Applying novel nucleic acid surveillance to malaria elimination in South Cotabato Province, Mindanao, The Philippines

Project Plan:

In endemic areas where malaria control efforts are successful in reducing the numbers of symptomatic cases, a larger proportion of the remaining malaria parasite population will be harboured by asymptomatic individuals. Novel methods are required to identify those individuals carrying such infections, which are usually of low density in the peripheral blood and thus harder to detect. In 2013, a cross‐sectional sampling of several villages in South Cotabato Province in Mindanao, with parasite detection by nested PCR, identified a handful of people carrying such infections. These included individuals harbouring P. vivax, and others infected by P. falciparum. No symptomatic cases of malaria were seen, and overall parasite prevalence by PCR was less than 5% in each village. Such infections may represent a reservoir of parasites which successfully maintains a low level of transmission year to year in this remote part of the Philippines. Reduction or elimination of this reservoir is probably necessary for malaria elimination to be achieved in this setting.

The parasite detection methods available to field teams in South Cotabato, rapid diagnostic tests based on detection of circulating parasite antigens, and microscopic examination of stained blood films, lack the sensitivity to detect low-density infections, but can be used in, or close to, real-time for near‐patient diagnosis. These asymptomatic cases were previously identified post hoc and therefore could not be given antimalarial therapy at the time. The DNA extracts for nested PCR were prepared from dried filter‐paper blood spots shipped back to LSHTM, UK, and results were obtained months or even more than a year after sample collection. A portable molecular diagnostic test that could travel to, or nearby, the communities of interest and deliver rapid, sensitive parasite detection would overcome this problem, and permit infected individuals to receive antimalarial treatment within several hours, or at most a few days, of identification.

A recent study in Uganda described the application of a new, commercially available molecular diagnostic test, Malaria LAMP, for real-time diagnosis of malaria infections in a rural clinic.1 This test was also found to perform with excellent sensitivity and specificity in a UK clinical setting.2 The provision of LAMP parasite detection less than one day’s travel from the villages of interest would provide an opportunity to evaluate a “test and treat” strategy in South Cotabato. However, the performance of LAMP under these conditions has only been demonstrated once, and never in an Asian setting where P. vivax is prevalent. Some form of retrospective quality control step, performed after completion of the “test and treat” phase and using a different methodology, would be of great value and would permit determination of the sensitivity and specificity of the LAMP strategy in South Cotabato.

The project would visit three villages found to harbour asymptomatic individuals in 2013, and test for parasites cross‐sectionally, using a temporary molecular diagnostic lab with local LAMP capacity. Everyone found to be positive would then be treated with artemether-lumefantrine. Each sample taken would then also be tested, post hoc, by RNA detection methods (Singapore) and by species‐specific nested PCR (London), to generate an estimate of the diagnostic accuracy of the field‐based LAMP. A follow‐up LAMP survey would then be carried out in the same villages 12 months after the initial test and treat, to evaluate parasite carriage one year after the original intervention.

1 – Hopkins H et al. 2013. J Infect Dis 208: 645 – 652.
2 – Polley SD et al. 2013. J Infect Dis 208: 637 – 644.

This study has been terminated.

Diagnostics
Parasite Genetic Diversity
Residual Transmission
Surveillance

May 2014 — Sep 2015

$174,297

Philippines

Malaria Eradication Scientific Alliance (MESA)

Mass Test and Treat (MTaT) strategies
Malaria Molecular Surveillance (MMS)