Bacterial infections and antibiotic susceptibility in children with sickle-cell anemia on malaria chemoprevention using Dihydroartemisinin-piperaquine (DP) or Sulfadoxine-pyrimethamine (SP) in Uganda
11 affiliations
- 1Department of Pharmacy, College of Health Sciences, Makerere University, Kampala, Uganda
- 2Department of Pharmacology and Therapeutics, College of Health Sciences, Makerere University, Kampala, Uganda
- 3Department of Paediatrics and Child Health, College of Health Sciences, Makerere University, Kampala, Uganda
- 4Global Health Uganda, Kampala, Uganda
- 5National Microbiology Reference Laboratory, National Health Laboratory and Diagnostic Services, Ministry of Health, Kampala, Uganda
- 6Department of Immunology and Molecular Biology, College of Health Sciences, Makerere University, Kampala, Uganda
- 7Training and Research Unit of Excellence, Blantyre, Malawi
- 8Department of Epidemiology and Biostatistics, Makerere University, College of Health Sciences, Kampala, Uganda
- 9Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
- 10School of Global and Public Health, Kamuzu University of Health Sciences, Blantyre, Malawi
- 11Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
Abstract
Introduction: Over 300,000 babies are born annually with sickle cell anemia (SCA) in sub-Saharan Africa. Despite malaria chemoprevention and early penicillin prophylaxis, these children develop febrile illnesses. The effect of malaria chemoprevention regimens on the incidence of bacterial infections and antimicrobial resistance is unclear. We assessed incidence of bacterial infections and resistance patterns in children with SCA receiving weekly DP or monthly SP. Methods: This study was nested in a randomized, double-blind clinical trial comparing weekly DP with monthly SP. Participants were children aged 6 months to 15 years with SCA, followed every two months for a median of 14.7 months (IQR 11.2–18.2) and evaluated at all sick visits. Blood cultures were obtained for episodes of fever (axillary temperature >38℃) and processed using the BD BACTEC automated system. Bacterial identification was by phenotypic and genotypic methods. Whole-genome sequencing was performed using Illumina DNA Prep Kit, and antimicrobial resistance genes were characterized using AMRFinderPlus. Analyses were conducted in STATA 18.0 and limited to Ugandan participants. Results: Of 725 enrolled participants, 437 were from Uganda (221 DP; 216 SP). The mean (SD) age was 7.3 (3.8) years, and 52.4% were male. Pathogenic bacteria were rarely isolated, including Escherichia coli (3), Klebsiella pneumoniae (2), Staphylococcus aureus (2), Streptococcus agalactiae. (1), and Enterococcus faecalis (1). The cumulative incidence of bacterial growth over 22 months of follow-up was 2.3% (95% CI: 1.12–4.73). Children with positive cultures tended to have higher fevers and more hospitalizations. All isolates were multidrug-resistant. Multiple resistance genes were identified, including plasmid-mediated sulfonamide resistance via sul2 in both Klebsiella pneumoniae and Escherichia coli. Conclusion: Pathogenic bacteria were infrequently isolated from Ugandan children with SCA receiving malaria chemoprevention. The presence of sul2 indicates the possibility of plasmid-mediated sulfonamide resistance.
Related
- Factors associated with the optimal uptake of intermittent preventive treatment in pregnancy with sulfadoxine–pyrimethamine: The experiences of postpartum women attending child welfare clinics in three rural districts in the Western Region of Ghana
- Dihydroartemisinin as a pharmacokinetically constrained immune-conditioning pulse in cancer therapy
- Delivery strategies for malaria chemoprevention in the post-discharge management of children hospitalised with severe anaemia or severe malaria: protocol for a cluster randomised controlled implementation trial in Benin
- Translation elongation factor EF-P drives susceptibility to fluoroquinolone antibiotics in Bacillus subtilis
- Association between H19 polymorphisms and susceptibility to pediatric central nervous system tumors in Chinese children
BibTeX
@article{nambatya2026bacterial,
title = {{Bacterial infections and antibiotic susceptibility in children with sickle-cell anemia on malaria chemoprevention using Dihydroartemisinin-piperaquine (DP) or Sulfadoxine-pyrimethamine (SP) in Uganda}},
author = {Winnie Nambatya and Moses Ocan and Grace Ndeezi and Dennis Kalibbala and Ritah Namusoosa and Freddie Bwanga and Thandile Nkosi-Gondwe and Joanita Kirikumwino and Alisen Ayitewala and Isaac Ssewanyana and John Ssenkusu and Robert Opoka and Feiko O. ter Kuile and Kamija S. Phiri and Bjarne Robberstad and Richard Idro},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0340838},
url = {https://doi.org/10.1371/journal.pone.0340838},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Bacterial infections and antibiotic susceptibility in children with sickle-cell anemia on malaria chemoprevention using Dihydroartemisinin-piperaquine (DP) or Sulfadoxine-pyrimethamine (SP) in Uganda
AU - Winnie Nambatya
AU - Moses Ocan
AU - Grace Ndeezi
AU - Dennis Kalibbala
AU - Ritah Namusoosa
AU - Freddie Bwanga
AU - Thandile Nkosi-Gondwe
AU - Joanita Kirikumwino
AU - Alisen Ayitewala
AU - Isaac Ssewanyana
AU - John Ssenkusu
AU - Robert Opoka
AU - Feiko O. ter Kuile
AU - Kamija S. Phiri
AU - Bjarne Robberstad
AU - Richard Idro
PY - 2026
DA - 2026/10/15
JO - PLOS One
DO - 10.1371/journal.pone.0340838
UR - https://doi.org/10.1371/journal.pone.0340838
AB - Introduction: Over 300,000 babies are born annually with sickle cell anemia (SCA) in sub-Saharan Africa. Despite malaria chemoprevention and early penicillin prophylaxis, these children develop febrile illnesses. The effect of malaria chemoprevention regimens on the incidence of bacterial infections and antimicrobial resistance is unclear. We assessed incidence of bacterial infections and resistance patterns in children with SCA receiving weekly DP or monthly SP. Methods: This study was nested in a randomized, double-blind clinical trial comparing weekly DP with monthly SP. Participants were children aged 6 months to 15 years with SCA, followed every two months for a median of 14.7 months (IQR 11.2–18.2) and evaluated at all sick visits. Blood cultures were obtained for episodes of fever (axillary temperature >38℃) and processed using the BD BACTEC automated system. Bacterial identification was by phenotypic and genotypic methods. Whole-genome sequencing was performed using Illumina DNA Prep Kit, and antimicrobial resistance genes were characterized using AMRFinderPlus. Analyses were conducted in STATA 18.0 and limited to Ugandan participants. Results: Of 725 enrolled participants, 437 were from Uganda (221 DP; 216 SP). The mean (SD) age was 7.3 (3.8) years, and 52.4% were male. Pathogenic bacteria were rarely isolated, including Escherichia coli (3), Klebsiella pneumoniae (2), Staphylococcus aureus (2), Streptococcus agalactiae. (1), and Enterococcus faecalis (1). The cumulative incidence of bacterial growth over 22 months of follow-up was 2.3% (95% CI: 1.12–4.73). Children with positive cultures tended to have higher fevers and more hospitalizations. All isolates were multidrug-resistant. Multiple resistance genes were identified, including plasmid-mediated sulfonamide resistance via sul2 in both Klebsiella pneumoniae and Escherichia coli. Conclusion: Pathogenic bacteria were infrequently isolated from Ugandan children with SCA receiving malaria chemoprevention. The presence of sul2 indicates the possibility of plasmid-mediated sulfonamide resistance.
SN - 1932-6203
ER -