Magnitude and factors associated with post-tuberculosis lung disease in low- and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: Emerging evidence suggests that after completion of treatment for tuberculosis (TB) a significant proportion of patients experience sequelae. However, there is limited synthesized evidence on this from low-income countries, from Sub-Saharan Africa, and in HIV infected individuals. We seek to provide an updated comprehensive systematic review and meta-analysis on the magnitude and factors associated with post-TB lung disease (PTLD) in low- and middle-income countries (LMICs). METHODS: We searched PubMed, Embase and CINAHL for studies from LMICs with data on post-TB lung health in patients who had previously completed treatment for pulmonary TB. Data on study characteristics, prevalence of PTLD-specifically abnormal lung function (spirometry), persisting respiratory symptoms and radiologic abnormalities were abstracted. Statistical analysis was performed using Microsoft Excel and R version 4.1 software, and random effects meta-analysis conducted to compute pooled prevalence of PTLD, evaluate heterogeneity, and assess factors associated with PTLD. RESULTS: We identified 32 eligible studies with 6225 participants. Twenty-one studies were from Africa, 16 included HIV infected participants, spirometry was conducted in 20 studies, symptom assessment in 16 and chest imaging in eight. Pooled prevalence of abnormal lung function was 46.7%, persistent respiratory symptoms 41.0%, and radiologic abnormalities 64.6%. Magnitude of any type of PTLD varied by HIV status (HIV- 66.9%, HIV+ 32.8%, p = 0.0013), across geographic setting (SE Asia 57.5%, Southern America 50.8%, and Africa 38.2%, p = 0.0118), and across urban-rural settings (symptom prevalence: rural 68.8%, urban 39.1%, mixed settings 27.9%, p = 0.0035), but not by income settings, sex or age-group. CONCLUSIONS: There is high burden of post-TB persistent respiratory symptoms, functional lung impairment and radiologic structural abnormalities in individuals living in LMICs. Burden varies across settings and by HIV status. This evidence may be valuable to advocate for and inform implementation of structured health care specific to the needs of this vulnerable population of individuals.

Incentivizing appropriate malaria case management in the private sector: a study protocol for two linked cluster randomized controlled trials to evaluate provider- and client-focused interventions in western Kenya and Lagos, Nigeria.

BACKGROUND: A large proportion of artemisinin-combination therapy (ACT) anti-malarial medicines is consumed by individuals that do not have malaria. The over-consumption of ACTs is largely driven by retail sales in high malaria-endemic countries to clients who have not received a confirmatory diagnosis. This study aims to target ACT sales to clients receiving a confirmatory diagnosis using malaria rapid diagnostic tests (mRDTs) at retail outlets in Kenya and Nigeria. METHODS: This study comprises two linked four-arm 2 × 2 factorial cluster randomized controlled trials focused on malaria diagnostic testing and conditional ACT subsidies with the goal to evaluate provider-directed and client-directed interventions. The linked trials will be conducted at two contrasting study sites: a rural region around Webuye in western Kenya and the urban center of Lagos, Nigeria. Clusters are 41 and 48 participating retail outlets in Kenya and Nigeria, respectively. Clients seeking care at participating outlets across all arms will be given the option of paying for a mRDT-at a study-recommended price-to be conducted at the outlet. In the provider-directed intervention arm, the outlet owner receives a small monetary incentive to perform the mRDT. In the client-directed intervention arm, the client receives a free ACT if they purchase an mRDT and receive a positive test result. Finally, the fourth study arm combines both the provider- and client-directed interventions. The diagnosis and treatment choices made during each transaction will be captured using a mobile phone app. Study outcomes will be collected through exit interviews with clients, who sought care for febrile illness, at each of the enrolled retail outlets. RESULTS: The primary outcome measure is the proportion of all ACTs that are sold to malaria test-positive clients in each study arm. For all secondary outcomes, we will evaluate the degree to which the interventions affect purchasing behavior among people seeking care for a febrile illness at the retail outlet. CONCLUSIONS: If our study demonstrates that malaria case management can be improved in the retail sector, it could reduce overconsumption of ACTs and enhance targeting of publicly funded treatment reimbursements, lowering the economic barrier to appropriate diagnosis and treatment for patients with malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT04428307 , registered June 9, 2020, and NCT04428385 , registered June 9, 2020.

Therapeutic monitoring of anti-seizure medications in low- and middle-income countries: a systematic review.

Background: The treatment gap for epilepsy is large in low- and middle-income countries (LMICs) and the effectiveness and safety of the available anti-seizure medication (ASMs) is not fully understood. We systematically reviewed available evidence on therapeutic drug monitoring (TDM) of ASM in LMIC. Methods: We searched four main databases (PubMed, Psych-Info, CINAHL and Embase) up to 31 st December 2020, with eligible articles screened using a PRISMA checklist and a set of exclusion and inclusion criteria. Full texts were examined to evaluate the extent and practice of TDM in LMICs. Analyses were performed using Stata 13 and descriptive statistics were used to pool median distribution of TDM across studies. Results: Of the 6,309 articles identified in the initial search, 65 (1.0%) met the eligibility criteria. TDM of ASMs was mostly done to assess toxicity (42.8%), but rarely to monitor adherence (9.0%). TDM differed by economic status and infrastructural status with majority of the studies coming from Europe (53.8%) and upper-middle-income countries (87.6%). First generation ASMs (82.3%) were more likely to be monitored than second generation ASMs (17.6%) and carbamazepine was the most frequently monitored drug. Fluorescence Polarization Immunoassay (FPIA) was the most common technique used for TDM (41.5%) followed by High-Performance Liquid Chromatography (HPLC) (16.9%). In addition, FPIA was the cheapest method of TDM based on approximated costs ($1000, TDx system). Assay validation and quality control were reported variably, and reference ranges used during TDM of ASMs were relatively uniform. Conclusions: TDM is mostly done to evaluate ASM toxicity, but rarely for other reasons such as evaluating adherence or assessing clinical efficacy. There is a need for more investment in comprehensive and targeted TDM in LMICs when initiating treatment, switching therapies, adding or removing ASM and evaluating treatment response and safety of both first generation and second generation ASMs.