Association between serum transferrin receptor levels and malaria recurrence in a malaria endemic area in Tanzania

Background: The relationship between body iron levels and malaria presents a complex interaction that provide variable and contradicting results. We designed a study to investigate associations between concentrations of biomarkers of body iron and malaria recurrence among children.Methods: We conducted a longitudinal descriptive community based study in a malaria endemic area in north- eastern Tanzania. The study involved 428 children of ≤5 years of age who were positive for malaria. Over a period of 6 months, sick children visited the study clinic for screening of malaria and measurement of iron storage biomarkers by serological assays. Correlations between levels of biomarkers and malaria was determined by Spearman correlations and Mann-Whitney U-Test. Associations between malaria recurrence and serum levels of iron biomarkers were determined by odds ratio (OR) with significance cut-off points of <0.15 in univariate and <0.05 in multivariate logistic regression analyses.Results: Only serum Transferrin Receptor (sTfR) levels had a positive correlation with malaria recurrence. When Mann-Whitney U test was used higher Hepcidin, sTfR and Leptin levels were significantly associated with malaria recurrence when malaria incidence was grouped into ‘once’ versus ‘more than once’. When malaria incidence was recategorised to ‘up to twice’ versus ‘more than twice’, only higher level of sTfR was associated with recurrence of malaria. With univariate regression analysis, only sTfR was found to be significantly associated with malaria recurrence, although this associated was not observed in Multivariate analyses.Conclusion: Despite the absence of association in multivariate analyses, univariate analyses suggest elevated levels of sTFR as a likely predictor of Plasmodium falciparum re-infection.      

A counseling intervention to address HIV stigma at entry into antenatal care in Tanzania (Maisha): study protocol for a pilot randomized controlled trial.

BACKGROUND: HIV-related stigma significantly impacts HIV care engagement, including in prevention of mother-to-child transmission of HIV (PMTCT) programs. Maisha is a stigma-based counseling intervention delivered during the first antenatal care (ANC) visit, complementing routine HIV counseling and testing. The goal of Maisha is to promote readiness to initiate and sustain treatment among those who are HIV-positive, and to reduce HIV stigmatizing attitudes among those who test negative. METHODS: A pilot randomized control trial will assess the feasibility and acceptability of delivering Maisha in a clinical setting, and the potential efficacy of the intervention on HIV care engagement outcomes (for HIV-positive participants) and HIV stigma constructs (for all participants). A total of 1000 women and approximately 700 male partners will be recruited from two study clinics in the Moshi municipality of Tanzania. Participants will be enrolled at their first ANC visit, prior to HIV testing. It is estimated that 50 women (5%) will be identified as HIV-positive. Following consent and a baseline survey, participants will be randomly assigned to either the control (standard of care) or the Maisha intervention. The Maisha intervention includes a video and counseling session prior to HIV testing, and two additional counseling sessions if the participant tests positive for HIV or has an established HIV diagnosis. A subset of approximately 500 enrolled participants (all HIV-positive participants, and a random selection of HIV-negative participants who have elevated stigma attitude scores) will complete a follow-up assessment at 3 months. Measures will include health outcomes (care engagement, antiretroviral adherence, depression) and HIV stigma outcomes. Quality assurance data will be collected and the feasibility and acceptability of the intervention will be described. Statistical analysis will examine potential differences between conditions in health outcomes and stigma measures, stratified by HIV status. DISCUSSION: ANC provides a unique and important entry point to address HIV stigma. Interventions are needed to improve retention in PMTCT care and to improve community attitudes toward people living with HIV. Results of the Maisha pilot trial will be used to generate parameter estimates and potential ranges of values to estimate power for a full cluster-randomized trial in PMTCT settings, with extended follow-up and enhanced adherence measurement using a biomarker.

Unlocking the health system barriers to maximise the uptake and utilisation of molecular diagnostics in low- and middle- income country setting

The study was funded by the European and Developing Countries Clinical Trials Partnership (EDCTP), grant TWENDE-EDCTP-CSA-2014-283.Background : Early access to diagnosis is crucial for effective management of any disease including tuberculosis (TB). We investigated the barriers and opportunities to maximise uptake and utilisation of molecular diagnostics in routine healthcare settings. Methods : Using the implementation of World Health Organisation approved TB diagnostics, Xpert MTB/RIF and Line Probe Assay (LPA) as a benchmark we evaluated the barriers and how they could be unlocked to maximise uptake and utilisation of molecular diagnostics. Results : Health officers representing 190 districts/counties participated in the survey across Kenya, Tanzania and Uganda. The survey findings were corroborated by 145 healthcare facility (HCF) audits and 11 policymaker engagement workshops. Xpert MTB/RIF coverage was 66%, falling behind microscopy and clinical diagnosis by 33% and 1% respectively. Stratified by HCF type, Xpert MTB/RIF implementation was 56%, 96% and 95% at district-, regional- and national referral- hospital levels. LPA coverage was 4%, 3% below culture across the three countries. Out of 111 HCFs with Xpert MTB/RIF, 37 (33%) utilised it to full capacity, performing ≥8 tests per day of which 51% of these were level five (zonal consultant and national referral) HCFs. Likewise, 75% of LPA was available at level five HCFs. Underutilisation of Xpert MTB/RIF and LPA was mainly attributed to inadequate- utilities, 26% and human resource, 22%. Underfinancing was the main reason underlying failure to acquire molecular diagnostics. Second to underfinancing was lack of awareness with 33% healthcare administrators and 49% practitioners were unaware of LPA as TB diagnostic. Creation of a health tax and decentralising its management was proposed by policymakers as a booster of domestic financing needed to increase access to diagnostics. Conclusion : Our findings suggest higher uptake and utilisation of molecular diagnostics at tertiary level HCFs contrary to the WHO recommendation. Country-led solutions are crucial for unlocking barriers to increase access to diagnostics.Publisher PDFPeer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

"Mä oon aina kunnolla" : uhmakkuus- ja käytöshäiriödiagnoosin saaneen lapsen oman käytöksen käsittely perheterapiassa ja aikuisten rooli lapsen siihen ohjaamisessa

Tässä pro gradu -tutkielmassa tarkastelemme uhmakkuus- ja käytöshäiriödiagnoosin saaneen lapsen tapoja käsitellä omaa käytöstään perheterapiassa. Olemme myös kiinnostuneita terapeuttien ja vanhempien tavoista ohjata lasta käsittelemään käytöstään. Havainnoimme oman käytöksen käsittelyä kattavasta näkökulmasta, joka pitää sisällään sanallisen itsereflektion lisäksi myös muita terapeuttiseen keskusteluun reagoimisen tapoja. Tutkimme terapiassa tapahtunutta vuorovaikutusta multimodaalisella keskustelunanalyysilla, joka mahdollistaa myös nonverbaalisen viestinnän monipuolisen analysoinnin. Aineistomme koostuu yhden perheen kotona toteutetuista perheterapiatapaamisista, joista tarkastelemme tässä tutkielmassa kolmessa eri tapaamisessa tapahtunutta kuutta vuorovaikutustilannetta. Kolme aineisto-otetta käsittelee lasta oman käytöksen käsittelijänä ja kaksi terapeuttien ja vanhempien tapoja ohjata lasta. Analyysin monipuolistamiseksi valitsimme tarkasteluun myös yhden otteen, jossa havainnoimme terapeutin tapaa ohjata samanaikaisesti vanhempaa ja lasta. Aineisto on kerätty Jyväskylän yliopiston Psykoterapian opetus- ja tutkimusklinikan ja Kuopion yliopistollisen sairaalan lastenpsykiatrian poliklinikan kanssa yhteistyössä toteutetun tutkimusprojektin yhteydessä. Tulokset osoittivat, että uhmakkuus- ja käytöshäiriödiagnoosin saaneen lapsen tavoissa käsitellä omaa käytöstään oli paljon vaihtelua. Lapsi osoitti oman käytöksen käsittelyä tilasta poistumalla, jäämällä tilanteeseen haastavasti käyttäytyen ja prososiaalisesti reflektoiden omaa käytöstään. Myös terapeuttien ja vanhempien tavoissa ohjata lasta oli eroja. Terapeutit ohjasivat lasta useammin kannustaen ja motivoiden, kun taas vanhempien ohjaus piti sisällään uhkauksia, kiristämistä ja negatiivista vahvistusta. Terapeutin tapa ohjata samanaikaisesti vanhempaa ja lasta keskittyi yhteistyön tärkeyden korostamiseen. Tuloksemme tarjoavat tärkeää tietoa lapsen monipuolisista tavoista osallistua ja käsitellä omaa käytöstään perheterapiassa. Aikuisten on tärkeä nähdä nämä kaikki tavat merkityksellisinä ja ottaa ne huomioon lapsen osallistamisessa. Lisäksi tuloksemme painottavat erityisesti lapsen ja vanhemman samanaikaista ohjaamista, jonka avulla terapeutit voivat tukea perheen vuorovaikutussuhteita

Depression and anxiety among pregnant women living with HIV in Kilimanjaro region, Tanzania.

IntroductionMental health disorders in pregnant women living with HIV are associated with poor maternal and child outcomes, and undermine the global goals of prevention of mother-to-child transmission of HIV (PMTCT). This study aimed to determine prevalence of depression and anxiety and identify factors associated with these common mental health disorders among HIV-infeced pregnant women in Tanzania.MethodsWe enrolled 200 pregnant women living with HIV from antenatal care clinics in the Kilimanjaro region. Women were eligible if they were in the second or third trimester of pregnancy and had been in PMTCT care for a minimum of one month. Data were collected via interviewer administered surveys. Participants self reported depression symptoms (Edinburgh Postnatal Depression Scale, EPDS) and anxiety symptoms (Brief Symptom Index, BSI). Multivariate logistic regression models examined factors associated with depression, anxiety, and comorbid depression and anxiety.Results25.0% of women met screening criteria for depression (EPDS ≥10). Depression was significantly associated with being single (aOR = 4.2, 95% CI = 1.1-15.5), food insecurity (aOR = 2.4, 95% CI = 1.0-6.4), and HIV shame (aOR = 1.2, 95% CI = 1.1-1.3). 23.5% of participants met screening criteria for anxiety (BSI ≥1.01). Anxiety was associated with being single (aOR = 3.6, 95%CI = 1.1-11.1), HIV shame (aOR = 1.1, 95% CI = 1.1-1.2) and lifetime experience of violence (aOR = 2.3, 95% CI = 1.0-5.1). 17.8% of the sample met screening criteria for both depression and anxiety. Comorbid depression and anxiety was associated with being single (aOR = 4.5, 95%CI = 1.0-19.1), HIV shame (aOR = 1.2, 95%CI = 1.1-1.3) and lifetime experience of violence (aOR = 3.4, 95% CI = 1.2-9.6).ConclusionDepression and anxiety symptomatology was common in this sample of pregnant women living with HIV, with a sizable number screening positive for comorbid depression and anxiety. In order to successfully engage women in PMTCT care and support their well-being, strategies to screen for mental health disorders and support women with mental illnesses are needed