Yukari C Manabe

Infectious Diseases Institute, Makerere University, Kampala, Central Region, Uganda

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Publications (127)534.62 Total impact


  • No preview · Article · Feb 2016
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    ABSTRACT: Perceived social standing (PSS) was evaluated as a determinant of differences in health outcomes among Ugandan HIV-infected adults from Kampala using cross-sectional study design. PSS was defined using the MacArthur scale of subjective social status translated and adapted for the study setting. Socio-demographic and psychosocial correlates of PSS ranking at enrollment were determined using linear regression models. High versus low PSS was defined based on the median PSS score and evaluated as a determinant of body mass index, hemoglobin, quality of life (QOL) and frailty-related phenotype via linear regression. A log-binomial regression model estimated the relative-risk of good, very good or excellent versus fair or poor self-rated health (SRH) in relation to PSS. Older age, increasing social support and material wealth were correlated with high PSS ranking, whereas female sex, experience of multiple stigmas and multiple depressive symptoms were correlated with low PSS ranking. High PSS participants were on average 1.1 kg/m(2) heavier, had 4.7 % lower frailty scores and 3.6 % higher QOL scores compared to low PSS patients (all p < 0.05); they were also more likely to self-classify as high SRH (RR 1.4, 95 % confidence interval 1.1, 1.7) but had comparable hemoglobin levels (p = 0.634). Low PSS correlated with poor physical and psychosocial wellbeing in HIV-positive Ugandan adults. The assessment of PSS as part of clinical management, combined with efforts to reduce stigma and improve social support, may identify and possibly reduce PSS-associated health inequality in Ugandan adults with HIV.
    Full-text · Article · Jan 2016 · Journal of Behavioral Medicine
  • Janneke A. Cox · Robert Colebunders · Yukari C. Manabe

    No preview · Article · Jan 2016 · Journal of Clinical Microbiology
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    ABSTRACT: Purpose of review: Cryptococcal meningitis causes significant mortality among HIV-infected patients, despite antifungal therapy and use of antiretroviral therapy (ART). In patients with cryptococcal meningitis, ART is often complicated by immune reconstitution inflammatory syndrome (IRIS), manifesting as unmasking of previously unrecognized subclinical infection (unmasking CM-IRIS) or paradoxical worsening of symptoms in the central nervous system after prior improvement with antifungal therapy (paradoxical CM-IRIS). We review our current understanding of the pathogenesis of this phenomenon, focusing on unifying innate and adaptive immune mechanisms leading to the development of this often fatal syndrome. Recent findings: We propose that HIV-associated CD4 T-cell depletion, chemokine-driven trafficking of monocytes into cerebrospinal fluid in response to cryptococcal meningitis, and poor localized innate cytokine responses lead to inadequate cryptococcal killing and clearance of the fungus. Subsequent ART-associated recovery of T-cell signaling and restored cytokine responses, characterized by IFN-γ production, triggers an inflammatory response. The inflammatory response triggered by ART is dysregulated because of impaired homeostatic and regulatory mechanisms, culminating in the development of CM-IRIS. Summary: Despite our incomplete understanding of the immunopathogenesis of CM-IRIS, emerging data exploring innate and adaptive immune responses could be exploited to predict, prevent and manage CM-IRIS and associated morbid consequences.
    Full-text · Article · Dec 2015 · Current Opinion in Infectious Diseases
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    ABSTRACT: Efficacy trials investigating the effect of multivitamin (MV) supplementations among patients on Highly Active Antiretroviral Therapy (HAART) have so far been inconclusive. We conducted a randomized, double blind, placebo controlled trial to determine the effect of one recommended daily allowance (RDA) of MV supplementation on disease progression in patients initiating HAART. Eligible subjects were randomized to receive placebo or MV supplementation including vitamins B-complex, C and E. Participants were followed for up to 18 months. Primary endpoints were: change in CD4 cell count, weight and quality of life (QoL). Secondary endpoints were: i) development of a new or recurrent HIV disease progression event, including all-cause mortality; ii) switching from first- to second-line antiretroviral therapy (ART); and iii) occurrence of an adverse event. Intent-to-treat analysis, using linear regression mixed effects models were used to compare changes over time in the primary endpoints between the study arms. Kaplan-Meier time-to-event analysis and the log-rank test was used to compare HIV disease progression events and all-cause mortality. Four hundred participants were randomized, 200 onto MV and 200 onto placebo. By month 18, the average change in CD4 cell count in the MV arm was 141 cells/uL compared to 147 cells/uL in the placebo arm, a mean difference of -6 · 17 [95 % CI -29 · 3, 16 · 9]. The average change in weight in the MV arm was 3 · 9 kg compared to 3 · 3 kg in the placebo arm, a mean difference of 0 · 54 [95 % CI -0 · 40, 1 · 48]; whereas average change in QoL scores in the MV arm was 6 · 8 compared to 8 · 8 in the placebo arm, a mean difference of -2.16 [95 % CI -4 · 59,0 · 27]. No significant differences were observed in these primary endpoints, or in occurrence of adverse events between the trial arms. One RDA of MV supplementation was safe but did not have an effect on indicators of disease progression among HIV infected adults initiating HAART. Clinical trials NCT01228578 , registered on 15th October 2010.
    No preview · Article · Dec 2015 · BMC Infectious Diseases
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    ABSTRACT: Human antibacterial exposure occur in different ways including consumption of animal and agricultural products as well as use of prescribed and non-prescribed agents. We estimated the prevalence and explored the predictors of antibacterial use among patients presenting to hospitals in northern Uganda. Four hundred fifty (450) patients were randomly selected and antibacterial use prior to hospital visit measured using a questionnaire and urine antibacterial activity assay. Urine antibacterial bioassays were performed using American type culture collections of Escherichia coli, Bacillus subtilis and Streptococcus pyogenes. Data were analysed using STATA 12.0 at 95 % confidence level. Of 450 patients interviewed, 62.2 % had used antibacterial agents. Urine antibacterial activity was detected in 30.4 % of the samples tested. Of the 85 patients who reported not taking any antibacterial at home, 16 (18.8 %) had urine with antibacterial activity. Most test bacteria, E. coli (74.5 %), B. subtilis (72.6 %) and S. pyogens (86.7 %) were sensitive to urine of patients who reported using antibacterial drugs before hospital visit. From the interview, metronidazole 15.6 % (70/450), amoxicillin 12 % (54/450), and ciprofloxacin 10.4 % (47/450) were the most used antibacterial agents. Patient age (OR, 2.45: 95 % CI: 1.02–5.91: P = 0.024), time-lag between last drug intake and hospital visit (OR: 3.18: 95 % CI: 1.44–7.0: P < 0.0001), and time-lag between illness onset and hospital visit (OR: 1.89: 95 % CI: 0.38–5.1: P = 0.027) predicted the use of antibacterial agents before hospital visit. Community antibacterial use continues to take place in an unregulated manner. In addition, physiciansrarely seek to ascertain prior use of antibacterial agents among patients presenting to hospitals. This couldhave a bearing on patient treatment outcomes. Knowledge of prior antibacterial use among patients presenting to hospitals is useful to physicians in ensuring antibacterial stewardship.
    Full-text · Article · Sep 2015 · BMC pharmacology & toxicology
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    ABSTRACT: Background & aims: We implemented a prospective study among human immunodeficiency virus (HIV)-positive adults to examine the association between vitamin-D deficiency (VDD) and insufficiency (VDI) vs sufficiency (VDS) and CD4+T-cell improvement over 18 months of highly active antiretroviral therapy (HAART). Methods: We used data from a randomized placebo-controlled micronutrient trial with 25-hydroxy vitamin-D (25(OH)D) measured at enrollment in 398 adults. CD4+T-cell count was measured repeatedly at months 0, 3, 6, 12 and 18. Linear mixed models quantified the vitamin-D-related differences in CD4+T-cell count and associated 99% confidence intervals at baseline and respective follow-up intervals. Results: At baseline 23%, 60% and 17% of participants were VDS, VDI and VDD, respectively. Absolute CD4+T- cell counts recovered during follow-up were persistently lower for baseline VDD and VDI relative to VDS participants. The greatest deficit in absolute CD4+T-cells recovered occurred in VDD vs VDS participants with estimates ranging from a minimum deficit of 26 cells/μl (99% CI: -77, 26) to a maximum deficit of 65 cells/μl (99% CI: -125, -5.5) during follow-up. This VDD-associated lower absolute CD4+T-cell gain was strongest among patients 35 years old or younger and among participants with a baseline body mass index of less than 25 kg/m(2). Conclusions: VDD is associated with lower absolute CD4+T-cell count recovery in HIV-positive patients on HAART. Vitamin-D supplementation may improve CD4+T-cell recovery during HAART. However, future intervention studies are needed to definitively evaluate the effectiveness of this vitamin as an adjunct therapy during HAART.
    No preview · Article · Sep 2015 · Clinical nutrition (Edinburgh, Scotland)
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    ABSTRACT: Classroom-based learning is often insufficient to ensure high quality care and application of health care guidelines. Educational outreach is garnering attention as a supplemental method to enhance health care worker capacity, yet there is little information about the timing and duration required to improve facility performance. We sought to evaluate the effects of an infectious disease training program followed by either immediate or delayed on-site support (OSS), an educational outreach approach, on nine facility performance indicators for emergency triage, assessment, and treatment; malaria; and pneumonia. We also compared the effects of nine monthly OSS visits to extended OSS, with three additional visits over six months.
    Full-text · Article · Sep 2015 · PLoS ONE
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    Full-text · Article · Aug 2015 · Implementation Science
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    ABSTRACT: The existing World Health Organization diagnostic algorithms for smear-negative TB perform poorly in HIV-infected individuals. New TB diagnostics such as urine TB lipoarabinomannan (LAM) could improve the accuracy and reduce delays in TB diagnosis in HIV-infected smear-negative presumptive TB. We sought to determine predictors for MTB culture-positivity among these patients. METHODS: This study was nested into a prospective evaluation of HIV-infected outpatients and inpatients clinically suspected to have TB who were screened by smear-microscopy on two spot sputum samples. Data on socio-demographics, clinical symptoms, antiretroviral therapy, CXR, CD4 count, mycobacterial sputum and blood cultures and TB-LAM were collected. Logistic regression and conditional inference tree analysis were used to determine the most predictive indicators for MTB culture-positivity. RESULTS: Of the 418 smear-negative participants [female, 64%; median age (IQR) 32 (28-39) years, median CD4 106 (IQR 22 - 298) cells/mm3], 96/418 (23%) were sputum and/ or blood culture-positive for Mycobacterium tuberculosis (MTB) complex. Abnormal CXR (aOR 3.68, 95% CI 1.76- 7.71, p=0.001) and positive urine TB-LAM (aOR 6.21, 95% CI 3.14-12.27, p< 0.001) were significantly associated with MTB culture-positivity. Previous TB treatment (aOR 0.41, 95% CI 0.17-0.99, p=0.049) reduced the likelihood of a positive MTB culture. A conditional inference tree analysis showed that positive urine TB-LAM and abnormal CXR were the most predictive indicators of MTB culture-positivity. A combination of urine TB-LAM test and CXR had sensitivity and specificity of 50% and 86.1% respectively overall, and 70.8% and 84.1% respectively among those with CD4<100 cells/mm3. CONCLUSIONS: A positive urine TB-LAM test and an abnormal CXR significantly predict MTB culture-positivity among smear-negative HIV-infected presumptive TB patients while previous TB treatment reduces the likelihood of a positive MTB culture. Validation studies to assess the performance of diagnostic algorithms that include urine TB-LAM in the diagnosis of smear-negative TB in HIV-infected individuals are warranted.
    Full-text · Article · Jul 2015 · PLoS ONE
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    Full-text · Dataset · Jul 2015
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    ABSTRACT: Background: Among HIV-infected individuals with CD4 less than 200 cells/mm3, tuberculosis often has an atypical presentation, is more likely to be disseminated and is diagnostically challenging. We sought to understand the genotypic discordance of concurrent sputum and blood M. tuberculosis (MTB) isolates from HIV-infected individuals. Methods: From a prospective diagnostic accuracy study with 182 HIV-infected culture-positive TB adults, isolates were obtained from 51 of 66 participants who were MTB culture-positive by both sputum and blood. Isolates were subjected to susceptibility testing to 1st line drugs, spoligotyping and 24 locus- MIRU-VNTR. Results: The median age of the participants was 31 (IQR; 27-38) years and 51% were male. The median CD4 count was 29 (IQR; 10-84) cells/mm3 with 20% taking ART; 8.0% were previously treated for TB, and 63% were AFB smear-negative. The isolates belonged to two of the main global MTB-lineages; East-African-Indian (L3) 17 (16.7%) and Euro-American (L4) 85 (83.3%). We identified 26 (51.0%) participants with discordant MTB-genotypes between sputum and blood, including two patients with evidence of mixed infection in either compartment. Having discordant MTB-genotypes was not predicted by the MTB-lineage in either blood or sputum, CD4 cell count, or any other clinical characteristic. Conclusions: There is a high genotypic discordance among M. tuberculosis concurrently isolated from sputum and blood of HIV-infected individuals. These findings suggest that infection with more than one strain of M. tuberculosis occurs in at least half of patients with advanced HIV infection.
    Full-text · Article · Jul 2015 · PLoS ONE
  • Yukari C Manabe · Richard D Moore

    No preview · Article · Jul 2015 · Clinical Infectious Diseases
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    ABSTRACT: Untreated syphilis in pregnancy is associated with adverse clinical outcomes to the infant. The study aimed to estimate the public health burden resulting from adverse pregnancy outcomes due to syphilis infection among pregnant women not screened for syphilis in 43 countries in sub-Saharan Africa. Estimated country-specific incidence of syphilis was generated from annual number of live births, the proportion of women with at least 1 antenatal care (ANC) visit, the syphilis prevalence rate, and the proportion of women screened for syphilis during ANC.Adverse pregnancy outcome data (stillbirth, neonatal death, low birth weight, and congenital syphilis) were obtained from published sources. Disability-adjusted life-year (DALY) estimates were calculated using undiscounted local life expectancy, the neonatal standard loss function, and relevant disability weights. The model assessed the potential impact of raising ANC coverage to at least 95% and syphilis screening to at least 95% (World Health Organization targets). For all 43 sub-Saharan Africa countries, the estimated incidence of adverse pregnancy outcomes was 205,901 (95% confidence interval [CI], 113,256-383,051) per year, including stillbirth (88,376 [95% CI, 60,854-121,713]), neonatal death (34,959 [95% CI, 23,330-50,076]), low birth weight (22,483 [95% CI, 0-98,847]), and congenital syphilis (60,084 [95% CI, 29,073-112,414]), resulting in approximately 12.5 million DALYs. Countries with the greatest burden are (in DALYs, millions) Democratic Republic of the Congo (1.809), Nigeria (1.598), Ethiopia (1.466), and Tanzania (0.961). Attaining World Health Organization targets could reduce the burden by 8.5 million DALYs. Substantial infant mortality and morbidity results from maternal syphilis infection concentrated in countries with low access to ANC or low rates of syphilis screening.
    No preview · Article · Jul 2015 · Sex Transm Dis
  • Sabine Hermans · Yukari Manabe

    No preview · Article · Jun 2015 · The Lancet Infectious Diseases
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    ABSTRACT: Point-of-care tests for TB meningitis (TBM) are needed. We studied the diagnostic accuracy of lipoarabinomannan (LAM) lateral flow assay (LFA), LAM ELISA and Xpert MTB/RIF in cerebrospinal fluid (CSF) in an autopsy cohort of Ugandan HIV-infected adults. We obtained written informed consent from the next of kin postmortem. A complete autopsy was done and CSF obtained. We performed LAM LFA (on unprepared and supernatant CSF after heating and spinning), LAM ELISA and Xpert MTB/RIF on the CSF. Accuracy parameters were calculated for histopathological TBM and also for the composite standard including Xpert MTB/RIF positive cases. We tested CSF of 91 patients. LAM LFA had a sensitivity of 75% for definite histopathological TBM, ELISA of 43% and Xpert MTB/RIF of 100% and a specificity of 87%, 91% and 87% respectively. For definite and probable histopathological TBM LAM LFA had a sensitivity of 50%, ELISA of 38% and Xpert MTB/RIF of 86% and a specificity of 70%, 91% and 87% respectively. For the composite standard, LAM LFA had a sensitivity of 68% and ELISA of 48% and a specificity of 78% and 98% respectively. The rapid diagnostic tests detected 22-78% of TBM in patients not on anti-TB treatment. Point-of-care tests have high accuracy to diagnose TBM in deceased HIV-infected adults. LAM LFA in CSF is a useful additional diagnostic tool. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Full-text · Article · Jun 2015 · Journal of clinical microbiology
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    ABSTRACT: Objective: The detection of urinary lipoarabinomannan (LAM), a mycobacterial cell wall component, is used to diagnose tuberculosis (TB). How LAM enters the urine is not known. To investigate if urinary LAM-positivity is the result of renal TB infection we correlated the outcomes of urinary LAM-antigen testing to renal histology in an autopsy cohort of hospitalized, Ugandan, HIV-infected adults. Methods: We performed a complete autopsy, including renal sampling, in HIV-infected adults that died during hospitalization after written informed consent was obtained from the next of kin. Urine was collected postmortem through post-mortem catheterisation or by bladder puncture and tested for LAM with both a lateral flow assay (LFA) and an ELISA assay. Two pathologists assessed the kidney histology. We correlated the LAM-assay results and the histology findings. Results: Of the 13/36 (36%) patients with a positive urinary LAM ELISA and/or LFA, 8/13 (62%) had renal TB. The remaining 5 LAM-positive patients had disseminated TB without renal involvement. Of the 23 LAM-negative patients, 3 had disseminated TB without renal involvement. The remaining LAM-negative patients had no TB infection and died mostly of fungal and bacterial infections. LAM LFA had a sensitivity of 81% and specificity of 100% to diagnose TB at any location, and the LAM ELISA a sensitivity of 63% and a specificity of 100%. 54% (7/13) LAM LFA-positive patients were not on anti-TB treatment at the time of death. Conclusion: Renal TB infection explained LAM-positivity in the majority of patients. Patients with disseminated TB without renal involvement can also be diagnosed with LAM. This suggests that other mechanisms that lead to urinary LAM-positivity exist in a minority of patients.
    Full-text · Article · Apr 2015 · PLoS ONE
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    ABSTRACT: To demonstrate the feasibility of integrated screening for cryptococcal antigenemia and tuberculosis (TB) before antiretroviral therapy (ART) initiation and to assess disease specific and all-cause mortality in the first 6 months of follow-up. We enrolled a cohort of HIV-infected, ART-naive adults with CD4 counts ≤250 cells per microliter in rural Uganda who were followed for 6 months after ART initiation. All subjects underwent screening for TB; those with CD4 ≤100 cells per microliter also had cryptococcal antigen (CrAg) screening. For those who screened positive, standard treatment for TB or preemptive treatment for cryptococcal infection was initiated, followed by ART 2 weeks later. Of 540 participants enrolled, pre-ART screening detected 10.6% (57/540) with prevalent TB and 6.8% (12/177 with CD4 count ≤100 cells/μL) with positive serum CrAg. After ART initiation, 13 (2.4%) patients were diagnosed with TB and 1 patient developed cryptococcal meningitis. Overall 7.2% of participants died (incidence rate 15.6 per 100 person-years at risk). Death rates were significantly higher among subjects with TB and cryptococcal antigenemia compared with subjects without these diagnoses. In multivariate analysis, significant risk factors for mortality were male sex, baseline anemia of hemoglobin ≤10 mg/dL, wasting defined as body mass index ≤15.5 kg/m, and opportunistic infections (TB, positive serum CrAg). Pre-ART screening for opportunistic infections detects many prevalent cases of TB and cryptococcal infection. However, severely immunosuppressed and symptomatic HIV patients continue to experience high mortality after ART initiation.
    No preview · Article · Apr 2015 · JAIDS Journal of Acquired Immune Deficiency Syndromes
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    ABSTRACT: Background. Tuberculosis (TB) control is a public health priority with 3 million cases unrecognized by the public health system each year. We assessed the impact of improved TB diagnostics and on-site training on TB case detection and treatment outcomes in rural healthcare facilities. Methods. Fluorescence microscopy, Xpert MTB/RIF, and on-site training were introduced at 10 healthcare facilities. Using quasi-experimental methods, these 10 intervention healthcare facilities were compared with 2 controls and their own performance the previous year. Results. From January to October 2012, 186 357 and 32 886 outpatients were seen in the 10 intervention and 2 control facilities, respectively. The intervention facilities had a 52.04% higher proportion of presumptive TB cases with a sputum examination (odds ratio [OR] = 12.65; 95% confidence interval [CI], 5.60–28.55). After adjusting for age group and gender, the proportion of smear-positive patients initiated on treatment was 37.76% higher in the intervention than in the control facilities (adjusted OR [AOR], 7.59; 95% CI, 2.19–26.33). After adjusting for the factors above, as well as human immunodeficiency virus and TB retreatment status, the proportion of TB cases who completed treatment was 29.16% higher (AOR, 4.89; 95% CI, 2.24–10.67) and the proportion of TB cases who were lost to follow-up was 66.98% lower (AOR, 0.04; 95% CI, 0.01–0.09). When compared with baseline performance, the intervention facilities had a significantly higher proportion of presumptive TB cases with a sputum examination (64.70% vs 3.44%; OR, 23.95; 95% CI, 12.96–44.25), and these facilities started 56.25% more smear-positive TB cases on treatment during the project period (AOR, 15.36; 95% CI, 6.57–35.91). Conclusions. Optimizing the existing healthcare workforce through a bundled diagnostics and on-site training intervention for nonphysician healthcare workers will rapidly improve TB case detection and outcomes towards global targets.
    Full-text · Article · Apr 2015 · Open Forum Infectious Diseases
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    Full-text · Article · Feb 2015 · Annals of Global Health

Publication Stats

2k Citations
534.62 Total Impact Points

Institutions

  • 2011-2015
    • Infectious Diseases Institute, Makerere University
      Kampala, Central Region, Uganda
  • 1999-2015
    • Johns Hopkins University
      • • Department of Medicine
      • • Center for Tuberculosis Research
      Baltimore, Maryland, United States
  • 1996-2015
    • Johns Hopkins Medicine
      • • Department of Medicine
      • • Division of Infectious Diseases
      Baltimore, Maryland, United States
  • 2011-2014
    • Makerere University
      • Infectious Diseases Institute
      Kampala, Central Region, Uganda
  • 2010-2011
    • Mulago Hospital
      Kampala, Central Region, Uganda
  • 2003-2005
    • George Washington University
      Washington, Washington, D.C., United States
    • Boston University
      Boston, Massachusetts, United States
  • 2002
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States