Malaria, Falciparum Clinical Trial
Official title:
Time to Become Negative of Three Rapid Diagnostic Tests for Malaria in Children Under 5 Years of Age. Evaluation in Two Different Malaria Epidemiological Settings in Greater Mbarara District, South Western Uganda
Background: Antigen-detecting rapid diagnostic tests (RDTs) for malaria provide the
possibility of a parasite-based diagnosis in areas where good quality microscopy can not be
achieved.
P. falciparum tests targeting the histidine-rich protein (HRP2) antigen are generally more
sensitive than tests targeting the Plasmodium lactate dehydrogenase (pLDH) antigen. However,
as the HRP2 antigen is eliminated from the bloodstream more slowly than the pLDH antigen,
HRP2-based tests can give a positive result two weeks or more after the patient has taken an
effective treatment, while pLDH tests generally turn negative a few days after. The use of
an RDT positive result in a routine patient care is therefore challenged by the
interpretation of whether the result is due to a lasting effect of the already treated
infection or to a new infection. The interpretation might also be affected by the level of
malaria transmission in the area.
Objective: The objective of this study is to estimate the proportion of positive tests in
patients successfully treated for malaria (smear negative) at different time points in time
after treatment, for three rapid diagnostic tests: SD Bioline Malaria Antigen P.f.
(catalogue number: 05FK50-02-4), CareStart Malaria HRP2 (Pf) (catalogue number: G0141) and
CareStart Malaria pLDH (PAN) (catalogue number: G0111). The study will be carried out in two
settings with known low and high malaria transmission levels in order to provide guidance of
interpretation of a RDT positive result depending on the intensity of malaria transmission.
Secondary objectives will be to measure the sensitivity and specificity of the malaria rapid
tests compared to smear microscopy, to estimate the median time to become negative for each
of the tests and to estimate the proportion of positive tests and the median time to become
negative according to the initial parasitaemia and the presence of gametocytes.
The study population will be patients under 5 years of age who attend the consultation
service of one health centre of Mbarara municipality (low transmission setting) and one
health centre in Kazo sub-county (high transmission setting) and for whom the clinical
diagnosis of malaria is confirmed by smear microscopy and with at least one positive RDT.
Patients with general signs of danger of severe malaria or who took a full course of
antimalarial treatment in the previous 2 weeks will be excluded. Written consent will be
sought from all participants.
A total of 212 patients will be included in each setting. The sample size was based of a
minimum accuracy of 8% around a proportion of 50% positive RDTs to which a 15% was added for
patients who will not be positive for all RDTs or will be secondarily excluded from the
analysis.
A three-day artemether-lumefantrine will be given to enrolled cases and treatment intake
will be supervised. RDTs and a blood smear microscopy will be repeated at day 2, 3, 5, 7,
14, 21, 28, 35 and 42 after inclusion until all RDTs become negative. Follow-up will not
last longer than 42 days.
The proportion and 95% confidence intervals of positive tests among patients with a negative
thick smear will be calculated for each day of follow-up. Moreover the investigators will
identify for each test a regression model to estimate the number of days required to obtain
a 50, 25, 10 and 5% probability of having a false positive RDT result.
Sensitivity, specificity, positive and negative predictive values will be estimated for each
RDT independently using the result of microscopy as a reference. The analysis will be
performed using the day 0 results for all patients enrolled in the study.
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Observational Model: Cohort, Time Perspective: Prospective
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