Nutritional supplementation during pulmonary rehabilitation in COPD: A systematic review

Uptake of nutritional supplementation during pulmonary rehabilitation (PR) for people with chronic obstructive pulmonary disease (COPD) has been limited by an absence of rigorous evidence-based studies supporting use. The objective was to report and summarise the current evidence supporting the use of nutritional supplementation to improve outcomes during PR in stable COPD patients. A systematic search was conducted up to 7 August 2019 (registration number CRD42018089142). The preferred reporting items for systematic reviews and meta-analyses guidelines were used. Six databases were included: Medical Literature Analysis and Retrieval System Online or MEDLARS Online, Allied and Complementary Medicine Database, the Cochrane Database of Systematic Reviews, Excerpta Medica dataBASE, Cumulative Index of Nursing and Allied Health Literature and Web of Science. This systematic search generated 580 initial matches, of which 22 studies (917 COPD participants) met the pre-specified criteria and were included. Sixteen of 19 studies that used nutritional supplements in addition to PR did not show additional benefit compared to PR alone when measuring exercise capacity. Nutritional supplements significantly increased body weight in 7 of 11 studies. Body mass index increased significantly in two of six studies. Handgrip strength did not improve, while quadriceps muscle strength significantly improved in 3 of 11 studies. Four of eight studies showed a significant improvement in inspiratory muscle function. Only 2 of 14 studies demonstrated a significant improvement in quality of life with supplementation in addition to PR. There remains insufficient evidence on the effect of nutritional supplementation on improving outcomes during PR in patients with COPD due to heterogeneity in supplements, outcome measures and PR programmes. Therefore, controversy remains and further research is needed

Adaptation of the Mullen Scales of Early Learning for use among infants aged 5- to 24-months in rural Gambia

Infants in low‐resource settings are at heightened risk for compromised cognitive development due to a multitude of environmental insults in their surroundings. However, the onset of adverse outcomes and trajectory of cognitive development in these settings is not well understood. The aims of the present study were to adapt the Mullen Scales of Early Learning (MSEL) for use with infants in a rural area of The Gambia, to examine cognitive development in the first 24‐months of life and to assess the association between cognitive performance and physical growth. In Phase 1 of this study, the adapted MSEL was tested on 52 infants aged 9‐ to 24‐months (some of whom were tested longitudinally at two time points). Further optimization and training were undertaken and Phase 2 of the study was conducted, where the original measures were administered to 119 newly recruited infants aged 5‐ to 24‐months. Infant length, weight and head circumference were measured concurrently in both phases. Participants from both phases were split into age categories of 5–9 m (N = 32), 10–14 m (N = 92), 15–19 m (N = 53) and 20–24 m (N = 43) and performance was compared across age groups. From the ages of 10–14 m, Gambian infants obtained lower MSEL scores than US norms. Performance decreased with age and was lowest in the 20–24 m old group. Differential onsets of reduced performance were observed in the individual MSEL domains, with declines in visual perception and motor performance detected as early as at 10–14 months, while reduced language scores became evident after 15–19 months of age. Performance on the MSEL was significantly associated with measures of growth

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 community based field research project investigating anaemia amongst young children living in rural Karnataka, India: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Anaemia is an important problem amongst young children living in rural India. However, there has not previously been a detailed study of the biological aetiology of this anaemia, exploring the relative contributions of iron, vitamin B12, folate and Vitamin A deficiency, inflammation, genetic haemoglobinopathy, hookworm and malaria. Nor have studies related these aetiologic biological factors to household food security, standard of living and child feeding practices. Barriers to conducting such work have included perceived reluctance of village communities to permit their children to undergo venipuncture, and logistical issues. We have successfully completed a community based, cross sectional field study exploring in detail the causes of anaemia amongst young children in a rural setting.</p> <p>Methods and design</p> <p>A cross sectional, community based study. We engaged in extensive community consultation and tailored our study design to the outcomes of these discussions. We utilised local women as field workers, harnessing the capacity of local health workers to assist with the study. We adopted a programmatic approach with a census rather than random sampling strategy in the village, incorporating appropriate case management for children identified to have anaemia. We developed a questionnaire based on existing standard measurement tools for standard of living, food security and nutrition. Specimen processing was conducted at the Primary Health Centre laboratory prior to transport to an urban research laboratory.</p> <p>Discussion</p> <p>Adopting this study design, we have recruited 415 of 470 potentially eligible children who were living in the selected villages. We achieved support from the community and cooperation of local health workers. Our results will improve the understanding into anaemia amongst young children in rural India. However, many further studies are required to understand the health problems of the population of rural India, and our study design and technique provide a useful demonstration of a successful strategy.</p

Prescribing practice for malaria following introduction of artemether-lumefantrine in an urban area with declining endemicity in West Africa

<p>Abstract</p> <p>Background</p> <p>The decline in malaria coinciding with the introduction of newer, costly anti-malarials has prompted studies into the overtreatment for malaria mostly in East Africa. The study presented here describes prescribing practices for malaria at health facilities in a West African country.</p> <p>Methods</p> <p>Cross-sectional surveys were carried out in two urban Gambian primary health facilities (PHFs) during and outside the malaria transmission season. Facilities were comparable in terms of the staffing compliment and capability to perform slide microscopy. Patients treated for malaria were enrolled after consultations and blood smears collected and read at a reference laboratory. Slide reading results from the PHFs were compared to the reference readings and the proportion of cases treated but with a negative test result at the reference laboratory was determined.</p> <p>Results</p> <p>Slide requests were made for 33.2% (173) of those enrolled, being more frequent in children (0-15 yrs) than adults during the wet season (p = 0.003). In the same period, requests were commoner in under-fives compared to older children (p = 0.022); however, a positive test result was 4.4 times more likely in the latter group (p = 0.010). Parasitaemia was confirmed for only 4.7% (10/215) and 12.5% (37/297) of patients in the dry and wet seasons, respectively. The negative predictive value of a PHF slide remained above 97% in both seasons.</p> <p>Conclusions</p> <p>The study provides evidence for considerable overtreatment for malaria in a West African setting comparable to reports from areas with similar low malaria transmission in East Africa. The data suggest that laboratory facilities may be under-used, and that adherence to negative PHF slide results could significantly reduce the degree of overtreatment. The "peak prevalence" in 5-15 year olds may reflect successful implementation of malaria control interventions in under-fives, but point out the need to extend such interventions to older children.</p

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

Effect of a Russian-backbone live-attenuated influenza vaccine with an updated pandemic H1N1 strain on shedding and immunogenicity among children in The Gambia : an open-label, observational, phase 4 study

Background The efficacy and effectiveness of the pandemic H1N1 (pH1N1) component in live attenuated influenza vaccine (LAIV) is poor. The reasons for this paucity are unclear but could be due to impaired replicative fitness of pH1N1 A/California/07/2009-like (Cal09) strains. We assessed whether an updated pH1N1 strain in the Russian-backbone trivalent LAIV resulted in greater shedding and immunogenicity compared with LAIV with Cal09. Methods We did an open-label, prospective, observational, phase 4 study in Sukuta, a periurban area in The Gambia. We enrolled children aged 24–59 months who were clinically well. Children received one dose of the WHO prequalified Russian-backbone trivalent LAIV containing either A/17/California/2009/38 (Cal09) or A/17/New York/15/5364 (NY15) based on their year of enrolment. Primary outcomes were the percentage of children with LAIV strain shedding at day 2 and day 7, haemagglutinin inhibition seroconversion, and an increase in influenza haemagglutinin-specific IgA and T-cell responses at day 21 after LAIV. This study is nested within a randomised controlled trial investigating LAIV–microbiome interactions (NCT02972957). Findings Between Feb 8, 2017, and April 12, 2017, 118 children were enrolled and received one dose of the Cal09 LAIV from 2016–17. Between Jan 15, 2018, and March 28, 2018, a separate cohort of 135 children were enrolled and received one dose of the NY15 LAIV from 2017–18, of whom 126 children completed the study. Cal09 showed impaired pH1N1 nasopharyngeal shedding (16 of 118 children [14%, 95% CI 8·0–21·1] with shedding at day 2 after administration of LAIV) compared with H3N2 (54 of 118 [46%, 36·6–55·2]; p<0·0001) and influenza B (95 of 118 [81%, 72·2–87·2]; p<0·0001), along with suboptimal serum antibody (seroconversion in six of 118 [5%, 1·9–10·7]) and T-cell responses (CD4+ interferon γ-positive and/or CD4+ interleukin 2-positive responses in 45 of 111 [41%, 31·3–50·3]). After the switch to NY15, a significant increase in pH1N1 shedding was seen (80 of 126 children [63%, 95% CI 54·4–71·9]; p<0·0001 compared with Cal09), along with improvements in seroconversion (24 of 126 [19%, 13·2–26·8]; p=0·011) and influenza-specific CD4+ T-cell responses (73 of 111 [66%, 60·0–75·6; p=0·00028]). The improvement in pH1N1 seroconversion with NY15 was even greater in children who were seronegative at baseline (24 of 64 children [38%, 95% CI 26·7–49·8] vs six of 79 children with Cal09 [8%, 2·8–15·8]; p<0·0001). Persistent shedding to day 7 was independently associated with both seroconversion (odds ratio 12·69, 95% CI 4·1–43·6; p<0·0001) and CD4+ T-cell responses (odds ratio 7·83, 95% CI 2·99–23·5; p<0·0001) by multivariable logistic regression. Interpretation The pH1N1 component switch that took place between 2016 and 2018 might have overcome the poor efficacy and effectiveness reported with previous LAIV formulations. LAIV effectiveness against pH1N1 should, therefore, improve in upcoming influenza seasons. Our data highlight the importance of assessing replicative fitness, in addition to antigenicity, when selecting annual LAIV components

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

The impact of the COVID-19 pandemic on the provision & utilisation of primary health care services in Goma, Democratic Republic of the Congo, Kambia district, Sierra Leone & Masaka district, Uganda.

INTRODUCTION: This study aimed to determine whether the COVID-19 pandemic had an impact on essential primary healthcare services at public primary healthcare facilities. METHODS: The number of weekly consultations for antenatal care (ANC), outpatient (OPD), immunisations (EPI), family planning (FP) and HIV services, between January 2018 and December 2020, were collected from 25 facilities in Masaka district, Uganda, 21 in Goma, and 29 in Kambia district, Sierra Leone. Negative binomial regression models accounting for clustering and season were used to analyse changes in activity levels between 2018, 2019 and 2020. RESULTS: In Goma, we found no change in OPD, EPI or ANC consultations, FP was 17% lower in March-July 2020 compared to 2019, but this recovered by December 2020. New diagnoses of HIV were 34% lower throughout 2020 compared to 2019. In Sierra Leone, compared to the same periods in 2019, facilities had 18-29% fewer OPD consultations throughout 2020, and 27% fewer DTP3 doses in March-July 2020. There was no evidence of differences in other services. In Uganda there were 20-35% fewer under-5 OPD consultations, 21-66% fewer MCV1 doses, and 48-51% fewer new diagnoses of HIV throughout 2020, compared to 2019. There was no difference in the number of HPV doses delivered. CONCLUSIONS: The level of disruption varied across the different settings and qualitatively appeared to correlate with the strength of lockdown measures and reported attitudes towards the risk posed by COVID-19. Mitigation strategies such as health communications campaigns and outreach services may be important to limit the impact of lockdowns on primary healthcare services

Impact of fortified versus unfortified lipid-based supplements on morbidity and nutritional status: A randomised double-blind placebo-controlled trial in ill Gambian children

Multiple micronutrients (MMN) are commonly prescribed in pediatric primary healthcare in sub-Saharan Africa to improve nutritional status and appetite without evidence for their effectiveness or international clinical guidelines. Community-wide MMN supplementation has shown limited and heterogeneous impact on growth and morbidity. Short-term ready-to-use therapeutic foods in acutely sick children in a hospital setting also had limited efficacy regarding subsequent growth. The effectiveness of MMN in improving morbidity or growth in sick children presenting for primary care has not been assessed.We undertook a double-blind randomised controlled trial of small-quantity lipid-based nutrient supplements (SQ-LNS) fortified with 23 micronutrients in children aged 6 months (mo) to 5 years (y) presenting with an illness at a rural primary healthcare centre in The Gambia. Primary outcomes were repeat clinic presentations and growth over 24 wk. Participants were randomly assigned to receive 1 of 3 interventions: (1) supplementation with micronutrient-fortified SQ-LNS for 12 wk (MMN-12), (2) supplementation with micronutrient-fortified SQ-LNS for 6 wk followed by unfortified SQ-LNS for 6 wk (MMN-6), or (3) supplementation with unfortified SQ-LNS for 12 wk (MMN-0) to be consumed in daily portions. Treatment masking used 16 letters per 6-wk block in the randomisation process. Blinded intention-to-treat analysis based on a prespecified statistical analysis plan included all participants eligible and correctly enrolled. Between December 2009 and June 2011, 1,101 children (age 6-60 mo, mean 25.5 mo) were enrolled, and 1,085 were assessed (MMN-0 = 361, MMN-6 = 362, MMN-12 = 362). MMN supplementation was associated with a small increase in height-for-age z-scores 24 wk after recruitment (effect size for MMN groups combined: 0.084 SD/24 wk, 95% CI: 0.005, 0.168; p = 0.037; equivalent to 2-5 mm depending on age). No significant difference in frequency of morbidity measured by the number of visits to the clinic within 24 wk follow-up was detected with 0.09 presentations per wk for all groups (MMN-0 versus MMN-6: adjusted incidence rate ratio [IRR] 1.03, 95% CI: 0.92, 1.16; MMN-0 versus MMN-12: 1.05, 95% CI: 0.93, 1.18). In post hoc analysis, clinic visits significantly increased by 43% over the first 3 wk of fortified versus unfortified SQ-LNS (adjusted IRR 1.43; 95% CI: 1.07, 1.92; p = 0.016), with respiratory presentations increasing by 52% with fortified SQ-LNS (adjusted IRR 1.52; 95% CI: 1.01, 2.30; p = 0.046). The number of severe adverse events during supplementation were similar between groups (MMN-0 = 20 [1 death]; MMN-6 = 21 [1 death]; MMN-12 = 20 [0 death]). No participant withdrew due to adverse effects. Study limitations included the lack of supervision of daily supplementation.Prescribing micronutrient-fortified SQ-LNS to ill children presenting for primary care in rural Gambia had a very small effect on linear growth and did not reduce morbidity compared to unfortified SQ-LNS. An early increase in repeat visits indicates a need for the establishment of evidence-based guidelines and caution with systematic prescribing of MMN. Future research should be directed at understanding the mechanisms behind the lack of effect of MMN supplementation on morbidity measures and limited effect on growth.ISRCTN 73571031