Effectiveness of handwashing with soap for preventing acute respiratory infections in low-income and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Acute respiratory infection (ARI) is a leading cause of morbidity and mortality globally, with 83% of ARI mortality occurring in low-income and middle-income countries (LMICs) before the COVID-19 pandemic. We aimed to estimate the effect of interventions promoting handwashing with soap on ARI in LMICs. METHODS: In our systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, Global Health, and Global Index Medicus for studies of handwashing with soap interventions in LMICs from inception to May 25, 2021. We included randomised and non-randomised controlled studies of interventions conducted in domestic, school, or childcare settings. Interventions promoting hand hygiene methods other than handwashing with soap were excluded, as were interventions in health-care facilities or the workplace. The primary outcome was ARI morbidity arising from any pathogen for participants of any age. Secondary outcomes were lower respiratory infection, upper respiratory infection, influenza confirmed by diagnostic test, COVID-19 confirmed by diagnostic test, and all-cause mortality. We extracted relative risks (RRs), using random-effects meta-analysis to analyse study results, and metaregression to evaluate heterogeneity. We assessed risk of bias in individual studies using an adapted Newcastle-Ottawa scale, and assessed the overall body of evidence using a Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The study is registered with PROSPERO, CRD42021231414. FINDINGS: 26 studies with 161 659 participants met inclusion criteria, providing 27 comparisons (21 randomised). Interventions promoting handwashing with soap reduced any ARI compared with no handwashing intervention (RR 0·83 [95% CI 0·76-0·90], I2 88%; 27 comparisons). Interventions also reduced lower respiratory infections (0·78 [0·64-0·94], I2 64%; 12 comparisons) and upper respiratory infections (0·74 [0·59-0·93], I2 91%; seven comparisons), but not test-confirmed influenza (0·94 [0·42-2·11], I2 90%; three comparisons), test-confirmed COVID-19 (no comparisons), or all-cause mortality (prevalence ratio 0·95 [95% CI 0·71-1·27]; one comparison). For ARI, no heterogeneity covariates were significant at p<0·1 and the GRADE rating was moderate certainty evidence. INTERPRETATION: Interventions promoting handwashing with soap can reduce ARI in LMICs, and could help to prevent the large burden of respiratory disease. FUNDING: Bill & Melinda Gates Foundation, Reckitt Global Hygiene Institute, and UK FCDO.

Significant risk of COVID-19 and related-hospitalization among patients with adrenal insufficiency: A large multinational survey.

Objective: To determine self-reported incidence and potential risk factors for COVID-19 in patients with adrenal insufficiency (AI). Methods: A 27-item AI survey was developed for AI and COVID-19 status, vetted by specialists and patients, and distributed via social media, websites, and advocacy groups. Participation was voluntary and anonymous. Data were collected from September 20th, 2020 until December 31st, 2020. Results: Respondents (n=1291) with self-reported glucocorticoid treatment for AI, completed the survey, with 456 who reported having symptoms and were screened for COVID-19 during 2020; 40 tested positive (+ve), representing an 8.8% incidence. Of the COVID-19+ve, 31 were female (78%), with mean age of 39.9 years. COVID-19 among AI patients occurred most commonly in those aged 40-59 years (n=17; 42.5%); mean time since AI diagnosis was 13.5 years (range 0.2-42.0 years). Pulmonary disease, congenital adrenal hyperplasia, and higher maintenance doses of glucocorticoids were significantly associated with +ve COVID-19 (p=0.04, p=0.01, and p=0.001, respectively. In respondents the cumulative incidence of COVID-19+ve during 2020 was 3.1%; greater than the 1.03% worldwide-incidence reported by WHO, by December 31st, 2020. There was a 3-fold (95% CI 2.16-3.98) greater relative risk (RR) of COVID-19 infection and a 23.8- fold (95% CI 20.7-31.2) RR of hospitalization in patients with AI, compared with the global population. Conclusion: A markedly raised RR of COVID-19 and hospitalization in respondents reporting chronic AI was detected. We found that a diagnosis of congenital adrenal hyperplasia, age>40 years, male gender, pulmonary disease, and higher maintenance doses of glucocorticoids were associated with greatest risk.

Puberty health intervention to improve menstrual health and school attendance among adolescent girls in The Gambia: study methodology of a cluster-randomised controlled trial in rural Gambia (MEGAMBO TRIAL).

BACKGROUND: Menstrual health (MH) is a recognised global public health challenge. Poor MH may lead to absence from school and work, and adverse health outcomes. However, reviews suggest a lack of rigorous evidence for the effectiveness of MH interventions on health and education outcomes. The objective of this paper is to describe the methods used in a cluster-randomised controlled trial to estimate the effect of a multi-component intervention to improve MH and school attendance in The Gambia. METHODS: The design ensured half the schools (25) were randomised to receive the intervention which comprised of the following components: (i) Peer education camps and menstrual hygiene laboratories in schools, (ii) Mother's outreach sessions, (iii) Community meetings, and (iv) minor improvements of school Water Sanitation and Hygiene (WASH) facilities and maintenance. The intervention was run over a three-month period, and the evaluation was conducted at least three months after the last intervention activity was completed in the school or community. The other 25 schools acted as controls. Of these 25 control schools one Arabic school dropped out due to COVID-19. The primary outcome was the prevalence of girls missing at least one day of school during their last period. Secondary outcomes included: Urinary Tract Infection (UTI) symptoms, biochemical markers of UTI in urine, Reproductive Tract Infection symptoms, self-reported menstruation related wellbeing, social support and knowledge, perceptions and practices towards menstruation and MH in target school girls. In addition, a process evaluation using observations, routine monitoring data, survey data and interviews was undertaken to assess dose and reach (quantitative data) and assess acceptability, fidelity, context and possible mechanisms of impact (qualitative data). Cost and cost-effectiveness of the intervention package will also be assessed. CONCLUSION: Results will add to scarce resources available on effectiveness of MH interventions on school attendance. A positive result may encourage policy makers to increase their commitment to improve operation and maintenance of school WASH facilities and include more information on menstruation into the curriculum and help in the reporting and management of infections related to adolescent menstruation. Trial Registration PACTR, PACTR201809769868245, Registered 14th August 2018, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3539.

Outcome of COVID-19 infections in patients with adrenal insufficiency and excess.

Background: Information on clinical outcomes of coronavirus disease 19 (COVID-19) infection in patients with adrenal disorders is scarce. Methods: A collaboration between the European Society of Endocrinology (ESE) Rare Disease Committee and European Reference Network on Rare Endocrine Conditions via the European Registries for Rare Endocrine Conditions allowed the collection of data on 64 cases (57 adrenal insufficiency (AI), 7 Cushing's syndrome) that had been reported by 12 centres in 8 European countries between January 2020 and December 2021. Results: Of all 64 patients, 23 were males and 41 females (13 of those children) with a median age of 37 and 51 years. In 45/57 (95%) AI cases, COVID-19 infection was confirmed by testing. Primary insufficiency was present in 45/57 patients; 19 were affected by Addison's disease, 19 by congenital adrenal hyperplasia and 7 by primary AI (PAI) due to other causes. The most relevant comorbidities were hypertension (12%), obesity (n = 14%) and diabetes mellitus (9%). An increase by a median of 2.0 (IQR 1.4) times the daily replacement dose was reported in 42 (74%) patients. Two patients were administered i.m. injection of 100 mg hydrocortisone, and 11/64 were admitted to the hospital. Two patients had to be transferred to the intensive care unit, one with a fatal outcome. Four patients reported persistent SARS-CoV-2 infection, all others complete remission. Conclusion: This European multicentre questionnaire is the first to collect data on the outcome of COVID-19 infection in patients with adrenal gland disorders. It suggests good clinical outcomes in case of duly dose adjustments and emphasizes the importance of patient education on sick day rules.

Significant risk of COVID-19 and related-hospitalization among patients with adrenal insufficiency: A large multinational survey

Objective To determine self-reported incidence and potential risk factors for COVID-19 in patients with adrenal insufficiency (AI). Methods A 27-item AI survey was developed for AI and COVID-19 status, vetted by specialists and patients, and distributed via social media, websites, and advocacy groups. Participation was voluntary and anonymous. Data were collected from September 20th, 2020 until December 31st, 2020. Results Respondents (n=1291) with self-reported glucocorticoid treatment for AI, completed the survey, with 456 who reported having symptoms and were screened for COVID-19 during 2020;40 tested positive (+ve), representing an 8.8% incidence. Of the COVID-19+ve, 31 were female (78%), with mean age of 39.9 years. COVID-19 among AI patients occurred most commonly in those aged 40–59 years (n=17;42.5%);mean time since AI diagnosis was 13.5 years (range 0.2−42.0 years). Pulmonary disease, congenital adrenal hyperplasia, and higher maintenance doses of glucocorticoids were significantly associated with +ve COVID-19 (p=0.04, p=0.01, and p=0.001, respectively. In respondents the cumulative incidence of COVID-19+ve during 2020 was 3.1%;greater than the 1.03% worldwide-incidence reported by WHO, by December 31st, 2020. There was a 3-fold (95% CI 2.16-3.98) greater relative risk (RR) of COVID-19 infection and a 23.8- fold (95% CI 20.7-31.2) RR of hospitalization in patients with AI, compared with the global population. Conclusion A markedly raised RR of COVID-19 and hospitalization in respondents reporting chronic AI was detected. We found that a diagnosis of congenital adrenal hyperplasia, age>40 years, male gender, pulmonary disease, and higher maintenance doses of glucocorticoids were associated with greatest risk.

Costs of hand hygiene for all in household settings: estimating the price tag for the 46 least developed countries.

INTRODUCTION: Domestic hand hygiene could prevent over 500 000 attributable deaths per year, but 6 in 10 people in least developed countries (LDCs) do not have a handwashing facility (HWF) with soap and water available at home. We estimated the economic costs of universal access to basic hand hygiene services in household settings in 46 LDCs. METHODS: Our model combines quantities of households with no HWF and prices of promotion campaigns, HWFs, soap and water. For quantities, we used estimates from the WHO/UNICEF Joint Monitoring Programme. For prices, we collated data from recent impact evaluations and electronic searches. Accounting for inflation and purchasing power, we calculated costs over 2021-2030, and estimated total cost probabilistically using Monte Carlo simulation. RESULTS: An estimated US$12.2-US$15.3 billion over 10 years is needed for universal hand hygiene in household settings in 46 LDCs. The average annual cost of hand hygiene promotion is US$334 million (24% of annual total), with a further US$233 million for 'top-up' promotion (17%). Together, these promotion costs represent US$0.47 annually per head of LDC population. The annual cost of HWFs, a purpose-built drum with tap and stand, is US$174 million (13%). The annual cost of soap is US$497 million (36%) and water US$127 million (9%). CONCLUSION: The annual cost of behavioural change promotion to those with no HWF represents 4.7% of median government health expenditure in LDCs, and 1% of their annual aid receipts. These costs could be covered by mobilising resources from across government and partners, and could be reduced by harnessing economies of scale and integrating hand hygiene with other behavioural change campaigns where appropriate. Innovation is required to make soap more affordable and available for the poorest households.

Risk factors for COVID-19 hospitalisation and death in people living with diabetes: A virtual cohort study from the Western Cape Province, South Africa.

BACKGROUND: COVID-19 outcomes and risk factors, including comorbidities and medication regimens, in people living with diabetes (PLWD) are poorly defined for low- and middle-income countries. METHODS: The Provincial Health Data Centre (Western Cape, South Africa) is a health information exchange collating patient-level routine health data for approximately 4 million public sector health care seekers. Data from COVID-19 patients diagnosed between March and July 2020, including PLWD, were analysed to describe risk factors, including dispensed diabetes medications and comorbidities, and their association with COVID-19 outcomes in this population. FINDINGS: There were 64,476 COVID-19 patients diagnosed. Of 9305 PLWD, 44.9% were hospitalised, 4.0% admitted to ICU, 0.6% received ventilation and 15.4% died. In contrast, proportions of COVID-19 patients without diabetes were: 12.2% hospitalised, 1.0% admitted, 0.1% ventilated and 4.6% died. PLWD were significantly more likely to be admitted (OR:3.73, 95 %CI: 3.53, 3.94) and to die (OR:3.01, 95 %CI: 2.76,3.28). Significant hospitalised risk factors included HIV infection, chronic kidney disease, current TB, male sex and increasing age. Significant risk factors for mortality were CKD, male sex, HIV infection, previous TB and increasing age. Pre-infection use of insulin was associated with a significant increased risk for hospitalisation (OR:1·39, 95 %CI:1·24,1·57) and mortality (OR1·49, 95 %CI:1·27; 1·74) and metformin was associated with a reduced risk for hospitalisation (OR:0·62,95 %CI:0·55, 0·71) and mortality (OR 0·77, 95 %CI:0·64; 0·92). INTERPRETATION: Using routine health data from this large virtual cohort, we have described the association of infectious and noncommunicable comorbidities as well as pre-infection diabetes medications with COVID-19 outcomes in PLWD in the Western Cape, South Africa. FUNDING: This research was funded in part, by the Wellcome Trust 203135/Z/16/Z, through support of NT. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The Wellcome Centre for Infectious Diseases Research in Africa is supported by core funding from the Wellcome Trust [203135/Z/16/Z]. NT receives funding from the CIDRI-Africa Wellcome Trust grant (203135/Z/16/Z), and NT and TT receive funding from the NIH H3ABioNET award (U24HG006941). NT receives funding from the UKRI/MRC (MC_PC_MR/T037733/1).