Malaria: A genetic intervention
Malaria cases may have decreased over the last 15 years, but the number of parasites resistant to treatment is rising, particularly in Southeast Asia. Indeed, some Plasmodium falciparum parasites (which cause the most severe form of the disease) no longer respond to the most widely used antimalarial drugs (Blasco et al., 2017; Menard and Dondorp, 2017). This includes artemisinin-based combination therapy (ACT), the first line of defense recommended by National Malaria Control Programs (Noedl et al., 2008; Dondorp et al., 2009; Cheeseman et al., 2012; Ariey et al., 2014; Takala-Harrison et al., 2015; Amato et al., 2018; Hamilton et al., 2019; Imwong et al., 2020; Stokes et al., 2021). The reduced susceptibility to artemisinin and its partner drugs has resulted in ACT therapy failing to treat over 50% of malaria cases in some regions of Cambodia, Thailand and Vietnam (van der Pluijm et al., 2020; van der Pluijm et al., 2019).
In order to make rapid, effective decisions on how best to tackle this rise in resistance, policymakers need to be aware of which strains are present in different regions. However, clinical studies of malaria are logistically difficult and expensive to implement. An alternative approach is to study molecular markers in the blood of malaria patients, which can also provide an earlier indication of where resistant parasites have emerged (World Health Organization, 2020). Now, in eLife, Olivo Miotto and colleagues – including Christopher Jacob (Wellcome Sanger Institute) as first author – report a new genetic surveillance platform called ‘GenRe-Mekong’ which monitors the spread of resistant parasites in the Greater Mekong Subregion (Jacob et al., 2021).
Jacob et al. collaborated with various National Malaria Control Programs and scientific partners to collect 9,623 blood samples from patients diagnosed with P. falciparum malaria in eight countries (Vietnam, Laos, Cambodia, Thailand, Myanmar, Bangladesh, India and Democratic Republic of Congo). A cutting-edge sequencing technology was then applied to extract and amplify specific genes from the parasitic genome. Jacob et al. analyzed this genetic data for variants which are known to reduce parasites’ susceptibility to the most widely used treatments, including artemisinin (Figure 1). Based on the proportion of variants present in each gene, each sample was then classified as having a ‘sensitive’, ‘resistant’ or ‘undetermined’ response to an antimalarial drug.
Data from the genetic surveillance platform were delivered to National Malaria Control Programs as maps which simply describe how the presence and absence of resistant parasites is changing over time. Notably, the team (who are based in the United States, United Kingdom, Vietnam, Laos, Cambodia, Thailand, Bangladesh, Switzerland, Democratic Republic of Congo, France, Myanmar and India) provided concrete examples of how this information can be translated into policy decisions. For example, the database found that parasites less susceptible to artemisinin and one of its partner drugs (originally identified in Cambodia and Thailand) had spread to southern provinces in Vietnam and Laos which were previously unaffected by these resistant strains. This led National Malaria Control Programs in these regions to reassess which frontline therapies to use and where to allocate resources to help combat the rise in drug resistance.
Beyond providing actionable information on the spread of resistance, the approach could also shed light on the complexity of infection, revealing whether a patient was carrying different species or strains of parasites at the same time. It could also be used to infer where the strains detected originated, which could help to reconstruct how parasites resistant to multiple drugs spread to different regions.
Although this platform could rapidly become an essential, complementary strategy for eliminating malaria, additional work is needed to overcome some drawbacks. First, the changes in drug susceptibility caused by the genetic variants is not directly tested, but assumed on the basis of earlier research (Figure 1). Second, the platform will be unable to capture new resistant strains, unless newly discovered variants are continuously added to the GenRe-Mekong database. Last, the current approach is unlikely to be applicable to countries in the African continent. This is because patients are often infected by multiple strains of P. falciparum at the same time, which makes it difficult to apply the method across many variant genes and classify the resistance profile. Nevertheless, the work by Jacob et al. demonstrates how genetic data can be a tremendously practical tool that can help policy makers rapidly adapt their treatment strategies in response to rising levels of drug resistance.
Origins of the current outbreak of multidrug-resistant malaria in Southeast Asia: a retrospective genetic studyThe Lancet Infectious Diseases 18:337–345.https://doi.org/10.1016/S1473-3099(18)30068-9
Artemisinin resistance in Plasmodium falciparum malariaNew England Journal of Medicine 361:455–467.https://doi.org/10.1128/microbiolspec.EI10-0013-2016
Evolution and expansion of multidrug-resistant malaria in Southeast Asia: a genomic epidemiology studyThe Lancet Infectious Diseases 19:943–951.https://doi.org/10.1016/S1473-3099(19)30392-5
Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong Subregion: an observational studyThe Lancet Infectious Diseases 20:1470–1480.https://doi.org/10.1016/S1473-3099(20)30228-0
Antimalarial drug resistance: a threat to malaria eliminationCold Spring Harbor Perspectives in Medicine 7:a025619.https://doi.org/10.1101/cshperspect.a025619
Evidence of artemisinin-resistant malaria in western CambodiaNew England Journal of Medicine 359:2619–2620.https://doi.org/10.1056/NEJMc0805011
Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast AsiaThe Journal of Infectious Diseases 211:670–679.https://doi.org/10.1093/infdis/jiu491
Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic studyThe Lancet Infectious Diseases 19:952–961.https://doi.org/10.1016/S1473-3099(19)30391-3
ReportReport on Antimalarial Drug Efficacy, Resistance and Response: 10 Years of Surveillance (2010–2019) GenevaWorld Health Organization.
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Denmark was one of the few countries where it was politically decided to continue cancer screening during the COVID-19 pandemic. We assessed the actual population uptake of mammography and cervical screening during this period.
The first COVID-19 lockdown in Denmark was announced on 11 March 2020. To investigate possible changes in cancer screening activity due to the COVID-19 pandemic, we analysed data from the beginning of 2017 until the end of 2021. A time series analysis was carried out to discover possible trends and outliers in the screening activities in the period 2017–2021. Data on mammography screening and cervical screening were retrieved from governmental pandemic-specific monitoring of health care activities.
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Denmark continued cancer screening during the pandemic, but following the first lockdown a temporary drop was seen in breast and cervical screening activity.
Region Zealand (R22-A597).