Molecular surveillance of anti-malarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance

Abstract Background: The loss of chloroquine (CQ) effectiveness has led to its withdrawal from national policies as a first-line treatment for uncomplicated malaria in several endemic countries, such as the Democratic Republic of Congo (DRC). The K76T mutation on the pfcrt gene has been identified as a marker of CQ resistance and the SVMNT haplotype in codons 72–76 on the same gene has been associated with resistance to amodiaquine (AQ). In the DRC, the prevalence of K76T has decreased from 100% in 2000 to 63.9% in 2014. The purpose of this study was to determine the prevalence of K76T mutations in circulating strains of Plasmodium falciparum, sixteen years after CQ withdrawal in the DRC and to investigate the presence of the SVMNT haplotype. Methods : In 2017, ten geographical sites across the DRC were selected. Dried blood samples were collected from patients attending health centres. Malaria was first detected by a rapid diagnostic test (RDT) available on site (SD Bioline Malaria Ag Pf or CareStart Malaria Pf) or thick blood smear and then confirmed by a P. falciparum species-specific real-time PCR assay. A pfcrt gene segment containing a fragment that encodes amino acids at positions 72-76 was amplified by conventional PCR before sequencing. Results: A total of 1070 patients were enrolled. Of the 806 PCR-confirmed P. falciparum positive samples, 764 were successfully sequenced. The K76T mutation was detected in 218 samples (28.5%; 95% CI: 25.4%–31.9%), mainly (96%) with the CVIET haplotype. Prevalence of CQ resistance marker was unequally distributed across the country, ranging from 1.5% in Fungurume to 89.5% in Katana. The SVMNT haplotype, related to AQ resistance, was not detected. Conclusion: Overall, the frequency of the P. falciparum CQ resistance marker has decreased significantly and no resistance marker to AQ was detected in the DRC in 2017. However, the between regions variability of CQ resistance remains high in the country. Further studies are needed for continuous monitoring of the CQ resistance level for its prospective re-use in malaria management. The absence of the AQ resistance marker is in line with the use of this drug in the current DRC malaria treatment policy.

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Falciparum malaria molecular drug resistance in the Democratic Republic of Congo: a systematic review

Malaria Journal ◽

10.1186/s12936-015-0892-z ◽

2015 ◽

Vol 14 (1) ◽

Cited By ~ 16

Author(s):

Dieudonné Makaba Mvumbi ◽

Jean-Marie Kayembe ◽

Hippolyte Situakibanza ◽

Thierry L. Bobanga ◽

Célestin N. Nsibu ◽

...

Keyword(s):

Systematic Review ◽

Drug Resistance ◽

Falciparum Malaria ◽

Democratic Republic ◽

Democratic Republic Of Congo ◽

Republic Of Congo

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Genetic Diversity and Antiretroviral Drug Resistance among Drug-Naïve HIV Type 1 Infected Patients attending Clinics in Kinshasa, Democratic Republic of Congo

Journal of HIV and AIDS ◽

10.16966/2380-5536.101 ◽

2015 ◽

Vol 1 (1) ◽

Cited By ~ 1

Author(s):

Kamangu Erick Ntambwe

Keyword(s):

Genetic Diversity ◽

Drug Resistance ◽

Democratic Republic ◽

Democratic Republic Of Congo ◽

Republic Of Congo ◽

Antiretroviral Drug Resistance ◽

Antiretroviral Drug ◽

Drug Naïve ◽

Hiv Type 1

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Drug-Resistance and Population Structure of Plasmodium falciparum Across the Democratic Republic of Congo Using High-Throughput Molecular Inversion Probes

The Journal of Infectious Diseases ◽

10.1093/infdis/jiy223 ◽

2018 ◽

Vol 218 (6) ◽

pp. 946-955 ◽

Cited By ~ 28

Author(s):

Ozkan Aydemir ◽

Mark Janko ◽

Nick J Hathaway ◽

Robert Verity ◽

Melchior Kashamuka Mwandagalirwa ◽

...

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Population Structure ◽

High Throughput ◽

Democratic Republic ◽

Democratic Republic Of Congo ◽

Republic Of Congo ◽

Molecular Inversion Probes

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Challenges Related to Antimalarial Abuse in Coronavirus Disease-2019 Treatment in the Democratic Republic of Congo

Epidemiology - Open Journal ◽

10.17140/epoj-5-121 ◽

2020 ◽

Vol 5 (1) ◽

pp. 17-18

Author(s):

Anselme Manyong ◽

◽

Ange Landela ◽

Keyword(s):

Drug Resistance ◽

Supply Chain ◽

Democratic Republic ◽

Democratic Republic Of Congo ◽

African Countries ◽

Self Medication ◽

Supply Chain System ◽

Republic Of Congo ◽

Chain System ◽

Health Authorities

Malaria is endemic to many African countries and geographies and remains the leading cause of morbidity and mortality on the continent. Ongoing efforts by health authorities to reverse the scale of malaria are often faced to the challenges of drug resistance often generated by therapeutic abuses relating to self-medication, sub-therapeutic under dosages and poor storage and handling of drugs throughout the pharmacy supply chain system.

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Molecular surveillance of antimalarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance

10.21203/rs.2.18017/v2 ◽

2020 ◽

Author(s):

Doudou Malekita Yobi ◽

Nadine Kalenda Kayiba ◽

Dieudonné Makaba Mvumbi ◽

Raphael Boreux ◽

Pius Zakayi Kabututu ◽

...

Keyword(s):

Democratic Republic ◽

Democratic Republic Of Congo ◽

Gene Segment ◽

Resistance Marker ◽

Antimalarial Drug Resistance ◽

Resistance Level ◽

Molecular Surveillance ◽

Republic Of Congo ◽

Pfcrt Gene ◽

Species Specific

Abstract Background The loss of chloroquine (CQ) effectiveness has led to its withdrawal from national policies as first-line treatment for uncomplicated malaria in several endemic countries such as in the Democratic Republic of Congo (DRC). The K76T mutation on the pfcrt gene has been identified as a marker of CQ resistance and the SVMNT haplotype in codons 72–76 on the same gene has been associated with resistance to amodiaquine (AQ). In DRC, the prevalence of K76T has decreased from 100% in 2000 to 63.9% in 2014. The purpose of the study was to determine the prevalence of K76T mutations in P. falciparum circulating strains, sixteen years after CQ withdrawal in DRC and to investigate the presence of SVMNT haplotype. Methods In 2017, ten geographical sites across DRC were selected. Dried blood samples were collected from patients attending health centers. Malaria was first detected by rapid diagnostic test (RDT) available on site (SD Bioline malaria Ag Pf or CareStart Malaria Pf) or thick blood smear and then confirmed by a P. falciparum species-specific real-time PCR assay. A pfcrt gene segment containing a fragment that encodes amino acids at positions 72-76 was amplified by conventional PCR before sequencing. Results A total of 1070 patients were enrolled. Of the 806 PCR-confirmed P. falciparum positive samples, 764 were successfully sequenced. The K76T mutation was detected in 218 (28.5%; 95% CI: 25.4% – 31.9%) samples, mainly (96%) with the CVIET haplotype. The CQ resistance prevalence was unequally distributed across the country ranging from 1.5% in Fungurume to 89.5% in Katana. The SVMNT haplotype, related to AQ resistance, was not detected. Conclusion Overall, the frequency of P. falciparum CQ resistance marker has decreased significantly and no resistance marker to AQ was detected in DRC in 2017. However, the between regions variability of CQ resistance remains high in the country. Further studies are needed for a continuous monitoring of the CQ resistance level for a prospective re-use in malaria management. The absence of AQ resistance is in line with the use of this drug in the current DRC malaria treatment policy.

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Molecular surveillance of antimalarial drug resistance in the Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance

10.21203/rs.2.18017/v3 ◽

2020 ◽

Author(s):

Doudou Malekita Yobi ◽

Nadine Kalenda Kayiba ◽

Dieudonné Makaba Mvumbi ◽

Raphael Boreux ◽

Pius Zakayi Kabututu ◽

...

Keyword(s):

Democratic Republic ◽

Democratic Republic Of Congo ◽

Gene Segment ◽

Resistance Marker ◽

Antimalarial Drug Resistance ◽

Resistance Level ◽

Molecular Surveillance ◽

Republic Of Congo ◽

Pfcrt Gene ◽

Species Specific

Abstract Background The loss of chloroquine (CQ) effectiveness has led to its withdrawal from national policies as a first-line treatment for uncomplicated malaria in several endemic countries, such as the Democratic Republic of Congo (DRC). The K76T mutation on the pfcrt gene has been identified as a marker of CQ resistance and the SVMNT haplotype in codons 72–76 on the same gene has been associated with resistance to amodiaquine (AQ). In the DRC, the prevalence of K76T has decreased from 100% in 2000 to 63.9% in 2014. The purpose of this study was to determine the prevalence of K76T mutations in circulating strains of P. falciparum , sixteen years after CQ withdrawal in the DRC and to investigate the presence of the SVMNT haplotype. Methods In 2017, ten geographical sites across the DRC were selected. Dried blood samples were collected from patients attending health centres. Malaria was first detected by a rapid diagnostic test (RDT) available on site (SD Bioline Malaria Ag P.f or CareStart Malaria Pf ) or thick blood smear and then confirmed by a P. falciparum species-specific real-time PCR assay. A pfcrt gene segment containing a fragment that encodes amino acids at positions 72-76 was amplified by conventional PCR before sequencing. Results A total of 1070 patients were enrolled. Of the 806 PCR-confirmed P. falciparum positive samples, 764 were successfully sequenced. The K76T mutation was detected in 218 samples (28.5%; 95% CI: 25.4%–31.9%), mainly (96%) with the CVIET haplotype. Prevalence of CQ resistance marker was unequally distributed across the country, ranging from 1.5% in Fungurume to 89.5% in Katana. The SVMNT haplotype, related to AQ resistance, was not detected. Conclusion Overall, the frequency of the P. falciparum CQ resistance marker has decreased significantly and no resistance marker to AQ was detected in the DRC in 2017. However, the between regions variability of CQ resistance remains high in the country. Further studies are needed for continuous monitoring of the CQ resistance level for its prospective re-use in malaria management. The absence of the AQ resistance marker is in line with the use of this drug in the current DRC malaria treatment policy.

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Molecular surveillance of antimalarial drug resistance in Democratic Republic of Congo: high variability of chloroquinoresistance and lack of amodiaquinoresistance

10.21203/rs.2.18017/v1 ◽

2019 ◽

Author(s):

Doudou Malekita Yobi ◽

Nadine Kalenda Kayiba ◽

Dieudonné Makaba Mvumbi ◽

Raphael Boreux ◽

Pius Zakayi Kabututu ◽

...

Keyword(s):

Democratic Republic ◽

Democratic Republic Of Congo ◽

Gene Segment ◽

Resistance Rate ◽

Antimalarial Drug Resistance ◽

Resistance Level ◽

Molecular Surveillance ◽

Republic Of Congo ◽

Pfcrt Gene ◽

Species Specific

Abstract Background The loss of chloroquine (CQ) effectiveness has led to its withdrawal from national policies as first-line treatment for uncomplicated malaria in several endemic countries such as in the Democratic Republic of Congo (DRC). The K76T mutation on the pfcrt gene has been identified as a marker of CQ resistance and the SVMNT haplotype in codons 72–76 on the same gene has been associated with resistance to amodiaquine (AQ). In DRC, the prevalence of K76T has decreased from 100% in 2000 to 63.9% in 2014. The purpose of the study was to determine the prevalence of K76T mutations in P. falciparum circulating strains, sixteen years after CQ withdrawal in DRC and to investigate the presence of SVMNT haplotype. Methods In 2017, ten geographical sites across DRC were selected. Dried blood samples were collected from patients attending health centers. Malaria was first detected by rapid diagnostic test (RDT) available on site (SD Bioline malaria Ag Pf or CareStart Malaria Pf) or thick blood smear and then confirmed by a P. falciparum species-specific real-time PCR assay. A pfcrt gene segment containing a fragment that encodes amino acids at positions 72-76 was amplified by conventional PCR before sequencing. Results A total of 1070 patients were enrolled. Of the 806 PCR-confirmed P. falciparum positive samples, 764 were successfully sequenced. The K76T mutation was detected in 218 (28.5%; IC95%: 25.4% – 31.9%) samples, mainly (96%) with the CVIET haplotype. The CQ resistance prevalence was unequally distributed across the country ranging from 1.5% in Fungurume to 89.5% in Katana. The SVMNT haplotype, related to AQ resistance, was not detected. Conclusion Overall, the P. falciparum CQ resistance rate has decreased significantly and no resistance marker to AQ was detected in DRC in 2017. However, the between regions variability of CQ resistance remains high in the country. Further studies are needed for a continuous monitoring of the CQ resistance level for a prospective re-use in malaria management. The absence of AQ resistance is in line with the use of this drug in the current DRC malaria treatment policy.

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High drug resistance levels could compromise the control of HIV infection in paediatric and adolescent population in Kinshasa, the Democratic Republic of Congo

PLoS ONE ◽

10.1371/journal.pone.0248835 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0248835

Author(s):

Marina Rubio-Garrido ◽

Gabriel Reina ◽

Adolphe Ndarabu ◽

Ana Rodriguez-Galet ◽

Ana Valadés-Alcaraz ◽

...

Keyword(s):

Drug Resistance ◽

Children And Adolescents ◽

Democratic Republic ◽

Democratic Republic Of Congo ◽

Rescue Therapy ◽

High Rate ◽

Resistance Mutations ◽

Republic Of Congo ◽

Resistance Monitoring ◽

Hiv 1

Background The inadequacy of HIV viraemia and resistance monitoring in Africa leads to uncontrolled circulation of HIV strains with drug resistance mutations (DRM), compromising antiretroviral therapy (ART) effectiveness. This study describes the DRM prevalence and its therapeutic impact in HIV-infected pediatric patients from Kinshasa (Democratic Republic of Congo, DRC). Methods From 2016–2018, dried blood were collected from 71 HIV-infected children and adolescents under ART in two hospitals in Kinshasa for HIV-1 DRM pol analysis, predicted ARV-susceptibility by Stanford and phylogenetic characterization. Results HIV-1 sequences were recovered from 55 children/adolescents with 14 years of median-age. All had received nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI, NNRTI), 9.1% protease inhibitors (PI) and only one integrase inhibitor (INI). Despite the use of ART, 89.1% showed virological failure and 67.3% carried viruses with major-DRM to one (12.7%), two (47.3%), or three (5.5%) ARV-families. Most children/adolescents harbored DRM to NNRTI (73.5%) or NRTI (61.2%). Major-DRM to PI was present in 8.3% and minor-DRM to INI in 15%. Dual-class-NRTI+NNRTI resistance appeared in 53.1% of patients. Viruses presented high/intermediate resistance to nevirapine (72.9% patients), efavirenz (70.9%), emtricitabine/lamivudine (47.9%), rilpivirine (41.7%), etravirine (39.6%), doravidine (33.3%), zidovudine (22.9%), among others. Most participants were susceptible to INI and PI. Great diversity of variants was found, with a high rate (40%) of unique recombinants. Conclusion The high DRM prevalence observed among HIV-infected children and adolescents in Kinshasa could compromise the 95-95-95-UNAIDS targets in the DRC. It also reinforces the need for routine resistance monitoring for optimal rescue therapy election in this vulnerable population to control the spread of resistant HIV in the country.

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