Effect of topography on the risk of malaria in the Usambara Mountains, Tanzania

There has been a progressive rise in malaria in parts of the African highlands over the last 50 years. In this area of unstable malaria, devastating epidemics are experienced at irregular intervals. Altitude plays a very important role in determining malaria transmission and infection. However, other landscape features may also influence this relationship. This research investigates whether the risk of malaria is related to the shape of the surrounding land, at various altitudes. We hypothesized that households situated close to flat areas where water is expected to accumulate, and are thus potential mosquitoes breeding sites, are at greater risk from malaria than those further away. Cross-sectional clinical surveys were carried out in seven villages along an altitudinal transect rising from 300 m to 1650 m in the western Usambara Mountains, Tanzania. Each village was mapped and incorporated within a geographical information system (GIS). Univariate analysis showed that the risk of an enlarged spleen was positively correlated with decreasing altitude. Other influential topographic variables identified were: water accumulation, flatness and swampiness. Logistic regression analysis produced two models and their equations were used in the GIS to map the risk of malaria infection within each village area. Model 1 included only altitude and correctly predicted the malaria status of 73% of households, whereas Model 2 incorporated altitude and the amount of swampiness within 400 m radius of each household to predict with 76% accuracy whether households were positive or not. We have identified that between 750 m and 1200 m, characteristics of the landscape play an important role in governing malaria risk. At these elevations malaria is highly unstable, and favourable meteorological conditions can cause malaria epidemics. This novel approach of exploring how topography affects the risk of malaria could be used to identify epidemic-prone areas m other African highland regions and help to improve the targeting of control activities in high-risk areas

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570