Risk factors for non-participation in ivermectin and dihydroartemisinin-piperaquine mass drug administration for malaria control in the MASSIV trial.

BACKGROUND: Mass Drug Administration (MDA) has become a mainstay for the control of several diseases over the last two decades. Successful implementation of MDA programmes requires community participation and can be threatened by systematic non-participation. Such concerns are particularly pertinent for MDA programmes against malaria, as they require multi-day treatment over several consecutive months. Factors associated with non-participation to the MDA campaign with ivermectin (IVM) and dihydroartemisinin-piperaquine (DHP) implemented within the MASSIV cluster randomized trial were determined. METHODS: Coverage data was extracted from the MASSIV trial study database, with every datapoint being a directly observed therapy (DOT). A complete month of MDA was classified as receiving all three daily doses of treatment. For both ivermectin and DHP, ordinal logistic regression was used to identify individual and household level variables associated with non-participation. RESULTS: For ivermectin, 51.5% of eligible participants received all 3 months of treatment while 30.7% received either one or two complete months. For DHP, 56.7% of eligible participants received all 3 months of treatment and 30.5% received either one or two complete months. Children aged 5-15 years and adults aged more than 50 years were more likely to receive at least one complete month of MDA than working age adults, both for ivermectin (aOR 4.3, 95% CI 3.51-5.28 and aOR of 2.26, 95% CI 1.75-2.95) and DHP (aOR 2.47, 95%CI 2.02-3.02 and aOR 1.33, 95%CI 1.01-1.35), respectively. Members of households where the head received a complete month of MDA were more likely to themselves have received a complete month of MDA, both for ivermectin (aOR 1.71, 95%CI 1.35-2.14) and for DHP (aOR 1.64, 95%CI 1.33-2.04). CONCLUSION: Personal and household-level variables were associated with participation in the MDA programme for malaria control. Specific strategies to (increase participation amongst some groups may be important to ensure maximum impact of MDA strategies in achieving malaria elimination. TRIAL REGISTRATION: The MASSIV trial is registered under NCT03576313.

Asymptomatic Plasmodium falciparum carriage and clinical disease: a 5-year community-based longitudinal study in The Gambia.

BACKGROUND: Carriers of persistent asymptomatic Plasmodium falciparum infections constitute an infectious reservoir that maintains malaria transmission. Understanding the extent of carriage and characteristics of carriers specific to endemic areas could guide use of interventions to reduce infectious reservoir. METHODS: In eastern Gambia, an all-age cohort from four villages was followed up from 2012 to 2016. Each year, cross-sectional surveys were conducted at the end of the malaria transmission season (January) and just before the start of the next one (June) to determine asymptomatic P. falciparum carriage. Passive case detection was conducted during each transmission season (August to January) to determine incidence of clinical malaria. Association between carriage at the end of the season and at start of the next one and the risk factors for this were assessed. Effect of carriage before start of the season on risk of clinical malaria during the season was also examined. RESULTS: A total of 1403 individuals-1154 from a semi-urban village and 249 from three rural villages were enrolled; median age was 12 years (interquartile range [IQR] 6, 30) and 12 years (IQR 7, 27) respectively. In adjusted analysis, asymptomatic P. falciparum carriage at the end of a transmission season and carriage just before start of the next one were strongly associated (adjusted odds ratio [aOR] = 19.99; 95% CI 12.57-31.77, p < 0.001). The odds of persistent carriage (i.e. infected both in January and in June) were higher in rural villages (aOR = 13.0; 95% CI 6.33-26.88, p < 0.001) and in children aged 5-15 years (aOR = 5.03; 95% CI 2.47-10.23, p = < 0.001). In the rural villages, carriage before start of the season was associated with a lower risk of clinical malaria during the season (incidence risk ratio [IRR] 0.48, 95% CI 0.27-0.81, p = 0.007). CONCLUSIONS: Asymptomatic P. falciparum carriage at the end of a transmission season strongly predicted carriage just before start of the next one. Interventions that clear persistent asymptomatic infections when targeted at the subpopulation with high risk of carriage may reduce the infectious reservoir responsible for launching seasonal transmission.

Plasmodium falciparum merozoite invasion ligands, linked antimalarial resistance loci and ex vivo responses to antimalarials in The Gambia.

BACKGROUND: Artemether/lumefantrine is the most commonly used artemisinin-based combination treatment (ACT) for malaria in sub-Saharan Africa. Drug resistance to ACT components is a major threat to malaria elimination efforts. Therefore, rigorous monitoring of drug efficacy is required for adequate management of malaria and to sustain the effectiveness of ACTs. OBJECTIVES: This study identified and described genomic loci that correlate with differences in ex vivo responses of natural Plasmodium falciparum isolates from The Gambia to antimalarial drugs. METHODS: Natural P. falciparum isolates from The Gambia were assayed for IC50 responses to four antimalarial drugs (artemether, dihydroartemisinin, amodiaquine and lumefantrine). Genome-wide SNPs from 56 of these P. falciparum isolates were applied to mixed-model regression and network analyses to determine linked loci correlating with drug responses. Genomic regions of shared haplotypes and positive selection within and between Gambian and Cambodian P. falciparum isolates were mapped by identity-by-descent (IBD) analysis of 209 genomes. RESULTS: SNPs in 71 genes, mostly involved in stress and drug resistance mechanisms correlated with drug responses. Additionally, erythrocyte invasion and permeability loci, including merozoite surface proteins (Pfdblmsp, Pfsurfin), and high-molecular-weight rhoptry protein 2 (Pfrhops2) were correlated with responses to multiple drugs. Haplotypes of pfdblmsp2 and known drug resistance loci (pfaat1, pfcrt and pfdhfr) from The Gambia showed high IBD with those from Cambodia, indicating co-ancestry, with significant linkage disequilibrium between their alleles. CONCLUSIONS: Multiple linked genic loci correlating with drug response phenotypes suggest a genomic backbone may be under selection by antimalarials. This calls for further analysis of molecular pathways to drug resistance in African P. falciparum.

Does the perception of HIV risk among Female sex workers affect HIV prevention behavior? application of the Health Belief Model (HBM).

BACKGROUND: High prevalence of Human Immune virus/Acquired immunodeficiency syndrome (HIV/AIDS) in Female Sex Workers (FSWs) is identified as a bottleneck in fighting against HIV/AIDS. To this end, the international community planned a strategy of 'Ending inequality' and 'Ending the AIDS epidemic' by 2030. This could not be achieved without due attention to FSWs. Thus, this study attempted to assess HIV prevention behavior and associated factors among FSWs in Dima district of Gambella region, Ethiopia by using the Health Belief Model. METHODS: A community-based cross-sectional study was conducted from March to May 2019 among 449 FSWs selected using the snowball sampling technique. Socio-demographic features, knowledge about HIV, attitude toward HIV prevention methods, and Health Belief Model (HBM) constructs (perceived susceptibility to and severity of HIV, perceived barriers, and benefits of performing the recommended HIV prevention methods, self-efficacy, and cues to practice HIV prevention methods) were collected using face to face interview. Data were entered into Epi-data 3.1 and analyzed using SPSS version 23. Bivariable and multivariable binary logistic regression analysis was done to identify the association between dependent and independent variables. P-value < 5% with 95 CI was used as a cutoff point to decide statistical significance of independent variables. RESULTS: In this study, 449 FSWs participated making a response rate of 98.90%. Of these, 64.8% had high HIV prevention behavior. Age (AOR = 1.911, 95% CI: 1.100, 3.320), knowledge of HIV (AOR = 1.632, 95% CI: 1.083, 2.458), attitude towards HIV prevention methods (AOR = 2.335, 95% CI: 1.547, 3.523), perceived barriers (AOR = .627, 95% CI: .423, .930), and self-efficacy (AOR = 1.667, 95% CI: 1.107, 2.511) were significantly associated with high HIV prevention behavior. CONCLUSION: The study identified that about two third of FSWs practiced the recommended HIV prevention methods. Age of respondents, knowledge of HIV, favorable attitude towards the recommended HIV prevention methods, high self-efficacy, and low perceived barrier were associated with high HIV prevention behavior. Therefore, focusing on these factors would be instrumental for improving effectiveness of the ongoing HIV prevention efforts and attaining the 'Sustainable Development Goals of 'Ending inequality' and 'Ending the AIDS epidemic' by 2030.

Intense and Mild First Epidemic Wave of Coronavirus Disease, The Gambia.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is evolving differently in Africa than in other regions. Africa has lower SARS-CoV-2 transmission rates and milder clinical manifestations. Detailed SARS-CoV-2 epidemiologic data are needed in Africa. We used publicly available data to calculate SARS-CoV-2 infections per 1,000 persons in The Gambia. We evaluated transmission rates among 1,366 employees of the Medical Research Council Unit The Gambia (MRCG), where systematic surveillance of symptomatic cases and contact tracing were implemented. By September 30, 2020, The Gambia had identified 3,579 SARS-CoV-2 cases, including 115 deaths; 67% of cases were identified in August. Among infections, MRCG staff accounted for 191 cases; all were asymptomatic or mild. The cumulative incidence rate among nonclinical MRCG staff was 124 infections/1,000 persons, which is >80-fold higher than estimates of diagnosed cases among the population. Systematic surveillance and seroepidemiologic surveys are needed to clarify the extent of SARS-CoV-2 transmission in Africa.

Reactive, self-administered malaria treatment against asymptomatic malaria infection: results of a cluster randomized controlled trial in The Gambia.

BACKGROUND: Selectively targeting and treating malaria-infected individuals may further decrease parasite carriage in low-burden settings. Using a trans-disciplinary approach, a reactive treatment strategy to reduce Plasmodium falciparum prevalence in participating communities was co-developed and tested. METHODS: This is a 2-arm, open-label, cluster-randomized trial involving villages in Central Gambia during the 2017 and 2018 malaria transmission season. Villages were randomized in a 1:1 ratio using a minimizing algorithm. In the intervention arm, trained village health workers delivered a full course of pre-packed dihydroartemisinin-piperaquine to all residents of compounds where clinical cases were reported while in the control arm, compound residents were screened for infection at the time of the index case reporting. All index cases were treated following national guidelines. The primary endpoint was malaria prevalence, determined by molecular methods, at the end of the intervention period. RESULTS: The trial was carried out in 50 villages: 34 in 2017 and 16 additional villages in 2018. At the end of the 2018 transmission season, malaria prevalence was 0.8% (16/1924, range 0-4%) and 1.1% (20/1814, range 0-17%) in the intervention and control arms, respectively. The odds of malaria infection were 29% lower in the intervention than in the control arm after adjustment for age (OR 0.71, 95% CI 0.27-1.84, p = 0.48). Adherence to treatment was high, with 98% (964/979) of those treated completing the 3-day treatment. Over the course of the study, only 37 villages, 20 in the intervention and 17 in the control arm, reported at least one clinical case. The distribution of clinical cases by month in both transmission seasons was similar and the odds of new clinical malaria cases during the trial period did not vary between arms (OR 1.04, 95% CI 0.57-1.91, p = 0.893). All adverse events were classified as mild to moderate and resolved completely. CONCLUSION: The systematic and timely administration of an anti-malarial treatment to residents of compounds with confirmed malaria cases did not significantly decrease malaria prevalence and incidence in communities where malaria prevalence was already low. Treatment coverage and adherence was very high. Results were strongly influenced by the lower-than-expected malaria prevalence, and by no clinical cases in villages with asymptomatic malaria-infected individuals. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, NCT02878200. Registered 25 August 2016. https://clinicaltrials.gov/ct2/show/NCT02878200 .

Geospatial analysis and impact of targeted development of breast cancer care in The Gambia: a cross-sectional study.

BACKGROUND: The Gambia has one of the lowest survival rates for breast cancer in Africa. Contributing factors are late presentation, delays within the healthcare system, and decreased availability of resources. We aimed to characterize the capacity and geographic location of healthcare facilities in the country and calculate the proportion of the population with access to breast cancer care. METHODS: A facility-based assessment tool was administered to secondary and tertiary healthcare facilities and private medical centers and clinics in The Gambia. GPS coordinates were obtained, and proximity of service availability and population analysis were performed. Distance thresholds of 10, 20, and 45 km were chosen to determine access to screening, pathologic diagnosis, and surgical management. An additional population analysis was performed to observe the potential impact of targeted development of resources for breast cancer care. RESULTS: All 102 secondary and tertiary healthcare facilities and private medical centers and clinics in The Gambia were included. Breast cancer screening is mainly performed through clinical breast examination and is available in 52 facilities. Seven facilities provide pathologic diagnosis and surgical management of breast cancer. The proportion of the Gambian population with access to screening, pathologic diagnosis, and surgical management is 72, 53, and 62%, respectively. A hypothetical targeted expansion of resources would increase the covered population to 95, 62, and 84%. CONCLUSIONS: Almost half of the Gambian population does not have access to pathologic diagnosis and surgical management of breast cancer within the distance threshold utilized in the study. Mapping and population analysis can identify areas for targeted development of resources to increase access to breast cancer care.

Tolerance of Gambian Plasmodium falciparum to Dihydroartemisinin and Lumefantrine Detected by Ex Vivo Parasite Survival Rate Assay.

Monitoring of Plasmodium falciparum sensitivity to antimalarial drugs in Africa is vital for malaria elimination. However, the commonly used ex vivo/in vitro 50% inhibitory concentration (IC50) test gives inconsistent results for several antimalarials, while the alternative ring-stage survival assay (RSA) for artemisinin derivatives has not been widely adopted. Here, we applied an alternative two-color flow cytometry-based parasite survival rate assay (PSRA) to detect ex vivo antimalarial tolerance in P. falciparum isolates from The Gambia. The PSRA infers parasite viability by quantifying reinvasion of uninfected cells following 3 consecutive days of drug exposure (10-fold the IC50 of drug for field isolates). The drug survival rate is obtained for each isolate from the slope of the growth/death curve. We obtained parasite survival rates of 41 isolates for dihydroartemisinin (DHA) and lumefantrine (LUM) out of 51 infections tested by ring-stage survival assay (RSA) against DHA. We also determined the genotypes for known drug resistance genetic loci in the P. falciparum genes Pfdhfr, Pfdhps, Pfmdr, Pfcrt, and Pfk13 The PSRA results determined for 41 Gambian isolates showed faster killing and lower variance after treatment with DHA than after treatment with LUM, despite a strong correlation between the two drugs. Four and three isolates were tolerant to DHA and LUM, respectively, with continuous growth during drug exposure. Isolates with the PfMDR1-Y184F mutant variant showed increased LUM survival, though the results were not statistically significant. Sulfadoxine/pyrimethamine (SP) resistance markers were fixed, while all other antimalarial variants were prevalent in more than 50% of the population. The PSRA detected ex vivo antimalarial tolerance in Gambian P. falciparum This calls for its wider application and for increased vigilance against resistance to artemisinin combination therapies (ACTs) in this population.

Occupational exposure to inhaled pollutants and risk of airflow obstruction: a large UK population-based UK Biobank cohort.

BACKGROUND: Although around 10% to 15% of COPD burden can be attributed to workplace exposures, little is known about the role of different airborne occupational pollutants (AOP). The main aim of the study was to assess the effect size of the relationship between various AOP, their level and duration of exposure with airflow obstruction (AFO). METHODS: A cross-sectional analysis was conducted in 228 614 participants from the UK Biobank study who were assigned occupational exposure using a job exposure matrix blinded to health outcome. Adjusted prevalence ratios (PRs) and 95% CI for the risk of AFO for ever and years of exposure to AOPs were estimated using robust Poisson model. Sensitivity analyses were conducted for never-smokers, non-asthmatic and bi-pollutant model. RESULTS: Of 228 614 participants, 77 027 (33.7%) were exposed to at least one AOP form. 35.5% of the AFO cases were exposed to vapours, gases, dusts or fumes (VGDF) and 28.3% to dusts. High exposure to vapours increased the risk of occupational AFO by 26%. Exposure to dusts (adjusted PR=1.05; 95% CI 1.01 to 1.08), biological dusts (1.05; 1.01 to 1.10) and VGDF (1.04; 1.01 to 1.07) showed a significantly increased risk of AFO, however, statistically not significant following multiple testing. There was no significant increase in risk of AFO by duration (years) of exposure in current job. The results were null when restricted to never-smokers and when a bi-pollutant model was used. However, when data was analysed based on the level of exposure (low, medium and high) compared with no exposure, directionally there was increase in risk for those with high exposure to vapours, gases, fumes, mists and VGDF but statistically significant only for vapours. CONCLUSION: High exposure (in current job) to airborne occupational pollutants was suggestive of higher risk of AFO. Future studies should investigate the relationship between lifetime occupational exposures and COPD.

Mass Drug Administration With Dihydroartemisinin-piperaquine and Malaria Transmission Dynamics in The Gambia: A Prospective Cohort Study.

BACKGROUND: Mass drug administration (MDA) may further reduce malaria transmission in low-transmission areas. The impact of MDA on the dynamics of malaria transmission was determined in a prospective cohort study. METHODS: Annual rounds of MDA with dihydroartemisinin-piperaquine (DP) were implemented were implemented in 2014 and 2015 in six village pairs before the malaria transmission season. Blood samples were collected from residents between July and December for microscopy and nested PCR. Incidence and prevalence of infection, clinical disease, and risk of malaria reinfection post-MDA were determined. RESULTS: Coverage of three DP doses was 68.2% (2014) and 65.6% (2015), compliance was greater than 80%. Incidence of infection was significantly lower in 2014 (incidence rate [IR] = 0.2 per person year [PPY]) than in 2013 (IR = 1.1 PPY; P < .01); monthly infection prevalence declined in the first three months post-MDA. Clinical malaria incidence was lower in 2014 (IR = 0.1 PPY) and 2015 (IR = 0.2 PPY) than in 2013 (IR = 0.4 PPY; P < .01), but remained higher in eastern Gambia. Individuals infected before MDA had a 2-fold higher odds of reinfection post-MDA (adjusted odds ratio = 2.5, 95% confidence interval 1.5-4.3; P < .01). CONCLUSIONS: MDA reduced malaria infection and clinical disease during the first months. The reduction was maintained in low-transmission areas, but not in eastern Gambia. Annual MDA could be followed by focal MDA targeting individuals infected during the dry season. Repeated MDA rounds, some during the dry season over larger geographical areas, may result in a more marked and sustained decrease of malaria transmission.

Hospital-based Surveillance for Pediatric Bacterial Meningitis in the Era of the 13-Valent Pneumococcal Conjugate Vaccine in Ghana.

BACKGROUND: Global surveillance for vaccine preventable invasive bacterial diseases has been set up by the World Health Organization to provide disease burden data to support decisions on introducing pneumococcal conjugate vaccine (PCV). We present data from 2010 to 2016 collected at the 2 sentinel sites in Ghana. METHODS: Data were collected from children <5 years of age presenting at the 2 major teaching hospitals with clinical signs of meningitis. Cerebrospinal fluid specimens were collected and tested first at the sentinel site laboratory with conventional microbiology methods and subsequently with molecular analysis, at the World Health Organization Regional Reference Laboratory housed at the Medical Research Council Unit The Gambia, for identification of Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, the 3 most common bacteria causing meningitis. RESULTS: There were 4008 suspected cases of meningitis during the surveillance period, of which 31 (0.8%) were laboratory confirmed. Suspected meningitis cases decreased from 923 in 2010 to 219 in 2016. Of 3817 patients with available outcome data, 226 (5.9%) died. S. pneumoniae was the most common bacterial pathogen, accounting for 68.5% of confirmed cases (50 of 73). H. influenzae and N. meningitidis accounted for 6.8% (5 of 73) and 21.9% (16 of 73), respectively. The proportion of pneumococcal vaccine serotypes causing meningitis decreased from 81.3% (13 of 16) before the introduction of 13-valent PCV (2010-2012) to 40.0% (8 of 20) after its introduction (2013-2016). CONCLUSIONS: Cases of suspected meningitis decreased among children <5 years of age between 2010 and 2016, with declines in the proportion of vaccine-type pneumococcal meningitis after the introduction of 13-valent PCV in Ghana.

A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia.

BACKGROUND: Infant DNA methylation profiles are associated with their mother's periconceptional nutritional status. DNA methylation relies on nutritional inputs for one-carbon metabolic pathways, including the efficient recycling of homocysteine. This randomised controlled trial in nonpregnant women in rural Gambia tests the efficacy of a novel nutritional supplement designed to improve one-carbon-related nutrient status by reducing plasma homocysteine, and assesses its potential future use in preconception trials. METHODS AND FINDINGS: We designed a novel drink powder based on determinants of plasma homocysteine in the target population and tested it in a three-arm, randomised, controlled trial. Nonpregnant women aged between 18 and 45 from the West Kiang region of The Gambia were randomised in a 1:1:1 allocation to 12 weeks daily supplementation of either (a) a novel drink powder (4 g betaine, 800 µg folic acid, 5.2 µg vitamin B12, and 2.8 mg vitamin B2), (b) a widely used multiple micronutrient tablet (United Nations Multiple Micronutrient Preparation [UNIMMAP]) containing 15 micronutrients, or (c) no intervention. The trial was conducted between March and July 2018. Supplementation was observed daily. Fasted venepuncture samples were collected at baseline, midline (week 5), and endline (week 12) to measure plasma homocysteine. We used linear regression models to determine the difference in homocysteine between pairs of trial arms at midline and endline, adjusted for baseline homocysteine, age, and body mass index (BMI). Blood pressure and pulse were measured as secondary outcomes. Two hundred and ninety-eight eligible women were enrolled and randomised. Compliance was >97.8% for both interventions. At endline (our primary endpoint), the drink powder and UNIMMAP reduced mean plasma homocysteine by 23.6% (-29.5 to -17.1) and 15.5% (-21.2 to -9.4), respectively (both p < 0.001), compared with the controls. Compared with UNIMMAP, the drink powder reduced mean homocysteine by 8.8% (-15.8 to -1.2; p = 0.025). The effects were stronger at midline. There was no effect of either intervention on blood pressure or pulse compared with the control at endline. Self-reported adverse events (AEs) were similar in both intervention arms. There were two serious AEs reported over the trial duration, both in the drink powder arm, but judged to be unrelated to the intervention. Limitations of the study include the use of a single targeted metabolic outcome, homocysteine. CONCLUSIONS: The trial confirms that dietary supplements can influence metabolic pathways that we have shown in previous studies to predict offspring DNA methylation. Both supplements reduced homocysteine effectively and remain potential candidates for future epigenetic trials in pregnancy in rural Gambia. TRIAL REGISTRATION: Clinicaltrials.gov Reference NCT03431597.

Clinically meaningful and lasting HbA1c improvement rarely occurs after 5 years of type 1 diabetes: an argument for early, targeted and aggressive intervention following diagnosis.

AIMS/HYPOTHESIS: Our objectives were to explore whether the phenomenon of HbA1c 'tracking' occurs in individuals with type 1 diabetes, how long after diagnosis does tracking take to stabilise, and whether there is an effect of sex and age at diagnosis on tracking. METHODS: A total of 4525 individuals diagnosed with type 1 diabetes between 1 January 1995 and 1 May 2015 were identified from The Health Improvement Network (THIN) database. Mixed models were applied to assess the variability of HbA1c levels over time with random effects on general practices (primary care units) and individuals within practices. RESULTS: 4525 individuals diagnosed with type 1 diabetes were identified in THIN over the study period. The greatest difference in mean HbA1c measurement (-7.0 [95% CI -8.0, -6.1] mmol/mol [0.6%]) was seen when comparing measurements made immediately after diagnosis (0-1 year since diagnosis) with those at 10 or more years (the reference category). The mean difference in HbA1c for the successive periods compared with 10 or more years after diagnosis declined and was no longer statistically significant after 5 years. In the stratified analysis using sex and age group there was considerable heterogeneity with adult onset type 1 diabetes appearing to track earlier and at a lower mean HbA1c. CONCLUSIONS/INTERPRETATION: In individuals with type 1 diabetes, glycaemic control measured by HbA1c settles onto a long-term 'track' and this occurs on average by 5 years following diagnosis. Age at diagnosis modifies both the rate at which individuals settle into their track and the absolute HbA1c tracking level for the next 10 years.

Correction to: Clinically meaningful and lasting HbA1c improvement rarely occurs after 5 years of type 1 diabetes: an argument for early, targeted and aggressive intervention following diagnosis.

AbstractIn Table 1 the data for age group, sex and Townsend index were incorrectly identified as mean ± SD instead of n (%). The table is corrected here.

Cognitive Function Declines Significantly during Haemodialysis in a Majority of Patients: A Call for Further Research.

INTRODUCTION: Cognitive impairment (CI) is very common condition that occurs in haemodialysis patients and it is associated with reduced functional capacity and mortality. We assessed the change in cognitive function during haemodialysis and associated risk factors. METHODS: All patients ≥50 years, on haemodialysis for ≥3 months, no dementia from 2 dialysis centres were selected. Cognition was assessed before and after a haemodialysis session using parallel versions of the Montreal Cognitive Assessment (MOCA) tool. Multiple regression was used to examine potential confounders. RESULTS: Eight-two patients completed both tests - median age 73 (52-91) years, 59% male, dialysis vintage 41 (3-88) months. Sixty-two (76%) had CI at baseline. Cognition declined over dialysis (MOCA 21 ± 4.8 to 19.1 ± 4.1, p < 0.001) and domains affected were attention, language, abstraction and delayed recall. Age and dialysis vintage were independently associated with decline. CONCLUSION: Cognitive function declines over a haemodialysis session and this has significant clinical implications over health literacy, self-management and tasks like driving. More research is needed to find the cause for this decline in cognition.

Occupational airborne exposure in relation to Chronic Obstructive Pulmonary Disease (COPD) and lung function in individuals without childhood wheezing illness: A 50-year cohort study.

BACKGROUND: Evidence from longitudinal population-based studies relating occupational exposure to the full range of different forms of airborne pollutants and lung function and airway obstruction is limited. OBJECTIVE: To relate self-reported COPD and lung function impairment to occupational exposure to different forms of airborne chemical pollutants in individuals who did not have childhood wheeze. METHODS: A prospective cohort study was randomly selected in 1964 at age 10-15 years and followed up in 1989, 1995, 2001 and 2014 (aged 58-64) by spirometry and respiratory questionnaire. Occupational histories were recorded in 2014 and occupational exposures assigned using an airborne chemical job exposure matrix. The risk of COPD and lung function impairment was analyzed in subjects, who did not have childhood wheeze, using logistic and linear regression and linear mixed effects models. RESULTS: 237 subjects without childhood wheeze (mean age 60.6 years, 47% male) were analyzed. There was no association between any respiratory outcomes and exposure to gases, fibers, mists or mineral dusts and no consistent associations with exposure to fumes. Reduced FEV1 was associated with longer duration (years) of exposure to any of the six main pollutant forms - vapors, gases, dusts, fumes, fibers and mists (VGDFFiM) with evidence of a dose-response relationship (p-trend=0.004). Exposure to biological dusts was associated with self-reported COPD and FEV1

Urinary metabolites of polycyclic aromatic hydrocarbons in Saudi Arabian schoolchildren in relation to sources of exposure.

Polycyclic aromatic hydrocarbons contain a number of known carcinogenic compounds, and urinary biomarkers have been widely used as a measure of exposure but quantitative relationships with exposure variables have proved elusive. This study aimed to quantify the relationship between exposures to phenanthrene and pyrene from atmospheric and dietary sources with the excretion of 1-hydroxypyrene and hydroxyphenanthrenes in urine as biomarkers of exposure. The study population consisted of 204 male schoolchildren attending three schools in different parts of Jeddah, Saudi Arabia who provided urine samples on each of three consecutive days. Outdoor air measurements of polycyclic aromatic hydrocarbons were made at the schools and the children provided information on diet, exposure to environmental tobacco smoke and incense, and various lifestyle factors through a questionnaire. Mixed models with random effects for subjects nested within site were fitted in order to examine the relationship between exposure variables and urinary PAH metabolites. A unit increase (1 ng m(-3)) in ambient pyrene (particulate plus gaseous phase) was associated with a 3.5% (95% CI: 1.01%, 5.13%) increase in urinary 1-hydroxypyrene concentration. A unit increase in ambient phenanthrene was associated with a 1.01% (95% CI: 0.03%, 2.02%) increase in total hydroxyphenanthrene concentrations. Consumption of chargrilled food increased the 1-hydroxypyrene and hydroxyphenanthrene concentrations by 24% (95% CI: 11%, 37%) and 17% (95% CI: 8%, 26%) respectively. We did not find evidence of association for environmental tobacco smoke exposure or incense burning. It is concluded that both respiratory exposure and consumption of chargrilled food are considerable sources of PAH exposure in this population as reflected by concentrations of urinary biomarkers.

Haematological and biochemical reference values of Gambian infants.

OBJECTIVE: To establish haematological and biological reference values for Gambian infants. METHODS: Basic haematological and biochemical indices were analysed in blood samples obtained from healthy infants from Sukuta in the Western Division of The Gambia. The 2.5 and the 97.5 centiles for these indices were estimated. RESULTS: Reference ranges for haematological and biochemical indices were determined. Haemoglobin, total white cell count (WBC) and platelet levels decreased with age (P < 0.001), whereas most of the white cell count subsets except monocytes did not vary with age. Potassium and alkaline phosphatase fell significantly with increasing age (P < 0.001; P < 0.001), whereas urea and creatinine rose with increasing age (P = 0.002; P < 0.001, respectively). CONCLUSION: Our set of haematological and biochemical reference values for healthy infants in The Gambia differs from values in other settings, thus underscoring the importance of establishing region-specific paediatric reference ranges to ensure optimal patient management and evaluate the impact of interventions in clinical research.

Evaluating the sensitivity and specificity of Determine™ HIV-1/2 rapid test using a 0.01M phosphate-buffered saline produced at the Medical Research Council Unit The Gambia for the diagnosis of HIV.

BACKGROUND: Human immunodeficiency virus (HIV) rapid diagnostic tests (RDTs) are widely used. However, buffer stockouts commonly lead to utilising non-approved liquids, resulting in errors. Our aim was to evaluate the diagnostic accuracy of an alternative buffer. METHODS: Paired Determine HIV-1/2 rapid tests with commercial buffer and locally produced 0.01M phosphate-buffered saline (PBS) were performed on consecutive consenting individuals requiring HIV testing. Serum samples were sent for confirmation through the local gold-standard algorithm (Murex HIV Ag/Ab, Hexagon HIV with/without Geenius HIV 1/2). Test accuracy, κ and exact McNemar's test were also carried out. RESULTS: Of 167 participants, 137 had confirmatory testing. The sensitivity of the Determine HIV-1/2 test using PBS compared with the gold standard was 100% (95% confidence interval [CI] 90.5 to 100) with a specificity of 98% (95% CI 92.9 to 99.8). The κ value was 0.94 compared with the gold standard and 0.92 compared with the Determine HIV-1/2 test using the commercial buffer. McNemar's test showed no evidence of differing sensitivities. Due to operational constraints, the study included 37 of the 49 positive cases as determined by the sample size calculation, resulting in an attained power of 80% instead of the intended 90%. CONCLUSIONS: These results suggest that 0.01M PBS is an alternative solution for Determine HIV-1/2 when buffer stockouts occur.

Diagnostic accuracy of Xpert MTB/RIF Ultra for childhood tuberculosis in West Africa - a multicenter pragmatic study.

OBJECTIVE: To evaluate the performance of Xpert Mycobacterium Tuberculosis/rifampicin (MTB/RIF) Ultra (Ultra) for diagnosis of childhood tuberculosis (TB) within public health systems. METHODS: In this cross-sectional study, children aged <15 years with presumptive pulmonary TB were consecutively recruited and evaluated for TB at tertiary-level hospitals in Benin, Mali, and Ghana. Bivariate random-effects models were used to determine the pooled sensitivity and specificity of Ultra against culture. We also estimated its diagnostic yield against a composite microbiological reference standard (cMRS) of positive culture or Ultra. RESULTS: Overall, 193 children were included in the analyses with a median (interquartile range) age of 4.0 (1.1-9.2) years, 88 (45.6%) were female, and 36 (18.7%) were HIV-positive. Thirty-one (16.1%) children had confirmed TB, 39 (20.2%) had unconfirmed TB, and 123 (63.7%) had unlikely TB. The pooled sensitivity and specificity of Ultra verified by culture were 55.0% (95% confidence interval [CI]: 28.0-79.0%) and 95.0% (95% CI: 88.0-98.0%), respectively. Against the cMRS, the diagnostic yield of Ultra and culture were 67.7% (95% CI: 48.6-83.3%) and 70.9% (95% CI: 51.9-85.8%), respectively. CONCLUSION: Ultra has suboptimal sensitivity in children with TB that were investigated under routine conditions in tertiary-level hospitals in three West African countries.