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Lillian B. Brown

Bio: Lillian B. Brown is an academic researcher from University of California, San Francisco. The author has contributed to research in topics: Population & Partner notification. The author has an hindex of 21, co-authored 42 publications receiving 1588 citations. Previous affiliations of Lillian B. Brown include University of North Carolina at Chapel Hill & University of Michigan.

Papers
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Journal ArticleDOI
TL;DR: This study provides the first evidence of the effectiveness of partner notification in sub-Saharan Africa and shows active partner notification was feasible, acceptable, and effective among sexually transmitted infections clinic patients.
Abstract: BACKGROUND: Sexual partners of persons with newly diagnosed HIV infection require HIV counseling testing and if necessary evaluation for therapy. However many African countries do not have a standardized protocol for partner notification and the effectiveness of partner notification has not been evaluated in developing countries . METHODS: Individuals with newly diagnosed HIV infection presenting to sexually transmitted infection clinics in Lilongwe Malawi were randomized to 1 of 3 methods of partner notification: passive referral contract referral or provider referral. The passive referral group was responsible for notifying their partners themselves. The contract referral group was given seven days to notify their partners after which a health care provider contacted partners who had not reported for counseling and testing. In the provider referral group a health care provider notified partners directly. RESULTS: Two hundred forty-five index patients named 302 sexual partners and provided locator information for 252. Among locatable partners 107 returned for HIV counseling and testing; 20 of 82 [24%; 95% confidence interval (CI): 15% to 34%] partners returned in the passive referral arm 45 of 88 (51%; 95% CI: 41% to 62%) in the contract referral arm and 42 of 82 (51%; 95% CI: 40% to 62%) in the provider referral arm (P < 0.001). Among returning partners (n = 107) 67 (64%) of were HIV infected with 54 (81%) newly diagnosed. DISCUSSION: This study provides the first evidence of the effectiveness of partner notification in sub-Saharan Africa. Active partner notification was feasible acceptable and effective among sexually transmitted infections clinic patients. Partner notification will increase early referral to care and facilitate risk reduction among high-risk uninfected partners.

160 citations

Journal ArticleDOI
TL;DR: Universal HIV treatment did not result in a significantly lower incidence of HIV infection than standard care, probably owing to the availability of comprehensive baseline HIV testing and the rapid expansion of ART eligibility in the control group.
Abstract: Background Universal antiretroviral therapy (ART) with annual population testing and a multidisease, patient-centered strategy could reduce new human immunodeficiency virus (HIV) infection...

160 citations

Journal ArticleDOI
TL;DR: This systematic review of immunochromatographic strip (ICS) syphilis tests describes the sensitivity and specificity in two important clinical settings: sexually transmitted infection clinics and antenatal clinics and the development of a new rapid treponemal test provides an opportunity to scale up syphilis screening in many settings where traditional tests are unavailable.
Abstract: Syphilis is a persistent public health issue in many low-income countries that have limited capacity for testing, which traditionally relies on a sensitive non-treponemal test and then a specific treponemal test. However, the development of a new rapid treponemal test provides an opportunity to scale up syphilis screening in many settings where traditional tests are unavailable. This systematic review of immunochromatographic strip (ICS) syphilis tests describes the sensitivity and specificity in two important clinical settings: sexually transmitted infection (STI) clinics and antenatal clinics. Clinical data from more than 22 000 whole blood, plasma, or fingerstick ICS tests obtained at STI or antenatal clinics were retrieved from 15 studies. ICS syphilis tests have a high sensitivity (median 0.86, interquartile range 0.75-0.94) and a higher specificity (0.99, 0.98-0.99), both comparable with non-treponemal screening test characteristics. Further research evaluating ICS syphilis tests among primary syphilis cases and among patients infected with HIV will be essential for the effective roll-out of syphilis screening programmes.

135 citations

Journal ArticleDOI
TL;DR: Combo RT displayed excellent performance for detecting established HIV infection and poor performance forDetecting acute HIV infection in this setting, suggesting that it is no more useful than current algorithms.
Abstract: Point-of-care rapid tests for human immunodeficiency virus (HIV) antibody (Ab) detection have facilitated the scale-up of HIV counseling and testing throughout sub-Saharan Africa [1, 2]. The sensitivity of these tests approaches 100% for antibody detection [3, 4]. However, the tests cannot identify persons with acute HIV infection who have not yet developed HIV-specific antibodies [5–7]. Persons with acute HIV infection are often hyperinfectious because of high viral loads [8–12]. Integrating acute HIV infection detection into HIV testing algorithms would enable acutely infected persons to learn their true HIV status, rather than being informed that they were HIV seronegative. Identifying these persons with acute HIV infection could enable intervention to prevent transmission and early treatment, potentially preserving immune function [13, 14]. Identification of acute HIV infection requires detection of HIV nucleic acids or p24 antigens. Available assays are laboratory based, resource intensive, and require follow-up. HIV RNA polymerase chain reaction (PCR), used for either individual or pooled samples, is the reference standard for detecting antibody-negative acute HIV infection, but it is expensive and difficult to implement in resource-poor settings. HIV p24 antigen (Ag) enzyme-linked immunosorbent assays (ELISAs) have good performance characteristics compared with HIV RNA PCR analysis, but they have been challenging to implement on a wide scale. Fourth-generation HIV ELISAs detect both antibodies and antigens [6, 15, 16] but do not distinguish between the two and require venipuncture, a laboratory, and patient follow-up, limiting routine use in most settings. A rapid point-of-care test capable of distinguishing established from acute HIV infection could improve the sensitivity of existing algorithms and enable provision of acute HIV infection results in real time [17]. The Determine® HIV-1/2 Ag/Ab Combo (Combo RT) is a point-of-care rapid test with separate indicators for HIV antibodies and p24 antigen. The Combo RT was designed to identify HIV earlier than other conventional rapid tests. The antibody portion is reported to be analogous to the Determine® HIV-1/2 antibody test, a widely used rapid test for HIV identification. The antigen component of the test is intended to expand the diagnostic spectrum to identify persons with circulating free p24 antigen, unbound to antibodies. During development, Combo RT antigen was assessed using stored serum from commercial seroconversion panels [18]. For primary HIV samples in the pre- or periseroconversion period, the reported sensitivity of the antigen portion of the Combo RT was 92.2%, compared with a fourth-generation HIV ELISA as the reference standard. Specificity of the antigen portion of the test was reported at 96.6%. The Combo RT is currently commercially available outside the United States. We conducted a field evaluation in Lilongwe, Malawi, to assess the accuracy of the antigen portion of Combo RT to detect persons with acute HIV infection. The Roche Monitor HIV RNA PCR assay was used to identify persons with acute HIV infection after routine HIV rapid test evaluation for established HIV infection. We also performed an “ultrasensitive” heat-dissociated p24 antigen ELISA. Finally, in a subset of the study population, we assessed the antibody portion of Combo RT against a standard rapid test antibody algorithm.

130 citations

Journal ArticleDOI
06 Jun 2017-JAMA
TL;DR: Implementation of community-based testing and treatment in rural Kenya and Uganda was associated with an increased proportion of HIV-positive adults who achieved viral suppression, along with increased HIV diagnosis and initiation of antiretroviral therapy.
Abstract: Importance Antiretroviral treatment (ART) is now recommended for all HIV-positive persons. UNAIDS has set global targets to diagnose 90% of HIV-positive individuals, treat 90% of diagnosed individuals with ART, and suppress viral replication among 90% of treated individuals, for a population-level target of 73% of all HIV-positive persons with HIV viral suppression. Objective To describe changes in the proportions of HIV-positive individuals with HIV viral suppression, HIV-positive individuals who had received a diagnosis, diagnosed individuals treated with ART, and treated individuals with HIV viral suppression, following implementation of a community-based testing and treatment program in rural East Africa. Design, Setting, and Participants Observational analysis based on interim data from 16 rural Kenyan (n = 6) and Ugandan (n = 10) intervention communities in the SEARCH Study, an ongoing cluster randomized trial. Community residents who were 15 years or older (N = 77 774) were followed up for 2 years (2013-2014 to 2015-2016). HIV serostatus and plasma HIV RNA level were measured annually at multidisease health campaigns followed by home-based testing for nonattendees. All HIV-positive individuals were offered ART using a streamlined delivery model designed to reduce structural barriers, improve patient-clinician relationships, and enhance patient knowledge and attitudes about HIV. Main Outcomes and Measures Primary outcome was viral suppression (plasma HIV RNA Results Among 77 774 residents (male, 45.3%; age 15-24 years, 35.1%), baseline HIV prevalence was 10.3% (7108 of 69 283 residents). The proportion of HIV-positive individuals with HIV viral suppression at baseline was 44.7% (95% CI, 43.5%-45.9%; 3464 of 7745 residents) and after 2 years of intervention was 80.2% (95% CI, 79.1%-81.2%; 5666 of 7068 residents), an increase of 35.5 percentage points (95% CI, 34.4-36.6). After 2 years, 95.9% of HIV-positive individuals had been previously diagnosed (95% CI, 95.3%-96.5%; 6780 of 7068 residents); 93.4% of those previously diagnosed had received ART (95% CI, 92.8%-94.0%; 6334 of 6780 residents); and 89.5% of those treated had achieved HIV viral suppression (95% CI, 88.6%-90.3%; 5666 of 6334 residents). Conclusions and Relevance Among individuals with HIV in rural Kenya and Uganda, implementation of community-based testing and treatment was associated with an increased proportion of HIV-positive adults who achieved viral suppression, along with increased HIV diagnosis and initiation of antiretroviral therapy. In these communities, the UNAIDS population-level viral suppression target was exceeded within 2 years after program implementation. Trial Registration clinicaltrials.gov Identifier:NCT01864683

126 citations


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01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

4,408 citations

Journal ArticleDOI
TL;DR: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015, with evidence of continued acceleration in the MMR, and MMR was highest in the oldest age groups in both 1990 and 2013.

1,383 citations

Journal ArticleDOI
TL;DR: It is hypothesize that the different COVID-19 patterns found at presentation in the emergency department depend on the interaction between three factors: the severity of the infection, the host response, physiological reserve and comorbidities; the ventilatory responsiveness of the patient to hypoxemia; and the time elapsed between the onset of the disease and the observation in the hospital.
Abstract: The Surviving Sepsis Campaign panel recently recommended that “mechanically ventilated patients with COVID-19 should be managed similarly to other patients with acute respiratory failure in the ICU [1].” Yet, COVID-19 pneumonia [2], despite falling in most of the circumstances under the Berlin definition of ARDS [3], is a specific disease, whose distinctive features are severe hypoxemia often associated with near normal respiratory system compliance (more than 50% of the 150 patients measured by the authors and further confirmed by several colleagues in Northern Italy). This remarkable combination is almost never seen in severe ARDS. These severely hypoxemic patients despite sharing a single etiology (SARS-CoV-2) may present quite differently from one another: normally breathing (“silent” hypoxemia) or remarkably dyspneic; quite responsive to nitric oxide or not; deeply hypocapnic or normo/hypercapnic; and either responsive to prone position or not. Therefore, the same disease actually presents itself with impressive non-uniformity. Based on detailed observation of several cases and discussions with colleagues treating these patients, we hypothesize that the different COVID-19 patterns found at presentation in the emergency department depend on the interaction between three factors: (1) the severity of the infection, the host response, physiological reserve and comorbidities; (2) the ventilatory responsiveness of the patient to hypoxemia; (3) the time elapsed between the onset of the disease and the observation in the hospital. The interaction between these factors leads to the development of a time-related disease spectrum within two primary “phenotypes”: Type L, characterized by Low elastance (i.e., high compliance), Low ventilation-to-perfusion ratio, Low lung weight and Low recruitability and Type H, characterized by High elastance, High right-toleft shunt, High lung weight and High recruitability.

1,378 citations

Journal ArticleDOI
TL;DR: By understanding the evolution, emergence, and spread of AMR in N. gonorrhoeae, including its molecular and phenotypic mechanisms, resistance to antimicrobials used clinically can be anticipated, and future methods for genetic testing for AMR might permit region-specific and tailor-made antimicrobial therapy, the design of novel antimicroBials to circumvent the resistance problems can be undertaken more rationally.
Abstract: Neisseria gonorrhoeae is evolving into a superbug with resistance to previously and currently recommended antimicrobials for treatment of gonorrhea, which is a major public health concern globally. Given the global nature of gonorrhea, the high rate of usage of antimicrobials, suboptimal control and monitoring of antimicrobial resistance (AMR) and treatment failures, slow update of treatment guidelines in most geographical settings, and the extraordinary capacity of the gonococci to develop and retain AMR, it is likely that the global problem of gonococcal AMR will worsen in the foreseeable future and that the severe complications of gonorrhea will emerge as a silent epidemic. By understanding the evolution, emergence, and spread of AMR in N. gonorrhoeae, including its molecular and phenotypic mechanisms, resistance to antimicrobials used clinically can be anticipated, future methods for genetic testing for AMR might permit region-specific and tailor-made antimicrobial therapy, and the design of novel antimicrobials to circumvent the resistance problems can be undertaken more rationally. This review focuses on the history and evolution of gonorrhea treatment regimens and emerging resistance to them, on genetic and phenotypic determinants of gonococcal resistance to previously and currently recommended antimicrobials, including biological costs or benefits; and on crucial actions and future advances necessary to detect and treat resistant gonococcal strains and, ultimately, retain gonorrhea as a treatable infection.

840 citations

Journal ArticleDOI
TL;DR: This review addresses recent advances in the understanding of the transmission of HIV-1 and of acute HIV- 1 infection.
Abstract: More than 33 million people are living with HIV-1, and more than 2.5 million additional cases are detected each year. This review addresses recent advances in our understanding of the transmission of HIV-1 and of acute HIV-1 infection.

594 citations