Journal Article > Pre-PrintFull Text
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.
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.
Journal Article > ResearchFull Text
Malar J. 10 November 2023; Volume 22 (Issue 1); 345.; DOI:10.1186/s12936-023-04740-x
Molina-de la Fuente I, Sagrado Benito MJ, Lasry E, Ousley J, García L, et al.
Malar J. 10 November 2023; Volume 22 (Issue 1); 345.; DOI:10.1186/s12936-023-04740-x
BACKGROUND
Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine plus amodiaquine (SP-AQ), is a community-based malaria preventive strategy commonly used in the Sahel region of sub-Saharan Africa. However, to date it has not been implemented in East Africa due to high SP resistance levels. This paper is a report on the implementation of SMC outside of the Sahel in an environment with a high level of presumed SP-resistance: five cycles of SMC using SPAQ were administered to children 3–59 months during a period of high malaria transmission (July–December 2019) in 21 villages in South Sudan.
METHODS
A population-based SMC coverage survey was combined with a longitudinal time series analysis of health facility and community health data measured after each SMC cycle. SMC campaign effectiveness was assessed by Poisson model. SPAQ molecular resistance markers were additionally analysed from dried blood spots from malaria confirmed patients.
RESULTS
Incidence of uncomplicated malaria was reduced from 6.6 per 100 to an average of 3.2 per 100 after SMC administration (mean reduction: 53%) and incidence of severe malaria showed a reduction from 21 per 10,000 before SMC campaign to a mean of 3.3 per 10,000 after each cycle (mean reduction: 84%) in the target group when compared to before the SMC campaign. The most prevalent molecular haplotype associated with SP resistance was the IRNGE haplotype (quintuple mutant, with 51I/59R/108N mutation in pfdhfr + 437G/540E in pfdhps). In contrast, there was a low frequency of AQ resistance markers and haplotypes resistant to both drugs combined (< 2%).
CONCLUSIONS
The SMC campaign was effective and could be used as an additional preventive tool in seasonal malaria settings outside of the Sahel, especially in areas where access to health care is unstable. Malaria case load reduction was observed despite the high level of resistance to SP.
Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine plus amodiaquine (SP-AQ), is a community-based malaria preventive strategy commonly used in the Sahel region of sub-Saharan Africa. However, to date it has not been implemented in East Africa due to high SP resistance levels. This paper is a report on the implementation of SMC outside of the Sahel in an environment with a high level of presumed SP-resistance: five cycles of SMC using SPAQ were administered to children 3–59 months during a period of high malaria transmission (July–December 2019) in 21 villages in South Sudan.
METHODS
A population-based SMC coverage survey was combined with a longitudinal time series analysis of health facility and community health data measured after each SMC cycle. SMC campaign effectiveness was assessed by Poisson model. SPAQ molecular resistance markers were additionally analysed from dried blood spots from malaria confirmed patients.
RESULTS
Incidence of uncomplicated malaria was reduced from 6.6 per 100 to an average of 3.2 per 100 after SMC administration (mean reduction: 53%) and incidence of severe malaria showed a reduction from 21 per 10,000 before SMC campaign to a mean of 3.3 per 10,000 after each cycle (mean reduction: 84%) in the target group when compared to before the SMC campaign. The most prevalent molecular haplotype associated with SP resistance was the IRNGE haplotype (quintuple mutant, with 51I/59R/108N mutation in pfdhfr + 437G/540E in pfdhps). In contrast, there was a low frequency of AQ resistance markers and haplotypes resistant to both drugs combined (< 2%).
CONCLUSIONS
The SMC campaign was effective and could be used as an additional preventive tool in seasonal malaria settings outside of the Sahel, especially in areas where access to health care is unstable. Malaria case load reduction was observed despite the high level of resistance to SP.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 25 September 2023; Online ahead of print; tpmd230382.; DOI:10.4269/ajtmh.23-0382
Molina-de la Fuente I, Sagrado Benito MJ, Ousley J, Gisbert FdB, García L, et al.
Am J Trop Med Hyg. 25 September 2023; Online ahead of print; tpmd230382.; DOI:10.4269/ajtmh.23-0382
Artemisinin-combined treatments are the recommended first-line treatment of Plasmodium falciparum malaria, but they are being threatened by emerging artemisinin resistance. Mutations in pfk13 are the principal molecular marker for artemisinin resistance. This study characterizes the presence of mutations in pfk13 in P. falciparum in Western Equatoria State, South Sudan. We analyzed 468 samples from patients with symptomatic malaria and found 15 mutations (8 nonsynonymous and 7 synonymous). Each mutation appeared only once, and none were validated or candidate markers of artemisinin resistance. However, some mutations were in the same or following position of validated and candidate resistance markers, suggesting instability of the gene that could lead to resistance. The R561L nonsynonymous mutation was found in the same position as the R561H validated mutation. Moreover, the A578S mutation, which is widespread in Africa, was also reported in this study. We found a high diversity of other pfk13 mutations in low frequency. Therefore, routine molecular surveillance of resistance markers is highly recommended to promptly detect the emergence of resistance-related mutations and to limit their spread.
Journal Article > Short ReportFull Text
Emerg Infect Dis. 1 January 2023; Volume 29 (Issue 1); 154-159.; DOI:10.3201/eid2901.220775
Molina-de la Fuente I, Benito MJS, Flevaud L, Ousley J, Pasquale HA, et al.
Emerg Infect Dis. 1 January 2023; Volume 29 (Issue 1); 154-159.; DOI:10.3201/eid2901.220775
Pfhrp2 and pfhrp3 gene deletions threaten the use of Plasmodium falciparum malaria rapid diagnostic tests globally. In South Sudan, deletion frequencies were 15.6% for pfhrp2, 20.0% for pfhrp3, and 7.5% for double deletions. Deletions were approximately twice as prevalent in monoclonal infections than in polyclonal infections.