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Background <p>Typhoid fever is a serious infection that primarily affects humans, with approximately 20&#xa0;million cases reported each year, mostly in low- and middle-income countries (LMICs). Continuous monitoring of <i>Salmonella enterica</i> serovar Typhi (<i>S</i>. Typhi) in these endemic areas is crucial for tracking trends in antimicrobial resistance (AMR) and developing effective control measures. This study focused on <i>S</i>. Typhi isolates from children aged ≤ 16 years who showed symptoms of fever in Mukuru and Kibera informal settlements in Nairobi County, Kenya.</p> Methods <p>Blood samples for culture were collected from participants at four health facilities within Nairobi County. Antimicrobial susceptibility profiles were assessed using the Kirby–Bauer disc diffusion technique, and whole-genome sequencing (WGS) was performed on selected multidrug-resistant (MDR) isolates. The genomes were assembled and analysed using <a href="https://pathogen.watch/">https://pathogen.watch/</a> to identify genotypes, resistance genes, and phylogenetic relationships.</p> Results <p>Out of 120 <i>S</i>. Typhi isolates tested, 50% were found to be MDR. Resistance to first-line antibiotics was common, with 65.6% resistant to ampicillin, 62.3% to sulfamethoxazole-trimethoprim, and 59% to chloramphenicol. Thirty-seven selected MDR isolates underwent WGS, all belonging to the genotype 4.3.1 (H58), which is the most prevalent MDR clade globally. These were further categorised into sublineage 4.3.1.1 EA (East Africa 1), accounting for 40.5% of the sequenced isolates. Genomic analysis identified several AMR genes, including <i>bla</i><sub>TEM−1D</sub>, <i>catA1</i>,<i> dfrA7</i>,<i> sul1</i>, and <i>sul2</i>. Additionally, point mutations in the quinolone resistance-determining region (QRDR) of <i>gyrA</i> were found in 67.6% of the isolates, with the most common mutation being <i>S83Y</i>. These mutations are linked to decreased susceptibility to ciprofloxacin, a key treatment for typhoid in Kenya.</p> Conclusion <p>The high rate of MDR <i>S</i>. Typhi, especially in children who are most affected by the disease, raises significant public health concerns. The presence of QRDR mutations further complicates treatment options for typhoid fever, highlighting the urgent need for alternative approaches. These may include broader use of typhoid conjugate vaccines (TCVs), strengthening antimicrobial stewardship programs, and investing in improvements in water, sanitation, and hygiene (WASH) infrastructure in these endemic settings in Kenya.</p>

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High prevalence of multi-drug resistant H58 Salmonella Typhi and emerging fluoroquinolone resistance among febrile children in Nairobi County, Kenya

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月10日

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  • Susan Mutile Kavai,
  • Cecilia Mbae,
  • Michael Mugo,
  • Peter Njoroge,
  • Jessica Chepchirchir,
  • Naomi Wambui,
  • Steve Anyona,
  • Diana Imoli,
  • Ronald Ng’etich,
  • Evans Kibet,
  • Georgina Odityo,
  • Sheillah Mundalo,
  • Celestine Wairimu,
  • Mary Kariuki,
  • Amos Njuguna,
  • Evelyn Wamucii,
  • Winfred Mbithi,
  • Darius Owegi,
  • Peter Muturi,
  • Collins Kebenei,
  • Humphrey Miriti,
  • Naomi Komen,
  • Christine Kioko,
  • Maureen Kawira,
  • June Kavai,
  • Rahma Osman,
  • Zillah Wakio,
  • Beatrice Ongadi,
  • Robert Onsare,
  • Kelvin Kering,
  • Samuel Kariuki

摘要

Background

Typhoid fever is a serious infection that primarily affects humans, with approximately 20 million cases reported each year, mostly in low- and middle-income countries (LMICs). Continuous monitoring of Salmonella enterica serovar Typhi (S. Typhi) in these endemic areas is crucial for tracking trends in antimicrobial resistance (AMR) and developing effective control measures. This study focused on S. Typhi isolates from children aged ≤ 16 years who showed symptoms of fever in Mukuru and Kibera informal settlements in Nairobi County, Kenya.

Methods

Blood samples for culture were collected from participants at four health facilities within Nairobi County. Antimicrobial susceptibility profiles were assessed using the Kirby–Bauer disc diffusion technique, and whole-genome sequencing (WGS) was performed on selected multidrug-resistant (MDR) isolates. The genomes were assembled and analysed using https://pathogen.watch/ to identify genotypes, resistance genes, and phylogenetic relationships.

Results

Out of 120 S. Typhi isolates tested, 50% were found to be MDR. Resistance to first-line antibiotics was common, with 65.6% resistant to ampicillin, 62.3% to sulfamethoxazole-trimethoprim, and 59% to chloramphenicol. Thirty-seven selected MDR isolates underwent WGS, all belonging to the genotype 4.3.1 (H58), which is the most prevalent MDR clade globally. These were further categorised into sublineage 4.3.1.1 EA (East Africa 1), accounting for 40.5% of the sequenced isolates. Genomic analysis identified several AMR genes, including blaTEM−1D, catA1, dfrA7, sul1, and sul2. Additionally, point mutations in the quinolone resistance-determining region (QRDR) of gyrA were found in 67.6% of the isolates, with the most common mutation being S83Y. These mutations are linked to decreased susceptibility to ciprofloxacin, a key treatment for typhoid in Kenya.

Conclusion

The high rate of MDR S. Typhi, especially in children who are most affected by the disease, raises significant public health concerns. The presence of QRDR mutations further complicates treatment options for typhoid fever, highlighting the urgent need for alternative approaches. These may include broader use of typhoid conjugate vaccines (TCVs), strengthening antimicrobial stewardship programs, and investing in improvements in water, sanitation, and hygiene (WASH) infrastructure in these endemic settings in Kenya.