Effect of HIV/AIDS and Malaria on the Context for Introduction of Zinc Treatment and Low-osmolarity ORS for Childhood Diarrhoea*

Diarrhoea was estimated to account for 18% of the estimated 10.6 million deaths of children aged less than five years annually in 2003. Two—Africa and South-East Asia—of the six regions of the World Health Organization accounted for approximately 40% and 31% of these deaths respectively, or almost three-quarters of the global annual deaths of children aged less than five years attributable to diarrhoea. Much of the effort to roll out low-osmolarity oral rehydration solution (ORS) and supplementation of zinc for the management of diarrhoea accordingly is being devoted to sub-Saharan Africa and to South and South-East Asia. A number of significant differences exist in diarrhoea-treatment behaviours and challenges of the public-health systems between Africa and Asia. The differences in rates of ORS use are the most common indicator of treatment of diarrhoea and vary dramatically by and within region and may significantly influence the roll-out strategy for zinc and low-osmolarity ORS. The prevalence of HIV/AIDS and the endemi-city of malaria also differ greatly between regions; both the diseases consume the attention and financial commitment of public-health programmes in regions where rates are high. This paper examined how these differences could affect the context for the introduction of zinc and low-osmolarity ORS at various levels, including the process of policy dialogue with local decision-makers, questions to be addressed in formative research, implementation approaches, and strategies for behaviour-change communication and training of health workers

Effect of HIV/AIDS and Malaria on the Context for Introduction of Zinc Treatment and Low-osmolarity ORS for Childhood Diarrhoea

Diarrhoea was estimated to account for 18% of the estimated 10.6 million deaths of children aged less than five years annually in 2003. Two-Africa and South-East Asia-of the six regions of the World Health Organization accounted for approximately 40% and 31% of these deaths respectively, or almost three-quarters of the global annual deaths of children aged less than five years attributable to diarrhoea. Much of the effort to roll out low-osmolarity oral rehydration solution (ORS) and supplementation of zinc for the management of diarrhoea accordingly is being devoted to sub-Saharan Africa and to South and South-East Asia. A number of significant differences exist in diarrhoea-treatment behaviours and challenges of the public-health systems between Africa and Asia. The differences in rates of ORS use are the most common indicator of treatment of diarrhoea and vary dramatically by and within region and may significantly influence the roll-out strategy for zinc and low-osmolarity ORS. The prevalence of HIV/AIDS and the endemi-city of malaria also differ greatly between regions; both the diseases consume the attention and financial commitment of public-health programmes in regions where rates are high. This paper examined how these differences could affect the context for the introduction of zinc and low-osmolarity ORS at various levels, including the process of policy dialogue with local decision-makers, questions to be addressed in formative research, implementation approaches, and strategies for behaviour-change communication and training of health workers

Quality of sick child care delivered by Health Surveillance Assistants in Malawi

Objective To assess the quality of care provided by Health Surveillance Assistants (HSAs)—a cadre of community-based health workers—as part of a national scale-up of community case management of childhood illness (CCM) in Malawi. Methods Trained research teams visited a random sample of HSAs (n = 131) trained in CCM and provided with initial essential drug stocks in six districts, and observed the provision of sick child care. Trained clinicians conducted ‘gold-standard' reassessments of the child. Members of the survey team also interviewed caregivers and HSAs and inspected drug stocks and patient registers. Findings HSAs provided correct treatment with antimalarials to 79% of the 241 children presenting with uncomplicated fever, with oral rehydration salts to 69% of the 93 children presenting with uncomplicated diarrhoea and with antibiotics to 52% of 58 children presenting with suspected pneumonia (cough with fast breathing). About one in five children (18%) presented with danger signs. HSAs correctly assessed 37% of children for four danger signs by conducting a physical exam, and correctly referred 55% of children with danger signs. Conclusion Malawi's CCM programme is a promising strategy for increasing coverage of sick child treatment, although there is much room for improvement, especially in the correct assessment and treatment of suspected pneumonia and the identification and referral of sick children with danger signs. However, HSAs provided sick child care at levels of quality similar to those provided in first-level health facilities in Malawi, and quality should improve if the Ministry of Health and partners act on the results of this assessmen

Operational Issues and Trends Associated with the Pilot Introduction of Zinc for Childhood Diarrhoea in Bougouni District, Mali

Zinc for the treatment of childhood diarrhoea was introduced in a pilot area in southern Mali to prepare for a cluster-randomized effectiveness study and to inform policies on how to best introduce and promote zinc at the community level. Dispersible zinc tablets in 14-tablet blister packs were provided through community health centres and drug kits managed by community health workers (CHWs) in two health zones in Bougouni district, Mali. Village meetings and individual counselling provided by CHWs and head nurses at health centres were the principal channels of communication. A combination of methods were employed to (a) detect problems in communication about the benefits of zinc and its mode of administration; (b) identify and resolve obstacles to implementation of zinc through existing health services; and (c) describe household-level constraints to the adoption of appropriate home-management practices for diarrhoea, including administration of both zinc and oral rehydration solution (ORS). Population-based household surveys with caretakers of children sick in the previous two weeks were carried out before and four months after the introduction of zinc supplementation. Household follow-up visits with children receiving zinc from the health centres and CHWs were conducted on day 3 and 14 after treatment for a subsample of children. A qualitative process evaluation also was conducted to investigate operational issues. Preliminary evidence from this study suggests that the introduction of zinc does not reduce the use of ORS and may reduce inappropriate antibiotic use for childhood diarrhoea. Financial access to treatments, management of concurrent diarrhoea and fever, and high use of unauthorized drug vendors were identified as factors affecting the effectiveness of the intervention in this setting. The introduction of zinc, if not appropriately integrated with other disease-control strategies, has the potential to decrease the appropriate presumptive treatment of childhood malaria in children with diarrhoea and fever in malaria-endemic areas

Operational Issues and Trends Associated with the Pilot Introduction of Zinc for Childhood Diarrhoea in Bougouni District, Mali

Zinc for the treatment of childhood diarrhoea was introduced in a pilot area in southern Mali to prepare for a cluster-randomized effectiveness study and to inform policies on how to best introduce and promote zinc at the community level. Dispersible zinc tablets in 14-tablet blister packs were provided through community health centres and drug kits managed by community health workers (CHWs) in two health zones in Bougouni district, Mali. Village meetings and individual counselling provided by CHWs and head nurses at health centres were the principal channels of communication. A combination of methods were employed to (a) detect problems in communication about the benefits of zinc and its mode of administration; (b) identify and resolve obstacles to implementation of zinc through existing health services; and (c) describe household-level constraints to the adoption of appropriate home-management practices for diarrhoea, including administration of both zinc and oral rehydration solution (ORS). Population-based household surveys with caretakers of children sick in the previous two weeks were carried out before and four months after the introduction of zinc supplementation. Household follow-up visits with children receiving zinc from the health centres and CHWs were conducted on day 3 and 14 after treatment for a subsample of children. A qualitative process evaluation also was conducted to investigate operational issues. Preliminary evidence from this study suggests that the introduction of zinc does not reduce the use of ORS and may reduce inappropriate antibiotic use for childhood diarrhoea. Financial access to treatments, management of concurrent diarrhoea and fever, and high use of unauthorized drug vendors were identified as factors affecting the effectiveness of the intervention in this setting. The introduction of zinc, if not appropriately integrated with other disease-control strategies, has the potential to decrease the appropriate presumptive treatment of childhood malaria in children with diarrhoea and fever in malaria-endemic areas

A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution

Frozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most fibrotic diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTKlowCD48+ macrophages and MERTK + LYVE1 + MRC1+ macrophages enriched for negative regulators of inflammation which co-exist in frozen shoulder capsule tissues. Micro-cultures of patient-derived cells identify integrin-mediated cell-matrix interactions between MERTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in frozen shoulder resolution. Cross-tissue analysis reveals a shared gene expression cassette between shoulder capsule MERTK+ macrophages and a respective population enriched in synovial tissues of rheumatoid arthritis patients in disease remission, supporting the concept that MERTK+ macrophages mediate resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identify MERTK + LYVE1 + MRC1+ macrophages and DKK3+ and POSTN+ fibroblast populations analogous to those in frozen shoulder, suggesting that the template to resolve fibrosis is established during shoulder development. Crosstalk between MerTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts could facilitate resolution of frozen shoulder, providing a basis for potential therapeutic resolution of persistent fibrotic diseases

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant