Timing of the Infancy-Childhood Growth Transition in Rural Gambia.

The Karlberg model of human growth describes the infancy, childhood, and puberty (ICP) stages as continuous and overlapping, and defined by transitions driven by sequential additional effects of several endocrine factors that shape the growth trajectory and resultant adult size. Previous research has suggested that a delayed transition from the infancy to the childhood growth stage contributes to sub-optimal growth outcomes. A new method developed to analyze the structure of centile crossing in early life has emerged as a potential tool for identifying the infancy-childhood transition (ICT), through quantifying patterns of adjacent monthly weight-for-age z-score (WAZ) deviation correlations. Using this method, the infancy-childhood transition was identified as taking place at around 12 months of age in two cohorts of UK infants. Here, we apply this method to data collected as part of a longitudinal growth study in rural Gambia [the Hormonal and Epigenetic Regulators of Growth, or HERO-G study, N = 212 (F = 99, M = 113)], in order to identify the ICT and assess whether timing of this transition differs across groups based on sex or birth seasonality. We calculated Pearson correlation coefficients for adjacent monthly WAZ score deviations. Based on the patterns of change in the correlation structure over time, our results suggest that the infancy-childhood transition occurs at around 9 months of age in rural Gambian infants. This points to an accelerated ICT compared to UK infants, rather than a delayed ICT. A comparatively later transition, seen in UK infants, allows maximal extension of the high rates of growth during the infancy stage; an earlier transition as seen in Gambian infants cuts short this period of rapid growth, potentially impacting on growth outcomes in childhood while diverting energy into other processes critical to responses to acute infectious challenges. Growth in later developmental stages in this population offers an extended window for catch-up

Sex-differential non-vaccine specific immunological effects of diphtheria-tetanus-pertussis and measles vaccination

Vaccines can have nontargeted heterologous effects that manifest as increased protection against nonvaccine infections, as described for measles vaccine (MV), or increased susceptibility to infections and death, as described following diphtheria-tetanus-whole cell pertussis (DTP) vaccination. The mechanisms are unknown, and high-quality immunological studies are lacking. This study was designed to investigate the heterologous effects of MV and DTP in 302 Gambian infants. The results support a sex-differential immunosuppressive effect of DTP on innate proinflammatory responses and T-cell immunity. Males but not females receiving MV had enhanced proinflammatory innate responses. The results point to modified signaling via Toll-like receptor 4 (TLR4) as a possible mechanism for the effects on innate immunity. When both vaccines were administered together, purified protein derivative responses were enhanced in females but downregulated in males. Collectively, these data indicate immunological effects that could account for heterologous effects of MV and DTP, to take forward into prospective trials

A Novel method for the identification and quantification of weight faltering

Abstract: Objective: We describe a new method for identifying and quantifying the magnitude and rate of short‐term weight faltering episodes, and assess how (a) these episodes relate to broader growth outcomes, and (b) different data collection intervals influence the quantification of weight faltering. Materials and methods: We apply this method to longitudinal growth data collected every other day across the first year of life in Gambian infants (n = 124, males = 65, females = 59). Weight faltering episodes are identified from velocity peaks and troughs. Rate of weight loss and regain, maximum weight loss, and duration of each episode were calculated. We systematically reduced our dataset to mimic various potential measurement intervals, to assess how these intervals affect the ability to derive information about short‐term weight faltering episodes. We fit linear models to test whether metrics associated with growth faltering were associated with growth outcomes at 1 year, and generalized additive mixed models to determine whether different collection intervals influence episode identification and metrics. Results: Three hundred weight faltering episodes from 119 individuals were identified. The number and magnitude of episodes negatively impacted growth outcomes at 1 year. As data collection interval increases, weight faltering episodes are missed and the duration of episodes is overestimated, resulting in the rate of weight loss and regain being underestimated. Conclusions: This method identifies and quantifies short‐term weight faltering episodes, that are in turn negatively associated with growth outcomes. This approach offers a tool for investigators interested in understanding how short‐term weight faltering relates to longer‐term outcomes

A Novel method for the identification and quantification of weight faltering

Abstract: Objective: We describe a new method for identifying and quantifying the magnitude and rate of short‐term weight faltering episodes, and assess how (a) these episodes relate to broader growth outcomes, and (b) different data collection intervals influence the quantification of weight faltering. Materials and methods: We apply this method to longitudinal growth data collected every other day across the first year of life in Gambian infants (n = 124, males = 65, females = 59). Weight faltering episodes are identified from velocity peaks and troughs. Rate of weight loss and regain, maximum weight loss, and duration of each episode were calculated. We systematically reduced our dataset to mimic various potential measurement intervals, to assess how these intervals affect the ability to derive information about short‐term weight faltering episodes. We fit linear models to test whether metrics associated with growth faltering were associated with growth outcomes at 1 year, and generalized additive mixed models to determine whether different collection intervals influence episode identification and metrics. Results: Three hundred weight faltering episodes from 119 individuals were identified. The number and magnitude of episodes negatively impacted growth outcomes at 1 year. As data collection interval increases, weight faltering episodes are missed and the duration of episodes is overestimated, resulting in the rate of weight loss and regain being underestimated. Conclusions: This method identifies and quantifies short‐term weight faltering episodes, that are in turn negatively associated with growth outcomes. This approach offers a tool for investigators interested in understanding how short‐term weight faltering relates to longer‐term outcomes

Safety and Immunogenicity of ChAd63 and MVA ME-TRAP in West African Children and Infants.

Malaria remains a significant global health burden and a vaccine would make a substantial contribution to malaria control. Chimpanzee Adenovirus 63 Modified Vaccinia Ankara Multiple epitope thrombospondin adhesion protein (ME-TRAP) and vaccination has shown significant efficacy against malaria sporozoite challenge in malaria-naive European volunteers and against malaria infection in Kenyan adults. Infants are the target age group for malaria vaccination; however, no studies have yet assessed T-cell responses in children and infants. We enrolled 138 Gambian and Burkinabe children in four different age-groups: 2-6 years old in The Gambia; 5-17 months old in Burkina Faso; 5-12 months old, and also 10 weeks old, in The Gambia; and evaluated the safety and immunogenicity of Chimpanzee Adenovirus 63 Modified Vaccinia Ankara ME-TRAP heterologous prime-boost immunization. The vaccines were well tolerated in all age groups with no vaccine-related serious adverse events. T-cell responses to vaccination peaked 7 days after boosting with Modified Vaccinia Ankara, with T-cell responses highest in 10 week-old infants. Heterologous prime-boost immunization with Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara ME-TRAP was well tolerated in infants and children, inducing strong T-cell responses. We identify an approach that induces potent T-cell responses in infants, which may be useful for preventing other infectious diseases requiring cellular immunity

Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants.

Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine

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

“One Wishes for Nothing More than to Be Free from This Chemical Shackle” : A Qualitative Study of Participants’ Experience of Opioid Substitution Treatment

Studiens syfte är att undersöka individens subjektiva upplevelse av att genomgå läkemedelsassisterad behandling för opioidberoende (LARO). För att besvara studiens syfte och frågeställningar har vi använt oss av kvalitativ metod i form av både fokusgruppintervju och individuella intervjuer. I fokusgruppintervjun intervjuade vi tre yrkesverksamma för att bredda våra kunskaper inom ämnet och även för hjälp till utformningen av intervjuguiden för de individuella intervjuerna. De individuella intervjuerna bestod av sex intervjupersoner, tre som har LARO-behandling i dagsläget och tre som tidigare har haft det. Materialet från fokusgrupp- och de individuella intervjuerna presenteras i empirin med hjälp av en tematisk analys. Empirin har sedan analyserats med hjälp av tidigare forskning och Goffmans teori om stigma. Studien visar att det finns flera olika aspekter som framkommer som viktiga i individens upplevelse av att ha LARO-behandling. I studien har särskilt fysiska biverkningar och känslomässig avstängdhet lyfts som en viktig aspekt. Även sidomissbruk verkar vara något studiens deltagare anser vara ett viktigt problem. Hämtningen av medicin och kontroll är också en aspekt som verkar vara en stor del av att ha LARO-behandling. En viktig aspekt är även behandlingens livräddande förmåga, men trots denna verkar dessutom en bundenhet till behandlingen upplevas som ett problem av deltagarna. Studien visar en variation i hur individen med LARO-behandling påverkas av sociala sammanhang. Å ena sidan verkar relationerna till närstående och familj i vissa fall ha fortsatt varit fungerande, eller till och med bättre. Å andra sidan beskrivs relationerna ha försämrats. Vi kan även se hos samtliga deltagare att de varit varsamma med vilka de var öppna för om sin behandling. Studien visar att i vissa fall kunde omgivningen vara förstående, i andra fall kunde omgivningen se ner på individen. Hos våra intervjudeltagare är upplevelsen av personalens bemötande i stort positiv. Studien diskuterar skillnader i åsikter gällande frågan kring huruvida man kan vara drogfri under pågående LARO-behandling. Vissa respondenter anser att man kan vara drogfri, men lyfter sidomissbruk som ett hinder. Andra respondenter anser att man inte riktigt kan klassas som drogfri ifall man erhåller substitutionsbehandling.The purpose of the study is to examine individuals’ subjective experiences of undergoing medication-assisted treatment for opioid dependency (LARO). To address the study’s purpose and research questions we used a qualitative method, utilizing both focus group interviews and individual interviews. In the focus group interview we interviewed three professionals to broaden our knowledge of the subject and to assist in the development of the interview guide for the individual interviews. The individual interviews included six participants: three currently undergoing LARO-treatment and three who have previously undergone it. The material from the focus group and individual interviews is presented in the empirical section using thematic analysis. The empirical data were then analyzed with the help of previous research and Goffman’s theory of stigma. The study reveals several important aspects of individuals’ experiences with LARO treatment. Physical side effect and emotional numbness were highlighted as significant issues. Concurrent substance abuse also appears to be a major concern among the study’s participants. The process of medication retrieval and monitoring is another significant aspect of LARO treatment. While the treatment’s life-saving potential is acknowledged, participants also expressed a sense of dependency on the treatment as problematic. The study shows variability in how individuals undergoing LARO-treatment are affected by social contexts. On one hand, relationships with close ones and family sometimes remained functional or even improved. On the other hand, some relationships are described as deteriorated. All participants were cautious about whom they disclosed their treatment to. The study shows that the surrounding environment could be understanding in some cases. While in other cases, individuals were looked down upon. The participants’ experiences with the staff’s attitude are generally positive. The study discusses differing opinions on whether one can be considered drug-free while undergoing LARO treatment. Some respondents believe that one can be drug-free but highlight concurrent substance abuse as an obstacle. Other believe that one cannot be truly considered drug-free if receiving substitution treatment

“One Wishes for Nothing More than to Be Free from This Chemical Shackle” : A Qualitative Study of Participants’ Experience of Opioid Substitution Treatment

Studiens syfte är att undersöka individens subjektiva upplevelse av att genomgå läkemedelsassisterad behandling för opioidberoende (LARO). För att besvara studiens syfte och frågeställningar har vi använt oss av kvalitativ metod i form av både fokusgruppintervju och individuella intervjuer. I fokusgruppintervjun intervjuade vi tre yrkesverksamma för att bredda våra kunskaper inom ämnet och även för hjälp till utformningen av intervjuguiden för de individuella intervjuerna. De individuella intervjuerna bestod av sex intervjupersoner, tre som har LARO-behandling i dagsläget och tre som tidigare har haft det. Materialet från fokusgrupp- och de individuella intervjuerna presenteras i empirin med hjälp av en tematisk analys. Empirin har sedan analyserats med hjälp av tidigare forskning och Goffmans teori om stigma. Studien visar att det finns flera olika aspekter som framkommer som viktiga i individens upplevelse av att ha LARO-behandling. I studien har särskilt fysiska biverkningar och känslomässig avstängdhet lyfts som en viktig aspekt. Även sidomissbruk verkar vara något studiens deltagare anser vara ett viktigt problem. Hämtningen av medicin och kontroll är också en aspekt som verkar vara en stor del av att ha LARO-behandling. En viktig aspekt är även behandlingens livräddande förmåga, men trots denna verkar dessutom en bundenhet till behandlingen upplevas som ett problem av deltagarna. Studien visar en variation i hur individen med LARO-behandling påverkas av sociala sammanhang. Å ena sidan verkar relationerna till närstående och familj i vissa fall ha fortsatt varit fungerande, eller till och med bättre. Å andra sidan beskrivs relationerna ha försämrats. Vi kan även se hos samtliga deltagare att de varit varsamma med vilka de var öppna för om sin behandling. Studien visar att i vissa fall kunde omgivningen vara förstående, i andra fall kunde omgivningen se ner på individen. Hos våra intervjudeltagare är upplevelsen av personalens bemötande i stort positiv. Studien diskuterar skillnader i åsikter gällande frågan kring huruvida man kan vara drogfri under pågående LARO-behandling. Vissa respondenter anser att man kan vara drogfri, men lyfter sidomissbruk som ett hinder. Andra respondenter anser att man inte riktigt kan klassas som drogfri ifall man erhåller substitutionsbehandling.The purpose of the study is to examine individuals’ subjective experiences of undergoing medication-assisted treatment for opioid dependency (LARO). To address the study’s purpose and research questions we used a qualitative method, utilizing both focus group interviews and individual interviews. In the focus group interview we interviewed three professionals to broaden our knowledge of the subject and to assist in the development of the interview guide for the individual interviews. The individual interviews included six participants: three currently undergoing LARO-treatment and three who have previously undergone it. The material from the focus group and individual interviews is presented in the empirical section using thematic analysis. The empirical data were then analyzed with the help of previous research and Goffman’s theory of stigma. The study reveals several important aspects of individuals’ experiences with LARO treatment. Physical side effect and emotional numbness were highlighted as significant issues. Concurrent substance abuse also appears to be a major concern among the study’s participants. The process of medication retrieval and monitoring is another significant aspect of LARO treatment. While the treatment’s life-saving potential is acknowledged, participants also expressed a sense of dependency on the treatment as problematic. The study shows variability in how individuals undergoing LARO-treatment are affected by social contexts. On one hand, relationships with close ones and family sometimes remained functional or even improved. On the other hand, some relationships are described as deteriorated. All participants were cautious about whom they disclosed their treatment to. The study shows that the surrounding environment could be understanding in some cases. While in other cases, individuals were looked down upon. The participants’ experiences with the staff’s attitude are generally positive. The study discusses differing opinions on whether one can be considered drug-free while undergoing LARO treatment. Some respondents believe that one can be drug-free but highlight concurrent substance abuse as an obstacle. Other believe that one cannot be truly considered drug-free if receiving substitution treatment