Journal Article > ResearchFull Text
Medical Research Archives. 24 January 2025; Volume 13 (Issue 1); 1-12.; DOI:10.18103/mra.v13i1.6155
Otshudiema J, Essomba R, Diagne M, Bitoungui V, Ebogo Y, et al.
Medical Research Archives. 24 January 2025; Volume 13 (Issue 1); 1-12.; DOI:10.18103/mra.v13i1.6155
BACKGROUND
Two sub variants (BA.4 and BA.5) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant are concerning as they are spreading rapidly worldwide; however, no published data concerning these variants are available in Cameroon. We report the early detection of these new sub variants that are associated with the onset of the fifth wave of coronavirus 2019 (COVID-19) in Cameroon.
METHODS
Positive samples were selected for next-generation sequencing (NGS). BA.4 and BA.5 complete genome sequences underwent sequence data analysis, epidemiology analysis of COVID-19’s resurgence and wave, recombination and pairwise matrix analysis, and phylogenetic analysis. We selected the first nine SARS-CoV-2 Omicron BA.4 and BA.5 sub variants detected in Cameroon using local whole genome sequencing for the NGS analysis.
RESULTS
During the fifth wave of resurgence of COVID-19 cases in Cameroon, it was found that the Northwest and Littoral regions were the most affected areas, while the Center and Littoral regions recorded the highest number of new deaths. The study identified evidence of recombination between the BA.2 sub variant and BA.4 and BA.5 Cameroonian strains. This result highlights the dynamic nature of SARS-CoV-2 evolution. The BA.5 strain (entitled hCoV-19/Cameroon/23850/2022) showed the highest sequence similarity to the first reported genome of the Omicron strain with 497 mutations. Phylogenetic analysis revealed that these nine Omicron sub variants were grouped into a distinct and highly distant cluster separate from the first Omicron variant detected in Botswana and were intermixed with sequences from other countries (the United States, Denmark, Scotland, and England), thus implying multiple introductions of the BA.4 and BA.5 sub variants in Cameroon.
CONCLUSIONS
Omicron BA.4 and BA.5 sub-lineages are associated with the onset of the fifth wave of COVID-19 in Cameroon. In addition to providing early warning of COVID-19 resurgence, continuous local genome sequencing of emerging variants is essential for detecting variants of concern, thereby guiding the country's response. This study emphasizes the value of real-time surveillance.
Conference Material > Poster
Nacis JS, Serafico ME, Frane RD, Domalanta-Ronquillo DGA, Licayan JJSL, et al.
MSF Paediatric Days 2024. 3 May 2024; DOI:10.57740/sde6xMYtNR
Journal Article > Pre-PrintFull Text
medRxiv. 18 February 2024; DOI:10.1101/2024.02.16.24302942
de Vrij N, Vandoren R, Ramadan K, Van Hul A, Kassa M, et al.
medRxiv. 18 February 2024; DOI:10.1101/2024.02.16.24302942
Human immunodeficiency virus (HIV) co-infection is a major challenge for visceral leishmaniasis (VL) control, particularly in Ethiopia where the incidence of both pathogens is high. VL-HIV often leads to high rates of antileishmanial treatment failure and recurrent VL disease relapses. Considering the high prevalence of HIV and Leishmania in the Ethiopian population, preventing the progression of asymptomatic Leishmania infection to disease would be a valuable asset to VL disease control and to the clinical management of people living with HIV (PLWH). However, such a strategy requires good understanding of risk factors for VL development. In immunocompetent individuals living in Brazil, India, or Iran, the Human Leukocyte Antigen (HLA) gene region has been associated with VL development. We used NanoTYPE, an Oxford Nanopore Technologies sequencing-based HLA genotyping method, to detect associations between HLA genotype and VL development by comparing 78 PLWH with VL history and 46 PLWH that controlled a Leishmania infection, all living in a VL endemic region of North-West Ethiopia. We identified a strong association between HLA-A*03:01 and increased risk of VL development (OR = 3.89). These data provide candidate HLA alleles that can be further explored for inclusion in a potential Leishmania screen-and-treat strategy in VL endemic regions.
Journal Article > ResearchFull Text
Sci Rep. 8 December 2023; Volume 13 (Issue 1); 21654.; DOI:10.1038/s41598-023-48773-3
Fokam J, Essomba RG, Njouom R, Okomo MCA, Eyangoh S, et al.
Sci Rep. 8 December 2023; Volume 13 (Issue 1); 21654.; DOI:10.1038/s41598-023-48773-3
While the SARS-CoV-2 dynamic has been described globally, there is a lack of data from Sub-Saharan Africa. We herein report the dynamics of SARS-CoV-2 lineages from March 2020 to March 2022 in Cameroon. Of the 760 whole-genome sequences successfully generated by the national genomic surveillance network, 74% were viral sub-lineages of origin and non-variants of concern, 15% Delta, 6% Omicron, 3% Alpha and 2% Beta variants. The pandemic was driven by SARS-CoV-2 lineages of origin in wave 1 (16 weeks, 2.3% CFR), the Alpha and Beta variants in wave 2 (21 weeks, 1.6% CFR), Delta variants in wave 3 (11 weeks, 2.0% CFR), and omicron variants in wave 4 (8 weeks, 0.73% CFR), with a declining trend over time (p = 0.01208). Even though SARS-CoV-2 heterogeneity did not seemingly contribute to the breadth of transmission, the viral lineages of origin and especially the Delta variants appeared as drivers of COVID-19 severity in Cameroon.
Journal Article > ResearchFull Text
Sci Rep. 13 October 2023; Volume 13 (Issue 1); 17363.; DOI:10.1038/s41598-023-44457-0
Acford-Palmer H, Campos M, Bandibabone JB, N’Do S, Bantuzeko C, et al.
Sci Rep. 13 October 2023; Volume 13 (Issue 1); 17363.; DOI:10.1038/s41598-023-44457-0
Français
Vector control strategies have been successful in reducing the number of malaria cases and deaths globally, but the spread of insecticide resistance represents a significant threat to disease control. Insecticide resistance has been reported across Anopheles (An.) vector populations, including species within the An. funestus group. These mosquitoes are responsible for intense malaria transmission across sub-Saharan Africa, including in the Democratic Republic of the Congo (DRC), a country contributing > 12% of global malaria infections and mortality events. To support the continuous efficacy of vector control strategies, it is essential to monitor insecticide resistance using molecular surveillance tools. In this study, we developed an amplicon sequencing (“Amp-seq”) approach targeting An. funestus, and using multiplex PCR, dual index barcoding, and next-generation sequencing for high throughput and low-cost applications. Using our Amp-seq approach, we screened 80 An. funestus field isolates from the DRC across a panel of nine genes with mutations linked to insecticide resistance (ace-1, CYP6P4, CYP6P9a, GSTe2, vgsc, and rdl) and mosquito speciation (cox-1, mtND5, and ITS2). Amongst the 18 non-synonymous mutations detected, was N485I, in the ace-1 gene associated with carbamate resistance. Overall, our panel represents an extendable and much-needed method for the molecular surveillance of insecticide resistance in An. funestus populations.
Journal Article > ResearchAbstract Only
J. Infect.. 25 June 2023; Volume S0163-4453 (Issue 23); 00336-5.; DOI:10.1016/j.jinf.2023.06.015
Jacquier H, Assao B, Chau F, Guindo O, Condamine B, et al.
J. Infect.. 25 June 2023; Volume S0163-4453 (Issue 23); 00336-5.; DOI:10.1016/j.jinf.2023.06.015
OBJECTIVE
Whole genome sequencing (WGS) of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. coli faecal isolates in rural Southern Niger.
METHODS
Stools of 383 healthy participants were collected among which 92.4% were ESBL-Enterobacterales carriers. A subset of 90 ESBL-E. coli containing stools (109 ESBL-E. coli isolates) were further analysed by WGS, using short- and long-reads.
RESULTS
Most isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. The blaCTX-M-15 gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne, blaCTX-M-15 was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis of blaCTX-M-15 in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome.
CONCLUSIONS
Massive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration of blaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.
Whole genome sequencing (WGS) of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. coli faecal isolates in rural Southern Niger.
METHODS
Stools of 383 healthy participants were collected among which 92.4% were ESBL-Enterobacterales carriers. A subset of 90 ESBL-E. coli containing stools (109 ESBL-E. coli isolates) were further analysed by WGS, using short- and long-reads.
RESULTS
Most isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. The blaCTX-M-15 gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne, blaCTX-M-15 was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis of blaCTX-M-15 in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome.
CONCLUSIONS
Massive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration of blaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.
Journal Article > ResearchFull Text
Public Health Action. 21 June 2023; Volume 13 (Issue 2); 43-49.; DOI:10.5588/pha.22.0041
Iyer AS, Ndlovu Z, Sharma J, Mansoor H, Bharati M, et al.
Public Health Action. 21 June 2023; Volume 13 (Issue 2); 43-49.; DOI:10.5588/pha.22.0041
English
Français
BACKGROUND
Phenotypic drug susceptibility testing (pDST) for Mycobacterium tuberculosis can take up to 8 weeks, while conventional molecular tests identify a limited set of resistance mutations. Targeted next-generation sequencing (tNGS) offers rapid results for predicting comprehensive drug resistance, and this study sought to explore its operational feasibility within a public health laboratory in Mumbai, India.
METHODS
Pulmonary samples from consenting patients testing Xpert MTB-positive were tested for drug resistance by conventional methods and using tNGS. Laboratory operational and logistical implementation experiences from study team members are shared below.
RESULTS
Of the total number of patients tested, 70% (113/161) had no history of previous TB or treatment; however, 88.2% (n = 142) had rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB). There was a high concordance between resistance predictions of tNGS and pDST for most drugs, with tNGS more accurately identifying resistance overall. tNGS was integrated and adapted into the laboratory workflow; however, batching samples caused significantly longer result turnaround time, fastest at 24 days. Manual DNA extraction caused inefficiencies; thus protocol optimisations were performed. Technical expertise was required for analysis of uncharacterised mutations and interpretation of report templates. tNGS cost per sample was US$230, while for pDST this was US$119.
CONCLUSIONS
Implementation of tNGS is feasible in reference laboratories. It can rapidly identify drug resistance and should be considered as a potential alternative to pDST.
Phenotypic drug susceptibility testing (pDST) for Mycobacterium tuberculosis can take up to 8 weeks, while conventional molecular tests identify a limited set of resistance mutations. Targeted next-generation sequencing (tNGS) offers rapid results for predicting comprehensive drug resistance, and this study sought to explore its operational feasibility within a public health laboratory in Mumbai, India.
METHODS
Pulmonary samples from consenting patients testing Xpert MTB-positive were tested for drug resistance by conventional methods and using tNGS. Laboratory operational and logistical implementation experiences from study team members are shared below.
RESULTS
Of the total number of patients tested, 70% (113/161) had no history of previous TB or treatment; however, 88.2% (n = 142) had rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB). There was a high concordance between resistance predictions of tNGS and pDST for most drugs, with tNGS more accurately identifying resistance overall. tNGS was integrated and adapted into the laboratory workflow; however, batching samples caused significantly longer result turnaround time, fastest at 24 days. Manual DNA extraction caused inefficiencies; thus protocol optimisations were performed. Technical expertise was required for analysis of uncharacterised mutations and interpretation of report templates. tNGS cost per sample was US$230, while for pDST this was US$119.
CONCLUSIONS
Implementation of tNGS is feasible in reference laboratories. It can rapidly identify drug resistance and should be considered as a potential alternative to pDST.
Journal Article > ResearchFull Text
Lancet Microbe. 6 June 2023; Volume S2666-5247 (Issue 23); 00110-6.; DOI:10.1016/S2666-5247(23)00110-6
Goig GA, Menardo F, Salaam-Dreyer Z, Dippenaar A, Streicher EM, et al.
Lancet Microbe. 6 June 2023; Volume S2666-5247 (Issue 23); 00110-6.; DOI:10.1016/S2666-5247(23)00110-6
BACKGROUND
Experimental data show that drug-resistance-conferring mutations are often associated with a decrease in the replicative fitness of bacteria in vitro, and that this fitness cost can be mitigated by compensatory mutations; however, the role of compensatory evolution in clinical settings is less clear. We assessed whether compensatory evolution was associated with increased transmission of rifampicin-resistant tuberculosis in Khayelitsha, Cape Town, South Africa.
METHODS
We did a genomic epidemiological study by analysing available M tuberculosis isolates and their associated clinical data from individuals routinely diagnosed with rifampicin-resistant tuberculosis in primary care and hospitals in Khayelitsha, Cape Town, South Africa. Isolates were collected as part of a previous study. All individuals diagnosed with rifampicin-resistant tuberculosis and with linked biobanked specimens were included in this study. We applied whole-genome sequencing, Bayesian reconstruction of transmission trees, and phylogenetic multivariable regression analysis to identify individual and bacterial factors associated with the transmission of rifampicin-resistant M tuberculosis strains.
FINDINGS
Between Jan 1, 2008, and Dec 31, 2017, 2161 individuals were diagnosed with multidrug-resistant or rifampicin-resistant tuberculosis in Khayelitsha, Cape Town, South Africa. Whole-genome sequences were available for 1168 (54%) unique individual M tuberculosis isolates. Compensatory evolution was associated with smear-positive pulmonary disease (adjusted odds ratio 1·49, 95% CI 1·08-2·06) and a higher number of drug-resistance-conferring mutations (incidence rate ratio 1·38, 95% CI 1·28-1·48). Compensatory evolution was also associated with increased transmission of rifampicin-resistant disease between individuals (adjusted odds ratio 1·55; 95% CI 1·13-2·12), independent of other patient and bacterial factors.
INTERPRETATION
Our findings suggest that compensatory evolution enhances the in vivo fitness of drug-resistant M tuberculosis genotypes, both within and between patients, and that the in vitro replicative fitness of rifampicin-resistant M tuberculosis measured in the laboratory correlates with the bacterial fitness measured in clinical settings. These results emphasise the importance of enhancing surveillance and monitoring efforts to prevent the emergence of highly transmissible clones capable of rapidly accumulating new drug resistance mutations. This concern becomes especially crucial at present, because treatment regimens incorporating novel drugs are being implemented.
Experimental data show that drug-resistance-conferring mutations are often associated with a decrease in the replicative fitness of bacteria in vitro, and that this fitness cost can be mitigated by compensatory mutations; however, the role of compensatory evolution in clinical settings is less clear. We assessed whether compensatory evolution was associated with increased transmission of rifampicin-resistant tuberculosis in Khayelitsha, Cape Town, South Africa.
METHODS
We did a genomic epidemiological study by analysing available M tuberculosis isolates and their associated clinical data from individuals routinely diagnosed with rifampicin-resistant tuberculosis in primary care and hospitals in Khayelitsha, Cape Town, South Africa. Isolates were collected as part of a previous study. All individuals diagnosed with rifampicin-resistant tuberculosis and with linked biobanked specimens were included in this study. We applied whole-genome sequencing, Bayesian reconstruction of transmission trees, and phylogenetic multivariable regression analysis to identify individual and bacterial factors associated with the transmission of rifampicin-resistant M tuberculosis strains.
FINDINGS
Between Jan 1, 2008, and Dec 31, 2017, 2161 individuals were diagnosed with multidrug-resistant or rifampicin-resistant tuberculosis in Khayelitsha, Cape Town, South Africa. Whole-genome sequences were available for 1168 (54%) unique individual M tuberculosis isolates. Compensatory evolution was associated with smear-positive pulmonary disease (adjusted odds ratio 1·49, 95% CI 1·08-2·06) and a higher number of drug-resistance-conferring mutations (incidence rate ratio 1·38, 95% CI 1·28-1·48). Compensatory evolution was also associated with increased transmission of rifampicin-resistant disease between individuals (adjusted odds ratio 1·55; 95% CI 1·13-2·12), independent of other patient and bacterial factors.
INTERPRETATION
Our findings suggest that compensatory evolution enhances the in vivo fitness of drug-resistant M tuberculosis genotypes, both within and between patients, and that the in vitro replicative fitness of rifampicin-resistant M tuberculosis measured in the laboratory correlates with the bacterial fitness measured in clinical settings. These results emphasise the importance of enhancing surveillance and monitoring efforts to prevent the emergence of highly transmissible clones capable of rapidly accumulating new drug resistance mutations. This concern becomes especially crucial at present, because treatment regimens incorporating novel drugs are being implemented.
Journal Article > ResearchFull Text
Emerg Infect Dis. 1 January 2023; Volume 29 (Issue 1); 149-153.; DOI:10.3201/eid2901.220641
Hounmanou YM, Njamkepo E, Rauzier J, Gallandat K, Jeandron A, et al.
Emerg Infect Dis. 1 January 2023; Volume 29 (Issue 1); 149-153.; DOI:10.3201/eid2901.220641
Africa’s Lake Tanganyika basin is a cholera hotspot. During 2001–2020, Vibrio cholerae O1 isolates obtained from the Democratic Republic of the Congo side of the lake belonged to 2 of the 5 clades of the AFR10 sublineage. One clade became predominant after acquiring a parC mutation that decreased susceptibility to ciprofloxacin.
Journal Article > LetterFull Text
Int J Tuberc Lung Dis. 1 December 2022; Volume 26 (Issue 12); 1180-1182.; DOI:10.5588/ijtld.22.0335
Memani B, Furin J, Cox HS, Reuter A
Int J Tuberc Lung Dis. 1 December 2022; Volume 26 (Issue 12); 1180-1182.; DOI:10.5588/ijtld.22.0335