Cost-Effectiveness of Monovalent Rotavirus Vaccination of Infants in Malawi: A Postintroduction Analysis Using Individual Patient-Level Costing Data.

Background. Rotavirus vaccination reduces childhood hospitalization in Africa, but cost-effectiveness has not been determined using real-world effectiveness and costing data. We sought to determine monovalent rotavirus vaccine cost-effectiveness in Malawi, one of Africa's poorest countries and the first Gavi-eligible country to report disease reduction following introduction in 2012. Methods. This was a prospective cohort study of children with acute gastroenteritis at a rural primary health center, a rural first referral–level hospital and an urban regional referral hospital in Malawi. For each participant we itemized household costs of illness and direct medical expenditures incurred. We also collected Ministry of Health vaccine implementation costs. Using a standard tool (TRIVAC), we derived cost-effectiveness. Results. Between 1 January 2013 and 21 November 2014, we recruited 530 children aged <5 years with gastroenteritis. Costs did not differ by rotavirus test result, but were significantly higher for admitted children and those with increased severity on Vesikari scale. Adding rotavirus vaccine to the national schedule costs Malawi $0.42 per dose in system costs. Vaccine copayment is an additional$0.20. Over 20 years, the vaccine program will avert 1 026 000 cases of rotavirus gastroenteritis, 78 000 inpatient admissions, 4300 deaths, and 136 000 disability-adjusted-life-years (DALYs). For this year's birth cohort, it will avert 54 000 cases of rotavirus and 281 deaths in children aged <5 years. The program will cost $10.5 million and save$8.0 million in averted healthcare costs. Societal cost per DALY averted was $10, and the cost per rotavirus case averted was$1. Conclusions. Gastroenteritis causes substantial economic burden to Malawi. The rotavirus vaccine program is highly cost-effective. Together with the demonstrated impact of rotavirus vaccine in reducing population hospitalization burden, its cost-effectiveness makes a strong argument for widespread utilization in other low-income, high-burden settings

Recruitment strategies used to enrol healthy volunteers in the first pneumococcal human infection study in Africa: Lessons from Blantyre, Malawi

Background Human infection studies (HIS) also known as Controlled Human Infection Models (CHIM) are a relatively new concept in African countries to clinicians, scientists, and communities alike. We have introduced HIS/CHIM studies to Malawi during the last four years by developing an experimental human pneumococcal carriage model. This CHIM was used to test the efficacy of a licensed 13-valent Pneumococcal Conjugate Vaccine (PCV13) against experimental nasal pneumococcal carriage. Traditional and digital recruitment strategies into this novel trial were explored. Objectives To describe various methods of recruitment in this first CHIM study in Malawi. Methods The clinical trial within the context of which these data were recorded was registered with the Pan African Clinical Trials Registry (REF: PACTR202008503507113) on 03 August 2020. The project was conducted at the Malawi Liverpool Wellcome Programme (MLW) in Blantyre, Malawi between April 2021, and September 2022. Source populations were college students and community members within Blantyre. Recruitment strategies included sharing study information in written or visual form, community sensitization meetings, snowball contacts (word of mouth from previous volunteers), branded clothing and participating in radio and television programs. Results 299 volunteers attended screening clinic, of whom 278 were recruited. Sixty-six recruited volunteers (23.7%) were college students and 212 (76.3%) were from the community. Snowball word-of-mouth contacting was the most successful recruitment strategy, with 201 (72.3%) participants recruited using this method. 195 (70.1%) were men of whom 149 (76.4%) joined the study through snowballing. Conclusion or recommendation Using a variety of recruitment strategies led to successful recruitment in this novel controlled human infection study. Most participants were recruited through snowballing

Determinants of survival in very low birth weight neonates in a public sector hospital in Johannesburg

<p>Abstract</p> <p>Background</p> <p>Audit of disease and mortality patterns provides essential information for health budgeting and planning, as well as a benchmark for comparison. Neonatal mortality accounts for about 1/3 of deaths < 5 years of age and very low birth weight (VLBW) mortality for approximately 1/3 of neonatal mortality. Intervention programs must be based on reliable statistics applicable to the local setting; First World data cannot be used in a Third World setting. Many neonatal units participate in the Vermont Oxford Network (VON); limited resources prevent a significant number of large neonatal units from developing countries taking part, hence data from such units is lacking. The purpose of this study was to provide reliable, recent statistics relevant to a developing African country, useful for guiding neonatal interventions in that setting.</p> <p>Methods</p> <p>This was a retrospective chart review of 474 VLBW infants admitted within 24 hours of birth, between 1 July 2006 and 30 June 2007, to the neonatal unit of Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in Johannesburg, South Africa. Binary outcome logistic regression on individual variables and multiple logistic regression was done to identify those factors determining survival.</p> <p>Results</p> <p>Overall survival was 70.5%. Survival of infants below 1001 grams birth weight was 34.9% compared to 85.8% for those between 1001 and 1500 grams at birth. The main determinant of survival was birth weight with an adjusted survival odds ratio of 23.44 (95% CI: 11.22 - 49.00) for babies weighing between 1001 and 1500 grams compared to those weighing below 1001 grams. Other predictors of survival were gender (OR 3. 21; 95% CI 1.6 - 6.3), birth before arrival at the hospital (BBA) (OR 0.23; 95% CI: 0.08 - 0.69), necrotising enterocolitis (NEC) (OR 0.06; 95% CI: 0.02 - 0.20), hypotension (OR 0.05; 95% CI 0.01 - 0.21) and nasal continuous positive airways pressure (NCPAP) (OR 4.58; 95% CI 1.58 - 13.31).</p> <p>Conclusions</p> <p>Survival rates compare favourably with other developing countries, but can be improved; especially in infants < 1001 grams birth weight. Resources need to be allocated to preventing the birth of VLBW babies outside hospital, early neonatal resuscitation, provision of NCPAP and prevention of NEC.</p

Piloting electronic informed consenting in a pneumococcal human infection study in Blantyre, Malawi

Background Electronic consent can potentially improve accuracy, workflow, and overall patient experience in clinical research but has not been used in Malawi, owing to uncertainty about data security and technical support. Objectives We explored the feasibility of using electronic consent (e-consent) in an ongoing human infection study in Blantyre Malawi. We dual-consented participants by both electronic and paper methods to assess the feasibility of electronic consent, and then compared benefits and challenges of the two methods. Methods The approved paper consent forms were digitized using Open Data Kit (ODK). Following participant information giving by the research staff, healthy literate adult participants with no audio-visual impairments completed a self-administered e-consent and provided an electronic signature. Signed e-consent forms were uploaded to a secure study server. While the participants were in clinic, the signed electronic consent form was printed as a copy for the participant. The feasibility, advantages and disadvantages including data safety consideration for e-consenting were evaluated by exploring issues surrounding use of e-consenting versus paper-based consenting. Consent forms were analysed by research staff for errors such as overwriting and legibility. Results We piloted 109 participants to e-consenting. It was found to be user friendly, had 0% (n 0/109) errors compared to 43.1% (n 47/109) in paper based methods along with enhanced data safety. The challenges included difficult digitization of ethics stamped documents, volunteer unfamiliarity with tablet user interface and its requirement for a working internet and printer. Conclusion E-consenting was feasible but required additional resource investment. Benefits included error minimization and data security

Practical considerations for a TB controlled human infection model (TB-CHIM); the case for TB-CHIM in Africa, a systematic review of the literature and report of 2 workshop discussions in UK and Malawi

Background: Tuberculosis (TB) remains a major challenge in many domains including diagnosis, pathogenesis, prevention, treatment, drug resistance and long-term protection of the public health by vaccination. A controlled human infection model (CHIM) could potentially facilitate breakthroughs in each of these domains but has so far been considered impossible owing to technical and safety concerns. Methods: A systematic review of mycobacterial human challenge studies was carried out to evaluate progress to date, best possible ways forward and challenges to be overcome. We searched MEDLINE (1946 to current) and CINAHL (1984 to current) databases; and Google Scholar to search citations in selected manuscripts. The final search was conducted 3rd February 2022. Inclusion criteria: adults ≥18 years old; administration of live mycobacteria; and interventional trials or cohort studies with immune and/or microbiological endpoints. Exclusion criteria: animal studies; studies with no primary data; no administration of live mycobacteria; retrospective cohort studies; case-series; and case-reports. Relevant tools (Cochrane Collaboration for RCTs and Newcastle-Ottawa Scale for non-randomised studies) were used to assess risk of bias and present a narrative synthesis of our findings. Results: The search identified 1,388 titles for review; of these 90 were reviewed for inclusion; and 27 were included. Of these, 15 were randomised controlled trials and 12 were prospective cohort studies. We focussed on administration route, challenge agent and dose administered for data extraction. Overall, BCG studies including fluorescent BCG show the most immediate utility, and genetically modified Mycobacteria tuberculosis is the most tantalising prospect of discovery breakthrough. Conclusions: The TB-CHIM development group met in 2019 and 2022 to consider the results of the systematic review, to hear presentations from many of the senior authors whose work had been reviewed and to consider best ways forward. This paper reports both the systematic review and the deliberations

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Practical considerations for a TB controlled human infection model (TB-CHIM); the case for TB-CHIM in Africa, a systematic review of the literature and report of 2 workshop discussions in UK and Malawi [version 1; peer review: 2 approved, 1 approved with reservations]

Background: Tuberculosis (TB) remains a major challenge in many domains including diagnosis, pathogenesis, prevention, treatment, drug resistance and long-term protection of the public health by vaccination. A controlled human infection model (CHIM) could potentially facilitate breakthroughs in each of these domains but has so far been considered impossible owing to technical and safety concerns. Methods: A systematic review of mycobacterial human challenge studies was carried out to evaluate progress to date, best possible ways forward and challenges to be overcome. We searched MEDLINE (1946 to current) and CINAHL (1984 to current) databases; and Google Scholar to search citations in selected manuscripts. The final search was conducted 3rd February 2022. Inclusion criteria: adults ≥18 years old; administration of live mycobacteria; and interventional trials or cohort studies with immune and/or microbiological endpoints. Exclusion criteria: animal studies; studies with no primary data; no administration of live mycobacteria; retrospective cohort studies; case-series; and case-reports. Relevant tools (Cochrane Collaboration for RCTs and Newcastle-Ottawa Scale for non-randomised studies) were used to assess risk of bias and present a narrative synthesis of our findings. Results: The search identified 1,388 titles for review; of these 90 were reviewed for inclusion; and 27 were included. Of these, 15 were randomised controlled trials and 12 were prospective cohort studies. We focussed on administration route, challenge agent and dose administered for data extraction. Overall, BCG studies including fluorescent BCG show the most immediate utility, and genetically modified Mycobacteria tuberculosis is the most tantalising prospect of discovery breakthrough. Conclusions: The TB-CHIM development group met in 2019 and 2022 to consider the results of the systematic review, to hear presentations from many of the senior authors whose work had been reviewed and to consider best ways forward. This paper reports both the systematic review and the deliberations. Registration: PROSPERO (CRD42022302785; 21 January 2022)