Analysing malaria events from 1840 to 2020: the narrative told through postage stamps

The role played by postage stamps in the history of malaria control and eradication has largely gone unrecognized. Scientific investigators of malaria, especially Nobel laureates, were commemorated with special issues, but the work of the World Health Organization (WHO), which promoted an ambitious and global philatelic initiative in 1962 to support global eradication, is generally overlooked. This review examines the philatelic programme that helped to generate international commitment to the goal of malaria eradication in 1962 and established philatelic malaria icons that had worldwide recognition. Malaria-related postage stamps have continued to be issued since then, but the initial failure of malaria eradication and the changing goals of each new malaria programme, inevitably diluted their role. After the first Global Malaria Eradication Campaign was discontinued in 1969, few Nations released philatelic issues. Since the Spirit of Dakar Call for Action in 1996 a resurgence of postage stamp releases has occurred, largely tracking global malaria control initiatives introduced between 1996 and 2020. These releases were not co-ordinated by the WHO as before, were more commercialized and targeted stamp collectors, especially with attractive miniature sheets, often produced by photomontage. Having a different purpose, they demonstrated a much wider diversity in symbolism than the earlier stylized issues and at times, have been scientifically inaccurate. Nonetheless postage stamps greatly helped to communicate the importance of malaria control programmes to a wide audience and to some extent, have supported preventive health messages.

APPLICATION OF HERBICIDES IN THE CONTROL OF THE INVASIVE SPECIES HERACLEUM SOSNOWSKYI MANDEN. (SOSNOWSKY’S HOGWEED) IN FORESTRY

A representative of the family Apiacea, Sosnowsky's hogweed ( Heracleum sosnowskyi Manden.) previously cultivated as a fodder plant and now occupying vast territories along roads and railways, in and near settlements, uncultivated agricultural lands, on farms and in many other areas, poses a serious threat to human health. On these lands, an active eradication campaign has been going on for over 15 years. This invasive species also spreads actively on the lands of the forest fund including plantations, felling sites, young stands of natural origin, clearings and hayfields, forest stands of different ages with a small basal area, and in the most productive forest conditions. As a result, in forest plantations growth of woody plants (primarily of coniferous species) is inhibited, their death is observed, and environmental, aesthetic and industrial damage increases due to the growth and dominance of Sosnowsky's hogweed. As a result of field experiments in the Leningrad Region, a high effectiveness of a number of modern herbicides (Roundup, Anchor-85, and Magnum) for control of Sosnowsky's hogweed and other unwanted herbaceous vegetation, as well as their selectivity in relation to pine and spruce, has been demonstrated.

Managing non-target wildlife mortality whilst using rodenticides to eradicate invasive rodents on islands

Invasive rodents are one of the greatest threats to island biodiversity. Eradicating these species from islands has become increasingly practicable in recent decades, primarily using anticoagulant rodenticides. However, this approach also poses risks to native wildlife, and there has been corresponding development in the management of risks to non-target wildlife species. Here we review strategies and tactics used in operational management of non-target risk, using examples from rodent eradication projects conducted on 178 islands where non-target risk assessment and mitigation was a component of the rodent eradication campaign. We identified 17 different tactics within a framework of three strategic approaches: avoidance of risk, minimization of risk, and remediation of the impact of non-target wildlife mortality. We summarize these tactics in terms of their applicability, strengths, and weaknesses for rodent eradication projects in general, plus the potential interactions with achieving rodent eradication. There remains great potential for further innovation in reducing non-target wildlife risks from rodenticide used for invasive rodent eradications on islands, supporting advancement of the social acceptability of the toolset and biodiversity conservation.

Surveillance of Human Guinea Worm in Chad, 2010–2018

The total number of Guinea worm cases has been reduced by 99.9% since the mid-1980s when the eradication campaign began. Today, the greatest number of cases is reported from Chad. In this report, we use surveillance data collected by the Chad Guinea Worm Eradication Program to describe trends in human epidemiology. In total, 114 human cases were reported during the years 2010–2018, with highest rates of containment (i.e., water contamination prevented) in the years 2013, 2014, 2016, and 2017 (P < 0.0001). Approximately half of case-patients were female, and 65.8% of case-patients were aged 30 years or younger (mean: 26.4 years). About 34.2% of case-patients were farmers. Cases were distributed across many ethnicities, with a plurality of individuals being of the Sara Kaba ethnicity (21.3%). Most cases occurred between the end of June and the end of August and were clustered in the Chari Baguirmi (35.9%) and Moyen Chari regions (30.1%). Cases in the northern Chari River area peaked in April and in August, with no clear pattern in the southern Chari River area. History of travel within Chad was reported in 7.0% of cases, and male subjects (12.5%) were more likely than female subjects (1.7%) to have reported a history of travel (P = 0.03). Our findings confirm that human Guinea worm is geographically disperse and rare. Although the proportion of case-patients with travel history is relatively small, this finding highlights an additional challenge of surveillance in mobile populations in the final stages of the global eradication campaign.

Some lessons for malaria from the Global Polio Eradication Initiative

The Global Polio Eradication Initiative (GPEI) was launched in 1988 with the aim of completely clearing wild polio viruses by 2000. More than three decades later, the goal has not been achieved, although spectacular advances have been made, with wild polio virus reported in only 2 countries in 2019. In spite of such progress, novel challenges have been added to the equation, most importantly outbreaks of vaccine-derived polio cases resulting from reversion to neurovirulence of attenuated vaccine virus, and insufficient coverage of vaccination. In the context of the latest discussions on malaria eradication, the GPEI experience provides more than a few lessons to the malaria field when considering a coordinated eradication campaign. The WHO Strategic Advisory Committee on Malaria Eradication (SAGme) stated in 2020 that in the context of more than 200 million malaria cases reported, eradication was far from reach in the near future and, therefore, efforts should remain focused on getting back on track to achieve the objectives set by the Global Technical Strategy against Malaria (2016–2030). Acknowledging the deep differences between both diseases and the stages they are in their path towards eradication, this paper draws from the history of GPEI and highlights relevant insights into what it takes to eradicate a pathogen in fields as varied as priority setting, global governance, strategy, community engagement, surveillance systems, and research. Above all, it shows the critical need for openness to change and adaptation as the biological, social and political contexts vary throughout the time an eradication campaign is ongoing.

Selecting an anti-malarial clinical candidate from two potent dihydroisoquinolones

Background The ongoing global malaria eradication campaign requires development of potent, safe, and cost-effective drugs lacking cross-resistance with existing chemotherapies. One critical step in drug development is selecting a suitable clinical candidate from late leads. The process used to select the clinical candidate SJ733 from two potent dihydroisoquinolone (DHIQ) late leads, SJ733 and SJ311, based on their physicochemical, pharmacokinetic (PK), and toxicity profiles is described. Methods The compounds were tested to define their physicochemical properties including kinetic and thermodynamic solubility, partition coefficient, permeability, ionization constant, and binding to plasma proteins. Metabolic stability was assessed in both microsomes and hepatocytes derived from mice, rats, dogs, and humans. Cytochrome P450 inhibition was assessed using recombinant human cytochrome enzymes. The pharmacokinetic profiles of single intravenous or oral doses were investigated in mice, rats, and dogs. Results Although both compounds displayed similar physicochemical properties, SJ733 was more permeable but metabolically less stable than SJ311 in vitro. Single dose PK studies of SJ733 in mice, rats, and dogs demonstrated appreciable oral bioavailability (60–100%), whereas SJ311 had lower oral bioavailability (mice 23%, rats 40%) and higher renal clearance (10–30 fold higher than SJ733 in rats and dogs), suggesting less favorable exposure in humans. SJ311 also displayed a narrower range of dose-proportional exposure, with plasma exposure flattening at doses above 200 mg/kg. Conclusion SJ733 was chosen as the candidate based on a more favorable dose proportionality of exposure and stronger expectation of the ability to justify a strong therapeutic index to regulators.

Selecting an anti-malarial clinical candidate from two potent dihydroisoquinolones

Background: The ongoing global malaria eradication campaign requires development of potent, safe, and cost-effective drugs lacking cross-resistance with existing chemotherapies. One critical step in drug development is selecting a suitable clinical candidate from late leads. Herein we present the process used to select the clinical candidate SJ733 from two potent dihydroisoquinolone (DHIQ) late leads, SJ733 and SJ311, based on their physicochemical, pharmacokinetic (PK), and toxicity profiles. Methods: The compounds were tested to define their physicochemical properties including kinetic and thermodynamic solubility, partition coefficient, permeability, ionization constant, and binding to plasma proteins. Metabolic stability was assessed in both microsomes and hepatocytes derived from mice, rats, dogs, and humans. Cytochrome P450 inhibition was assessed using recombinant human cytochrome enzymes. The pharmacokinetic profiles of single intravenous or oral doses were investigated in mice, rats, and dogs. Results: Although both compounds displayed similar physicochemical properties, SJ733 was more permeable but metabolically less stable than SJ311 in vitro. Single dose PK studies of SJ733 in mice, rats, and dogs demonstrated appreciable oral bioavailability (60-100%), whereas SJ311 had lower oral bioavailability (mice 23%, rats 40%) and higher renal clearance (10-30 fold higher than SJ733 in rats and dogs), suggesting less favorable exposure in humans. SJ311 also displayed a narrower range of dose-proportional exposure, with plasma exposure flattening at doses above 200 mg/kg. Conclusion: SJ733 was chosen as the candidate based on a more favorable dose proportionality of exposure and stronger expectation of the ability to justify a strong therapeutic index to regulators.

Population genomic evidence that human and animal infections in Africa come from the same populations of Dracunculus medinensis

Background Guinea worm–Dracunculus medinensis–was historically one of the major parasites of humans and has been known since antiquity. Now, Guinea worm is on the brink of eradication, as efforts to interrupt transmission have reduced the annual burden of disease from millions of infections per year in the 1980s to only 54 human cases reported globally in 2019. Despite the enormous success of eradication efforts to date, one complication has arisen. Over the last few years, hundreds of dogs have been found infected with this previously apparently anthroponotic parasite, almost all in Chad. Moreover, the relative numbers of infections in humans and dogs suggests that dogs are currently the principal reservoir on infection and key to maintaining transmission in that country. Principal findings In an effort to shed light on this peculiar epidemiology of Guinea worm in Chad, we have sequenced and compared the genomes of worms from dog, human and other animal infections. Confirming previous work with other molecular markers, we show that all of these worms are D. medinensis, and that the same population of worms are causing both infections, can confirm the suspected transmission between host species and detect signs of a population bottleneck due to the eradication efforts. The diversity of worms in Chad appears to exclude the possibility that there were no, or very few, worms present in the country during a 10-year absence of reported cases. Conclusions This work reinforces the importance of adequate surveillance of both human and dog populations in the Guinea worm eradication campaign and suggests that control programs aiming to interrupt disease transmission should stay aware of the possible emergence of unusual epidemiology as pathogens approach elimination.