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1.
Front Immunol ; 12: 637114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815390

RESUMO

Introduction: The immunogenicity of BCG vaccination in infants differs between populations. We hypothesized that prenatal exposure to mycobacterial antigens might explain the differences in immune responses to BCG seen in other studies of infants in Africa and the United Kingdom (UK) and we explored this in birth cohorts in Uganda and the UK. Materials and Methods: Blood samples were obtained from BCG-immunized infants of mothers with (n = 110) and without (n = 121) latent Mycobacterium tuberculosis infection (LTBI) in Uganda and BCG-immunized infants of mothers without LTBI (n = 25) in the UK at 10 and 52 weeks after birth. Cytokine and chemokine responses to PPD were measured to assess responses to BCG immunization, and to ESAT6/CFP10 to assess exposure to or infection with M. tuberculosis or non-tuberculous mycobacteria (NTM) in 6-day whole blood culture supernatants by a 17-plex Luminex assay. Median responses were compared between Ugandan infants (together, and separated by maternal LTBI status) and UK infants. Results: The IFN-γ response to BCG vaccination was similar between Ugandan and UK infants at 10 and 52 weeks. At week 52, TNF production was marginally higher in Ugandan infants, but after adjusting for multiple comparisons this difference was not significant. At weeks 10 and 52, stimulation of blood with ESAT6/CFP10 produced significantly higher IFN-γ, TNF, IL-12p40, IL-1α, IL-1ß, IL-1Ra, IP-10, MIP-1α, MIP-1ß, and GM-CSF in Ugandan compared to UK infants. Stimulation of blood with ESAT6/CFP10 produced significantly higher amounts of IL-8 (p = 0.0001), IL-10 (p = 0.0022), and IL-13 (p = 0.0020) in the UK than in Ugandan infants of mothers without LTBI at week 10, but not at week 52. Conclusions: Immune responses to mycobacterial antigens following BCG immunization are similar for PPD, but differ for ESAT6/CFP10, between infants in Uganda and the UK. Neither maternal LTBI nor infant exposure to or infection with mycobacteria impacts the response to BCG. The observed global differences in immune response to BCG immunization are likely to be due to other causes.

2.
J Clin Microbiol ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33903166

RESUMO

Background: We assessed the performance of CoronaCHEK lateral flow assay on samples from Uganda and Baltimore to determine the impact of geographic origin on assay performance.Methods: Plasma samples from SARS-CoV-2 PCR+ individuals (Uganda: 78 samples from 78 individuals and Baltimore: 266 samples from 38 individuals) and from pre-pandemic individuals (Uganda 1077 and Baltimore 532) were evaluated. Prevalence ratios (PR) were calculated to identify factors associated with a false-positive test.Results: After first positive PCR in Ugandan samples the sensitivity was: 45% (95% CI 24,68) at 0-7 days; 79% (95%CI 64,91) 8-14 days; and 76% (95%CI 50,93) >15 days. In samples from Baltimore, sensitivity was: 39% (95% CI 30, 49) 0-7 days; 86% (95% CI 79,92) 8-14 days; and 100% (95% CI 89,100) 15 days post positive PCR. The specificity of 96.5% (95% CI 97.5,95.2) in Ugandan samples was significantly lower than samples from Baltimore 99.3% (95% CI 98.1,99.8), p<0.01. In Ugandan samples, individuals with a false positive result were more likely to be male (PR 2.04, 95% CI 1.03,3.69) or individuals who had a fever more than a month prior to sample acquisition (PR 2.87, 95% CI 1.12,7.35).Conclusions: Sensitivity of the CoronaCHEK was similar in samples from Uganda and Baltimore. The specificity was significantly lower in Ugandan samples than in Baltimore samples. False positive results in Ugandan samples appear to correlate with a recent history of a febrile illness, potentially indicative of a cross-reactive immune response in individuals from East Africa.

3.
Front Immunol ; 12: 565625, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679730

RESUMO

Sub-Saharan Africa has generally experienced few cases and deaths of coronavirus disease 2019 (COVID-19). In addition to other potential explanations for the few cases and deaths of COVID-19 such as the population socio-demographics, early lockdown measures and the possibility of under reporting, we hypothesize in this mini review that individuals with a recent history of malaria infection may be protected against infection or severe form of COVID-19. Given that both the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium falciparum (P. falciparum) merozoites bind to the cluster of differentiation 147 (CD147) immunoglobulin, we hypothesize that the immunological memory against P. falciparum merozoites primes SARS-CoV-2 infected cells for early phagocytosis, hence protecting individuals with a recent P. falciparum infection against COVID-19 infection or severity. This mini review therefore discusses the potential biological link between P. falciparum infection and COVID-19 infection or severity and further highlights the importance of CD147 immunoglobulin as an entry point for both SARS-CoV-2 and P. falciparum into host cells.


Assuntos
Basigina/imunologia , Memória Imunológica , Malária Falciparum , Plasmodium falciparum/imunologia , /imunologia , África ao Sul do Saara/epidemiologia , /imunologia , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Merozoítos/imunologia , Índice de Gravidade de Doença
4.
Sci Rep ; 11(1): 7017, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33782485

RESUMO

The design of HIV prevention trials in the context of effective HIV preventive methods is a challenge. Alternate designs, including using non-randomised 'observational control arms' have been proposed. We used HIV simulated vaccine efficacy trials (SiVETs) to show pitfalls that may arise from using such observational controls and suggest how to conduct the analysis in the face of the pitfalls. Two SiVETs were nested within previously established observational cohorts of fisherfolk (FF) and female sex workers (FSW) in Uganda. SiVET participants received a licensed Hepatitis B vaccine in a schedule (0, 1 and 6 months) similar to that for a possible HIV vaccine efficacy trial. All participants received HIV counselling and testing every quarter for one year to assess HIV incidence rate ratio (IRR) between SiVET and non-SiVET (observational data). Propensity scores, conditional on baseline characteristics were calculated for SiVET participation and matched between SiVET and non-SiVET in the period before and during the SiVET study. We compared IRR before and after propensity score matching (PSM). In total, 3989 participants were enrolled into observational cohorts prior to SiVET, (1575 FF prior to Jul 2012 and 2414 FSW prior to Aug 2014). SiVET enrolled 572 participants (Jul 2012 to Apr 2014 in FF and Aug 2014 to Apr 2017 in FSW), with 953 non-SiVET participants observed in the SiVET concurrent period and 2928 from the pre-SiVET period (before Jul 2012 in FF or before Apr 2014 in FSW). Imbalances in baseline characteristics were observed between SiVET and non-SiVET participants in both periods before PSM. Similarly, HIV incidence was lower in SiVET than non-SiVET; SiVET-concurrent period, IRR = 0.59, 95% CI 0.31-0.68, p = 0.033 and pre-SiVET period, IRR = 0.77, 95% CI 0.43-1.29, p = 0.161. After PSM, participants baseline characteristics were comparable and there were minimal differences in HIV incidence between SiVET and non-SiVET participants. The process of screening for eligibility for efficacy trial selects participants with baseline characteristics different from the source population, confounding any observed differences in HIV incidence. Propensity score matching can be a useful tool to adjust the imbalance in the measured participants' baseline characteristics creating a counterfactual group to estimate the effect of interventions on HIV incidence.

5.
PLoS Negl Trop Dis ; 15(3): e0008983, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33657099

RESUMO

BACKGROUND: Cryptococcal meningitis (CCM) remains one of the leading causes of mortality among HIV infected patients. Due to factors such as the severity of CCM pathology, the quality of life (QOL) of patients post-treatment is likely to be poor. Few studies have reported on QOL of CCM patients post treatment completion. We used data collected among patients in the CryptoDex trial (ISRCTN59144167) to determine QOL and associated factors at week 10 and six months from treatment initiation. METHODOLOGY: CryptoDex was a double-blind placebo-controlled trial of adjunctive dexamethasone in HIV infected adults with CCM, conducted between 2013 and 2015 in six countries in Asia and Africa. QOL was determined using the descriptive and Visual Analog Scales (VAS) of the EuroQol Five-Dimension-Three-Level (EQ-5D-3L) tool. We derived index scores, and described these and the VAS scores at 10 weeks and 6 months; and used linear regression to determine the relationship between various characteristics and VAS scores at both time points. VAS scores were interpreted as very good (81-100), good (51-80), normal (31-50) and bad/very bad (0-30). RESULTS: Of 451 patients enrolled in the trial, 238 had QOL evaluations at week 10. At baseline, their mean age (SD) was 35.2(8.5) years. The mean index scores (SD) were 0.785(0.2) and 0.619(0.4) among African and Asian patients respectively at week 10, and 0.879(0.2) and 0.731(0.4) among African and Asian patients respectively at month six. The overall mean VAS score (SD) at 10 weeks was 57.2 (29.7), increasing significantly to 72(27.4) at month six (p<0.001). At week 10, higher VAS score was associated with greater weight (p = 0.007) and being African (p<0.001), while lower VAS score was associated with positive yeast culture at day 14 (p = 0.026). At month six, higher VAS score remained associated with African origin (p = 0.006) while lower VAS score was associated with positive yeast culture (p = 0.006). Lower VAS scores were associated with higher number of inpatient days at 10 weeks and 6 months (p = 0.003 and 0.002 respectively). CONCLUSION: QOL was good among patients that had completed therapy for CCM, but below perfect. Strategies to improve QOL among CCM survivors are required.

6.
Hum Mol Genet ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33783510

RESUMO

BACKGROUND: Genome-wide association studies (GWAS) of kidney function have uncovered hundreds of loci, primarily in populations of European ancestry. We have undertaken the first continental African GWAS of estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). METHOD: We conducted GWAS of eGFR in 3288 East Africans from the Uganda General Population Cohort (GPC) and replicated in 8224 African Americans from the Women's Health Initiative. Loci attaining genome-wide significant evidence for association (p < 5x10-8) were followed up with Bayesian fine-mapping to localise potential causal variants. The predictive power of a genetic risk score (GRS) constructed from previously reported trans-ancestry eGFR lead SNPs was evaluated in the Uganda GPC. FINDINGS: We identified and validated two eGFR loci. At the GATM locus, the association signal (lead SNP rs2433603, p = 1.0x10-8) in the Uganda GPC GWAS was distinct from previously reported signals at this locus. At the HBB locus, the association signal (lead SNP rs141845179, p = 3.0x10-8) has been previously reported. The lead SNP at the HBB locus accounted for 88% of the posterior probability of causality after fine-mapping, but did not colocalise with kidney expression quantitative trait loci. The trans-ancestry GRS of eGFR was not significantly predictive into the Ugandan population. INTERPRETATION: In the first GWAS of eGFR in continental Africa, we validated two previously reported loci at GATM and HBB. At the GATM locus, the association signal was distinct from that previously reported. These results demonstrate the value of performing GWAS in continental Africans, providing a rich genomic resource to larger consortia for further discovery and fine-mapping. The study emphasizes that additional large-scale efforts in Africa are warranted to gain further insight into the genetic architecture of CKD.

7.
BMJ Open ; 11(2): e040425, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593767

RESUMO

INTRODUCTION: Vaccine-specific immune responses vary between populations and are often impaired in low income, rural settings. Drivers of these differences are not fully elucidated, hampering identification of strategies for optimising vaccine effectiveness. We hypothesise that urban-rural (and regional and international) differences in vaccine responses are mediated to an important extent by differential exposure to chronic infections, particularly parasitic infections. METHODS AND ANALYSIS: Three related trials sharing core elements of study design and procedures (allowing comparison of outcomes across the trials) will test the effects of (1) individually randomised intervention against schistosomiasis (trial A) and malaria (trial B), and (2) Bacillus Calmette-Guérin (BCG) revaccination (trial C), on a common set of vaccine responses. We will enrol adolescents from Ugandan schools in rural high-schistosomiasis (trial A) and rural high-malaria (trial B) settings and from an established urban birth cohort (trial C). All participants will receive BCG on day '0'; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. Primary outcomes are BCG-specific IFN-γ responses (8 weeks after BCG) and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine effects of interventions on correlates of protective immunity, vaccine response waning, priming versus boosting immunisations, and parasite infection status and intensity. Overarching analyses will compare outcomes between the three trial settings. Sample archives will offer opportunities for exploratory evaluation of the role of immunological and 'trans-kingdom' mediators in parasite modulation of vaccine-specific responses. ETHICS AND DISSEMINATION: Ethics approval has been obtained from relevant Ugandan and UK ethics committees. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications. TRIAL REGISTRATION NUMBERS: ISRCTN60517191, ISRCTN62041885, ISRCTN10482904.

8.
Clin Infect Dis ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588436

RESUMO

BACKGROUND: Acute retroviral syndrome (ARS) is associated with HIV-1 subtype and disease progression, but the underlying immunopathological pathways are poorly understood. We aimed to elucidate associations between innate immune responses during hyperacute HIV-1 infection (hAHI) and ARS. METHODS: Plasma samples obtained from volunteers (≥18.0 years) before and during hAHI, defined as HIV-1 antibody negative and RNA or p24 antigen positive from Kenya, Rwanda, Uganda, Zambia and Sweden were analysed. Forty soluble innate immune markers were measured using multiplexed assays. Immune responses were differentiated into volunteers with stronger and comparatively weaker responses using principal component analysis. Presence or absence of ARS was defined based on eleven symptoms using latent class analysis. Logistic regression was used to determine associations between immune responses and ARS. RESULTS: Of 55 volunteers, 31 (56%) had ARS. Volunteers with stronger immune responses (n=36 [65%]) had increased odds of ARS which was independent of HIV-1 subtype, age, and risk group (adjusted odds ratio, 7.1 [95% CI: 1.7-28.8], p=0.003). IP-10 was fourteen-fold higher during hAHI, elevated in seven of the eleven symptoms, and independently associated with ARS. IP-10 threshold >466.0 pg/mL differentiated stronger immune responses with a sensitivity of 84.2% (95% CI: 60.4-96.6) and specificity of 100.0% (95% CI: 90.3-100.0). CONCLUSIONS: A stronger innate immune response during hAHI was associated with ARS. Plasma IP-10 may be a candidate biomarker of stronger innate immunity. Our findings provide further insights on innate immune responses in regulating ARS and may inform the design of vaccine candidates harnessing innate immunity.

9.
BMC Med Genomics ; 14(1): 15, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407441

RESUMO

BACKGROUND: Internalizing mental disorders (IMDs) (depression, anxiety and post-traumatic stress disorder) have been associated with accelerated telomere length (TL) attrition; however, this association has not been investigated in the context of genetic variation that has been found to influence TL. We have previously reported an association between IMDs and accelerated TL attrition among Ugandan HIV+ children and adolescents. This study investigated the moderating effects of selected single nucleotide polymorphisms in the telomerase reverse transcriptase gene (TERT) (rs2736100, rs7726159, rs10069690 and rs2853669) and the telomerase RNA component gene (TERC) (rs12696304, rs16847897 and rs10936599) on the association between IMDs and TL, among Ugandan HIV+ children (aged 5-11 years) and adolescents (aged 12-17 years). RESULTS: We found no significant interaction between IMDs as a group and any of the selected SNPs on TL at baseline. We observed significant interactions of IMDs with TERT rs2736100 (p = 0.007) and TERC rs16847897 (p = 0.012), respectively, on TL at 12 months. CONCLUSIONS: TERT rs2736100 and TERC rs16847897 moderate the association between IMDs and TL among Ugandan HIV+ children and adolescents at 12 months. Understanding the nature of this association may shed light on the pathophysiological mechanisms underlying advanced cellular aging in IMDs.

10.
Viruses ; 13(2)2021 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-33498793

RESUMO

The ability to efficiently establish a new infection is a critical property for human immunodeficiency virus type 1 (HIV-1). Although the envelope protein of the virus plays an essential role in receptor binding and internalization of the infecting virus, the structural proteins, the polymerase and the assembly of new virions may also play a role in establishing and spreading viral infection in a new host. We examined Ugandan viruses from newly infected patients and focused on the contribution of the Gag-Pol genes to replication capacity. A panel of Gag-Pol sequences generated using single genome amplification from incident HIV-1 infections were cloned into a common HIV-1 NL4.3 pol/env backbone and the influence of Gag-Pol changes on replication capacity was monitored. Using a novel protein domain approach, we then documented diversity in the functional protein domains across the Gag-Pol region and identified differences in the Gag-p6 domain that were frequently associated with higher in vitro replication.


Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , Replicação Viral , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética , Adulto , Feminino , Protease de HIV/genética , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Domínios Proteicos , Uganda , Adulto Jovem
11.
Artigo em Inglês | MEDLINE | ID: mdl-33499732

RESUMO

Point of care rapid recency testing for HIV-1 may be a cost-effective tool to identify recently infected individuals for incidence estimation, and focused HIV prevention through intensified contact tracing. We validated the Asante™ HIV-1 rapid recency® assay for use in Uganda. Archived specimens (serum/plasma), collected from longitudinally observed HIV-1 recently and long-term infected participants, were tested with the Asante HIV-1 rapid recency assay per manufacturer's instructions. Previously identified antiretroviral therapy (ART)-naive samples with known seroconversions within 6 months of follow-up were tested in independent laboratories: the Rakai Health Sciences Program (RHSP) and the Uganda Virus Research Institute HIV Reference Laboratory (UVRI-HRL). In addition, samples from participants who seroconverted within 6-18 months and samples from individuals with chronic HIV-1 infection of at least 18 months duration were classified into three categories: ART naive, ART exposed with suppressed viral loads, and ART exposed with detectable viremia. Of the 85 samples seroconverting in ≤6 months, 27 and 42 samples were identified as "recent" by the Asante HIV-1 rapid recency test at the RHSP laboratory and UVRI-HRL, corresponding to sensitivities of 32% and 49%, respectively. There was 72% agreement between the laboratories (Cohen's kappa = 0.481, 95% CI = 0.317-0.646, p < .0001). Specificity was 100% (200/200) among chronically infected ART-naive samples. The Asante HIV-1 rapid recency assay had low sensitivity for detection of recent HIV-1 infections in Uganda, with substantial interlaboratory variability due to differential interpretation of the test strip bands. Specificity was excellent. Assessment of assay performance in other settings is needed to guide decisions on test utility.

12.
J Acquir Immune Defic Syndr ; 86(1): 98-103, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33306565

RESUMO

BACKGROUND: WHO treatment guidelines recommend tenofovir plus lamivudine or emtricitabine as the nucleoside reverse transcriptase inhibitor backbone in first-line regimens for HIV-infected adults. Lamivudine alone is not recommended, because of the risk of hepatitis B virus (HBV) resistance. We studied HBV responses in a large cohort of co-infected patients in a resource-limited setting. SETTING: Clinical centers in Uganda and Zimbabwe. METHODS: DART was a randomized trial of monitoring practices in HIV-infected adults starting antiretroviral therapy. Baseline samples were tested retrospectively for HBV serological markers and HBV DNA. Longitudinal HBV DNA testing at 48 weeks and the last available sample before HBV-relevant modification of antiretroviral therapy was performed on patients with detectable HBV DNA at baseline. RESULTS: Two hundred twenty-four hepatitis B surface antigen-positive patients were followed for up to 4.8 years. Of the drugs with anti-HBV activity, 166 were prescribed lamivudine-tenofovir and 58 lamivudine alone. Ninety-eight percent (96/98) patients with baseline HBV DNA <6 log10 IU/mL achieved viral suppression at 48 weeks (HBV DNA <48 IU/mL), regardless of regimen, compared with 50%(26/52) for HBV DNA >6 log10 IU/mL. Of the 83 patients suppressed at 48 weeks and with follow-up data, only 7(8%) experienced viral rebound (range 200-3460 IU/mL). Of the 20 patients not suppressed at 48 weeks and with follow-up data, HBV DNA levels generally declined with lamivudine-tenofovir, but increased with lamivudine alone. Alanine transaminase flares were not observed in any patient who experienced viral rebound. CONCLUSIONS: The suppressive effect of lamivudine alone was highly durable (up to 5 years) in HIV-HBV co-infected patients with baseline HBV DNA <6 log10 IU/mL. It may be feasible to develop stratified approaches using lamivudine as the only drug with anti-HBV activity.

13.
PLoS Negl Trop Dis ; 14(11): e0008823, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33253210

RESUMO

Globally, early initiation of antiretroviral therapy for HIV led to a reduction in the estimated mortality from cryptococcal meningitis (CCM) from 624,700 in 2009 to 181,100 in 2014. However, CCM remains one of the leading causes of mortality among HIV infected patients especially in sub-Saharan Africa where 75% of the deaths occur. Most of the studies evaluating mortality have reported short-term mortality (at or before 10 weeks of therapy). We determined mortality and associated factors among patients treated for CCM in the CryptoDex trial (ISRCTN59144167) in Uganda, and the effect of dexamethasone adjunctive therapy on mortality at two years. We conducted a retrospective cohort study between May 2017 and July 2017 to determine the long term survival (up to 2 years post-randomization) of all patients who had been enrolled into the CryptoDex trial in Uganda. The CryptoDex trial recruited between April 2013 and February 2015. We estimated mortality rates and determined factors affecting mortality at two years using Cox regression. The study followed up 211 participants, 127 (60.2%) of whom were male. Sixteen participants (7.58%) were diagnosed with HIV at the same admission when CCM was diagnosed. By two years following randomization 127 (60%) participants had died, a mortality rate of 67 deaths per 100 person-years. Mortality was associated with Glasgow coma score (GCS) below 15 (adjusted Hazard ratio (aHR) 1.77, 95% CI: 1.02-2.44), p = 0.040; weight (aHR 0.97, per 1 Kg increase; 95% CI: 0.94-0.99), p = 0.003; and presence of convulsions (aHR 2.31, 95% CI: 1.32-4.04), p = 0.004, while dexamethasone use and fungal burden had no effect. Long-term mortality in CCM patients remains high even among patients receiving recommended therapy. Strategies to improve long-term survival in CCM patients are urgently needed, especially targeting those with reduced GCS, low weight, and convulsions.

14.
Viruses ; 12(11)2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33182587

RESUMO

The General Population Cohort (GPC) in south-western Uganda has a low HIV-1 incidence rate (<1%). However, new infections continue to emerge. In this research, 3796 HIV-1 pol sequences (GPC: n = 1418, non-GPC sites: n = 1223, Central Uganda: n = 1010 and Eastern Uganda: n = 145) generated between 2003-2015 were analysed using phylogenetic methods with demographic data to understand HIV-1 transmission in this cohort and inform the epidemic response. HIV-1 subtype A1 was the most prevalent strain in the GPC area (GPC and non-GPC sites) (39.8%), central (45.9%) and eastern (52.4%) Uganda. However, in the GPC alone, subtype D was the predominant subtype (39.1%). Of the 524 transmission clusters identified by Cluster Picker, all large clusters (≥5 individuals, n = 8) involved individuals from the GPC. In a multivariate analysis, clustering was strongly associated with being female (adjusted Odds Ratio, aOR = 1.28; 95% CI, 1.06-1.54), being >25 years (aOR = 1.52; 95% CI, 1.16-2.0) and being a resident in the GPC (aOR = 6.90; 95% CI, 5.22-9.21). Phylogeographic analysis showed significant viral dissemination (Bayes Factor test, BF > 3) from the GPC without significant viral introductions (BF < 3) into the GPC. The findings suggest localized HIV-1 transmission in the GPC. Intensifying geographically focused combination interventions in the GPC would contribute towards controlling HIV-1 infections.

15.
BMJ Open ; 10(11): e039258, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148749

RESUMO

OBJECTIVES: To assess the prevalence and risk factors of overweight and obesity among type 2 diabetes mellitus (T2DM) patients in Uganda. DESIGN: Retrospective chart review. SETTING: This study was conducted in the outpatient's T2DM clinic in St. Francis Hospital-Nsambya, Uganda between March and May 2017. PARTICIPANTS: Type 2 diabetes patients registered in the diabetes clinic between July 2003 and September 2016. OUTCOME MEASURES: Overweight and obesity defined as body mass index (kg/m2) of 25.0-29.9 and obesity as 30.0 or higher. RESULTS: Of 1275 T2DM patients, the median age was 54 (IQR: 44-65) years, 770 (60.40%) were females, 887 (69.6%) had hypertension, 385 (28%) had controlled glycaemia, 349 (27%) were obese, while 455 (36%) were overweight. Overweight/obesity were lower among men (OR: 0.45, 95% CI: 0.340 to 0.593, p≤0.001) and among patients aged ≥65 years (OR: 0.52, 95% CI: 0.350 to 0.770, p=0.001); patients who rarely ate fruits and vegetables (OR: 0.66, 95% CI: 0.475 to 0.921, p=0.014) but higher among patients of middle (OR: 1.83, 95% CI: 1.320 to 2.550, p≤0.001) and upper (OR: 2.10, 95% CI: 1.450 to 2.990, p≤0.001) socioeconomic status; on dual therapy (OR: 2.17, 95% CI: 1.024 to 4.604, p=0.043); with peripheral neuropathy (OR: 1.40, 95% CI: 1.039 to 1.834, p=0.026) and hypertension (OR: 1.70, 95% CI: 1.264 to 2.293, p≤0.001). CONCLUSIONS: Overweight and obesity are high among T2DM patients in this population and may contribute significantly to poor outcomes of T2DM. Therefore, strategies to address this problem are urgently needed.

16.
Int J Infect Dis ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33130198

RESUMO

OBJECTIVES: There is a high demand for SARS-CoV-2 testing to identify COVID-19 cases. Real-time, quantitative PCR (qRT-PCR) is the recommended diagnostic test but a number of constraints, including cost prevent its widespread implementation. The aim of this study was to evaluate a low cost, easy-to-use rapid antigen test for diagnosing COVID-19 at the point-of-care. METHODS: Nasopharyngeal swabs from suspect COVID-19 cases and from low-risk volunteers were tested on the STANDARD Q COVID-19 Ag Test and results compared with the qRT-PCR results. RESULTS: 262 samples were collected including 90 qRT-PCR positives. The majority were from males (89%) with a mean age of 34 years and only 13 (14%) of the positives were mildly symptomatic. Sensitivity and specificity of the antigen test were 70.0% (95% CI: 60 - 79) and 92% (95% CI: 87 - 96) respectively; diagnostic accuracy was 84% (95% CI: 79 - 88). The antigen test was more likely to be positive in samples with qRT-PCR Ct values ≤29 reaching a sensitivity of 92%. CONCLUSIONS: The STANDARD Q COVID-19 Ag Test performed less than optimally in this evaluation. However, the test may still have an important role to play early in infection when timely access to molecular testing is not available but results should be confirmed by qRT-PCR.

17.
Glob Health Action ; 13(1): 1829829, 2020 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-33073737

RESUMO

BACKGROUND: The 2013-2016 Ebola epidemic in West Africa is the worst ever caused by Ebolaviruses with over 28,000 human cases and 11,325 deaths. The World Health Organisation (WHO) declared the epidemic a public health crisis that required accelerated development of novel interventions including vaccines. The Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit (MRC/UVRI & LSHTM Uganda Research Unit) was among the African research sites that implemented the VAC52150EBL1004 Ebola vaccine trial. OBJECTIVE: We report on the strategies utilised by the Unit and sponsor in ensuring expedited clinical trial approval and accelerated conduct. METHODS: Janssen Vaccines and Prevention B.V. conducted a phase 1 trial to evaluate the safety, tolerability, and immunogenicity of heterologous two-dose vaccination regimens using Ad26.ZEBOV and MVA-BN-Filo, in healthy adults in Africa. Accelerated implementation strategies are hereby presented. RESULTS: Strategies included: holding the African Vaccine Regulatory Forum (AVAREF) joint review meeting; expedited review by institutional ethics and country-specific regulatory bodies; competitive recruitment between sites; electronic data capture (EDC); frequent study monitoring schedule; involvement of a community advisory board (CAB); and utilization of a 'phased' study information-sharing approach in community engagement and participant recruitment. These strategies enabled the site to acquire approvals within 2 months and enrol 47 participants within a spurn of five. The same milestone is usually acquired in at least 1 year without accelerated implementation. CONCLUSION: The use of well-thought strategies by sponsors and research sites can enable the implementation of accelerated research. We recommend the use of similar strategies in other settings.

19.
Trials ; 21(1): 707, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778139

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

20.
Emerg Infect Dis ; 26(10): 2411-2415, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32614767

RESUMO

We established rapid local viral sequencing to document the genomic diversity of severe acute respiratory syndrome coronavirus 2 entering Uganda. Virus lineages closely followed the travel origins of infected persons. Our sequence data provide an important baseline for tracking any further transmission of the virus throughout the country and region.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Viagem Aérea , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Variação Genética , Genoma , Política de Saúde , Humanos , Programas de Rastreamento , Veículos Automotores , Filogeografia , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Quarentena , Uganda/epidemiologia
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