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The incidence of malaria caused by Plasmodium vivax is about 16 million cases worldwide

Malaria causes 3100 deaths worldwide, with 86% occurring outside Africa, especially in Southeast Asia and the
Eastern Mediterranean region

The aim of this study was to develop a tool to identify patients infected with P. vivax who are at high risk of
recurrence in Malaysia

Research design

A retrospective study was conducted from 2011 to 2016. The data were obtained through the
National Malaria Case Registry (NMCR) under the Borne Vector Disease Sector, Disease Control
Division, Ministry of Health, Malaysia.

patients diagnosed with P. vivax infection and treated with primaquine were included in the study.
Patients with missing data and those not monitored for at least 6 months after exclusion were
excluded from the study. To develop a predictive risk recurrence model, the study sample was
divided into 2 groups.
Definitions used in the study

all cases categorized in relapse, are called recurrence because of the inability to distinguish between relapse,
reinfection or recrudescence. Clinical outcomes were measured by relapse during
follow ups of 6- to 12 months, as determined from a positive blood smear parasite (BFMP) test. Patient
are actively monitored due to parasites on monthly basis by the health office as recommended
by current clinical practice in P. vivax management

A total of 2044 patients infected with P. vivax between

2011 and 2016 were included for development and
validation of total scores in predicting presence and
absence of recurrence
Among the study population, 553 (27.1%) patients were children aged
The number of days for recurrence of P. vivax infection ranged
between 31 and 267 days after the start of antimalarial treatment.
In a survival analysis, the overall median time to recurrence
obtained by the Kaplan-Meier curve was 78 days (95% CI: 86.1–
112.6), which means 50% of the recurrence cases occurred in less
than 78 days after start of the treatment
Two-thirds (n = 1362) of the study participants were used for
development of the predictor scores. A univariate logistic regression
analysis showed that patient (age, gender, nationality, WHO region
countries, pregnancy, case locality (rural), and status of case-locality
(prone); disease (gametocyte count and malaria transmission type); and
treatment characteristics (the antimalarial treatment used) were risks
of recurrence
strong multi-collinearity was found among nationalities, Western-Pacific
countries, pregnancy, and case locality; these were excluded from the
final model. When all variables with a p-value of ≤0.1 in the univariate
analysis were tested in a multivariate analysis, age, gametocyte sexual
count, indigenous type of transmission, type of treatment used, and
incomplete primaquine-treatment were found to be predictors of
recurrence after controlling for other confounding factors; these were
included in the final model
The performance and accuracy of the model in predicting both presence
and absence of recurrence was measured by the area under the ROC curve
of the developed model, which was 0.728 (95% CI: 0.670– 0.785; p < 0.001;
Fig. 2A

The area under the ROC curve demonstrated the model was reliable with a
value of 0.766 (95% CI: 0.700–0.833; p < 0.001; Fig. 2B)
indicating that the accuracy of the model was good [23]. The trade-
off value of the score was 3.5, which represents 91.5% sensitivity and
57.7% specificity in predicting the presence or absence of recurrence
The growing evidence suggests that malaria caused by P. vivax is no longer considered a benign
and non-fatal disease. Although various precautions, complete elimination of P. vivax has become
very challenging because of its ability to recur within weeks and months after primary

tight monitoring of patients with P. vivax infection and identifying those at higher risk of recurrence is
essential for better control and eradication of the disease

Recent studies have shown that predictors of recurrence of P. vivax infection At local settings
younger age, higher gametocyte upon admission, native transmission, combination of
treatment with chloroquine and primaquine as well as incomplete primaquine treatment
supervision of primaquine administration every day to ensure that primaquine
treatment is completed is a better approach in high-risk populations. This can
ensure the success of primaquine in the management of P. vivax infections.

this is the first time a clinical recurrence predictor has been developed using
national data. Evidently, this tool is found as a good redictor, and can be used when
released by health care workers to identify high recurrence risk among treated

In this study proposes to apply a strict malaria program in patients, with a>> 3.5
score, which has a higher risk of recurrence

Possible researchers have not identified all patients with recurrence, because of the
loss of follow-up of a large number of cases

In the registry, details not identified in variables such as G6PD, case locality, case
locality status, previous malaria infection, presence of gametocytes during
admission, severity, and status of primary treatment were categorized unknown

A specific lack of contribution can contribute to moderate ROC values and

therefore thorough data collection is required before entering data into the
malaria registry
Additional information not available in current employment such as co-morbidities, use of other drugs, and
previous types of malaria infections are also possible. affecting positive or negative test results, and may be
included to correct future ROC values

Generalization of current research should also be done with caution. Due to differences in population
demographics, and management of clinical and antimalarial medications in Malaysia, compared to other regions,
the results of the scores may differ

Current research has successfully developed a simple repetition of P. vivax

recurrence tool, and this is the first assessment system that can predict patients
at high risk of recurrence in Malaysia. The use of an assessment system in a
clinical setting requires minimal training. In addition, it is also ideal for use in field
trips in less developed areas. Preparation of these clinical predictors into a
follow-up protocol for the past year may strengthen monitoring and eradication
of P. vivax infection in Malaysia in the future
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