Multidrug-resistant NontyphoidalSalmonellaHotspots as Targets for Vaccine Use in Management of Infections in Endemic Settings

Abstract

Background Salmonella infections cause a disproportionately high number of deaths in Africa, especially among poor urban populations. The increasing level of multidrug-resistant (MDR) infections is a major cause of concern in these settings where alternative effective treatment is unavailable. Other options for management of these infections must be sought. The knowledge of hotspots in endemic settings can help to prioritize management and control measures in Kenya and the region. MethodsUsing blood cultures, we investigated children presenting with fever of unknown origin for Salmonella infections. We performed antimicrobial susceptibility testing and whole genome sequencing to further characterize Salmonella isolates. Using Global Positioning System technologies, we mapped Salmonella isolates to households of patients in the study site and determined risk factors associated with high concentration of cases in particular sites. ResultsA total of 281 Salmonella species (149 from blood and 132 from fecal samples) from febrile children <5 years of age were studied. These consisted of 85 Salmonella Typhimurium, 58 Salmonella Enteritidis, 32 other nontyphoidal Salmonella (NTS) serotypes, and 126 Salmonella Typhi. The prevalence of MDR invasive NTS (iNTS) was 77.2%, with 15% resistant to ceftriaxone, a drug that is last-line treatment for iNTS and other severe gram-negative infections in Kenya. Invasive NTS and S. Typhi together mapped around common water vending points and close to sewer convergence points in the highly populated village.ConclusionsThese hotspots could be targeted for management and control strategies, including a combined introduction of typhoid and iNTS vaccines, aimed at reducing transmission in these endemic settings.

Non-typhoidal Salmonella bloodstream infections in Kisantu, DR Congo: Emergence of O5-negative Salmonella Typhimurium and extensive drug resistance

“…Pefloxacin disk diffusion methods flawlessly predicted DCS and nalidixic acid performed relatively well. A similar concurrent emergence of ceftriaxone resistance and DCS was seen in Kenya with 15% ceftriaxone resistance and 6% DCS in NTS (on a total of 281 NTS isolates) [66] and in South-Africa with ceftriaxone resistance in 9% of Salmonella Typhimurium (n = 2420) and DCS in around 30% of NTS (Salmonella Typhimurium: n = 2420; Salmonella Enteritidis: n = 1149), including some fully fluoroquinolone resistant isolates [61] In Mali, 18.2% of Salmonella Enteritidis were ceftriaxone resistant [47]. Recently, one DCS Salmonella Typhimurium was reported in Ghana [67] and NTS presenting ceftriaxone resistance (n = 4) or DCS (n = 1) were reported in Malawi [45].…”

Factors associated with occurrence of salmonellosis among children living in Mukuru slum, an urban informal settlement in Kenya

“…In sub-Saharan Africa (SSA) non-typhoidal Salmonella (NTS) is a major cause of invasive bacterial infections in infants and young children, the elderly, immunocompromised and the malnourished [1][2][3][4][5][6]. Invasive NTS disease is caused mainly by Salmonella enterica subspecies enterica serovars Typhimurium and Enteritidis [6][7][8][9].…”

“…In sub-Saharan Africa (SSA) non-typhoidal Salmonella (NTS) is a major cause of invasive bacterial infections in infants and young children, the elderly, immunocompromised and the malnourished [1][2][3][4][5][6]. Invasive NTS disease is caused mainly by Salmonella enterica subspecies enterica serovars Typhimurium and Enteritidis [6][7][8][9]. Multi-drug resistant (MDR) iNTS is common in resourcepoor settings in Kenya [10], and in other parts of SSA [11][12][13][14][15][16] posing a major challenge to treatment and management options available.…”

“…Typhoid fever, caused by S. Typhi is also endemic in SSA, partly because the supply of clean drinking water and sanitation have not kept pace with the rapid population growth [17]. Typhoid is now estimated to have an average annual incidence of 263/100,000 pyo (95% CI: 199-347) in all age groups in Kenya [18] and causes more illness among older children compared to NTS [6]. These rates are very similar to what has been documented in slums in Pakistan [19], India [20,21] and Bangladesh [22].…”

Inhibition of invasive salmonella by orally administered IgA and IgG monoclonal antibodies

“…Episodes of MSD and LSD can each have long term impacts on child health, most notably linear growth faltering. Other pathogens like multidrug resistant typhoid and invasive non-typhoidal Salmonella (iNTS) caused by different serovars of Salmonella enterica are also a source of infections in sub-Saharan Africa that can have short-and long-term health consequences [4][5][6]. The dire need for vaccines against enteric bacterial pathogens like C. jejuni, Shigella, ETEC and Salmonella has been recognized for decades, especially within military settings [2].…”