msp1, msp2, and glurp genotyping to differentiate Plasmodium falciparum recrudescence from reinfections during prevention of reestablishment phase, Sri Lanka, 2014-2019.

BACKGROUND: Sri Lanka after eliminating malaria in 2012, is in the prevention of re-establishment (POR) phase. Being a tropical country with high malariogenic potential, maintaining vigilance is important. All malaria cases are investigated epidemiologically and followed up by integrated drug efficacy surveillance (iDES). Occasionally, that alone is not adequate to differentiate Plasmodium falciparum reinfections from recrudescences. This study evaluated the World Health Organization and Medicines for Malaria Venture (MMV) recommended genotyping protocol for the merozoite surface proteins (msp1, msp2) and the glutamate-rich protein (glurp) to discriminate P. falciparum recrudescence from reinfection in POR phase. METHODS: All P. falciparum patients detected from April 2014 to December 2019 were included in this study. Patients were treated and followed up by iDES up to 28 days and were advised to get tested if they develop fever at any time over the following year. Basic socio-demographic information including history of travel was obtained. Details of the malariogenic potential and reactive entomological and parasitological surveillance carried out by the Anti Malaria Campaign to exclude the possibility of local transmission were also collected. The msp1, msp2, and glurp genotyping was performed for initial and any recurrent infections. Classification of recurrent infections as recrudescence or reinfection was done based on epidemiological findings and was compared with the genotyping outcome. RESULTS: Among 106 P. falciparum patients, six had recurrent infections. All the initial infections were imported, with a history of travel to malaria endemic countries. In all instances, the reactive entomological and parasitological surveillance had no evidence for local transmission. Five recurrences occurred within 28 days of follow-up and were classified as recrudescence. They have not travelled to malaria endemic countries between the initial and recurrent infections. The other had a recurrent infection after 105 days. It was assumed a reinfection, as he had travelled to the same malaria endemic country in between the two malaria attacks. Genotyping confirmed the recrudescence and the reinfection. CONCLUSIONS: The msp1, msp2 and glurp genotyping method accurately differentiated reinfections from recrudescence. Since reinfection without a history of travel to a malaria endemic country would mean local transmission, combining genotyping outcome with epidemiological findings will assist classifying malaria cases without any ambiguity.

Malaria elimination does not cost more than malaria control: Sri Lanka a case in point.

BACKGROUND: Malaria was endemic in Sri Lanka for centuries and was eliminated in 2012. It is widely assumed that the costs of elimination are generally greater than that of control. The costs of malaria elimination in Sri Lanka with that of malaria control in the past using periods in which starting transmission dynamics were similar were compared. METHODS: The expenditure of the Anti-Malaria Campaign (AMC), total and by budget category, during 2002-2010 is compared with that of malaria control during the period 1980-1989, using regression analyses and the Mann Whitney U statistic. RESULTS: The expenditure on malaria control and malaria elimination was similar ranging from 21 to 45 million USD per year when adjusted for inflation. In both periods, external funding for the malaria progamme constituted around 24% of the total budget; during the control phase in the 1980s, external funds came from bilateral agencies and were disbursed in accordance with government budget guidelines. In the elimination phase in the 2000s, most of external funding was from the Global Fund and had flexibility of disbursement. In the 1980s, most funds were expended on commodities-insecticides, diagnostics and medicines and their delivery; in the elimination phase, they were spent on programme management, human resources, technical assistance and monitoring and evaluation; monitoring and evaluation was not a budget line in the 1980s. Although the cost per case of malaria was considerably higher during the elimination phase than in the control phase, expenditure was not on individual cases but on general systems strengthening. CONCLUSION: Malaria elimination in Southeast Asia may not require more funding than malaria control. But sustained funding for an agile programme with flexibility in fund utilization and improved efficiencies in programme management with stringent monitoring and evaluation appears to be critically important.

Epidemiological profile of imported malaria cases in the prevention of reestablishment phase in Sri Lanka.

Sri Lanka reported the last case of indigenous malaria in October 2012, and received malaria-free certification from WHO in September 2016. Malaria cases have since, shifted from indigenous to imported, and the country remains receptive and vulnerable to malaria. A case-based epidemiological study was conducted on all imported malaria cases reported in the country in 2015 and 2016 with the aim of profiling imported malaria to improve the effectiveness of the surveillance and case management system for malaria. Data were obtained from case reports of the Anti Malaria Campaign, hospital records and laboratory registers. Over the 2 years, 77 imported malaria infections were diagnosed in 54 Sri Lankans and 23 foreign nationals. A majority of the infections were reported among males (93%) in the age group of 21-50 years (85.8%), and all were recent travelers overseas. Most patients were detected by passive case detection, but 10% of cases were detected by Active Case Detection. Only 25% of patients were diagnosed within 3 days of the onset of symptoms. In 32% of patients, the diagnosis was delayed by more than 10 days after the onset of symptoms. Plasmodium falciparum infections manifested significantly earlier after arrival in Sri Lanka than did P.vivax infections. The majority of patients (74%) were diagnosed in the Western Province, which was not endemic for malaria. A third of patients were diagnosed in the private sector. The shift in the epidemiology of malaria infection from before to after elimination has implications for preventing the reestablishment of malaria.

A comparative analysis of the outcome of malaria case surveillance strategies in Sri Lanka in the prevention of re-establishment phase.

BACKGROUND: Sri Lanka sustained its malaria-free status by implementing, among other interventions, three core case detection strategies namely Passive Case Detection (PCD), Reactive Case Detection (RACD) and Proactive Case Detection (PACD). The outcomes of these strategies were analysed in terms of their effectiveness in detecting malaria infections for the period from 2017 to 2019. METHODS: Comparisons were made between the surveillance methods and between years, based on data obtained from the national malaria database and individual case reports of malaria patients. The number of blood smears examined microscopically was used as the measure of the volume of tests conducted. The yield from each case detection method was calculated as the proportion of blood smears which were positive for malaria. Within RACD and PACD, the yield of sub categories of travel cohorts and spatial cohorts was ascertained for 2019. RESULTS: A total of 158 malaria cases were reported in 2017-2019. During this period between 666,325 and 725,149 blood smears were examined annually. PCD detected 95.6 %, with a yield of 16.1 cases per 100,000 blood smears examined. RACD and PACD produced a yield of 11.2 and 0.3, respectively. The yield of screening the sub category of travel cohorts was very high for RACD and PACD being 806.5 and 44.9 malaria cases per 100,000 smears, respectively. Despite over half of the blood smears examined being obtained by screening spatial cohorts within RACD and PACD, the yield of both was zero over all three years. CONCLUSIONS: The PCD arm of case surveillance is the most effective and, therefore, has to continue and be further strengthened as the mainstay of malaria surveillance. Focus on travel cohorts within RACD and PACD should be even greater. Screening of spatial cohorts, on a routine basis and solely because people are resident in previously malarious areas, may be wasteful, except in situations where the risk of local transmission is very high, or is imminent. These findings may apply more broadly to most countries in the post-elimination phase.

Technical and operational underpinnings of malaria elimination from Sri Lanka.

Malaria was eliminated from Sri Lanka in 2012, and the country received WHO-certification in 2016. The objective of this paper is to describe the epidemiology of malaria elimination in Sri Lanka, and the key technical and operational features of the elimination effort, which may have been central to achieving the goal, even prior to schedule, and despite an ongoing war in parts of the country. Analysis of information and data from the Anti Malaria Campaign (AMC) of Sri Lanka during and before the elimination phase, and the experiences of the author(s) who directed and/or implemented the elimination programme or supported it form the basis of this paper. The key epidemiological features of malaria on the path to elimination included a steady reduction of case incidence from 1999 onwards, and the simultaneous elimination of both Plasmodium falciparum and Plasmodium vivax. Against the backdrop of a good health infrastructure the AMC, a specialized programme within the Ministry of Health operated through a decentralized provincial health system to implement accepted strategies for the elimination of malaria. Careful planning combined with expertise on malaria control at the Central level with dedicated staff at all levels at the Centre and on the ground in all districts, for several years, was the foundation of this success. The stringent implementation of anti-relapse treatment for P. vivax through a strong collaboration with the military in whose cadres most of the malaria cases were clustered in the last few years of transmission would have supported the relatively rapid elimination of P. vivax. A robust case and entomological surveillance and investigation system described here enabled a highly focused approach to delivering interventions leading to the interruption of transmission.

Effectiveness of passive case detection for imported malaria in a hospital setting in Sri Lanka during the prevention of re-introduction phase of malaria.

Introduction: The effectiveness of the passive case detection (PCD) system for imported malaria was assessed in government hospitals in Sri Lanka post-elimination of malaria. Methods: In 18 medical wards (test wards) in four government hospitals, the referral for malaria testing and the diagnosis of malaria by the ward physicians were monitored. Concurrently, in-ward febrile patients were assessed independently for their eligibility for referral for malaria diagnosis and were tested for malaria. The malaria incidence in 16 other wards (control wards), which the study did not screen, served as controls. Results: Four imported malaria patients were diagnosed within the PCD system among 25 874 febrile patients admitted during the 14-month study period, two of whom were diagnosed in the test wards and two in the control wards. The study's screening programme did not detect any more malaria patients than detected by the routine PCD system of the wards. However, far fewer patients were screened for malaria (1.3%) than were eligible for screening (29.4%), and some infections were detected incidentally, rather than by a request for a malaria test. Conclusion: A continuous effort to maintain awareness of the disease among physicians would be required if the PCD system is to be effective for the detection of imported malaria, post-elimination.

Response of imported malaria patients to antimalarial medicines in Sri Lanka following malaria elimination.

After eliminating local malaria transmission and being certified as a malaria-free country, Sri Lanka is facing the challenge of imported malaria. At the same time, the country has the unique opportunity to be a case study for other countries in a similar situation by approaching this issue systematically, guided by evidence. This study demonstrates the importance of developing a mechanism to detect imported malaria and adopting an evidence-based approach to study the resistance of imported malaria to anti-malarial medicines. This is a prospective study of patients diagnosed with imported malaria in Sri Lanka and treated according to the national treatment guidelines, over 24 months (2015/2016). The clinical features, time to diagnosis, origin of the infection, infecting species, parasite density and the treatment given were recorded. All patients were followed up for 28 days, and in the case of Plasmodium vivax and P. ovale infections, the follow up period was extended to 12 months to establish treatment failures and relapses. Fifty nine uncomplicated and 15 severe imported malaria cases were reported in Sri Lanka during the study period. Most of these infections originated in either Sub-Saharan Africa or South and Southeast Asia. Having a P. vivax infection and low parasitic counts were significantly associated with relative diagnostic delay. One of the 14 uncomplicated P. falciparum patients and two of the 12 severe P. falciparum malaria patients who were followed up till day 28 had a late clinical failure. The others responded adequately to treatment both clinically and parasitologically. There was no treatment failure reported amongst any other species. This study, which is the first to assess the therapeutic response of imported malaria in Sri Lanka after elimination, demonstrates that the current antimalarial treatment policies and strategies in Sri Lanka have been effective against infections acquired overseas up until the end of year 2016.

An Investment Case to Prevent the Reintroduction of Malaria in Sri Lanka.

Sri Lanka has made remarkable gains in reducing the burden of malaria, recording no locally transmitted malaria cases since November 2012 and zero deaths since 2007. The country was recently certified as malaria free by World Health Organization in September 2016. Sri Lanka, however, continues to face a risk of resurgence due to persistent receptivity and vulnerability to malaria transmission. Maintaining the gains will require continued financing to the malaria program to maintain the activities aimed at preventing reintroduction. This article presents an investment case for malaria in Sri Lanka by estimating the costs and benefits of sustaining investments to prevent the reintroduction of the disease. An ingredient-based approach was used to estimate the cost of the existing program. The cost of potential resurgence was estimated using a hypothetical scenario in which resurgence assumed to occur, if all prevention of reintroduction activities were halted. These estimates were used to compute a benefit-cost ratio and a return on investment. The total economic cost of the malaria program in 2014 was estimated at U.S. dollars (USD) 0.57 per capita per year with a financial cost of USD0.37 per capita. The cost of potential malaria resurgence was, however, much higher estimated at 13 times the cost of maintaining existing activities or 21 times based on financial costs alone. This evidence suggests a substantial return on investment providing a compelling argument for advocacy for continued prioritization of funding for the prevention of reintroduction of malaria in Sri Lanka.

Contribution of the private sector healthcare service providers to malaria diagnosis in a prevention of re-introduction setting.

BACKGROUND: Sri Lanka is currently in the prevention of re-introduction phase of malaria. The engagement of the private sector health care institutions in malaria surveillance is important. The purpose of the study was to determine the number of diagnostic tests carried out, the number of positive cases identified and the referral system for diagnosis in the private sector and to estimate the costs involved. METHODS: This prospective study of private sector laboratories within the Colombo District of Sri Lanka was carried out over a 6-month period in 2015. The management of registered private sector laboratories was contacted individually and the purpose of the study was explained. A reporting format was developed and introduced for monthly reporting. RESULTS: Forty-one laboratories were eligible to be included in the study and 28 participated by reporting data on a monthly basis. Excluding blood bank samples and routine testing for foreign employment, malaria diagnostic tests were carried out on 973 individuals during the 6-month period and nine malaria cases were identified. In 2015, a total of 36 malaria cases were reported from Sri Lanka. Of these, 24 (67 %) were diagnosed in the Colombo District and 50 % of them were diagnosed in private hospitals. CONCLUSIONS: An equal number of cases were diagnosed from the private sector and government sector in the Colombo District in 2015. The private sector being a major contributor in the detection of imported malaria cases in the country should be actively engaged in the national malaria surveillance system.

The risk of imported malaria in security forces personnel returning from overseas missions in the context of prevention of re-introduction of malaria to Sri Lanka.

BACKGROUND: Sri Lanka is a malaria-free country. However it remains surrounded by countries with endemic malaria transmission. Since the last indigenous case of malaria was reported in October 2012, only imported malaria cases have been diagnosed with 36 cases detected in 2015, which includes 17 cases each of Plasmodium vivax and Plasmodium falciparum and two cases of Plasmodium ovale. METHODS: This study investigated the knowledge and practices regarding malaria chemoprophylaxis among all the Sri Lankan security forces personnel returning from peacekeeping missions in malaria endemic countries over a 7 month period. Adherence to other malaria prevention measures, occurrence of adverse events and incident cases of malaria were also recorded maintaining the anonymity of the respondents. Potential associations for non-compliance were studied. RESULTS: Interviews were carried out with 559 security forces personnel returning home from foreign deployments in malaria-endemic regions (males: 550, 98.4 %). The majority (553, 98.9 %) was well aware of the need for chemoprophylaxis during the overseas stay and its regular use as prescribed. The overall adherence to chemoprophylaxis was good with 78.7 % (440/559) reporting regular, as prescribed, use. Having better educational qualifications, being female, being prescribed mefloquine, having fever during deployment and belonging to a security force other than the army were significantly associated with poor compliance (p < 0.05). CONCLUSIONS: The study reveals that knowledge regarding malaria chemoprophylaxis among Sri Lankan security forces personnel serving abroad was good, a fact that may have contributed to absence/extremely low incidence of malaria during deployment.

Challenges to malaria surveillance following elimination of indigenous transmission: findings from a hospital-based study in rural Sri Lanka.

INTRODUCTION: Sri Lanka has eliminated local transmission of malaria. Assessing physician preparedness for early case detection is important, in order to prevent re-establishment of local transmission. METHODS: Adherence to malaria screening practices in patients admitted with fever to 12 hospitals in a previously malaria endemic district was evaluated using a cross sectional survey. In addition, knowledge and attitudes among doctors on current malaria surveillance practices and treatment recommendations was assessed. RESULTS: Of 403 fever patients, 150 warranted screening for malaria under the criteria defined by the Anti Malaria Campaign (AMC), with 93 of them having fever for over 7 days. Of these eligible patients, 12.6% (19/150) were investigated by doctors (including 3 persons with fever over 7 days), 14.6% (22/150) by laboratory staff and 72.6% (109/150) by the research team. The majority of doctors were not familiar with the treatment guidelines for malaria (76.5%, 75/98). CONCLUSIONS: Mandatory continuous medical education programmes need to continue to ensure that malaria remains on the differential diagnosis of a fever patient, especially in patients with fever over 7 days. It is essential to publicize the availability of free-of-charge malaria diagnostic facilities, and to ensure that proper notification procedures are followed when a malaria patient is diagnosed.

Patterns and predictive factors of long-lasting insecticidal net usage in a previously high malaria endemic area in Sri Lanka: a cross-sectional survey.

BACKGROUND: Long-lasting insecticidal nets (LLINs) have been widely distributed in Sri Lanka for malaria control. Their effectiveness depends on proper utilisation and maintenance at the household level. METHODS: A cross-sectional study was performed to examine the patterns and predictive factors of LLIN maintenance and use in Anuradhapura district. Data was collected and analysed from 530 LLIN-owning households, selected by a multi-stage cluster sampling technique. Multivariable logistic regression identified factors associated with proper maintenance at the household level. Hierarchical linear modelling identified factors associated with LLIN use the previous night. RESULTS: Almost 75% (377/504) of households had used all their LLINs the previous night, while 82.9% (418/504) had used at least one. Only 3.2% (15/474) were maintaining the LLIN in such a way as to maximise its insecticidal efficacy. Six variables were significantly associated (p<0.05) with use the previous night: more residents, fewer plain nets, reporting practical benefits of LLINs, conical shape, newer nets and lack of side effects. Two variables were significantly associated with proper maintenance: increasing level of education and taking safety precautions while washing. CONCLUSIONS: Results suggest LLIN practices could improve in settings of low malaria transmission if distribution programmes took into account recipient preferences, promoted LLIN use over plain nets, and emphasised the techniques and significance of proper net maintenance.

Characterization of imported malaria, the largest threat to sustained malaria elimination from Sri Lanka.

Sri Lanka has reached zero indigenous malaria cases in November 2012, two years before its targeted deadline for elimination. Currently, the biggest threat to the elimination efforts are the risk of resurgence of malaria due to imported cases. This paper describes two clusters of imported malaria infections reported in 2013 and 2014, one among a group of Pakistani asylum-seekers resident in Sri Lanka, and the other amongst local fishermen who returned from Sierra Leone. The two clusters studied reveal the potential impact of imported malaria on the risk of reintroducing the disease, as importation is the only source of malaria in the country at present. In the event of a case occurring, detection is a major challenge both amongst individuals returning from malaria endemic countries and the local population, as malaria is fast becoming a "forgotten" disease amongst health care providers. In spite of a very good coverage of diagnostic services (microscopy and rapid diagnostic tests) throughout the country, malaria is being repeatedly overlooked by health care providers even when individuals present with fever and a recent history of travel to a malaria endemic country. Given the high receptivity to malaria in previously endemic areas of the country due to the prevalence of the vector mosquito, such cases pose a significant threat for the reintroduction of malaria to Sri Lanka. The challenges faced by the Anti Malaria Campaign and measures taken to prevent the resurgence of malaria are discussed here.

Educating the security forces, a high risk group in malaria elimination efforts: an example from Sri Lanka.

BACKGROUND: The security forces are a high risk group for malaria transmission in Sri Lanka. Interrupting transmission and maintaining surveillance in this group is an important component of elimination efforts. The objective of the study was to develop a prototype educational programme on malaria for security forces serving in endemic areas. METHODS: An interactive seminar was designed to deliver the required knowledge. The content was on current status, transmission, signs and symptoms and the role of security personnel in identification and prevention of malaria. Each seminar was preceded by a pre-test and followed by a post test to assess the improvement of knowledge. RESULTS: Fifty seminars were held in eight districts over 2 months with 2301 security forces personnel participating. Pre seminar knowledge on malaria was significantly better in the medical corps, those who had completed secondary education and in the Army compared to other security forces (p<0.001). Participation in the seminar resulted in an improvement in all domains tested as shown by test scores in post seminar assessment (p<0.001). CONCLUSIONS: Conducting a formal educational programme is an effective strategy to improve awareness on malaria amongst security forces personnel who are a high risk group for re-introduction of malaria into the country.

Effects of modifying the World Health Organization standard operating procedures for malaria microscopy to improve surveillance in resource poor settings.

BACKGROUND: Individuals with fever are screened for malaria in specially-established malaria diagnostic laboratories set up in rural hospitals in the Northern and Eastern Provinces of Sri Lanka. Large numbers of blood smears negative for malaria parasites are being screened daily. Good quality smears are essential to maintain a high diagnostic competency among the technical staff. The modifications made to the World Health Organization (WHO) standard operating procedures to improve the quality of smears have been studied. METHODS: A blinded, controlled, interventional study was conducted in 22 intervention and 21 control malaria diagnostic laboratories. Changes were made to the WHO standard operating procedure protocols to prepare, stain and examine blood smears for malaria parasite detection which were implemented in intervention laboratories. These included wipe-cleaning slides, preparing both thick and thin smears on the same slide, reversing the order of collecting blood for thick and thin smears, dry fixing thick smear for 20-25 minutes under table lamp, polishing the edge of spreader slide with sand paper and fixing the thin smear with methanol if not stained within four hours. Parameters with respect to quality of the smear as per WHO criteria were studied using randomly selected slides, and time taken for the report to be issued was recorded in both groups before and after the intervention. RESULTS: There were no significant differences observed in the parameters studied at baseline between the two groups or pre and post intervention in the control group. In the intervention group streak formation in thin smears was reduced from 29.4% to 5.0%. The average fixing time of thick smears was reduced from 2.4 hours to 20 minutes. Inappropriate thickness of thick smears reduced from 18.3% to 1.5%. Overall quality of thick smears and thin smears increased from 76.1% to 98.0% and 81.7% to 87.0%, respectively. The quality of slides bearing both thick and thin smears increased from 60.0% to 87.0%. CONCLUSIONS: New protocols with amendments to the WHO standard technical procedures ensure that good quality blood smears are prepared rapidly to diagnose malaria and the time required to issue the reports was reduced.

Malaria elimination in Sri Lanka: what it would take to reach the goal.

Fifty years after narrowly missing the opportunity to eliminate malaria from Sri Lanka in the 1960s, the country has now interrupted malaria transmission and sustained this interruption for more than 12 months - no indigenous malaria cases have been reported since October 2012. This was achieved through a period overlapping with a 30-year separatist war in areas that were endemic for malaria. The challenge now, of sustaining a malaria-free country and preventing the reintroduction of malaria to Sri Lanka, is examined here in the context of rapid postwar developments in the country. Increased travel to and from the country to expand development projects, businesses and a booming tourist industry, and the influx of labour and refugees from neighbouring malarious countries combine with the continued presence of malaria vectors in formerly endemic areas, to make the country both receptive and vulnerable to the reintroduction of malaria. The absence of indigenous malaria has led to a loss of awareness among the medical profession, resulting in delayed diagnosis of malaria despite the availability of an extensive malaria diagnosis service. Highly prevalent vector-borne diseases such as dengue are competing for health-service resources. Interventions that are necessary at this critical time include sustaining a state-of-the-art surveillance and response system for malaria, and advocacy to maintain awareness among the medical profession and at high levels of government, sustained funding for the Anti-Malaria Campaign and for implementation research and technical guidance on elimination. The malaria-elimination effort should be supported by rigorous analyses to demonstrate the clear economic and health benefits of eliminating malaria, which exceed the cost of a surveillance and response system. An annual World Health Organization review of the programme may also be required.

High attack rate for malaria through irregular migration routes to a country on verge of elimination.

Irregular migration in the form of human smuggling and human trafficking is recognized as a global public health issue. Thirty-two cases of Plasmodium falciparum were detected in 534 irregular migrants returning to Sri Lanka via failed human smuggling routes from West Africa in 2012, contributing to the largest burden of imported cases in Sri Lanka as it entered elimination phase. Beyond the criminality and human rights abuse, irregular migration plays an important, but often forgotten, pathway for malaria re-introduction. Active surveillance of the growing numbers of irregular migrant flows becomes an important strategy as Sri Lanka advances towards goals of malaria elimination.