This document discusses relapse in malaria. It defines relapse as the return of malaria symptoms after apparent cure of the disease. Relapse is caused by dormant liver stages called hypnozoites in Plasmodium vivax and Plasmodium ovale infections. Several theories are presented to explain the mechanisms of relapse, and the latent tissue stage/hypnozoite theory best accounts for observed relapse patterns. Factors that influence relapse include the number of sporozoites inoculated, acquisition of blood stage immunity, and differences between tropical and temperate regions. The hypnozoite is described as an exoerythrocytic schizont in the liver that causes delayed primary development and relapses.

1. INTRODUCTION DETERMINANTS OF RELAPSE
PREVENTION OF RELAPSE
THEORIES OF RELAPSEABSTRACT
Neha Pillai Vinod
RA1841002010087
Microbiology
Department
SRM Medical College
and Research Center
Recur rent malaria is a
puzzling clinical problem and
limited scien tific data is
available on its diag nostic
approach, and manage ment.
Symptoms of malaria can recur
after varying symptom-free
periods. Depending upon the
cause, recurrence can be
classified as either
recrudescence, relapse, or
reinfection. It is caused by
parasites surviving in the blood
as a result of inadequate or
ineffective treatment.
v MARCHOUX THEORY OF PARTHENOGENESIS
v ROSS-THOMPSON MOSQUITO MALARIA THEORY
v THE CYCLIC THEORY OF RELAPSE
v LATENT STAGE THEORY OF RELAPSE/
STRAIN/HYPNOZOITE THEORY OF RELAPSE
The theory of latent tissue stages best accounts for
relapse patterns, delayed prepatent periods, and sporozoite
dilution experiments and provides quantitative evidence of
support. The existence of the hypnozoite in
three species of Plasmodium that cause relapsing malarias
provides morphological confirmation of this theory
v CHLOROQUINE + SINGLE DOSE TAFENOQUINE
v CHLOROQUINE + PRIMAQUINE
v CHLOROQUINE + PLACEBO
REFERENCES
https://malariajournal.biomedcentral.com/articles/10.118
6/1475-2875-10-297
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC358221/p
df/cmr00038-0038.pdf
Relapse is a term used widely in medicine to mean a
return of the clinical symptoms of a disease after its
apparent cessation.
CLASSIFICATION OF RECURRENCE OF MALARIA
v RELAPSE: In P. vivax and P. ovale some sporozoites on
entering the hepatocytes remain dormant in a cryptobiotic
phase called hypnozoites (sleeping sporozoites) as they do
not enter pre-erythrocytic schizogony. After variable
intervals of weeks or months, these hepatic schizonts burst
and release merozites into the blood stream. When
reactivated they have a new focus of transmission.
v RECRUDESCENCE:It is recurrence of infection with
species that lack hypnozoites, that is P. falciparum , P.
malariae and P. knowlesi as well as with P. vivax or P.
ovale. It occurs due to persistent/drug-resistant blood
stages of the parasite. During this phase there is no
clearance of parasitemia but they are reduced to sub-patent
levels. A period of 8 weeks is required to exclude
recrudescence of drug resistant parasites.
The factors which control relapse and determine their
remarkable periodicity are not completely known. The
most probable possibilities are-
v Tropical P. vivax relapses at three week intervals, whereas
in temperate regions and parts of the sub-tropics P.
vivax infections are characterized either by a long
incubation or a long-latency period
v The number of sporozoites inoculated by the anopheline
mosquito is an important determinant of both the timing and
the number of relapses
v high proportion of heterologous genotypes in relapses
v higher rates of relapse in people living in endemic areas
v Acquisition of blood stage immunity against the single
infecting genotype
v the proportion of infections which relapse and the number
of symptomatic relapses per mosquito sporozoite
inoculation decline with age
THE HYPNOZOITE
Exoerythrocytic schizozoite of Plasmodium vivax or P.
ovale in the human liver, characterized by delayed
primary development isthought to be responsible for
malarial relapse.They appear as nearly oval, well-
defined, brightly fluorescing bodies approximately 5
µm in diameter within the cytoplasm of a hepatic
parenchymal cell. Restained with Giemsa-
colophonium, hypnozoites exhibit a light blue,slightly
variegated cytoplasm with a distinct limiting
membrane. The nucleus appears to be characteristic
chromatin,with staining properties.There is sometimes
a partial "halo" of pinkish, clear cytoplasm around the
nucleus.