Assessing the asymptomatic reservoir and dihydroartemisinin–piperaquine effectiveness in a low transmission setting threatened by artemisinin resistant Plasmodium falciparum View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-09-01

AUTHORS

Grégoire Falq, Rafael Van Den Bergh, Martin De Smet, William Etienne, Chea Nguon, Huy Rekol, Mallika Imwong, Arjen Dondorp, Jean-Marie Kindermans

ABSTRACT

BackgroundIn Cambodia, elimination of artemisinin resistance through direct elimination of the Plasmodium falciparum parasite may be the only strategy. Prevalence and incidence at district and village levels were assessed in Chey Saen district, Preah Vihear province, North of Cambodia. Molecular and clinical indicators for artemisinin resistance were documented.MethodsA cross sectional prevalence survey was conducted at village level in the district of Chey Saen from September to October 2014. Plasmodium spp. was assessed with high volume quantitative real-time polymerase chain reaction (qPCR). Plasmodium falciparum-positive samples were screened for mutations in the k13-propeller domain gene. Treatment effectiveness was established after 28 days (D28) using the same qPCR technique. Data from the provincial surveillance system targeting symptomatic cases, supported by Médecins Sans Frontières (MSF), were used to assess incidence.ResultsDistrict P. falciparum prevalence was of 0.74 % [0.41; 1.21]; village prevalence ranged from 0 to 4.6 % [1.4; 10.5]. The annual incidence of P. falciparum was 16.8 cases per 1000 inhabitants in the district; village incidence ranged from 1.3 to 54.9 for 1000 inhabitants. Two geographical clusters with high number of cases were identified by both approaches. The marker for artemisinin resistance was found in six samples out of the 11 tested (55 %). 34.9 % of qPCR blood analysis of symptomatic patients were still positive at D28.ConclusionsThe overall low prevalence of P. falciparum was confirmed in Chey Saen district in Cambodia, while there were important variations between villages. Symptomatic cases had a different pattern and were likely acquired outside the villages. It illustrates the importance of prevalence surveys in targeting interventions for elimination. Mutations in the k13-propeller domain gene (C580Y), conferring artemisinin resistance, were highly prevalent in both symptomatic and asymptomatic cases (realizing the absolute figures remain low). Asymptomatic individuals could be an additional reservoir for artemisinin resistance. The low effectiveness of dihydroartemisinin–piperaquine (DHA–PPQ) for symptomatic cases indicates that PPQ is no longer able to complement the reduced potency of DHA to treat falciparum malaria and highlights the need for an alternative first-line treatment. More... »

PAGES

446

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12936-016-1487-z

DOI

http://dx.doi.org/10.1186/s12936-016-1487-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1009489943

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27585957


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38 schema:description BackgroundIn Cambodia, elimination of artemisinin resistance through direct elimination of the Plasmodium falciparum parasite may be the only strategy. Prevalence and incidence at district and village levels were assessed in Chey Saen district, Preah Vihear province, North of Cambodia. Molecular and clinical indicators for artemisinin resistance were documented.MethodsA cross sectional prevalence survey was conducted at village level in the district of Chey Saen from September to October 2014. Plasmodium spp. was assessed with high volume quantitative real-time polymerase chain reaction (qPCR). Plasmodium falciparum-positive samples were screened for mutations in the k13-propeller domain gene. Treatment effectiveness was established after 28 days (D28) using the same qPCR technique. Data from the provincial surveillance system targeting symptomatic cases, supported by Médecins Sans Frontières (MSF), were used to assess incidence.ResultsDistrict P. falciparum prevalence was of 0.74 % [0.41; 1.21]; village prevalence ranged from 0 to 4.6 % [1.4; 10.5]. The annual incidence of P. falciparum was 16.8 cases per 1000 inhabitants in the district; village incidence ranged from 1.3 to 54.9 for 1000 inhabitants. Two geographical clusters with high number of cases were identified by both approaches. The marker for artemisinin resistance was found in six samples out of the 11 tested (55 %). 34.9 % of qPCR blood analysis of symptomatic patients were still positive at D28.ConclusionsThe overall low prevalence of P. falciparum was confirmed in Chey Saen district in Cambodia, while there were important variations between villages. Symptomatic cases had a different pattern and were likely acquired outside the villages. It illustrates the importance of prevalence surveys in targeting interventions for elimination. Mutations in the k13-propeller domain gene (C580Y), conferring artemisinin resistance, were highly prevalent in both symptomatic and asymptomatic cases (realizing the absolute figures remain low). Asymptomatic individuals could be an additional reservoir for artemisinin resistance. The low effectiveness of dihydroartemisinin–piperaquine (DHA–PPQ) for symptomatic cases indicates that PPQ is no longer able to complement the reduced potency of DHA to treat falciparum malaria and highlights the need for an alternative first-line treatment.
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46 DHA
47 Frontières
48 Médecins Sans Frontières
49 P. falciparum
50 P. falciparum prevalence
51 PPQ
52 Plasmodium falciparum
53 Plasmodium falciparum parasites
54 Plasmodium falciparum positive samples
55 Preah Vihear Province
56 Province
57 Saen
58 Sans Frontières
59 additional reservoir
60 alternative first-line treatment
61 analysis
62 annual incidence
63 approach
64 artemisinin resistance
65 artemisinin-resistant Plasmodium falciparum
66 asymptomatic cases
67 asymptomatic individuals
68 asymptomatic reservoir
69 blood analysis
70 cases
71 chain reaction
72 clinical indicators
73 clusters
74 data
75 days
76 different patterns
77 direct elimination
78 district
79 domain genes
80 effectiveness
81 elimination
82 falciparum
83 falciparum malaria
84 falciparum parasites
85 falciparum positive samples
86 first-line treatment
87 genes
88 geographical clusters
89 higher number
90 importance
91 important variations
92 incidence
93 indicators
94 individuals
95 inhabitants
96 intervention
97 levels
98 low effectiveness
99 low prevalence
100 low transmission
101 malaria
102 markers
103 mutations
104 need
105 north
106 number
107 only strategy
108 overall low prevalence
109 parasites
110 patients
111 patterns
112 polymerase chain reaction
113 potency
114 prevalence
115 prevalence survey
116 provincial surveillance system
117 qPCR technique
118 quantitative real-time polymerase chain reaction
119 reaction
120 real-time polymerase chain reaction
121 reservoir
122 resistance
123 resistant Plasmodium falciparum
124 samples
125 strategies
126 surveillance system
127 survey
128 symptomatic cases
129 symptomatic patients
130 system
131 technique
132 transmission
133 treatment
134 treatment effectiveness
135 variation
136 village level
137 village prevalence
138 villages
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