In vivo monitoring of dihydroartemisinin-piperaquine sensitivity in Plasmodium falciparum along the China-Myanmar border of Yunnan Province, China from 2007 to 2013

Abstract

BackgroundArtemisinin-based combination therapy (ACT) is the recommended first-line treatment of falciparum malaria in all endemic countries. Artemisinin resistance in Plasmodium falciparum has been confirmed in the Greater Mekong subregion (GMS). Dihydroartemisinin-piperaquine (DAPQ) is the most commonly used ACT in China. To understand the DAPQ sensitivity of P. falciparum, DAPQ resistance was monitored in vivo along the China-Myanmar border from 2007 to 2013.MethodsEligible patients with mono-infections of P. falciparum were recruited to this study after obtaining full informed consent. DAPQ tablets for different categories of kg body weight ranges were given once a day for three days. Patients were followed up for 42 days. Polymerase chain reaction (PCR) was conducted to distinguish between re-infection and recrudescence, to confirm the Plasmodium species. The data were entered and analysed by the Kaplan-Meier method. Treatment outcome was assessed according to the WHO recommended standards.Results243 patients were completed valid follow-up. The fever clearance time (FCT) and asexual parasite clearance times (APCT) were, respectively, 36.5 ± 10.9 and 43.5 ± 11.8 hours, and there was an increasing trend of both FCT (F = 268.41, P < 0.0001) and APCT (F = 88.6, P < 0.0001) from 2007 to 2013. Eight (3.3%, 95% confidence interval, 1.4–6.4%) patients present parasitaemia on day three after medication; however they were spontaneous cure on day four. 241 (99.2%; 95% CI, 97.1–99.9%) of the patients were adequate clinical and parasitological response (ACPR) and the proportions of ACPR had not changed significantly from 2007 to 2013 (X2 = 2.81, P = 0.7288).ConclusionIn terms of efficacy, DAPQ is still an effective treatment for falciparum malaria. DAPQ sensitivity in P. falciparum had not significantly changed along the China-Myanmar border of Yunnan Province, China. However more attentions should be given to becoming slower fever and parasite clearance.

Therapeutic efficacy and artemisinin resistance in northern Myanmar: evidence from in vivo and molecular marker studies

“…The efficacy of all ACT in the studies were high (>97%) in both PCR uncorrected and corrected analyses, meeting the WHO recommendation that cure rates for falciparum malaria should be at least 90% [9]. These results are similar to results found in other studies in northern Myanmar [12, 13]. …”

Evidence of Plasmodium falciparum Malaria Multidrug Resistance to Artemisinin and Piperaquine in Western Cambodia: Dihydroartemisinin-Piperaquine Open-Label Multicenter Clinical Assessment

“…The rapid development of DHA-PP treatment failure in western Cambodia appears to be highly correlated with the presence of K13 mutations and the increased sensitivity of P. falciparum isolates to mefloquine (36,37). Interestingly, DHA-PP treatment failures have not been reported in other countries of the Greater Mekong Subregion, such as Myanmar and Vietnam, despite high prevalence rates of K13 mutant alleles in these countries and many years of intense use (18,19,38,39). However, in countries where artemisinin resistance is prevalent, we speculate that through the exposure of greater parasite biomasses to ACTs in vivo, artemisinin resistance could promote the evolution of resistance to partner drugs such as PP.…”

“…Since 2008, dihydroartemisinin plus piperaquine (DHA-PP), the latest ACT to be recommended by the WHO, has been used as the first-line treatment for uncomplicated falciparum malaria in the western Cambodian provinces; in 2010, it was extended to other provinces. Several studies have demonstrated that this ACT was safe and highly efficacious against falciparum malaria in Cambodia (15,16), in Asia (17)(18)(19)(20), and elsewhere (21). However, reports from DHA-PP therapeutic efficacy studies (42-day follow-up) performed from 2008 to 2010 have shown worrying downward trends in cure rates, from 89.4% to 75.0% in Pailin and from 98.7% to 89.3% in Pursat in western Cambodia, while cure rates in the provinces of Preah Vihear (northern Cambodia) (100% in 2009) and Ratanakiri (northeast Cambodia) (100% in 2009 to 2010) remained high (22).…”

Significant Divergence in Sensitivity to Antimalarial Drugs between Neighboring Plasmodium falciparum Populations along the Eastern Border of Myanmar

“…Clinical isolates P. falciparum were collected in 2008 in malaria clinics in two sites, Wa Special Region 2 of Shan State and Kachin State of eastern Myanmar (see Fig. S1 in the supplemental material), as part of the efforts for malaria surveillance, control, and resistance monitoring in these regions (31). Malaria was identified by microscopic examination of Giemsa-stained blood smears from patients attending local clinics.…”