Hannah Kibuuka

Makerere University, Kampala, Central Region, Uganda

Are you Hannah Kibuuka?

Claim your profile

Publications (36)173.94 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Attrition within the CD4+ T cell compartment, high viremia and a cytokine storm characterize the early days after HIV infection. When the first emerging HIV-specific CD8+ T cell responses gain control over viral replication, it is incomplete, and clearance of HIV infection is not achieved even in the rare cases of individuals who spontaneously control viral replication to near to immeasurable low levels. Thus, despite their partial ability to control viremia, HIV-specific CD8+ T cell responses are insufficient to clear HIV infection. Studying individuals in the first few days of acute HIV infection, we detected the emergence of a unique population of CD38+CD27-CD8+ T cells characterized by a low expression of the CD8 receptor (CD8 dim ). Interestingly, while a high frequency of HIV-specific CD8+ T cell responses are within the CD38+CD27-CD8 dim T cell population, the minority populations of CD8 bright T cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8 dim T cells directly correlates with viral load and clinical predictors of more rapid disease progression. We found that a canonical burst of proliferative cytokines coincides with the emergence CD8 dim T cells and the size of this population inversely correlates with the acute loss of CD4+ T cells. These data indicate, for the first time, that early CD4+ T cell loss coincides with the expansion of a functionally impaired HIV specific CD8 dim T cell population less efficient in controlling HIV viremia. Importance: A distinct population of activated CD8+ T cells appears during acute HIV infection with diminished capacity to inhibit HIV replication and is predictive of viral set-point, offering the first immunologic evidence of CD8+ T cell dysfunction during acute infection.
    No preview · Article · Feb 2016 · Journal of Virology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Management of patient care and interpretation of research data require evaluation of laboratory results in the context of reference data from populations with known health status to adequately diagnose disease or make a physiological assessment. Few studies have addressed the diversity of lymphocyte subsets in rural and urban Ugandan populations. Here, 663 healthy blood bank donors from semi-urban centers of Kampala consented to participate in a study to define lymphocyte reference ranges. Whole blood immunophenotyping was performed to determine the frequency and absolute counts of T, B, and NK cells using clinical flow cytometry. Results from blood bank donors were compared to a rural cohort from the district of Kayunga and more urban clinical trial participants from the capital city, Kampala. Relationships between hematological and lymphocyte parameters were also explored. In the semi-urban blood donors, females were significantly different from males in all parameters except the frequency of CD8 T and B cells. Females had higher absolute counts of CD4 T, CD8 T and B cells, whereas males had higher NK cell counts. NK cell frequency and counts were significantly higher in semi-urban blood donors, regardless of sex, compared to more urban study participants. CD8 T cell frequency and counts were significantly higher in the blood donors compared to the rural participants, irrespective of sex. Interestingly, basophil counts were positively associated with overall T cell counts. These findings suggest that both sex and level of cohort urbanicity may influence lymphocyte subset distributions in Ugandans.
    Full-text · Article · Jan 2016 · PLoS ONE
  • [Show abstract] [Hide abstract]
    ABSTRACT: The limited data available for long-term Ebola virus disease health outcomes suggest that sequelae persist for longer than 1 year after infection. The magnitude of the present outbreak in west Africa necessitates a more complete understanding of the health effects and future medical needs of these patients. We invited adult survivors of the 2007 Bundibugyo Ebola virus outbreak in Uganda and their contacts to take part in an observational study roughly 29 months after the outbreak. We collected information about health status, functional limitations, and demographics. We collected blood samples for clinical chemistry, haematology, and filovirus antibodies using ELISA. Analyses were restricted to probable and confirmed survivors and their seronegative contacts. We recruited 70 survivors of the 2007 Bundibugyo Ebola virus and 223 contacts. We did analyses for 49 probable and confirmed survivors and 157 seronegative contacts. Survivors of the Bundibugyo Ebola virus were at significantly increased risk of ocular deficits (retro-orbital pain [RR 4·3, 95% CI 1·9-9·6; p<0·0001], blurred vision [1·9, 1·1-3·2; p=0·018]), hearing loss (2·3, 1·2-4·5; p=0·010), difficulty swallowing (2·1, 1·1-3·9; p=0·017), difficulty sleeping (1·9, 1·3-2·8; p=0·001), arthralgias (2·0, 1·1-3·6; p=0·020), and various constitutional symptoms controlling for age and sex. Chronic health problems (prevalence ratio [PR] 2·1, 95% CI 1·2-3·6; p=0·008) and limitations due to memory loss or confusion (PR 5·8, 1·5-22·4; p=0·010) were also reported more frequently by survivors of Bundibugyo Ebola virus. Long-term sequelae persist for more than 2 years after Ebola virus disease. Definition of health consequences related to Ebola virus disease could improve patient care for survivors and contribute to understanding of disease pathogenesis. Chemical Biological Technologies Directorate, Defense Threat Reduction Agency. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Apr 2015 · The Lancet Infectious Diseases
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Ugandan Ministry of Health has endorsed voluntary medical male circumcision as an HIV prevention strategy and has set ambitious goals (e.g., 4.2 million circumcisions by 2015). Innovative strategies to improve access for hard to reach, high risk, and poor populations are essential for reaching such goals. In 2009, the Makerere University Walter Reed Project began the first facility-based VMMC program in Uganda in a non-research setting. In addition, a mobile clinic began providing VMMC services to more remote, rural locations in 2011. The primary objective of this study was to estimate the average cost of performing VMMCs in the mobile clinic compared to those performed in health facilities (fixed sites). The difference between such costs is the cost of improving access to VMMC. A micro-costing approach was used to estimate costs from the service provider's perspective of a circumcision. Supply chain and higher-level program support costs are not included. The average cost (US$2012) of resources used per circumcision was $61 in the mobile program ($72 for more remote locations) compared to $34 at the fixed site. Costs for community mobilization, HIV testing, the initial medical exam, and staff for performing VMMC operations were similar for both programs. The cost of disposable surgical kits, the additional upfront cost for the mobile clinic, and additional costs for staff drive the differences in costs between the two programs. Cost estimates are relatively insensitive to patient flow over time. The MUWRP VMMC program improves access for hard to reach, relatively poor, and high-risk rural populations for a cost of $27-$38 per VMMC. Costs to patients to access services are almost certainly less in the mobile program, by reducing out-of-pocket travel expenses and lost time and associated income, all of which have been shown to be barriers for accessing treatment.
    Full-text · Article · Mar 2015 · PLoS ONE
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ebola virus and Marburg virus cause serious disease outbreaks with high case fatality rates. We aimed to assess the safety and immunogenicity of two investigational DNA vaccines, one (EBO vaccine) encoding Ebola virus Zaire and Sudan glycoproteins and one (MAR) encoding Marburg virus glycoprotein. RV 247 was a phase 1b, double-blinded, randomised, placebo-controlled clinical trial in Kampala, Uganda to examine the safety and immunogenicity of the EBO and MAR vaccines given individually and concomitantly. Healthy adult volunteers aged 18-50 years were randomly assigned (5:1) to receive three injections of vaccine or placebo at weeks 0, 4, and 8, with vaccine allocations divided equally between three active vaccine groups: EBO vaccine only, MAR vaccine only, and both vaccines. The primary study objective was to investigate the safety and tolerability of the vaccines, as assessed by local and systemic reactogenicity and adverse events. We also assessed immunogenicity on the basis of antibody responses (ELISA) and T-cell responses (ELISpot and intracellular cytokine staining assays) 4 weeks after the third injection. Participants and investigators were masked to group assignment. Analysis was based on the intention-to-treat principle. This trial is registered at ClinicalTrials.gov, number NCT00997607. 108 participants were enrolled into the study between Nov 2, 2009, and April 15, 2010. All 108 participants received at least one study injection (including 100 who completed the injection schedule) and were included in safety and tolerability analyses; 107 for whom data were available were included in the immunogenicity analyses. Study injections were well tolerated, with no significant differences in local or systemic reactions between groups. The vaccines elicited antibody and T-cell responses specific to the glycoproteins received and we detected no differences between the separate and concomitant use of the two vaccines. 17 of 30 (57%, 95% CI 37-75) participants in the EBO vaccine group had an antibody response to the Ebola Zaire glycoprotein, as did 14 of 30 (47%, 28-66) in the group that received both vaccines. 15 of 30 (50%, 31-69) participants in the EBO vaccine group had an antibody response to the Ebola Sudan glycoprotein, as did 15 of 30 (50%, 31-69) in the group that received both vaccines. Nine of 29 (31%, 15-51) participants in the MAR vaccine groups had an antibody response to the Marburg glycoprotein, as did seven of 30 (23%, 10-42) in the group that received both vaccines. 19 of 30 (63%, 44-80) participants in the EBO vaccine group had a T-cell response to the Ebola Zaire glycoprotein, as did 10 of 30 (33%, 17-53) in the group that received both vaccines. 13 of 30 (43%, 25-63) participants in the EBO vaccine group had a T-cell response to the Ebola Sudan glycoprotein, as did 10 of 30 (33%, 17-53) in the group that received both vaccines. 15 of 29 (52%, 33-71) participants in the MAR vaccine group had a T-cell response to the Marburg glycoprotein, as did 13 of 30 (43%, 25-63) in the group that received both vaccines. This study is the first Ebola or Marburg vaccine trial done in Africa, and the results show that, given separately or together, both vaccines were well tolerated and elicited antigen-specific humoral and cellular immune responses. These findings have contributed to the accelerated development of more potent Ebola virus vaccines that encode the same wild-type glycoprotein antigens as the EBO vaccine, which are being assessed during the 2014 Ebola virus disease outbreak in west Africa. US Department of Defense Infectious Disease Clinical Research Program and US National Institutes of Health Intramural Research Program. Copyright © 2014 Elsevier Ltd. All rights reserved.
    No preview · Article · Dec 2014 · The Lancet
  • [Show abstract] [Hide abstract]
    ABSTRACT: Following rapid scale up of ART, attention is now focused on improving quality of care and identifying populations and interventions to maximize impact and long-term effectiveness. Viral load, considered the most important indicator of response to ART, can be used to assess HIV treatment program quality. This study evaluates quality using clinic and patient level indicators impacting VL outcome. Patients on treatment for >6 months were randomly selected and recruited for RV:288, A Virological Assessment of Patients on ART in the US Military HIV Research Program (MHRP)/PEPFAR-Supported Programs in Africa at 15 randomly selected clinics across 3 MHRP programs in Kenya (n = 650), Tanzania (n = 702) and Uganda (n = 325). Clinic and program level quality were assessed using the WHO-promoted quality assurance benchmark of >=70% of ART patients showing virological suppression, defined as VL <= 999 copies/ml. While all 3 programs exceeded the benchmark, 2 clinics (C4 and C5, both part of WRP-Kenya) failed to meet this standard. Clinic and patient level indicators were evaluated for their impact on VL outcome. At 9 clinics-C4 and C5, as well as all 7 WRP-Tanzania clinics-more than 60% of patients had ART duration of >2 years. Interestingly, patients with this ART duration represent 76% and 68% of non-suppressed patients at C4 and C5, respectively. Staffing at the program and clinic level interacted with ART duration to impact program quality: WRP-Tanzania clinics had mean personnel surplus of 14.4 when comparing positions allocated with positions filled; WRP-Kenya clinics of had a mean shortage of 11.5 staff. Importantly, staff shortage at C4 and C5 included the physician/medical officer. Combining VL with patient and facility indicators is useful for assessing HIV treatment program quality. Findings point to the importance of addressing shifting needs for resource allocation, specifically the interaction between staffing levels and duration of treatment across the patient population as the ART-experienced population matures.
    No preview · Article · Nov 2014 · JAIDS Journal of Acquired Immune Deficiency Syndromes
  • Source

    Full-text · Article · Oct 2014 · AIDS Research and Human Retroviruses
  • Source

    Full-text · Article · Oct 2014 · AIDS Research and Human Retroviruses
  • Source

    Full-text · Article · Oct 2014 · AIDS Research and Human Retroviruses
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Efficacy trials of adenovirus 5-vectored candidate HIV vaccines [recombinant Ad5 (rAd5)-HIV] were halted for futility due to lack of vaccine efficacy and unexpected excess HIV infections in the vaccine recipients. The potential immunologic basis for these observations is unclear. We comparatively evaluated the HIV susceptibility and phenotypes of human CD4 T cells specific to Ad5 and CMV, two viruses that have been used as HIV vaccine vectors. We show that Ad5-specific CD4 T cells, either induced by natural Ad5 exposure or expanded by rAd5 vaccination, are highly susceptible to HIV in vitro and are preferentially lost in HIV-infected individuals compared with CMV-specific CD4 T cells. Further investigation demonstrated that Ad5-specific CD4 T cells selectively display a proinflammatory Th17-like phenotype and express macrophage inflammatory protein 3α and α4β7 integrin, suggestive of gut mucosa homing potential of these cells. Analysis of HIV p24 and cytokine coexpression using flow cytometry revealed preferential infection of IL-17- and IL-2-producing, Ad5-specific CD4 T cells by HIV in vitro. Our data suggest a potential mechanism explaining the excess HIV infections in vaccine recipients after rAd5-HIV vaccination and highlight the importance of testing the HIV susceptibility of vaccine-generated, vector and insert-specific CD4 T cells in future HIV vaccine studies.
    Full-text · Article · Sep 2014 · Proceedings of the National Academy of Sciences
  • K W Crawford · S Wakabi · F Magala · H Kibuuka · M Liu · T E Hamm
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Viral load (VL) monitoring is recommended, but seldom performed, in resource-constrained countries. RV288 is a US President's Emergency Plan for AIDS Relief (PEPFAR) basic programme evaluation to determine the proportion of patients on treatment who are virologically suppressed and to identify predictors of virological suppression and recovery of CD4 cell count. Analyses from Uganda are presented here.Methods In this cross-sectional, observational study, patients on first-line antiretroviral therapy (ART) (efavirenz or nevirapine + zidovudine/lamivudine) from Kayunga District Hospital and Kagulamira Health Center were randomly selected for a study visit that included determination of viral load (HIV-1 RNA), CD4 cell count and clinical chemistry tests. Subjects were recruited by time on treatment: 6–12, 13–24 or > 24 months. Logistic regression modelling identified predictors of virological suppression. Linear regression modelling identified predictors of CD4 cell count recovery on ART.ResultsWe found that 85.2% of 325 subjects were virologically suppressed (viral load < 47 HIV-1 RNA copies/ml). There was no difference in the proportion of virologically suppressed subjects by time on treatment, yet CD4 counts were higher in each successive stratum. Women had higher median CD4 counts than men overall (406 vs. 294 cells/μL, respectively; P < 0.0001) and in each time-on-treatment stratum. In a multivariate logistic regression model, predictors of virological suppression included efavirenz use [odds ratio (OR) 0.47; 95% confidence interval (CI) 0.22–1.02; P = 0.057], lower cost of clinic visits (OR 0.815; 95% CI 0.66–1.00; P = 0.05), improvement in CD4 percentage (OR 1.06; 95% CI 1.014–1.107; P = 0.009), and care at Kayunga vs. Kangulamira (OR 0.47; 95% CI 0.23–0.92; P = 0.035). In a multivariate linear regression model of covariates associated with CD4 count recovery, time on highly active antiretroviral therapy (ART) (P < 0.0001), patient satisfaction with care (P = 0.038), improvements in total lymphocyte count (P < 0.0001) and haemoglobin concentration (P = 0.05) were positively associated, whereas age at start of ART (P = 0.0045) was negatively associated with this outcome.Conclusions High virological suppression rates are achievable on first-line ART in Uganda. The odds of virological suppression were positively associated with efavirenz use and improvements in CD4 cell percentage and total lymphocyte count and negatively associated with the cost of travel to the clinic. CD4 cell reconstitution was positively associated with CD4 count at study visit, time on ART, satisfaction with care at clinic, haemoglobin concentration and total lymphocyte count and negatively associated with age.
    No preview · Article · Sep 2014 · HIV Medicine
  • [Show abstract] [Hide abstract]
    ABSTRACT: Live bird markets (LBMs) are essential for marketing of poultry, but can be a hub for the rapid spread of diseases including avian influenza (AI). We assessed the status of biosecurity in 108 LBMs in 37 districts of Uganda. In all LBMs, carcasses were disposed of in the open and birds were introduced in the markets without initial quarantine. A high proportion of markets lacked a dedicated site for unloading of birds (86.1%) and a programme for disinfection (99.1%), had dirty feed/water troughs (93.5%), were accessed by stray animals (97.2%), and had sick and healthy birds (96.3%) or different bird species (86.1%) sold together. Differences in practices occurred among geographical regions and market location. Birds were more likely to be slaughtered in the open in urban compared to rural LBMs (OR=14.6, 95% CI: 1.50 - 142), while selling of un-caged birds was less likely in central compared to western region (OR=0.2, 95% CI: 0.04 - 0.17). Different poultry species confined in the same cage were more likely to be sold in urban (OR=22, 95% CI: 1.14 - 435) compared to rural markets. We conclude that LBMs in Uganda are a potential risk for spread of AI to poultry and humans.
    No preview · Article · Jun 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: HIV-1 viral load (VL) monitoring is recommended but seldom performed in resource-constrained countries.. An evaluation of patients receiving first-line anti-retroviral therapy in a multi-country PEPFAR program (RV288) was performed to determine rates and predictors of virologic suppression. Resistance data from treatment failures are available from Uganda and Nigeria. Methods: Each country enrolled 325 subjects into this cross-sectional study. Subjects on first line therapy were randomly selected for HIV RNA testing (viral load). Regimens included efavirenz or nevirapine with zidovudine/lamivudine or tenofovir/lamivudine. Viral load (VL) was determined from plasma using the Roche COBAS® TaqMan® HIV-1 Test, High Pure System (47 c/ml). Genotypic resistance testing was performed on samples with VL>1000 cps/ml. Results: From Uganda, 85% of subjects were undetectable while 7% (23/325) had VL>1000 cps/ml. The HIV-1 subtype distribution was as follows: A=43%, C =14% and D=50%. No resistance was found in 14% of subjects. All subjects with resistance had the M184V mutation. Of subjects failing a zidovudine-regimen < one year, 88% (7/8) had no TAM's, compared to 50% (4/8) failing > one year. Four subjects (25%) had > 2 mutations from the TAM-1 pathway (41L, 210W, 215Y). In Nigeria, 82% were undetectable while 14% (45/325) had VL >1000 cps/ml. HIV-1 subtype distribution was as follows: 62.8%=CRF02_AG, 34%=pure G and 2.8%= A. Of the 35 genotyped subjects , 14% (5/35) had no resistance mutations. Of the remainder, 10% (3/30) had no nucleoside analogue mutations while 33% (10/30) had only M184V along with NNRTI-mutations. There were 40% (10/25) of subjects on zidovudine that failed without TAMs. Another 25% (5/25) of subjects failing on zidovudine had >2 TAM-1 mutations. Conclusions: Individuals failing first-line ART may retain sensitivity to one or more nucleoside analogues from the regimen. Knowledge of drug resistance patterns allow for selection of drugs that can be recycled in future regimens. Accumulation of resistance mutations may compromise future treatment options.
    Full-text · Article · May 2014 · AIDS research and human retroviruses
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Avian influenza viruses may cause severe disease in a variety of domestic animal species worldwide, with high mortality in chickens and turkeys. To reduce the information gap about prevalence of these viruses in animals in Uganda, this study was undertaken. Influenza A virus prevalence by RT-PCR was 1.1% (45/4,052) while seroprevalence by ELISA was 0.8% (24/2,970). Virus prevalence was highest in domestic ducks (2.7%, 17/629) and turkeys (2.6%, 2/76), followed by free-living waterfowl (1.3%, 12/929) and swine (1.4%, 7/511). A lower proportion of chicken samples (0.4%, 7/1,865) tested positive. No influenza A virus was isolated. A seasonal prevalence of these viruses in waterfowl was 0.7% (4/561) for the dry and 2.2% (8/368) for the wet season. In poultry, prevalence was 0.2% (2/863) for the dry and 1.4% (24/1,713) for the wet season, while that of swine was 0.0% (0/159) and 2.0% (7/352) in the two seasons, respectively. Of the 45 RT-PCR positive samples, 13 (28.9%) of them were H5 but none was H7. The 19 swine sera positive for influenza antibodies by ELISA were positive for H1 antibodies by HAI assay, but the subtype(s) of ELISA positive poultry sera could not be determined. Antibodies in the poultry sera could have been those against subtypes not included in the HAI test panel. The study has demonstrated occurrence of influenza A viruses in animals in Uganda. The results suggest that increase in volumes of migratory waterfowl in the country could be associated with increased prevalence of these viruses in free-living waterfowl and poultry.
    Full-text · Article · Feb 2014 · BMC Veterinary Research

  • No preview · Conference Paper · Nov 2013

  • No preview · Conference Paper · Nov 2013

  • No preview · Conference Paper · Nov 2013
  • Source

    Full-text · Conference Paper · Feb 2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Influenza B viruses can cause morbidity and mortality in humans but due to the lack of an animal reservoir are not associated with pandemics. Because of this, there is relatively limited genetic sequences available for influenza B viruses, especially from developing countries. Complete genome analysis of one influenza B virus and several gene segments of other influenza B viruses isolated from Uganda from May 2009 through December 2010 was therefore undertaken in this study. Methods Samples were collected from patients showing influenza like illness and screened for influenza A and B by PCR. Influenza B viruses were isolated on Madin-Darby Canine Kidney cells and selected isolates were subsequently sequenced and analyzed phylogenetically. Findings Of the 2,089 samples collected during the period, 292 were positive by PCR for influenza A or B; 12.3% of the PCR positives were influenza B. Thirty influenza B viruses were recovered and of these 25 that grew well consistently on subculture were subjected to further analysis. All the isolates belonged to the B/Victoria-lineage as identified by hemagglutination inhibition assay and genetic analysis except one isolate that grouped with the B-Yamagata-lineage. The Ugandan B/Victoria-lineage isolates grouped in clade 1 which was defined by the N75K, N165K and S172P substitutions in hemagglutinin (HA) protein clustered together with the B/Brisbane/60/2008 vaccine strain. The Yamagata-like Ugandan strain, B/Uganda/MUWRP-053/2009, clustered with clade 3 Yamagata viruses such as B/Bangladesh/3333/2007 which is characterized by S150I and N166Y substitutions in HA. Conclusion In general there was limited variation among the Ugandan isolates but they were interestingly closer to viruses from West and North Africa than from neighboring Kenya. Our isolates closely matched the World Health Organization recommended vaccines for the seasons.
    Full-text · Article · Jan 2013 · Virology Journal
  • Source

    Full-text · Article · Sep 2012 · Retrovirology