@article{Taylor2012,

title = {Low Prevalence of Pneumocystis pneumonia (PCP) but High Prevalence of Pneumocystis dihydropteroate synthase ( dhps ) Gene Mutations in HIV-Infected Persons in Uganda},

author = {Steve M. Taylor and Steven R. Meshnick and William Worodria and Alfred Andama and Adithya Cattamanchi and J. Lucian Davis and Samuel D. Yoo and Patrick Byanyima and Sylvia Kaswabuli and Carol D. Goodman and Laurence Huang},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Low-Prevalence-of-Pneumocystis-pneumonia-.....pdf},

doi = {10.1371/journal.pone.0049991},

year  = {2012},

date = {2012-11-06},

journal = {PloS One},

volume = {7},

number = {11},

abstract = {Pneumocystis jirovecii pneumonia (PCP) is an important opportunistic infection in patients infected with HIV, but its burden is incompletely characterized in those areas of sub-Saharan Africa where HIV is prevalent. We explored the prevalence of both PCP in HIV-infected adults admitted with pneumonia to a tertiary-care hospital in Uganda and of putative P. jirovecii drug resistance by mutations in fungal dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr). In 129 consecutive patients with sputum smears negative for mycobacteria, 5 (3.9%) were diagnosed with PCP by microscopic examination of Giemsa-stained bronchoalveolar lavage fluid. Concordance was 100% between Giemsa stain and PCR (dhps and dhfr). PCP was more prevalent in patients newly-diagnosed with HIV (11.4%) than in patients with known HIV (1.1%; p = 0.007). Mortality at 2 months after discharge was 29% overall: 28% among PCP-negative patients, and 60% (3 of 5) among PCP-positive patients. In these 5 fungal isolates and an additional 8 from consecutive cases of PCP, all strains harbored mutant dhps haplotypes; all 13 isolates harbored the P57S mutation in dhps, and 3 (23%) also harbored the T55A mutation. No non-synonymous dhfr mutations were detected. PCP is an important cause of pneumonia in patients newly-diagnosed with HIV in Uganda, is associated with high mortality, and putative molecular evidence of drug resistance is prevalent. Given the reliability of field diagnosis in our cohort, future studies in sub-Saharan Africa can investigate the clinical impact of these genotypes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Yoon2012,

title = {Impact of Xpert MTB/RIF Testing on Tuberculosis Management and Outcomes in Hospitalized Patients in Uganda},

author = {Christina Yoon and Adithya Cattaman and J. Lucian Davis and William Worodria and Saskia den Boon and Nelson Kalema and Winceslaus Katagira and Sylvia Kaswabuli and Cecily Miller and Alfred Andama and Heidi Albert and Pamela Nabeta and Christen Gray and Irene Ayakaka and Laurence Huang},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Impact-of-Xpert.....pdf},

doi = {10.1371/journal.pone.0048599},

year  = {2012},

date = {2012-11-06},

journal = {PloS One},

volume = {1},

number = {11},

abstract = {RATIONALE:



The clinical impact of Xpert MTB/RIF for tuberculosis (TB) diagnosis in high HIV-prevalence settings is unknown.

OBJECTIVE:



To determine the diagnostic accuracy and impact of Xpert MTB/RIF among high-risk TB suspects.

METHODS:



WE PROSPECTIVELY ENROLLED CONSECUTIVE, HOSPITALIZED, UGANDAN TB SUSPECTS IN TWO PHASES: baseline phase in which Xpert MTB/RIF results were not reported to clinicians and an implementation phase in which results were reported. We determined the diagnostic accuracy of Xpert MTB/RIF in reference to culture (solid and liquid) and compared patient outcomes by study phase.

RESULTS:



477 patients were included (baseline phase 287, implementation phase 190). Xpert MTB/RIF had high sensitivity (187/237, 79%, 95% CI: 73-84%) and specificity (190/199, 96%, 95% CI: 92-98%) for culture-positive TB overall, but sensitivity was lower (34/81, 42%, 95% CI: 31-54%) among smear-negative TB cases. Xpert MTB/RIF reduced median days-to-TB detection for all TB cases (1 [IQR 0-26] vs. 0 [IQR 0-1], p<0.001), and for smear-negative TB (35 [IQR 22-55] vs. 22 [IQR 0-33], p=0.001). However, median days-to-TB treatment was similar for all TB cases (1 [IQR 0-5] vs. 0 [IQR 0-2], p=0.06) and for smear-negative TB (7 [IQR 3-53] vs. 6 [IQR 1-61], p=0.78). Two-month mortality was also similar between study phases among 252 TB cases (17% vs. 14%, difference +3%, 95% CI: -21% to +27%, p=0.80), and among 87 smear-negative TB cases (28% vs. 22%, difference +6%, 95% CI: -34 to +46%, p=0.77).

CONCLUSIONS:



Xpert MTB/RIF facilitated more accurate and earlier TB diagnosis, leading to a higher proportion of TB suspects with a confirmed TB diagnosis prior to hospital discharge in a high HIV/low MDR TB prevalence setting. However, our study did not detect a decrease in two-month mortality following implementation of Xpert MTB/RIF possibly because of insufficient powering, differences in empiric TB treatment rates, and disease severity between study phases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakiyingi2012,

title = {Destructive rib lesions in an HIV sero-negative male: an unusual presentation of tuberculosis in a high tuberculosis prevalence setting},

author = {Lydia Nakiyingi and John M Bwanika and Robert Lukande and Bruce Kirenga and Tom P Mwambu and William Worodria and Martin Okot-Nwang},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Destructive-rib-lesions-in-an-HIV-sero-negative-male.pdf},

doi = { 10.1258/td.2012.110342},

year  = {2012},

date = {2012-11-06},

journal = {Tropical Doctor },

volume = {42},

number = {4},

pages = {217-8},

abstract = {Tuberculosis (TB) of the rib is a very rare form of skeletal TB and its diagnosis may be difficult because of a low index of suspicion by clinicians. The presentation often mimics malignant disease clinically and radiologically and diagnosis may only be confirmed by tissue biopsy. We present a 32-year-old HIV-negative man who presented with a three-month history of progressively worsening pleuritic chest pain, weight loss, fatigue, anorexia and low-grade fever with night sweats. A chest computerized tomography (CT) scan showed destructive lesions in the right fourth and seventh ribs with no pulmonary lesions. A diagnosis of TB of the rib was made after surgical resection and histopathology of the affected tissue. There was significant improvement when anti-TB therapy was initiated. This case report emphasizes the importance of a high index of suspicion of TB in patients presenting with destructive bone lesions in regions with high prevalence of TB.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Miremba2012,

title = {Performance of Frontloading for Smear Microscopy in the Diagnosis of Pulmonary Tuberculosis: A Cross- Sectional Study at a Referral Hospital in Uganda},

author = {Penelope Miremba and Joan N. Kalyango and William Worodria and Henry Mugerwa and Ethel Nakakawa and Benon B. Asiimwe

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/Performance-of-frontloading-....pdf},

doi = {10.1371/journal.pone.0048531},

year  = {2012},

date = {2012-10-29},

journal = {PloS One},

volume = {7},

number = {10},

abstract = {OBJECTIVE:



To compare the performance of frontloading and the standard WHO method for diagnosis of pulmonary TB at Mulago Hospital in order to validate the technique in this setting.

METHODS:



This was a cross-sectional study in which 229 adult (≥18 years) TB suspects were consecutively enrolled. Suspects submitted three sputum samples as follows: at initial presentation, one hour after the first sample, and the next morning. The first and next morning samples formed the standard WHO method, while the first and the one hour later samples formed the frontloading method. Sample processing was by the standard N-acetyl L-cystein (NALC)-NaOH method, and fluorescent microscopy was done for both methods, while cultures of the first sample on Lowenstein-Jensen slants acted as a gold standard. The sensitivity, specificity and predictive values for the WHO standard and frontloading methods were compared.

RESULTS:



The sensitivity of both the frontloading and standard schemes was 91.1% while their specificities were 86.2% and 91.7% respectively. There was excellent agreement between the diagnostic capacity of the two methods (kappa statistic = 0.87, P<0.0001). The positive predictive value for the frontloading scheme was 87.2% and that for the standard approach was 91.9%, while the negative predictive values were 90.4% and 90.9%, respectively. Among the HIV positive patients, frontloading identified 59/79 (74.7%) culture positive samples while the standard approach identified 55/79 (69.6%). In the HIV sero-negative category, on the other hand, front-loading identified 48/110 (43.6%) culture positive samples compared to 45/110 (40.9%) by the standard approach.

CONCLUSION:



Frontloading based on smear examination of two same-day sputum samples has a similar performance to the current standard method and would not be associated with any significant missed diagnosis. It may therefore be advocated for use in our setting so as to reduce time to completion of diagnosis and patient loss to follow-up},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rajasingham2012,

title = {Cryptococcal Meningitis Treatment Strategies in Resource-Limited Settings: A Cost-Effectiveness Analysis},

author = {Radha Rajasingham and Melissa A. Rolfes and Kate E. Birkenkamp and David B. Meya and David R. Boulware},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Cryptococcal-Meningitis-Treatment-Strategies-in-resource-limited-satting.pdf},

doi = { 10.1371/journal.pmed.1001316},

year  = {2012},

date = {2012-09-25},

journal = {PloS Medicine},

volume = {9},

number = {9},

abstract = {BACKGROUND:



Cryptococcal meningitis (CM) is the most common form of meningitis in Africa. World Health Organization guidelines recommend 14-d amphotericin-based induction therapy; however, this is impractical for many resource-limited settings due to cost and intensive monitoring needs. A cost-effectiveness analysis was performed to guide stakeholders with respect to optimal CM treatment within resource limitations.

METHODS AND FINDINGS:



We conducted a decision analysis to estimate the incremental cost-effectiveness ratio (ICER) of six CM induction regimens: fluconazole (800-1,200 mg/d) monotherapy, fluconazole + flucytosine (5FC), short-course amphotericin (7-d) + fluconazole, 14-d of amphotericin alone, amphotericin + fluconazole, and amphotericin + 5FC. We computed actual 2012 healthcare costs in Uganda for medications, supplies, and personnel, and average laboratory costs for three African countries. A systematic review of cryptococcal treatment trials in resource-limited areas summarized 10-wk survival outcomes. We modeled one-year survival based on South African, Ugandan, and Thai CM outcome data, and survival beyond one-year on Ugandan and Thai data. Quality-adjusted life years (QALYs) were determined and used to calculate the cost-effectiveness ratio and ICER. The cost of hospital care ranged from $154 for fluconazole monotherapy to $467 for 14 d of amphotericin + 5FC. Based on 18 studies investigating outcomes for HIV-infected individuals with CM in resource-limited settings, the estimated mean one-year survival was lowest for fluconazole monotherapy, at 40%. The cost-effectiveness ratio ranged from $20 to $44 per QALY. Overall, amphotericin-based regimens had higher costs but better survival. Short-course amphotericin (1 mg/kg/d for 7 d) with fluconazole (1,200 mg/d for14 d) had the best one-year survival (66%) and the most favorable cost-effectiveness ratio, at $20.24/QALY, with an ICER of $15.11 per additional QALY over fluconazole monotherapy. The main limitation of this study is the pooled nature of a systematic review, with a paucity of outcome data with direct comparisons between regimens.

CONCLUSIONS:



Short-course (7-d) amphotericin induction therapy coupled with high-dose (1,200 mg/d) fluconazole is "very cost effective" per World Health Organization criteria and may be a worthy investment for policy-makers seeking cost-effective clinical outcomes. More head-to-head clinical trials are needed on treatments for this neglected tropical disease. Please see later in the article for the Editors' Summary.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wiesner2012,

title = {Cryptococcal Genotype Influences Immunologic Response and Human Clinical Outcome after Meningitis},

author = {Darin L. Wiesner and Oleksandr Moskalenko and Jennifer M. Corcoram and Tami McDonald and Melissa A. Rolfes and David B. Meya and Henry Kajumbula and Andrew Kambugu and Paul R. Bohjanen and Joseph F. Knight and David R. Boulware and

Kirsten Nielsen},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Cryptococcal-Genotype-Influences-Immunologic-Response-and-Human-clinical-outcome-after-meningitis.pdf},

doi = {10.1128/mBio.00196-12. Print 2012},

year  = {2012},

date = {2012-09-25},

journal = {MBio},

volume = {3},

number = {5},

pages = {3-5},

abstract = {In sub-Saharan Africa, cryptococcal meningitis (CM) continues to be a predominant cause of AIDS-related mortality. Understanding virulence and improving clinical treatments remain important. To characterize the role of the fungal strain genotype in clinical disease, we analyzed 140 Cryptococcus isolates from 111 Ugandans with AIDS and CM. Isolates consisted of 107 nonredundant Cryptococcus neoformans var. grubii strains and 8 C. neoformans var. grubii/neoformans hybrid strains. Multilocus sequence typing (MLST) was used to characterize genotypes, yielding 15 sequence types and 4 clonal clusters. The largest clonal cluster consisted of 74 isolates. The results of Burst and phylogenetic analysis suggested that the C. neoformans var. grubii strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). Patient mortality was differentially associated with the different evolutionary groups (P = 0.04), with the highest mortality observed among Burst group 1, Burst group 2, and hybrid strains. Compared to Burst group 3 strains, Burst group 1 strains were associated with higher mortality (P = 0.02), exhibited increased capsule shedding (P = 0.02), and elicited a more pronounced Th(2) response during ex vivo cytokine release assays with strain-specific capsule stimulation (P = 0.02). The results of these analyses suggest that cryptococcal strain variation can be an important determinant of human immune responses and mortality.

IMPORTANCE:



Cryptococcus neoformans is a common life-threatening human fungal pathogen that is responsible for an estimated 1 million cases of meningitis in HIV-infected patients annually. Virulence factors that are important in human disease have been identified, yet the impacts of the fungal strain genotype on virulence and outcomes of human infection remain poorly understood. Using an analysis of strain variation based on in vitro assays and clinical data from Ugandans living with AIDS and cryptococcal infection, we report that strain genotype predicts the type of immune response and mortality risk. These studies suggest that knowledge of the strain genotype during human infections could be used to predict disease outcomes and lead to improved treatment approaches aimed at targeting the specific combination of pathogen virulence and host response.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakiyingi2012b,

title = {Evaluation of in-house PCR for diagnosis of smear-negative pulmonary tuberculosis in Kampala, Uganda},

author = {Lydia Nakiyingi and David P Kateete and Ponsiano Ocama and William Worodria and Joseph B Sempa and Benon B Asiimwe and Fred A Katabazi and Achilles Katamba and Laurence Huang and Moses L Joloba and Harriet Mayanja-Kizza},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Evaluating-the-cost-effectiveness-of-combination-antiretroviral-therapy-...-1.pdf},

doi = {10.1186/1756-0500-5-487},

year  = {2012},

date = {2012-09-05},

journal = {BMC Research Notes},

abstract = {BACKGROUND:



Nucleic acid amplification tests (NAATs) have offered hope for rapid diagnosis of tuberculosis (TB). However, their efficiency with smear-negative samples has not been widely studied in low income settings. Here, we evaluated in-house PCR assay for diagnosis of smear-negative TB using Lowenstein-Jensen (LJ) culture as the baseline test. Two hundred and five pulmonary TB (PTB) suspects with smear-negative sputum samples, admitted on a short stay emergency ward at Mulago Hospital in Kampala, Uganda, were enrolled. Two smear-negative sputum samples were obtained from each PTB suspect and processed simultaneously for identification of MTBC using in-house PCR and LJ culture.

RESULTS:



Seventy two PTB suspects (35%, 72/205) were LJ culture positive while 128 (62.4%, 128/205) were PCR-positive. The sensitivity and specificity of in-house PCR for diagnosis of smear-negative PTB were 75% (95% CI 62.6-85.0) and 35.9% (95% CI 27.2-45.3), respectively. The positive and negative predictive values were 39% (95% CI 30.4-48.2) and 72.4% (95% CI 59.1-83.3), respectively, while the positive and negative likelihood ratios were 1.17 (95% CI 0.96-1.42) and 0.70 (95% CI 0.43-1.14), respectively. One hundred and seventeen LJ culture-negative suspects (75 PCR-positive and 42 PCR-negative) were enrolled for follow-up at 2 months. Of the PCR-positive suspects, 45 (60%, 45/75) were still alive, of whom 29 (64.4%, 29/45) returned for the follow-up visit; 15 (20%, 15/75) suspects died while another 15 (20%, 15/75) were lost to follow-up. Of the 42 PCR-negative suspects, 22 (52.4%, 22/42) were still alive, of whom 16 (72.7%, 16/22) returned for follow-up; 11 (26.2%, 11/42) died while nine (21.4%, 9/42) were lost to follow-up. Overall, more PCR-positive suspects were diagnosed with PTB during follow-up visits but the difference was not statistically significant (27.6%, 8/29 vs. 25%, 4/16, p = 0.9239). Furthermore, mortality was higher for the PCR-negative suspects but the difference was also not statistically significant (26.2% vs. 20% p = 0.7094).

CONCLUSION:



In-house PCR correlates poorly with LJ culture for diagnosis of smear-negative PTB. Therefore, in-house PCR may not be adopted as an alternative to LJ culture.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sempa2012,

title = {Cost-effectiveness of early initiation of first-line combination antiretroviral therapy in Uganda},

author = {Joseph Sempa and Mark Ssennono and Andreas Kuznik and Mohammed Lamorde and Stefanie Sowinski and Aggrey Semeere and Sabine Hermans and Barbara Castelnuovo and Yukari C Manabe

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Cost-effectieness-of-early-intiation-of-the-first-line-combination-antiretroviral-therapy-in-uganda.pdf},

doi = {10.1186/1471-2458-12-736},

year  = {2012},

date = {2012-09-04},

journal = {BMC Public Health},

abstract = {BACKGROUND:



Ugandan national guidelines recommend initiation of combination antiretroviral therapy (cART) at CD4+ T cell (CD4) count below 350 cell/μl, but the implementation of this is limited due to availability of medication. However, cART initiation at higher CD4 count increases survival, albeit at higher lifetime treatment cost. This analysis evaluates the cost-effectiveness of initiating cART at a CD4 count between 250-350 cell/μl (early) versus <250 cell/μl (delayed).

METHODS:



Life expectancy of cART-treated patients, conditional on baseline CD4 count, was modeled based on published literature. First-line cART costs $192 annually, with an additional $113 for patient monitoring. Delaying initiation of cART until the CD4 count falls below 250 cells/μl would incur the cost of the bi-annual CD4 count tests and routine maintenance care at $85 annually. We compared lifetime treatment costs and disability adjusted life-expectancy between early vs. delayed cART for ten baseline CD4 count ranges from 250-350 cell/μl. All costs and benefits were discounted at 3% annually.

RESULTS:



Treatment delay varied from 6-18 months. Early cART initiation increased life expectancy from 1.5-3.5 years and averted 1.33-3.10 disability adjusted life years (DALY's) per patient. Lifetime treatment costs were $4,300-$5,248 for early initiation and $3,940-$4,435 for delayed initiation. The cost/DALY averted of the early versus delayed start ranged from $260-$270.

CONCLUSIONS:



In HIV-positive patients presenting with CD4 count between 250-350 cells/μl, immediate initiation of cART is a highly cost-effective strategy using the recommended one-time per capita GDP threshold of $490 reported for Uganda. This would constitute an efficient use of scarce health care funds.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Semeere2012b,

title = {Impact of Antiretroviral Therapy on the Incidence of Kaposi’s Sarcoma in Resource-rich and Resource-limited Settings},

author = {Aggrey S. Semeere and Naftali Busakhala and Jeffrey N. Martin},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Impact-of-Antiretroviral-Therapy-on-the-Incidence-of-Kaposi’s....pdf},

doi = {10.1097/CCO.0b013e328355e14b},

year  = {2012},

date = {2012-09-01},

journal = {Current Opinin in Oncology},

volume = {24},

number = {5},

pages = {522-30},

abstract = {PURPOSE OF REVIEW:



Given the recent availability of antiretroviral therapy (ART) in resource-limited settings and the significant burden exacted by Kaposi's sarcoma in these areas, we reviewed data regarding the impact of ART on Kaposi's sarcoma incidence. We summarized the sizeable literature in resource-rich settings as well as emerging data from resource-limited regions. Importantly, we delineated ways impact can be defined, including individual patient-level effectiveness; population-level effectiveness; change in population-level incidence; and residual risk of Kaposi's sarcoma.

RECENT FINDINGS:



In resource-rich settings, there are now ample data demonstrating beneficial individual patient-level and population-level effects of ART on Kaposi's sarcoma incidence. There is, however, considerable variability between studies and important methodologic shortcomings. Data from resource-limited settings are much more limited; although they preliminarily indicate individual patient-level effectiveness, they do not yet provide insight on population-level effects.

SUMMARY:



ART has had a substantial impact on Kaposi's sarcoma incidence in resource-rich settings, but more attention is needed on validly quantifying this effect in order to determine whether additional interventions are needed. Emerging data from resource-limited regions also suggest beneficial impact of ART on Kaposi's sarcoma incidence, but - given the scope of Kaposi's sarcoma in these settings - more data are needed to understand the breadth and magnitude of the effect.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kyabayinze2012,

title = {Parasite-based malaria diagnosis: Are Health Systems in Uganda equipped enough to implement the policy?},

author = {Daniel J Kyabayinze and Jane Achan and Damalie Nakanjako and Betty Mpeka and Henry Mawejje and Rukaaka Mugizi and Joan N Kalyango and Umberto D and Alessandro and Ambrose Talisuna and Van geertruyden Jean-Pierre},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Parasite-based-Malaria-diagnosis.pdf},

doi = {10.1186/1471-2458-12-695},

year  = {2012},

date = {2012-08-24},

journal = {BMC Public Health},

abstract = {BACKGROUND:



Malaria case management is a key strategy for malaria control. Effective coverage of parasite-based malaria diagnosis (PMD) remains limited in malaria endemic countries. This study assessed the health system's capacity to absorb PMD at primary health care facilities in Uganda.

METHODS:



In a cross sectional survey, using multi-stage cluster sampling, lower level health facilities (LLHF) in 11 districts in Uganda were assessed for 1) tools, 2) skills, 3) staff and infrastructure, and 4) structures, systems and roles necessary for the implementing of PMD.

RESULTS:



Tools for PMD (microscopy and/or RDTs) were available at 30 (24%) of the 125 LLHF. All LLHF had patient registers and 15% had functional in-patient facilities. Three months' long stock-out periods were reported for oral and parenteral quinine at 39% and 47% of LLHF respectively. Out of 131 health workers interviewed, 86 (66%) were nursing assistants; 56 (43%) had received on-job training on malaria case management and 47 (36%) had adequate knowledge in malaria case management. Overall, only 18% (131/730) Ministry of Health approved staff positions were filled by qualified personnel and 12% were recruited or transferred within six months preceding the survey. Of 186 patients that received referrals from LLHF, 130(70%) had received pre-referral anti-malarial drugs, none received pre-referral rectal artesunate and 35% had been referred due to poor response to antimalarial drugs.

CONCLUSION:



Primary health care facilities had inadequate human and infrastructural capacity to effectively implement universal parasite-based malaria diagnosis. The priority capacity building needs identified were: 1) recruitment and retention of qualified staff, 2) comprehensive training of health workers in fever management, 3) malaria diagnosis quality control systems and 4) strengthening of supply chain, stock management and referral systems.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Seden2012,

title = {Global patient safety and antiretroviral drug–drug interactions in the resource-limited setting},

author = {Kay Seden and Saye H. Khoo and David Back and Pauline Byakika-Kibwika and Mohammed Lamorde and Mairin Ryan and Concepta Merry

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Global-patient-safety-and-antiretroviral-drug–drug-interactions....pdf},

doi = {10.1093/jac/dks346},

year  = {2012},

date = {2012-08-22},

journal = {Journal of Antimicrobial Chemotherapy},

volume = {68},

number = {1},

pages = {1-3},

abstract = {Scale-up of HIV treatment services may have contributed to an increase in functional health facilities available in resource-limited settings and an increase in patient use of facilities and retention in care. As more patients are reached with medicines, monitoring patient safety is increasingly important. Limited data from resource-limited settings suggest that medication error and antiretroviral drug-drug interactions may pose a significant risk to patient safety. Commonly cited causes of medication error in the developed world include the speed and complexity of the medication use cycle combined with inadequate systems and processes. In resource-limited settings, specific factors may contribute, such as inadequate human resources and high disease burden. Management of drug-drug interactions may be complicated by limited access to alternative medicines or laboratory monitoring. Improving patient safety by addressing the issue of antiretroviral drug-drug interactions has the potential not just to improve healthcare for individuals, but also to strengthen health systems and improve vital communication among healthcare providers and with regulatory agencies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hermans2012b,

title = {Implementation and effect of intensified case finding on diagnosis of tuberculosis in a large urban HIV clinic in Uganda: a retrospective cohort study.},

author = {Sabine Hermans and Esther Nasuuna and Frank van Leth and Elena Byhoff and Miriam Schwarz and Andy Hoepelman and Joep Lange and Yukari C Manabe},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Implementation-and-effect-of-intensified-case-finding-on-diagnosis....pdf},

doi = {10.1186/1471-2458-12-674},

year  = {2012},

date = {2012-08-20},

journal = {BMC Public Health},

abstract = {BACKGROUND:



Increased detection of tuberculosis (TB) using intensified or active case finding (ICF) is one of the cornerstones of the Stop TB Strategy, and contrasts with passive case finding (PCF) which relies on self-reported symptoms. There is no clear guidance on implementation strategies. We implemented ICF in addition to ongoing PCF in our large urban HIV clinic in July 2010 using a twice-daily announcement screen method by a trained peer educator, asking waiting patients to self-refer to a trained peer supporter for screening of TB symptoms. We sought to determine the associated effect on TB case detection.

METHODS:



Suspects were investigated by sputum smear, chest X-ray and ultrasound, if indicated. Routinely collected clinical and laboratory data were merged with the ICF register and TB clinic data for patients attending the clinic in 2010. We compared the yield of TB cases (defined as the prevalence of newly diagnosed TB cases in the screened population), the type of TB diagnosed and the total cost per TB case identified (in United States Dollars [USD]) for the period before and after ICF implementation.

RESULTS:



Of the 20,456 patients who visited the clinic in 2010, 614 were identified as TB suspects, 220 pre-ICF and 394 post-ICF (229 via PCF and 165 via ICF). The proportion diagnosed with TB dropped from 66% to 48% (60% in suspects identified through PCF and 31% through ICF). During the post-ICF period, TB suspects identified through ICF compared to PCF identification were more likely to be female, older, on ART and to have been enrolled in HIV care for a longer duration. The yield of combined PCF and ICF screening was 1.4% pre-ICF and 1.7% post-ICF with a cost per TB case identified of 12.29 USD and 21.80 USD, respectively.

CONCLUSIONS:



Implementation of ICF in a large HIV clinic yielded more TB suspects and cases, but substantially increased costs and was unable to capture the majority of TB suspects who were referred for diagnosis by clinicians through PCF. The overall yield of TB cases in a mature HIV clinic was low, although targeted screening of those recently enrolled in care may increase the yield},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Aizire2012,

title = {Kinetics of Nevirapine and Its Impact on HIV-1 RNA Levels in Maternal Plasma and Breast Milk Over Time After Perinatal Single-Dose Nevirapine},

author = {Jim Aizire and Michelle S. McConnell and Peter Mudiope and Michael Mubiru and Flavia Matovu and Teresa L. Parsons and Ali Elbireer and Monica Nolan and Edward N. Janoff and Mary Glenn Fowler},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Kinetics-of-Nevirapine....pdf},

doi = {10.1097/QAI.0b013e318246bf9e},

year  = {2012},

date = {2012-08-15},

journal = {Journal of Acquired Imune Dificiency syndrome},

volume = {60},

number = {5},

pages = {483-8},

abstract = {Objective: To determine kinetics after single-dose nevirapine and the impact on HIV RNA [viral load (VL)] in maternal plasma and breast milk (BM). Methods: Cohort of 120 HIV-1–infected pregnant Ugandan women received perinatal single-dose nevirapine alone and followed up with their infants through 24 weeks postdelivery. We assessed the relationship of nevirapine concentration (tandem mass spectroscopy) and HIV-1 VL (Roche AMPLICOR HIV-1 Kit, version 1.5) in maternal plasma and BM over time. Results: At week 1 postpartum, NVP ($10 ng/mL) was detected in all 53 plasma and 47 of 51 (92.2%) BM samples with median (interquartile ranges) of, respectively, 171 (78–214) ng/mL and 112 (64–158) ng/mL, P = 0.075, which decreased subsequently with traces persisting through week 4 in plasma. Plasma and BM VL dropped by week 1 and were highly correlated at delivery

(R = 0.71, P , 0.001) and week 1 (R = 0.69, P , 0.001) but not thereafter. At week 1, VL correlated inversely with NVP concentration in plasma (R = 0.39, P = 0.004) and BM (R = 0.48, P = 0.013). There was a VL rebound in both compartments, which peaked at week 4 to levels greater than those at week 1 [significantly in plasma (P , 0.001) but not in BM] and remained stable thereafter. Median VL was consistently greater (11- to 50-fold) in plasma than BM at all time points (all P , 0.001). Conclusions: After single-dose nevirapine, NVP concentration was comparably high through week 1, accompanied by suppression of plasma and BM VL. A longer “tail” (.1 week) of potent postnatal antiretroviral drugs is warranted to minimize the observed VL rebound and potential for NVP resistance as a result of persistent NVP traces.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Coutinho2012,

title = {The Expanding Role of Civil Society in the Global HIV/AIDS Response: What Has The President’s Emergency Program For AIDS Relief’s Role Been?},

author = {Alex Coutinho and Uchechi Roxo and Henry Epino and Alex Muganzi and Emily Dorward and Billy Pick},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/The_Expanding_Role_of_Civil_Society_in_the_Global.15.pdf},

doi = { 10.1097/QAI.0b013e31825d0383},

year  = {2012},

date = {2012-08-15},

journal = {Journal of Acquired Imune Dificiency syndrome},

volume = {60},

number = {3},

pages = {152-7},

abstract = {Civil society has been part of the HIV/AIDS response from the very beginning of the epidemic, often becoming engaged before national governments. Traditional roles of civil society--advocacy, activism, serving as government watchdog, and acting as community caretaker--have been critical to the response. In addition, civil society organizations (CSOs) play an integral part in providing world-class HIV prevention and treatment services and helping to ensure continuity of care. The President's Emergency Program for AIDS Relief (PEPFAR) has significantly increased the global scale-up of combination antiretroviral therapy reaching for more than 5 million people in developing countries, as well as implementation of effective evidence-based combination prevention approaches. PEPFAR databases in 5 countries and annual reports from a centrally managed initiative were mined and analyzed to determine the numbers and types of CSOs funded by PEPFAR over a 5-year period (2006-2011). Data are also presented from Uganda showing the overall resource growth in CSO working for HIV. Case studies document the evolution of 3 indigenous CSOs that increased the capacity to implement activities with PEPFAR funding. A legacy of PEPFAR has been the growth of civil society to address social and health issues as well as recognition by governments that partnerships with beneficiaries and civil society result in better outcomes. Scale-up of the global response could not have happened without the involvement of civil society and people living with HIV. This game changing partnership to jointly tackle the problems that countries face may well be the greatest benefit emerging from the HIV epidemic.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kuznik2012,

title = {Evaluating the cost-effectiveness of combination antiretroviral therapy  for the prevention of mother-to-child transmission of HIV in Uganda},

author = {Andreas Kuznik and Mohammed Lamorde and Sabine Hermans and Barbara Castelnuovo and Brandon Auerbach and Aggrey Semeere and Joseph Sempa and Mark Ssennono and Fred Ssewankambo and Yukari C Manabe},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Evaluating-the-cost-effectiveness-of-combination-antiretroviral-therapy-....pdf},

doi = {10.2471/BLT.11.095430},

year  = {2012},

date = {2012-08-01},

journal = {Bulletin of the World Health Organization},

volume = {90},

number = {8},

pages = {595-603},

abstract = {OBJECTIVE:



To model the cost-effectiveness in Uganda of combination antiretroviral therapy (ART) to prevent mother-to-child transmission of human immunodeficiency virus (HIV).

METHODS:



The cost-effectiveness of ART was evaluated on the assumption that ART reduces the risk of an HIV-positive pregnant woman transmitting HIV to her baby from 40% (when the woman is left untreated) to 25.8%, 17.4% and 3.8%, respectively, when the woman is given: (i) single-dose nevirapine (at an estimated total drug cost of 0.06 United States dollars [US$]); (ii) dual therapy with zidovudine and lamivudine for 7 weeks (at a total drug cost of US$ 15.63); or (iii) ART for 18 months (at a total annual cost of US$ 469.77). Lifetime ART (US$ 6883), recommended for pregnant women with < 350 CD4+ T lymphocytes per mm(3), was assumed to give the same reduction in transmission risk in each subsequent pregnancy.

FINDINGS:



Compared with single-dose nevirapine, dual therapy and no therapy, 18 months of ART averted 5.21, 3.22 and 8.58 disability-adjusted life years (DALYs), respectively, at a cost of US$ 46, US$ 99 and US$ 34 per DALY averted. The corresponding figures for lifetime ART are, respectively, 19.20, 11.87 and 31.60 DALYs averted, at a cost of US$ 205, US$ 354 and US$ 172 per DALY averted.

CONCLUSION:



In Uganda, ART appears highly cost-effective for the prevention of mother-to-child HIV transmission, even if continued over the patients' lifetimes. Given the additional public health benefits of ART, efforts to ensure that all HIV-positive pregnant women have access to lifelong ART should be intensified.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nakanjako2012,

title = {Mentorship needs at academic institutions in resource-limited settings: a survey at makerere university college of health sciences},

author = {Damalie Nakanjako and Pauline Byakika-Kibwika and Kenneth Kintu and Jim Aizire and Fred Nakwagala and Simon Luzige and Charles Namisi and Harriet Mayanja-Kizza and Moses R Kamya

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Mentorship-needs-at-academic-institutions-in-resource-limited-settings....pdf},

doi = {10.1186/1472-6920-11-53},

year  = {2012},

date = {2012-07-29},

journal = {BMC Medical Education},

volume = {11},

number = {1},

abstract = {

Background



Mentoring is a core component of medical education and career success. There is increasing global emphasis on mentorship of young scientists in order to train and develop the next leaders in global health. However, mentoring efforts are challenged by the high clinical, research and administrative demands. We evaluated the status and nature of mentoring practices at Makerere University College of Health Sciences (MAKCHS).

Methods



Pre-tested, self-administered questionnaires were sent by email to all Fogarty alumni at the MAKCHS (mentors) and each of them was requested to complete and email back the questionnaire. In addition to training level and number of mentors, the questionnaires had open-ended questions covering themes such as; status of mentorship, challenges faced by mentors and strategies to improve and sustain mentorship within MAKCHS. Similarly, open-ended questionnaires were sent and received by email from all graduate students (mentees) registered with the Uganda Society for Health Scientists (USHS). Qualitative data from mentors and mentees was analyzed manually according to the pre-determined themes.

Results



Twenty- two out of 100 mentors responded (14 email and 8 hard copy responses). Up to 77% (17/22) of mentors had Master's-level training and only 18% (4/22) had doctorate-level training. About 40% of the mentors had ≥ two mentees while 27% had none. Qualitative results showed that mentors needed support in terms of training in mentoring skills and logistical/financial support to carry out successful mentorship. Junior scientists and students reported that mentorship is not yet institutionalized and it is currently occurring in an adhoc manner. There was lack of awareness of roles of mentors and mentees. The mentors mentioned the limited number of practicing mentors at the college and thus the need for training courses and guidelines for faculty members in regard to mentorship at academic institutions.

Conclusions



Both mentors and mentees were willing to improve mentorship practices at MAKCHS. There is need for institutional commitment to uphold and sustain the mentorship best practices. We recommend a collaborative approach by the stakeholders in global health promotion to build local capacity in mentoring African health professionals},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Baeten2012,

title = {Antiretroviral Prophylaxis for HIV Prevention in Heterosexual Men and Women.},

author = {J.M. Baeten and D. Donnell and P. Ndase and N.R. Mugo and J.D. Campbell and J. Wangisi and J.W. Tappero and E.A. Bukusi, C.R. Cohen and E. Katabira and A. Ronald and E. Tumwesigye and E. Were and K.H. Fife, J. Kiarie and C. Farquhar and G. John-Stewart and A. Kakia, J. Odoyo, 

A. Mucunguzi and E. Nakku-Joloba and R. Twesigye, K. Ngure and C. Apaka and H. Tamooh and F. Gabona, A. Mujugira, 

D. Panteleeff and K.K. Thomas and L. Kidoguchi, M. Krows and J. Revall and S. Morrison and H. Haugen, M. Emmanuel-Ogier and L. Ondrejcek, and R.W. Coombs and L. Frenkel and C. Hendrix, N.N. Bumpus and D. Bangsberg, J.E. Haberer and W.S. Stevens and J.R. Lingappa, and C. Celum, for the Partners PrEP Study Team},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Antiretroviral-Prophylaxis-for-HIV-Prevention-in-Heterosexual-.pdf},

doi = {10.1056/NEJMoa1108524},

year  = {2012},

date = {2012-07-12},

journal = {The New England Journal of Medicine },

volume = {367},

number = {5},

pages = {399-411},

abstract = {Background

Antiretroviral preexposure prophylaxis is a promising approach for preventing hu

-

man immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations.

Method

s

We conducted a randomized trial of oral antiretroviral therapy for use as preexposure 

prophylaxis among HIV-1–serodiscordant heterosexual couples from Kenya and 

Uganda. The HIV-1–seronegative partner in each couple was randomly assigned to 

one of three study regimens — once-daily tenofovir (TDF), combination tenofovir–

emtricitabine (TDF–FTC), or matching placebo — and followed monthly for up to 

36 months. At enrollment, the HIV-1–seropositive partners were not eligible for anti

-

retroviral therapy, according to national guidelines. All couples received standard 

HIV-1 treatment and prevention services.

Results

We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to 

TDF, 1579 to TDF–FTC, and 1584 to placebo. For 62% of the couples followed, the 

HIV-1–seronegative partner was male. Among HIV-1–seropositive participants, the 

median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). 

A total of 82 HIV-1 infections occurred in seronegative participants during the study, 

17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF–FTC group 

(incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 

per 100 person-years), indicating a relative reduction of 67% in the incidence of 

HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with 

TDF–FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF–FTC and TDF alone 

against HIV-1 were not significantly different (P

=

0.23), and both study medications 

significantly reduced the HIV-1 incidence among both men and women. The rate of 

serious adverse events was similar across the study groups. Eight participants re

-

ceiving active treatment were found to have been infected with HIV-1 at baseline, 

and among these eight, antiretroviral resistance developed in two during the study.

Conclusions

Oral TDF and TDF–FTC both protect against HIV-1 infection in heterosexual men 

and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP 

ClinicalTrials.gov number, NCT00557245.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kalema2012,

title = {Oral Antimicrobial Rinse to Reduce Mycobacterial Culture Contamination among Tuberculosis Suspects in Uganda: A Prospective Study},

author = {Nelson Kalema and Saskia Den Boon and Adithya Cattamanchi and J. Lucian Davis and Alfred Andama and Winceslaus Katagira and Charles Everett and Nicholas Walter and Patrick Byanyima and Sylvia Kaswabuli and William Worodria and Laurence Huang},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Oral-Antimicrobial-Rinse-to-Reduce-Mycobacterial-Culture-Contamination-among-Tuberculosis-Suspects-in-Uganda.pdf},

doi = { 10.1371/journal.pone.0038888},

year  = {2012},

date = {2012-07-12},

journal = {PloS One},

volume = {7},

number = {7},

abstract = {RATIONALE:



Contamination by bacterial or fungal organisms reduces the effectiveness of mycobacterial culture for diagnosis of pulmonary tuberculosis (TB). We evaluated the effect of an anti-microbial and an anti-fungal oral rinse prior to expectoration on culture-contamination rates.

METHODS:



We enrolled a consecutive random sample of adults with cough for ≥ 2 weeks and suspected TB admitted to Mulago Hospital (Kampala, Uganda) between October 2008 and June 2009. We randomly assigned patients to oral rinse (60 seconds with chlorhexidine followed by 60 seconds with nystatin) vs. no oral rinse prior to initial sputum collection. Uganda National Tuberculosis Reference Laboratory technicians blinded to the method of sputum collection (with or without oral rinse) processed all sputum specimens for smear microscopy (direct Ziehl-Neelsen) and mycobacterial culture (Lowenstein-Jensen media).

RESULTS:



Of 220 patients enrolled, 177 (80%) were HIV-seropositive (median CD4-count 37 cells/uL, IQR 13-171 cells/uL). Baseline characteristics were similar between patients in the oral-rinse (N = 110) and no oral-rinse (N = 110) groups. The proportion of contaminated cultures was significantly lower in the oral-rinse group compared to the no oral-rinse group (4% vs. 15%, risk difference -11%, 95% CI -18 to -3%, p = 0.005). Oral rinse significantly reduced the proportion of contaminated cultures among HIV-infected patients (3% vs. 18%, risk difference -14%, 95% CI -23 to -6%, p = 0.002) but not HIV-uninfected (6% vs. 4%, risk difference 2%, 95% CI -12 to +15%, p = 0.81) patients. However, the proportion of smear-positive specimens (25% vs. 35%, p = 0.10) and culture-positive specimens (48% vs. 56%, p = 0.24) were lower in the oral-rinse compared to the no oral-rinse group, although the differences were not statistically significant.

CONCLUSIONS:



Oral rinse prior to sputum expectoration is a promising strategy to reduce mycobacterial culture contamination in areas with high HIV prevalence, if strategies can be devised to reduce the adverse impact of oral rinse on smear- and culture-positivity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Semeere2012,

title = {Sub-Optimal Vitamin B-12 Levels among ART-Naı  ̈ ve HIV- Positive Individuals in an Urban Cohort in Uganda},

author = {Aggrey S. Semeere and Damalie Nakanjako and Henry Ddungu and Andrew Kambugu and Yukari C. Manabe and Robert Colebunders

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Sub-Optimal-Vitamin-B-12-Levels-among-ART-Naıve-HIV-positive....pdf},

doi = {10.1371/journal.pone.0040072},

year  = {2012},

date = {2012-07-02},

journal = {PloS One},

volume = {7},

number = {7},

abstract = {Malnutrition is common among HIV-infected individuals and is often accompanied by low serum levels of micronutrients. Vitamin B-12 deficiency has been associated with various factors including faster HIV disease progression and CD4 depletion in resource-rich settings. To describe prevalence and factors associated with sub-optimal vitamin B-12 levels among HIV-infected antiretroviral therapy (ART) naïve adults in a resource-poor setting, we performed a cross-sectional study with a retrospective chart review among individuals attending either the Mulago-Mbarara teaching hospitals' Joint AIDS Program (MJAP) or the Infectious Diseases Institute (IDI) clinics, in Kampala, Uganda. Logistic regression was used to determine factors associated with sub-optimal vitamin B-12. The mean vitamin B-12 level was 384 pg/ml, normal range (200-900). Sub-optimal vitamin B-12 levels (<300 pg/ml) were found in 75/204 (36.8%). Twenty-one of 204 (10.3%) had vitamin B-12 deficiency (<200 pg/ml) while 54/204 (26.5%) had marginal depletion (200-300 pg/ml). Irritable mood was observed more among individuals with sub-optimal vitamin B-12 levels (OR 2.5, 95% CI; 1.1-5.6, P=0.03). Increasing MCV was associated with decreasing serum B-12 category; 86.9 fl (± 5.1) vs. 83 fl (± 8.4) vs. 82 fl (± 8.4) for B-12 deficiency, marginal and normal B-12 categories respectively (test for trend, P=0.017). Compared to normal B-12, individuals with vitamin B-12 deficiency had a longer known duration of HIV infection: 42.2 months (± 27.1) vs. 29.4 months (± 23.8; P=0.02). Participants eligible for ART (CD4<350 cells/µl) with sub-optimal B-12 had a higher mean rate of CD4 decline compared to counterparts with normal B-12; 118 (± 145) vs. 22 (± 115) cells/µl/year, P=0.01 respectively. The prevalence of a sub-optimal vitamin B-12 was high in this HIV-infected, ART-naïve adult clinic population in urban Uganda. We recommend prospective studies to further clarify the causal relationships of sub-optimal vitamin B-12, and explore the role of vitamin B-12 supplementation in immune recovery.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Piloya2012,

title = {Lipodystrophy among HIV-infected children and adolescents on highly active antiretroviral therapy in Uganda: a cross sectional study},

author = {Thereza Piloya and Sabrina Bakeera-Kitaka and Adeodata Kekitiinwa and Moses R Kamya},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Lipodystrophy-among-HIV-infected-children-and-adolescents-on-highly-active-antiretroviral-therapy-in-Uganda.pdf},

doi = {10.7448/IAS.15.2.17427},

year  = {2012},

date = {2012-07-02},

journal = {Journal of the Intrernational AIDS society},

volume = {15},

number = {2},

abstract = {BACKGROUND:



With widespread use of antiretroviral therapy (ART) and prolonged survival of HIV-infected children, toxicities like lipodystrophy are becoming more evident. Little is known about lipodystrophy in children in Uganda yet there is increased use of ART. The aim of this study was to determine the prevalence and factors associated with fat redistribution and metabolic abnormalities among HIV-infected children on highly active antiretroviral therapy (HAART) in Uganda.

METHODS:



A cross-sectional study of 364 HIV positive children aged between 2 and 18 years on ART were enrolled after consent and assent as appropriate. Sociodemographic, clinical and immunological data were collected and recorded in a questionnaire. Fat redistribution was assessed clinically for physical findings of lipohypertrophy and lipoatrophy. A fasting blood sample was taken for lipid profile and blood glucose analysis. Lipodystrophy was defined as presence of abnormal fat redistribution or metabolic abnormalities or both. The proportion of children with fat redistribution and metabolic abnormalities was calculated. We conducted multivariate analysis for factors associated with lipodystrophy among children with lipodystrophic features and those without.

RESULTS:



The median age of the participants was eight years (range 2 to 18), with 43% of these aged ≥ 10 years and a male to female ratio of 1.1:1. Majority (65%) had advanced HIV (WHO Stage III/IV) at ART initiation with a mean duration on ART of 3.8 years (± 1.2). The prevalence of fat redistribution and hyperlipidemia was 27.0% and 34.0%, respectively. None of the children had hyperglycaemia. Among the children with hyperlipidemia, 16.8% exhibited hypercholesterolemia and 83% had hypertriglyceridemia. Only 29% of children with fat redistribution had hyperlipidemia. We found significant association between fat redistribution and Tanner stages 2 to 5 OR=2.3 (95%CI 1.3 to 3.8), age ≥ 5 years OR=3.9 (95%CI 1.5 to 9.9) and d4T exposure OR=3.4 (95%CI 2.0 to 5.8). A Tanner stage 2 to 5 was independently associated with hyperlipidemia. No significant association was observed with HIV clinical stage and any of the anthropometric measurements.

CONCLUSION:



The prevalence of lipodystrophy is high among HIV-infected children on ART with a likelihood of developing fat redistribution and metabolic abnormalities increased during puberty.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jacob2012,

title = {The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention study},

author = {Shevin T Jacob and Patrick Banura and Jared M Baeten and Christopher C Moore and David Meya and Lydia Nakiyingi and Rebecca Burke and Cheryl Lynn Horton and Boaz Iga and Anna Wald and Steven J Reynolds and Harriet Mayanja-Kizza,},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/The-impact-of-early-monitored-management-on-survival-in-hospitalized-adult-Ugandan-patients....pdf},

doi = {10.1097/CCM.0b013e31824e65d7},

year  = {2012},

date = {2012-07-01},

journal = {Critical Care Medicine},

volume = {40},

number = {7},

pages = {2050–2058},

abstract = {In sub-Saharan Africa, sepsis is an important cause of mortality. Optimal sepsis management including fluid resuscitation, early antibiotic administration, and patient monitoring is limited by lack of supplies and skilled health workers.

OBJECTIVE:



To evaluate whether early, monitored sepsis management provided by a study medical officer can improve survival among patients with severe sepsis admitted to two public hospitals in Uganda.

DESIGN, SETTING, AND PATIENTS:



A prospective before and after study of an intervention cohort (n = 426) with severe sepsis receiving early, monitored sepsis management compared to an observation cohort (n = 245) of similarly ill patients with severe sepsis receiving standard management after admission to the medical wards of two Ugandan hospitals.

INTERVENTION:



Early sepsis management provided by a dedicated study medical officer comprising fluid resuscitation, early antibiotics, and regular monitoring in the first 6 hrs of hospitalization.

MEASUREMENTS:



Kaplan-Meier survival and unadjusted and adjusted Cox proportional hazards analysis were used to compare the effect of early, monitored sepsis management on 30-day mortality between the intervention cohort (enrolled May 2008 to May 2009) and observation cohort (enrolled July 2006 to November 2006).

RESULTS:



The majority (86%) of patients in both cohorts were human immuno-deficiency virus-infected. Median fluid volume provided in the first 6 hrs of hospitalization was higher in intervention than observation cohort patients (3000 mL vs. 500 mL, p < .001) and a greater proportion of intervention cohort patients received antibacterial therapy in <1 hr (67% vs. 30.4%, p < .001). Mortality at 30 days was significantly lower in the intervention cohort compared to the observation cohort (33.0% vs. 45.7%, log-rank p = .005). After adjustment for potential confounders, the hazard of 30-day mortality was 26% less in the intervention cohort compared to the observation cohort (adjusted hazards ratio 0.74, 95% confidence interval 0.55-0.98). Mortality among the 13% of intervention patients who developed signs of respiratory distress was associated with baseline illness severity rather than fluid volume administered.

CONCLUSION:



Early, monitored management of severely septic patients in Uganda improves survival and is feasible and safe even in a busy public referral hospital.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cattamanchi2012,

title = {Bronchoalveolar Lavage Enzyme-Linked Immunospot for Diagnosis of Smear-Negative Tuberculosis in HIV- Infected Patients},

author = {Adithya Cattamanchi and Isaac Ssewenyana and Rose Nabatanzi and Cecily R. Miller and Saskia Den Boon and J. Lucian Davis and Alfred Andama and William Worodria and Samuel D. Yoo and Huyen Cao and Laurence Huang},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Bronchoalveolar-Lavage-Enzyme-Linked-Immunospot-for-Diagnosis-of-Smear-Negative-Tuberculosis-in-HIVInfected-Patients-1.pdf},

doi = {10.1371/journal.pone.0039838},

year  = {2012},

date = {2012-06-26},

journal = {PloS One},

volume = {7},

number = {6},

abstract = {BACKGROUND:



Peripheral blood interferon-gamma release assays (IGRAs) have sub-optimal sensitivity and specificity for diagnosis of active pulmonary tuberculosis (TB). However, assessment of local immune responses has been reported to improve the accuracy of TB diagnosis.

METHODS:



We enrolled HIV-infected adults with cough ≥2 weeks' duration admitted to Mulago Hospital in Kampala, Uganda and referred for bronchoscopy following two negative sputum acid-fast bacillus smears. We performed an ELISPOT-based IGRA (T-SPOT.TB®, Oxford Immunotec, Oxford, UK) using peripheral blood and bronchoalveolar lavage (BAL) fluid mononuclear cells, and determined the accuracy of IGRAs using mycobacterial culture results as a reference standard.

RESULTS:



94 HIV-infected patients with paired peripheral blood and BAL IGRA results were included. The study population was young (median age 34 years [IQR 28-40 years]) and had advanced HIV/AIDS (median CD4+ T-lymphocyte count 60 cells/µl [IQR 22-200 cells/µl]). The proportion of indeterminate IGRA results was higher in BAL fluid than in peripheral blood specimens (34% vs. 14%, difference 20%, 95% CI 7-33%, p = 0.002). BAL IGRA had moderate sensitivity (73%, 95% CI 50-89%) but poor specificity (48%, 95% CI 32-64%) for TB diagnosis. Sensitivity was similar (75%, 95% CI 57-89%) and specificity was higher (78%, 95% CI 63-88%) when IGRA was performed on peripheral blood.

CONCLUSIONS:



BAL IGRA performed poorly for the diagnosis of smear-negative TB in a high HIV/TB burden setting. Further studies are needed to examine reasons for the large proportion of indeterminate results and low specificity of BAL IGRA for active TB in high HIV/TB burden settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{AK2012,

title = {Challenges in diagnosis and management of  Cryptococcal immune reconstitution inflammatory syndrome (IRIS) in resource limited settings},

author = {Musubire AK and Meya BD and Mayanja-Kizza H and Lukande R and Wiesner LD and Bohjanen P and R. Boulware},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Challenges-in-diagnosis-and-management-of-Cryptococcal-immune.pdf},

doi = { 10.4314/ahs.v12i2.23},

year  = {2012},

date = {2012-06-12},

journal = {African Health Sciences},

volume = {2},

number = {2},

pages = {226-30},

abstract = {In many resource-limited settings, cryptococcal meningitis (CM) contributes up to 20% of all deaths with further complications due to Immune Reconstitution Inflammatory Syndrome (IRIS). We present a case report on a patient who developed CM-IRIS and then subsequent CM-relapse with a fluconazole-resistant organism and then later CM-IRIS once again, manifesting as cystic cryptococcomas, hydrocephalus, and sterile CSF. In this case we, demonstrate that CM-IRIS and persistent low level cryptococcal infection are not mutually exclusive phenomena. The management of IRIS with corticosteroids may increase the risk of culture positive CM-relapse which may further increase the risk of recurrent IRIS and resulting complications including death. We also highlight the role of imaging and fluconazole resistance testing in patients with recurrent meningitis and the importance of CSF cultures in guiding treatment decisions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Byakika-Kibwika2012,

title = {Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults},

author = {Pauline Byakika-Kibwika and Mohammed Lamorde and Jonathan Mayita and Lillian Nabukeera and Rhoda Namakula and Harriet Mayanja-Kizza and Elly Katabira and Muhammad Ntale and Nadine Pakker and Mairin Ryan and Warunee Hanpithakpong and Joel Tarning and Niklas Lindegard and Peter J. de Vries and Saye Khoo and David Back and Concepta Merry

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Significant-pharmacokinetic-interactions-between....pdf},

doi = {10.1093/jac/dks207},

year  = {2012},

date = {2012-06-11},

journal = {Journal of Antimicrobial Chemotherapy},

volume = {67},

number = {9},

pages = {2213-21},

abstract = {OBJECTIVES:



Co-administration of artemether/lumefantrine with antiretroviral therapy has potential for pharmacokinetic drug interactions. We investigated drug-drug interactions between artemether/lumefantrine and efavirenz or nevirapine.

METHODS:



We performed a cross-over study in which HIV-infected adults received standard six-dose artemether/lumefantrine 80/480 mg before and at efavirenz or nevirapine steady state. Artemether, dihydroartemisinin, lumefantrine, efavirenz and nevirapine plasma concentrations were measured and compared.

RESULTS:



Efavirenz significantly reduced artemether maximum concentration (C(max)) and plasma AUC (median 29 versus 12 ng/mL, P < 0.01, and 119 versus 25 ng · h/mL, P < 0.01), dihydroartemisinin C(max) and AUC (median 120 versus 26 ng/mL, P < 0.01, and 341 versus 84 ng · h/mL, P < 0.01), and lumefantrine C(max) and AUC (median 8737 versus 6331 ng/mL, P = 0.03, and 280 370 versus 124 381 ng · h/mL, P < 0.01). Nevirapine significantly reduced artemether C(max) and AUC (median 28 versus 11 ng/mL, P < 0.01, and 123 versus 34 ng · h/mL, P < 0.01) and dihydroartemisinin C(max) and AUC (median 107 versus 59 ng/mL, P < 0.01, and 364 versus 228 ng · h/mL, P < 0.01). Lumefantrine C(max) and AUC were non-significantly reduced by nevirapine. Artemether/lumefantrine reduced nevirapine C(max) and AUC (median 8620 versus 4958 ng/mL, P < 0.01, and 66 329 versus 35 728 ng · h/mL, P < 0.01), but did not affect efavirenz exposure.

CONCLUSIONS:



Co-administration of artemether/lumefantrine with efavirenz or nevirapine resulted in a reduction in artemether, dihydroartemisinin, lumefantrine and nevirapine exposure. These drug interactions may increase the risk of malaria treatment failure and development of resistance to artemether/lumefantrine and nevirapine. Clinical data from population pharmacokinetic and pharmacodynamic trials evaluating the impact of these drug interactions are urgently needed},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{S2012e,

title = {Using a clinic based creativity initiative to reduce HIV related stigma at the Infectious Diseases Institute, Mulago National Referral Hospital, Uganda},

author = {Neema S and Atuyambe LM and Otolok-Tanga E and Twijukye C and Kambugu A and Thayer L and McAdam K},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Using-a-clinic-based-creativity-initiative-to-reduce-HIV-related-stigma....pdf},

doi = { 10.4314/ahs.v12i2.24},

year  = {2012},

date = {2012-06-02},

journal = {African Health Sciences},

volume = {12},

number = {2},

pages = {231-9},

abstract = {BACKGROUND:



Stigma has been associated with chronic health conditions such as HIV/AIDS, leprosy, tuberculosis, Mental illness and Epilepsy. Different forms of stigma have been identified: enacted stigma, perceived stigma, and self stigma. Stigma is increasingly regarded as a key driver of the HIV/AIDS epidemic and has a major impact on public health interventions.

OBJECTIVES:



The initiative was to provide activities in the clinic while patients waited to be seen by healthcare professionals. It was envisaged this would contribute to reduction of clinic based stigma felt by clients.

METHODS:



This was a repeated cross-sectional survey (October-November 2005 and March-April 2007) that was conducted at the Infectious Diseases Institute clinic (IDC) at Mulago, the national referral hospital in Uganda. We utilized quantitative (survey) and qualitative (key informants, focus group discussions) methods to collect the data. Data were collected on stigma before the creativity initiative intervention was implemented, and a second phase survey was conducted to assess effectiveness of the interventions.

RESULTS:



Clients who attended the IDC before the creativity intervention were about twice as likely to fear catching an infection as those who came after the intervention. The proportion that had fears to be seen by a friend or relative at the clinic decreased. Thus during the implementation of the Creativity intervention, HIV related stigma was reduced in this clinic setting.

CONCLUSIONS:



The creativity intervention helped to build self esteem and improved communication among those attending the clinic; there was observed ambiance at the clinic and clients became empowered, with creative, communication and networking skills. Improved knowledge and communication are key in addressing self stigma among HIV positive individuals.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hermans2012c,

title = {Integration of HIV and TB services results in improved TB treatment outcomes and earlier, prioritized ART initiation in a large urban HIV clinic in Uganda},

author = {Sabine M Hermans and Barbara Castelnuovo and Catherine Katabira and Peter Mbidde and Joep MA Lange and Andy IM Hoepelman and Alex Coutinhonand 

Yukari C Manabe},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Integration-of-HIV-and-TB-services-results-in-improved-TB-treatment-outcomesand-earlier....pdf},

doi = { 10.1097/QAI.0b013e318251aeb4},

year  = {2012},

date = {2012-06-01},

journal = {Journal of Acquired Immune Dificiency syndrome},

number = {60},

pages = {29-35},

abstract = {BACKGROUND:



The World Health Organization recommends that treatment of tuberculosis (TB) in HIV-infected patients should be integrated with HIV care. In December 2008, a separate outdoor-integrated TB/HIV clinic was instituted for attendees of a large urban HIV clinic in Uganda. We sought to evaluate associated TB and HIV treatment outcomes.

METHODS:



Routinely collected clinical, pharmacy, and laboratory data were merged with TB clinic data for patients initiating TB treatment in 2009 and with TB register data for patients in 2007. TB treatment outcomes and (timing of) antiretroviral therapy (ART) initiation in ART-naive patients [overall and stratified by CD4+ T cell (CD4) count] in 2007 and 2009 were compared. Nosocomial transmission rates could not be assessed.

RESULTS:



Three hundred forty-six patients were initiated on TB treatment in 2007 and 366 in 2009. Median CD4 counts at TB diagnosis did not differ. TB treatment cure or completion increased from 62% to 68%, death or default decreased from 33% to 25% (P < 0.001). Fewer ART-naive TB patients were initiated on ART in 2009 versus 2007 (57% and 66%, P = 0.031), but this decrease was only in patients with CD4 counts >250 cells per cubic millimeter (19% vs. 48%, P = 0.003). More patients were started on ART during TB treatment (94% vs. 78%, P < 0.001). Moreover, the majority were now initiated during intensive phase (60% vs. 23%, P < 0.001).

CONCLUSIONS:



Integration of TB and HIV care has led to improved TB treatment outcomes and earlier, prioritized ART initiation. This supports rollout of a fully integrated TB/HIV service delivery model throughout high-prevalence TB and HIV settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{KISEMBO2012,

title = {Chest radiographic findings of pulmonary tuberculosis in severely immunocompromised patients with the human immunodeficiency virus},

author = {H N KISEMBO and S DEN BOON and J L DAVIS and R OKELLO and W WORODRIA and A CATTAMANCH and L HUANG and M G KAWOOYA},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Chest-radiographic-findings-of-pulmonary-tuberculosis-in.pdf},

doi = {10.1259/bjr/70704099},

year  = {2012},

date = {2012-06-01},

journal = {British Journal of Radiology},

volume = {85},

number = {1014},

pages = {130-9},

abstract = {OBJECTIVE:



We describe chest radiograph (CXR) findings in a population with a high prevalence of human immunodeficiency virus (HIV) and tuberculosis (TB) in order to identify radiological features associated with TB; to compare CXR features between HIV-seronegative and HIV-seropositive patients with TB; and to correlate CXR findings with CD4 T-cell count.

METHODS:



Consecutive adult patients admitted to a national referral hospital with a cough of duration of 2 weeks or longer underwent diagnostic evaluation for TB and other pneumonias, including sputum examination and mycobacterial culture, bronchoscopy and CXR. Two radiologists blindly reviewed CXRs using a standardised interpretation form.

RESULTS:



Smear or culture-positive TB was diagnosed in 214 of 403 (53%) patients. Median CD4+ T-cell count was 50 cells mm(-3) [interquartile range (IQR) 14-150]. TB patients were less likely than non-TB patients to have a normal CXR (12% vs 20%, p = 0.04), and more likely than non-TB patients to have a diffuse pattern of opacities (75% vs 60%, p = 0.003), reticulonodular opacities (45% vs 12%, p < 0.001), nodules (14% vs 6%, p = 0.008) or cavities (18% vs 7%, p = 0.001). HIV-seronegative TB patients more often had consolidation (70% vs 42%, p = 0.007) and cavities (48% vs 13%, p < 0.001) than HIV-seropositive TB patients. TB patients with a CD4+ T-cell count of ≤ 50 cells mm(-3) less often had consolidation (33% vs 54%, p = 0.006) and more often had hilar lymphadenopathy (30% vs 16%, p = 0.03) compared with patients with CD4 51-200 cells mm(-3).

CONCLUSION:



Although different CXR patterns can be seen in TB and non-TB pneumonias there is considerable overlap in features, especially among HIV-seropositive and severely immunosuppressed patients. Providing clinical and immunological information to the radiologist might improve the accuracy of radiographic diagnosis of TB},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Alamo2012,

title = {Return to Normal Life After AIDS as a Reason for Lost to Follow- up in a Community-Based Antiretroviral Treatment Program},

author = {Stella T. Alamo and Robert Colebunders and Joseph Ouma and Pamela Sunday and Glenn Wagner and Fred Wabwire-Mangen and Marie Laga},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Return-to-Normal-Life-After-AIDS-as-a-Reason-for-Lost-to-Follow-up....pdf},

doi = { 10.1097/FTD.0b013e3182526e6a},

year  = {2012},

date = {2012-06-01},

journal = {Journal of Acquired Immune Dificiency syndrome},

volume = {60},

number = {2},

pages = {36-45},

abstract = {OBJECTIVES:



To understand reasons for lost-to-follow-up (LTFU) from a community-based antiretroviral therapy program in Uganda.

STUDY DESIGN:



Retrospective cohort of patients LTFU between May 31, 2001, to May 31, 2010, was examined. A representative sample of 579 patients traced to ascertain their outcomes.

METHODS:



Mixed methods were used. Using "stopped care" as the hazard and "self-transferred" as the comparator, we examined using Cox proportional multivariable model risk factors for stopping care.

RESULTS:



Overall, 2933 of 3954 (74.0%) patients were LTFU. Of 579 of 2933 (19%) patients sampled for tracing, 32 (5.5%) were untraceable, 66(11.4 %) were dead, and 481 (83.0%) found alive. Of those found alive, 232 (40.0%) stopped care, 249 (43.0%) self-transferred, whereas 61 (12.7%) returned to care at Reach Out Mbuya HIV/AIDS Initiative. In adjusted hazards ratios, born-again religion, originating from outside Kampala, resident in Kampala for <5 years but >1 year, having school-age children who were out of school, non-HIV disclosure, CD4 counts >250 cells per cubic millimeter and pre-antiretroviral therapy were associated with increased risk of stopping care. Qualitative interviews revealed return to a normal life as a key reason for LTFU. Of 61 patients who returned to care, their median CD4 count at LTFU was higher than on return into care (401/mm³ vs. 205/mm³, P < 0.0001).

CONCLUSIONS:



Many patients become LTFU during the course of years, necessitating the need for effective mechanisms to identify those in need of close monitoring. Efforts should be made to improve referrals and mechanisms to track patients who transfer to different facilities. Additionally, tracing of patients who become LTFU is required to convince them to return.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gibb2012,

title = {Pregnancy and Infant Outcomes among HIV-Infected Women Taking Long-Term ART with and without Tenofovir in the DART Trial},

author = {Diana M. Gibb and Hilda Kizito and Elizabeth C. Russell and Ennie Chidziva and Eva Zalwango and Ruth Nalumenya and Moira Spyer and Dinah Tumukunde and Kusum Nathoo and Paula Munderi and Hope Kyomugisha and James Hakim and Heiner Grosskurth and Charles F. Gilks and A. Sarah Walker and Phillipa Musoke and on behalf of the DART trial

team

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Pregnancy-and-Infant-Outcomes-among-HIV-Infected....pdf},

doi = {10.1371/journal.pmed.1001217},

year  = {2012},

date = {2012-05-15},

journal = {PloS Medicine},

volume = {9},

number = {5},

abstract = {BACKGROUND:



Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)-recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure.

METHODS AND FINDINGS:



Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models. 382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0-4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths (≥22 wk), and 137 (35%) terminations/miscarriages (<22 wk). Of 226 live-births, seven (3%) infants died <2 wk from perinatal causes and there were seven (3%) congenital abnormalities, with no effect of in utero tenofovir exposure (p>0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12-38) months. From mothers' ART, 62/9/111 infants had no/20%-89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75-212) days. Overall, 14 infants died at median (IQR) age 9 (3-23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14 children with no effect of in utero tenofovir (p>0.1). There was no evidence that in utero tenofovir affected growth after 2 years (p = 0.38). Attained height- and weight for age were similar to general (HIV-uninfected) Ugandan populations. Study limitations included relatively small size and lack of randomisation to maternal ART regimens.

CONCLUSIONS:



Overall 1-year 5% infant mortality was similar to the 2%-4% post-neonatal mortality observed in this region. No increase in congenital, renal, or growth abnormalities was observed with in utero tenofovir exposure. Although some infants died untested, absence of recorded HIV infection with combination ART in pregnancy is encouraging. Detailed safety of tenofovir for pre-exposure prophylaxis will need confirmation from longer term follow-up of larger numbers of exposed children.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ssali2012,

title = {HIV Clients as Agents for Prevention: A Social Network Solution},

author = {Sarah Ssali and Glenn Wagner and Christopher Tumwine and Annette Nannungi and and Harold Green},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/HIV-Clients-as-Agents-for-Prevention....pdf},

doi = {10.1155/2012/815823},

year  = {2012},

date = {2012-05-15},

journal = {AIDS Research and Treatment},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sendagire2012,

title = {Urban movement and alcohol intake strongly predict defaulting from tuberculosis treatment: an operational study. Directorate of Health, Kampala Capital City Authority, Kampala, Uganda},

author = {Ibrahim Sendagire and Maarten Schim Van der Loeff and Andrew Kambugu and Joseph Konde-Lule and Frank Cobelens},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Urban-Movement-and-Alcohol-Intake-Strongly-Predict....pdf},

doi = {10.1371/journal.pone.0035908},

year  = {2012},

date = {2012-05-02},

journal = {PloS One},

volume = {7},

number = {5},

abstract = {Background:

High levels of defaulting from treatment challenge tuberculosis control in many African cities. We assessed

defaulting from tuberculosis treatment in an African urban setting.

Methods:

An observational study among adult patients with smear-positive pulmonary tuberculosis receiving treatment at

urban primary care clinics in Kampala, Uganda. Defaulting was defined as having missed two consecutive monthly clinic

visits while not being reported to have died or continued treatment elsewhere. Defaulting patients were actively followed-

up and interviewed. We assessed proportions of patients abandoning treatment with and without the information obtained

through active follow-up and we examined associated factors through multivariable logistic regression.

Results:

Between April 2007 and April 2008, 270 adults aged

$

15 years were included; 54 patients (20%) were recorded as

treatment defaulters. On active follow-up vital status was established of 28/54 (52%) patients. Of these, 19 (68%) had

completely stopped treatment, one (4%) had died and eight (29%) had continued treatment elsewhere. Extrapolating this

to all defaulters meant that 14% rather than 20% of all patients had truly abandoned treatment. Daily consumption of

alcohol, recorded at the start of treatment, predicted defaulting (adjusted odds ratio [OR

adj

] 4.4, 95%CI 1.8–13.5), as did

change of residence during treatment (OR

adj

8.7, 95%CI 1.8–41.5); 32% of patients abandoning treatment had changed

residence.

Conclusions:

A high proportion of tuberculosis patients in primary care clinics in Kampala abandon treatment. Assessing

change of residence during scheduled clinic appointments may serve as an early warning signal that the patient may

default and needs adherence counseling.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Worodria2012,

title = {Clinical spectrum, risk factors and outcome of immune reconstitution inflammatory syndrome in patients with tuberculosis-HIV coinfection},

author = {W. Worodria and Menten J and Massinga-Loembe M and Mazakpwe D and Bagenda D, Koole O and Mayanja-Kizza H and Kestens L and Mugerwa R and Reiss P and Colebunders R},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Clinical-spectrum-risk-factors-and-outcome-of-immune-reconstitution-inflammatory-syndrome-in-patients-with-tuberculosis-HIV-coinfection-1.pdf},

doi = {10.3851/IMP2108},

year  = {2012},

date = {2012-04-27},

journal = {Antiviral Therapy},

volume = {17},

number = {5},

pages = {841-8},

abstract = {BACKGROUND:



Here, we aimed to determine the clinical spectrum, predictors and outcomes of paradoxical tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) in a resource-limited setting.

METHODS:



In a prospective cohort, we studied 254 patients with tuberculosis and HIV coinfection commencing antiretroviral therapy (ART). We identified patients with TB-IRIS using the International Network for Studies Against HIV-Associated IRIS (INSHI) case definition. Risk factors and clinical outcomes of TB-IRIS were determined and reported.

RESULTS:



A total of 53 (21%) patients developed TB-IRIS a median of 2 weeks (IQR 12-22 days) after starting ART. The majority of the patients (70%) with TB-IRIS had extrapulmonary manifestations of TB-IRIS. In a multiple logistic regression model, baseline haemoglobin <100 g/l (OR 2.23 [95% CI 1.08-4.60]; P=0.031) and baseline CD4(+) T-cell count <50 cells/μl (OR 4.13 [95% CI 1.80-9.51]; P=0.001) were significant predictors of IRIS. Seven additional patients fulfilled all INSHI criteria of TB-IRIS but had the episode of TB-IRIS later than 3 months after ART start.

CONCLUSIONS:



TB-IRIS was a frequent reason for clinical deterioration among patients with TB commencing ART but was not a primary contributor to mortality. Patients with advanced CD4 depletion and anaemia were at increased risk of TB-IRIS. Some patients developed late-onset TB-IRIS and/or a recurrent TB-IRIS episode},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Byakika-Kibwika2012b,

title = {Pharmacokinetics and pharmacodynamics of intravenous artesunate during severe malaria treatment in Ugandan adults},

author = {Pauline Byakika-Kibwika and Mohammed Lamorde and Jonathan Mayito and Lillian Nabukeera and Harriet Mayanja-Kizza and Elly Katabira and Warunee Hanpithakpong and Celestino Obua and Nadine Pakker and Niklas Lindegardh and Joel Tarning and Peter J de Vries and Concepta Merry},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Pharmacokinetics-and-pharmacodynamics-of-intravenous-artesunate-during-severe-malaria-treatment-in-Uganda-adults.pdf},

doi = {10.1186/1475-2875-11-132},

year  = {2012},

date = {2012-04-27},

journal = {Malaria Journal},

abstract = {BACKGROUND:



Severe malaria is a medical emergency with high mortality. Prompt achievement of therapeutic concentrations of highly effective anti-malarial drugs reduces the risk of death. The aim of this study was to assess the pharmacokinetics and pharmacodynamics of intravenous artesunate in Ugandan adults with severe malaria.

METHODS:



Fourteen adults with severe falciparum malaria requiring parenteral therapy were treated with 2.4 mg/kg intravenous artesunate. Blood samples were collected after the initial dose and plasma concentrations of artesunate and dihydroartemisinin measured by solid-phase extraction and liquid chromatography-tandem mass spectrometry. The study was approved by the Makerere University Faculty of Medicine Research and Ethics Committee (Ref2010-015) and Uganda National Council of Science and Technology (HS605) and registered with ClinicalTrials.gov (NCT01122134).

RESULTS:



All study participants achieved prompt resolution of symptoms and complete parasite clearance with median (range) parasite clearance time of 17 (8-24) hours. Median (range) maximal artesunate concentration (Cmax) was 3260 (1020-164000) ng/mL, terminal elimination half-life (T1/2) was 0.25 (0.1-1.8) hours and total artesunate exposure (AUC) was 727 (290-111256) ng·h/mL. Median (range) dihydroartemisinin Cmax was 3140 (1670-9530) ng/mL, with Tmax of 0.14 (0.6 - 6.07) hours and T1/2 of 1.31 (0.8-2.8) hours. Dihydroartemisinin AUC was 3492 (2183-6338) ng·h/mL. None of the participants reported adverse events.

CONCLUSIONS:



Plasma concentrations of artesunate and dihydroartemisinin were achieved rapidly with rapid and complete symptom resolution and parasite clearance with no adverse events.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Manabe2012b,

title = {Rifampicin for Continuation Phase Tuberculosis Treatment in Uganda: A Cost-Effectiveness Analysis},

author = {Yukari C. Manabe and Sabine M. Hermans and Mohammed Lamorde and Barbara Castelnuovo and C.Daniel Mullins and Andreas Kuznik},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Rifampicin-for-Continuation-Phase-Tuberculosis....pdf},

doi = {10.1371/journal.pone.0039187},

year  = {2012},

date = {2012-04-27},

journal = {PloS One},

volume = {7},

number = {6},

abstract = {BACKGROUND:



In Uganda, isoniazid plus ethambutol is used for 6 months (6HE) during the continuation treatment phase of new tuberculosis (TB) cases. However, the World Health Organization (WHO) recommends using isoniazid plus rifampicin for 4 months (4HR) instead of 6HE. We compared the impact of a continuation phase using 6HE or 4HR on total cost and expected mortality from the perspective of the Ugandan national health system.

METHODOLOGY/PRINCIPAL FINDINGS:



Treatment costs and outcomes were determined by decision analysis. Median daily drug price was US$0.115 for HR and US$0.069 for HE. TB treatment failure or relapse and mortality rates associated with 6HE vs. 4HR were obtained from randomized trials and systematic reviews for HIV-negative (46% of TB cases; failure/relapse -6HE: 10.4% vs. 4HR: 5.2%; mortality -6HE: 5.6% vs. 4HR: 3.5%) and HIV-positive patients (54% of TB cases; failure or relapse -6HE: 13.7% vs. 4HR: 12.4%; mortality -6HE: 16.6% vs. 4HR: 10.5%). When the initial treatment is not successful, retreatment involves an additional 8-month drug-regimen at a cost of $110.70. The model predicted a mortality rate of 13.3% for patients treated with 6HE and 8.8% for 4HR; average treatment cost per patient was predicted at $26.07 for 6HE and $23.64 for 4HR. These results were robust to the inclusion of MDR-TB as an additional outcome after treatment failure or relapse.

CONCLUSIONS/SIGNIFICANCE:



Combination therapy with 4HR in the continuation phase dominates 6HE as it is associated with both lower expected costs and lower expected mortality. These data support the WHO recommendation to transition to a continuation phase comprising 4HR.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rajasingham2012b,

title = {Integrating Cryptococcal Antigen Screening and Preemptive Treatment into Routine HIV care},

author = {Radha Rajasingham and David B Meya and David R Boulware,},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Integrating-Cryptococcal-Antigen-Screening-and-Preemptive....pdf},

doi = {10.1097/QAI.0b013e31824c837e},

year  = {2012},

date = {2012-04-15},

journal = {Journal of Acquired Immune Dificiency syndrome},

volume = {59},

number = {5},

pages = {85-91},

abstract = {Cryptococcal meningitis is a leading cause of death in AIDS patients in sub-Saharan Africa. Cryptococcal antigen (CRAG) can be detected weeks before onset of symptoms, and those who are asymptomatic but CRAG positive have a high risk of subsequent cryptococcal meningitis and mortality. A new CRAG point of care immunochromatographic test is available that is remarkably easy to administer without laboratory infrastructure or expertise and has excellent sensitivity and specificity. We review the benefits of targeted CRAG screening, developments in CRAG diagnostics, and evidence regarding treatment options that can be implemented into routine HIV care in areas of high cryptococcal burden. Based on published CRAG+ prevalence rates of 2%-12%, the cost to save one life is between $20 to $140 in sub-Saharan Africa. We provide recommendations for implementation, pre-emptive treatment, and identify the gaps in our current knowledge.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Oyella2012,

title = {Prevalence and factors associated with cryptococcal antigenemia among severely immunosuppressed HIV-infected adults in Uganda: a cross-sectional study},

author = {Jacinta Oyella and David Meya and Francis Bajunirwe and Moses R Kamy },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Prevalence-and-factors-associated-with-cryptococcal....pdf},

doi = { 10.1186/1758-2652-15-15},

year  = {2012},

date = {2012-04-14},

journal = {Journal of the Intrernational AIDS society},

volume = {15},

number = {1},

abstract = {BACKGROUND:



Cryptococcal infection is a common opportunistic infection among severely immunosuppressed HIV patients and is associated with high mortality. Positive cryptococcal antigenemia is an independent predictor of cryptococcal meningitis and death in patients with severe immunosuppression. We evaluated the prevalence and factors associated with cryptococcal antigenemia among patients with CD4 counts of 100 cells/mm(3) or less in Mulago Hospital, Kampala, Uganda. Screening of a targeted group of HIV patients may enable early detection of cryptococcal infection and intervention before initiating antiretroviral therapy. Factors associated with cryptococcal antigenemia may be used subsequently in resource-limited settings in screening for cryptococcal infection, and this data may also inform policy for HIV care.

METHODS:



In this cross-sectional study, HIV-infected patients aged 18 years and older with CD4 counts of up to 100 cells/mm(3) were enrolled between December 2009 and March 2010. Data on socio-demographics, physical examinations and laboratory tests were collected. Factors associated with cryptococcal antigenemia were analyzed using multiple logistic regression.

RESULTS:



We enrolled 367 participants and the median CD4 count was 23 (IQR 9-51) cells/mm(3). Sixty-nine (19%) of the 367 participants had cryptococcal antigenemia. Twenty-four patients (6.5%) had cryptococcal meningitis on cerebrospinal fluid analysis and three had isolated cryptococcal antigenemia. Factors associated with cryptococcal antigenemia included: low body mass index of 15.4 kg/m2 or less (adjusted odds ratio, AOR = 0.5; 95% CI 0.3-1.0), a CD4(+) T cell count of less than 50 cells/mm(3) (AOR = 2.7; 95% CI1.2-6.1), neck pain (AOR = 2.3; 95% CI 1.2-4.6), recent diagnosis of HIV infection (AOR = 1.9; 95% CI 1.1-3.6), and meningeal signs (AOR = 7.9; 95% CI 2.9-22.1). However, at sub-analysis of asymptomatic patients, absence of neck pain (AOR = 0.5), photophobia (AOR = 0.5) and meningeal signs (AOR = 0.1) were protective against cryptococcal infection.

CONCLUSIONS:



Cryptococcal antigenemia is common among severely immunosuppressed HIV patients in Mulago Hospital, Kampala, Uganda. Independent predictors of positive serum cryptococcal antigenemia were CD4(+) T cell counts of less than 50 cells/mm, low body mass index, neck pain, signs of meningeal irritation, and a recent diagnosis of HIV infection. Routine screening of this category of patients may detect cryptococcosis, and hence provide an opportunity for early intervention. Absence of neck pain, photophobia and meningeal signs were protective against cryptococcal infection compared with symptomatic patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Manabe2012,

title = {Evaluation of Portable Point-of-Care CD4 Counter with High Sensitivity for Detecting Patients Eligible for Antiretroviral Therapy},

author = {Yukari C. Manabe and Yaping Wang and Ali Elbireer and Brandon Auerbach and Barbara Castelnuovo

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Evaluation-of-Portable-Point-of-Care-CD4-Counter-with.pdf},

doi = { 10.1371/journal.pone.0034319},

year  = {2012},

date = {2012-04-01},

journal = {PloS One},

volume = {7},

number = {4},

abstract = {BACKGROUND:



Accurate, inexpensive point-of-care CD4+ T cell testing technologies are needed that can deliver CD4+ T cell results at lower level health centers or community outreach voluntary counseling and testing. We sought to evaluate a point-of-care CD4+ T cell counter, the Pima CD4 Test System, a portable, battery-operated bench-top instrument that is designed to use finger stick blood samples suitable for field use in conjunction with rapid HIV testing.

METHODS:



Duplicate measurements were performed on both capillary and venous samples using Pima CD4 analyzers, compared to the BD FACSCalibur (reference method). The mean bias was estimated by paired Student's t-test. Bland Altman plots were used to assess agreement.

RESULTS:



206 participants were enrolled with a median CD4 count of 396 (range; 18-1500). The finger stick PIMA had a mean bias of -66.3 cells/µL (95%CI -83.4-49.2, P<0.001) compared to the FACSCalibur; the bias was smaller at lower CD4 counts (0-250 cells/µL) with a mean bias of -10.8 (95%CI -27.3-+5.6, P = 0.198), and much greater at higher CD4 cell counts (>500 cells/µL) with a mean bias of -120.6 (95%CI -162.8, -78.4, P<0.001). The sensitivity (95%CI) of the Pima CD4 analyzer was 96.3% (79.1-99.8%) for a <250 cells/ul cut-off with a negative predictive value of 99.2% (95.1-99.9%).

CONCLUSIONS:



The Pima CD4 finger stick test is an easy-to-use, portable, relatively fast device to test CD4+ T cell counts in the field. Issues of negatively-biased CD4 cell counts especially at higher absolute numbers will limit its utility for longitudinal immunologic response to ART. The high sensitivity and negative predictive value of the test makes it an attractive option for field use to identify patients eligible for ART, thus potentially reducing delays in linkage to care and ART initiation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Katusiime2012,

title = {A rare entity of primary extranodal diffuse large B cell lymphoma of the lower limb calf in an HIV-infected young adult on highly active antiretroviral therapy},

author = { Christine Katusiime and Andrew Kambugu },

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/A-rare-entity-of-primary-extranodal-diffuse-large-B-cell-lymphoma-of-the-lower-limb-calf-in-an-HIV-infected-young-adult-on-highly-active-antiretroviral-therapy.pdf},

doi = { 10.1136/bcr.12.2011.5444},

year  = {2012},

date = {2012-03-27},

journal = {BMC Case Reports},

abstract = {Primary cutaneous and skeletal muscle lymphomas are particularly rare phenomena in HIV sero-positive patients. The authors report a case of primary extranodal malignant diffuse large B cell lymphoma of the left gastrocnemius in a 21-year-old young adult who presented to the Infectious Diseases Institute, Kampala, Uganda having been on antiretroviral therapy for 2 years. The patient is still undergoing chemotherapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cox2012,

title = {An Autopsy Study Describing Causes of Death and Comparing Clinico-Pathological Findings among Hospitalized Patients in Kampala, Uganda},

author = {Janneke A. Cox and Robert L. Lukande and Ann M. Nelson and Harriet Mayanja-Kizza and Robert

Colebunders and Eric Van Marck and Yukari C. Manabe},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/An-Autopsy-Study-Describing-Causes-of-Death-and-comparing-clinico-pathological-finding....pdf},

doi = { 10.1371/journal.pone.0033685},

year  = {2012},

date = {2012-03-14},

journal = {PloS One},

volume = {7},

number = {3},

abstract = {BACKGROUND:



Information on causes of death in HIV-infected patients in Sub-Saharan Africa is mainly derived from observational cohort and verbal autopsy studies. Autopsy is the gold standard to ascertain cause of death. We conducted an autopsy study to describe and compare the clinical and autopsy causes of death and contributory findings in hospitalized HIV-infected and HIV-uninfected patients in Uganda.

METHODS:



Between May and September 2009 a complete autopsy was performed on patients that died on a combined infectious diseases gastroenterology ward in Mulago Hospital in Kampala, Uganda. Autopsy cause of death and contributing findings were based on the macro- and microscopic post-mortem findings combined with clinical information. Clinical diagnoses were reported by the ward doctor and classified as confirmed, highly suspected, considered or not considered, based on information derived from the medical chart. Results are reported according to HIV serostatus.

RESULTS:



Fifty-three complete autopsies were performed in 66% HIV-positive, 21% HIV-negative and 13% patients with an unknown HIV serological status. Infectious diseases caused death in 83% of HIV-positive patients, with disseminated TB as the main diagnosis causing 37% of deaths. The spectrum of illness and causes of death were substantially different between HIV-positive and HIV-negative patients. In HIV-positive patients 12% of postmortem diagnoses were clinically confirmed, 27% highly suspected, 16% considered and 45% not considered. In HIV-negative patients 17% of postmortem diagnoses were clinically highly suspected, 42% considered and 42% not considered.

CONCLUSION:



Autopsy examination remains an important tool to ascertain causes of death particularly in settings with limited access to diagnostic testing during life. HIV-positive patients continue to die from treatable and clinically undiagnosed infectious diseases. Until rapid-point of care testing is available to confirm common infections, empiric treatment should be further investigated.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lamorde2012,

title = {Effect of Food on the Steady-State Pharmacokinetics of Tenofovir and Emtricitabine plus Efavirenz in Ugandan Adults},

author = {Mohammed Lamorde and Pauline Byakika-Kibwika and William S. Tamale and Francis Kiweewa and Mairin Ryan and Alieu Amara and John Tjia and David Back and Saye Khoo and Marta Boffito and Cissy Kityo and Concepta Merry},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/EffectofFoodontheSteady-StatePharmacokineticsofTenofovir-andEmtricitabineplusEfavirenzinUgandanAdults.pdf},

doi = {10.1155/2012/105980},

year  = {2012},

date = {2012-02-20},

journal = {AIDS Research and Treatment},

abstract = {We investigated the effect of food on the steady-state pharmacokinetics of a proprietary fixed-dose combination (FDC) tablet containing tenofovir disoproxil fumarate (TDF)/emtricitabine/efavirenz. Fifteen Ugandan HIV-1 patients at steady-state dosing with TDF/emtricitabine/efavirenz were admitted for 24-hour intensive pharmacokinetic sampling after dosing in the fasting state. Blood sampling was repeated seven days later with TDF/emtricitabine/efavirenz administered with food (19 g fat). Drug concentrations in plasma were determined by liquid chromatography and tandem mass spectrometry. Geometric mean ratios (GMRs) and confidence intervals (CIs) of parameters were calculated (reference, fasting). For efavirenz, GMRs (90% CIs) for C(max), AUC(0-24), and C(24) were 1.47 (1.24-1.75), 1.13 (1.03-1.23), and 1.01 (0.91-1.11), respectively. Corresponding GMRs were 1.04 (0.84-1.27), 1.19 (1.10-1.29), and 0.99 (0.82-1.19) for tenofovir, 0.83 (0.76-0.92), 0.87 (0.78-0.97), and 0.91 (0.73-1.14) for emtricitabine. Stable patients may take the FDC without meal restrictions. The FDC should be taken without food by patients experiencing central nervous system toxicities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tumwine2012,

title = {Atypical presentation of colon adenocarcinoma: a case report},

author = {Lynnette K Tumwine and Magid Kagimu and Ponsiano Ocama and Innocent Segamwenge and Noah Masiira-Mukasa and Dan Wamala and Otto Dworak and Christopher K Opio},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Atypical-presentation-of-colon-adenocarcinima....pdf},

doi = {doi: 10.1186/1752-1947-6-58},

year  = {2012},

date = {2012-02-13},

journal = {Journal of Medical Case Reports},

abstract = {INTRODUCTION:



Adenocarcinoma of the colon is the most common histopathological type of colorectal cancer. In Western Europe and the United States, it is the third most common type and accounts for 98% of cancers of the large intestine. In Uganda, as elsewhere in Africa, the majority of patients are elderly (at least 60 years old). However, more recently, it has been observed that younger patients (less than 40 years of age) are presenting with the disease. There is also an increase in its incidence and most patients present late, possibly because of the lack of a comprehensive national screening and preventive health-care program. We describe the clinicopathological features of colorectal carcinoma in the case of a young man in Kampala, Uganda.

CASE PRESENTATION:



A 27-year-old man from Kampala, Uganda, presented with gross abdominal distension, progressive loss of weight, and fever. He was initially screened for tuberculosis, hepatitis, and lymphoma, and human immunodeficiency virus/acquired immunodeficiency syndrome infection. After a battery of tests, a diagnosis of colorectal carcinoma was finally established with hematoxylin and eosin staining of a cell block made from the sediment of a liter of cytospun ascitic fluid, which showed atypical glands floating in abundant extracellular mucin, suggestive of adenocarcinoma. Ancillary tests with alcian blue/periodic acid Schiff and mucicarmine staining revealed that it was a mucinous adenocarcinoma. Immunohistochemistry showed strong positivity with CDX2, confirming that the origin of the tumor was the colon.

CONCLUSIONS:



Colorectal carcinoma has been noted to occur with increasing frequency in young adults in Africa. Most patients have mucinous adenocarcinoma, present late, and have rapid disease progression and poor outcome. Therefore, colorectal malignancy should no longer be excluded from consideration only on the basis of a patient's age. A high index of suspicion is important in the diagnosis of colorectal malignancy in young African patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hermans2012d,

title = {Earlier initiation of antiretroviral therapy, increased tuberculosis case finding and reduced mortality in a setting of improved HIV care: a retrospective cohort study},

author = {SM Hermans and F van Leth and YC Manabe and AIM Hoepelman and JMA Lange and A Kambugu

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Hermans_et_al-2012-HIV_Medicine.pdf},

doi = {10.1111/j.1468-1293.2011.00980.x},

year  = {2012},

date = {2012-02-05},

journal = {HIV Medicine},

volume = {13},

number = {6},

pages = {337-44},

abstract = {OBJECTIVES:



High early mortality after antiretroviral therapy (ART) initiation in resource-limited settings is associated with low baseline CD4 cell counts and a high burden of opportunistic infections. Our large urban HIV clinic in Uganda has made concerted efforts to initiate ART at higher CD4 cell counts and to improve diagnosis and care of patients coinfected with tuberculosis (TB). We sought to determine associated treatment outcomes.

METHODS:



Routinely collected data for all patients who initiated ART from 2005 to 2009 were analysed. Median baseline CD4 cell counts by year of ART initiation were compared using the Cuzick test for trend. Mortality and TB incidence rates in the first year of ART were computed. Hazard ratios (HRs) were calculated using multivariable Cox proportional hazards models.

RESULTS:



First-line ART was initiated in 7659 patients; 64% were women, and the mean age was 37 years (standard deviation 9 years). Median baseline CD4 counts increased from 2005 to 2009 [82 cells/μL (interquartile range (IQR) 24, 153) to 148 cells/μL (IQR 61, 197), respectively; P<0.001]. The mortality rate fell from 6.5/100 person-years at risk (PYAR) [95% confidence interval (CI) 5.5-7.6 PYAR] to 3.6/100 PYAR (95% CI 2.2-5.8 PYAR). TB incidence rates increased from 8.2/100 PYAR (95% CI 7.1-9.5 PYAR) to 15.6/100 PYAR (95% CI 12.4-19.7 PYAR). A later year of ART initiation was independently associated with decreased mortality (HR 0.91; 95% CI 0.83-1.00; P=0.04).

CONCLUSIONS:



Baseline CD4 cell counts have increased over time and are associated with decreased mortality. Additional reductions in mortality might be a result of a better standard of care and increased TB case finding. Further efforts to initiate ART earlier should be prioritized even in a setting of capped or reduced funding for ART programmes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Taylor2012b,

title = {Low prevalence of  Pneumocystis jirovecii  lung colonization in Ugandan HIV-infected patients hospitalized with non- Pneumocystis  pneumonia},

author = {Steve M Taylor and Steven R Meshnick and William Worodria and Alfred Andama and J. Lucian Davis and Adithya Cattamanchi and Saskia den Boon and Samuel D Yoo and Carol D. Goodman and Laurence Huang},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Low-prevalence-of-pneumocystis-jirovecii-lung-colonizatio-in-Ugandan-HIV-infected-patients....pdf},

doi = {10.1016/j.diagmicrobio.2011.10.009},

year  = {2012},

date = {2012-02-01},

journal = {Diagnostic Microbiology and Infectious Diseases},

volume = {72},

number = {2},

pages = {139-43},

abstract = {Pneumocystis jirovecii is an important opportunistic infection in human immunodeficiency virus (HIV)-infected patients. In the developed world, P. jirovecii epidemiology is marked by frequent colonization in immunosuppressed patients, but data on the prevalence of colonization are very limited in sub-Saharan Africa, where the majority of persons living with HIV reside. Our objective was to describe the epidemiology of P. jirovecii colonization among HIV-positive patients in a cross-sectional, hospital-based study of patients admitted with suspected pneumonia in Kampala, Uganda. P. jirovecii was detectable in bronchoalveolar lavage fluid from 7 (6%) of 124 consecutive patients with non-Pneumocystis pneumonia. Colonization was not associated with patient demographic or clinical information. This prevalence is substantially lower than in published studies in the developed world and suggests that there is a limited reservoir of organisms for clinical infections in this Ugandan population. These findings may partially explain the low incidence of Pneumocystis pneumonia in Uganda and other sub-Saharan African countries.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ataher2012,

title = {The epidemiology and clinical correlates of HIV-1 co-receptor tropism in non-subtype B infections from India, Uganda and South Africa},

author = {Quazi Ataher and Simon Portsmouth and Laura A Napolitano and Sybil Eng and Anna Greenacre and Andrew Kambugu and Robin Wood and Sharlaa Badal-Faesen and Randy Tressler

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/08/The-epidemic-and-clinical-correlates-of-HIV-1-co-recepter-tropism-in-non-subtype-B-infections-from-india-Uganda-and-S.A.pdf},

doi = {10.1186/1758-2652-15-2},

year  = {2012},

date = {2012-01-22},

journal = {Journal of the Intrernational AIDS society},

volume = {15},

number = {1},

abstract = {BACKGROUND:



The introduction of C-C chemokine receptor type-5 (CCR5) antagonists as antiretroviral therapy has led to the need to study HIV co-receptor tropism in different HIV-1 subtypes and geographical locations. This study was undertaken to evaluate HIV-1 co-receptor tropism in the developing world where non-B subtypes predominate, in order to assess the therapeutic and prophylactic potential of CCR5 antagonists in these regions.

METHODS:



HIV-1-infected patients were recruited into this prospective, cross-sectional, epidemiologic study from HIV clinics in South Africa, Uganda and India. Patients were infected with subtypes C (South Africa, India) or A or D (Uganda). HIV-1 subtype and co-receptor tropism were determined and analyzed with disease characteristics, including viral load and CD4(+) and CD8(+) T cell counts.

RESULTS:



CCR5-tropic (R5) HIV-1 was detected in 96% of treatment-naïve (TN) and treatment-experienced (TE) patients in India, 71% of TE South African patients, and 86% (subtype A/A1) and 71% (subtype D) of TN and TE Ugandan patients. Dual/mixed-tropic HIV-1 was found in 4% of Indian, 25% of South African and 13% (subtype A/A1) and 29% (subtype D) of Ugandan patients. Prior antiretroviral treatment was associated with decreased R5 tropism; however, this decrease was less in subtype C from India (TE: 94%, TN: 97%) than in subtypes A (TE: 59%; TN: 91%) and D (TE: 30%; TN: 79%). R5 virus infection in all three subtypes correlated with higher CD4(+) count.

CONCLUSIONS:



R5 HIV-1 was predominant in TN individuals with HIV-1 subtypes C, A, and D and TE individuals with subtypes C and A. Higher CD4(+) count correlated with R5 prevalence, while treatment experience was associated with increased non-R5 infection in all subtypes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Conesa-Botella2011,

title = {Urinary Lipoarabinomannan as Predictor for the Tuberculosis Immune Reconstitution Inflammatory Syndrome },

author = {Anali Conesa-Botella and Marguerite Massinga Loembé and Yukari C. Manabe and William Worodria, and Doreen Mazakpwe and Kenneth Luzinda and Harriet Mayanja-Kizza and Mitra Miri and Olive Mbabazi and Olivier Koole and Luc Kestens and Robert Colebunders},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Urinary_Lipoarabinomannan_as_Predictor_for_the.7.pdf},

doi = {     10.1097/QAI.0b013e31823801de},

year  = {2011},

date = {2011-12-15},

journal = {Journal of Acquired Imune Dificiency syndrome},

volume = {58},

number = {5},

pages = {463-8},

abstract = {BACKGROUND:



Upon initiation of antiretroviral therapy (ART), 15.7% [95% confidence interval (CI): 9.7% to 24.5%] of tuberculosis (TB)-HIV-coinfected individuals experience paradoxical worsening of their clinical status with exuberant inflammation consistent with immune reconstitution inflammatory syndrome (IRIS). We investigated whether a positive urinary TB lipoarabinomannan (LAM) antigen enzyme-linked immunosorbent assay test before ART initiation was associated with development of paradoxical TB-IRIS.

METHODS:



In a prospective observational cohort in Mulago Hospital, Kampala, Uganda, we measured pre-ART urinary LAM concentrations in HIV-infected patients on TB treatment. Patients who developed TB-IRIS (according to the International Network for the Study of HIV-associated IRIS case definition) were compared with patients who remained IRIS free for at least 3 months.

RESULTS:



Twenty-six individuals with TB-IRIS and 64 without IRIS were included in the analysis. The median time to TB-IRIS was 14 days (interquartile range: 11-14 days). Univariate analysis showed that a positive pre-ART urinary LAM test [OR: 4.6 (95% CI: 1.5 to 13.8), P = 0.006] and a CD4 count <50 cells/mL [OR: 21 (95% CI: 2.6 to 169.4), P = 0.004] were associated with an increased risk of TB-IRIS. In multivariate analysis, only a baseline CD4 T-cell count <50 cells/mL was predictive of IRIS (P < 0.004). Sensitivity and specificity of a positive pre-ART urinary LAM test to diagnose IRIS were 80.8% (95% CI: 60.6 to 93.4) and 52.4% (95% CI: 39.4 to 65.1), respectively.

CONCLUSIONS:



If CD4 T-cell count testing is available, a pre-highly active antiretroviral therapy urinary LAM test has no added value to predict TB-IRIS. When CD4 T-cell count is not available, a positive LAM test could identify patients at increased risk of TB-IRIS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fillekes2011,

title = {Pediatric Underdosing of Efavirenz: A Pharmacokinetic Study in Uganda},

author = {Quirine Fillekes and Eva Natukunda and Jackie Balungi and Lindsay Kendall and Mutsa Bwakura-Dangarembizi and Rosette Keishanyu and Alex Ferrier and Joseph Lutakome and Diana M. Gibb and David M. Burger and A. Sarah Walker},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Pediatric_Underdosing_of_Efavirenz___A.6.pdf},

doi = { 10.1097/QAI.0b013e318235e560},

year  = {2011},

date = {2011-12-01},

journal = {Journal of Acquired Imune Dificiency syndrome},

volume = {58},

number = {4},

pages = {58(4):392-8},

abstract = {OBJECTIVES:



To evaluate international pediatric efavirenz dosing recommendations using full pharmacokinetic (PK) information.

DESIGN:



Open-label, multicenter, PK study.

METHODS:



Forty-one HIV-infected Ugandan children (3-12 years) on efavirenz + lamivudine + abacavir were enrolled in a study of twice-daily to once-daily lamivudine + abacavir 36 weeks after antiretroviral therapy initiation in the ARROW trial. Once-daily efavirenz doses were 200, 250, 300, 350 mg for children weighing 10 to <15, 15 to <20, 20 to <25, 25 to <30 kg, respectively, using 200/50 mg capsules or halved 600 mg tablets in case of 300 and 350 mg doses. Intensive plasma PK sampling (t = 0, 1, 2, 4, 6, 8, 12 hours postobserved ingestion) was performed at steady state (PK1) and repeated 4 weeks later (PK2, including a further 24-hour sample).

RESULTS:



Forty-one and 39 children had evaluable efavirenz profiles at PK1 and PK2, respectively. Seventeen (41%) were boys. Five, 16, 17, 3 were in the 10 to <15, 15 to <20, 20 to <25, 25 to <30 kg weight bands. The geometric mean (%CV) the area under the concentration-time curve 0-24 hours postdose was 50.8 (90.8%) and 55.5 (82.7%) h·mg·L(-1) at PK1 and PK2, respectively. Six children at PK1 and 7 at PK2 had subtherapeutic C(8h) and/or C(12h) (<1.0 mg/L), 7 of 41 (17%) at either visit. At PK2, 15 of 39 (38%) children had C(24h) <1.0 mg/L (median (interquartile range) [range] 1.1 (0.7-2.9) [0.3-18.4]). Ten children at PK1 and 11 at PK2 had C(8h) and/or C(12h) >4.0 mg/L; 12 of 41 (29%) at either visit.

CONCLUSIONS:



African children aged 3-12 years, on efavirenz dosed according to 2006 WHO/manufacturer's recommendations, had lower and highly variable efavirenz PK parameters compared with adult data from manufacturer's leaflet. There were no differences across weight bands, suggesting no major effect of using half tablets. Higher pediatric efavirenz doses, as per WHO 2010 recommendations, should be used and investigated further but may risk increasing the proportion of children with potentially toxic levels.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Worodria2011,

title = {The Role of Speciation in Positive Lowenstein-Jensen Culture Isolates from a High Tuberculosis Burden Country},

author = {William Worodria and Jillian Anderson and Adithya Cattamanchi and J. Lucian Davis and Saskia den and Boon and Alfred Andama and Samuel D. Yoo and Moses Joloba and Laurence Huang and Midori Kato-

Maeda

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/The-Role-of-Speciation-in-Positive-Lowenstein-Jensen....pdf},

doi = { 10.1371/journal.pone.0027017},

year  = {2011},

date = {2011-11-04},

journal = {PloS One},

volume = {6},

number = {11},

abstract = {OBJECTIVE:



To determine the need for routine speciation of positive Lowenstein-Jensen mycobacterial cultures in HIV-infected patients suspected of having pulmonary tuberculosis at Mulago Hospital in Kampala, Uganda.

METHODS:



Sputum and bronchoalveolar lavage Lowenstein-Jensen mycobacterial culture isolates from consecutive, HIV-infected patients admitted to Mulago Hospital with 2 weeks or more of cough were subjected to IS6110 PCR and rpoB genetic analysis to determine the presence of Mycobacterium tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM).

RESULTS:



Eighty (100%) mycobacterial cultures from 65 patients were confirmed to be members of MTBC. Subsequent analysis of the cultures from 54 patients by PCR and sequence analyses to identify co-infection with NTM confirmed the presence of MTBC as well as the presence of Micrococcus luteus (n = 4), Janibacter spp. (n = 1) and six cultures had organisms that could not be identified.

CONCLUSIONS:



Presumptive diagnosis of tuberculosis on the basis of a positive Lowenstein-Jensen culture is sufficient in HIV-infected Ugandans suspected of having tuberculosis. Routine molecular confirmation of positive Lowenstein-Jensen cultures is unnecessary in this low resource setting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lamorde2011,

title = {Nevirapine pharmacokinetics when initiated at 200 mg or 400 mg daily in HIV-1 and tuberculosis co-infected Ugandan adults on rifampicin},

author = {Mohammed Lamorde and Pauline Byakika-Kibwika and Violet Okaba-Kayom and Mairin Ryan and Peter Coakley and Marta Boffito and Rhoda Namakula and Francis Kalemeera and Robert Colebunders and David Back and Saye Khoo and Concepta Merry

},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Nevirapine-pharmacokinetics-when-initiated-at-200-mg-or-400-mg-daily....pdf},

year  = {2011},

date = {2011-11-02},

journal = {Journal of Antimicrobial Chemotherapy},

volume = {66},

number = {1},

pages = {180-3},

abstract = {Background:

Rifampicin lowers nevirapine plasma concentrations by inducing cytochrome P450. However, few

data are available on this interaction during the lead-in period of nevirapine treatment.

Methods:

Eighteen HIV-1/tuberculosis co-infected adults receiving rifampicin daily as part of anti-tuberculosis

therapy were evenly randomized to nevirapine initiation by dose escalation (NVP200) or nevirapine initiation at

200 mg twice daily (NVP400). Subjects underwent 12 h intensive pharmacokinetic sampling on Days 7, 14 and

21 of nevirapine treatment. A minimum effective concentration (MEC) of 3000 ng/mLwas used to interpret nevir-

apine concentrations 12 h after dosing (

C

12

). Trial registration number: NCT00617643 (www.clinicaltrials.gov).

Results:

Day 7 geometric mean nevirapine

C

12

[90% confidence interval (CI)] was 1504 (1127–2115) ng/mL and

3148 (2451–4687) ng/mL in the NVP200 and NVP400 arms, respectively (

P

,

0.01). Nevirapine

C

12

on Days 14

and 21 was similar. On Day 21, nevirapine concentration in 64% of patients was below the MEC. On Day 7,

geometric mean area under the curve (AUC

0–12

) was lower in the NVP200 arm, 25223 (90% CI, 21978–

29695) ng

.

h/mLversus 43195 (35607–57035) ng

.

h/mL in the NVP400 arm (

P

,

0.01). Similarly, on Day 14, nevir-

apine AUC

0–12

was lower in the NVP200 arm 23668 (18253–32218) ng

.

h/mL versus the NVP400 arm 44918

(36264–62769) ng

.

h/mL (

P

¼

0.03).

Conclusions:

In co-treated patients, nevirapine concentrations were below the MEC during initiation with dose

escalation. Nevirapine initiation at the maintenance dose of 200 mg twice daily is preferred. Sub-therapeutic

nevirapine concentrations were common at Day 21 with either regimen. Evaluation of higher nevirapine main-

tenance doses may be considered},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ssekitoleko2011,

title = {Hypoglycemia at admission is associated with inhospital mortality in Ugandan patients with severe sepsis.},

author = {Richard Ssekitoleko and Shevin T. Jacob and Patrick Banura and Relana Pinkerton and David B. Meya and Steven J. Reynolds and Nathan Kenya-Mugisha and Harriet Mayanja-Kizza and Rose Muhindo and Sanjay Bhagani and W. Michael Scheld and 

Christopher C. Moore},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Hypoglycemia-at-admission....pdf},

doi = { 10.1097/CCM.0b013e3182227bd2},

year  = {2011},

date = {2011-10-01},

journal = {Critical Care Medicine},

volume = {39},

number = {10},

pages = {2271-6},

abstract = {BJECTIVE:



Dysglycemia during sepsis is associated with poor outcomes in resource-rich settings. In resource-limited settings, hypoglycemia is often diagnosed clinically without the benefit of laboratory support. We studied the utility of point-of-care glucose monitoring to predict mortality in severely septic patients in Uganda.

DESIGN:



Prospective observational study.

SETTING:



One national and two regional referral hospitals in Uganda.

PATIENTS:



We enrolled 532 patients with sepsis at three hospitals in Uganda. The analysis included 418 patients from the three sites with inhospital mortality data, a documented admission blood glucose concentration, and evidence of organ dysfunction at admission (systolic blood pressure≤100 mm Hg, lactate>4 mmol/L, platelet number<100,000/μL, or altered mental status).

INTERVENTIONS:



None.

MEASUREMENTS AND MAIN RESULTS:



We evaluated the association between admission point-of-care blood glucose concentration and inhospital mortality. We also assessed the accuracy of altered mental status as a predictor of hypoglycemia. Euglycemia occurred in 33.5% (140 of 418) of patients, whereas 16.3% (68 of 418) of patients were hypoglycemic and 50.2% (210 of 418) were hyperglycemic. Univariate Cox regression analyses comparing in-hospital mortality among hypoglycemic (35.3% [24 of 68], hazard ratio 2.0, 95% confidence interval 1.2-3.6, p=.013) and hyperglycemic (29.5% [62 of 210], hazard ratio 1.5, 95% confidence interval 0.96-2.4, p=.08) patients to euglycemic (19.3% [27 of 140]) patients showed statistically significantly higher rates of inhospital mortality for patients with hypoglycemia. Hypoglycemia (adjusted hazard ratio 1.9, 95% confidence interval 1.1-3.3, p=.03) remained significantly and independently associated with inhospital mortality in the multivariate model. The sensitivity and specificity of altered mental status for hypoglycemia were 25% and 86%, respectively.

CONCLUSION:



Hypoglycemia is an independent risk factor for inhospital mortality in patients with severe sepsis and cannot be adequately assessed by clinical examination. Correction of hypoglycemia may improve outcomes of critically ill patients in resource-limited settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Worodria2011b,

title = {Incidence and Predictors of Mortality and the Effect of Tuberculosis Immune Reconstitution Inflammatory Syndrome in a Cohort of TB/HIV Patients Commencing Antiretroviral Therapy},

author = {William Worodria and Marguerite Massinga-Loembe and Doreen Mazakpwe and Kenneth Luzinda and Joris Menten abd Frank Van Leth and Harriet Mayanja-Kizza and Luc Kestens and Roy D. Mugerwaad Peter Reiss and kand Robert Colebunders},

url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Incidence-and-Predictors.pdf},

doi = {10.1097/QAI.0b013e3182255dc2.},

year  = {2011},

date = {2011-09-01},

journal = {Journal of Acquired Immune Dificiency syndrome},

volume = {58},

number = {1},

pages = {32-7.},

abstract = {BACKGROUND:



Tuberculosis-HIV (TB-HIV) coinfection remains an important cause of mortality in antiretroviral therapy (ART) programs. In a cohort of TB-HIV-coinfected patients starting ART, we examined the incidence and predictors of early mortality.

METHODS:



Consecutive TB-HIV-coinfected patients eligible for ART were enrolled in a cohort study at the Mulago National Tuberculosis and Leprosy Program clinic in Kampala, Uganda. Predictors of mortality were assessed using Cox proportional hazards analysis.

RESULTS:



Three hundred and two patients [median CD4 count 53 cells/μL (interquartile range, 20-134)] were enrolled. Fifty-three patients died, 36 (68%) of these died within the first 6 months of TB diagnosis. Male sex [hazard (HR): 2.19; 95% confidence interval (CI): 1.19 to 4.03; P = 0.011], anergy to tuberculin skin test [HR: 2.59 (1.10 to 6.12); P = 0.030], a positive serum cryptococcal antigen result at enrollment (HR: 4.27; 95% CI: 1.50 to 12.13; P = 0.006) and no ART use (HR: 4.63; 95% CI: 2. 37 to 9.03; P < 0.001) were independent predictors of mortality by multivariate analysis. Six (10%) patients with TB immune reconstitution inflammatory syndrome died, and in most, an alternative contributing cause of death was identified.

CONCLUSIONS:



Mortality among these TB-HIV-coinfected patients was high particularly when presenting with advanced HIV disease and not starting ART, reinforcing the need for timely and joint treatment for both infections. Screening for a concomitant cryptococcal infection and antifungal treatment for patients with cryptococcal antigenemia may further improve clinical outcome.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}