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Original Article

Therapeutic Assessment of Primaquine for Radical Cure of Plasmodium vivax Malaria at Primary and Tertiary Care Centres in Southwestern India

Rishikesh Kumar1, Vasudeva Guddattu2, Kavitha Saravu1,3,*
The Korean Journal of Parasitology 2016;54(6):733-742.
Published online: December 31, 2016

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*Corresponding author (kavithasaravu@gmail.com)
• Received: July 5, 2016   • Revised: August 26, 2016   • Accepted: September 27, 2016

Copyright © 2016 by The Korean Society for Parasitology and Tropical Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Therapeutic Assessment of Primaquine for Radical Cure of Plasmodium vivax Malaria at Primary and Tertiary Care Centres in Southwestern India
Korean J Parasitol. 2016;54(6):733-742.   Published online December 31, 2016
DOI: https://doi.org/10.3347/kjp.2016.54.6.733
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Therapeutic Assessment of Primaquine for Radical Cure of Plasmodium vivax Malaria at Primary and Tertiary Care Centres in Southwestern India
Korean J Parasitol. 2016;54(6):733-742.   Published online December 31, 2016
DOI: https://doi.org/10.3347/kjp.2016.54.6.733
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Therapeutic Assessment of Primaquine for Radical Cure of Plasmodium vivax Malaria at Primary and Tertiary Care Centres in Southwestern India
Image Image Image Image
Fig. 1 Flow diagram depicting the study protocol and outcome.
Fig. 2 Geographical locations of Kasturba Hospital, Manipal and primary health centres of Hiriadka, Kolalagiri, Malpe, Pethri and Shirva of Udupi taluk, Karnataka, India. Image adapted from USGS Earth Resources Observatory and Science (EROS) Center (public domain): http://earthexplorer.usgs.gov/.
Fig. 3 (A) Kaplan-Meier survival plot showing recurrence probability up to 15 months among participants from KH, Manipal and PHCs, Udupi taluk. (B) Kaplan-Meier survival plot showing recurrence probability up to 15 months among participants with and without history of P. vivax malaria. (C) Kaplan-Meier survival plot showing recurrence probability up to 15 months among participants diagnosed with P. vivax mono-infection and mixed malaria by nested PCR test at initial presentation. (D) Drop-line graph depicting relation between months of initial appearance and first recurrence stratified by duration of recurrences.
Fig. 4 Flow diagram depicting results of nested PCR test in recurrence cohort at different recurrence stages.

Fig. 1

Fig. 2

Fig. 3

Fig. 4

Therapeutic Assessment of Primaquine for Radical Cure of Plasmodium vivax Malaria at Primary and Tertiary Care Centres in Southwestern India

Comparison of demographic and clinical variables between no-recurrence and recurrence groups at initial presentation

Variablesa No-recurrence (N=86) (%) Recurrence (N=28) (%) P-valuea
Mean±SD or median (IQR) Mean±SD or median (IQR)
Settings 0.03b
 Kasturba Hospital, Manipal 68 (79.1) 16 (57.1)
 Primary Health Centres, Udupi taluk 18 (20.9) 12 (42.9)
Point-of-care 0.19
 Ambulatory 36 (41.9) 16 (57.1)
 Inpatient 50 (58.1) 12 (42.9)
Age in years 38.9±12.1 38.9±13.6 1.00
Gender 0.69
 Male 80 (93) 25 (89.3)
 Female 6 (7) 3 (10.7)
History 0.67
 Fever in days 4 (3–5) 3 (2–5) 1.00
 Headache 72 (83.7) 24 (85.7) 0.66
 Cough 35 (40.7) 13 (46.4) 0.51
 Vomiting 33 (38.4) 13 (46.4) 0.29
 Diarrhea 11 (12.8) 1 (3.6) 0.08
 Malaria 31 (36) 16 (57.1) 0.02b
 P. vivax malaria 27 (31.4) 16 (57.1)
Vitals 0.30
 Axillary temperature at presentation (0F) 100±1.5 99.7±1.5 0.08
 Pulse rate (beats/minute) 85.9±11.3 91.3±10.2 0.71
 Respiratory rate (breaths/minute) 22±3.9 21.6±4.2 0.14
 Systolic blood pressure (/mmHg) 120.9±15.5 114.4±16.3 0.43
 Diastolic blood pressure (/mmHg) 78.4±10.7 76±12.3
nPCR diagnosis 0.78
 P. vivax mono-infection 71 (82.6) 22 (78.6)
 Mixed P. vivax and P. falciparum 15 (17.4) 6 (21.4)
Severe malariac 10 (11.6) 3 (10.7) 1.00
Antimalarial treatment at KH, Manipal N=68 N=16 0.08
 CQ-PQ 57 (83.8) 10 (62.5)
 ACT-PQ 11 (16.2) 6 (37.5)

aCategorical variables are summarized as frequency with proportion whereas continuous variables are summarized as either mean (±SD) or median (IQR). χ2-test or Fischer’s exact test and independent sample t-test or Mann Whitney U test was performed.

bP-value less than 0.05 showing a statistically significant difference.

cAs per the WHO’s guideline for management of severe malaria in the year 2012 [17].

Comparison of laboratory variables between no-recurrence and recurrence groups at initial presentation

Variables No-recurrence (N=86) Recurrence (N=28) P-valuea
Mean±SD or median (IQR) Mean±SD or median (IQR)
Total leucocyte count (cells/mm3) 5,056±1,658 5,907±1,905 0.03b
Total platelet count (cells/mm3) 85,000 (52,750–113,250) 91,500 (48,250–138,000) 0.65
Hemoglobin (gm/dl) 13.9±1.9 13.3±1.5 0.10
Hematocrit (%) 41.4±5.4 40±4.3 0.20
Random blood sugar (mg/dl) 109 (99–132) 111 (102–122) 0.85
Total bilirubin (mg/dl) 1.3 (0.8–2.1) 1.6 (0.8–2.4) 0.87
Direct bilirubin (mg/dl) 0.5 (0.3–0.8) 0.5 (0.3–1.1) 0.81
Serum aspartate aminotransferase (IU/L) 37 (25.5–58) 28.5 (19–45.8) 0.05
Serum alanine aminotransferase (IU/L) 41 (24.5–69) 26.5 (18–44.3) 0.01b
Serum alkaline phosphatase (U/L) 88 (69.5–114.5) 85.5 (73.5–106.8) 0.97
Serum urea (mg/dl) 24 (17–31.3) 25 (21–33.5) 0.44
Serum creatinine (mg/dl) 1.0±0.3 1.0±0.4 0.92
Parasite index (parasites/μl blood)c 1,232 (936–1,623) 1,599 (1,048–2,440) 0.36

aIndependent sample t-test or Mann Whitney U test was performed.

bP-value less than 0.05 showing statistically significant differences.

cGeometric mean with 95% confidence interval.

Comparison of demographic and clinical variables during initial presentation and first recurrence among recurrence group

Variables At initial presentation (N=28) (%) At first recurrence (N=28) (%) P-valuea
Point-of-care 0.02b
 Ambulatory 16 (57.1) 25 (89.3)
 Inpatient 12 (42.9) 3 (10.7)
History 0.01b
 Headache 24 (85.7) 14 (50.0) 0.11
 Cough 13 (46.4) 7 (25.0) 0.04b
 Vomiting 13 (46.4) 5 (17.9) 1.00
 Diarrhea 1 (3.6) 2 (7.1)
nPCR diagnosis 1.00
 P. vivax mono-infection 22 (78.6) 22 (78.6)
 Mixed P. vivax and P. falciparum 6 (21.4) 5 (17.9)c
Severe malariad 3 (10.7) 0 0.24
Antimalarial treatment 0.07
 CQ-PQ 22 (78.6) 27 (96.4)
 ACT-PQ 6 (21.4) 1 (3.6)

aMcNemar chi-square test.

bP-value less than 0.05 showing statistically significant differences.

cBlood sample could not be obtained at first recurrence for DNA extraction.

dAs per the WHO’s guideline for management of severe malaria in the year 2012.

Comparison of laboratory variables during initial presentation and first recurrence among recurrence group

Variables At initial presentation (N=28) At first recurrence (N=28) P-valuea
Mean±SD or median (IQR) Mean±SD or median (IQR)
Total leucocyte count (cells/mm3) 5,907±1,905 6,250±1,417 0.36
Total platelet count (cells/mm3) 91,500 (48,250–138,000) 113,000 (96,250–142,750) 0.27
Hemoglobin (gm/dl) 13.3±1.5 13.8±1.7 0.03b
Hematocrit (%) 40±4.3 42.2±5.1 0.03b
Random blood sugar (mg/dl) 111 (102–122) 111 (93.5–140.5) 0.40
Total bilirubin (mg/dl) 1.6 (0.8–2.4) 1.1 (0.6–1.5) 0.07
Direct bilirubin (mg/dl) 0.5 (0.3–1.1) 0.4 (0.2–0.6) 0.10
Serum aspartate aminotransferase (IU/L) 28.5 (19–45.8) 22 (19.8–30.3) 0.23
Serum alanine aminotransferase (IU/L) 26.5 (18–44.3) 19 (13.8–34.3) 0.26
Serum alkaline phosphatase (U/L) 85.5 (73.5–106.8) 72 (57–87) 0.10
Serum urea (mg/dl) 25 (21–33.5) 23.5 (18.3–26.8) 0.35
Serum creatinine (mg/dl) 1.0±0.4 0.9±0.1 0.22
Parasite index (parasites/μl blood)c 1,599 (1,048–2,440) 2,079 (1,211–3,569) 0.39

aPaired t-test or Willcoxon sign rank test was performed.

bP-value less than 0.05 shows statistically significant difference and shown in bold font.

cGeometric mean with 95% confidence interval.

Table 1 Comparison of demographic and clinical variables between no-recurrence and recurrence groups at initial presentation

Categorical variables are summarized as frequency with proportion whereas continuous variables are summarized as either mean (±SD) or median (IQR). χ2-test or Fischer’s exact test and independent sample t-test or Mann Whitney U test was performed.

P-value less than 0.05 showing a statistically significant difference.

As per the WHO’s guideline for management of severe malaria in the year 2012 [17].

Table 2 Comparison of laboratory variables between no-recurrence and recurrence groups at initial presentation

Independent sample t-test or Mann Whitney U test was performed.

P-value less than 0.05 showing statistically significant differences.

Geometric mean with 95% confidence interval.

Table 3 Comparison of demographic and clinical variables during initial presentation and first recurrence among recurrence group

McNemar chi-square test.

P-value less than 0.05 showing statistically significant differences.

Blood sample could not be obtained at first recurrence for DNA extraction.

As per the WHO’s guideline for management of severe malaria in the year 2012.

Table 4 Comparison of laboratory variables during initial presentation and first recurrence among recurrence group

Paired t-test or Willcoxon sign rank test was performed.

P-value less than 0.05 shows statistically significant difference and shown in bold font.

Geometric mean with 95% confidence interval.

Table 1

Table 2

Table 3

Table 4

PHD : Parasites, Hosts and Diseases

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