Malaria, caused by Plasmodium parasites, is a global public health problem. Almost half of world population is at risk of malaria, and in 2018 there were 228 million cases and 405,000 deaths, globally (WHO 2019). In Africa, where Plasmodium falciparum infections dominate, six countries (Nigeria, the Democratic Republic of the Congo, Uganda, Côte d’Ivoire, Mozambique and Niger) accounted for more than half of all malaria cases worldwide. Further, 94% of all malaria deaths occurred in the African continent. Due to malaria control activities, such as improved case management and roll out of insecticide-treated nets and indoor residual spraying, the number of countries moving toward towards disease elimination has increased. In particular, the number of countries with < 100 indigenous cases increased from 17 in 2010 to 27 in 2018 (WHO, 2019).
Cape Verde (population size: ~500,000) is one of the African countries in a pre-elimination phase of malaria control, with < 1 case per 1,000 population per year (DePina et al, 2018). There were 583 indigenous cases and 5 deaths between 2010 and 2018. However, in 2017, 423 (72.6%) cases occurred in an outbreak. This year was an outlier as it corresponds to an increase of 89.9% of cases compared to previous years, and excluding it, the number of cases reported yearly since 2010 has varied between 1 and 48 (average < 20 cases) (WHO, 2019). Despite the control efforts implemented by health authorities, autochthonous cases persist and could delay elimination targets. Malaria prevalence is unstable and autochthonous cases are restricted to the islands of Santiago (96%) and Boavista (4%), while imported cases from countries with disease transmission are recorded in all nine islands. In recent years, local transmission has been restricted to the island of Santiago, especially in Praia city, capital of the country, where it recorded 158 cases, more than 90% of autochthonous cases from 2010 to 2016 (DePina et al, 2018). There is typically low malaria endemicity, but there are fluctuations in morbidity depending on rainfall, with transmission normally occurring between the months of September and November (Arez AP, et al, 1999). However, in 2017, the malaria outbreak occurred before the rainy season, where all the 423 autochthonous P. falciparum cases were reported in Praia city, the capital of the country (WHO, 2018; DePina, et al, 2019). Eighteen patients had at least two relapse episodes in that year, 23 further imported cases were registered (DePina, et al, 2019).
All non-complicated malaria cases in Cape Verde are hospitalized and treated with the artemisin-based combination therapies (ACT; artemether and lumefantrine), which target the parasite erythrocytic asexual stage. All cases also receive the gametocytocidal primaquine drug at the start of treatment, to prevent transmission and interrupt the spread of the disease. Severe cases are treated with intravenous artesunate. Levels of parasitaemia are monitored at the health facilities during the period of the disease and followed-up on multiple occasions up to 42 days (Ministério da Saúde de Cape Verde, 2015). The success in the control and treatment of malaria depends on the clinical efficiency of ACT and avoiding drug resistance (Lubell et al, 2014). Therefore, understanding the epidemiology of drug resistance is vital for an effective drug policy specially within the Cape Verde elimination settings (Khatoon et al, 2009).
The non-temporary movement of people between Cape Verde and malaria endemic countries, particularly to and from West Africa, increases the potential for case importation, and poses a challenge to malaria elimination on the archipelago (WHO, 2012). The circulation of parasites between regions also increases the risk of importing drug resistance, which is underpinned by mutations in the P. falciparum genome. For example, polymorphisms associated with resistance to several anti-malarial drugs have been identified in P. falciparum genes pfdhfr (target for anti-malaria drug pryrimethamine), pfdhps (target for sulphadoxine), pfcrt (target for chloroquine), pfk13 (target for artemisin) and pfmdr1 (target for mefloquine, chloroquine) Similarly, P. falciparum genetics (e.g. pfama1 gene) also gives the parasite the ability to evade the immune response of the host. Therefore, there is a need to understand the genetic diversity of circulating parasites to inform on drug resistance and transmission networks identified by finding near identical parasite genomic sequences. To support this, we collected epidemiological data and blood samples from close contacts of patients, including neighbours and family members, thereby informing on potential risk factors for malaria susceptibility, transmission, and the emergence and spread of outbreaks. Further, our study on the molecular characterization of P. falciparum isolates collected from patients during the 2017 outbreak will provide a baseline assessment of malaria parasite drug resistance profile and genetics in Cape Verde, from which to design population-specific diagnostics, and contribute to strengthening the country’s measures for prevention and control, in order to achieve its elimination targets.