Ethics statement

This study is based on routine malaria surveillance information from the Ministry of Health in Suriname. The confidentiality of the study subjects was protected, and personal data was not shared. All patients provided informed verbal consent for malaria research at the time of enrollment in the National Malaria Gene Bank (NMGB). Ethical clearance for the NMGB was obtained by the National Ethics Committee within the Ministry of Health (VG007–08)”.

Surveillance was performed in compliance with relevant laws and guidelines from the Ministry of Health and the national ethics committee.

Study design

This descriptive study of the latest P. vivax outbreak in Suriname presents malaria surveillance data and describes the use of conventional and innovative methods to manage the outbreak, along with the subsequent interventions and their effectiveness. These interventions were implemented during the outbreak from November 2019 to August 2021 by the Medical Mission Primary Health Care Suriname (MM), with support from the National Malaria Program (NMP), the Pan-American Health Organization (PAHO-Suriname) and under the supervision of the Malaria Elimination Taskforce (MET).

Study settings and study population

Suriname is a small tropical, upper-middle income country on the northeastern coast of South America, part of the Guiana Shield and bordering Guyana, French Guiana, and Brazil. During endemic years, malaria transmission in Suriname was year‑round. The country’s coastal area, where the majority of the population lives, has been free of malaria since 1968. The primary malaria vector in the interior of Suriname is the anthropophilic Anopheles darlingi, which is a competent vector even in low mosquito densities [12]. In the last decade, malaria has also been almost non-existent in the Amazonian tropical rainforests in the interior of the country, where tribal communities of the Maroons (descendants of African slaves) and Amerindians live in settlements along the major rivers. However, a continuous influx of malaria is maintained through the uncontrolled cross border movement of people, mostly miners, from illegal gold mining settlements across the Amazon. In addition, Surinamese villagers also travel across borders for family visits. The Indigenous groups in southern Suriname belong to the Trio and Wayana tribes. The Trio tribe populates the northern Amazon Region on both sides of the Suriname-Brazil border, while the Wayana tribe is primarily found along the Tapanahony River in Suriname and on both banks of the Lawa River, at the Suriname-French Guiana border. Cross border visits are therefore a common phenomenon and inhabitants of areas within and across country borders sometimes congregate to partake in religious conferences.

Pelele Tepoe is an Amerindian village, located in the southern part of the country’s rainforest with a low population density of 513 registered inhabitants, predominantly of the Trio tribe. Indigenous tribes in the interior are ruled by traditional authorities with a socio-cultural and administrative role addressing the day-to-day issues within their territory and coordinating activities with the central Government [13]. Road infrastructure is not available, and boats (dugout canoes) and small airplanes are the main mode of transportation. Housing conditions in this area are traditional, with inhabitants sleeping in hammocks under wooden stilt huts with palm-thatched roofs. There is no access to running water, and electricity is provided solely by diesel generators, and their use depends on the local availability of fuel.

The combination of limited infrastructure and geographical remoteness creates a complex web of logistics challenges to access the population for the delivery of healthcare services.

Malaria surveillance and response system

The NMP of the Ministry of Health (MoH) maintains the national surveillance database and coordinates malaria activities throughout the country with a focus on mobile migrant populations. Since 2005, the NMP has also spearheaded the implementation of the national malaria elimination strategy with financial support from several international partners, especially the Global Fund to fight AIDS, Tuberculosis and Malaria. The malaria activities of the NMP are complemented by the Medical Mission Primary Health Care Suriname (MM), a non-governmental health organization providing primary health care to remote villages in the interior of the country. All malaria diagnosis, care, treatment and response measures in Suriname are provided free of charge.

The MET is a technical advisory committee to the MoH, composed of malaria experts, with specialized knowledge across various fields. The MET oversees the national malaria elimination effort, guides the national malaria response, and aligns strategies and activities. During the elimination phase, the MET also reviewed each case to assess the best suited response and determined the actual response measures.

Microscopy is the gold standard for malaria diagnosis in Suriname and is a prerequisite for the diagnosis for each case [14]. Since microscopists are not available at all MM clinics in the remote areas for immediate blood smear examination, rapid diagnostic tests (RDTs) are also used in the field and treatment in these areas can be initiated based on a positive RDT result. However, all RDT results are cross-checked with blood smears, as all microscopic slides are sent to the capital (MM Headquarters) either for confirmation after microscopic screening on site or for first reading.

Upon a positive diagnosis or positive RDT, immediate treatment is administered, in accordance with the national malaria treatment guidelines [14]. Since 2009, Dried Blood Spots (DBSs) are collected from all positive cases to enable molecular analysis, when needed, for molecular confirmation of unreliable microscopy results, for differentiation between recrudescence and reinfection, for drug resistance and for outbreak investigations. DBSs are also stored in the National Malaria Gene Bank (NMGB) for future use.

Malaria diagnosis, care and treatment were delivered to the inhabitants of Pelele Tepoe by trained healthcare assistants of MM, with support from the NMP. These healthcare assistants (GZA, gezondheidszorg assistent) are often recruited from the local communities and their shared language/dialect, local beliefs and traditions facilitate easy access to care. GZA’s are trained by the MM to follow standardized medical guidelines and protocols for malaria screening with malaria RDTs, preparation and staining of microscopic slides and to provide basic treatment upon phone instructions of the supporting medical doctor. They also gather demographic and epidemiological data, including travel history. GZA’s are supervised during regular clinic visits of the medical doctors assigned to their region and they maintain constant communication with them through telehealth with high frequency short wave radio, smart phones, or satellite phones.

Outbreak management approach and measures

Traditional outbreak management strategies and corresponding tools and interventions for 1-3-7 surveillance, community health education and vector control were implemented at the onset of the outbreak. Continuous monitoring of the outbreak trend, examination of each case and thorough evaluation of collected surveillance data guided the selection of additional, less conventional strategies and measures, which were incorporated into the multi-pronged approach. This multi-faceted approach focusing on six key management areas was designed to more effectively contain the outbreak and prevent the reintroduction of malaria in a malaria-eliminating country.

1. “1-3-7” surveillance and response approach

The “1-3-7” surveillance and response strategy for malaria elimination [16] was already adopted by Suriname as surveillance system since 2019.

The numbers 1, 3, and 7 represent the respective deadlines (in days) for each stage of the process. Report a malaria diagnosis within 1 day, complete case investigation within 3 days after reporting, and execute focused investigation and targeted response to prevent further transmission within 7 days.

Although this approach is part of the national malaria prevention and response strategy, the community and local healthcare assistants were not anticipating malaria transmission, due to consecutive years without malaria in Pelele Tepoe. Unfortunately, this misconception resulted in some delays in testing, treatment, and reporting to the NMP at the start of the outbreak. In addition, the screening of migrants and travelers, the timely detection of all malaria cases and implementations of some outbreak measures were negatively impacted by management changes at the MoH and the consequences of the SARS CoV-2 (COVID-19) pandemic.

1. Malaria Health Education and Community Participation

Community engagement had a key role in the implemented awareness program, as increasing malaria knowledge, malaria awareness and community participation are known strategies to keep communities invested and committed to interrupt and prevent malaria transmission. Fostering trust between the MM and the local dignitaries was a vital aspect. In consultation with the community leaders, specifically tailored community awareness sessions, referred to as “Krutu” or traditional community meetings, were organized during the outbreak in November 2019, April, August, October and November 2020, and February, April, August and September 2021. In these meetings, attended by community leaders and villagers, a respectful approach was adopted during the sharing of data, while also encouraging lively interaction with community feedback to evade any unwanted patronizing dynamics. The Information, Education, and Communication (IEC) material regarded contextual malaria information, featuring topics as the causes, transmission, prevention methods, symptoms, testing sites and treatments. The IEC material was reinforced with customized materials such as posters and flyers in the local native language, complemented with vivid illustrations, tailored to the education level of the target population.

The community’s active involvement was evident in the efforts of leaders, who encouraged travelling villagers to test upon returning to the village and advocated for the testing of visiting participants, especially during religious conferences. Additionally, the community was kept regularly updated on the outbreak’s progress through visual displays, including charts showing trends in case numbers. Daily, the total number of positive cases was updated on a writing board at the general meeting site by an appointed community member, after consultation with MM headquarters. Optimized scheduling and execution of visits to the village (only accessible by air) was severely hampered not only by heavy rainfall, which flooded the unpaved grass and sand airstrip throughout the whole rainy season, but also by COVID-19 related lockdowns. Malaria health education and community participation activities were sustained after the outbreak.

1. Vector Control Measures

Another conventional tool during malaria outbreaks are vector control interventions targeting the transmission hotspots to limit the spread of malaria from these high-risk zones to nearby areas. Core vector control interventions such as free of charge provision of long-lasting insecticide-treated nets (LLINs) and mosquito repellant in adult and children’s formulations were deployed throughout the outbreak in collaboration between the MM and the NMP. The local MM health post distributed 840 LLINs, exceeding the village’s population to also allow for old net replacements and provision of LLINs for passing nomad Amerindians.

Furthermore, the community was instructed on the use and washing of LLINs. Also, one round of indoor residual spraying (IRS) with alpha-cypermethrin (Fendona, BASF) was performed on all interior walls and surface areas of each hut, aimed to decrease the density of the adult malaria vectors.

In addition to the aforementioned measures, introduced at the onset of the outbreak, the following prongs were implemented at various stages throughout the outbreak, depending on the evolving needs.

1. Mass Screening and Tailored Treatment

The standard treatment for vivax malaria in Suriname consists of Chloroquine 25 mg/kg for 3 days/Primaquine (0.50 mg/kg for 14 days). While Chloroquine (CQ) is effective against the asexual blood stages of P. vivax, Primaquine (PQ) tackles the dormant liver-stage parasites (hypnozoites). As the effectiveness of the treatment depends on adherence, all medication was provided as treatment under direct observation therapy (DOT) since the start of the outbreak.

An overview of the different treatment regimens used throughout the outbreak are presented in the Additional file 1: S1 Table.

In line with the country’s policies, ‘accelerator’/reactive strategies were deployed to contain the outbreak.

The timeline in Fig 1 illustrates the outbreak cases as bars for weekly reported cases alongside the implemented interventions.

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Fig 1. Timeline outbreak cases & interventions.

https://doi.org/10.1371/journal.pntd.0013970.g001

These measures included intensified malaria screening in response to the local cases, Reactive Case Detections (RACDs) to contain local malaria foci and Mass Drug Administrations (MDAs) to prevent onward malaria transmission, also targeting asymptomatic P. vivax carriers.

Starting from November 2019, all febrile patients were tested for malaria by GZA’s from the MM.

The first RACD was implemented four weeks after the first infection, taking into account the parasite incubation period, time lapse for the development of symptoms and logistical challenges at the time, such as transportation and access to remote areas. This RACD reached 448 persons and resulted in 19 additional positive cases.

The second RACD was conducted as the initial outbreak was subsiding, as depicted in Fig 1. The roll-out of an MDA using a Coartem + PQ regimen was also organized, targeting all eligible residents. This MDA reached more than 88.1% of the residing population, with over 95% completing the full course. However, after a 15-weeks hiatus with zero cases, new positive cases were reported, prompting the deployment of a semi-continuous RACD between Aug 29 and December 6, comprising 7 short events, each lasting between one and three days. In addition, a second MDA was implemented, which however had a substantially lower completion rate (68%). In 2021, the persistent but low-level caseload was addressed through semi-continuous RACD efforts as illustrated in Fig 1.

Each MDA reduced the parasite burden in the community as visualized in Fig 1. In addition, a microscopist was stationed at the health post from October 2020 till June 2021 to perform swift microscopic examination of slides, enabling timely response to new cases and allowing the collection and processing of thick smears on site from all participants every two weeks after the second MDA.

Glucose-6-phosphate dehydrogenase (G6PD)-deficiency testing of positive cases was expanded to village wide mapping since April 2020, through on-site G6PD screening with SD BioSensor as G6PD-enzyme activity analyzer. More than 80% of the population could be tested during this endeavor and the overall G6PD deficiency in Pelele Tepoe was estimated at 9.3% (personal communication dr. S. Vreden). During the outbreak, just 2 persons were not eligible to receive Primaquine on-site, due to G6PD deficiency.

1. Molecular outbreak reconstruction to guide interventions

In an earlier outbreak in another Amerindian village in Suriname, we demonstrated that molecular genotyping of circulating parasite populations utilizing well characterized polymorphic regions within the gene encoding the merozoite surface protein-3α (Pvmsp-3α) [17] and merozoite surface protein-1 F2 (Pvmsp-1 F2) [18], combined with polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) can be a useful tool in regions with low malaria transmission, where the genetic diversity of the parasite population is limited [15].

Therefore, molecular tools for malaria outbreak reconstruction were also utilized in this outbreak to complement the traditional strategies to guide the selection of interventions during this outbreak.

Molecular reconstruction of the outbreak revealed a single clonal lineage, as almost all the tested samples exhibited the same haplotype. The only divergent strains (n = 3) identified during the study [15] were collected from patients with a travel history to Brazil. Their classification as import case was based on the combination of travel history and their genetic profile. The investigated cases with recurring malaria exhibited the same genetic profile. The demonstration of a single clonal lineage during the outbreak enabled the NMP to act accordingly and implement targeted measures such as, allocation of resources to the affected areas, more severe monitoring of travel to and from Pelele Tepoe to other villages in Suriname or neighboring countries and a more stringent screening of travelers. In addition, a more detailed investigation was deployed into the impact of non-Primaquine users on the prolongation of the outbreak, leading to a treatment regimen change aimed at curtailing P. vivax relapses.

1. Tackling Malaria Recurrences

The finding of a single clonal lineage throughout the outbreak, accentuated the need to tweak the outbreak control strategies to include interventions, explicitly addressing recurrent infections.

Tackling malaria recurrences can significantly reduce transmission and requires a holistic approach, particularly addressing the challenge posed by P. vivax, which can remain dormant in the liver as hypnozoites and then reactivate weeks, months or even years after the initial infection [19].

Adherence to treatment during the outbreak was safeguarded through implementation of direct observation therapy (DOT) for all positive patients during their full course of treatment. The focus in this prong was therefore on the non-use of Primaquine.

According to WHO recommendations [20] and national guidelines, Primaquine was not administered to pregnant or breastfeeding women and infants younger than 6 months of age. PQ was also not provided to G6PD deficient patients, as its potential hemolytic toxicity in these patients, requires close medical supervision during treatment, which is not feasible in the hinterland.

Pregnant or breastfeeding women and G6PD deficient patients with a non-Primaquine-containing antimalarial regimen accounted for 6.5% of the infected villagers. In pregnant or breastfeeding women, even the re-treatment with PQ was delayed in most cases, due to breastfeeding periods or an alternating status between pregnancy and breastfeeding.

During the outbreak, 26 recurrent episodes were recorded in eighteen patients (Table 1). Eleven villagers (n = 11) who had completed a full course of either CQ-PQ or Coartem-PQ treatment under DOT, still experienced recurrent infections, resulting in a recurrence rate of 4.9%, as measured till day 180, which corresponds to a PQ efficacy of 95.1%.

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Table 1. Primaquine treatment distribution and rate of recurrence.

https://doi.org/10.1371/journal.pntd.0013970.t001

G6PD deficiency was identified in two villagers infected with malaria and resulted in their treatment with only CQ (Table 1). One G6PD-deficient patient had a single infection, while the other patient experienced five malaria episodes during the outbreak, with just a nine-month interval between the first and last infection. One month after the fifth episode, this patient was brought to the capital and CQ/PQ treatment was administered under supervision to monitor any potential hemolysis induced by Primaquine.

The recurrence rate by day 180 was significantly higher in the non-PQ category, even reaching 60.0%, compared to just 4.9% in the patients who received PQ (p-value is < 0.001). The difference became even more striking when not just single relapses, but multiple recurrences were taken into account (Table 1). Four individuals in the non-PQ category experienced multiple recurrences and even one person in the PQ category endured two recurrent episodes.

The number of multiple recurrences varied between 2–4 recurrent episodes during the outbreak (Table 1) and the periods between multiple recurrences ranged from 1 to 5 months.

More than half of the recurrent malaria episodes originated from just the few PQ-ineligible individuals, triggering additional interventions and subsequently even adjustment of the treatment regimen. The MET recommended strict follow-up of pregnant or breastfeeding women and G6PD deficient patients, with biweekly microscopic monitoring and prompt full treatment (CQ/PQ) upon concluding of breastfeeding.

As relapses seemed to fuel the outbreak, a new re-treatment protocol was introduced as “Radical Cure” (“cura radical”; CR) for the PQ-treated subpopulation in August 2020, consisting of a full re-treatment with CQ/PQ for all diagnosed Category I cases, six weeks after the end of initial treatment (Additional file 1 S1 Table).