This paper provides evidence that the COVID-19-related mortality rate of national government ministers and heads of state has been substantially higher than that of people with a similar sex and age profile in the general population, a trend that is driven by African cases (17 out of 24 reported deaths worldwide, as of 6 February 2021). Ministers' work frequently puts them in close contact with diverse groups, and therefore at higher risk of contracting SARS-CoV-2, but this is not specific to Africa. This paper discusses five non-mutually exclusive hypotheses for the Africa-specific trend, involving comorbidity, poorly resourced healthcare and possible restrictions in accessing out-of-country health facilities, the underreporting of cases, and, later, the disproportionate impact of the so-called 'South African' variant (501Y.V2). The paper then turns its attention to the public health and political implications of the trend. While governments have measures in place to cope with the sudden loss of top officials, the COVID-19-related deaths have been associated with substantial changes in public health policy in cases where the response to the pandemic had initially been contested or minimal. Ministerial deaths may also result in a reconfiguration of political leadership, but we do not expect a wave of younger and more gender representative replacements. Rather, we speculate that a disconnect may emerge between the top leadership and the public, with junior ministers filling the void and in so doing putting themselves more at risk of infection.  https://www.selleckchem.com/products/mrt67307.html  Opposition politicians may also be at significant risk of contracting SARS-CoV-2.
  Inadequate water and sanitation is a central challenge in global health. Since 2008, the Democratic Republic of Congo government has implemented a national programme, Healthy Villages and Schools (
  (VEA), with support from UNICEF, financed by UK's Foreign, Commonwealth and Development Office.
 
  A cluster-level randomised controlled trial of VEA was implemented throughout 2019 across 332 rural villages, grouped into 50 treatment and 71 control clusters. Primary outcomes included time spent collecting water; quantity of water collected; prevalence of improved primary source of drinking water; and prevalence of improved primary defecation site. Secondary outcomes included child health, water governance, water satisfaction, handwashing practices, sanitation practices, financial cost of water, school attendance and water storage practices. All outcomes were self-reported. The primary analysis was on an intention-to-treat basis, using linear models. Outcomes were measured October-December 2019, median 5 months post-intervention.
 
  The programme increased access to improved water sources by 33 percentage points (pp) (95% CI 22 to 45), to improved sanitation facilities by 26 pp (95% CI 14 to 37), and improved water governance by 1.3 SDs (95% CI 1.1 to 1.5), water satisfaction by 0.6 SD (95% CI 0.4 to 0.9), handwashing practices by 0.5 SD (95% CI 0.3 to 0.7) and sanitation practices by 0.3 SD (95% CI 0.1 to 0.4). There was no significant difference in financial cost of water, school attendance, child health or water storage practices.
 
  VEA produced large increases in access to and satisfaction with water and sanitation services, in self-reported hygiene and sanitation behaviour, and in measures of water governance.
 
  AEARCTR-0004648; American Economic Association RCT registry.
 AEARCTR-0004648; American Economic Association RCT registry.The vaginal environment with candidiasis has a pH of 3.8 to 4.5 and this has a negative effect on the activity of antifungals. Ibrexafungerp was evaluated against 187 Candida isolates, including fluconazole-sensitive and -resistant Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, and Candida tropicalis with the media adjusted to pH 7.0 and pH 4.5. Ibrexafungerp MIC values were not adversely affected when tested at pH 4.5. Ibrexafungerp exhibited significant activity against all isolates at pH 4.5.New, more-effective drugs for the treatment of lung disease caused by nontuberculous mycobacteria (NTM) are needed. Among NTM opportunistic pathogens, Mycobacterium abscessus is the most difficult to cure and intrinsically multidrug resistant. In a whole-cell screen of a compound collection active against Mycobacterium tuberculosis, we previously identified the piperidine-4-carboxamide (P4C) MMV688844 (844) as a hit against M. abscessus. Here, we identified a more potent analog of 844 and showed that both the parent and improved analog retain activity against strains representing all three subspecies of the M. abscessus complex. Furthermore, P4Cs showed bactericidal and antibiofilm activity. Spontaneous resistance against the P4Cs emerged at a frequency of 10-8/CFU and mapped to gyrA and gyrB encoding the subunits of DNA gyrase. Biochemical studies with recombinant M. abscessus DNA gyrase showed that P4Cs inhibit the wild-type enzyme but not the P4C-resistant mutant. P4C-resistant strains showed limited cross-resistance to the fluoroquinolone moxifloxacin, which is in clinical use for the treatment of macrolide-resistant M. abscessus disease, and no cross-resistance to the benzimidazole SPR719, a novel DNA gyrase inhibitor in clinical development for the treatment of mycobacterial diseases. Analyses of P4Cs in recA promoter-based DNA damage reporter strains showed induction of recA promoter activity in the wild type but not in the P4C-resistant mutant background. This indicates that P4Cs, similar to fluoroquinolones, cause DNA gyrase-mediated DNA damage. Together, our results show that P4Cs present a novel class of mycobacterial DNA gyrase inhibitors with attractive antimicrobial activities against the M. abscessus complex.In the present report, we describe two small molecules with broad-spectrum antiviral activity. These drugs block the formation of the nodosome. The studies were prompted by the observation that infection of human fetal brain cells with Zika virus (ZIKV) induces the expression of nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a host factor that was found to promote ZIKV replication and spread. A drug that targets NOD2 was shown to have potent broad-spectrum antiviral activity against other flaviviruses, alphaviruses, enteroviruses, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Another drug that inhibits receptor-interacting serine/threonine protein kinase 2 (RIPK2), which functions downstream of NOD2, also decreased the replication of these pathogenic RNA viruses. The antiviral effect of this drug was particularly potent against enteroviruses. The broad-spectrum action of nodosome-targeting drugs is mediated in part by the enhancement of the interferon response.