Relapse - Advances in Parasitology - page 113

relevancetomalariatherapeuticassessment,control,andelimination.Thenumberof
sporozoites inoculated by the anophelinemosquito is an important determinant of
both the timing and the number of relapses.The intervals between P. vivax relapses
displayaremarkableperiodicitywhichhasnotbeenexplained.Evidenceispresented
thattheproportionofpatientswhohavesuccessiverelapsesisrelativelyconstantand
thatthefactorwhichactivateshypnozoitesandleadstoregularintervalrelapseinvivax
malariaisthesystemicfebrileillnessitself.Itisproposedthatinendemicareas,alarge
proportionofthepopulationharbours latenthypnozoiteswhichcanbeactivatedby
a systemic illness such as vivax or falciparummalaria.This explains the high rates of
vivaxfollowingfalciparummalaria,thehighproportionofheterologousgenotypesin
relapses,thehigherratesofrelapseinpeoplelivinginendemicareascomparedwith
artificial infectionstudies,and,by facilitating recombinationbetweendifferentgeno-
types,contributesto P. vivax geneticdiversityparticularlyinlowtransmissionsettings.
Long-latency P. vivax phenotypesmaybemorewidespreadandmoreprevalentthan
currentlythought.Theseobservationshaveimportantimplicationsfortheassessment
ofradicaltreatmentefficacyandformalariacontrolandelimination.
1. INTRODUCTION
Plasmodium vivax malaria is characterised by relapses after resolution
of the primary infection which derive from activation of dormant liver
stage parasites 'hypnozoites'. It is this propensity to relapse, which makes
P. vivax more difficult to control and eliminate than Plasmodium falciparum .
In endemic areas, relapse of vivax malaria is a major cause of malaria in
young children, and an important source of malaria transmission. Relapse
also occurs in Plasmodium ovale infections and in several of the simian
Terminology
Recrudescence: The blood-stage infection declines initially following treatment
but then increases again to produce a recurrent infection. Such recrudescent
infections are genetically homologous (i.e. they are with one or more of the same
genotypes which caused the original infection).
Relapse: A recurrent infection resulting from persistent liver stages or hyp-
nozoites. In tropical areas, the interval from primary infection to relapse is short
- typically 3 weeks following a rapidly eliminated drug treatment and 6 weeks
following chloroquine or another slowly eliminated drug. These relapses can be
either genetically homologous, or heterologous arising from activation of previ-
ously acquired hypnozoites ( White, 2011 ).
In some sub-tropical areas, the interval from inoculation to first infection,
or from primary illness to first relapse is approximately 9 months (long latency).