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41 result(s)
Journal Article > ResearchFull Text

Phenotypic and genotypic resistance to bedaquiline in patients with multi-drug-resistant tuberculosis—experiences from Armenia

Antimicrob Agents Chemother. 9 April 2025; Online ahead of print; DOI:10.1128/aac.01839-24
Ardizzoni E, Mulders W, De Diego Fuertes M, Hayrapetyan A, Mirzoyan A,  et al.
Antimicrob Agents Chemother. 9 April 2025; Online ahead of print; DOI:10.1128/aac.01839-24

Risk factors for baseline bedaquiline (BDQ) resistance, amplification during treatment, and correlations with treatment outcomes are not fully understood. This cohort included Armenian patients with multidrug-resistant TB predominantly fluoroquinolone-resistant enrolled between 2013 and 2015 in a BDQ compassionate use program. BDQ resistance at baseline and during treatment was assessed using MGIT (pDSTMGIT), minimal inhibitory concentration in 7H11 (MIC7H11), and whole-genome sequencing. Risk factors, such as treatment effectiveness or stage of the disease, were analyzed for association with baseline BDQ resistance, acquired BDQ resistance, and treatment outcome. Among 39 patients, baseline BDQ resistance was 6% (2/33) by pDSTMGIT and 7% (2/29) by MIC7H11. All four baseline isolates with an Rv0678 mutation were phenotypically resistant. During treatment, 48% of the patients acquired BDQ resistance by pDSTMGIT, and 52% acquired mutations at various frequencies (97% in Rv0678). None of the factors significantly contributed to baseline or acquired BDQ resistance. Unfavorable treatment outcome (41%) was more frequent in the presence of acquired Rv0678 mutations [odds ratio (OR) 132, 95% confidence interval (CI) 7.43, 2375], phenotypic BDQ resistance (OR 176, 95% CI 6.48, 2423), or MIC increase above or below the critical concentration (both OR 84.3, 95% CI 2.93, 2423) during treatment. For these highly treatment-experienced patients, low baseline prevalence but high incidence of acquired BDQ resistance was observed. Acquisition of mutations in BDQ candidate resistance genes, regardless of their frequency, or increased MICs during treatment, even below the critical concentration, should be seen as a warning sign of resistance amplification and increased risk of unfavorable treatment outcome.

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Journal Article > ResearchFull Text

Initial detection of SARS-CoV-2 Omicron BA.4 and BA.5 subvariants associated with the onset of the fifth wave of COVID-19 in Cameroon between December 2021 and June 2022: Phylogenetic and whole genome analysis

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.

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Journal Article > ResearchFull Text

The genetic diversity of Nipah virus across spatial scales

J Infect Dis. 16 December 2024; Volume 230 (Issue 6); e1235-e1244.; DOI:10.1093/infdis/jiae221
Cortes-Azuero O, Lefrancq N, Nikolay B, McKee C, Cappelle J,  et al.
J Infect Dis. 16 December 2024; Volume 230 (Issue 6); e1235-e1244.; DOI:10.1093/infdis/jiae221

BACKGROUND

Nipah virus (NiV), a highly lethal virus in humans, circulates in Pteropus bats throughout South and Southeast Asia. Difficulty in obtaining viral genomes from bats means we have a poor understanding of NiV diversity.


METHODS

We develop phylogenetic approaches applied to the most comprehensive collection of genomes to date (N = 257, 175 from bats, 73 from humans) from 6 countries over 22 years (1999–2020). We divide the 4 major NiV sublineages into 15 genetic clusters. Using Approximate Bayesian Computation fit to a spatial signature of viral diversity, we estimate the presence and the average size of genetic clusters per area.


RESULTS

We find that, within any bat roost, there are an average of 2.4 co-circulating genetic clusters, rising to 5.5 clusters at areas of 1500–2000 km2. We estimate that each genetic cluster occupies an average area of 1.3 million km2 (95% confidence interval [CI], .6–2.3 million km2), with 14 clusters in an area of 100 000 km2 (95% CI, 6–24 km2). In the few sites in Bangladesh and Cambodia where genomic surveillance has been concentrated, we estimate that most clusters have been identified, but only approximately 15% of overall NiV diversity has been uncovered.


CONCLUSIONS

Our findings are consistent with entrenched co-circulation of distinct lineages, even within roosts, coupled with slow migration over larger spatial scales.

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Conference Material > Poster

Eastern Visayas Birth Cohort (EVBC) study protocol: Unraveling the integrative omics and nutritional determinants of child development from prenatal to early childhood

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

Genetic diversity and allelic variability of pfmsp1 y pfmsp2 of P. falciparum and its association with syntomatology and antimalarial drugs resistance markers in Yambio county, South Sudan

Malar J. 21 February 2024; DOI:10.21203/rs.3.rs-3959166/v1
Fuente IMdl, Benito MJS, Gisbert FB, García L, González V,  et al.
Malar J. 21 February 2024; DOI:10.21203/rs.3.rs-3959166/v1
BACKGROUND
Malaria genetic diversity is an important indicator of malaria transmission. Pfmsp1 and pfmsp2 are a frequent molecular epidemiology tool to assess the genetic diversity. This study aims to assess the genetic diversity and the description of multiplicity of infection (MOI) of P. falciparum in Yambio County, South Sudan. Additionally, it assesses the association of specific alleles or multiplicity of infection with antimalarial drugs resistance haplotypes and severity of infection, major challenges in malaria control strategies.

METHODS
There were collected 446 malaria samples from patients in Yambio county. After P. falciparum confirmation, pfmsp1 and pfmsp2 allelic families were genotyped. Frequencies of each alleles were described and multiplicity of infection was calculated. The association between MOI and complicated malaria was assessed using U-Mann Whitney test. The Kruskal-Wallis test was used to compare MOI between collection sites, age groups and antimalarial resistance haplotypes.

RESULTS
For pfmsp1, monomorphic K1 allele infection was predominant (37.0%) in every location and for pfmsp2 locus, monomorphic 3D7 was predominant (44.8%). 71.9% of samples were polyclonal infections (overall MOI = 1.96). The high diversity and polyclonal infections are associated with molecular markers of resistance, and high MOI has been related with a lower risk of severity of infections. There was not find evidence of association between a specific allele and an infection trait.

CONCLUSION
High genetic diversity and high level of polyclonal infections have been found in this study, confirming the general high transmission, and highlighting the need for control measures to be intensified in Yambio county, South Sudan.
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Journal Article > Pre-PrintFull Text

HLA-A*03:01 is associated with visceral leishmaniasis development in people living with HIV in Ethiopia

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.More
Journal Article > ResearchFull Text

Genomic surveillance of SARS-CoV-2 reveals highest severity and mortality of delta over other variants: evidence from Cameroon

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.More
Journal Article > ResearchFull Text

Effect of amoxicillin on the gut microbiome of children with severe acute malnutrition in Madarounfa, Niger: a retrospective metagenomic analysis of a placebo-controlled trial

Lancet Microbe. 19 October 2023; Online ahead of print; DOI:10.1016/S2666-5247(23)00213-6
Schwartz DJ, Langdon A, Sun X, Langendorf C, Berthé F,  et al.
Lancet Microbe. 19 October 2023; Online ahead of print; DOI:10.1016/S2666-5247(23)00213-6
BACKGROUND
Children with severe acute malnutrition are treated with antibiotics as outpatients. We aimed to determine the effect of 7 days of amoxicillin on acute and long-term changes to the gut microbiome and antibiotic resistome in children treated for severe acute malnutrition.

METHODS
We conducted a secondary analysis of a randomised, double-blinded, placebo-controlled trial (NCT01613547) of amoxicillin in children (aged 6-59 months) with severe acute malnutrition treated as outpatients in Madarounfa, Niger. We randomly selected 161 children from the overall cohort (n=2399) for initial 12-week follow-up from Sept 23, 2013 to Feb 3, 2014. We selected a convenience sample of those 161 children, on the basis of anthropometric measures, for follow-up 2 years later (Sept 28 to Oct 27, 2015). Children provided faecal samples at baseline, week 1, week 4, week 8, week 12, and, for those in the 2-year follow-up cohort, week 104. We conducted metagenomic sequencing followed by microbiome and resistome profiling of faecal samples. 38 children without severe acute malnutrition and six children with severe acute malnutrition matching the baseline ages of the original cohort were used as reference controls.

FINDINGS
In the 12-week follow-up group, amoxicillin led to an immediate decrease in gut microbiome richness from 37·6 species (95% CI 32·6-42·7) and Shannon diversity index (SDI) 2·18 (95% CI 1·97-2·39) at baseline to 27·7 species (95% CI 22·9-32·6) species and SDI 1·55 (95% CI 1·35-1·75) at week 1. Amoxicillin increased gut antibiotic resistance gene abundance to 6044 reads per kilobase million (95% CI 4704-7384) at week 1, up from 4800 (3391-6208) at baseline, which returned to baseline 3 weeks later. 35 children were included in the 2-year follow-up; the amoxicillin-treated children (n=22) had increased number of species in the gut microbiome compared with placebo-treated children (n=13; 60·7 [95% CI 54·7-66·6] vs 36·9 [29·4-44·3]). Amoxicillin-treated children had increased Prevotella spp and decreased Bifidobacterium spp relative to age-matched placebo-treated children, indicating a more mature, adult-like microbiome.

INTERPRETATION
Amoxicillin treatment led to acute but not sustained increases in antimicrobial resistance genes and improved gut microbiome maturation 2 years after severe acute malnutrition treatment.
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Journal Article > ResearchFull Text

Detection of insecticide resistance markers in Anopheles funestus from the Democratic Republic of the Congo using a targeted amplicon sequencing panel

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.More
Journal Article > ResearchAbstract Only

Faecal carriage of extended-spectrum ß-lactamase-producing Escherichia coli in a remote region of Niger

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.
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