Imported malaria: a possible threat to the elimination of malaria from Sri Lanka?

Authors


Corresponding Author G. N. L. Galappaththy, Anti-Malaria Campaign Headquarters, P.O. Box 1472, Colombo 5, Sri Lanka. Tel.: +94-011 2368173/4; E-mail: hapugalleg@gmail.com

Abstract

Objective

To discuss epidemiological aspects of imported malaria and the potential impact of imported malaria cases reported in Sri Lanka 2008–2011 in terms of a possible resurgence of the disease.

Methods

The national malaria database was used to assess details regarding country where the infection was possibly acquired, species of Plasmodium, number of days lapsed between disembarkation in Sri Lanka and diagnosis, compliance with national treatment guidelines including percentage of patients followed up as per the national guidelines.

Results

After the strengthening of malaria surveillance, during the 4-year period, 152 imported malaria cases were recorded: an increase of 176% in the number of cases. Most of the imported malaria infections were acquired by Sri Lankan Nationals mainly from South Asia, especially India. Plasmodium vivax accounted for 64% of the infections. Approximately 50% of the cases were diagnosed in the Western Province. The average period from disembarkation in Sri Lanka to malaria diagnosis was 3.6 days. Patients were managed and treated according to the national guidelines. 82% of the patients were followed up for 28 days to ensure parasite clearance.

Conclusions

There is a possible increasing risk of re-introduction of malaria to the country from imported cases. Enhanced surveillance activities and the increase in international travel have contributed to an increase in recorded case numbers. There is a need to further strengthen surveillance, especially for monitoring and timely addressing of imported malaria, if the country is to prevent the re-establishment of transmission within. The importance of having an efficient response mechanism to deal with imported malaria is also highlighted.

Abstract

Objectif

Discuter des aspects épidémiologiques du paludisme importé et l'impact potentiel des cas de paludisme importé signalés au Sri Lanka entre 2008 et 2011, en termes d'une résurgence possible de la maladie.

Méthodes

La base de données nationale de lutte antipaludique a été utilisée pour évaluer les détails concernant le pays où l'infection a probablement été acquise, les espèces de Plasmodium, le nombre de jours écoulés entre l'arrivée au Sri Lanka et le diagnostic, le respect des directives nationales de traitement, y compris le pourcentage de patients suivis selon les directives nationales.

Résultats

Après le renforcement de la surveillance du paludisme au cours de la période de quatre ans, 152 cas importés de paludisme ont été enregistrés, soit une augmentation de 176% du nombre de cas. La plupart des cas de paludisme importés ont été acquis par des ressortissants sri-lankais, principalement de l'Asie du Sud, notamment en Inde. Plasmodium vivax représentait 64% des infections. Environ 50% des cas ont été diagnostiqués dans la province de l'Ouest. Le délai moyen entre l'arrivée au Sri Lanka et le diagnostic du paludisme était de 3,6 jours. Les patients ont été pris en charge et traités selon les directives nationales. 82% des patients ont été suivis pendant 28 jours afin de s'assurer de l’élimination des parasites.

Conclusions

Il existe un risque possible croissant de la réintroduction du paludisme dans le pays à partir de cas importés. Des activités de surveillance accrue et l'augmentation des voyages internationaux ont contribué à une augmentation du nombre de cas enregistrés. Il est nécessaire de renforcer la surveillance, en particulier dans la réponse au paludisme importé par le suivi et en temps opportun, si le pays veut empêcher le rétablissement de la transmission à l'intérieur. L'importance d'avoir un mécanisme de réponse efficace pour traiter le paludisme d'importation est également soulignée.

Abstract

Objetivo

Discutir aspectos epidemiológicos de la malaria importada y el impacto potencial de los casos de malaria importada reportada en Sri Lanka entre el 2008–2011 en términos del posible resurgir de la enfermedad.

Métodos

La base de datos nacional para malaria se utilizó para evaluar los detalles con respecto al país en el que posiblemente se había adquirido la infección, las especies de Plasmodium, el número de días que pasaron desde el desembarco en Sri Lanka y el diagnóstico, cumplimiento con las guías nacionales de tratamiento incluyendo el porcentaje de pacientes con seguimiento según las guías nacionales.

Resultados

Después de fortalecer la vigilancia de malaria, se registraron 152 casos de malaria importada durante un periodo de cuatro: un aumento del 176% en el número de casos. La mayoría de las infecciones importadas fueron adquiridas por nacionales de Sri Lanka principalmente en Sud Asia, y especialmente en India. Plasmodium vivax era responsable del 64% de las infecciones. Aproximadamente un 50% de los casos fueron diagnosticados en la Provincia del Oeste. El periodo medio entre el desembarco en Sri Lanka y el diagnóstico de malaria era de 3.6 días. Los pacientes fueron manejados y tratados según las guías nacionales. Un 82% de los pacientes fueron seguidos durante 28 días para asegurar la limpieza de parásitos.

Conclusiones

Hay un posible aumento en el riesgo de reintroducción de la malaria en el país debido a los casos importados. Una mejora en las actividades de vigilancia y el aumento de viajes internacionales han contribuido a un aumento en el número de casos registrados. Es necesario reforzar la vigilancia, especialmente para monitorizar y ocuparse a tiempo de la malaria importada, si el país ha de prevenir el reestablecimiento de la transmisión interna. Se enfatiza la importancia de tener un mecanismo de respuesta eficiente para manejar la malaria importada.

Introduction

Sri Lanka adopted the Global Malaria Control Strategy recommended by WHO in 1994, focusing on early detection and prompt treatment of cases with selected use of vector control methods. Stratification of malarious areas began in 1996 and has been reviewed periodically facilitating the more effective use of available resources. Since 2002, there has been an >99% reduction in the annually reported number of malaria cases from a high of 264,549 in 1999 to 196 in 2007 (Anti-Malaria-Campaign 2008).

Influenced by this sustained reduction in the morbidity and mortality over several years, and the availability of external financing, the National Anti-Malaria Campaign (AMC) developed a strategic plan for the phased elimination of malaria from the country by the end of 2014. Based on this plan, the country successfully applied for a malaria elimination grant in Round 8 from the Global Fund to Fight AIDS, Tuberculosis & Malaria (GFATM). The end of the long conflict and the additional funding provided by the GFATM has made it possible for the country to actually target the planned interruption of P. falciparum transmission in the country by the end of 2012 and that of P. vivax transmission by the end of 2014. One of the key elements that have been captured in the strategic plan for Elimination of Malaria 2008–2012 is prevention of re-introduction of malaria through strengthening surveillance and management of imported malaria (Anti-Malaria-Campaign 2008). Already Sri Lanka has made excellent progress towards elimination of malaria by effective control of local malaria transmission by active parasitological and entomological surveillance (Anti-Malaria-Campaign 2011). AMC introduced artemisinin combination therapy (ACT) for the treatment of uncomplicated falciparum malaria country wide in 2008, with a view of preventing the establishment of imported falciparum foci in the country (Ministry of Healthcare & Nutrition 2008). Although malaria is a notifiable disease in Sri Lanka and a significant strengthening of surveillance has occurred, it is still possible that cases go unreported.

The conducive climate prevailing throughout the year resulting in an abundance of vectors, a large population who has little or no immunity to malaria due to the low prevalence reported during the past decade, and a growing number of foreign arrivals in the country have increased the likelihood that imported malaria could possibly be the most likely source of a resurgence of disease transmission in the country. This situation has been further compounded by short-term overseas employment opportunities provided through the United Nations for the armed forces personnel to serve in malaria-endemic countries with civil conflict (Sudan, South Sudan, Liberia, Haiti, etc.) and the local employment (legal and illegal) of cheap labour from adjoining malaria-endemic countries in the region.

Our aim was to describe epidemiological aspects of imported malaria and the potential impact of imported malaria cases reported in Sri Lanka 2008–2011 in terms of a possible resurgence of the disease.

Methods

Imported malaria is defined as a case of malaria that has been acquired in another country and diagnosed in Sri Lanka by a blood smear examination and/or rapid diagnostic test (RDT). All imported malaria cases are recorded in the national database of malaria cases and could include Sri Lankan citizens who have recently visited a malaria-endemic country and returned to Sri Lanka or foreign nationals (including non-resident Sri Lankans) who have visited Sri Lanka for holiday/business/employment after spending time recently in a malaria-endemic location. The case-based collection of data pertaining to imported malaria commenced in 2008, with the planned elimination of malaria from the country. We reviewed the database of all malaria cases, recorded and selected those listed as imported or having acquired the disease out of the country. This group of cases was further analysed to determine characteristics of the population, country where the infection was acquired, species of Plasmodium, district in Sri Lanka where the case was reported, number of days elapsed since arrival in Sri Lanka to the diagnosis of malaria, compliance with national treatment guidelines and percentage of patients followed up for 28 days to ensure parasite clearance as per the national guidelines.

Cases were detected through a mix of strengthened passive detection from facilities and active case detection through screening of returning security forces personnel completing UN mission.

Results

Between 2008 and 2012, 152 imported malaria cases were reported, 138 in Sri Lankan citizens and 14 in foreign nationals. The end of the civil conflict brought not only a significant reduction in the number of indigenous malaria cases reported (from a high of 670 cases in 2008 to 124 in 2011; P < 0.05) but also a marked rise in the proportion of imported malaria cases recorded due to strengthened surveillance and an increase in travel both to and from the country. Indigenous malaria cases have remained more or less stable from 2008 (670) to 2009 (558) to 2010 (684), followed by a dramatic drop to only 124 cases in 2011. Although the imported malaria cases recorded during this period accounted for only 7.4% (152/2036) of the total cases, figures in 2011 indicate that 29% of cases reported during the year were imported (51/175) (Figure 1).

Figure 1.

Number of imported malaria cases vs. number of indigenous cases reported in the country from 2008 to 2012. Imported cases vs. indigenous cases 2008: 23 vs. 670; 2009: 27 vs. 558; 2010: 51 vs. 684 and 2011 51 vs. 124.

There has been a significant rise in the number of imported malaria cases originating from South Asia, which has doubled from 2010 onwards (i.e. from 15 in 2008 to 40 in 2010 annually). A greater proportion of these cases are being reported from travellers returning from India (106/152); this proportion has been increasing substantially since 2008. This is followed by malaria imported from Africa, which accounts for the origin of 34 cases. Proportion and number of cases originating from Africa and other continents have remained relatively similar over the years (Table 1).

Table 1. Number of indigenous and imported malaria cases and probable continent of origin of imported malaria cases
Continent2008200920102011Total
Imported malaria cases
South Asia15164240113
India14154136106
Pakistan0101010407
Africa71071034
Caribbean10203
Australia and Oceana00011
South-East Asia01001
Total23275151152
Indigenous malaria cases6705586841242036

Amongst the imported infections reported during the 4-year period under review, 64% were due to P. vivax (n = 97), 26% to P. falciparum (n = 39), 9% (n = 14) to mixed infections with both and 1% (n = 2) to P. malariae (Table 2). The number and proportion of P. vivax cases being reported has steadily increased over the past 4 years with 89% (n = 86) vivax infections being reported after arriving from India. Of these, 12 (14%) were Indian nationals who visited Sri Lanka for sightseeing (8), employment (2) or business (2) and the rest (74 persons) of Sri Lankan origin, a majority returning after sightseeing or business. Individuals returning from Africa were more likely to be infected with P. falciparum infection. The two cases of P. malariae were also contracted in Africa. Sri Lankan forces returning from UN missions to Hiati and Africa accounted for 13 cases, a majority (69%) suffering from falciparum malaria.

Table 2. Epidemiological aspects of imported malaria
CharacteristicTotal P. falciparum P. vivax Mixed P. malariae
Year
20082371141
200927111420
201051123351
20115193930
Age (years)
<1540400
15–35681442111
>3580255131
Sex
Male1283580112
Female2441730
Probable Continent of origin
South Asia113169160
India106148660
Pakistan72500
Africa3420482
Caribbean32100
Australia and Oceania11000
South-East Asia10100
Nationality
Sri Lankan1383985122
Non-Sri Lankan14012020
Purpose of overseas travel to India by Sri Lankan Nationals (n = 92)
Sightseeing4583520
Business4063310
Employed and returned30300
Other40310
Purpose of overseas travel to other countries by Sri Lankan Nationals (n = 46)
 Sightseeing206851
 Business042110
 Armed forces on UN missions139121
Employed and returned96300
Hospitalised
Yes913742102
No61025540
Drugs used in management
Coartem + Primquine44300140
CQ + Primaquine10349702
Quinine55000

Approximately 50% of the imported malaria cases were reported directly to the AMC from the Western Province. This is significant as this Province is, and has been, a non-endemic area for malaria. Figure 2 shows the other districts from which imported malaria cases were reported. The number of indigenous malaria cases being reported from each district over the 4-year period is shown in Figure 3.

Figure 2.

Number of imported malaria cases being reported by district in Sri Lanka.

Figure 3.

Number of indigenous malaria cases by district in Sri Lanka.

The average duration to diagnose malaria after disembarkation in Sri Lanka was 3.6 days (1–18 days). The guidelines for management of malaria patients in Sri Lanka require that patients be followed up with periodic visits and blood smear testing up to 28 days after diagnosis and treatment. However, only 82% of patients could be followed up for the required period to ensure parasite clearance. Patients were lost to follow because they could not be located (change in residence, incorrect address or not being available at the given address) or left the country after diagnosis or due to districts' inability to rapidly mobilise resources and personnel for follow-up.

Some socio demographic characteristics of the population with imported malaria are described in Table 2. The majority of cases (84%, n = 128) were males. 97% were older than 15 years (n = 148), reflecting the larger proportion of adults likely to travel out of the country. 91 individuals have been admitted to hospital for management; this included 95% (n = 37) of falciparum malaria patients, as required by the national treatment guidelines. Vivax-infected malaria patients (n = 42) who showed signs of severe disease or requested inpatient care were also admitted and treated (although this is not required by the national guidelines).

Discussion

Sri Lanka has reported an Annual Parasite Incidence of <0.01 for at risk populations since 2008. However, with a high transmission potential of malaria in much of the country and the increased possibility of a resurgence due to imported infections, it is imperative to have a proper understanding of imported malaria and plan out effective preventive strategies. In the post-conflict era, when Sri Lankan tourism surges to new heights and the country experiences a year on year rise in the rate of arrivals (Report of the Sri Lanka Tourist Board 2011), malaria surveillance including surveillance for imported malaria was strengthened as part of the elimination programme. This resulted in an increase in the proportion of imported malaria cases, since 2008, with 29% of all reported cases being imported in 2011, indicating the increasing significance of imported malaria in the country.

Since 2009, the National Anti-Malaria Campaign has considerably strengthened the malaria surveillance system in preparation for malaria elimination by the end of 2014. Steps have been taken to recruit and train Public Health Laboratory Technicians for malaria diagnosis in existing especially designated malaria diagnosis laboratories of government hospitals. 45 new diagnostic facilities have been established in partnership with the private sector in government hospitals situated in the Northern and Eastern Province, which still report the highest number of cases. Human resources capacity for malaria diagnosis has been increased with their assistance. RDTs were procured in greater numbers and distributed to hospitals where microscopists are not available to confirm malaria diagnosis in individuals who present with a clinical suspicion of the disease. Sufficient RDTs are also made available with the Regional Malaria Officers (RMOs) of each district and can be obtained free of charge on request by government or private practitioners. In addition to passive case detection for malaria, active case detection by mobile malaria clinics plays a significant role in diagnosing malaria in high-risk populations such as armed forces and persons living in previous high malaria-endemic communities. Vector surveillance has been enhanced with a view to predicting possible outbreaks of malaria, and vector control interventions (including distribution of long-lasting insecticide-treated nets to at risk populations, focal indoor residual spraying and antilarval measures) have been scaled up. With the end of the conflict, hospitals and road ways have been restored in the Northern and Eastern Provinces and healthcare personnel have returned to a region that is no longer a high-risk area.

Since the end of the conflict, most reported malaria was vivax, diagnosed mainly amongst security forces personnel. Many malaria infections were probably due to relapses of vivax and not newly acquired infections. Molecular epidemiological studies were not carried out to exclude a new infection. However, circumstantial evidence based on the occurrence of continued episodes of malaria amongst soldiers in the absence of any cases amongst civilians led to suspicion that these were relapses. This was further confirmed by the fact that a supervised administration of a 14-day course of primaquine under directly observed treatment to vivax-infected security forces personnel through the Sri Lanka Army Medical Corps resulted in a decrease or near absence of cases amongst soldiers. This ensured rapid decline of the reported vivax in the country from 2010 to 2011, which together with the heightened surveillance activities could have led to a dramatic reduction in the number of indigenous cases in 2011. While the origin of infection was considered to be imported amongst soldiers returning from overseas duty, it may in some instances have been locally acquired before their departure. This was not excluded.

All 97 cases of imported P. vivax malaria responded to the standard treatment of chloroquine and primaquine (14 days). Early diagnosis and radical cure of individuals diagnosed with imported malaria ensured that further transmission of disease was prevented. After the confirmation of diagnosis, an individual with falciparum malaria is mandatorily admitted to a medical facility for directly observed treatment with ACT followed by a single dose of primaquine. In the period under study, chloroquine and primaquine have been used for the treatment of imported falciparum malaria in four patients, prior to the introduction of the new guidelines for treatment of malaria in 2008. To prevent the emergence and spread of drug resistant falciparum malaria, which is one of the most pressing issues facing malaria-endemic countries today, the importation and distribution of Coartem® are centrally controlled by the AMC and made available to government and private hospitals free of charge upon confirmation of diagnosis. With this policy in place and the requirement for mandatory in-patient management of all falciparum infections, the AMC is notified whenever falciparum cases are diagnosed and managed in public or private sector hospitals. Intravenous quinine, which is still the recommended first-line treatment for severe falciparum malaria in the country, was used to manage five patients who exhibited complications. Over this 4-year period, the AMC followed up 82% of imported malaria cases for 28 days to ensure successful cure. Inability to follow-up 100% of cases is attributed to several included in the results section.

The risk of onwards transmission by infected individuals will depend on the presence of a vector and climatic and environmental conditions suitable for transmission. Until the diagnosis is made and the individual treated, the person will remain infectious. The combined decline of locally reported cases and the increase in imported cases now means that imported cases could contribute to resurgence. The assumption is based on this evidence, and not on secondary cases appearing following reported imported cases, which the country has been able to prevent to date.

To minimise the number of imported malaria cases not being reported, a standard operations procedure issued by the AMC to all hospitals and healthcare providers indicates that a malaria case once detected has to be reported to the AMC Head Quarters directly or through the RMO. To enhance the reporting mechanisms, AMC has now embarked on a novel toll-free self-reporting system for the population utilising the high availability of mobile phones. A web-based surveillance system is also in place to report the cases electronically. With better diagnostic tools being available and sophisticated reporting systems in place, an increase in the proportion of imported malaria being reported is expected as the proportion of indigenous malaria decreases. However, with all imported malaria cases being detected within 18 days of arrival in the country, there is a possibility that some late-onset primary attacks and relapses could have been missed.

The majority of the imported malaria cases are being reported from the more urbanised Western Province, which is traditionally not malaria endemic, and where transmission of malaria has been very low or non-existent during the past couple of decades. This may be related to the fact that many people travelling overseas are from these areas, and tourists visiting the country often may be seeking treatment in case of illness from the more developed hospitals in these areas. While this argues well for limiting the possibility of onward transmission, it does not exclude the possibility. In addition, it may be an indication that further strengthening of surveillance, especially for imported malaria, is necessary in other areas of the country. Due to the current trend of decrease in the number of indigenous malaria cases in Sri Lanka, malaria is low on the list of diseases considered for differential diagnosis amongst clinicians examining a patient with fever even in previously high malaria-endemic areas. Clinicians have been made aware of the potential threat of imported malaria when treating patients who return from abroad through distant education programmes and lectures conducted by the AMC staff in association with the Independent Medical Practitioners Association, the largest single association of private healthcare providers in the country. The importance of thoroughly investigating patients with fever, including blood smear examination and/or RDTs to confirm malaria, has been stressed, especially if the person has travelled to a high malaria-endemic country or returned from such an area in the recent past.

Considering the fact that Sri Lanka almost reached a near eradication status with 17 cases being reported in 1963, one could argue that the key factors which led to the occurrence of an epidemic in 1967/68 were the premature withdrawal of funding and scaling down of surveillance activities. Tourism in Sri Lanka rapidly expanded only after 1966 with the establishment of the Ceylon Tourist Board. Although there was an increase in the arrival of tourists till 1983, thereafter the numbers declined rapidly as a result of the conflict situation that prevailed in the country (Country Profile on Sri Lanka 2010). Since the end of the civil conflict in 2009, tourism in Sri Lanka has expanded with India emerging as Sri Lanka's biggest market for tourist arrivals. Sri Lankans visiting India constitute a relatively small share of the 4.5 million tourists entering India every year, but in absolute numbers, they still outnumber Indians visiting Sri Lanka (Samarajiva & Herath, Ver 2.02). This Increased travel between India and Sri Lanka for sightseeing and business has led to a sharp increase in the number of annual malaria cases being imported from the neighbouring country (accounting for approximately 70% of the total cases). India, the largest country in South Asia, has an API < 2 in most of its country, particularly in districts in the North, West and South. Of the 1.2 billion people, 80.5% live in malaria-risk areas, and India is thought to be a P. vivax-dominated country (Kumar et al. 2012). This is not surprising taking into consideration that 89% of the imported vivax malaria cases diagnosed in Sri Lanka, originated in India. As the number of reported cases in Indians and Pakistanis is low (14 over a 4-year period), there is an urgent need to evaluate how many foreigners are arriving from malaria-endemic regions of these countries to determine their access to malaria diagnosis and treatment during their stay in the country with a view of improving case detection and reporting. Currently, it is not possible to carry this out as relevant data are not collected and may not be routinely collected under the provisions of the new International Health Regulations.

To screen disembarking patients with fever at Bandaranaike International Airport, a health centre specialised in malaria diagnosis was set up, where voluntary screening is encouraged for febrile persons. Wide publicity has been given to travellers departing Sri Lanka to malaria-endemic countries to obtain prophylaxis (mefloquine and chloroquine) that is issued free of charge at the point of exit from the Health Centre in the airport or AMC Headquarters and advice is also provided on mosquito preventive aspects such as use impregnated nets or repellents.

Funds received from the GFATM have made it possible to invest in preventing a resurgence of malaria due to imported malaria cases. Carrying out awareness campaigns targeting migrant workers, advocacy activities carried out at ports of entry and exit in Sri Lanka, including the tracking of all imported malaria cases, messages targeting travellers to endemic countries and awareness programmes amongst clinicians have all contributed in a progressive increase in the number of imported malaria cases detected and reported in the country.

Re-introduction of malaria to the country from imported cases may be a threat to the National Malaria Elimination Programme. Thus, a high level of commitment is required not only from the technical units of the AMC but sustained political and financial commitment is also required not only to prevent re-emergence of disease via imported cases but also re-emergence of disease due to a lack of surveillance as seen in the 1967/68 epidemic in Sri Lanka. As Sri Lanka is an island, preventing the reintroduction of malaria via imported cases is possible if sufficient emphasis is placed on disease surveillance, with adequate capacity for early detection of infections and capacity to ensure radical cure through compliance to national treatment guidelines. Early detection has to be augmented with swift and decisive action (implementing vector control measures and health education) to prevent secondary transmission and the establishment of foci.

Conclusions

We would like to suggest some practical courses of action that can be followed by the AMC: (i) increased collaboration with the army/security forces and United Nations on suitable malaria prevention for Sri Lankan troops on overseas assignments in malaria-endemic countries; (ii) improvement of case detection and reporting completeness both in the government hospitals and private sector, especially from the provinces a high number of cases are being reported as there is a possibility that some cases go unreported; (iii) improving follow-up of cases within the 28-day follow-up period and the possible need for legislation to minimise such loss to follow-up (although 18% loss to follow-up at present is due to travellers returning overseas); (iv) standardisation of hospital criteria for admission and management of vivax patients; (v) awareness and outreach programmes to companies that are based in receptive areas and recruit migrant labourers from India and Pakistan; (vi) Quality Assurance of diagnosis.

Ancillary