Gaps in research and capacity development for malaria surveillance and response in the Asia-Pacific: meeting report.

BACKGROUND: This report is based on the 2021 annual meeting of the Asia-Pacific Malaria Elimination Network Surveillance and Response Working Group held online on November 1-3, 2021. In light of the 2030 regional malaria elimination goal, there is an urgency for Asia-Pacific countries to accelerate progress towards national elimination and prevent re-establishment. The Asia Pacific Malaria Elimination Network (APMEN) Surveillance Response Working Group (SRWG) supports elimination goals of national malaria control programmes (NMCPs) by expanding the knowledge base, guiding the region-specific operational research agenda and addressing evidence gaps to improve surveillance and response activities. METHODS: An online annual meeting was hosted from 1 to 3 November 2021, to reflect on research needed to support malaria elimination in the region, challenges with malaria data quality and integration, current surveillance-related technical tools, and training needs of NMCPs to support surveillance and response activities. Facilitator-led breakout groups were held during meeting sessions to encourage discussion and share experience. A list of identified research priorities was voted on by attendees and non-attending NMCP APMEN contacts. FINDINGS: 127 participants from 13 country partners and 44 partner institutions attended the meeting, identifying strategies to address malaria transmission amongst mobile and migrant populations as the top research priority, followed by cost effective surveillance strategies in low resource settings, and integration of malaria surveillance into broader health systems. Key challenges, solutions and best practices for improving data quality and integrating epidemiology and entomology data were identified, including technical solutions to improve surveillance activities, guiding priority themes for hosting informative webinars, training workshops and technical support initiatives. Inter-regional partnerships and SRWG-led training plans were developed in consultation with members to be launched from 2022 onwards. CONCLUSION: The 2021 SRWG annual meeting provided an opportunity for regional stakeholders, both NMCPs and APMEN partner institutions, to highlight remaining challenges and barriers and identify research priorities pertaining to surveillance and response in the region, and advocate for strengthening capacity through training and supportive partnerships.

Evaluation of a haemozoin-based rapid diagnostic test for diagnosis of imported malaria during the phase of prevention of reestablishment in Sri Lanka.

BACKGROUND: Sri Lanka, an island nation, has eliminated endemic malaria transmission. Maintaining elimination in the continued presence of vectors requires vigilance in screening people travelling from high malaria-risk areas and a rapid response with focal screening for infections identified in the community. Such screening requires accurate and very rapid assays that enable an immediate response. Both microscopy and rapid diagnostic tests (RDTs) have limitations including sensitivity and speed in screening large numbers, while polymerase chain reaction (PCR) is practical only as laboratory confirmation. This study assessed the utility of 'Gazelle', a novel rapid malaria assay based on magneto-optical detection of haemozoin, a by-product of malaria parasite metabolism. METHODS: Between October 2020 and March 2021, two groups of individuals were screened for malaria by four methods, namely, microscopy, Rapid Diagnostic Test (RDT), Gazelle and PCR. Passive case detection was carried out for confirmation of diagnosis amongst individuals suspected of having malaria. Individuals at high-risk of acquiring malaria, namely persons returning from malaria endemic countries, were screened by active case detection. RESULTS: Of the 440 individuals screened for malaria, nine malaria positives were diagnosed by PCR, microscopy and the HRP2 band of RDT, which included five Plasmodium falciparum infections, two Plasmodium ovale, and one each of Plasmodium vivax and Plasmodium malariae. Gazelle correctly detected the P. vivax, P. ovale and P. malariae infections within the 2 min test time, but did not detect two P. falciparum infections giving a sensitivity of 77.8%. Specificity was 100%. DISCUSSION: The Gazelle, a portable bench top device proved useful to screen a large number of blood samples for non-falciparum parasites within 5 minutes of sample input. Species differentiation, and improvement in P. falciparum detection, will be important to broaden utility.

Transfusion-induced Plasmodium falciparum malaria in a beta thalassaemia patient during the prevention of re-establishment phase in Sri Lanka.

BACKGROUND: Malaria was eliminated from Sri Lanka in 2012, and since then 50-60 imported malaria cases have been reported yearly. The country has remained malaria-free since, except for a single case of indigenous malaria in 2018. Blood donors are routinely screened for malaria, and transfusion malaria has not been reported in the country since 1966. CASE PRESENTATION: A 17-year-old splenectomized beta thalassaemia patient developed a transfusion-induced Plasmodium falciparum malaria infection following a blood transfusion 18 days earlier. The blood donor was an armed forces personnel who returned from South Sudan following a United Nations peace-keeping mission. The blood recipient's malaria infection took a complicated clinical course with elevated liver enzymes, lowered blood pressure and a prolonged parasite clearance time of 7 days but he recovered fully after two courses of artemether-lumefantrine interrupted by a course of intravenous artesunate. The prolonged parasite clearance is likely due to lack of splenic clearance of dead or damaged intra-erythrocytic parasites (due to a splenectomy) rather than to the parasite strain being resistant to artemisinin or the partner drug. This is corroborated by the fact that the blood donor's infection responded to artemether-lumefantrine with parasites being cleared on day 3. The blood donor who had not displayed signs or symptoms of malaria, had been screened for malaria on arrival in Sri Lanka and was negative on both microscopy and RDT. At the point of blood donation a blood smear examined microscopically was also reported negative for malaria, but retrospectively, the preserved smear of the donor's blood was found to contain P. falciparum parasites at a very low density. The donor when tested after the transfusion-induced case was diagnosed, also tested positive for malaria and was treated. CONCLUSIONS: After malaria elimination, transfusion-induced malaria from blood donors returning from malaria endemic countries poses a threat to preventing the re-establishment of the disease. Improved surveillance of arrivals in Sri Lanka from malaria endemic countries using more sensitive methods for screening than microscopy may be required to reduce this risk. More stringent criteria for selecting blood donors, and more effective methods of screening donors for malaria than microscopy may also be necessary.

Thrombocytopenia in Malaria: A Red-Herring for Dengue, Delaying the Diagnosis of Imported Malaria.

INTRODUCTION: Fever and thrombocytopenia, often presenting features of malaria, are also the hallmarks of dengue infections. This study examines the degree and duration of thrombocytopenia in imported malaria infections in Sri Lanka and the extent to which this could provide a false trail in favor of a dengue diagnosis. METHODS: The data of all confirmed malaria cases reported in Sri Lanka from 2017 to 2019 were extracted from the national malaria database. These included detailed histories, the time to malaria diagnosis, platelet counts, and in 2019, the trail of diagnostic procedures. RESULTS: Over the 3 years, 158 malaria cases (157 imported and one introduced) were reported. Platelet counts were available in 90.5% (n = 143) of patients among whom 86% (n = 123) showed a thrombocytopenia (<150,000 cells/µl) and in nearly a third (n = 52) a severe thrombocytopenia (<50,000 cells/µl). Only 30% of patients (n = 48) were diagnosed with malaria within 3 days of the onset of symptoms, while in 37% (n = 58) it took 7 or more days. Platelet counts where significantly higher in patients who had symptoms for 7 days or more compared to those who had symptoms for <7 days (χ2 = 6.888, P = 0.009). Dengue fever was suspected first in 30% (n = 16) of the total malaria patients reported in 2019. CONCLUSIONS: Low platelet counts could delay suspecting and testing for malaria. Eliciting a history of travel to a malaria-endemic country could provide an important and discerning clue to suspect and test for malaria in such patients.

Case Report: The First Case of Genotypically Confirmed Plasmodium falciparum Kelch 13 Propeller Mutation in Sri Lanka and Its Implications on the Elimination Status of Malaria.

This case report discusses recrudescence of imported Plasmodium falciparum malaria, in the presence of P. falciparum Kelch13 (PfK13) propeller mutation, in a patient diagnosed and fully treated with artemether-lumefantrine under direct observation in Sri Lanka. This patient presented with a history of 5 days of fever following his arrival from the Democratic Republic of Congo (DRC). He had visited Rwanda 1 week before arrival to Sri Lanka. Treatment was commenced with artemisinin-based combination therapy, artemether-lumefantrine, which is the first-line drug recommended for uncomplicated falciparum malaria. Blood smears were negative for parasites by the third day of treatment. Approximately 2 weeks later, he developed fever again and was diagnosed as having a recrudescence of falciparum malaria. He was treated and responded to the second-line antimalarial dihydroartemisinin-piperaquine. Molecular testing of blood taken from the first infection revealed the presence of amino acid substitutions K189T and R561H within the PfK13 gene. R561H mutation is associated with delayed parasite clearance in Southeast Asia. Although seldom reported from DRC, an emergence and clonal expansion of parasites harboring R561H allele has been reported from Rwanda recently; thus, it is likely that this patient may have got the infection from Rwanda. Sri Lanka eliminated malaria in 2016. However, in the backdrop of continuing imported malaria cases, early diagnosis and prompt treatment is essential to prevent the re-establishment of the disease.

Preventing the re-establishment of malaria in Sri Lanka amidst the COVID-19 pandemic.

The COVID-19 pandemic has had a considerable impact on other health programmes in countries, including on malaria, and is currently under much discussion. As many countries are accelerating efforts to eliminate malaria or to prevent the re-establishment of malaria from recently eliminated countries, the COVID-19 pandemic has the potential to cause major interruptions to ongoing anti-malaria operations and risk jeopardizing the gains that have been made so far. Sri Lanka, having eliminated malaria in 2012, was certified by the World Health Organization as a malaria-free country in 2016 and now implements a rigorous programme to prevent its re-establishment owing to the high receptivity and vulnerability of the country to malaria. Sri Lanka has also dealt with the COVID-19 epidemic quite successfully limiting the cumulative number of infections and deaths through co-ordinated efforts between the health sector and other relevant sectors, namely the military, the Police Department, Departments of Airport and Aviation and Foreign Affairs, all of which have been deployed for the COVID-19 epidemic under the umbrella of a Presidential Task Force. The relevance of imported infections and the need for a multi-sectoral response are features common to both the control of the COVID-19 epidemic and the Prevention of Re-establishment (POR) programme for malaria. Sri Lanka's malaria POR programme has, therefore, creatively integrated its activities with those of the COVID-19 control programme. Through highly coordinated operations the return to the country of Sri Lankan nationals stranded overseas by the COVID-19 pandemic, many from malaria endemic countries, are being monitored for malaria as well as COVID-19 in an integrated case surveillance system under quarantine conditions, to the success of both programmes. Twenty-three imported malaria cases were detected from February to October through 2773 microscopic blood examinations performed for malaria in quarantine centres, this number being not much different to the incidence of imported malaria during the same period last year. This experience highlights the importance of integrated case surveillance and the need for a highly coordinated multi-sectoral approach in dealing with emerging new infections. It also suggests that synergies between the COVID-19 epidemic control programme and other health programmes may be found and developed to the advantage of both.