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

BACKGROUND: In 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. METHODS: A 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. RESULTS: District 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. CONCLUSIONS: The 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 BACKGROUND: In 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. METHODS: A 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. RESULTS: District 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. CONCLUSIONS: The 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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45 schema:keywords Cambodia
46 Chey Saen
47 Chey Saen district
48 D28
49 DHA
50 District P. falciparum prevalence
51 Frontières
52 Médecins Sans Frontières
53 North of Cambodia
54 P. falciparum prevalence
55 PPQ
56 Plasmodium falciparum
57 Plasmodium falciparum parasites
58 Plasmodium falciparum positive samples
59 Preah Vihear Province
60 Province
61 Saen
62 Saen district
63 Sans Frontières
64 Vihear province
65 additional reservoir
66 alternative first-line treatment
67 analysis
68 annual incidence
69 approach
70 artemisinin resistance
71 artemisinin-resistant Plasmodium falciparum
72 asymptomatic cases
73 asymptomatic individuals
74 asymptomatic reservoir
75 blood analysis
76 cases
77 chain reaction
78 clinical indicators
79 clusters
80 cross-sectional prevalence survey
81 data
82 days
83 different patterns
84 dihydroartemisinin–piperaquine effectiveness
85 direct elimination
86 district
87 domain genes
88 effectiveness
89 elimination
90 falciparum
91 falciparum malaria
92 falciparum parasites
93 falciparum positive samples
94 falciparum prevalence
95 first-line treatment
96 genes
97 geographical clusters
98 high volume quantitative real-time polymerase chain reaction
99 higher number
100 importance
101 important variations
102 incidence
103 indicators
104 individuals
105 inhabitants
106 intervention
107 k13-propeller domain gene
108 levels
109 low effectiveness
110 low prevalence
111 low transmission
112 malaria
113 markers
114 mutations
115 need
116 north
117 number
118 only strategy
119 overall low prevalence
120 parasites
121 patients
122 patterns
123 polymerase chain reaction
124 potency
125 potency of DHA
126 prevalence
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128 provincial surveillance system
129 qPCR blood analysis
130 qPCR technique
131 quantitative real-time polymerase chain reaction
132 reaction
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134 reservoir
135 resistance
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137 same qPCR technique
138 samples
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140 strategies
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143 symptomatic cases
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145 system
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147 transmission
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150 variation
151 village incidence
152 village level
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