Background
Malaria was eliminated from Sri Lanka in 2012 [
1] and the country received WHO certification of malaria-free status in 2016 [
2]. Malaria has been moderately endemic in Sri Lanka for centuries past, and transmission was typically unstable, with seasonal-causing epidemics every 10–15 years. About two-thirds of the country, in the dry and intermediate zones (defined on the basis of rainfall) and where the principal vector of malaria,
Anopheles culicifacies, was found are endemic for malaria [
3]. The southwestern and central mountainous parts of the country have been generally free of malaria transmission.
Prior to eliminating malaria, there was a predominance of
Plasmodium vivax infections in the country.
Plasmodium falciparum was also present and its incidence varied over the years. From 1999 onwards, under heightened control and later elimination efforts, the malaria incidence declined steadily until October 2012 when the last case of malaria was reported. From 2008 onwards when the Anti Malaria Campaign (AMC) began classifying cases as indigenous and imported, the number of imported malaria cases increased relative to indigenous cases. Malaria in Sri Lanka on the path to elimination and post elimination is described more fully elsewhere [
4,
5].
After elimination, between 2013 and 2017, 278 imported malaria cases were reported in the country [
1,
6]. A high receptivity has also been recorded in some parts of the country due to the presence of malaria vectors. There have been no introduced or indigenous cases of malaria for the past 6 years post elimination until 26 December, 2018, when the first introduced case was reported, a result of local transmission. With good surveillance and a rapid response, transmission was confined to a single case of malaria. This manuscript describes the probable index case and the introduced case of malaria, which was diagnosed, and the actions taken to curtail further onward spread of the disease.
Discussion
It is very likely that the Sri Lankan national acquired the P. vivax infection during his overnight stay at the construction site where the imported malaria patient resided, because he developed fever 12 days after his visit there. Irrespective of whether the initial fever was due to malaria, or the malaria infection developed subsequent to the respiratory tract infection at some point in time before 24 December, this would be consistent with the incubation period of the parasite. There had been no cases of introduced or indigenous malaria reported from anywhere else in the country since malaria elimination, nor had there been any other imported cases in this area; the patient had not travelled to a malaria-endemic country overseas; all this led to the conclusion that the Sri Lankan national acquired the infection at the construction site. Even though the patient gave a past history of malaria (in the absence of any supportive documentation to indicate the species), this being a relapse was highly unlikely because his anecdotal malaria event dates back two decades.
The Sri Lankan national visited the site from where it is believed he contracted the infection on 30 November 2018, which was before the imported malaria patient who was resident there reportedly developed symptoms. It is likely that the latter had a sub-clinical malaria infection, which was infectious to mosquitoes even at that time, and manifested clinically several days later. He was a resident of Uttar Pradesh, India, which is highly endemic for malaria [
18]. Several such asymptomatic malaria infections have been detected among foreign workers and refugees [
19] in the past few years. It has also been found that those who have been negative for malaria on screening develop symptomatic infections at various times, weeks to months after their arrival in the country on follow up, indicating that they harboured asymptomatic and/or sub-microscopic blood infections, or in the case of
P. vivax, even dormant liver stages.
The genetic analyses of P. vivax strains obtained from both cases showed an identical match at five polymorphic gene loci, suggesting a strong molecular epidemiological link between the imported case and the infection in the Sri Lankan national. The csp and msp1 (F1) gene sequences showed close relationship with P. vivax strains reported previously in India. The collective body of evidence points to the latter being an introduced case of malaria resulting from local transmission of P. vivax: the source of the mosquito infection, and the index case being the imported malaria patient from India who was resident at the construction site.
There was a delay of either 14 days or fewer, from the time the introduced case developed febrile symptoms to the time at which he was diagnosed as malaria, depending on whether the initial fever was the beginning of the malaria infection, or if malaria symptoms developed subsequent to a respiratory tract infection for which he was treated at the hospital. He had visited a private health care provider before presenting at the first government hospital, and had not been tested for malaria by either, but had, instead, been investigated and treated for a respiratory infection at the hospital. As reported earlier, one of the main challenges in the post-elimination phase of malaria is that, being a rare disease in Sri Lanka now, malaria tends to be overlooked by clinicians as a cause of fever in favour of other highly prevalent infections, such as those of viral and bacterial origin. However, in this case the failure to test for malaria may have been because the patient gave no history of overseas travel. The low parasitaemia of 246 parasites/μL, which he had at the time of the malaria diagnosis at the second hospital he presented to, is likely to have been due to the partial effects of medications, particularly the antibiotic that he had received during the past 14 days. The delay in diagnosis of the introduced case, though quite unacceptable, was fortunately not associated with a risk of onward transmission because the principal malaria vector is rarely found in Western Province, as was confirmed by the entomological surveillance carried out where he resided and in the vicinity of the Government Base Hospital where he was an inpatient.
The index case and the introduced case were diagnosed and treated radically. This, along with the thorough case investigation and a very rapid and thorough response (in terms of case and entomology surveillance, RCD, appropriate vector control and increasing clinician awareness), would have prevented the occurrence of any further cases, and the event was confined to a single introduced case.
Rapid response teams were mobilized from both AMC headquarters and other districts. While the parasitological and entomological activities continued in Moneragala district in relation to the index case, parasitological and entomological surveillance was conducted in Western Province, where the introduced case resided. Similar case surveillance activities were carried out promptly in all other provinces to where contacts of both cases were traced. The response to the cases by way of raising the awareness of the public and the medical professionals in the country was important because 6 years after malaria elimination clinicians are no longer familiar with the disease, and malaria is not being considered as a high probability in the differential diagnosis of febrile illnesses. Overall, the experience tested the capacity and the efficiency of the surveillance and rapid response system in Sri Lanka in the prevention of malaria re-introduction phase.
Given the heavy presence of imported labour in the country, mainly from India, and from other neighbouring malaria-endemic countries, and the high malaria receptivity in parts of Sri Lanka as documented here, the occurrence of an introduced case is not entirely unexpected. Nevertheless, this event highlights several important aspects relating to the prevention of re-establishment of malaria in the country and elsewhere.
Active case surveillance by regular screening of foreign worker groups for malaria, which is highly labour intensive, is a necessity, but may not be sufficient as a measure to reduce the risk of transmission in malaria-receptive areas. This is because many who are aparasitaemic at the time of screening by microscopy and RDT, but become clinically and parasitologically patent at various times subsequently, indicates that they harbour latent blood or liver stage infections [
19]. Radical mass treatment of such groups of foreign labour from endemic countries who are likely to be infected on account of their previous exposure may need to be considered as a strategy by AMC in areas of high receptivity.
The continuing role and extent of entomological surveillance in the country after malaria elimination, has been the subject of much debate over the past few years. However, this episode of local transmission and its effective management to prevent further transmission serve to highlight the importance of entomological surveillance. It was the routine entomological surveillance carried out in response to the imported case on 21 December (which was before the introduced case was detected on 26 December) that alerted the AMC to the high transmission risk at the site and led to the commencement of vector control. This would have averted any further transmission that could have occurred during the period between the detection of the two cases and possibly prevented an outbreak, not just at the site, but also in other parts of the country because there was considerable movement of labour between the construction site and other districts. Historically, the resurgence of malaria in Sri Lanka (then Ceylon) in 1963 after near elimination, which led to endemic malaria for the next 50 years, was traced to similar events. From a focus of transmission in a gem-mining city, where receptivity had been high, people carried malaria infections to various parts of the country [
20]. The current experience re-affirms the critical role of entomological surveillance for the purpose of estimating and mitigating the risk of malaria re-establishment under the continuing threat of imported malaria. It also emphasizes the need to now shift the focus of entomological surveillance from sentinel sites (which were used prior to malaria elimination) to vulnerable sites such as those areas inhabited by groups of foreign labour from endemic countries.
The prevention of malaria re-introduction programme is structured such that AMC is a central government body which provides technical guidance to Regional Malaria Offices, which are the implementing agencies in a devolved provincial authority. The Regional Malaria Offices have dedicated staff for malaria work and also undertake dengue control activities. Maintaining this structure even after elimination and malaria-free certification enabled the AMC to mount a rapid and effective response. A Technical Support Group comprising independent experts and Ministry of Health officials and chaired by the Director General of Health Services meets every 2 months and keeps the Ministry aware of malaria in terms of ensuring availability of resources in such an eventuality [
15]. In addition, the AMC publishes the number of imported malaria cases reported in the country in the monthly newsletter of the Sri Lanka Medical Association, which is widely read by clinicians to keep them updated on the situation. These measures were key to the rapidity and intensity of the response mounted.
The occurrence of this case was a test for the AMC and the Provincial Health System on their surveillance and response preparedness and capacity. It also highlighted, among others, the critical need to maintain adequate emergency stocks of malaria commodities: insecticides, diagnostics and medicines, even though their expiration dates may often be reached before they can be consumed on account of the rarity of use. The introduced case was detected at the year-end holiday period when non-essential administrative operations were at ebb. And so, the effective response was mounted amidst a host of administrative and logistical challenges. The scale of operations conducted by the AMC in collaboration with the provincial health system in this instance is laudable, and will need to be maintained if Sri Lanka is to remain malaria-free. It may, however, also raise the question of cost and sustainability of such a surveillance and response system. Studies have shown that the cost of sustaining an effective surveillance and response system for malaria is far less, in economic terms alone, than that if malaria were to return [
21]. When health and development costs of malaria are computed the return on an investment to prevent malaria re-introduction would be far greater.
Few countries, which have recently eliminated malaria and several that are progressing to elimination in the next few years, are in the tropical belt where receptivity remains high as in Sri Lanka [
22]. This case is a reminder that the global malaria elimination drive will make little sense unless investments are made to prevent the re-establishment of the disease from countries that achieve elimination. Population movement of the kind and magnitude that impose a high risk of re-introducing malaria tend to be highest within rather than outside of regions of the world. This is due to close social, cultural and economic ties that exist among neighbouring countries. Even Sri Lanka, being an island nation, is not exempt from rampant legal and illegal migration from countries in the region, carrying with it the risk of malaria importation as shown here. Many countries in Asia (Bhutan, Nepal, Timor Leste), Middle East (Saudi Arabia, Iran) and in the Americas (e.g., Costa Rica, Suriname) [
23], which are on track to achieve elimination in the next few years, share porous land borders with highly malaria-endemic neighbouring countries. The threat of re-introduction in those situations would be even greater than the one described here, and measures to mitigate that risk would be paramount. As this case serves to illustrate, it is imperative that elimination of malaria is pursued countrywide, but as a regional goal, it being the only sustainable outcome until such time that malaria eradication is achieved.
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