AbstractPapua is the most easterly province of Indonesia and has one of the highest burdens of malaria in Asia, with drug resistance documented for both P. falciparum and P. vivax. Improved surveillance systems are needed to overcome specific challenges arising from the declining transmission of malaria. This thesis aimed to investigate the benefits of incorporating molecular tools into traditional surveillance. Principal findings include the following:
Firstly asymptomatic and submicroscopic infections in this area constitute two thirds of detectable parasitaemia and are associated with significant morbidity, highlighting the importance of identifying and treating patients with low-level asymptomatic infection.
Secondly, co-endemic P. falciparum and P. vivax have contrasting micro-epidemiology. Molecular analyses demonstrate intense transmission of P. vivax, but more focal and lower transmission intensity in P. falciparum.
Thirdly, parasites from asymptomatic and symptomatic patients are from genetically similar populations, demonstrating that passive sampling is appropriate for molecular parasite surveillance.
Fourthly, the implementation of highly effective schizontocidal treatment with artemisininbased combination therapy (ACT) reduced the proportion of polyclonal infections in P. falciparum and P. vivax, suggesting reduction in transmission of both species. However, the reduction was greater in the P. falciparum population.
Finally, the expression of the P. vivax chloroquine resistance transporter orthologue (pvcrto) is not a primary determinant of ex vivo response to chloroquine, and thus not an appropriate molecular marker of drug resistant P. vivax.
This dissertation provides evidence of the benefit of incorporating molecular tools into malaria surveillance by characterising the asymptomatic reservoir and its impact on clinical disease and transmission dynamics, evaluating the suitability of passive molecular surveillance and its usefulness to measure the effect of malaria control interventions, and contributing to the validation of molecular markers of chloroquine resistance in P. vivax.
Note: Please note that article from Chapter 6 has been removed due to copyright restriction.
|Date of Award
|Jutta Marfurt (Supervisor) & Sarah Auburn (Supervisor)