Dataset Information

Monoclonal B-cell lymphocytosis in a hospital-based UK population and a rural Ugandan population: a cross-sectional study.

ABSTRACT:

Background

Reported incidence of B-cell malignancies shows substantial geographical variation, being more common in the Americas and Europe than in Africa. This variation might reflect differences in diagnostic capability, inherited susceptibility, and infectious exposures. Monoclonal B-cell lymphocytosis (MBL) is a precursor lesion that can be screened for in apparently healthy people, allowing comparison of prevalence across different populations independently of health-care provision. We aimed to compare the prevalence and phenotypic characteristics of MBL in age-and-sex-matched populations from rural Uganda and the UK.

Methods

In this cross-sectional study, we recruited volunteers aged at least 45 years who were seronegative for HIV-1 from the established Ugandan General Population Cohort and obtained their whole-blood samples. We also obtained blood samples from anonymised waste material of age-and-sex-matched individuals (aged >45 years, with a normal blood count and no history of cancer) in the UK. We used flow cytometry to determine the presence of MBL, defined according to standard diagnostic criteria, in the samples and compared differences in the proportion of cases with chronic lymphocytic leukaemia (CLL)-phenotype MBL and CD5-negative MBL, as well as differences in absolute monoclonal B-cell count between the two cohorts.

Findings

Between Jan 15 and Dec 18, 2012, we obtained samples from 302 Ugandan volunteers and 302 UK individuals who were matched by age and sex to the Ugandan population. Overall MBL prevalence was higher in the Ugandan participants (42 [14%] individuals) than in the UK cohort (25 [8%]; p=0·038). CLL-phenotype MBL was detected in three (1%) Ugandan participants and 21 (7%) UK participants (p=0·00021); all three Ugandan participants had absolute monoclonal B-cell count below one cell per ?L, whereas the 21 UK participants had a median absolute number of circulating neoplastic cells of 4·6 (IQR 2-12) cells per ?L. The prevalence of CD5-negative MBL was higher in the Ugandan cohort (41 [14%], of whom two [5%] also had CLL-phenotype MBL) than in the UK cohort (six [2%], of whom two [33%] also had CLL-phenotype MBL; p<0·0001), but the median absolute B-cell count was similar (227 [IQR 152-345] cells per ?L in the Ugandan cohort vs 135 [105-177] cells per ?L in the UK cohort; p=0·13).

Interpretation

MBL is common in both Uganda and the UK, but the substantial phenotypic differences might reflect fundamental differences in the pathogenesis of B-cell lymphoproliferative disorders.

Funding

UK Medical Research Council and UK Department for International Development.

SUBMITTER: Rawstron AC

PROVIDER: S-EPMC5493519 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Monoclonal B-cell lymphocytosis in a hospital-based UK population and a rural Ugandan population: a cross-sectional study.

Rawstron Andy C AC Ssemaganda Aloysius A de Tute Ruth R Doughty Chi C Newton Darren D Vardi Anna A Evans Paul A S PAS Stamatopoulos Kostas K Owen Roger G RG Lightfoot Tracy T Wakeham Katie K Karabarinde Alex A Asiki Gershim G Newton Robert R

The Lancet. Haematology 20170701 7

<h4>Background</h4>Reported incidence of B-cell malignancies shows substantial geographical variation, being more common in the Americas and Europe than in Africa. This variation might reflect differences in diagnostic capability, inherited susceptibility, and infectious exposures. Monoclonal B-cell lymphocytosis (MBL) is a precursor lesion that can be screened for in apparently healthy people, allowing comparison of prevalence across different populations independently of health-care provision. ...[more]

PMID: 28668191

Similar Datasets

Project description:ObjectiveTo examine mortality and morbidity patterns before and after premalignancy diagnosis in individuals with monoclonal gammopathy of undetermined significance (MGUS) and monoclonal B-cell lymphocytosis (MBL) and compare their secondary healthcare activity to that of the general population.DesignPopulation-based patient cohort, within which each patient is matched at diagnosis to 10 age-matched and sex-matched individuals from the general population. Both cohorts are linked to nationwide information on deaths, cancer registrations and Hospital Episode Statistics.SettingThe UK's Haematological Malignancy Research Network, which has a catchment population of around 4 million served by 14 hospitals and a central diagnostic laboratory.ParticipantsAll patients newly diagnosed during 2009-2015 with MGUS (n=2193) or MBL (n=561) and their age and sex-matched comparators (n=27 538).Main outcome measuresMortality and hospital inpatient and outpatient activity in the 5 years before and 3 years after diagnosis.ResultsIndividuals with MGUS experienced excess morbidity in the 5 years before diagnosis and excess mortality and morbidity in the 3 years after diagnosis. Increased rate ratios (RRs) were evident for nearly all clinical specialties, the largest, both before and after diagnosis, being for nephrology (before RR=4.29, 95% CI 3.90 to 4.71; after RR=13.8, 95% CI 12.8 to 15.0) and rheumatology (before RR=3.40, 95% CI 3.18 to 3.63; after RR=5.44, 95% CI 5.08 to 5.83). Strong effects were also evident for endocrinology, neurology, dermatology and respiratory medicine. Conversely, only marginal increases in mortality and morbidity were evident for MBL.ConclusionsMGUS and MBL are generally considered to be relatively benign, since most individuals with monoclonal immunoglobulins never develop a B-cell malignancy or any other monoclonal protein-related organ/tissue-related disorder. Nonetheless, our findings offer strong support for the view that in some individuals, monoclonal gammopathy has the potential to cause systemic disease resulting in wide-ranging organ/tissue damage and excess mortality.

Project description:BackgroundAs sub-Saharan Africa transitions to a new era of universal antiretroviral therapy (ART), up-to-date assessments of population-level HIV RNA suppression are needed to inform interventions to optimise ART delivery. We sought to measure population viral load metrics to assess viral suppression and characterise demographic groups and geographical locations with high-level detectable viraemia in east Africa.MethodsThe Sustainable East Africa Research in Community Health (SEARCH) study is a cluster-randomised controlled trial of an HIV test-and-treat strategy in 32 rural communities in Uganda and Kenya, selected on the basis of rural setting, having an approximate population of 10 000 people, and being within the catchment area of a President's Emergency Plan for AIDS Relief-supported HIV clinic. During the baseline population assessment in the SEARCH study, we did baseline HIV testing and HIV RNA measurement. We analysed stable adult (aged ≥15 years) community residents. We defined viral suppression as a viral load of less than 500 copies per mL. To assess geographical sources of transmission risk, we established the proportion of all adults (both HIV positive and HIV negative) with a detectable viral load (local prevalence of viraemia). We defined transmission risk hotspots as geopolitical subunits within communities with an at least 5% local prevalence of viraemia. We also assessed serodiscordant couples, measuring the proportion of HIV-positive partners with detectable viraemia. The SEARCH study is registered with ClinicalTrials.gov, number NCT01864603.FindingsBetween April 2, 2013, and June 8, 2014, of 303 461 stable residents, we enumerated 274 040 (90·3%), of whom 132 030 (48·2%) were adults. Of these, 117 711 (89·2%) had their HIV status established, of whom 11 964 (10·2%) were HIV positive. Of these, we measured viral load in 8828 (73·8%) people. Viral suppression occurred in 3427 (81·6%) of 4202 HIV-positive adults on ART and 4490 (50·9%) of 8828 HIV-positive adults. Regional viral suppression among HIV-positive adults occurred in 881 (48·2%) of 1827 people in west Uganda, 516 (45·0%) of 1147 in east Uganda, and 3093 (52·8%) of 5854 in Kenya. Transmission risk hotspots occurred in three of 21 parishes in west Uganda and none in east Uganda and in 24 of 26 Kenya geopolitical subunits. In Uganda, 492 (2·9%) of 16 874 couples were serodiscordant: in 287 (58·3%) of these couples, the HIV-positive partner was viraemic (and in 69 [14·0%], viral load was >100 000 copies per mL). In Kenya, 859 (10·0%) of 8616 couples were serodiscordant: in 445 (53·0%) of these couples, the HIV-positive partner was viraemic (and in 129 [15%], viral load was >100 000 copies per mL).InterpretationBefore the start of the SEARCH trial, 51% of east African HIV-positive adults had viral suppression, reflecting ART scale-up efforts to date. Geographical hotspots of potential HIV transmission risk and detectable viraemia among serodiscordant couples warrant intensified interventions.FundingNational Institute of Allergy and Infectious Diseases (National Institutes of Health) and the President's Emergency Plan for AIDS Relief.

Project description:BACKGROUND:Sex-based differences in cardiovascular disease (CVD) burden are widely acknowledged, with male sex considered a risk factor in high-income settings. However, these relationships have not been examined in sub-Saharan Africa (SSA). We aimed to apply the American Heart Association (AHA) ideal cardiovascular health (CVH) tool modified by the addition of C-reactive protein (CRP) to examine potential sex-based differences in the prevalence of CVD risk in rural Uganda. METHODS:In a cross-sectional study nested within a population-wide census, 857 community-living adults completed physical and laboratory-based assessments to calculate individual ideal CVH metrics including an eight category for CRP levels. We summarized sex-specific ideal CVH indices, fitting ordinal logistic regression models to identify correlates of improving CVH. As secondary outcomes, we assessed subscales of ideal CVH behaviours and factors. Models included inverse probability of sampling weights to determine population-level estimates. RESULTS:The weighted-population mean age was 39.2 (1.2) years with 52.0 (3.7) % females. Women had ideal scores in smoking (80.4% vs. 68.0%; p < 0.001) and dietary intake (26.7% vs. 16.8%; p = 0.037) versus men, but the opposite in body mass index (47.3% vs. 84.4%; p < 0.001), glycated hemoglobin (87.4% vs. 95.2%; p = 0.001), total cholesterol (80.2% vs. 85.0%; p = 0.039) and CRP (30.8% vs. 49.7%; p = 0.009). Overall, significantly more men than women were classified as having optimal cardiovascular health (6-8 metrics attaining ideal level) (39.7% vs. 29.0%; p = 0.025). In adjusted models, female sex was correlated with lower CVH health factors sub-scales but higher ideal CVH behaviors. CONCLUSIONS:Contrary to findings in much of the world, female sex in rural SSA is associated with worse ideal CVH profiles, despite women having better indices for ideal CVH behaviors. Future work should assess the potential role of socio-behavioural sex-specific risk factors for ideal CVH in SSA, and better define the downstream consequences of these differences.

Project description:BackgroundThe UK, like a number of other countries, has a refugee resettlement programme. External factors, such as higher prevalence of infectious diseases in the country of origin and circumstances of travel, are likely to increase the infectious disease risk of refugees, but published data is scarce. The International Organization for Migration carries out and collates data on standardised pre-entry health assessments (HA), including testing for infectious diseases, on all UK refugee applicants as part of the resettlement programme. From this data, we report the yield of selected infectious diseases (tuberculosis (TB), HIV, syphilis, hepatitis B and hepatitis C) and key risk factors with the aim of informing public health policy.MethodsWe examined a large cohort of refugees (n = 18,418) who underwent a comprehensive pre-entry HA between March 2013 and August 2017. We calculated yields of infectious diseases stratified by nationality and compared these with published (mostly WHO) estimates. We assessed factors associated with case positivity in univariable and multivariable logistic regression analysis.ResultsThe number of refugees included in the analysis varied by disease (range 8506-9759). Overall yields were notably high for hepatitis B (188 cases; 2.04%, 95% CI 1.77-2.35%), while yields were below 1% for active TB (9 cases; 92 per 100,000, 48-177), HIV (31 cases; 0.4%, 0.3-0.5%), syphilis (23 cases; 0.24%, 0.15-0.36%) and hepatitis C (38 cases; 0.41%, 0.30-0.57%), and varied widely by nationality. In multivariable analysis, sub-Saharan African nationality was a risk factor for several infections (HIV: OR 51.72, 20.67-129.39; syphilis: OR 4.24, 1.21-24.82; hepatitis B: OR 4.37, 2.91-6.41). Hepatitis B (OR 2.23, 1.05-4.76) and hepatitis C (OR 5.19, 1.70-15.88) were associated with history of blood transfusion. Syphilis (OR 3.27, 1.07-9.95) was associated with history of torture, whereas HIV (OR 1521.54, 342.76-6754.23) and hepatitis B (OR 7.65, 2.33-25.18) were associated with sexually transmitted infection. Syphilis was associated with HIV (OR 10.27, 1.30-81.40).ConclusionsTesting refugees in an overseas setting through a systematic HA identified patients with a range of infectious diseases. Our results reflect similar patterns found in other programmes and indicate that the yields for infectious diseases vary by region and nationality. This information may help in designing a more targeted approach to testing, which has already started in the UK programme. Further work is needed to refine how best to identify infections in refugees, taking these factors into account.

Project description:ObjectivesWe aimed to estimate the prevalence and correlates of QT interval prolongation in rural Uganda.BackgroundMajor electrocardiographic abnormalities, including prolonged QT interval, have been shown to be independently predictive of adverse cardiovascular events among Western populations. Cardiovascular diseases are on the rise in sub-Saharan Africa with poorly characterized context-specific risk factors. An important question is whether ECG screening might have value in cardiovascular disease risk stratification in SSA.MethodsWe conducted a cross-sectional survey in a sample of adults participating in an ongoing whole-population cohort in Mbarara, Uganda, in 2015. Of 1,814 subjects enrolled in the parent whole-population cohort, 856 (47%) participated in the study. Participants completed 12-lead electrocardiography and cardiovascular disease risk factors assessment. We summarized sex-specific, heart rate variation-adjusted QT (QTa) defining prolonged QTa as >460 ms in women and >450 ms in men. We fit linear and logistic regression models to estimate correlates of (continuous) QTa interval length and (dichotomous) prolonged QTa. Models included inverse probability of sampling weights to generate population-level estimates accounting for study nonparticipation.ResultsWe assessed data from 828 participants with electrocardiograms. The weighted population mean age was 38.4 years (95% confidence interval: 36.3-40.4). The weighted population was 50.4% female, 11.5% had elevated blood pressure, and 57.6% had a high-sensitivity C-reactive protein >1 mg/dl. The population mean QTa was 409.1 ms (95% confidence interval: 405.1-413.1), and 10.3% (95% confidence interval: 7.8-13.5) met criteria for prolonged QTa. Women had a higher mean QTa (421.6 ms vs. 396.3 ms; p < 0.001), and a higher proportion of women had a prolonged QTa (14.0% vs. 9.3%; p = 0.122) than did men. In multivariable-adjusted regression models, female sex and hypertension correlated with higher mean QTa and meeting criteria for prolonged QTa, respectively.ConclusionsQT interval prolongation is highly prevalent in rural Uganda and may be more common than in high-income settings. Female sex, age, and high blood pressure correlated with QT interval prolongation. Future work should assess whether genetic predisposition or environmental factors in sub-Saharan African populations contribute to prolonged QT and clarify consequences.

Dataset Information

Monoclonal B-cell lymphocytosis in a hospital-based UK population and a rural Ugandan population: a cross-sectional study.

Background

Methods

Findings

Interpretation

Funding

Publications

Monoclonal B-cell lymphocytosis in a hospital-based UK population and a rural Ugandan population: a cross-sectional study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets