UCU School of Medicine

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Towards a National AIDS-Control Program in Uganda
(PubMed Central, 1987-12) Okware, Samuel Ikwaras
A national AIDS-control program was developed in Uganda to deal with a potentially serious epidemic of the acquired immunodeficiency syndrome (AIDS). A cumulative total of 1, 138 cases of AIDS has been reported in Uganda between 1983-since AIDS was introduced into the country and March 1987. More than 80% of the victims are sexually active persons whereas less than 10% are infants and children younger than 5 years. Virtually no cases or seropositivity is reported in persons between the ages of 5 and 14 years or after the age of 60 years. Most transmission has been through the heterosexual route, and, unlike in the United States, the male-female ratio is 1:1. Heterosexual high-risk behavior is cited as an important mode of transmission. A survey of household contacts showed that despite the closeness, only the sexual partners were seropositive. A five-year plan of action has been developed, and health education is the main thrust. It also includes blood screening, improved sterile procedures, improved surveillance and notification, research and terminal patient care. The plan stresses integration based on primary health care. There are unresolved moral issues of whether or not to tell the truth to an AIDS victim or any healthy seropositive person in developing countries, especially unstable persons. The best approach is to sensitize everyone so that they become guardians of their lives because sexual behavior is an issue of individual responsibility.
Quantitative process evaluation of a community-based HIV/AIDS behavioural intervention in rural Uganda.
(2002) Kanyesigye, E.; Kisman, J.; Kamali, A.; Kamulegeya, I.; Basajja, V.; Nakiyingi, J.; Schenk, K.; Whitworth, J.
This paper describes the implementation of a large community-based HIV/AIDS behavioural intervention in rural Uganda and presents 4 years' worth of quantitative process data. The intervention involved 560 field-based workers (57% male, 76% subsistence farmers, mean age 35 years), supervised by six central staff. Intervention channels included drama and video shows, Community Educators (CEs), as well as leaflet and condom distribution. Activities focused on one or more of 16 key topics. In total, 392 000 attendances (51% female) were recorded--a mean of over 6 for each of the 64 000 target adults--at 81 000 activities, with CEs attracting 71% of the total attendance; 164 000 leaflets and 242 000 condoms were also distributed. The annual cost of the intervention per target individual was approximately US$1.76. Our voluntary workforce experienced an annual attrition rate of 11%, with 'stable' workers more likely to be older, married or opinion leaders in their community than those who dropped out. We calculate that even a significant increase in the proportion of female field workers would have made little difference either to the sex ratio of attendees or to overall attendance. In spite of some initial resistance to the intervention, particularly in relation to condoms, we have demonstrated that people in rural Africa can accept and actively participate in the dissemination of HIV/AIDS prevention messages throughout their own communities.
Infection of New- and Old-World Aedes albopictus (Diptera: Culicidae) by the Intracellular Parasite Wolbachia: Implications for Host Mitochondrial DNA Evolution
(Journal of Medical Entomology, 2003) Armbruster, Peter; Damsky, William E.; Giordano, Rosanna; Birungi, Josephine; Munstermann, Leonard E.; Conn, And Jan E.
Wolbachia are cytoplasmically inherited, endosymbiotic bacteria known to infect a wide variety of arthropods. Polymerase chain reaction (PCR) ampliÞcation of the Wolbachia surface protein (wsp) gene was used to assay the infection of geographically disparate populations of Aedes albopictus (Skuse) by Wolbachia. Nine North American, four South American, one Hawaiian, and four Old World populations of A. albopictus were all doubly infected with both the wAlbA and wAlbB strains of Wolbachia.A365-bp region of thewAlbA wsp gene was sequenced from seven geographically disparate host populations, and all sequences were identical. Similarly, a 474-bp region of the wAlbB wsp gene was sequenced from the same populations, and all sequences were identical. These results suggest a role for Wolbachia infection in causing the previously established pattern of low mitochondrial DNA variability, but average nuclear gene diversity, within and among populations of A. albopictus.
A good death in Uganda: survey of needs for palliative care for terminally ill people in urban areas
(2003-07) Kikule, Ekiria
Objective To identify the palliative care needs of terminally ill people in Uganda. Design Descriptive cross sectional study. Setting Home care programmes in and around Kampala that look after terminally ill people in their homes. Participants 173 terminally ill patients registered with the home care programmes. Results Most of the participants had either HIV/AIDS or cancer or both; 145 were aged under 50 years, and 107 were women. Three main needs were identified: the control or relief of pain and other symptoms; counselling; and financial assistance for basic needs such as food, shelter, and school fees for their children. The preferred site of care was the home, though all these people lived in urban areas with access to healthcare services within 5 km of their homes. Conclusion A “good death” in a developing country occurs when the dying person is being cared for at home, is free from pain or other distressing symptoms, feels no stigma, is at peace, and has their basic needs met without feeling dependent on others.
Participatory Planning for the Transformation of the Faculty of Medicine Into a College of Health Sciences
(African Health Sciences, 2003-08) Dodge, Cole P.; Sewankambo, Nelson; Kanyesigye, Edward
The study is about Participatory planning for the transformation of the Faculty of Medicine into a College of Health Sciences
Standardization of cytokine flow cytometry assays
(BioMed Central Ltd., 2005-06-24) Maecker, Holden T.; Rinfret, Aline; D'Souza, Patricia; Darden, Janice; Roig, Eva; Landry, Claire; Hayes, Peter; Birungi, Josephine; Anzala, Omu; Garcia, Miguel; Harari, Alexandre; Frank, Ian; Baydo, Ruth; Baker, Megan; Holbrook, Jennifer; Ottinger, Janet; Lamoreaux, Laurie; Epling, C. Lorrie; Sinclair, Elizabeth; Suni, Maria A.; Punt, Kara; Calarota, Sandra; El-Bahi, Sophia; Alter, Gailet; Maila, Hazel; Kuta, Ellen; Cox, Josephine; Gray, Clive; Altfeld, Marcus; Nougarede, Nolwenn; Boyer, Jean; Tussey, Lynda; Tobery, Timothy; Bredt, Barry; Roederer, Mario; Koup, Richard; Maino, Vernon C.; Weinhold, Kent; Pantaleo, Giuseppe; Gilmour, Jill; Horton, Helen; Sekaly, Rafick P.
Background: Cytokine flow cytometry (CFC) or intracellular cytokine staining (ICS) can quantitate antigen-specific T cell responses in settings such as experimental vaccination. Standardization of ICS among laboratories performing vaccine studies would provide a common platform by which to compare the immunogenicity of different vaccine candidates across multiple international organizations conducting clinical trials. As such, a study was carried out among several laboratories involved in HIV clinical trials, to define the inter-lab precision of ICS using various sample types, and using a common protocol for each experiment (see additional files online). Results: Three sample types (activated, fixed, and frozen whole blood; fresh whole blood; and cryopreserved PBMC) were shipped to various sites, where ICS assays using cytomegalovirus (CMV) pp65 peptide mix or control antigens were performed in parallel in 96-well plates. For one experiment, antigens and antibody cocktails were lyophilised into 96-well plates to simplify and standardize the assay setup. Results (CD4+cytokine+ cells and CD8+cytokine+ cells) were determined by each site. Raw data were also sent to a central site for batch analysis with a dynamic gating template. Mean inter-laboratory coefficient of variation (C.V.) ranged from 17–44% depending upon the sample type and analysis method. Cryopreserved peripheral blood mononuclear cells (PBMC) yielded lower inter-lab C.V.'s than whole blood. Centralized analysis (using a dynamic gating template) reduced the inter-lab C.V. by 5–20%, depending upon the experiment. The inter-lab C.V. was lowest (18–24%) for samples with a mean of >0.5% IFNγ + T cells, and highest (57–82%) for samples with a mean of <0.1% IFNγ + cells. Conclusion: ICS assays can be performed by multiple laboratories using a common protocol with good inter-laboratory precision, which improves as the frequency of responding cells increases. Cryopreserved PBMC may yield slightly more consistent results than shipped whole blood. Analysis, particularly gating, is a significant source of variability, and can be reduced by centralized analysis and/or use of a standardized dynamic gating template. Use of pre-aliquoted lyophilized reagents for stimulation and staining can provide further standardization to these assays.
Repeat Voluntary HIV Counseling and Testing (VCT), Sexual Risk Behavior and HIV Incidence in Rakai, Uganda
(Springer Science+Business Media, LLC, 2006) Matovu, Joseph K. B.; Gray, Ronald H.; Kiwanuka, Noah; Kigozi, Godfrey; Wabwire-Mangen, Fred; Nalugoda, Fred; Serwadda, David; Sewankambo, Nelson K.; Wawer, Maria J.
We examined the effects of repeat Voluntary HIV counseling and testing (VCT) on sexual risk behaviors and HIV incidence in 6,377 initially HIV-negative subjects enrolled in a prospective STD control for HIV prevention trial in rural Rakai district, southwestern Uganda. Sixty-four percent accepted VCT, and of these, 62.2% were first time acceptors while 37.8% were repeat acceptors. Consistent condom use was 5.8% in repeat acceptors, 6.1% in first time acceptors and 5.1% in non-acceptors. A higher proportion of repeat acceptors (15.9%) reported inconsistent condom use compared to first-time acceptors (12%) and non-acceptors (11.7%). Also, a higher proportion of repeat acceptors (18.1%) reported 2+ sexual partners compared to first-time acceptors (14.1%) and non-acceptors (15%). HIV incidence rates were 1.4/100 py (person-years) in repeat acceptors, 1.6/100 py in first time acceptors and 1.6/100 py in non-acceptors. These data suggest a need for intensive risk-reduction counseling interventions targeting HIV-negative repeat VCT acceptors as a special risk group.
Declining Maternal Mortality Ratio in Uganda: Priority Interventions to Achieve the Millennium Development Goal
(Elsevier, 2007-05-21) Anthony, Mbonye; Miriam, Mutabazi; John Bosco, Asiimwe; Olive, Sentumbe; Jane, Kabarangira; G., Nanda; V., Orinda
Purpose: We conducted a survey to determine availability of emergency obstetric care (EmOC) and to provide data for advocating for improved maternal and newborn health in Uganda. Methods: The survey, covering 54 districts and 553 health facilities, assessed availability of EmOC signal functions, documented maternal deaths and the related causes. Three levels of health were covered. Findings: Few health units had running water; electricity or a functional operating theater. Yet having these items had a protective effect on maternal deaths as follows: theater (OR 0.56, P b 0.0001); electricity (OR 0.39, P b 0.0001); laboratory (OR 0.71, P b 0.0001) and staffing levels (midwives) OR 0.20, P b 0.0001. The availability of midwives had the highest protective effect on maternal deaths, reducing the case fatality rate by 80%. Further, most (97.2%) health facilities expected to offer basic EmOC, were not doing so. This is the likely explanation for the high health facility-based maternal death rate of 671/100,000 live births in Uganda. Conclusion: Addressing health system issues, especially human resources, and increasing access to EmOC could reduce maternal mortality in Uganda and enable the country to achieve the Millennium Development Goal (MDG).
Expanding access to voluntary HIV counselling and testing in sub-Saharan Africa: alternative approaches for improving uptake, 2001–2007
(Tropical Medicine and International Health, 2007-11) Matovu, Joseph K. B.; Makumbi, Fredrick E.
The changing face of the HIV ⁄ AIDS epidemic has resulted in new opportunities to increase access to voluntary HIV counselling and testing (VCT), especially during the past 7 years (2001–2007). As access to HIV treatment becomes more widely available in sub-Saharan Africa, the need for enhanced access to VCT would become even greater. When given the opportunity, many more adults in sub-Saharan African would accept VCT, and many clearly express the desire to learn their HIV sero-status. However, in most parts of sub-Saharan Africa, fewer than one in 10 people know their HIV status. Stigma, fear of receiving an HIV-positive status, lack of confidentiality, long distances to VCT sites, and long delays in returning HIV test results limit people’s access to traditional VCT systems. Alternative VCT delivery models, such as mobile VCT, routine offer of VCT and home-based VCT increase access to and uptake of VCT. We recommend that these alternative models be implemented in more settings and on a much larger scale in sub-Saharan Africa, where VCT uptake rates remain low.
Use of WHO clinical stage for assessing patient eligibility to antiretroviral therapy in a routine health service setting in Jinja, Uganda
(AIDS Research and Therapy, 2008-02-28) Jaffar, Shabbar; Birungi, Josephine; Grosskurth, Heiner; Amuron, Barbara; Namara, Geoffrey; Nabiryo, Christine; Coutinho, Alex
In a routine service delivery setting in Uganda, we assessed the ability of the WHO clinical stage to accurately identify HIV-infected patients in whom antiretroviral therapy should be started. Among 4302 subjects screened for ART, the sensitivity and specificity (95% CI) of WHO stage III, IV against a CD4 count < 200 × 106/l were 52% (50, 54%) and 68% (66, 70%) respectively. Plasma viral load was tested in a subset of 1453 subjects in whom ART was initiated. Among 938 subjects with plasma viral load of 100,000 copies or more, 391 (42%, 95% CI 39, 45%) were at WHO stage I or II. In this setting, a large number of individuals could have been denied access to antiretroviral therapy if eligibility to ART was assessed on the basis of WHO clinical stage. There is an urgent need for greater CD4 count testing and evaluation of the utility of plasma viral load prior to initiation of ART to accompany the roll-out of ART.
Concordant Proficiency in Measurement of T-Cell Immunity in Human Immunodeficiency Virus Vaccine Clinical Trials by Peripheral Blood Mononuclear Cell and Enzyme-Linked Immunospot Assays in Laboratories from Three Continents
(Clinical and vaccine immunology, 2009-02) Boaz, Mark J.; Hayes, Peter; Tarragona, Tony; Seamons, Laura; Cooper, Andrew; Birungi, Josephine; Kitandwe, Paul; Semaganda, Aloysius; Kaleebu, Pontiano; Stevens, Gwynneth; Anzala, Omu; Farah, Bashir; Ogola, Simon; Indangasi, Jackton; Mhlanga, Patrick; Eeden, Melanie Van; Thakar, Madhuri; Pujari, Ashwini; Mishra, Shadri; Goonetilleke, Nilu; Moore, Stephen; Mahmoud, Abdul; Sathyamoorthy, Pattabiraman; Mahalingam, Jayashri; Narayanan, Paranji R.; Ramanathan, Vadakkuppattu D.; Cox, Josephine H.; Dally, Len; Gill, Dilbinder K.; Gilmour, Jill
The gamma interferon (IFN-_) enzyme-linked immunospot (ELISPOT) assay is used routinely to evaluate the potency of human immunodeficiency virus (HIV) vaccine candidates and other vaccine candidates. In order to compare candidates and pool data from multiple trial laboratories, validated standardized methods must be applied across laboratories. Proficiency panels are a key part of a comprehensive quality assurance program to monitor inter- and intralaboratory performance, as well as assay performance, over time. Seven International AIDS Vaccine Initiative-sponsored trial sites participated in the proficiency panels described in this study. At each laboratory, two operators independently processed identical sample sets consisting of frozen peripheral blood mononuclear cell (PBMC) samples from different donors by using four blind stimuli. PBMCM recovery and viability after overnight resting and the IFN-_ ELISPOT assay performance were assessed. All sites demonstrated good performance in PBMC thawing and resting, with a median recovery of 78% and median viability of 95%. The laboratories were able to detect similar antigen-specific T-cell responses, ranging from 50 to >3,000 spot-forming cells per million PBMC. An approximate range of a half log in results from operators within or across sites was seen in comparisons of antigen-specific responses. Consistently low background responses were seen in all laboratories. The results of these proficiency panels demonstrate the ability of seven laboratories, located across three continents, to process PBMC samples and to rank volunteers with differential magnitudes of IFN-_ ELISPOT responses. These findings also illustrate the ability to standardize the IFN-_ ELISPOT assay across multiple laboratories when common training methods, reagents such as fetal calf serum, and standard operating procedures are adopted. These results are encouraging for laboratories that are using cell-based immunology assays to test HIV vaccines and other vaccines.
CLSI-Derived Hematology and Biochemistry Reference Intervals for Healthy Adults in Eastern and Southern Africa
(2009-02-06) Karita, Etienne; Ketter, Nzeera; Price, Matt A; Kayitenkore, Kayitesi; Kaleebu, Pontiano; Nanvubya, Annet; Anzala, Omu; Jaoko, Walter; Mutua, Gaudensia; Ruzagira, Eugene; Mulenga, Joseph; Sanders, Eduard J.; Mwangome, Mary; Allen, Susan; Bwanika, Agnes; Bahemuka, Ubaldo; Awuondo, Ken; Omosa, Gloria; Farah, Bashir; Amornkul, Pauli; Birungi, Josephine; Yates, Sarah; Stoll-Johnson, Lisa; Gilmour, Jill; Stevens, Gwynn; Shutes, Erin; Manigart, Olivier; Hughes, Peter; Dally, Len; Scott, Janet; Stevens, Wendy; Fast, Pat; Kamali, Anatoli
Background: Clinical laboratory reference intervals have not been established in many African countries, and non-local intervals are commonly used in clinical trials to screen and monitor adverse events (AEs) among African participants. Using laboratory reference intervals derived from other populations excludes potential trial volunteers in Africa and makes AE assessment challenging. The objective of this study was to establish clinical laboratory reference intervals for 25 hematology, immunology and biochemistry values among healthy African adults typical of those who might join a clinical trial. Methods and Findings: Equal proportions of men and women were invited to participate in a cross sectional study at seven clinical centers (Kigali, Rwanda; Masaka and Entebbe, Uganda; two in Nairobi and one in Kilifi, Kenya; and Lusaka, Zambia). All laboratories used hematology, immunology and biochemistry analyzers validated by an independent clinical laboratory. Clinical and Laboratory Standards Institute guidelines were followed to create study consensus intervals. For comparison, AE grading criteria published by the U.S. National Institute of Allergy and Infectious Diseases Division of AIDS (DAIDS) and other U.S. reference intervals were used. 2,990 potential volunteers were screened, and 2,105 (1,083 men and 1,022 women) were included in the analysis. While some significant gender and regional differences were observed, creating consensus African study intervals from the complete data was possible for 18 of the 25 analytes. Compared to reference intervals from the U.S., we found lower hematocrit and hemoglobin levels, particularly among women, lower white blood cell and neutrophil counts, and lower amylase. Both genders had elevated eosinophil counts, immunoglobulin G, total and direct bilirubin, lactate dehydrogenase and creatine phosphokinase, the latter being more pronounced among women. When graded against U.S.-derived DAIDS AE grading criteria, we observed 774 (35.3%) volunteers with grade one or higher results; 314 (14.9%) had elevated total bilirubin, and 201 (9.6%) had low neutrophil counts. These otherwise healthy volunteers would be excluded or would require special exemption to participate in many clinical trials. Conclusions: To accelerate clinical trials in Africa, and to improve their scientific validity, locally appropriate reference ranges should be used. This study provides ranges that will inform inclusion criteria and evaluation of adverse events for studies in these regions of Africa.
Association between socio economic status and schistosomiasis infection in Jinja District, Uganda
(Wiley Online Library, 2009-04-20) Muhumuza, Simon; Kitimbo, George; Oryema-Lalobo, Michael; Nuwaha, Fred
Objective: To examine the role of socioeconomic situation in influencing the risk and intensity of infection with Schistosomiasis mansoni. Methods: Cross-sectional study in Walukuba Division bordering Lake Victoria, Jinja District. We assessed a random sample of 463 individuals aged 10–20 years for Schistosoma mansoni infection, water contact behaviour and treatment status with praziquantel as of the last mass treatment. Socio- economic conditions of the participants’ households were assessed by calculating a wealth index (based on type of housing and ownership of assets). Households were classified in four classes; multivariate logistic regression analysis was used to identify independent predictors of being infected with schisto-somiasis. Intensities of infection with S. mansoni were compared across the classes of wealth index. results Wealth index emerged a risk factor for infection with S. mansoni after controlling for water contact and treatment with praziquantel. The adjusted odds ratio of being infected for the lowest level of wealth index compared to the highest was 10.42 (95% CI 3.38–32.36 P < 0.001). The intensity of infection decreased with wealth index Linearity F-ratio 13.91, 1 df, P <0.001). The geometric egg count for those in the lowest wealth index was 230 (95% CI 199–279) compared to 114 (95% CI 80–162) for the highest wealth index. Conclusions: In addition to mass treatment with praziquantel, improving the socio-economic conditions of the population should be given priority.
Mortality and loss-to-follow-up during the pre-treatment period in an antiretroviral therapy programme under normal health service conditions in Uganda.
(BioMed Central Ltd., 2009-08-11) Amuron, Barbara; Namara, Geoffrey; Birungi, Josephine; Nabiryo, Christine; Levin, Jonathan; Grosskurth, Heiner; Coutinho, Alex; Jaffar, Shabbar
Background: In many HIV programmes in Africa, patients are assessed clinically and prepared for antiretroviral treatment over a period of 4–12 weeks. Mortality rates following initiation of ART are very high largely because patients present late with advanced disease. The rates of mortality and retention during the pre-treatment period are not well understood. We conducted an observational study to determine these rates. Methods: HIV-infected subjects presenting at The AIDS Support Clinic in Jinja, SE Uganda, were assessed for antiretroviral therapy (ART). Eligible subjects were given information and counselling in 3 visits done over 4–6 weeks in preparation for treatment. Those who did not complete screening were followed-up at home. Survival analysis was done using poisson regression. Results: 4321 HIV-infected subjects were screened of whom 2483 were eligible for ART on clinical or immunological grounds. Of these, 637 (26%) did not complete screening and did not start ART. Male sex and low CD4 count were associated independently with not completing screening. At follow-up at a median 351 days, 181 (28%) had died, 189 (30%) reported that they were on ART with a different provider, 158 (25%) were alive but said they were not on ART and 109 (17%) were lost to follow-up. Death rates (95% CI) per 100 person-years were 34 (22, 55) (n.18) within one month and 37 (29, 48) (n.33) within 3 months. 70/158 (44%) subjects seen at follow-up said they had not started ART because they could not afford transport. Conclusion: About a quarter of subjects eligible for ART did not complete screening and pretreatment mortality was very high even though patients in this setting were well informed. For many families, the high cost of transport is a major barrier preventing access to ART.
Rates of virological failure in patients treated in a home-based versus a facility-based HIV-care model in Jinja, southeast Uganda: a cluster-randomised equivalence trial
(Elsevier, 2009-12-19) Jaffar, Shabbar; Amuron, Barbara; Foster, Susan; Birungi, Josephine; Levin, Jonathan; Namara, Geoffrey; Nabiryo, Christine; Ndembi, Nicaise; Kyomuhangi, Rosette; Opio, Alex; Bunnell, Rebecca; Tappero, Jordan W.; Mermin, Jonathan; Coutinho, Alex; Grosskurth, Heiner
Background: Identification of new ways to increase access to antiretroviral therapy in Africa is an urgent priority. We assessed whether home-based HIV care was as effective as was facility-based care. Methods: We undertook a cluster-randomised equivalence trial in Jinja, Uganda. 44 geographical areas in nine strata, defined according to ratio of urban and rural participants and distance from the clinic, were randomised to home-based or facility-based care by drawing sealed cards from a box. The trial was integrated into normal service delivery. All patients with WHO stage IV or late stage III disease or CD4-cell counts fewer than 200 cells per μL who started antiretroviral therapy between Feb 15, 2005, and Dec 19, 2006, were eligible, apart from those living on islands. Follow-up continued until Jan 31, 2009. The primary endpoint was virological failure, defined as RNA more than 500 copies per mL after 6 months of treatment. The margin of equivalence was 9% (equivalence limits 0•69–1•45). Analyses were by intention to treat and adjusted for baseline CD4-cell count and study stratum. This trial is registered at http://isrctn.org, number ISRCTN 17184129. Findings: 859 patients (22 clusters) were randomly assigned to home and 594 (22 clusters) to facility care. During the first year, 93 (11%) receiving home care and 66 (11%) receiving facility care died, 29 (3%) receiving home and 36 (6%) receiving facility care withdrew, and 8 (1%) receiving home and 9 (2%) receiving facility care were lost to follow-up. 117 of 729 (16%) in home care had virological failure versus 80 of 483 (17%) in facility care: rates per 100 person-years were 8•19 (95% CI 6•84–9•82) for home and 8•67 (6•96–10•79) for facility care (rate ratio [RR] 1•04, 0•78–1•40; equivalence shown). Two patients from each group were immediately lost to follow-up. Mortality rates were similar between groups (0•95 [0•71–1•28]). 97 of 857 (11%) patients in home and 75 of 592 (13%) in facility care were admitted at least once (0•91, 0•64–1•28). Interpretation: This home-based HIV-care strategy is as effective as is a clinic-based strategy, and therefore could enable improved and equitable access to HIV treatment, especially in areas with poor infrastructure and access to clinic care. Funding: US Centers for Disease Control and Prevention and UK Medical Research Council.
The experience of “medicine companions” to support adherence to antiretroviral therapy: quantitative and qualitative data from a trial population in Uganda
(Routledge Taylor & Francis Group, 2010-08-02) Foster, S. D.; Nakamanya, S.; Kyomuhangi, R.; Amurwon, J.; Namara, G.; Amuron, B.; Nabiryo, C.; Birungi, Josephine; Wolff, B.; Jaffar, S.; Grosskurth, H.
Good adherence is critical for antiretroviral therapy (ART) in sub-Saharan Africa. We report on the characteristics of medicine companions (MCs) chosen by Ugandan patients enrolling on ART, and on how MCs were chosen, and what roles they played. Baseline data on MCs of 1453 participants in a randomized controlled trial comparing facility and home-based delivery of ART in Jinja, Uganda were analyzed. Textual data on experience with MCs were collected through in-depth interviews among a subsample of 40 trial participants equally divided by sex and trial arm. Significantly more women (71%) than men (29%) were recruited. The majority (75%) of women participants were either widowed (51%) or separated or divorced (24%), whereas most of the men (66%) were married. Women were most likely to choose a child as their MC while men were most likely to choose their spouse; 41% of women chose an MC under 21 compared with only 14% of men. Only 31% of married women chose their husband, compared with 66% of married men who chose their wife. Qualitative interviews suggested MCs proved useful for reminding and other supportive tasks in the first three months but were generally less essential by six months and beyond. Convenience, reliability, and trust were key considerations in choosing an MC. Children provided the only alternative for many unmarried women, but even some married women felt children made more reliable MCs than husbands. Participants who had disclosed their serostatus usually received drug-taking reminders from multiple household members. One participant in the qualitative sample with poor family relations delayed starting treatment due to unwillingness to identify an MC. MCs were generally welcome and useful in supporting early adherence. However, disclosure to an MC should not be a condition of obtaining treatment.
A Phase 2 Study to Evaluate the Safety and Immunogenicity of a Recombinant HIV Type 1 Vaccine Basedon Adeno-Associated Virus.
(Mary Ann Liebert, Inc., 2010-08-12) Vardas, Eftyhia; Kaleebu, Pontiano; Bekker, Linda-Gail; Hoosen, Anwar; Chomba, Elwyn; Johnson, Philip R.; Anklesaria, Pervin; Birungi, Josephine; Barin, Burc; Boaz, Mark; Cox, Josephine; Lehrman, Jennifer; Stevens, Gwynn; Gilmour, Jill; Tarragona, Tony; Hayes, Peter; Lowenbein, Sarah; Kizito, Eva; Fast, Patricia; Heald, Alison E.; Schmidt, Claudia
The recombinant vaccine, tgAAC09, based on an adeno-associated virus serotype 2 (AAV2) vector encoding HIV-1 subtype C Gag, protease, and part of reverse transcriptase, induced robust T cell and antibody responses in nonhuman primates. In a previous phase I study in 80 healthy HIV-seronegative European and Indian adults, the vaccine was generally safe, well tolerated, and modestly immunogenic when administered once at doses up to 3x10 11 DRP. This phase II double-blind, randomized, placebo-controlled trial tested two administrations and a higher dosage of tgAAC009. Ninety-one healthy HIV-seronegative adults from three African countries were given one of three dosage levels of tgAAC09 (3x1010, 3x10 11, or 3x10 12 DRP) intramuscularly, either at a 6- or 12-month interval; follow-up was 18 months. Overall, 65% and 57% of vaccine recipients experienced local and systemic signs and symptoms, respectively, most being mild. Frequency and severity were not dose related and were similar to those in placebo recipients. No vaccine-related serious adverse events were reported. Overall, HIV-specific T cell responses were detected by IFN-g ELISPOT in 17/69 (25%) vaccine recipients with 38% (10/26) responders in the highest dosage group. The response rate improved significantly with boosting at 6, but not 12 months, in the 3x10 11 and 3x10 12 dosage groups only. Neutralizing antibody titers to the AAV2 did not alter the frequency of immune responses to HIV. Two doses of tgAAC09 were well tolerated at the dosage levels given. Fewer than half the recipients of the highest vaccine dosage, 3x10 12 DRP, had T cell responses to HIV.
Feasibility, Reliability and Validity of Health-Related Quality of Life Questionnaire Among Adult Pulmonary Tuberculosis Patients in Urban Uganda: Cross-Sectional Study
(Health and Quality of Life Outcomes, 2010-09) Babikako, Harriet M; Neuhauser, Duncan; Katamba, Achilles; Mupere, Ezekiel
Background Despite the availability of standard instruments for evaluating health-related quality life (HRQoL), the feasibility, reliability, and validity of such instruments among tuberculosis (TB) patients in different populations of sub-Saharan Africa where TB burden is of concern, is still lacking. Objective We established the feasibility, reliability, and validity of the Medical Outcomes Survey (MOS) in assessing HRQoL among patients with pulmonary tuberculosis in Kampala, Uganda. Methods In a cross-sectional study, 133 patients with known HIV status and confirmed pulmonary TB disease were recruited from one public and one private hospital. Participants were enrolled based on duration of TB treatment according to the following categories: starting therapy, two months of therapy, and eight completed months of therapy. A translated and culturally adapted standardized 35-item MOS instrument was administered by trained interviewers. The visual analogue scale (VAS) was used to cross-validate the MOS. Results The MOS instrument was highly acceptable and easily administered. All subscales of the MOS demonstrated acceptable internal consistency with Cronbach's alpha above 0.70 except for role function that had 0.65. Each dimension of the MOS was highly correlated with the dimension measured concurrently using the VAS providing evidence of validity. Construct validity demonstrated remarkable differences in the functioning status and well-being among TB patients at different stages of treatment, between patients attending public and private hospitals, and between men and women of older age. Patients who were enrolled from public hospital had significantly lower HRQoL scores (0.78 (95% confidence interval (CI); 0.64-0.95)) for perceived health but significantly higher HRQoL scores (1.15 (95% CI; 1.06-1.26)) for health distress relative to patients from private hospital. Patients who completed an 8 months course of TB therapy had significantly higher HRQoL scores for perceived health (1.93 (95% CI; 1.19-3.13)), health distress subscales (1.29 (95% CI; 1.04-1.59)) and mental health summary scores (1.27 (95% CI; 1.09-1.48)) relative to patients that were starting therapy in multivariable analysis. Completion of 8 months TB therapy among patients who were recruited from the public hospital was associated with a significant increase in HRQoL scores for quality of life subscale (1.26 (95% CI; 1.08-1.49)), physical health summary score (1.22 995% CI; 1.04-1.43)), and VAS (1.08 (95% CI; 1.01-1.15)) relative to patients who were recruited from the private hospital. Older men were significantly associated with lower HRQoL scores for physical health summary score (0.68 (95% CI; 0.49-0.95)) and VAS (0.87 (95% CI; 0.75-0.99)) relative to women of the same age group. No differences were seen between HIV positive and HIV negative patients. Conclusion The study provides evidence that the MOS instrument is valid, and reliably measures HRQoL among TB patients, and can be used in a wide variety of study populations. The HRQoL differed by hospital settings, by duration of TB therapy, and by gender in older age groups.
Proportion of Deaths and Clinical Features in Bundibugyo Ebola Virus Infection, Uganda
(Emerging infectious disease, 2010-12) MacNeil, Adam; Farnon, Eileen C.; Wamala, Joseph; Okware, Sam; Cannon, Deborah L.; Reed, Zachary; Towner, Jonathan S.; Tappero, Jordan W.; Lutwama, Julius; Downing, Robert; Nichol, Stuart T.; Ksiazek, Thomas G.; Rollin, Pierre E.
The first known Ebola hemorrhagic fever (EHF) outbreak caused by Bundibugyo Ebola virus occurred in Bundibugyo District, Uganda, in 2007. Fifty-six cases of EHF were laboratory confirmed. Although signs and symptoms were largely nonspecific and similar to those of EHF outbreaks caused by Zaire and Sudan Ebola viruses, proportion of deaths among those infected was lower (≈40%).
Equivalence of ELISpot Assays Demonstrated between Major HIV Network Laboratories
(PLOS ONE, 2010-12-14) Gill, Dilbinder K.; Huang, Yunda; Levine, Gail L.; Sambor, Anna; Carter, Donald K.; Sato, Alicia; Kopycinski, Jakub; Hayes, Peter; Hahn, Bridget; Birungi, Josephine; Tarragona-Fiol, Tony; Wan, Hong; Randles, Mark; Cooper, Andrew Raxworthy; Ssemaganda, Aloysius; Clark, Lorna; Kaleebu, Pontiano; Self, Steven G.; Koup, Richard; Wood, Blake; McElrath, M. Juliana; Cox, Josephine H.; Hural, John; Gilmour, Jill
Background: The Comprehensive T Cell Vaccine Immune Monitoring Consortium (CTC-VIMC) was created to provide standardized immunogenicity monitoring services for HIV vaccine trials. The ex vivo interferon-gamma (IFN-c) ELISpot is used extensively as a primary immunogenicity assay to assess T cell-based vaccine candidates in trials for infectious diseases and cancer. Two independent, GCLP-accredited central laboratories of CTC-VIMC routinely use their own standard operating procedures (SOPs) for ELISpot within two major networks of HIV vaccine trials. Studies are imperatively needed to assess the comparability of ELISpot measurements across laboratories to benefit optimal advancement of vaccine candidates. Methods: We describe an equivalence study of the two independently qualified IFN-g ELISpot SOPs. The study design, data collection and subsequent analysis were managed by independent statisticians to avoid subjectivity. The equivalence of both response rates and positivity calls to a given stimulus was assessed based on pre-specified acceptance criteria derived from a separate pilot study. Findings: Detection of positive responses was found to be equivalent between both laboratories. The 95% C.I. on the difference in response rates, for CMV (21.5%, 1.5%) and CEF (20.4%, 7.8%) responses, were both contained in the prespecified equivalence margin of interval [215%, 15%]. The lower bound of the 95% C.I. on the proportion of concordant positivity calls for CMV (97.2%) and CEF (89.5%) were both greater than the pre-specified margin of 70%. A third CTC-VIMC central laboratory already using one of the two SOPs also showed comparability when tested in a smaller sub-study. Interpretation: The described study procedure provides a prototypical example for the comparison of bioanalytical methods in HIV vaccine and other disease fields. This study also provides valuable and unprecedented information for future vaccine candidate evaluations on the comparison and pooling of ELISpot results generated by the CTC-VIMC central core laboratories.

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