Prime index of suspicion of emergence/existence of resistance to anti-malarial drugs surfaces during therapeutic drug trials or surveillances. Present study was undertaken to determine the therapeutic efficacy of CQ–PQ combined regimen in
P. vivax malaria. The KH, Manipal caters for over 200 malaria patients annually from southwestern India comprising Goa, coastal Karnataka and Kerala. Notably,
P. vivax infection constitutes more than 55% of total annual malaria incidence in KH, Manipal. Male preponderance observed in the current study is a common finding and has also been reported from the same hospital [
7‐
9]. Significantly, (p < 0.05) high axillary temperature at presentation and longer time to defervescence among inpatients than outpatients is a reflection of more sick/febrile patients receiving in hospital care. Notably, about 99% therapeutic efficacy of CQ–PQ combined regimen as observed in the present study was reported previously from the same hospital during the years 2007–2009 [
10]. However, the previous study did lack the confirmation of
P. vivax mono-infection by PCR test and also did not have rigorous 28 days follow-up, as in the current study. Furthermore, similar therapeutic efficacy until day 28 has also been reported from other parts of India viz. 100% (41/41) from Mangalore [
11], 98.1% (105/107) from Chennai [
12] and 96.9% (63/65) from Gujarat [
13] for CQ only and 100% (103/103) from Kolkata [
14] for CQ–PQ combined regimen during the years 2003–2012. Notably, CQ–PQ combined regimen is known to have superior efficacy than CQ alone for preventing
P. vivax recurrences [
14‐
16]. Nonetheless, of the published literature from India, only a case report dating back over two decades confirms CQ failure in
P. vivax despite having adequate plasma concentration of CQ [
17].
The hub of global CQ resistance in
P. vivax is in Indonesia [
15,
18,
19]. Probable CQ-resistant
P. vivax in India has been documented from north, northeast and western parts, whereas CQ remains sensitive throughout southern India [
15]. Importantly, surging CQ resistance in
P. vivax across eastern neighbouring countries of India, including Myanmar [
20], Thailand [
21] and Vietnam [
22] is a matter of concern and this urges an immediate implementation of effective preventive measures to check the invasion of any resistant
P. vivax strain from those countries along with travellers and/or migrants.
Strengths and limitations
The present study poses considerable strength over studies which did not have PCR-proven mono-infection
P. vivax cases. Statistically, valid sample size, robust analysis and standard methodology render the study outcomes legitimately comparable with parallel series across the globe. Outstanding therapeutic efficacy of CQ–PQ combined regimen for
P. vivax malaria observed in the current study is augmenting evidence to support the continuation of the existing national anti-malarial drug policy for
P. vivax malaria in India. The probably resistant case of one therapeutic failure could not be ascertained as truly resistant
P. vivax strain. Arguably, persistence of fever and increasing parasitaemia from 2,200 parasite/µL on day 0 to 9,652 parasite/µL on day 2 and residual 7,012 parasite/µL on day 3 despite completion of CQ dosage features a true resistant
P. vivax strain. However, this argument could possibly have been true only if CQ and desethylchloroquine concentration in participant’s blood [
16,
23] was estimated on the day of therapeutic failure and/or analysis of molecular markers for CQ resistance [
14,
24,
25] was done.
The nPCR test proved an insubstantial proportion of participants to have mixed malaria infection. However those entities of mixed malaria seemed inconsequential clinically as nPCR proven mixed malaria did not affect either the nature of illness or treatment/outcome and conclusions of the study. Notably, this inference of clinical inconsequentiality of merely nPCR-proven mixed malaria must be methodically evaluated further as it is beyond the scope of the current study. Lost to follow-up ensued in only three patients but seemingly they all had ACPR until their day 3 follow-up. However, we cannot rule out the possibility of treatment failure beyond day 3. Remarkably, this study did not assess the efficacy of CQ alone as per the WHO protocol [
4], rather a permitted deviation from it i.e., assessment of CQ–PQ combined regimen as it was suitable in the respective study setting. Therefore, the findings of this study can only be applicable to population exempting any contraindications for PQ administration. Similar studies in future should withhold PQ administration till day 28 as recommended primarily by the WHO [
4].