@article{Parkes-Ratanshi2015,

title = {Cryptococcal disease and the burden of other fungal diseases in Uganda; Where are the knowledge gaps and how can we fill them?},

author = {R. Parkes-Ratanshi and B. Achan and R. Kwizera and A. Kambugu and D. Meya and D. W. Denning},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Cryptococcal-disease-and-the-burden-of-other-fungal-diseases-in.pdf},

doi = {doi: 10.1111/myc.12387},

year  = {2015},

date = {2015-10-06},

journal = {Mycoses},

volume = {58},

number = {5},

pages = {85-93},

abstract = {The HIV epidemic in Uganda has highlighted Cryptococcus and Candida infections as important opportunistic fungal infections. However, the burden of other fungal diseases is not well described. We aimed to estimate the burden of fungal infections in Uganda. All epidemiological papers of fungal diseases in Uganda were reviewed. Where there is no Ugandan data, global or East African data were used. Recurrent vaginal candidiasis is estimated to occur in 375 540 Uganda women per year; Candida in pregnant women affects up to 651,600 women per year. There are around 45,000 HIV-related oral and oesophageal candidosis cases per year. There are up to 3000 cases per year of post-TB chronic pulmonary aspergillosis. There are an estimated 40,392 people with asthma-related fungal conditions. An estimated 1,300,000 cases of tinea capitis occur in school children yearly in Uganda. There are approximately 800 HIV-positive adults with Pneumocystis jirovecii pneumonia (PJP) annually and up to 42 000 children with PJP per year. There are an estimated 4000 cryptococcal cases annually. There are an estimated 2.5 million fungal infections per year in Uganda. Cryptococcus and PJP cause around 28,000 deaths in adults and children per year. We propose replicating the model of research around cryptococcal disease to investigate and development management strategies for other fungal diseases in Uganda.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ford2015,

title = {The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An Application of Dynamic Marginal Structural Models},

author = {Deborah Ford and James M. Robins and Maya L. Petersen and Diana M. Gibb and Charles F. Gilks and Peter Mugyenyi and Heiner Grosskurth and James Hakim and Elly Katabira and Abdel G. Babiker and A. Sarah Walker on behalf of the DART Trial Team

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/The-Impact-of-Different-CD4-Cell-Count-Monitoring-and-Switching-Strategies-on-Mortality-in-HIV-Infected-African-Adults-on-Antiretroviral-Therapy.pdf},

doi = { 10.1093/aje/kwv083},

year  = {2015},

date = {2015-10-01},

journal = {Journal of Amarican Epidemiology},

volume = {182},

number = {7},

pages = {633-643},

abstract = {In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003–2004, investigatorsintheDevelopmentofAntiretroviralTherapyinAfrica(DART)TrialrandomizedpersonsinitiatingART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4cellcountsweremeasuredevery12weeksinbothgroupsbutwereonlyreturnedtotreatingcliniciansformanagementintheLCMgroup.Follow-upcontinuedthrough2008.Inobservationalanalyses,dynamicmarginalstructuralmodelsonpooledrandomizedgroupswereusedtoestimatesurvivalunderdifferentmonitoring-frequencyand clinical/immunologicalswitchingstrategies.Assumptionsincludednodirecteffectofrandomizedgrouponmortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates. After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 personyears of follow-up, 625 switches, and 179 deaths. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm3 or non-Candida World Health Organization stage 4 event (with CD4 count <250) was 0.96 (95% confidence interval (CI): 0.94, 0.97) with 12-weekly CD4 testing, 0.96 (95% CI: 0.95, 0.97) with 24-weekly CD4 testing, 0.95 (95% CI: 0.93, 0.96) with a single CD4 test at 48 weeks (baseline), and 0.92 (95% CI: 0.91, 0.94) with no CD4 testing. Comparing randomized groups by 48-weekCD4count,themortalityriskassociatedwithCDMversusLCMwasgreaterinpersonswithCD4countsof <100 (hazard ratio=2.4, 95% CI: 1.3, 4.3) than in those with CD4 counts of ≥100 (hazard ratio=1.1, 95% CI: 0.8, 1.7;interactionP=0.04).Thesefindingssupportabenefitfromidentifyingpatientsimmunologicallyfailingfirst-line ART at 48 weeks.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ezeamama2015,

title = {Vitamin-D deficiency impairs CD4+T-cell count recovery rate in HIV-positive adults on highly active antiretroviral therapy: A longitudinal study},

author = {Amara Esther Ezeamama and David Guwatudde and Molin Wang and Danstan Bagendab and Rachel Kyeyune and Christopher Sudfeld and Yukari C. Manabe and Wafaie W. Fawzi},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Vitamin-D-deficiency-impairs-CD4T-cell-count-recovery-rate-in-HIV-positive-adults-on-highly-active-antiretroviral-therapy.pdf},

doi = {10.1016/j.clnu.2015.08.007},

year  = {2015},

date = {2015-10-01},

journal = {Clinical nutrition},

volume = {35},

number = {5},

pages = {1110-1117},

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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ocan2015,

title = {Prevalence and predictors of prior antibacterial use among patients presenting to hospitals in Northern Uganda},

author = {Moses Ocan and Yukari C. Manabe and Hannington Baluku and Esther Atukwase and Jasper Ogwal-Okeng and Celestino Obua},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Prevalence-and-predictors-of-prior-antibacterial-use-among-patients-presenting-to-hospitals-in-Northern-Uganda.pdf},

doi = {10.1186/s40360-015-0027-8},

year  = {2015},

date = {2015-09-25},

journal = {BMC Phamacology & Toxicology},

volume = {16},

abstract = {BACKGROUND:



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.

METHODS:



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.

RESULTS:



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.

DISCUSSION:



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.

CONCLUSION:



Knowledge of prior antibacterial use among patients presenting to hospitals is useful to physicians in ensuring antibacterial stewardship.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cose2015,

title = {Immunology in Africa},

author = {Stephen Cose and Bernard Bagaya and Barbara Nerima and Moses Joloba and Andrew Kambugu and Robert Tweyongyere and David W. Dunne and Edward Mbidde and Pontiano Kaleebu and Alison M. Elliott},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Immunology-in-Africa.pdf},

doi = {10.1111/tmi.12599},

year  = {2015},

date = {2015-09-22},

journal = {Tropical Medicine and International Health},

volume = {20},

number = {12},

pages = {1771-7},

abstract = {Africa is a continent with a large burden of both infectious and non-communicable diseases. If we are to move forward as a continent, we need to equip our growing cadre of exceptional young scientists with the skills needed to tackle the diseases endemic to this continent. For this, immunology is among the key disciplines. Africans should be empowered to study and understand the diseases that affect them, and to perform their cutting-edge research in their country of origin. This requires a multifaceted approach, with buy-in from funders, overseas partners and perhaps, most important of all, African governments themselves.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{vonBraun2015,

title = {‘If at first you don't succeed, try again’. Looking beyond the initial results of a failed tuberculosis diagnosis },

author = {von Braun, A.; Sekaggya, C.; Henning, L.; Nakijoba, R ; Kambugu, A.; Fehr, J.; Castelnuovo, B. },

doi = {https://doi.org/10.5588/pha.15.0029},

year  = {2015},

date = {2015-09-21},

journal = {International Union Against Tuberculosis and Lung Disease},

volume = {5},

number = {3},

pages = {170-172(3)},

abstract = {We report the outcome of investigations conducted in 73 human immunodeficiency virus (HIV) infected Ugandan adults presumed to have pulmonary tuberculosis (PTB). Following initial investigations, 32 of 73 patients were diagnosed with PTB. Of the remaining 41 patients initially classified as ‘non-PTB’, six had a delayed PTB diagnosis after a median of 6 weeks. Of the six patients lost to follow-up, four (66%) were reported to have died. Active tracking and close monitoring of HIV-infected patients presumed to have PTB independently of initial investigation results may reduce morbidity and mortality among this vulnerable patient group. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Monroe-Wise2015,

title = {Training tomorrow's leaders in global health: impact of the Afya Bora Consortium Fellowship on the careers of its alumni.},

author = {Aliza Monroe-Wise and Yohana Mashalla and Gabrielle O’Malleya and Neal Nathanson and Esther Seloilwe and Onesmus Gachuno and Theresa Odero and Damalie Nakanjako and Nelson Sewankambo and Edith Tarimo and David Urassa and Yukari C. Manabe and Susan Chapman and Joachim G. Voss and Judith Wasserheit and Carey Farquhar and Afya Bora Consortium Working Group

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Training-tomorrow’s-leaders-in-global-health-impact-of-the-Afya-Bora-Consortium-Fellowship-on-the-careers-of-its-alumni.pdf},

doi = {10.1186/s12909-016-0750-x},

year  = {2015},

date = {2015-09-19},

journal = {BMC Medical Education},

volume = {16},

pages = {p.241},

abstract = {Background: Effective leadership is a cornerstone of successful healthcare delivery in resource limited settings throughout the world. However, few programs in Africa prepare healthcare professionals with the leadership skills vital to the success of the healthcare systems in which they work. One such program, the Afya Bora Consortium Fellowship in Global Health Leadership, has been training health professionals since 2011. The purpose of this study was to assess what career changes, if any, the Afya Bora Fellowship’s alumni have experienced since completing the fellowship, and to describe those changes. Methods: The Afya Bora Fellowship is a multidisciplinary, one-year training program that teaches health professionals leadership skills through didactic and experiential learning in four African countries. Between January 2011 and June 2013 the consortium trained 42 nurses and doctors. In November 2013, an electronic survey was sent to all alumni to assess their performance in the workplace post-fellowship. Results: Thirty-one (74 %) of 42 alumni completed surveys. Twenty-one (68 %) reported changes to their position at work; of those, sixteen (76 %) believed the change was due to participation in the fellowship. All alumni reported improved performance at work, and cited the application of a wide range of fellowship skills, including leadership, research, communication, and mentoring. Twenty-six (84 %) alumni spearheaded improvements in their workplaces and almost all (97 %) remained in contact with colleagues from the fellowship. Among the respondents there were five publications, nine manuscripts in preparation, and three international conference presentations. Conclusions: Afya Bora alumni overwhelmingly reported that the one year fellowship positively influenced both their work and career trajectory. Training health professionals in leadership skills through didactic modules with the opportunity to apply learned skills at attachment sites in the Afya Bora Fellowship has an impact on performance in the workplace and the potential to improve long-term institutional capacity. Keywords: Leadership training, Africa, Transformative leadership, Interprofessional, Transprofessional

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Obayo2015,

title = {Upper gastrointestinal diseases in patients for endoscopy in South-Western Uganda },

author = {S Obayo, C Muzoora, P Ocama, MM Cooney, T Wilson, CS Probert},

doi = {10.4314/ahs.v15i3.33 },

year  = {2015},

date = {2015-09-10},

journal = {African Health Sciences},

volume = {15},

number = {3},

abstract = {Background: There is a paucity of published data regarding upper gastrointestinal diseases in Ugandans with upper gastrointestinal symptoms referred for endoscopy.



Objectives: To study the presenting complaints, pathology and Helicobacter pylori prevalence among patients with upper gastrointestinal symptoms in South-Western Uganda.

Methods: Patients presenting with upper gastrointestinal symptoms underwent upper endoscopy and a urease test for Helicobacter Pylori, all suspicious lesions were biopsied for histopathology review as appropriate.



Results: The most common presenting complaints were epigastric pain (51.6%), dysphagia (13.6%) and odynophagia (7.1%). The most common endoscopy finding was gastritis (40.2%), followed by normal examination (15.2%), oesophageal cancer (13.6%), gastric ulcer (7.6%) and gastric cancer (7.1%). Patients older than 40 years (n=110) had significant findings including gastritis (50.9%), oesophageal cancer (22.7%) and gastric cancer (11.8%). However in younger patients, with the age range of 18-40 years (n=74), most examinations were normal (92.9%). Of the 176 patients able to undergo Helicobacter pylori testing 75.6% were positive. Helicobacter pylori infection was associated with statistically significant increase in gastritis, oesophageal cancer, gastric ulcer, gastric cancer, and duodenal ulcers (p-values< 0.05).



Conclusion: Gastritis, ulcerative disease, and upper gastrointestinal malignancies are common in South-Western Ugandansand are associated with a high prevalence of Helicobacter pylori.



Keywords: Upper gastrointestinal symptoms, Pathology, Urease test, Helicobacter pylori, Endoscopy, Uganda.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Petersena2015,

title = {Delayed switch of antiretroviral therapy after virologic failure associated with elevated mortality among HIV-infected adults in Africa},

author = {Maya L. Petersena and Linh Trana and Elvin H. Geng and Steven J. Reynoldsc and Andrew Kambugu and Robin Wood and David R. Bangsbergh and Constantin T. Yiannoutsos and Steven G. Deek and Jeffrey N. Martin},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Delayed-switch-of-antiretroviral-therapy-after-virologic-failure-associated-with-elevated-mortality-among-HIV-infected-adults-in-Africa.pdf},

doi = {10;28(14):2097-107},

year  = {2015},

date = {2015-09-10},

journal = {AIDS},

number = {28},

pages = {14},

abstract = {OBJECTIVE:



Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa.

DESIGN:



A cohort.

METHODS:



We examined patients with confirmed virologic failure on first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which switch time was randomly assigned. Inverse probability weights adjusted for measured confounders including time-updated CD4+ T-cell count and HIV RNA. Results: Among 823 patients with confirmed virologic failure, the cumulative incidence of switch 180 days after failure was 30% [95% confidence interval (CI) 27-33]. The majority of patients (74%) had not failed immunologically as defined by WHO criteria by the time of virologic failure. Adjusted mortality was higher for individuals who remained on first-line therapy than for those who had switched [odds ratio (OR) 2.1, 95% CI 1.1-4.2]. Among those without immunologic failure, the relative harm of failure to switch was similar (OR 2.4; 95% CI 0.99-5.8) to that of the entire cohort, although of borderline statistical significance.

CONCLUSION:



Among HIV-infected patients with confirmed virologic failure on first-line ART, remaining on first-line therapy led to an increase in mortality relative to switching. Our results suggest that detection and response to confirmed virologic failure could decrease mortality.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Burnett2015,

title = {Effect of Educational Outreach Timing and Duration on Facility Performance for Infectious Disease Care in Uganda: A Trial with Pre-Post and Cluster Randomized Controlled Components},

author = {Sarah M. Burnett and Martin K. Mbonye and Sarah Naikoba and Zawedde-Muyanja Stella and Stephen N. Kinoti and Allan Ronald and Timothy Rubashembusya and Kelly S. Willis and Robert Colebunders and Yukari C. Manabe and Marcia R. Weaver},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/EffectofEducationalOutreachTimingand-DurationonFacilityPerformancefor-InfectiousDiseaseCareinUganda.pdf},

doi = { 10.1371/journal.pone.0136966},

year  = {2015},

date = {2015-09-09},

journal = {PloS One},

volume = {10},

number = {9},

abstract = {BACKGROUND:



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.

METHODS:



This study was conducted at 36 health facilities in Uganda, covering 1,275,960 outpatient visits over 23 months. From April 2010 to December 2010, 36 sites received infectious disease training; 18 randomly selected sites in arm A received nine monthly OSS visits (immediate OSS) and 18 sites in arm B did not. From March 2011 to September 2011, arm A sites received three additional visits every two months (extended OSS), while the arm B sites received eight monthly OSS visits (delayed OSS). We compared the combined effect of training and delayed OSS to training followed by immediate OSS to determine the effect of delaying OSS implementation by nine months. We also compared facility performance in arm A during the extended OSS to immediate OSS to examine the effect of additional, less frequent OSS.

RESULTS:



Delayed OSS, when combined with training, was associated with significant pre/post improvements in four indicators: outpatients triaged (44% vs. 87%, aRR = 1.54, 99% CI = 1.11, 2.15); emergency and priority patients admitted, detained, or referred (16% vs. 31%, aRR = 1.74, 99% CI = 1.10, 2.75); patients with a negative malaria test result prescribed an antimalarial (53% vs. 34%, aRR = 0.67, 99% CI = 0.55, 0.82); and pneumonia suspects assessed for pneumonia (6% vs. 27%, aRR = 2.97, 99% CI = 1.44, 6.17). Differences between the delayed OSS and immediate OSS arms were not statistically significant for any of the nine indicators (all adjusted relative RR (aRRR) between 0.76-1.44, all p>0.06). Extended OSS was associated with significant improvement in two indicators (outpatients triaged: aRR = 1.09, 99% CI = 1.01; emergency and priority patients admitted, detained, or referred: aRR = 1.22, 99% CI = 1.01, 1.38) and decline in one (pneumonia suspects assessed for pneumonia: aRR: 0.93; 99% CI = 0.88, 0.98).

CONCLUSIONS:



Educational outreach held up to nine months after training had similar effects on facility performance as educational outreach started within one month post-training. Six months of bi-monthly educational outreach maintained facility performance gains, but incremental improvements were heterogeneous.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nabeta2015,

title = {Serum vitamin D status in children with protein-energy malnutrition admitted to a national referral hospital in Uganda},

author = {Henry W. Nabeta and Josephine Kasolo and Reuben K. Kiggunda and Agnes N. Kiragga and Sarah Kiguli 

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Serum-vitamin-D-status-in-children-with-protein-energy-malnutrition-admitted-to-a-national-referral-hospital-in-Uganda.pdf},

doi = {10.1186/s13104-015-1395-2},

year  = {2015},

date = {2015-09-07},

journal = {BMC Research Notes},

volume = {8},

abstract = {BACKGROUND:



Vitamin D deficiency is a world-wide epidemic with recent estimates indicating that greater than 50% of the global population is at risk. In Uganda, 80% of healthy community children in a survey were found to be vitamin D insufficient. Protein-energy malnutrition is likely to be associated with vitamin D intake deficiency. The aim of this study was to determine the prevalence of vitamin D deficiency and the associated factors among children admitted with protein-energy malnutrition to the pediatrics wards of Mulago hospital in Kampala, Uganda.

METHODS:



Consecutive sampling was done with 158 children, aged 6-24 months, enrolled in a cross sectional study. One hundred and seventeen malnourished and 41 non malnourished children were enrolled from the Acute Care unit, pediatrics in-patient wards, outpatient and immunization clinics, following informed consent obtained from the children's parents/guardians. Children with protein energy malnutrition were categorized based on anthropometric measurements of weight-for-height and weight for length compared with the recommended WHO reference Z-score. Serum 25-hydroxyvitamin D, calcium and phosphate were assayed.

RESULTS:



One hundred seventeen malnourished and 41 non malnourished children were enrolled. The majority of study participants were male, 91 (57.6%). The mean serum vitamin D levels among the malnourished was 32.5 mmol/L (±12.0 SD) and 32.2 mmol/L (10.9 SD) among the malnourished, p = 0.868. Fifteen (36.6%) of the non malnourished children and 51 (43.6%) of the malnourished had suboptimal levels, p = 0.689. Malnourished children admitted with meningitis and cerebral palsy had lower serum vitamin D levels than those with other infections.

CONCLUSION:



There was no statistically significant difference in vitamin D values between the malnourished and non malnourished children. Clinicians should actively screen for children for serum vitamin D levels regardless of nutritional status.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Byakika-Kibwika2015,

title = {Lessons Learned from Implementing a Rapid Test of a Technology Device in a Tertiary Hospital in Uganda.},

author = {Byakika-Kibwika and Muwonge M. and Watts W and Kange J and Watts R.},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Lessons-Learned-from-Implementing-a-Rapid-Test-of-a-Technology-Device-in-a-Tertiary-Hospital-in-Uganda..pdf},

doi = {10.1016/j.aogh.2015},

year  = {2015},

date = {2015-09-02},

journal = {Annals of Globol Health},

volume = {81},

number = {5},

pages = {725-730},

abstract = {BACKGROUND:



Many African hospitals participate in technology research studies that take many months or years. Fewer sites have experience with rapid studies, conducted over a period of weeks. Such studies can benefit the institution and its patients in the short term, and in the long term can help prepare the institution for adopting the new technology.

OBJECTIVES:



We conducted a rapid validation study of consumer fitness device at Mulago National Referral and Teaching Hospital in Kampala, Uganda. In doing so, we captured valuable lessons about how to conduct a rapid study that will be useful to future researchers conducting similar fast-paced studies.

METHODS:



We conducted a descriptive study of a convenience sample of 57 patients. Patients who volunteered wore a fitness wristband device. Study staff collected vital signs using standard approaches.

FINDINGS:



Our findings were as follows: (1) effective partnership by local experts can ensure success; (2) a PI with experience working with the hospital ethics committee is essential to a rapid study; (3) reassurance that the study design benefits patients and the institution can help speed approval; (4) conduct detailed assessment of patient population in advance; (5) allow sufficient time for logistics arrangements; (6) quickly pivot the approach as needed, consistent with the protocol; (7) conduct data quality review on every shift; (8) conduct a supplies inventory at the end of each shift; (9) make rapid decisions about hiring and discontinuing study staff; (10) implement a patient location protocol at the start of the study; and (11) ensure availability of study staff refreshments in the study room.

CONCLUSION:



A rapid study of innovative technology can be successful at a hospital in a resource-limited setting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Imani2015,

title = {Effect of integrated infectious disease training and on-site support on the management of childhood illnesses in Uganda: a cluster randomized trial},

author = {Peace Imani and Brian Jakech and Ibrahim Kirunda and Martin K. Mbonye4,6, Sarah Naikoba4,6 and Marcia R. Weaver2

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Effect-of-integrated-infectious-disease-training-and-on-site-support-on-the-management-of-childhood-illnesses-in-Uganda-1.pdf},

doi = { doi: 10.1186/s12887-015-0410-z},

year  = {2015},

date = {2015-08-28},

journal = {BMC Pediatrics},

volume = {15},

abstract = {BACKGROUND:



The Integrated Infectious Disease Capacity-Building Evaluation (IDCAP) was designed to test the effects of two interventions, Integrated Management of Infectious Disease (IMID) training and on-site support (OSS), on clinical practice of mid-level practitioners. This article reports the effects of these interventions on clinical practice in management of common childhood illnesses.

METHODS:



Two trainees from each of 36 health facilities participated in the IMID training. IMID was a three-week core course, two one-week boost courses, and distance learning over nine months. Eighteen of the 36 health facilities were then randomly assigned to arm A, and participated in OSS, while the other 18 health facilities assigned to arm B did not. Clinical faculty assessed trainee practice on clinical practice of six sets of tasks: patient history, physical examination, laboratory tests, diagnosis, treatment, and patient/caregiver education. The effects of IMID were measured by the post/pre adjusted relative risk (aRR) of appropriate practice in arm B. The incremental effects of OSS were measured by the adjusted ratio of relative risks (aRRR) in arm A compared to arm B. All hypotheses were tested at a 5% level of significance.

RESULTS:



Patient samples were comparable across arms at baseline and endline. The majority of children were aged under five years; 84% at baseline and 97% at endline. The effects of IMID on patient history (aRR = 1.12; 95% CI = 1.04-1.21) and physical examination (aRR = 1.40; 95% CI = 1.16-1.68) tasks were statistically significant. OSS was associated with incremental improvement in patient history (aRRR = 1.18; 95% CI = 1.06-1.31), and physical examination (aRRR = 1.27; 95% CI = 1.02-1.59) tasks. Improvements in laboratory testing, diagnosis, treatment, and patient/caregiver education were not statistically significant.

CONCLUSION:



IMID training was associated with improved patient history taking and physical examination, and OSS further improved these clinical practices. On-site training and continuous quality improvement activities support transfer of learning to practice among mid-level practitioners.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Arenas-Pinto2015,

title = {Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial},

author = {Alejandro Arenas-Pinto, Jennifer Thompson, Godfrey Musoro, Hellen Musana, Abbas Lugemwa, Andrew Kambugu, Aggrey Mweemba, Dickens Atwongyeire, Margaret J. Thomason, A. Sarah Walker & Nicholas I. Paton For the EARNEST Trial Team},

doi = {https://doi.org/10.1007/s13365-015-0374-7},

year  = {2015},

date = {2015-08-25},

journal = {Journal of NeuroVirology},

pages = {104–113},

abstract = {Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective combination anti-retroviral therapy (ART). Data on PN on second-line ART is scarce. We assessed PN using a standard tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in a large Randomised Clinical Trial in Sub-Saharan Africa. Factors associated with PN were investigated using logistic regression. Symptomatic PN (SPN) prevalence was 22 % at entry (N = 1,251) and was associated (p < 0.05) with older age (OR = 1.04 per year), female gender (OR = 1.64), Tuberculosis (TB; OR = 1.86), smoking (OR = 1.60), higher plasma creatinine (OR = 1.09 per 0.1 mg/dl increase), CD4 count (OR = 0.83 per doubling) and not consuming alcohol (OR = 0.55). SPN prevalence decreased to 17 % by week 96 (p = 0.0002) following similar trends in all study groups (p = 0.30). Asymptomatic PN (APN) increased over the same period from 21 to 29 % (p = 0.0002). Signs suggestive of PN (regardless of symptoms) returned to baseline levels by week 96. At weeks 48 and 96, after adjusting for time-updated associations above and baseline CD4 count and viral load, SPN was strongly associated with TB (p < 0.0001). In summary, SPN prevalence was significantly reduced with PI-based second-line therapy across all treatment groups, but we did not find any advantage to the NRTI-free regimens. The increase of APN and stability of PN-signs regardless of symptoms suggest an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. SPN was strongly associated with isoniazid given for TB treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Guwatudde2015,

title = {The effect of standard dose multivitamin supplementation on disease progression in HIV-infected adults initiating HAART: a randomized double blind placebo-controlled trial in Uganda},

author = {David Guwatudde and Molin Wang and Amara E. Ezeamama and Danstan Bagenda and Rachel Kyeyune and Henry Wamani and Yukari C. Manabe and Wafaie W. Fawzi},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/The-effect-of-standard-dose-multivitamin-supplementation-on-disease-progression-in-HIVinfected-adults-initiating-HAART.pdf},

doi = {10.1186/s12879-015-1082-x},

year  = {2015},

date = {2015-08-19},

journal = {BMC Infectious Diseases},

volume = {15},

abstract = {BACKGROUND:



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.

METHODS:



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.

RESULTS:



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.

CONCLUSIONS:



One RDA of MV supplementation was safe but did not have an effect on indicators of disease progression among HIV infected adults initiating HAART},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Seden2015,

title = {Prevalence and type of drug–drug interactions involving ART in patients attending a specialist HIV outpatient clinic in Kampala, Uganda},

author = { K. Seden, C. Merry, R. Hewson, M. Siccardi, M. Lamorde, P. Byakika-Kibwika, E. Laker, R. Parkes-Ratanshi, D. J. Back, S. H. Khoo},

doi = {https://doi.org/10.1093/jac/dkv259},

year  = {2015},

date = {2015-08-18},

journal = {Journal of Antimicrobial Chemotherapy},

volume = {70},

number = {12},

pages = {3317–3322},

abstract = {Objectives



Scale-up of HIV services in sub-Saharan Africa has rapidly increased, necessitating evaluation of medication safety in these settings. Drug–drug interactions (DDIs) involving antiretrovirals (ARVs) in sub-Saharan Africa are poorly characterized. We evaluated the prevalence and type of ARV DDIs in Ugandan outpatients and identified the patients most at risk.



Methods



A total of 2000 consecutive patients receiving ARVs at the Infectious Diseases Institute, Kampala were studied. The most recent prescription for each patient was screened for clinically significant DDIs using www.hiv-druginteractions.org. Univariable and multivariable logistic regression were used to identify risk factors for DDIs. A screening tool was developed using significant risk factors and tested in a further 500 patients.



Results



Clinically significant DDIs were observed in 374 (18.7%) patients, with a total of 514 DDIs observed. Only 0.2% of DDIs involved a contraindicated combination. Comedications commonly associated with DDIs were antibiotics (4.8% of 2000 patients), anthelmintics (2.2%) and antifungals (3.5%). Patient age, gender, CD4 count and weight did not affect risk of DDIs. In multivariable analysis, the patient factors that independently increased risk of DDIs were two or more comedications (P < 0.0001), a PI-containing ARV regimen (P < 0.0001), use of an anti-infective (P < 0.0001) and WHO clinical stage 3–4 (P = 0.04). A scoring system based on having at least two of these risk factors identified between 75% and 90% of DDIs in a validation cohort.



Conclusions



Significant ARV DDIs occur at similar rates in resource-limited settings and developed countries; however, the comedications frequently causing DDIs differ. Development of tools that are relevant to particular settings should be a priority to assist with prevention and management of DDIs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kibuuka2015,

title = {Bacteremia among Febrile Ugandan Children Treated with Antimalarials Despite a Negative Malaria Test},

author = {Afizi Kibuuka,* Pauline Byakika-Kibwika, Jane Achan, Adoke Yeka, Joan N. Nalyazi, Arthur Mpimbaza, Philip J. Rosenthal, and Moses R. Kamya},

doi = { doi: 10.4269/ajtmh.14-0494},

year  = {2015},

date = {2015-08-05},

journal = {American Journal of Tropical Medicine and Hygiene},

volume = {93},

number = {2},

pages = {276–280},

abstract = {Bacteremia may be inappropriately treated as malaria in children admitted with a febrile illness in Africa. We determined the prevalence, clinical features, and spectrum of bacteremia among febrile children younger than 5 years of age admitted with a negative malaria test, but prescribed antimalarials at a referral hospital in Jinja, Uganda. After initial evaluation, a blood sample was drawn from 250 children for a complete blood count and bacterial culture. Of 250 samples cultured, 15 grew organisms presumed to be skin contaminants, and of the remaining 235 samples, 45 (19.1%) had bacteremia. Staphylococcus aureus (42%), non-typhoidal Salmonella (24%), Pseudomonas aeruginosa (11%), and Streptococcus pneumoniae (9%) were the most common bacterial isolates. On multivariate analysis, history of weight loss (odds ratio [OR] = 2.75; 95% confidence interval [CI] = 1.27–5.95), presence of pulmonary crackles (OR = 3.63; 95% CI = 1.40–9.45), and leukocytosis (OR = 2.21; 95% CI = 1.09–4.47) were independent predictors of bacteremia. At a referral hospital in Uganda, bacteremia was a remarkably common finding in children with febrile illness who were treated for malaria despite negative malaria test results.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Williams2015,

title = {Evaluation of Fingerstick Cryptococcal Antigen Lateral Flow Assay in HIV-Infected Persons: A Diagnostic Accuracy Study},

author = {Darlisha A. Williams, Tadeo Kiiza, Richard Kwizera, Reuben Kiggundu, Sruti Velamakanni, David B. Meya, Joshua Rhein, David R. Boulware},

doi = {https://doi.org/10.1093/cid/civ263},

year  = {2015},

date = {2015-08-01},

journal = {Clinical Infectious Diseases},

volume = {61},

number = {3},

pages = {464–467},

abstract = {Background. Cryptococcus neoformans is the most common cause of adult meningitis in sub-Saharan Africa. The cryptococcal antigen (CRAG) lateral flow assay (LFA) has simplified diagnosis as a point-of-care test approved for serum or cerebrospinal fluid (CSF). We evaluated the accuracy of the CRAG LFA using fingerstick whole blood compared with serum/plasma and CSF for diagnosing meningitis.



Methods. From August 2013 to August 2014, CRAG LFA (IMMY, Norman, Oklahoma) tests were performed on fingerstick whole blood, plasma/serum, and CSF in 207 HIV-infected adults with suspected meningitis in Kampala, Uganda. Venous blood was also collected and centrifuged to obtain serum and/or plasma. CSF was tested after lumbar puncture.



Results. Of 207 participants, 149 (72%) had fingerstick CRAG-positive results. There was 100% agreement between fingerstick whole blood and serum/plasma. Of the 149 fingerstick CRAG-positive participants, 138 (93%) had evidence of cryptococcal meningitis with a positive CSF CRAG. Eleven participants (5%) had isolated cryptococcal antigenemia with a negative CSF CRAG and culture, of whom 8 had CSF abnormalities (n = 3 lymphocytic pleocytosis, n = 5 elevated protein, n = 4 increased opening pressure). No persons with cryptococcal meningitis had negative fingersticks.



Conclusions. The 100% agreement between whole blood, serum, and plasma CRAG LFA results demonstrates that fingerstick CRAG is a reliable bedside diagnostic test. Using point-of-care CRAG testing simplifies screening large numbers of patients and enables physicians to prioritize on whom to measure CSF opening pressure using manometers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Acen2015,

title = {The frequency distribution of vitamin D Receptor fok I gene polymorphism among Ugandan pulmonary TB patients},

author = {Ester L. Acen and William Worodria and Peter Mulamba and Andrew Kambugu and Joseph Erum},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/The-frequency-distribution-of-vitamin-D-Receptor-fok-I-gene-polymorphism-among-Ugandan-pulmonary-TB-patients.pdf},

doi = { 10.12688/f1000research.9109.1},

year  = {2015},

date = {2015-07-29},

journal = {5},

abstract = {Background: Mycobacterium tuberculosis and especially in Africa. Vitamin D deficiency has been linked to TB in the past and studies have found vitamin D deficiency to be common among Ugandan TB patients. The functional activity of vitamin D is dependent on the genotype of the vitamin D receptor (VDR) polymorphic genes. Recent findings have indicated that VDR polymorphisms may cause increased resistance or susceptibility to TB. The vitamin D ligand and its receptor play a pivotal role in innate immunity by eliciting antimicrobial activity, which is important in prevention of TB. The  vitamin D receptor gene has extensively been fok I examined in TB patients but findings so far have been inconclusive. : This study sought to investigate the frequency distribution of theObjectives VDR gene polymorphisms in pulmonary TB patients and controls. fok I : A pilot case control study of 41 newly diagnosed TB patients and 41Methods healthy workers was set up. Vitamin D receptor  I gene was genotyped. fok The frequency distribution of genotype in Ugandan TB patientsResults: fok I was 87.8% homozygous-dominant (FF), 7.3% (Ff) heterozygous and 4.8% (ff) homozygous recessive. For normal healthy subjects the frequencies were (FF) 92.6%, (Ff) 2.4% and (ff) 4.8%. No significant difference was observed in the FF and ff genotypes among TB patients and controls. The Ff heterozygous genotype distribution appeared more in TB patients than in controls. A significant difference was observed in the  genotype among gender p value fok I 0.02. No significant difference was observed in ethnicity, p value 0.30. The heterozygous Ff  genotype may be associated with TBConclusions: fok I in the Ugandan population.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakiyingi2015,

title = {Predictors for MTB Culture-Positivity among HIV-Infected Smear-Negative Presumptive Tuberculosis Patients in Uganda: Application of New Tuberculosis Diagnostic Technology.},

author = {Lydia Nakiyingi and Bareng A. S. Nonyane and Willy Ssengooba and Bruce J. Kirenga and Damalie Nakanjako and Gloria Lubega and Pauline Byakika-Kibwika and Moses L. Joloba and Jerry J. Ellner and Susan E. Dorman and Harriet Mayanja-Kizza and Yukari C. Manabe},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/PredictorsforMTBCulture-Positivity-among-HIV-InfectedSmear-Negative-Presumptive-TuberculosisPatientsinUganda.pdf},

doi = { doi: 10.1371/journal.pone.0133756},

year  = {2015},

date = {2015-07-29},

journal = {PloS One},

volume = {10},

number = {7},

abstract = {BACKGROUND:



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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Osingada2015,

title = {Nurses' knowledge in ethics and their perceptions regarding continuing ethics education: a cross-sectional survey among nurses at three referral hospitals in Uganda},

author = {Charles Peter Osingada and Gorrette Nalwadda and Tom Ngabirano and John Wakida and Nelson Sewankambo and Damalie Nakanjako

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Nurses-knowledge-in-ethics-and-their-perceptions-regarding-continuing-ethics-education-a-cross-sectional-survey-among-nurses-at-three-referral-hospitals-in-Uganda.pdf},

doi = {10.1186/s13104-015-1294-6},

year  = {2015},

date = {2015-07-29},

journal = {BMC Research Notes},

volume = {8},

abstract = {BACKGROUND:



High disease burden and scarcity of healthcare resources present complex ethical dilemmas for nurses working in developing countries. We assessed nurses' knowledge in ethics and their perceptions about Continuous Nurses' Ethics Education (CNEE) for in-service nurses.

METHODS:



Using an anonymous, pre-tested self-administered questionnaire, we assessed nurses' knowledge in basic ethics concepts at three regional hospitals in Uganda. Adequate knowledge was measured by a score ≥50% in the knowledge assessment test. Nurses' perceptions on CNEE were assessed using a six-point Likert scale.

RESULTS:



Of 114 nurses, 91% were female; with mean age 44.7 (SD 10) years. Half were diploma, 47 (41%) certificates, 6 (5%) bachelors' degrees and one masters' level training. Overall, 18 (16%) scored ≥50% in the ethics knowledge test. Nurses with diploma or higher level of nursing training were less likely to fail the ethics knowledge than certificate-level nurses (OR 0.14, 95% CI: 0.02-0.7). Only 45% had ever attended at least one CNEE session and up to 93% agreed that CNEE is required to improve nurses' ethics knowledge and practice.

CONCLUSIONS:



Nurses exhibited low knowledge in ethics and positive attitudes towards CNEE. We recommend structured CNEE programs to address basic concepts in nursing ethics and their application in clinical practice},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Goovaerts2015,

title = {Lower Pre-Treatment T Cell Activation in Early- and Late-Onset Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome. },

author = {Odin Goovaerts and Wim Jennes and Marguerite Massinga-Loembé and Pascale Ondoa and Ann Ceulemans and Chris Vereecken and William Worodria and Harriet Mayanja-Kizza and Robert Colebunders and LucKestens and TB-IRIS Study Group},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Lower-Pre-Treatment-T-Cell-Activation-in-Early-and-Late-Onset-Tuberculosis-Associated-Immune-Reconstitution-Inflammatory-Syndrome.-.pdf},

doi = {10.1371/journal.pone.0133924},

year  = {2015},

date = {2015-07-27},

journal = {PloS One},

volume = {10},

number = {1},

abstract = {BACKGROUND:



Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients receiving antiretroviral therapy (ART). The role of disturbed T cell reconstitution in TB-IRIS is not well understood. We investigated T cell activation and maturation profiles in patients who developed TB-IRIS at different intervals during ART.

METHODS:



Twenty-two HIV-TB patients who developed early-onset TB-IRIS and 10 who developed late-onset TB-IRIS were matched for age, sex and CD4 count to equal numbers of HIV-TB patients who did not develop TB-IRIS. Flow cytometry analysis was performed on fresh blood, drawn before and after ART initiation and during TB-IRIS events. T cell activation and maturation was measured on CD4+ and CD8+ T cells using CD45RO, CD38, HLA-DR, CCR7 and CD27 antibodies.

RESULTS:



CD8+ T cell activation before ART was decreased in both early-onset (77% vs. 82%, p = 0.014) and late-onset (71% vs. 83%, p = 0.012) TB-IRIS patients compared to non-IRIS controls. After ART initiation, the observed differences in T cell activation disappeared. During late-onset, but not early-onset TB-IRIS, we observed a skewing from memory to terminal effector CD4+ and CD8+ T cell populations (p≤0.028).

CONCLUSION:



Our data provide evidence of reduced CD8+ T cell activation before ART as a common predisposing factor of early- and late-onset TB-IRIS. The occurrence of TB-IRIS itself was not marked by an over-activated CD8+ T cell compartment. Late- but not early-onset TB-IRIS was characterized by a more terminally differentiated T cell phenotype.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cox2015b,

title = {Accuracy of Lipoarabinomannan and Xpert MTB/RIF Testing in Cerebrospinal Fluid To Diagnose Tuberculous Meningitis in an Autopsy Cohort of HIV-Infected Adults},

author = {Janneke A. Cox, Robert L. Lukande, Sam Kalungi, Eric Van Marck, Martin Lammens, Koen Van de Vijver, Andrew Kambugu, Ann M. Nelson, Robert Colebunders, Yukari C. Manabe},

doi = {DOI: https://doi.org/10.1128/JCM.00624-15},

year  = {2015},

date = {2015-07-20},

journal = {Journal of Clinical Microbiology},

volume = {53},

number = {8},

pages = {2667-2673},

abstract = {Point-of-care tests for tuberculous meningitis (TBM) are needed. We studied the diagnostic accuracy of the lipoarabinomannan (LAM) lateral flow assay (LFA), LAM enzyme-linked immunosorbent assay (ELISA), and Xpert MTB/RIF in cerebrospinal fluid (CSF) in an autopsy cohort of Ugandan HIV-infected adults. We obtained written informed consent postmortem from the next of kin. 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 samples. 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 a sensitivity of 43%, and Xpert MTB/RIF a sensitivity of 100% and specificities of 87%, 91%, and 87%, respectively. LAM LFA had a sensitivity of 50% for definite and probable histopathological TBM, ELISA a sensitivity of 38%, and Xpert MTB/RIF a sensitivity of 86% and specificities of 70%, 91%, and 87%, respectively. LAM LFA had a sensitivity of 68% for the composite standard and ELISA a sensitivity of 48% and specificities of 78% and 98%, respectively. The rapid diagnostic tests detected TBM in 22% to 78% of patients not on anti-TB treatment. Point-of-care tests have high accuracy in diagnosis of TBM in deceased HIV-infected adults. LAM LFA in CSF is a useful additional diagnostic tool},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Haas2015,

title = {Monitoring and Switching of First-line Antiretroviral Therapy in sub-Saharan Africa: Collaborative Analysis of Adult Treatment Cohorts},

author = {Andreas D. Haas and Olivia Keiser and Eric Balestre and Steve Brown and Emmanuel Bissagnene and Cleophas Chimbetete and François Dabis and Mary-Ann Davies and Christopher J. Hoffmann and Patrick Oyaro and Rosalind Parkes-Ratanshi and Steven J. Reynolds and Izukanji Sikazwe and Kara Wools-Kaloustian and Djimon Marcel Zannou and Gilles Wandeler and Matthias Egger and for IeDEA Southern Africa, East Africa and West Africa},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Monitoring-and-Switching-of-First-line-Antiretroviral-Therapy-in-sub-Saharan-Africa.pdf},

doi = {0.1016/S2352-3018(15)00087-9},

year  = {2015},

date = {2015-07-16},

journal = {The Lancent HIV},

volume = {2},

number = {7},

pages = {271-8},

abstract = {BACKGROUND:



HIV-1 viral load testing is recommended to monitor antiretroviral therapy (ART) but is not universally available. The aim of our study was to assess monitoring of first-line ART and switching to second-line ART in sub-Saharan Africa.

METHODS:



We did a collaborative analysis of cohort studies from 16 countries in east Africa, southern Africa, and west Africa that participate in the international epidemiological database to evaluate AIDS (IeDEA). We included adults infected with HIV-1 who started combination ART between January, 2004, and January, 2013. We defined switching of ART as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibitor, with adjustment of one or more nucleoside reverse-transcriptase inhibitors (NRTIs). Virological and immunological failures were defined according to WHO criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% CIs comparing routine viral load monitoring, targeted viral load monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and individual characteristics.

FINDINGS:



Of 297,825 eligible patients, 10,352 (3%) switched to second-line ART during 782 ,412 person-years of follow-up. Compared with CD4 monitoring, hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine viral load monitoring, 1·21 (1·13-1·30) for targeted viral load monitoring, and 0·49 (0·43-0·56) for clinical monitoring. Of 6450 patients with confirmed virological failure, 58·0% (95% CI 56·5-59·6) switched by 2 years, and of 15,892 patients with confirmed immunological failure, 19·3% (18·5-20·0) switched by 2 years. Of 10,352 patients who switched, evidence of treatment failure based on one CD4 count or viral load measurement ranged from 86 (32%) of 268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral load monitoring. Median CD4 counts at switching were 215 cells per μL (IQR 117-335) with routine viral load monitoring, but were lower with other types of monitoring (range 114-133 cells per μL).

INTERPRETATION:



Overall, few patients switched to second-line ART and switching happened late in the absence of routine viral load monitoring. Switching was more common and happened earlier after initiation of ART with targeted or routine viral load testing.

FUNDING:



National Institute of Allergy and Infectious Diseases, Swiss National Science Foundation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ssengooba2015,

title = {High Genotypic Discordance of Concurrent Mycobacterium tuberculosis Isolates from Sputum and Blood of HIV-Infected Individuals. },

author = {Willy Ssengooba and Frank G. Cobelens and LydiaNakiyingi and Gerald Mboowa and Derek T.Armstrong6,Yukari C. Manabe and Moses L. Joloba and Bouke C. deJong},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/High-Genotypic-Discordance-of-Concurrent-Mycobacterium-tuberculosis-Isolates-from-Sputum-and-Blood-of-HIV-Infected-Individuals.-.pdf},

doi = {10.1371/journal.pone.0132581},

year  = {2015},

date = {2015-07-15},

journal = {PloS One},

volume = {10},

number = {7},

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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Acuña-Villaorduña2015,

title = {High mortality associated with retreatment of tuberculosis in a clinic in Kampala, Uganda: a retrospective study},

author = {Carlos Acuña-Villaorduña, Irene Ayakaka, Scott Dryden-Peterson, Susan Nakubulwa, William Worodria, Nancy Reilly, Jennifer Hosford, Kevin P. Fennelly, Alphonse Okwera, and Edward C. Jones-López},

doi = { doi: 10.4269/ajtmh.14-0810},

year  = {2015},

date = {2015-07-08},

journal = {American Journal of Tropical Medicine and Hygiene},

volume = {93},

number = {1},

pages = {73–75},

abstract = {The World Health Organization recommends for tuberculosis retreatment a regimen of isoniazid (H), rifampicin (R), ethambutol (E), pyrazinamide (Z), and streptomycin (S) for 2 months, followed by H, R, E, and Z for 1 month and H, R, and E for 5 months. Using data from the National Tuberculosis and Leprosy Program registry, this study determined the long-term outcome under programmatic conditions of patients who were prescribed the retreatment regimen in Kampala, Uganda, between 1997 and 2003. Patients were traced to determine their vital status; 62% (234/377) patients were found dead. Having ≤ 2 treatment courses and not completing retreatment were associated with mortality in adjusted analyses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Castelnuovo2015b,

title = {Quantifying retention during pre-antiretroviral treatment in a large urban clinic in Uganda},

author = {Barbara Castelnuovo and Joseph Musaazi and Rachel Musomba and Rosalind Parkes Ratanshi and Agnes N. Kiragga

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Quantifying-retention-during-pre-antiretroviral-treatment-in-a-large-urban-clinic-in-Uganda.pdf},

doi = {10.1186/s12879-015-0957-1.},

year  = {2015},

date = {2015-07-01},

journal = {BMC Infectious Diseases},

volume = {15},

abstract = {BACKGROUND:



Retention studies are usually focused on patients on antiretroviral treatment (ART), however in Sub-Saharan Africa many patients get lost to program (LTP) in the pre-ART care period.. We investigated the proportion of patients not retained in care and factors associated with LTP (dead or lost to follow up ≥6 months) in the pre-ART care period.

METHODS:



We analyzed data from the Infectious Diseases Institute, Kampala, Uganda. We included all adult patients ≥18 years, ART naïve at program enrollment from 1(st)/Jan/2005. We described the number of patients not retained in care during the 3 steps of enrollment-to-treatment "cascade": Step 1) From enrollment to CD4 count testing, Step 2) ART eligibility assessment. Patients were initially considered eligible if CD4 count was <200 cell/μL, and <350 cell/μL from 2012 onwards; Step 3) From eligibility to ART start. We described cumulative probability of being LTP by gender and ART eligibility using Kaplan Meier estimates. We used a Cox proportional hazards model to identify factors associated with being LTP at any stage for all patients and for those with a CD4 count available. Factors considered were age, gender, year of enrollment, and WHO stage.

RESULTS AND DISCUSSION:



After enrollment in our program, cumulatively, a low proportion of patients (30.8 %) were retained and started on ART. The cumulative probability of being LTP was higher in males and patients not eligible for ART. In the multivariable Cox proportional Hazards model, male gender (HR: 1.19 CI 1.12-1.19) and clinical WHO stage 3 and 4 (HR: 1.20 CI 1.13-1.27) were associated with being LTP while older age was protective (HR: 0.98 0.96-0.99). Patients enrolled in the program more recently were also at lower risk of being LTP. In addition, among patients with CD4 count test, patients with higher CD4 count were at higher risk of being LTP.

CONCLUSIONS:



In our program there has been suboptimal retention of patients in pre-ART care, particularly of patients not eligible for ART. Since the proportion of eligible patients has recently increased due to the higher recommended threshold for ART eligibility (CD4 count > 500 cell/μL in 2014), this could lead to an increase in program retention as more people fall under the recommended threshold and seek care.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kuznik2015,

title = {Estimating the Public Health Burden Associated With Adverse Pregnancy Outcomes Resulting From Syphilis Infection Across 43 Countries in Sub-Saharan Africa.},

author = {Andreas Kuznik and Abdulrazaq G. Habib and Yukari C. Manabe and Mohammed Lamorde},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Estimating-the-public-health-burden-associated-with-adverse-pregnancy-outcomes-resulting-from-syphilis-infection-across-43-countries-in-sub-Saharan-Africa.pdf},

doi = {10.1097/OLQ.0000000000000291},

year  = {2015},

date = {2015-07-01},

journal = {Sexually Transmitted Diseases},

volume = {42},

number = {7},

pages = {369-375},

abstract = {BACKGROUND:



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.

METHODS:



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).

RESULTS:



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.

CONCLUSIONS:



Substantial infant mortality and morbidity results from maternal syphilis infection concentrated in countries with low access to ANC or low rates of syphilis screening.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Elliott2015,

title = {Capacity for science in sub-Saharan Africa},

author = {Alison Elliott, Barbara Nerima, Bernard Bagaya, Andrew Kambugu, Moses Joloba, Stephen Cose, Guiseppe Pantaleo, Maria Yazdanbakhsh, David Mabey, David Dunne, Ashley Moffett, Eli Katunguka Rwakishaya, Pontiano Kaleebu, Edward Katongole Mbidde},

url = {https://sci-hub.hkvisa.net/10.1016/S0140-6736(15)61111-4},

doi = {DOI:https://doi.org/10.1016/S0140-6736(15)61111-4},

year  = {2015},

date = {2015-06-20},

journal = {The Lancet},

volume = {385},

number = {9986},

pages = {2435-2437},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ocama2015,

title = {Hepatitis B and HIV co-infection is still treated using lamivudine-only antiretroviral therapy combination in Uganda },

author = {P Ocama, E Seremba, B Apica, K Opio

},

doi = { DOI: 10.4314/ahs.v15i2.4 },

year  = {2015},

date = {2015-06-01},

journal = {African Health Sciences},

volume = {15},

number = {2},

pages = {328-333},

abstract = {Background: 

Hepatitis B virus (HBV) and HIV are endemic in Uganda. Co-infection is common and leads to rapid progression of liver disease. Burden of co-infection is unknown yet most patients are on lamivudine-only ART where resistance is frequent. Most patients are initiated on antiretroviral therapy (ART) without knowing their HBV status.



Objectives: 

To determine burden of co-infection and HBV viral suppression among patients on ART in NorthernUganda.

Methods: We recruited HIV infected adult patients on ART in a cross-sectional study. Age, sex, ART regimen and duration were recorded. Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBcAb) and liver panel were performed. For those HBsAg+, hepatitis B e antigen (HBeAg) and HBV DNA were performed. CD4 cell count was recorded.



Results:

Three hundred patients were recruited. Twenty (6.7%) were co-infected, while 41% were anti-HBcAb+. Overall 188 (62.7%) were on lamivudine- only HBV active drug. Median ART duration 2 years (IQR 1-5), mean CD4+ cell count 317 cells/microlitre (SD 255-557). Of 20 HIV/HBV co-infected, 11/20 (55%) were on lamivudine-only ART, median duration 1.5 years. Nineteen (95%) had undetectable HBV DNA. Seventeen (85%) were HBeAg negative. Mean CD4+ cell count 327 cells/microlitre (SD 197-482).



Conclusion: 

A large proportion of patients were on lamivudine- only HBV-active ART. Resistance may occur long term thus testing for HBV and correct ART is recommended



Key words: HIV, HBV, Co-infection, Treatment},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kuznik2015b,

title = {Antenatal Syphilis Screening Using Point-Of-Care Testing in Low- and Middle-Income Countries in Asia and Latin America: A Cost-Effectiveness Analysis},

author = {Andreas Kuznik, Christine Muhumuza, Henry Komakech, Elsa M. R. Marques, Mohammed Lamorde},

doi = {https://doi.org/10.1371/journal.pone.0127379},

year  = {2015},

date = {2015-05-26},

journal = {PLOS ONE},

volume = {10},

number = {5},

pages = {e0127379},

abstract = {Background



Untreated syphilis in pregnancy is associated with adverse clinical outcomes to the infant. In low- and middle-income countries in Asia and Latin America, 20%-30% of women are not tested for syphilis during pregnancy. We evaluated the cost-effectiveness of increasing the coverage for antenatal syphilis screening in 11 Asian and 20 Latin American countries, using a point-of-care immunochromatographic strip (ICS) test.



Methods



The decision analytical cost-effectiveness models reported incremental costs per disability-adjusted life years (DALYs) averted from the perspectives of the national health care payer. Clinical outcomes were stillbirths, neonatal deaths, and congenital syphilis. DALYs were computed using WHO disability weights. Costs included the ICS test, three injections of benzathine penicillin, and nurse wages. Country-specific inputs included the antenatal prevalence of syphilis and the proportion of women in the antenatal care setting that are screened for syphilis infection as reported in the 2014 WHO baseline report on global sexually transmitted infection surveillance. Country-specific data on the annual number of live births, proportion of women with at least one antenatal care visit, and per capita gross national income were also included in the model.



Results



The incremental cost/DALY averted of syphilis screening is US$53 (range: US$10-US$332; Prob<1*per capita GDP=99.71%) in Asia and US$60 (range: US$5-US$225; Prob<1*per capita GDP=99.77%) in Latin America. Universal screening may reduce the annual number of stillbirths by 20,344 and 4,270, neonatal deaths by 8,201 and 1,721, cases of congenital syphilis by 10,952 and 2,298, and avert 925,039 and 197,454 DALYs in the aggregate Asian and Latin American panel, respectively.



Conclusion



Antenatal syphilis screening is highly cost-effective in all the 11 Asian and 20 Latin American countries assessed. Our findings support the decision to expand syphilis screening in countries with currently low screening rates or continue national syphilis screening programs in countries with high rates.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Meya2015b,

title = {Cellular Immune Activation in Cerebrospinal Fluid From Ugandans With Cryptococcal Meningitis and Immune Reconstitution Inflammatory Syndrome},

author = {David B. Meya, Samuel Okurut, Godfrey Zziwa, Melissa A. Rolfes, Melander Kelsey, Steve Cose, Moses Joloba, Prossy Naluyima, Brent E. Palmer, Andrew Kambugu, Harriet Mayanja-Kizza, Paul R. Bohjanen, Michael A. Eller, Sharon M. Wahl, David R. Boulware, Yuka C. Manabe, Edward N. Janoff},

doi = {https://doi.org/10.1093/infdis/jiu664},

year  = {2015},

date = {2015-05-15},

journal = {The Journal of Infectious Diseases},

volume = {211},

number = {10},

pages = {1597–1606},

abstract = {Background. 

Human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is characterized by high fungal burden and limited leukocyte trafficking to cerebrospinal fluid (CSF). The immunopathogenesis of CM immune reconstitution inflammatory syndrome (IRIS) after initiation of antiretroviral therapy at the site of infection is poorly understood.



Methods. 

We characterized the lineage and activation status of mononuclear cells in blood and CSF of HIV-infected patients with noncryptococcal meningitis (NCM) (n = 10), those with CM at day 0 (n = 40) or day 14 (n = 21) of antifungal therapy, and those with CM-IRIS (n = 10).



Results. 

At diagnosis, highly activated CD8+ T cells predominated in CSF in both CM and NCM. CM-IRIS was associated with an increasing frequency of CSF CD4+ T cells (increased from 2.2% to 23%; P = .06), a shift in monocyte phenotype from classic to an intermediate/proinflammatory, and increased programmed death ligand 1 expression on natural killer cells (increased from 11.9% to 61.6%, P = .03). CSF cellular responses were distinct from responses in peripheral blood.



Conclusions. 

After CM, T cells in CSF tend to evolve with the development of IRIS, with increasing proportions of activated CD4+ T cells, migration of intermediate monocytes to the CSF, and declining fungal burden. These changes provide insight into IRIS pathogenesis and could be exploited to more effectively treat CM and prevent CM-IRIS.



Key Terms

cryptococcal meningitis, cryptococcus, HIV, cerebrospinal fluid, immune responses, cell activation



Topic:

phenotype antifungal agents cryptococcal meningitis natural killer cells ligands monocytes t-lymphocytes cerebrospinal fluid diagnosis immune reconstitution inflammatory syndrome },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wandera2015,

title = {Alcohol Consumption among HIV-Infected Persons in a Large Urban HIV Clinic in Kampala Uganda: A Constellation of Harmful Behaviors},

author = {Bonnie Wandera, Nazarius Mbona Tumwesigye, Joaniter Immaculate Nankabirwa, Andrew Ddungu Kambugu, Rosalind Parkes-Ratanshi, David Kaawa Mafigiri, Saidi Kapiga, Ajay K. Sethi},

doi = {https://doi.org/10.1371/journal.pone.0126236},

year  = {2015},

date = {2015-05-11},

journal = {PLOS ONE},

volume = {10},

number = {5},

pages = {e0126236},

abstract = {Introduction



Alcohol use by persons living with HIV/AIDS (PLWHA) negatively impacts the public health benefits of antiretroviral therapy (ART). Using a standardized alcohol assessment tool, we estimate the prevalence of alcohol use, identify associated factors, and test the association of alcohol misuse with sexual risk behaviors among PLWHA in Uganda.



Methods



A cross-section of PLWHA in Kampala were interviewed regarding their sexual behavior and self-reported alcohol consumption in the previous 6 months. Alcohol use was assessed using the alcohol use disorders identification test (AUDIT). Gender-stratified log binomial regression analyses were used to identify independent factors associated with alcohol misuse and to test whether alcohol misuse was associated with risky sexual behaviors.



Results



Of the 725 subjects enrolled, 235 (33%) reported any alcohol use and 135 (18.6%) reported alcohol misuse, while 38 (5.2%) drank hazardous levels of alcohol. Alcohol misuse was more likely among subjects not yet on ART (adjusted prevalence ratio [aPR] was 1.65 p=0.043 for males and 1.79, p=0.019 for females) and those with self-reported poor adherence (aPR for males=1.56, p=0.052, and for females=1.93, p=0.0189). Belonging to Pentecostal or Muslim religious denominations was protective against alcohol misuse compared to belonging to Anglican and Catholic denominations in both sexes (aPR=0.11 for men, p<0.001, and aPR=0.32 for women, p=0.003). Alcohol misuse was independently associated with reporting risky sexual behaviors (aPR=1.67; 95% CI: 1.07–2.60, p=0.023) among males, but not significant among females (aPR=1.29; 95% CI: 0.95–1.74, p=0.098). Non-disclosure of HIV positive status to sexual partner was significantly associated with risky sex in both males (aPR=1.69; p=0.014) and females (aPR 2.45; p<0.001).



Conclusion



Alcohol use among PLWHA was high, and was associated with self-reported medication non-adherence, non-disclosure of HIV positive status to sexual partner(s), and risky sexual behaviors among male subjects. Interventions targeting alcohol use and the associated negative behaviors should be tested in this setting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Koss2015,

title = {A Clinical Predictor Score for 30-Day Mortality among HIV-Infected Adults Hospitalized with Pneumonia in Uganda.},

author = {Catherine A. Koss, Leah G. Jarlsberg, Saskia den Boon, Adithya Cattamanchi, J. Lucian Davis, William Worodria, Irene Ayakaka, Ingvar Sanyu, Laurence Huang, International HIV-associated Opportunistic Pneumonias (IHOP) Study},

doi = {https://doi.org/10.1371/journal.pone.0126591},

year  = {2015},

date = {2015-05-11},

journal = {PLOS ONE},

volume = {10},

number = {5},

pages = {e0126591},

abstract = {Background



Pneumonia is a major cause of mortality among HIV-infected patients. Pneumonia severity scores are promising tools to assist clinicians in predicting patients’ 30-day mortality, but existing scores were developed in populations infected with neither HIV nor tuberculosis (TB) and include laboratory data that may not be available in resource-limited settings. The objective of this study was to develop a score to predict mortality in HIV-infected adults with pneumonia in TB-endemic, resource-limited settings.



Methods



We conducted a secondary analysis of data from a prospective study enrolling HIV-infected adults with cough ≥2 weeks and <6 months and clinically suspected pneumonia admitted to Mulago Hospital in Kampala, Uganda from September 2008 to March 2011. Patients provided two sputum specimens for mycobacteria, and those with Ziehl-Neelsen sputum smears that were negative for mycobacteria underwent bronchoscopy with inspection for Kaposi sarcoma and testing for mycobacteria and fungi, including Pneumocystis jirovecii. A multivariable best subsets regression model was developed, and one point was assigned to each variable in the model to develop a clinical predictor score for 30-day mortality.



Results



Overall, 835 patients were studied (mean age 34 years, 53.4% female, 30-day mortality 18.2%). A four-point clinical predictor score was identified and included heart rate >120 beats/minute, respiratory rate >30 breaths/minute, oxygen saturation <90%, and CD4 cell count <50 cells/mm3. Patients’ 30-day mortality, stratified by score, was: score 0 or 1, 12.6%, score 2 or 3, 23.4%, score 4, 53.9%. For each 1 point change in clinical predictor score, the odds of 30-day mortality increased by 65% (OR 1.65, 95% CI 1.39-1.96, p <0.001).



Conclusions



A simple, four-point scoring system can stratify patients by levels of risk for mortality. Rapid identification of higher risk patients combined with provision of timely and appropriate treatment may improve clinical outcomes. This predictor score should be validated in other resource-limited settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Surowiec2015,

title = {Metabolic Signature Profiling as a Diagnostic and Prognostic Tool in Pediatric Plasmodium falciparum Malaria },

author = {Izabella Surowiec, Judy Orikiiriza, Elisabeth Karlsson, Maria Nelson, Mari Bonde, Patrick Kyamanwa, Ben Karenzi, Sven Bergström, Johan Trygg, Johan Normark},

doi = { https://doi.org/10.1093/ofid/ofv062},

year  = {2015},

date = {2015-05-04},

journal = {Open Forum Infectious Diseases},

volume = {2},

number = {2},

pages = {ofv062},

abstract = {Background. Accuracy in malaria diagnosis and staging is vital to reduce mortality and post infectious sequelae. In this study, we present a metabolomics approach to diagnostic staging of malaria infection, specifically Plasmodium falciparum infection in children.



Methods. A group of 421 patients between 6 months and 6 years of age with mild and severe states of malaria with age-matched controls were included in the study, 107, 192, and 122, individuals, respectively. A multivariate design was used as basis for representative selection of 20 patients in each category. Patient plasma was subjected to gas chromatography-mass spectrometry analysis, and a full metabolite profile was produced from each patient. In addition, a proof-of-concept model was tested in a Plasmodium berghei in vivo model where metabolic profiles were discernible over time of infection.



Results. A 2-component principal component analysis revealed that the patients could be separated into disease categories according to metabolite profiles, independently of any clinical information. Furthermore, 2 subgroups could be ide.jpegied in the mild malaria cohort who we believe represent patients with divergent prognoses.



Conclusions. Metabolite signature profiling could be used both for decision support in disease staging and prognostication.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Abassi2015,

title = {Cryptococcal Meningitis: Diagnosis and Management Update},

author = {Mahsa Abassi, David R. Boulware & Joshua Rhein },

doi = {https://doi.org/10.1007/s40475-015-0046-y},

year  = {2015},

date = {2015-04-25},

journal = {Current Tropical Medicine Reports volume},

pages = {90-99},

abstract = {Recent advances in the diagnosis and management of cryptococcal meningitis are promising and have been improving long-term survival. Point of care testing has made diagnosing cryptococcal meningitis rapid, practical, and affordable. Targeted screening and treatment programs for cryptococcal antigenemia are a cost-effective method for reducing early mortality on antiretroviral therapy (ART). Optimal initial management with amphotericin and flucytosine improves survival against alternative therapies, although amphotericin is difficult to administer and flucytosine is not available in middle- or low-income countries, where cryptococcal meningitis is most prevalent. Controlling increased intracranial pressure with serial therapeutic lumbar punctures has a proven survival benefit. Delaying ART initiation for 4 weeks after the diagnosis of cryptococcal meningitis is associated with improved survival. Fortunately, new approaches have been leading the way toward improving care for cryptococcal meningitis patients. New trials utilizing different combinations of antifungal therapy are reviewed, and we summarize the efficacy of different regimens.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cox2015,

title = {Is Urinary Lipoarabinomannan the Result of Renal Tuberculosis? Assessment of the Renal Histology in an Autopsy Cohort of Ugandan HIV-Infected Adults},

author = {Janneke A. Cox , Robert L. Lukande, Sam Kalungi, Eric Van Marck, Koen Van de Vijver, Andrew Kambugu, Ann M. Nelson, Robert Colebunders, Yukari C. Manabe

},

doi = {https://doi.org/10.1371/journal.pone.0123323},

year  = {2015},

date = {2015-04-21},

journal = {PLOS ONE},

volume = {10},

number = {4},

pages = { e0123323},

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.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Meya2015,

title = {Preventing Cryptococcosis-Shifting the Paradigm in the Era of Highly Active Antiretroviral Therapy. },

author = {David Meya, Radha Rajasingham, Elizabeth Nalintya, Mark Tenforde & Joseph N Jarvis },

doi = {https://doi.org/10.1007/s40475-015-0045-z},

year  = {2015},

date = {2015-04-21},

journal = {Current Tropical Medicine Reports volume},

abstract = {Cryptococcosis remains a significant cause of morbidity and mortality among HIV-infected patients, especially in sub-Saharan Africa where it causes up to 20 % of AIDS-related deaths in HIV programs. A new, highly sensitive, and affordable point of care diagnostic test for cryptococcal infection, the lateral flow assay, can detect early sub-clinical cryptococcosis especially in areas with limited laboratory infrastructure. With a prevalence of detectable sub-clinical cryptococcal infection averaging 7.2 % (95 % CI 6.8–7.6 %) among 36 cohorts with CD4 <100 cells/μL in Africa, together with data showing that preemptive fluconazole prevents overt cryptococcal disease in this population, implementing a screen and treat strategy as part of HIV care practice among patients with CD4 <100 cells/μL could prevent the incidence of often fatal cryptococcal meningitis in the setting of the HIV pandemic.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rana2015,

title = {Short Message Service (SMS)-Based Intervention to Improve Treatment Adherence among HIV-Positive Youth in Uganda: Focus Group Findings},

author = {Yashodhara Rana, Jessica Haberer, Haijing Huang, Andrew Kambugu, Barbara Mukasa, Harsha Thirumurthy, Peter Wabukala, Glenn J. Wagner, Sebastian Linnemayr

},

doi = {https://doi.org/10.1371/journal.pone.0125187},

year  = {2015},

date = {2015-04-16},

journal = {PLOS ONE},

volume = {10},

number = {4},

pages = { e0125187},

abstract = {This paper presents one of the first qualitative studies to discuss programmatic barriers to SMS-based interventions for HIV-positive youth and discusses pathways through which youth perceive them to work. We conducted six focus groups with 20 male and 19 female HIV-positive youths in two clinics in Kampala, Uganda. We find that youth commonly use SMS as over 90% of this study’s youths knew how to read, write and send messages and almost three-fourths of them had phones. Youth strongly felt that the success of this intervention hinged on ensuring confidentiality about their HIV-positive status. Key programmatic challenges discussed where restrictions on phone use and phone sharing that could exclude some youth. Participants felt that the intervention would improve their adherence by providing them with needed reminders and social support. Youths’ suggestions about intervention logistics related to content, frequency, timing and two-way messages will be helpful to practitioners in the field.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mbonye2015,

title = {Malaria Care in Infants Aged under Six Months in Uganda: An Area of Unmet Needs!},

author = {Martin Kayitale Mbonye, Sarah M. Burnett, Sarah Naikoba, Robert Colebunders, Kristien Wouters, Marcia R. Weaver, Jean Pierre Van Geertruyden},

doi = {https://doi.org/10.1371/journal.pone.0123283},

year  = {2015},

date = {2015-04-10},

journal = {PLOS ONE},

volume = {10},

number = {4},

pages = {e0123283},

abstract = {Background



Little information exists on malaria burden, artemisinin-based combination therapy (ACT) use, and malaria care provided to infants under six months of age. The perception that malaria may be rare in this age group has led to lack of clinical trials and evidence-based treatment guidelines. The objective of this study was to identify malaria parasitemia positivity rate (MPPR) among patients under six months, and practices and predictors of malaria diagnosis and treatment in this population.



Methods



Cross-sectional data collected from October 2010 to September 2011 on 25,997 individual outpatients aged <6 months from 36 health facilities across Uganda were analysed.



Findings



Malaria was suspected in 18,415 (70.8%) patients, of whom 7,785 (42.3%) were tested for malaria. Of those tested, the MPPR was 36.1%, with 63.9% testing negative, of which 1,545 (31.1%) were prescribed an antimalarial. Among children <5kgs, off-label prescription of ACT was high (104/285, 36.5%). Younger age (1-6 days, aOR=0.47, p=0.01; 7-31 days, aOR=0.43, p<0.001; and 1-2 months, aOR=0.61, p<0.001), pneumonia (aOR=0.78, p=0.01) or cough/cold (aOR=0.65, p<0.001) diagnosis, and fever (aOR=0.56, p=0.01) reduced the odds of receiving a malaria test. Fever (aOR=2.22, p<0.001), anemia diagnosis (aOR=3.51, p=0.01), consulting midwives (aOR=3.58, p=0.04) and other less skilled providers (aOR=4.75, p<0.001) relative to medical officers, consulting at hospitals (aOR=3.31, p=0.03), visiting health facilities in a medium-high malaria transmission area (aOR=2.20, p<0.001), and visiting during antimalarial (aOR=1.82, p=0.04) or antibiotic (aOR=2.23, p=0.04) shortages increased the odds of prescribing an antimalarial despite a negative malaria test result.



Conclusions



We found high malaria suspicion but low testing rates in outpatient children aged <6 months. Among those tested, MPPR was high. Despite a negative malaria test result, many infants were prescribed antimalarials. Off-label ACT prescription was common in children weighing <5kgs. Evidence-based malaria guidelines for infants weighing <5 kilograms and aged <6 months are urgently needed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dharan2015,

title = {Improving the Sensitivity of the Xpert MTB/RIF Assay on Sputum Pellets by Decreasing the Amount of Added Sample Reagent: a Laboratory and Clinical Evaluation},

author = {Nila J. Dharan, Danielle Amisano, Gerald Mboowa, Willy Ssengooba, Robert Blakemore, Rachel W. Kubiak, Derek T. Armstrong, Martin Jones, Yukari C. Manabe, Moses L. Joloba, Jerrold J. Ellner, Susan E. Dorman, David Alland},

doi = {https://doi.org/10.1128/JCM.03619-14 Check for updates on crossmark},

year  = {2015},

date = {2015-04-01},

journal = {Journal of Clinical Microbiology},

volume = {53},

number = {4},

pages = {1258-1263},

abstract = {ABSTRACT

The Xpert MTB/RIF (Xpert) assay permits rapid near-patient detection of Mycobacterium tuberculosis in sputum; however, the test sensitivity remains suboptimal in paucibacillary specimens that are negative for acid-fast bacilli using smear microscopy. Xpert testing includes dilution with sample reagent, and when processed sputum pellets are tested, the recommended sample reagent/pellet ratio is 3:1. We evaluated whether a decreased sample reagent/pellet ratio of 2:1 increased Xpert sensitivity compared to the recommended 3:1. The limit of detection was determined by inoculating serial dilutions of M. tuberculosis into sputum samples, preparing sputum pellets, and testing each pellet by Xpert at both sample reagent ratios. Processed sputum pellets obtained from M. tuberculosis culture-positive clinical specimens were also tested by Xpert at both ratios. Among spiked sputum pellets, the limit of detection was 1,478 CFU/ml (95% confidence interval [CI], 1,211 to 1,943) at a 3:1 ratio and decreased to 832 CFU/ml (95% CI, 671 to 1,134) at 2:1. The proportion of specimens in which M. tuberculosis was detected was greater at 2:1 than at 3:1 for almost all numbers of CFU/ml; this difference was most prominent at lower numbers of CFU/ml. Among 134 concentrated sputum pellets from the clinical study, the sensitivity of Xpert at 2:1 was greater than at 3:1 overall (80% versus 72%; P = 0.03) and for smear-negative specimens (67% versus 58%; P = 0.12). For Xpert testing of sputum pellets, using a lower sample reagent/pellet ratio increased M. tuberculosis detection, especially for paucibacillary specimens. Our study supports use of a 2:1 sample reagent/pellet dilution for Xpert testing of sputum pellets.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Odongo2015,

title = {Impaired renal function and associated risk factors in newly diagnosed HIV-infected adults in Gulu Hospital, Northern Uganda},

author = {Pancras Odongo, Ronald Wanyama, James Henry Obol, Paska Apiyo & Pauline Byakika-Kibwika },

doi = {https://doi.org/10.1186/s12882-015-0035-3},

year  = {2015},

date = {2015-03-31},

journal = {BMC Nephrology },

volume = {16},

number = {43},

abstract = {Background



Screening for renal diseases should be performed at the time of diagnosis of human immunodeficiency virus (HIV) infection. Despite the high prevalence of HIV/AIDS in Northern Uganda, little is known about the status of renal function and its correlates in the newly diagnosed HIV-infected individuals in this resource limited region. We aimed to determine the status of renal function and factors associated with impaired renal function in newly diagnosed HIV-infected adults in Northern Uganda.



Methods



This was a seven month cross-sectional hospital-based study, involving newly diagnosed HIV-infected patients, 18 years and older. Patients with history of diabetes mellitus, hypertension and renal disease were excluded. Estimated glomerular filtration rate (eGFR) was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (Table one). Factors associated with impaired renal function (eGFR < 60 ml/min/1.73 m2) were thus sought.



Results



We enrolled 361 participants (230, 63.7% female) with Mean ± standard deviation age of 31.4 ± 9.5 years. 52, (14.4%) had impaired renal function (eGFR <60 mL/min/1.73 m2) and of this 37 (71.2%) moderate renal impairment (eGFR 30–59.9 mL/min/1.73 m2) while 15 (28.8%) had severe renal impairment (eGFR <30 mL/min/1.73 m2). Proteinuria was recorded in 189 (52.4%) participants. Of these, 154 (81.5%) had mild (1+) while 8 (4.2%) had severe (3+) proteinuria. Using logistic regression, age, CD4 cell count, and proteinuria were significantly associated with impaired renal function; age >34 years (OR 2.8, 95% CI 1.3 – 5.9; P =0.009), CD4 count <350 cells/μL (OR 2.4, 95% CI 1.0-4.7; P =0.039) and proteinuria (OR 9.6, 95% CI 5.2–17.9; P < 0.001).



Conclusion



The prevalence of impaired renal function was high in new HIV-infected individuals in this region with limited resources. So, screening for renal disease in HIV is recommended at the time of HIV diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{R.Boulwareb2015,

title = {Gastrointestinal cryptococcoma – Immune reconstitution inflammatory syndrome or cryptococcal relapse in a patient with AIDS?},

author = {Abdu K.MusubireacDavid B.MeyaabcRobertLukandedAndrewKambuguabPaul R.BohjanenbDavid R.Boulwareb},

doi = {https://doi.org/10.1016/j.mmcr.2015.03.004},

year  = {2015},

date = {2015-03-26},

journal = {Medical Mycology Case Reports},

volume = {8},

pages = {40-43},

abstract = {Abstract



The introduction of antiretroviral therapy (ART) may lead to unusual paradoxical and unmasking presentations of opportunistic infections. Intra-abdominal cryptococcosis is a rare manifestation of Cryptococcus. We present the case of an HIV-infected patient on ART, with a history of cryptococcal meningitis who presented with subacute, worsening abdominal pain during immune recovery. This evolved into chronic abdominal pain, with thickened bowel, and abdominal lymphadenopathy, while receiving empiric tuberculosis treatment. At 6-months, he developed intestinal perforation due to a histologically confirmed cryptococcoma.



Keywords

HIV, AIDS, Cryptococcal meningitis, Cryptococcoma, Antiretroviral therapy, Immune reconstitution inflammatory syndrome},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Walter2015,

title = {Transcriptional Adaptation of Drug-tolerant Mycobacterium tuberculosis During Treatment of Human Tuberculosis},

author = {Nicholas D. Walter, Gregory M. Dolganov, Benjamin J. Garcia, William Worodria, Alfred Andama, Emmanuel Musisi, Irene Ayakaka, Tran T. Van, Martin I. Voskuil, Bouke C. de Jong, Rebecca M. Davidson, Tasha E. Fingerlin, Katerina Kechris, Claire Palmer, Payam Nahid, Charles L. Daley, Mark Geraci, Laurence Huang, Adithya Cattamanchi, Michael Strong, Gary K. Schoolnik, John Lucian Davis},

doi = {https://doi.org/10.1093/infdis/jiv149},

year  = {2015},

date = {2015-03-11},

journal = {The Journal of Infectious Diseases},

volume = {212},

number = {6},

pages = {990–998},

abstract = {Abstract



Background. 

Treatment initiation rapidly kills most drug-susceptible Mycobacterium tuberculosis, but a bacterial subpopulation tolerates prolonged drug exposure. We evaluated drug-tolerant bacilli in human sputum by comparing messenger RNA (mRNA) expression of drug-tolerant bacilli that survive the early bactericidal phase with treatment-naive bacilli.



Methods. 

M. tuberculosis gene expression was quantified via reverse-transcription polymerase chain reaction in serial sputa from 17 Ugandans treated for drug-susceptible pulmonary tuberculosis.



Results. 

Within 4 days, bacterial mRNA abundance declined >98%, indicating rapid killing. Thereafter, the rate of decline slowed >94%, indicating drug tolerance. After 14 days, 16S ribosomal RNA transcripts/genome declined 96%, indicating slow growth. Drug-tolerant bacilli displayed marked downregulation of genes associated with growth, metabolism, and lipid synthesis and upregulation in stress responses and key regulatory categories—including stress-associated sigma factors, transcription factors, and toxin-antitoxin genes. Drug efflux pumps were upregulated. The isoniazid stress signature was induced by initial drug exposure, then disappeared after 4 days.



Conclusions. 

Transcriptional patterns suggest that drug-tolerant bacilli in sputum are in a slow-growing, metabolically and synthetically downregulated state. Absence of the isoniazid stress signature in drug-tolerant bacilli indicates that physiological state influences drug responsiveness in vivo. These results identify novel drug targets that should aid in development of novel shorter tuberculosis treatment regimens.



Key Terms

gene expression profiling, Mycobacterium tuberculosis/genetics, Mycobacterium tuberculosis/physiology, pulmonary/epidemiology, sputum/microbiology, tuberculosis



Topic:

transcription, genetic stress response bacillus drug tolerance genes isoniazid mycobacterium tuberculosis rna, messenger sputum tuberculosis stress killing 



Issue Section:

Bacteria },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mbabazi2015,

title = {Accuracy of Two Malaria Rapid Diagnostic Tests (RDTS) for Initial Diagnosis and Treatment Monitoring in a High Transmission Setting in Uganda},

author = {Phoebe Mbabazi, Heidi Hopkins, Emmanuel Osilo, Michael Kalungu, Pauline Byakika-Kibwika, and Moses R. Kamya},

doi = { doi: 10.4269/ajtmh.14-0180},

year  = {2015},

date = {2015-03-04},

journal = {The American Journal of Tropical  Medicine and Hygiene},

volume = {92},

number = {3},

pages = {530–536},

abstract = {Malaria rapid diagnostic tests (RDTs) may improve fever management in areas without microscopy. We compared the accuracy of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH)-based RDTs, using expert microscopy as a gold standard, for initial diagnosis, treatment monitoring, and diagnosis of recurrent malaria in a cohort of children followed longitudinally in a high-transmission area in Uganda. For 305 initial fever episodes, sensitivity was 98% for HRP2 and 87% for pLDH, whereas specificity was 55% and 96%, respectively. The HRP2 gave 51% false-positive results on Day 28, whereas pLDH gave no false positives after Day 7. For 59 recurrent fever episodes during follow-up, sensitivity was 100% for HRP2 and 91% for pLDH, whereas specificity was 33% and 100%, respectively. The HRP2-based RDTs are useful for initial diagnosis of malaria caused by superior sensitivity; however, as a result of superior specificity, pLDH-based RDTs are more appropriate to monitor treatment and diagnose recurrent malaria.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Geng2015c,

title = {Estimation of mortality among HIV-infected people on antiretroviral treatment in east Africa: a sampling based approach in an observational, multisite, cohort study},

author = {Elvin H Geng, Thomas A Odeny, Rita E Lyamuya, Alice Nakiwogga-Muwanga, Lameck Diero, Mwebesa Bwana, Winnie Muyindike Paula Braitstein, Geoffrey R Somi, Andrew Kambugu, Elizabeth A Bukusi, Megan Wenger, Kara K Wools-Kaloustian, David V Glidden, Constantin T Yiannoutsos and Jeffrey N Martin},

doi = {https://doi.org/10.1016/S2352-3018(15)00002-8},

year  = {2015},

date = {2015-03-01},

journal = {The Lancet HIV},

volume = {2},

number = {3},

pages = {e107-e116},

abstract = {Background



Mortality in HIV-infected people after initiation of antiretroviral treatment (ART) in resource-limited settings is an important measure of the effectiveness and comparative effectiveness of the global public health response. Substantial loss to follow-up precludes accurate accounting of deaths and limits our understanding of effectiveness. We aimed to provide a better understanding of mortality at scale and, by extension, the effectiveness and comparative effectiveness of public health ART treatment in east Africa.



Methods



In 14 clinics in five settings in Kenya, Uganda, and Tanzania, we intensively traced a sample of patients randomly selected using a random number generator, who were infected with HIV and on ART and who were lost to follow-up (>90 days late for last scheduled visit). We incorporated the vital status outcomes for these patients into analyses of the entire clinic population through probability-weighted survival analyses.



Findings



We followed 34 277 adults on ART from Mbarara and Kampala in Uganda, Eldoret, and Kisumu in Kenya, and Morogoro in Tanzania. The median age was 35 years (IQR 30–42), 11 628 (34%) were men, and median CD4 count count before therapy was 154 cells per μL (IQR 70–234). 5780 patients (17%) were lost to follow-up, 991 (17%) were selected for tracing between June 10, 2011, and Aug 27, 2012, and vital status was ascertained for 860 (87%). With incorporation of outcomes from the patients lost to follow-up, estimated 3 year mortality increased from 3·9% (95% CI 3·6–4·2) to 12·5% (11·8–13·3). The sample-corrected, unadjusted 3 year mortality across settings was lowest in Mbarara (7·2%) and highest in Morogoro (23·6%). After adjustment for age, sex, CD4 count before therapy, and WHO stage, the sample-corrected hazard ratio comparing the settings with highest and lowest mortalities was 2·2 (95% CI 1·5–3·4) and the risk difference for death at 3 years was 11% (95% CI 5·0–17·7).



Interpretation



A sampling-based approach is widely feasible and important to an understanding of mortality after initiation of ART. After adjustment for measured biological drivers, mortality differs substantially across settings despite delivery of a similar clinical package of treatment. Implementation research to understand the systems, community, and patients' behaviours driving these differences is urgently needed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Laker-Oketta2015,

title = {Task shifting and skin punch for the histologic diagnosis of Kaposi's sarcoma in sub-Saharan Africa: A public health solution to a public health problem},

author = {Miriam O. Laker-Oketta, Megan Wenger, Aggrey Semeere, Barbara Castelnuovo, Andrew Kambugu, Robert Lukande, Chite Asirwa, Naftali Busakhala, Nathan Buziba, Lameck Diero, Kara Wools-Kaloustian, Robert Matthew Strother, Mwebesa Bwana, Winnie Muyindike, Erin Amerson, Edward Mbidde, Toby Maurer, Jeffrey Martin },

url = {https://sci-hub.hkvisa.net/10.1159/000375165},

doi = {DOI: 10.1159/000375165},

year  = {2015},

date = {2015-02-27},

journal = {Oncology},

volume = {89},

number = {1},

pages = {60-65},

abstract = {Abstract

Fueled by HIV, sub-Saharan Africa has the highest incidence of Kaposi’s sarcoma (KS) in the world. Despite this, KS diagnosis in the region is based mostly on clinical grounds. Where biopsy is available, it has traditionally been excisional and performed by surgeons, resulting in multiple appointments, follow-up visits for suture removal, and substantial costs. We hypothesized that a simpler approach skin punch biopsy would make histologic diagnosis more accessible. To address this, we provided training and equipment for skin punch biopsy of suspected KS to three HIV clinics in East Africa. The procedure consisted of local anesthesia followed by a disposable cylindrical punch blade to obtain specimens. Hemostasis is facilitated by Gelfoam®. Patients removed the dressing after 4 days. From 2007 to 2013, 2,799 biopsies were performed. Although originally targeted to be used by physicians, biopsies were performed predominantly by nurses (62%), followed by physicians (15%), clinical officers (12%) and technicians (11%). There were no reports of recurrent bleeding or infection. After minimal training and provision of inexpensive equipment (USD 3.06 per biopsy), HIV clinics in East Africa can integrate same-day skin punch biopsy for suspected KS. Task shifting from physician to non-physician greatly increases access. Skin punch biopsy should be part of any HIV clinic’s essential procedures. This example of task shifting may also be applicable to the diagnosis of other cancers (e.g., breast) in resource-limited settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{of(START)StudyGroup2015,

title = {Why START? Reflections that led to the conduct of this large long-term strategic HIV trial},

author = {INSIGHT Strategic Timing of AntiRetroviral Treatment (START)StudyGroup,(Benard Kakaire), Jens Lundgren, Babiker A, Gordin F, Emery S, Fatkenheuer G, Molina JM, Wood },

doi = {https://doi.org/10.1111/hiv.12227},

year  = {2015},

date = {2015-02-25},

journal = {HIV Medicine},

volume = {16},

number = {S1},

pages = {1-9},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Geng2015b,

title = {CD4+ T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa},

author = {Elvin H Geng, Torsten B Neilands, Rodolphe Thièbaut, Mwebesa Bosco Bwana, Denis Nash, Richard D Moore, Robin Wood, Djimon Marcel Zannou, Keri N Althoff, Poh Lian Lim, Jean B Nachega, Philippa J Easterbrook, Andrew Kambugu, Francesca Little, Gertrude Nakigozi, Damalie Nakanjako, Valerian Kiggundu, Patrick Chung Ki Li, David R Bangsberg, Matthew P Fox, Hans W Prozesky, Peter W Hunt, Mary-Ann Davies, Steven J Reynolds, Matthias Egger, Constantin T Yiannoutsos, Eric V Vittinghoff, Steven G Deeks, Jeffrey N Martin},

doi = {https://doi.org/10.1093/ije/dyu271},

year  = {2015},

date = {2015-02-19},

journal = {International Journal of Epidemiology},

volume = {44},

number = {1},

pages = {251–263},

abstract = {Abstract



Background: 

Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally.



Methods: 

We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitor-based regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/µl in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years.



Results: 

After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/µl was 529/µl [95% confidence interval (CI): 517–541] in North America, 494/µl (95% CI: 429–559) in West Africa, 515/µl (95% CI: 508–522) in Southern Africa, 503/µl (95% CI: 478–528) in Asia and 437/µl (95% CI: 425–449) in East Africa.



Conclusions: 

CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.

HIV, Africa, antiretroviral therapy, CD4 + T cell counts, immunological activation



Topic:

hiv efavirenz adult africa africa, eastern africa, southern africa, western antigens asia cd4 count determination procedure demography nevirapine nucleosides plasma rna-directed dna polymerase t-lymphocytes tropism genetics treatment outcome blood hiv rna hiv infections anti-retroviral agents ccl3l1 gene linear regression 



Issue Section:

Miscellaneous },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakiyingi2015b,

title = {Predictors and outcomes of mycobacteremia among HIV-infected smear- negative presumptive tuberculosis patients in Uganda},

author = {Lydia Nakiyingi, Willy Ssengooba, Damalie Nakanjako, Derek Armstrong, Molly Holshouser, Bruce J Kirenga, Maunank Shah, Harriet Mayanja-Kizza, Moses L Joloba, Jerrold J Ellner, Susan E Dorman & Yukari C Manabe },

year  = {2015},

date = {2015-02-15},

journal = {BMC Infectious Diseases},

volume = {15},

number = {62},

abstract = {Background



Sputum smear microscopy for tuberculosis (TB) diagnosis lacks sensitivity in HIV-infected symptomatic patients and increases the likelihood that mycobacterial infections particularly disseminated TB will be missed; delays in diagnosis can be fatal. Given the duration for MTB growth in blood culture, clinical predictors of MTB bacteremia may improve early diagnosis of mycobacteremia. We describe the predictors and mortality outcome of mycobacteremia among HIV-infected sputum smear-negative presumptive TB patients in a high prevalence HIV/TB setting.



Methods



Between January and November 2011, all consenting HIV-infected adults suspected to have TB (presumptive TB) were consecutively enrolled. Diagnostic assessment included sputum smear microscopy, urine Determine TB lipoarabinomannan (LAM) antigen test, mycobacterial sputum and blood cultures, chest X-ray, and CD4 cell counts in addition to clinical and socio-demographic data. Patients were followed for 12 months post-enrolment.



Results



Of 394 sputum smear-negative participants [female, 63.7%; median age (IQR) 32 (28–39) years], 41/394 (10.4%) had positive mycobacterial blood cultures (mycobacteremia); all isolates were M. tuberculosis (MTB). The median CD4 cell count was significantly lower among patients with mycobacteremia when compared with those without (CD4 31 versus 122 cells/μL, p < 0.001). In a multivariate analysis, male gender [OR 3.4, 95%CI (1.4-7.6), p = 0.005], CD4 count <100 cells/μL [OR 3.1, 95% CI (1.1-8.6), p = 0.030] and a positive lateral flow urine TB LAM antigen test [OR 15.3, 95%CI (5.7-41.1), p < 0.001] were significantly associated with mycobacteremia. At 12 months of follow-up, a trend towards increased mortality was observed in patients that were MTB blood culture positive (35.3%) compared with those that were MTB blood culture negative (23.3%) (p = 0.065).



Conclusions



Mycobacteremia occurred in 10% of smear-negative patients and was associated with higher mortality compared with smear-negative patients without mycobacteremia. Advanced HIV disease (CD4 < 100 cells/mm3), male gender and positive lateral flow urine TB LAM test predicted mycobacteremia in HIV-infected smear-negative presumptive TB patients in this high prevalence TB/HIV setting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}