Assessing the cost-effectiveness of integrated case management of Neglected Tropical Diseases in Liberia.

BACKGROUND: In 2017, Liberia became one of the first countries in the African region to develop and implement a national strategy for integrated case management of Neglected Tropical Diseases (CM-NTDs), specifically Buruli ulcer, leprosy, lymphatic filariasis morbidities, and yaws. Implementing this plan moves the NTD program from many countries' fragmented (vertical) disease management. This study explores to what extent an integrated approach offers a cost-effective investment for national health systems. METHODS: This study is a mixed-method economic evaluation that explores the cost-effectiveness of the integrated CM-NTDs approach compared to the fragmented (vertical) disease management. Primary data were collected from two integrated intervention counties and two non-intervention counties to determine the relative cost-effectiveness of the integrated program model vs. fragmented (vertical) care. Data was sourced from the NTDs program annual budgets and financial reports for integrated CM-NTDs and Mass Drug Administration (MDA) to determine cost drivers and effectiveness. RESULTS: The total cost incurred by the integrated CM-NTD approach from 2017 to 2019 was US$ 789,856.30, with the highest percentage of costs for program staffing and motivation (41.8%), followed by operating costs (24.8%). In the two counties implementing fragmented (vertical) disease management, approximately US$ 325,000 was spent on the diagnosis of 84 persons and the treatment of twenty-four persons suffering from NTDs. While 2.5 times as much was spent in integrated counties, 9-10 times more patients were diagnosed and treated. CONCLUSIONS: The cost of a patient being diagnosed under the fragmented (vertical) implementation is five times higher than integrated CM-NTDs, and providing treatment is ten times as costly. Findings indicate that the integrated CM-NTDs strategy has achieved its primary objective of improved access to NTD services. The success of implementing an integrated CM-NTDs approach in Liberia, presented in this paper, demonstrates that NTD integration is a cost-minimizing solution.

Financing care for Severe Stigmatizing Skin Diseases (SSSDs) in Liberia: challenges and opportunities.

INTRODUCTION: Neglected tropical diseases (NTDs) are an important global health challenge, however, little is known about how to effectively finance NTD related services. Integrated management in particular, is put forward as an efficient and effective treatment modality. This is a background study to a broader health economic evaluation, seeking to document the costs of integrated case management of NTDs versus standard care in Liberia. In the current study, we document barriers and facilitators to NTD care from a health financing perspective. METHODS: We carried out key informant interviews with 86 health professionals and 16 national health system policymakers. 46 participants were active in counties implementing integrated case management and 40 participants were active in counties implementing standard care. We also interviewed 16 patients and community members. All interviews were transcribed and analysed using the thematic framework approach. FINDINGS: We found that decentralization for NTD financing is not yet achieved - financing and reporting for NTDs is still centralized and largely donor-driven as a vertical programme; government involvement in NTD financing is still minimal, focused mainly on staffing, but non-governmental organisations (NGOs) or international agencies are supporting supply and procurement of medications. Donor support and involvement in NTDs are largely coordinated around the integrated case management. Quantification for goods and budget estimations are specific challenges, given the high donor dependence, particularly for NTD related costs and the government's limited financial role at present. These challenges contribute to stockouts of medications and supplies at clinic level, while delays in payments of salaries from the government compromise staff attendance and retention. For patients, the main challenges are high transportation costs, with inflated charges due to fear and stigma amongst motorbike taxi riders, and out-of-pocket payments for medication during stockouts and food/toiletries (for in-patients). CONCLUSION: Our findings contribute to the limited work on financing of SSSD services in West African settings and provide insight on challenges and opportunities for financing and large costs in accessing care by households, which is also being exacerbated by stigma.

Effectiveness of community-based burden estimation to achieve elimination of lymphatic filariasis: A comparative cross-sectional investigation in Côte d'Ivoire.

For lymphatic filariasis (LF) elimination, endemic countries must document the burden of LF morbidity (LFM). Community-based screening (CBS) is used to collect morbidity data, but evidence demonstrating its reliability is limited. Recent pilots of CBS for LFM alongside mass drug administration (MDA) in Côte d'Ivoire suggested low LFM prevalence (2.1-2.2 per 10,000). We estimated LFM prevalence in Bongouanou District, Côte d'Ivoire, using a comparative cross-sectional design. We compared CBS implemented independently of MDA, adapted from existing Ministry of Health protocols, to a population-based prevalence survey led by formally trained nurses. We evaluated the reliability of case identification, coverage, equity, and cost of CBS. CBS identified 87.4 cases of LFM per 10,000; the survey identified 47.5 (39.4-56.3; prevalence ratio [PR] 1.84; 95% CI 1.64-2.07). CBS identified 39.7 cases of suspect lymphoedema per 10,000; the survey confirmed 35.1 (29.2-41.5) filarial lymphoedema cases per 10,000 (PR 1.13 [0.98-1.31]). CBS identified 96.5 scrotal swellings per 10,000; the survey found 91.3 (83.2-99.8; PR 1.06 [0.93-1.21]); including 33.9 (27.7-38.8) filarial hydrocoele per 10,000 (PR of suspect to confirmed hydrocele 2.93 [2.46-3.55]). Positive predictive values for case identification through CBS were 65.0% (55.8-73.5%) for filarial lymphoedema; 93.7% (89.3-96.7%) for scrotal swellings; and 34.0% (27.3-41.2%) for filarial hydrocoele. Households of lower socioeconomic status and certain minority languages were at risk of exclusion. Direct financial costs were $0.17 per individual targeted and $69.62 per case confirmed. Our community-based approach to LFM burden estimation appears scalable and provided reliable prevalence estimates for LFM, scrotal swellings and LF-lymphoedema. The results represent a step-change improvement on CBS integrated with MDA, whilst remaining at programmatically feasible costs. Filarial hydrocoele cases were overestimated, attributable to the use of case definitions suitable for mass-screening by informal staff. Our findings are broadly applicable to countries aiming for LF elimination using CBS. The abstract is available in French in the S1 File.

Impact evaluation of a maternal and neonatal health training intervention in private Ugandan facilities.

Global and country-specific targets for reductions in maternal and neonatal mortality in low-resource settings will not be achieved without improvements in the quality of care for optimal facility-based obstetric and newborn care. This global call includes the private sector, which is increasingly serving low-resource pregnant women. The primary aim of this study was to estimate the impact of a clinical and management-training programme delivered by a non-governmental organization [LifeNet International] that partners with clinics on adherence to global standards of clinical quality during labour and delivery in rural Uganda. The secondary aim included describing the effect of the LifeNet training on pre-discharge neonatal and maternal mortality. The LifeNet programme delivered maternal and neonatal clinical trainings over a 10-month period in 2017-18. Direct clinical observations of obstetric deliveries were conducted at baseline (n = 263 pre-intervention) and endline (n = 321 post-intervention) for six faith-based, not-for-profit primary healthcare facilities in the greater Masaka area of Uganda. Direct observation comprised the entire delivery process, from initial client assessment to discharge, and included emergency management (e.g. postpartum haemorrhage and neonatal resuscitation). Data were supplemented by daily facility-based assessments of infrastructure during the study periods. Results showed positive and clinically meaningful increases in observed handwashing, observed delayed cord clamping, partograph use documentation and observed 1- and/or 5-minute APGAR assessments (rapid scoring system for assessing clinical status of newborn), in particular, between baseline and endline. High-quality intrapartum facility-based care is critical for reducing maternal and early neonatal mortality, and this evaluation of the LifeNet intervention indicates that their clinical training programme improved the practice of quality maternal and neonatal healthcare at all six primary care clinics in Uganda, at least over a relatively short-term period. However, for several of these quality indicators, the adherence rates, although improved, were still far from 100% and could benefit from further improvement via refresher trainings and/or a closer examination of the barriers to adherence.

The development of a capacity-strengthening program to promote self-care practices among people with lymphatic filariasis-related lymphedema in the Upper West Region of Ghana.

BACKGROUND: The Upper West region of Ghana is mostly made up of rural communities and is highly endemic for lymphatic filariasis (LF), with a significant burden of disability due to lymphedema and hydrocele. The aim of this paper is to describe an enhanced, evidence-based cascading training program for integrated lymphedema management in this region, and to present some initial outcomes. MAIN TEXT: A baseline evaluation in the Upper West Region was carried out in 2019. A cascaded training program was designed and implemented, followed by a roll-out of self-care activities in all 72 sub-districts of the Upper West Region. A post implementation evaluation in 2020 showed that patients practiced self-care more frequently and with more correct techniques than before the training program; they were supported in this by health staff and family members. CONCLUSIONS: Self-care for lymphedema is feasible and a program of short workshops in this cascaded training program led to significant improvements. Efforts to maintain momentum and sustain what has been achieved so far, will include regular training and supervision to improve coverage, the provision of adequate resources for limb care at home, and the maintenance of district registers of lymphedema cases, which must be updated regularly.

Beneath the Surface: A Comparison of Methods for Assessment of Quality of Care for Maternal and Neonatal Health Care in Rural Uganda.

OBJECTIVES: Efforts to improve access to healthcare in low-income countries will not achieve the maternal and child health (MCH) Sustainable Development Goals unless a concomitant improvement in the quality of care (QoC) occurs. This study measures infrastructure and QoC indicators in rural Ugandan health facilities. Valid measure of the quality of current clinical practices in resource-limited settings are critical for effectively intervening to reduce adverse maternal and neonatal outcomes. METHODS: Facility-based assessments of infrastructure and clinical quality during labor and delivery were conducted in six primary care health facilities in the greater Masaka area, Uganda in 2017. Data were collected using direct observation of clinical encounters and facility checklists. Direct observation comprised the entire delivery process, from initial client assessment to discharge, and included emergency management (e.g. postpartum hemorrhage, neonatal resuscitation). Health providers were assessed on their adherence to best practice standards of care. RESULTS: The quality of facility infrastructure was relatively high in facilities, with little variation in availability of equipment and supplies. However, heterogeneity in adherence to best clinical practices was noted across procedure type and facility. Adherence to crude measures of clinical quality were relatively high but more sensitive measures of the same clinical practice were found to be much lower. CONCLUSIONS FOR PRACTICE: Standard indicators of clinical practice may be insufficient to validly measure clinical quality for maternal and newborn care if we want to document evidence of impact.

Conversion of Serine-Type Aldehyde Tags by the Radical SAM Protein AtsB from Methanosarcina mazei.

Formylglycine-generating enzymes provide a convenient tool for site-specific protein derivatization. Their ability to oxidize cysteine or serine residues within a defined consensus sequence to Cα -formylglycine (FGly) allows for the targeted introduction of a unique chemical handle for various bioconjugation reactions. In recent years, oxygen-dependent FGly-generating enzyme saw broad use in protein functionalization and the generation of protein conjugates. Yet, the FGly-generating system AtsB, along with its capability to convert unusual aldehyde tag sequences, remains mostly unused. Herein, the ability of AtsB from Methanosarcina mazei to convert nonclassical aldehyde tags of the SX(A/P)XR-type and its potential use in bioconjugation chemistry are demonstrated.

Two-fold Bioorthogonal Derivatization by Different Formylglycine-Generating Enzymes.

Formylglycine-generating enzymes are of increasing interest in the field of bioconjugation chemistry. They catalyze the site-specific oxidation of a cysteine residue to the aldehyde-containing amino acid Cα -formylglycine (FGly). This non-canonical residue can be generated within any desired target protein and can subsequently be used for bioorthogonal conjugation reactions. The prototypic formylglycine-generating enzyme (FGE) and the iron-sulfur protein AtsB display slight variations in their recognition sequences. We designed specific tags in peptides and proteins that were selectively converted by the different enzymes. Combination of the different tag motifs within a single peptide or recombinant protein enabled the independent and consecutive introduction of two formylglycine residues and the generation of heterobifunctionalized protein conjugates.