Increasing the uptake of Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP) through seasonal malaria chemoprevention channel delivery: protocol of a multicenter cluster randomized implementation trial in Mali and Burkina Faso.

BACKGROUND: The uptake of Intermittent Preventive Treatment of malaria in pregnancy using Sulfadoxine-Pyrimethamine (IPTp-SP) remains unacceptably low, with more than two-thirds of pregnant women in sub-Saharan Africa still not accessing the three or more doses recommended by the World Health Organisation (WHO). In contrast, the coverage of Seasonal Malaria Chemoprevention (SMC), a more recent strategy recommended by the WHO for malaria prevention in children under five years living in Sahelian countries with seasonal transmission, including Mali and Burkina-Faso, is high (up to 90%). We hypothesized that IPTp-SP delivery to pregnant women through SMC alongside antenatal care (ANC) will increase IPTp-SP coverage, boost ANC attendance, and increase public health impact. This protocol describes the approach to assess acceptability, feasibility, effectiveness, and cost-effectiveness of the integrated strategy. METHODS AND ANALYSIS: This is a multicentre, cluster-randomized, implementation trial of IPTp-SP delivery through ANC + SMC vs ANC alone in 40 health facilities and their catchment populations (20 clusters per arm). The intervention will consist of monthly administration of IPTp-SP through four monthly rounds of SMC during the malaria transmission season (July to October), for two consecutive years. Effectiveness of the strategy to increase coverage of three or more doses of IPTp-SP (IPTp3 +) will be assessed using household surveys and ANC exit interviews. Statistical analysis of IPT3 + and four or more ANC uptake will use a generalized linear mixed model. Feasibility and acceptability will be assessed through in-depth interviews and focus group discussions with health workers, pregnant women, and women with a child < 12 months. DISCUSSION: This multicentre cluster randomized implementation trial powered to detect a 45% and 22% increase in IPTp-SP3 + uptake in Mali and Burkina-Faso, respectively, will generate evidence on the feasibility, acceptability, effectiveness, and cost-effectiveness of IPTp-SP delivered through the ANC + SMC channel. The intervention is designed to facilitate scalability and translation into policy by leveraging existing resources, while strengthening local capacities in research, health, and community institutions. Findings will inform the local national malaria control policies. TRIAL REGISTRATION: Retrospectively registered on August 11th, 2022; registration # PACTR202208844472053. Protocol v4.0 dated September 04, 2023. Trail sponsor: University of Sciences Techniques and Technologies of Bamako (USTTB), Mali.

Cost and quality of operational larviciding using drones and smartphone technology.

BACKGROUND: Larval Source Management (LSM) is an important tool for malaria vector control and is recommended by WHO as a supplementary vector control measure. LSM has contributed in many successful attempts to eliminate the disease across the Globe. However, this approach is typically labour-intensive, largely due to the difficulties in locating and mapping potential malarial mosquito breeding sites. Previous studies have demonstrated the potential for drone imaging technology to map malaria vector breeding sites. However, key questions remain unanswered related to the use and cost of this technology within operational vector control. METHODS: Using Zanzibar (United Republic of Tanzania) as a demonstration site, a protocol was collaboratively designed that employs drones and smartphones for supporting operational LSM, termed the Spatial Intelligence System (SIS). SIS was evaluated over a four-month LSM programme by comparing key mapping accuracy indicators and relative costs (both mapping costs and intervention costs) against conventional ground-based methods. Additionally, malaria case incidence was compared between the SIS and conventional study areas, including an estimation of the incremental cost-effectiveness of switching from conventional to SIS larviciding. RESULTS: The results demonstrate that the SIS approach is significantly more accurate than a conventional approach for mapping potential breeding sites: mean % correct per site: SIS = 60% (95% CI 32-88%, p = 0.02), conventional = 18% (95% CI - 3-39%). Whilst SIS cost more in the start-up phase, overall annualized costs were similar to the conventional approach, with a simulated cost per person protected per year of $3.69 ($0.32 to $15.12) for conventional and $3.94 ($0.342 to $16.27) for SIS larviciding. The main economic benefits were reduced labour costs associated with SIS in the pre-intervention baseline mapping of habitats. There was no difference in malaria case incidence between the three arms. Cost effectiveness analysis showed that SIS is likely to provide similar health benefits at similar costs compared to the conventional arm. CONCLUSIONS: The use of drones and smartphones provides an improved means of mapping breeding sites for use in operational LSM. Furthermore, deploying this technology does not appear to be more costly than a conventional ground-based approach and, as such, may represent an important tool for Malaria Control Programmes that plan to implement LSM.

Cost of digital technologies and family-observed DOT for a shorter MDR-TB regimen: a modelling study in Ethiopia, India and Uganda.

BACKGROUND: In 2017, the WHO recommended the use of digital technologies, such as medication monitors and video observed treatment (VOT), for directly observed treatment (DOT) of drug-susceptible TB. The WHO's 2020 guidelines extended these recommendations to multidrug-resistant tuberculosis (MDR-TB), based on low evidence. The impact of COVID on health systems and patients underscored the need to use digital technologies in the management of MDR-TB. METHODS: A decision-tree model was developed to explore the costs of several potential DOT alternatives: VOT, 99DOTS (Directly-observed Treatment, Short-course) and family-observed DOT. Assuming a 9-month, all-oral regimen (as evaluated within the STREAM trial), we constructed base-case cost models for the standard-of-care DOTs in Ethiopia, India, and Uganda, as well as for the three alternative DOT approaches. The models were populated with STREAM Stage 2 clinical trial outcome and cost data, supplemented with market prices data for the digital DOT strategies. Sensitivity analyses were conducted on key parameters. RESULTS: Modelling suggested that the standard-of-care DOT approach is the most expensive DOT strategy from a societal perspective in all three countries evaluated (Ethiopia, India, Uganda), with considerable direct- and indirect-costs incurred by patients. The second most expensive DOT approach is VOT, with high health-system costs, largely caused by up-front technology expenditure. Each of VOT, 99DOTS and family-observed DOT would reduce by more than 90% patients' direct and indirect costs compared to standard of care DOT. Results were robust to the sensitivity analyses. CONCLUSIONS: While data on the costs and efficacy of alternative DOT approaches in the context of shorter MDR-TB treatment is limited, our modelling suggests alternative DOT approaches can significantly reduce patient costs in all three countries. Health system costs are higher for VOT and lower for 99DOTS and family-observed therapy when compared to standard of care DOT, as low smartphone penetration and internet availability requires the VOT health system to fund the cost of making them available to patients.

Impact and cost-effectiveness of a lethal house lure against malaria transmission in central Côte d'Ivoire: a two-arm, cluster-randomised controlled trial.

BACKGROUND: New vector control tools are required to sustain the fight against malaria. Lethal house lures, which target mosquitoes as they attempt to enter houses to blood feed, are one approach. Here we evaluated lethal house lures consisting of In2Care (Wageningen, Netherlands) Eave Tubes, which provide point-source insecticide treatments against host-seeking mosquitoes, in combination with house screening, which aims to reduce mosquito entry. METHODS: We did a two-arm, cluster-randomised controlled trial with 40 village-level clusters in central Côte d'Ivoire between Sept 26, 2016, and April 10, 2019. All households received new insecticide-treated nets at universal coverage (one bednet per two people). Suitable households within the clusters assigned to the treatment group were offered screening plus Eave Tubes, with Eave Tubes treated using a 10% wettable powder formulation of the pyrethroid ß-cyfluthrin. Because of the nature of the intervention, treatment could not be masked for households and field teams, but all analyses were blinded. The primary endpoint was clinical malaria incidence recorded by active case detection over 2 years in cohorts of children aged 6 months to 10 years. This trial is registered with ISRCTN, ISRCTN18145556. FINDINGS: 3022 houses received screening plus Eave Tubes, with an average coverage of 70% across the intervention clusters. 1300 eligible children were recruited for active case detection in the control group and 1260 in the intervention group. During the 2-year follow-up period, malaria case incidence was 2·29 per child-year (95% CI 1·97-2·61) in the control group and 1·43 per child-year (1·21-1·65) in the intervention group (hazard ratio 0·62, 95% CI 0·51-0·76; p<0·0001). Cost-effectiveness simulations suggested that screening plus Eave Tubes has a 74·0% chance of representing a cost-effective intervention, compared with existing healthcare activities in Côte d'Ivoire, and is similarly cost-effective to other core vector control interventions across sub-Saharan Africa. No serious adverse events associated with the intervention were reported during follow-up. INTERPRETATION: Screening plus Eave Tubes can provide protection against malaria in addition to the effects of insecticide-treated nets, offering potential for a new, cost-effective strategy to supplement existing vector control tools. Additional trials are needed to confirm these initial results and further optimise Eave Tubes and the lethal house lure concept to facilitate adoption. FUNDING: The Bill & Melinda Gates Foundation.

Conditional trust: Community perceptions of drone use in malaria control in Zanzibar.

Background: The potential of drones to support public health interventions, such as malaria vector control, is beginning to be realised. Although permissions from civil aviation authorities are often needed for drone operations, the communities over which they fly tend to be ignored: How do affected communities perceive drones? Is drone deployment accepted by communities? How should communities be engaged? Methods: An initiative in Zanzibar, United Republic of Tanzania is using drones to map malarial mosqutio breeding sites for targeting larval source management interventions. A community engagement framework was developed, based on participatory research, across three communities where drones will be deployed, to map local perceptions of drone use. Costs associated with this exercise were collated. Results: A total of 778 participants took part in the study spanning a range of community and stakeholder groups. Overall there was a high level of acceptance and trust in drone use for public health research purposes. Despite this level of trust for drone operations this support was conditional: There was a strong desire for pre-deployment information across all stakeholder groups and regular updates of this information to be given about drone activities, as well as consent from community level governance. The cost of the perception study and resulting engagement strategy was US$24,411. Conclusions: Mapping and responding to community perceptions should be a pre-requisite for drone activity in all public health applications and requires funding. The findings made in this study were used to design a community engagement plan providing a simple but effective means of building and maintaining trust and acceptability. We recommend this an essential investment.

Cost of community-led larval source management and house improvement for malaria control: a cost analysis within a cluster-randomized trial in a rural district in Malawi.

BACKGROUND: House improvement (HI) to prevent mosquito house entry, and larval source management (LSM) targeting aquatic mosquito stages to prevent development into adult forms, are promising complementary interventions to current malaria vector control strategies. Lack of evidence on costs and cost-effectiveness of community-led implementation of HI and LSM has hindered wide-scale adoption. This study presents an incremental cost analysis of community-led implementation of HI and LSM, in a cluster-randomized, factorial design trial, in addition to standard national malaria control interventions in a rural area (25,000 people), in southern Malawi. METHODS: In the trial, LSM comprised draining, filling, and Bacillus thuringiensis israelensis-based larviciding, while house improvement (henceforth HI) involved closing of eaves and gaps on walls, screening windows/ventilation spaces with wire mesh, and doorway modifications. Communities implemented all interventions. Costs were estimated retrospectively using the 'ingredients approach', combining 'bottom-up' and 'top-down approaches', from the societal perspective. To estimate the cost of independently implementing each intervention arm, resources shared between trial arms (e.g. overheads) were allocated to each consuming arm using proxies developed based on share of resource input quantities consumed. Incremental implementation costs (in 2017 US$) are presented for HI-only, LSM-only and HI + LSM arms. In sensitivity analyses, the effect of varying costs of important inputs on estimated costs was explored. RESULTS: The total economic programme costs of community-led HI and LSM implementation was $626,152. Incremental economic implementation costs of HI, LSM and HI + LSM were estimated as $27.04, $25.06 and $33.44, per person per year, respectively. Project staff, transport and labour costs, but not larvicide or screening material, were the major cost drivers across all interventions. Costs were sensitive to changes in staff costs and population covered. CONCLUSIONS: In the trial, the incremental economic costs of community-led HI and LSM implementation were high compared to previous house improvement and LSM studies. Several factors, including intervention design, year-round LSM implementation and low human population density could explain the high costs. The factorial trial design necessitated use of proxies to allocate costs shared between trial arms, which limits generalizability where different designs are used. Nevertheless, costs may inform planners of similar intervention packages where cost-effectiveness is known. Trial registration Not applicable. The original trial was registered with The Pan African Clinical Trials Registry on 3 March 2016, trial number PACTR201604001501493.

Risk factors associated with house entry of malaria vectors in an area of Burkina Faso with high, persistent malaria transmission and high insecticide resistance.

BACKGROUND: In rural Burkina Faso, the primary malaria vector Anopheles gambiae sensu lato (s.l.) primarily feeds indoors at night. Identification of factors which influence mosquito house entry could lead to development of novel malaria vector control interventions. A study was therefore carried out to identify risk factors associated with house entry of An. gambiae s.l. in south-west Burkina Faso, an area of high insecticide resistance. METHODS: Mosquitoes were sampled monthly during the malaria transmission season using CDC light traps in 252 houses from 10 villages, each house sleeping at least one child aged five to 15 years old. Potential risk factors for house entry of An. gambiae s.l. were measured, including socio-economic status, caregiver's education and occupation, number of people sleeping in the same part of the house as the child, use of anti-mosquito measures, house construction and fittings, proximity of anopheline aquatic habitats and presence of animals near the house. Mosquito counts were compared using a generalized linear mixed-effect model with negative binomial and log link function, adjusting for repeated collections. RESULTS: 20,929 mosquitoes were caught, of which 16,270 (77.7%) were An. gambiae s.l. Of the 6691 An. gambiae s.l. identified to species, 4101 (61.3%) were An. gambiae sensu stricto and 2590 (38.7%) Anopheles coluzzii. Having a metal-roof on the child's sleeping space (IRR = 0.55, 95% CI 0.32-0.95, p = 0.03) was associated with fewer malaria vectors inside the home. CONCLUSION: This study demonstrated that the rate of An. gambiae s.l. was 45% lower in sleeping spaces with a metal roof, compared to those with thatch roofs. Improvements in house construction, including installation of metal roofs, should be considered in endemic areas of Africa to reduce the burden of malaria.

Socio-protective effects of active case finding on catastrophic costs from tuberculosis in Ho Chi Minh City, Viet Nam: a longitudinal patient cost survey.

BACKGROUND: Many tuberculosis (TB) patients incur catastrophic costs. Active case finding (ACF) may have socio-protective properties that could contribute to the WHO End TB Strategy target of zero TB-affected families suffering catastrophic costs, but available evidence remains limited. This study measured catastrophic cost incurrence and socioeconomic impact of an episode of TB and compared those socioeconomic burdens in patients detected by ACF versus passive case finding (PCF). METHODS: This cross-sectional study fielded a longitudinal adaptation of the WHO TB patient cost survey alongside an ACF intervention from March 2018 to March 2019. The study was conducted in six intervention (ACF) districts and six comparison (PCF) districts of Ho Chi Minh City, Viet Nam. Fifty-two TB patients detected through ACF and 46 TB patients in the PCF cohort were surveyed within two weeks of treatment initiation, at the end of the intensive phase of treatment, and after treatment concluded. The survey measured income, direct and indirect costs, and socioeconomic impact based on which we calculated catastrophic cost as the primary outcome. Local currency was converted into US$ using the average exchange rates reported by OANDA for the study period (VND1 = US$0.0000436, 2018-2019). We fitted logistic regressions for comparisons between the ACF and PCF cohorts as the primary exposures and used generalized estimating equations to adjust for autocorrelation. RESULTS: ACF patients were poorer than PCF patients (multidimensional poverty ratio: 16 % vs. 7 %; p = 0.033), but incurred lower median pre-treatment costs (US$18 vs. US$80; p < 0.001) and lower median total costs (US$279 vs. US$894; p < 0.001). Fewer ACF patients incurred catastrophic costs (15 % vs. 30 %) and had lower odds of catastrophic cost (aOR = 0.17; 95 % CI: [0.05, 0.67]; p = 0.011), especially during the intensive phase (OR = 0.32; 95 % CI: [0.12, 0.90]; p = 0.030). ACF patient experienced less social exclusion (OR = 0.41; 95 % CI: [0.18, 0.91]; p = 0.030), but more often resorted to financial coping mechanisms (OR = 5.12; 95 % CI: [1.73, 15.14]; p = 0.003). CONCLUSIONS: ACF can be effective in reaching vulnerable populations and mitigating the socioeconomic burden of TB, and can contribute to achieving the WHO End TB Strategy goals. Nevertheless, as TB remains a catastrophic life event, social protection efforts must extend beyond ACF.

A cohort study to identify risk factors for Plasmodium falciparum infection in Burkinabe children: implications for other high burden high impact countries.

BACKGROUND: Progress in controlling malaria has stalled in recent years. Today the malaria burden is increasingly concentrated in a few countries, including Burkina Faso, where malaria is not declining. A cohort study was conducted to identify risk factors for malaria infection in children in southwest Burkina Faso, an area with high insecticide-treated net (ITN) coverage and insecticide-resistant vectors. METHODS: Incidence of Plasmodium falciparum infection was measured in 252 children aged 5 to 15 years, using active and passive detection, during the 2017 transmission season, following clearance of infection. Demographic, socio-economic, environmental, and entomological risk factors, including use of ITNs and insecticide resistance were monitored. RESULTS: During the six-month follow-up period, the overall incidence of P. falciparum infection was 2.78 episodes per child (95% CI = 2.66-2.91) by microscopy, and 3.11 (95% CI = 2.95-3.28) by polymerase chain reaction (PCR). The entomological inoculation rate (EIR) was 80.4 infective bites per child over the six-month malaria transmission season. At baseline, 80.6% of children were reported as sleeping under an ITN the previous night, although at the last survey, 23.3% of nets were in poor condition and considered no longer protective. No association was found between the rate of P. falciparum infection and either EIR (incidence rate ratio (IRR): 1.00, 95% CI: 1.00-1.00, p = 0.08) or mortality in WHO tube tests when vectors were exposed to 0.05% deltamethrin (IRR: 1.05, 95% CI: 0.73-1.50, p = 0.79). Travel history (IRR: 1.52, 95% CI: 1.45-1.59, p < 0.001) and higher socio-economic status were associated with an increased risk of P. falciparum infection (IRR: 1.05, 95% CI: 1.00-1.11, p = 0.04). CONCLUSIONS: Incidence of P. falciparum infection remains overwhelmingly high in the study area. The study findings suggest that because of the exceptionally high levels of malaria transmission in the study area, malaria elimination cannot be achieved solely by mass deployment of ITNs and additional control measures are needed.

Coverage outcomes (effects), costs, cost-effectiveness, and equity of two combinations of long-lasting insecticidal net (LLIN) distribution channels in Kenya: a two-arm study under operational conditions.

BACKGROUND: Malaria-endemic countries distribute long-lasting insecticidal nets (LLINs) through combined channels with ambitious, universal coverage (UC) targets. Kenya has used eight channels with variable results. To inform national decision-makers, this two-arm study compares coverage (effects), costs, cost-effectiveness, and equity of two combinations of LLIN distribution channels in Kenya. METHODS: Two combinations of five delivery channels were compared as 'intervention' and 'control' arms. The intervention arm comprised four channels: community health volunteer (CHV), antenatal and child health clinics (ANCC), social marketing (SM) and commercial outlets (CO). The control arm consisted of the intervention arm channels except mass campaign (MC) replaced CHV. Primary analysis used random sample household survey data, service-provider costs, and voucher or LLIN distribution data to compare between-arm effects, costs, cost-effectiveness, and equity. Secondary analyses compared costs and equity by channel. RESULTS: The multiple distribution channels used in both arms of the study achieved high LLIN ownership and use. The intervention arm had significantly lower reported LLIN use the night before the survey (84·8% [95% CI 83·0-86·4%] versus 89·2% [95% CI 87·8-90·5%], p < 0·0001), higher unit costs ($10·56 versus $7·17), was less cost-effective ($86·44, 95% range $75·77-$102·77 versus $69·20, 95% range $63·66-$77·23) and more inequitable (Concentration index [C.Ind] = 0·076 [95% CI 0·057 to 0·095 versus C.Ind = 0.049 [95% CI 0·030 to 0·067]) than the control arm. Unit cost per LLIN distributed was lowest for MC ($3·10) followed by CHV ($10·81) with both channels being moderately inequitable in favour of least-poor households. CONCLUSION: In line with best practices, the multiple distribution channel model achieved high LLIN ownership and use in this Kenyan study setting. The control-arm combination, which included MC, was the most cost-effective way to increase UC at household level. Mass campaigns, combined with continuous distribution channels, are an effective and cost-effective way to achieve UC in Kenya. The findings are relevant to other countries and donors seeking to optimise LLIN distribution. TRIAL REGISTRATION: The assignment of the intervention was not at the discretion of the investigators; therefore, this study did not require registration.

Evaluating the impact of screening plus eave tubes on malaria transmission compared to current best practice in central Côte d'Ivoire: a two armed cluster randomized controlled trial.

BACKGROUND: Access to long-lasting insecticidal nets (LLINs) has increased and malaria has decreased globally, but malaria transmission remains high in parts of sub-Saharan Africa and insecticide resistance threatens current progress. Eave tubes are a new tool for the targeted delivery of insecticides against mosquitoes attempting to enter houses. The primary objective of this trial is to test whether screening plus eave tubes (SET) provides protection against malaria, on top of universal coverage with LLINs in an area of intense pyrethroid resistance. The trial will also assess acceptability and cost-effectiveness of the intervention. METHODS/DESIGN: A two-armed, cluster randomized controlled trial will be conducted to evaluate the effect of SET on clinical malaria incidence in children living in central Côte d'Ivoire. Forty villages will be selected based on population size and the proportion of houses suitable for modification with SET. Using restricted randomization, half the villages will be assigned to the treatment arm (SET + LLINs) and the remainder will be assigned to the control arm (LLINs only). In both arms, LLINs will be distributed and in the treatment arm, householders will be offered SET. Fifty children aged six months to eight years old will be enrolled from randomly selected households in each of the 40 villages. Cohorts will be cleared of malaria parasites at the start of the study and one year after recruitment, and will be monitored for clinical malaria case incidence by active case detection over two years. Mosquito densities will be assessed using CDC light traps and human landing catches and a subset of Anopheles mosquitoes will be examined for parity status and tested for sporozoite infection. Acceptability of SET will be monitored using surveys and focus groups. Cost-effectiveness analysis will measure the incremental cost per case averted and per disability-adjusted life year (DALY) averted of adding SET to LLINs. Economic and financial costs will be estimated from societal and provider perspective using standard economic evaluation methods. DISCUSSION: This study will be the first evaluation of the epidemiological impact of SET. Trial findings will show whether SET is a viable, cost-effective technology for malaria control in Côte d'Ivoire and possibly elsewhere. TRIAL REGISTRATION: ISRCTN18145556 , registered on 01 February 2017 - retrospectively registered.

Community-based strategies to increase coverage of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine in sub-Saharan Africa: a systematic review, meta-analysis, meta-ethnography, and economic assessment.

BACKGROUND: Community-based approaches might increase uptake of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). We assessed the effects of community-based approaches on IPTp-SP and antenatal care coverage, and barriers and facilitators to implementation in sub-Saharan Africa. METHODS: We did a systematic review, meta-analysis, meta-ethnography, and economic assessment. We searched the WHO International Clinical Trials Registry Platform, PubMed, the Malaria in Pregnancy Library database, Medline, Global Health and Global Health Archives, and the Cochrane Library for trials, mixed-methods, qualitative, and cost-effectiveness studies of community health worker promotion of antenatal care, IPTp-SP delivery, or both, with no language restrictions, published before March 21, 2024. Information on interventions, number of IPTp-SP doses, antenatal care visits, and barriers and facilitators were extracted. We did a meta-analysis (random effects) comparing effects on two or more or three or more IPTp-SP doses and one or more or four or more antenatal care visits. We followed Noblit and Hare's method of meta-ethnography to synthesise qualitative findings, using reciprocal translation and line-of-argument synthesis. We developed a theory for increased community IPTp-SP uptake. We also summarised cost and cost-effectiveness studies. This study is registered with PROSPERO, CRD42022364114. FINDINGS: Of 4753 records screened, we included 23 (0·5%) reporting on 15 studies. Community health worker involvement was associated with an increase in two or more IPTp-SP doses (pooled risk ratio 1·48, [95% CI 1·24-1·75]; 12 sub-studies; I2 94·7%) and three or more IPTp-SP doses (1·73 [1·19-2·50]; ten sub-studies, I2 97·5%), with no decrease in four or more antenatal care visits (1·17 [1·00-1·36]; 13 sub-studies; I2 90·3%). Cluster-randomised controlled trials showed a lower increase in coverage of three or more IPTp-SP doses (1·08 [1·00-1·16]; I2 0·0%; six studies) compared with before-and-after studies (2·86 [1·29-6·33]; I2 98·9%; four studies; subgroup analysis p=0·019). Barriers to community health worker delivery of IPTp-SP included women's fear of side-effects, lack of knowledge, lack of trust in community health workers, and sociocultural factors. Community sensitisation, engagement of husbands, pre-established community health worker networks, and trained and supported community health workers facilitated IPTp-SP delivery by community health workers. Incremental cost-effectiveness ratios ranged from $1·1 to $543 per disability-adjusted life-year averted. INTERPRETATION: Community-based approaches increased IPTp-SP coverage and might have a positive effect on the number of antenatal care visits in addition to being cost-effective, although we found high heterogeneity among studies. Community sensitisation and engagement in addition to established, trained, and supported community health workers can facilitate acceptability, delivery, and uptake of IPTp-SP delivered by community health workers. FUNDING: EDCTP-2 supported by the European Union. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Rethinking Tuberculosis Morbidity Quantification: A Systematic Review and Critical Appraisal of TB Disability Weights in Cost-Effectiveness Analyses.

BACKGROUND: The disability-adjusted life year (DALY), a key metric for health resource allocation, encompasses morbidity through disability weights. Widely used in tuberculosis cost-effectiveness analysis (CEAs), DALYs play a significant role in informing intervention adopt/reject decisions. This study reviews the values and consistency of disability weights applied in tuberculosis-related CEAs. METHODS: We conducted a systematic review using the Tufts CEA database, updated to July 2023 with searches in Embase, Scopus and PubMed. Eligible studies needed to have included a cost-per-DALY ratio, and additionally either evaluated a tuberculosis (TB) intervention or included tuberculosis-related weights. We considered all tuberculosis health states: with/without human immunodeficiency virus (HIV) coinfection, TB treatments and treatment side effects. Data were screened and extracted independently by combinations of two authors. FINDINGS: A total of 105 studies spanning 2002-2023 across 50 countries (mainly low- and middle-income countries) were extracted. Disability weights were sourced primarily from the Global Burden of Disease (GBD; 100/165; 61%), with 17 non-GBD studies additionally referenced, along with primary derivation. Inconsistencies in the utilisation of weights were evident: of the 100 usages of GBD-sourced weights, only in 47 instances (47%) had the weight value been explicitly specified with an appropriate up-to-date reference cited (constituting 28% of all weight usages, 47/165). Sensitivity analyses on weight values had been conducted in 30% of studies (31/105). Twelve studies did not clearly specify weights or their sources; nine further calculated DALYs without morbidity. The review suggests methodological gaps in current approaches for representing important aspects of TB, including TB-HIV coinfection, treatment, drug-resistance, extrapulmonary TB and psychological impacts. We propose a set of best practice recommendations. INTERPRETATION: There is a need for increased rigour in the application, sensitivity testing and reporting of TB disability weights. Furthermore, there appears a desire among researchers to reflect elements of the tuberculosis experience beyond those allowed for by GBD disability weights.

Multimorbidity-associated emergency hospital admissions: a "screen and link" strategy to improve outcomes for high-risk patients in sub-Saharan Africa: a prospective multicentre cohort study protocol.

Background: The prevalence of multimorbidity (the presence of two or more chronic health conditions) is rapidly increasing in sub-Saharan Africa. Hospital care pathways that focus on single presenting complaints do not address this pressing problem. This has the potential to precipitate frequent hospital readmissions, increase health system and out-of-pocket expenses, and may lead to premature disability and death. We aim to present a description of inpatient multimorbidity in a multicentre prospective cohort study in Malawi and Tanzania. Primary objectives: Clinical: Determine prevalence of multimorbid disease among adult medical admissions and measure patient outcomes. Health Economic: Measure economic costs incurred and changes in health-related quality of life (HRQoL) at 90 days post-admission. Situation analysis: Qualitatively describe pathways of patients with multimorbidity through the health system. Secondary objectives: Clinical: Determine hospital readmission free survival and markers of disease control 90 days after admission. Health Economic: Present economic costs from patient and health system perspective, sub-analyse costs and HRQoL according to presence of different diseases. Situation analysis: Understand health literacy related to their own diseases and experience of care for patients with multimorbidity and their caregivers. Methods: This is a prospective longitudinal cohort study of adult (≥18 years) acute medical hospital admissions with nested health economic and situation analysis in four hospitals: 1) Queen Elizabeth Central Hospital, Blantyre, Malawi; 2) Chiradzulu District Hospital, Malawi; 3) Hai District Hospital, Boma Ng'ombe, Tanzania; 4) Muhimbili National Hospital, Dar-es-Salaam, Tanzania. Follow-up duration will be 90 days from hospital admission. We will use consecutive recruitment within 24 hours of emergency presentation and stratified recruitment across four sites. We will use point-of-care tests to refine estimates of disease pathology. We will conduct qualitative interviews with patients, caregivers, healthcare providers and policymakers; focus group discussions with patients and caregivers, and observations of hospital care pathways.

Background: In sub-Saharan Africa, multimorbidity (defined as people living with two or more chronic health conditions) is increasing due to high infectious ( e.g., human immunodeficiency virus (HIV)) and non-communicable ( e.g., high blood pressure and diabetes) disease burdens. Multimorbidity increases as people live longer and can be worsened by HIV and HIV-medications. Patients delay seeking help until they are severely ill, meaning hospitals are key to healthcare delivery for chronic diseases, however hospital clinicians often focus on a single disease. Failure to identify and treat multimorbidity may lead to frequent readmissions, high costs, preventable disability and death. Aim: This cohort study is the first in a three-phase study with the overarching goal to design and test a system to identify patients suffering from multimorbidity when they seek emergency care in sub-Saharan African hospitals. This could improve early disease treatment (reducing death), ensure better follow-up and prevent disability, readmission and excess costs. The cohort study aims to determine multimorbidity prevalence, outcomes and costs. The results will help us co-create with key stakeholders the most cost-effective way to deliver improved care for patients before testing this strategy in a randomised trial. Methods in Brief: In Malawi and Tanzania, we will identify multimorbidity among patients admitted to hospital (focusing on high blood pressure, diabetes, HIV and chronic kidney disease), by enhancing diagnostic tests in hospital departments treating acutely admitted medical patients. With the help of healthcare professional, patients and community groups we will find how best to link patients to long-term care and improve self-management. After mapping health system pathways, we will work with stakeholders (policymakers, healthcare worker representatives, community and patient groups) to co-develop an intervention to improve outcomes for patients with multimorbidity. This study will allow us to collect clinical, health economic and health system data to inform this process.

Causes, outcomes and diagnosis of acute breathlessness hospital admissions in Malawi: protocol for a multicentre prospective cohort study.

Background: Hospital admission due to breathlessness carries a significant burden to patients and healthcare systems, particularly impacting people in low-income countries. Prompt appropriate treatment is vital to improve outcomes, but this relies on accurate diagnostic tests which are of limited availability in resource-constrained settings. We will provide an accurate description of acute breathlessness presentations in a multicentre prospective cohort study in Malawi, a low resource setting in Southern Africa, and explore approaches to strengthen diagnostic capacity. Objectives: Primary objective: Delineate between causes of breathlessness among adults admitted to hospital in Malawi and report disease prevalence. Secondary objectives : Determine patient outcomes, including mortality and hospital readmission 90 days after admission; determine the diagnostic accuracy of biomarkers to differentiate between heart failure and respiratory infections (such as pneumonia) including brain natriuretic peptides, procalcitonin and C-reactive protein. Methods: This is a prospective longitudinal cohort study of adults (≥18 years) admitted to hospital with breathlessness across two hospitals: 1) Queen Elizabeth Central Hospital, Blantyre, Malawi; 2) Chiradzulu District Hospital, Chiradzulu, Malawi. Patients will be consecutively recruited within 24 hours of emergency presentation and followed-up until 90 days from hospital admission. We will conduct enhanced diagnostic tests with robust quality assurance and quality control to determine estimates of disease pathology. Diagnostic case definitions were selected following a systematic literature search. Discussion: This study will provide detailed epidemiological description of adult hospital admissions due to breathlessness in low-income settings, which is currently poorly understood. We will delineate between causes using established case definitions and conduct nested diagnostic evaluation. The results have the potential to facilitate development of interventions targeted to strengthen diagnostic capacity, enable prompt and appropriate treatment, and ultimately improve both patient care and outcomes.

BACKGROUND: People admitted to hospital with symptoms of breathlessness are often severely ill and need quick, accurate assessment to facilitate timely initiation of appropriate treatments. In low resource settings, such as Malawi, limited access to diagnostic equipment impedes patient assessment. Failure to identify and treat the underlying diagnosis may lead to preventable death. AIMS: This cohort study aims to delineate between common, treatable causes of breathlessness among adult patients admitted to hospital in Malawi and measure survival. We will also evaluate the performance of blood markers to diagnose and differentiate between conditions. The results will help us develop context-appropriate diagnostic and treatment algorithms based on resources available in the health system Methods in brief: We will recruit adult patients who present to hospital with breathlessness in a central national referral hospital (Queen Elizabeth Central Hospital, Blantyre), and a district hospital (Chiradzulu District Hospital, Chiradzulu). We will conduct enhanced diagnostic tests to determine causes of breathlessness against internationally accepted diagnostic guidelines. Patients will be followed up throughout their hospital admission and after discharge, until 90 days. INTERPRETATION: This study aligns with World Health Assembly resolutions on 'Strengthening diagnostics capacity' and on 'Integrated emergency, critical and operative care for universal health coverage and protection from health emergencies'. The results of this study will have the potential to facilitate development of interventions targeted to strengthen diagnostic capacity, enable prompt and appropriate treatment, and ultimately improve care and outcomes for acutely unwell patients.

Interdisciplinary perspectives on multimorbidity in Africa: Developing an expanded conceptual model.

Multimorbidity is an emerging challenge for health systems globally. It is commonly defined as the co-occurrence of two or more chronic conditions in one person, but its meaning remains a lively area of academic debate, and the utility of the concept beyond high-income settings is uncertain. This article presents the findings from an interdisciplinary research initiative that drew together 60 academic and applied partners working in 10 African countries to answer the questions: how useful is the concept of multimorbidity within Africa? Can the concept be adapted to context to optimise its transformative potentials? During a three-day concept-building workshop, we investigated how the definition of multimorbidity was understood across diverse disciplinary and regional perspectives, evaluated the utility and limitations of existing concepts and definitions, and considered how to build a more context-sensitive, cross-cutting description of multimorbidity. This iterative process was guided by the principles of grounded theory and involved focus- and whole-group discussions during the workshop, thematic coding of workshop discussions, and further post-workshop development and refinement. Three thematic domains emerged from workshop discussions: the current focus of multimorbidity on constituent diseases; the potential for revised concepts to centre the priorities, needs, and social context of people living with multimorbidity (PLWMM); and the need for revised concepts to respond to varied conceptual priorities amongst stakeholders. These themes fed into the development of an expanded conceptual model that centres the catastrophic impacts multimorbidity can have for PLWMM, families and support structures, service providers, and health systems.

Job satisfaction among community drug distributors in the Mass Drug Administration programme in Nigeria: a cross-sectional study.

BACKGROUND: Despite having one of the largest human resources for health in Africa, the delivery of neglected tropical disease (NTD) health interventions in Nigeria has been hampered by health worker shortages. This study assessed factors associated with job satisfaction among community drug distributors (CDDs) supporting the Nigerian NTD programme, with the goal of identifying opportunities to improve job satisfaction in support of NTD control and elimination efforts in Nigeria. METHODS: A health facility-based cross-sectional survey was conducted in 2019 among CDDs in two states with sharply contrasting NTD programme support, Kaduna and Ogun. A multivariate logistic regression model was used to determine the association between respondent characteristics, programme delivery modalities and job satisfaction. RESULTS: Overall, 75.3% and 74.0% of CDDs were categorised as being satisfied with their job in Kaduna and Ogun states, respectively. The component with the highest reported satisfaction was motivation, where 98.9% and 98.6% of CDDs were satisfied, in Kaduna and Ogun, respectively. Participants were least satisfied with remuneration, communication, supplies and materials, as well as workload. Location (rural/urban) and state, years of experience, who delivers training and reimbursement of transport fare during medicine distribution were significantly associated with job satisfaction. CONCLUSIONS: Including multiple health staff and NTD programme cadres in CDD training and providing remuneration to cover transport fares spent during MDA delivery may improve CDDs' job satisfaction both in Ogun and Kaduna states. Given these two states are at opposite ends of the programme support spectrum, such adaptative measures might help improve CDD job satisfaction in the wider Nigerian NTD programme context.

A health systems approach to critical care delivery in low-resource settings: a narrative review.

There is a high burden of critical illness in low-income countries (LICs), adding pressure to already strained health systems. Over the next decade, the need for critical care is expected to grow due to ageing populations with increasing medical complexity; limited access to primary care; climate change; natural disasters; and conflict. In 2019, the 72nd World Health Assembly emphasised that an essential part of universal health coverage is improved access to effective emergency and critical care and to "ensure the timely and effective delivery of life-saving health care services to those in need". In this narrative review, we examine critical care capacity building in LICs from a health systems perspective. We conducted a systematic literature search, using the World Heath Organisation (WHO) health systems framework to structure findings within six core components or "building blocks": (1) service delivery; (2) health workforce; (3) health information systems; (4) access to essential medicines and equipment; (5) financing; and (6) leadership and governance. We provide recommendations using this framework, derived from the literature identified in our review. These recommendations are useful for policy makers, health service researchers and healthcare workers to inform critical care capacity building in low-resource settings.

Economic evaluation of shortened, bedaquiline-containing treatment regimens for rifampicin-resistant tuberculosis (STREAM stage 2): a within-trial analysis of a randomised controlled trial.

BACKGROUND: The STREAM stage 2 trial assessed two bedaquiline-containing regimens for rifampicin-resistant tuberculosis: a 9-month all-oral regimen and a 6-month regimen containing an injectable drug for the first 2 months. We did a within-trial economic evaluation of these regimens. METHODS: STREAM stage 2 was an international, phase 3, non-inferiority randomised trial in which participants with rifampicin-resistant tuberculosis were randomly assigned (1:2:2:2) to the 2011 WHO regimen (terminated early), a 9-month injectable-containing regimen (control regimen), a 9-month all-oral regimen with bedaquiline (oral regimen), or a 6-month regimen with bedaquiline and an injectable for the first 2 months (6-month regimen). We prospectively collected direct and indirect costs and health-related quality of life data from trial participants until week 76 of follow-up. Cost-effectiveness of the oral and 6-month regimens versus control was estimated in four countries (oral regimen) and two countries (6-month regimen), using health-related quality of life for cost-utility analysis and trial efficacy for cost-effectiveness analysis. This trial is registered with ISRCTN, ISRCTN18148631. FINDINGS: 300 participants were included in the economic analyses (Ethiopia, 61; India, 142; Moldova, 51; Uganda, 46). In the cost-utility analysis, the oral regimen was not cost-effective in Ethiopia, India, Moldova, and Uganda from either a provider or societal perspective. In Moldova, the oral regimen was dominant from a societal perspective. In the cost-effectiveness analysis, the oral regimen was likely to be cost-effective from a provider perspective at willingness-to-pay thresholds per additional favourable outcome of more than US$4500 in Ethiopia, $1900 in India, $3950 in Moldova, and $7900 in Uganda, and from a societal perspective at thresholds of more than $15 900 in Ethiopia, $3150 in India, and $4350 in Uganda, while in Moldova the oral regimen was dominant. In Ethiopia and India, the 6-month regimen would cost tuberculosis programmes and participants less than the control regimen and was highly likely to be cost-effective in both cost-utility analysis and cost-effectiveness analysis. Reducing the bedaquiline price from $1·81 to $1·00 per tablet made the oral regimen cost-effective in the provider-perspective cost-utility analysis in India and Moldova and dominate over the control regimen in the provider-perspective cost-effectiveness analysis in India. INTERPRETATION: At current costs, the oral bedaquiline-containing regimen for rifampicin-resistant tuberculosis is unlikely to be cost-effective in many low-income and middle-income countries. The 6-month regimen represents a cost-effective alternative if injectable use for 2 months is acceptable. FUNDING: USAID and Janssen Research & Development.

Vector control and entomological capacity for onchocerciasis elimination.

Mass drug administration (MDA) of ivermectin is currently the main strategy to achieve elimination of transmission (EoT) of onchocerciasis. Modelling suggests that EoT may not be reached in all endemic foci using annual MDA alone. Onchocerciasis and loiasis are coendemic in forest areas of Central Africa where ivermectin treatment can lead to severe adverse events in individuals with heavy loiasis load, rendering MDA inappropriate. Vector control has been proposed as a complementary intervention strategy. Here, we discuss (i) achievements and pitfalls of previous interventions; (ii) epidemiological impact, feasibility, and combination with MDA to accelerate and/or protect EoT; (iii) role of modelling; (iv) opportunities for innovative methods of vector monitoring and control; and (v) strengthening entomological capacity in endemic countries.