 2,520 abstracts screened, 126 met eligibility criteria. Community HIV testing and counselling had high coverage and uptake and identified HIV-positive people at higher CD4 counts than facility testing. Mobile HIV testing reached the highest proportion of men of all modalities examined (50%, 95% confidence interval (CI) = 47-54%) and home with self-testing reached the highest proportion of young adults (66%, 95% CI = 65-67%). Few studies evaluated HIV testing for key populations (commercial sex workers and men who have sex with men), but these interventions yielded high HIV positivity (38%, 95% CI = 19-62%) combined with the highest proportion of first-time testers (78%, 95% CI = 63-88%), indicating service gaps. Community testing with facilitated linkage (for example, counsellor follow-up to support linkage) achieved high linkage to care (95%, 95% CI = 87-98%) and antiretroviral initiation (75%, 95% CI = 68-82%). Expanding home and mobile testing, self-testing and outreach to key populations with facilitated linkage can increase the proportion of men, young adults and high-risk individuals linked to HIV treatment and prevention, and decrease HIV burden.