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  1. Abu Hasan Z', Williams H, Ismail NM, Othman H, Cozier GE, Acharya KR, et al.
    Sci Rep, 2017 03 27;7:45409.
    PMID: 28345667 DOI: 10.1038/srep45409
    The control of mosquitoes is threatened by the appearance of insecticide resistance and therefore new control chemicals are urgently required. Here we show that inhibitors of mosquito peptidyl dipeptidase, a peptidase related to mammalian angiotensin-converting enzyme (ACE), are insecticidal to larvae of the mosquitoes, Aedes aegypti and Anopheles gambiae. ACE inhibitors (captopril, fosinopril and fosinoprilat) and two peptides (trypsin-modulating oostatic factor/TMOF and a bradykinin-potentiating peptide, BPP-12b) were all inhibitors of the larval ACE activity of both mosquitoes. Two inhibitors, captopril and fosinopril (a pro-drug ester of fosinoprilat), were tested for larvicidal activity. Within 24 h captopril had killed >90% of the early instars of both species with 3rd instars showing greater resistance. Mortality was also high within 24 h of exposure of 1st, 2nd and 3rd instars of An. gambiae to fosinopril. Fosinopril was also toxic to Ae. aegypti larvae, although the 1st instars appeared to be less susceptible to this pro-drug even after 72 h exposure. Homology models of the larval An. gambiae ACE proteins (AnoACE2 and AnoACE3) reveal structural differences compared to human ACE, suggesting that structure-based drug design offers a fruitful approach to the development of selective inhibitors of mosquito ACE enzymes as novel larvicides.
  2. Agarwal D, Hanafi NS, Chippagiri S, Brakema EA, Pinnock H, Khoo EM, et al.
    NPJ Prim Care Respir Med, 2019 05 08;29(1):17.
    PMID: 31068586 DOI: 10.1038/s41533-019-0129-7
    This protocol describes a systematic scoping review of chronic respiratory disease surveys in low/middle-income countries (LMICs) undertaken as part of the Four Country ChrOnic Respiratory Disease (4CCORD) study within the National Institute for Health Research Global Health Research Unit on Respiratory Health (RESPIRE). Understanding the prevalence and burden of chronic respiratory disease (CRD) underpins healthcare planning. We will systematically scope the literature to identify existing strategies (definitions/questionnaires/diagnostics/outcomes) used in surveys of CRDs in adults in low-resource settings. We will search MEDLINE, EMBASE, ISI WoS, Global Health and WHO Global Health Library [search terms: prevalence AND CRD (COPD, asthma) AND LMICs, from 1995], and two reviewers will independently extract data from selected studies onto a piloted customised data extraction form. We will convene a workshop of the multidisciplinary 4CCORD research team with representatives from the RESPIRE partners (Bangladesh, India, Malaysia, Pakistan and Edinburgh) at which the findings of the scoping review will be presented, discussed and interpreted. The findings will inform a future RESPIRE 4CCORD study, which will estimate CRD burden in adults in Asian LMICs.
  3. Hanafi NS, Agarwal D, Chippagiri S, Brakema EA, Pinnock H, Sheikh A, et al.
    J Glob Health, 2021 Jun 19;11:04026.
    PMID: 34221357 DOI: 10.7189/jogh.11.04026
    Background: Chronic respiratory diseases (CRDs) contribute significantly towards the global burden of disease, but the true prevalence and burden of these conditions in adults is unknown in the majority of low- and middle-income countries (LMICs). We aimed to identify strategies - in particular the definitions, study designs, sampling frames, instruments, and outcomes - used to conduct prevalence surveys for CRDs in LMICs. The findings will inform a future RESPIRE Four Country ChrOnic Respiratory Disease (4CCORD) study, which will estimate CRD prevalence, including disease burden, in adults in LMICs.

    Methods: We conducted a scoping review to map prevalence surveys conducted in LMICs published between 1995 and 2018. We followed Arksey and O'Malley's six-step framework. The search was conducted in OVID Medline, EMBASE, ISI Web of Science, Global Health, WHO Global Index Medicus and included three domains: CRDs, prevalence and LMICs. After an initial title sift, eight trained reviewers undertook duplicate study selection and data extraction. We charted: country and populations, random sampling strategies, CRD definitions/phenotypes, survey procedure (questionnaires, spirometry, tests), outcomes and assessment of individual, societal and health service burden of disease.

    Results: Of 36 872 citations, 281 articles were included: 132 from Asia (41 from China). Study designs were cross-sectional surveys (n = 260), cohort studies (n = 11) and secondary data analysis (n = 10). The number of respondents in these studies ranged from 50 to 512 891. Asthma was studied in 144 studies, chronic obstructive pulmonary disease (COPD) in 112. Most studies (100/144) based identification of asthma on symptom-based questionnaires. In contrast, COPD diagnosis was typically based on spirometry findings (94/112); 65 used fixed-ratio thresholds, 29 reported fixed-ratio and lower-limit-of-normal values. Only five articles used the term 'phenotype'. Most studies used questionnaires derived from validated surveys, most commonly the European Community Respiratory Health Survey (n = 47). The burden/impact of CRD was reported in 33 articles (most commonly activity limitation).

    Conclusion: Surveys remain the most practical approach for estimating prevalence of CRD but there is a need to identify the most predictive questions for diagnosing asthma and to standardise diagnostic criteria.

  4. Agarwal D, Hanafi NS, Khoo EM, Parker RA, Ghorpade D, Salvi S, et al.
    J Glob Health, 2021;11:04065.
    PMID: 34737865 DOI: 10.7189/jogh.11.04065
    Background: Our previous scoping review revealed limitations and inconsistencies in population surveys of chronic respiratory disease. Informed by this review, we piloted a cross-sectional survey of adults in four South/South-East Asian low-and middle-income countries (LMICs) to assess survey feasibility and identify variables that predicted asthma or chronic obstructive pulmonary disease (COPD).

    Methods: We administered relevant translations of the BOLD-1 questionnaire with additional questions from ECRHS-II, performed spirometry and arranged specialist clinical review for a sub-group to confirm the diagnosis. Using random sampling, we piloted a community-based survey at five sites in four LMICs and noted any practical barriers to conducting the survey. Three clinicians independently used information from questionnaires, spirometry and specialist reviews, and reached consensus on a clinical diagnosis. We used lasso regression to identify variables that predicted the clinical diagnoses and attempted to develop an algorithm for detecting asthma and COPD.

    Results: Of 508 participants, 55.9% reported one or more chronic respiratory symptoms. The prevalence of asthma was 16.3%; COPD 4.5%; and 'other chronic respiratory disease' 3.0%. Based on consensus categorisation (n = 483 complete records), "Wheezing in last 12 months" and "Waking up with a feeling of tightness" were the strongest predictors for asthma. For COPD, age and spirometry results were the strongest predictors. Practical challenges included logistics (participant recruitment; researcher safety); misinterpretation of questions due to local dialects; and assuring quality spirometry in the field.

    Conclusion: Detecting asthma in population surveys relies on symptoms and history. In contrast, spirometry and age were the best predictors of COPD. Logistical, language and spirometry-related challenges need to be addressed.

  5. Sheikh A, Campbell H, Balharry D, Baqui AH, Bogaert D, Cresswell K, et al.
    J Glob Health, 2018 Dec;8(2):020101.
    PMID: 30603074 DOI: 10.7189/jogh.08.020101
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