The increasing healthcare burden of enteric fever in a low-incidence setting.

OBJECTIVES: Enteric fever carries appreciable morbidity in non-endemic settings, particularly in returned travelers. This study aimed to characterize the healthcare burden of enteric fever in a low-incidence setting and to identify risk factors and opportunities for preventative interventions. METHODS: Analysis of a retrospective case series from a tertiary pediatric center (2015-2019), augmented by public health notification and microbiological laboratory data (2018-2019), from Western Sydney, Australia, a region with frequent travel links to South Asia. RESULTS: Eighty-nine (89) patients were diagnosed with enteric fever, including 43 children with complete demographic and travel data. Enteric fever cases increased over time (by 4.9 % per year) and incidence was three times higher in the pediatric population (<15 years old) compared to adults. Travel to India and visiting friends and relatives (VFR) travel were risk factors. Few children received enteric fever vaccination prior to travel, as pre-travel advice most commonly was not sought. CONCLUSIONS: Children visiting relatives in high-incidence countries are increasingly at risk for enteric fever, particularly when travelling to South Asia. Targeted health advice to travelers visiting friends and relatives is warranted to mitigate the healthcare burden of enteric fever in low-incidence settings.

Fiebre tifoidea: una etiología poco frecuente de síndrome febril prolongado en pediatría / Typhoid fever: a rare etiology of prolonged febrile illness in pediatrics / Febre tifoide: uma etiología rara de síndrome febril prolongada em pediatría

Introducción: Las infecciones representan la etiología más frecuente del síndrome febril prolongado (SFP). Si bien las fiebres entéricas constituyen una causa posible, en Uruguay su prevalencia ha disminuido significativamente con la mejora de las condiciones socio sanitarias. Objetivo: Comunicar el caso de un adolescente con una etiología actualmente excepcional de SFP. Caso clínico 14 años, sano, zona suburbana. Comienza 2 semanas previo al ingreso con dolor en hemiabdomen superior. Agrega cefalea holocraneana leve y vómitos ocasionales. 5 días previos al ingreso fiebre 40°C axilar, un pico diario, sin otra sintomatología. Tránsito digestivo bajo y urinario normal. Examen físico: lúcido, buen aspecto general, abdomen doloroso a la palpación profunda en epigastrio. Sin irritación peritoneal. Resto normal. Analítica: Leucocitos 5200mm3, Proteína C reactiva 71.4mg/dL, hemocultivo sin desarrollo. Ecografía abdominal, radiografía de tórax y ecocardiograma normales. Serologías para Virus Epstein Barr, Citomegalovirus, y Bartonella henselae negativas. Orina normal, urocultivo sin desarrollo. Persiste con fiebre, agrega exantema macropapular evanescente en tronco, sin otros síntomas. Al 7° día de internación nuevo hemocultivo: Salmonella Typhi sensible a ampicilina que recibe por 14 días. Buena evolución. Discusión: La fiebre tifoidea es una enfermedad infectocontagiosa, aguda, potencialmente mortal. Las condiciones socioeconómicas son determinantes en su transmisión. La sensibilidad del hemocultivo es mayor durante la primera semana de enfermedad, por lo que en ocasiones es necesario reiterarlo. Sus manifestaciones clínicas inespecíficas y la baja incidencia hacen que esta etiología no sea habitualmente sospechada en nuestro medio. Por tanto, es importante aumentar el índice de sospecha y considerar entre los diagnósticos diferenciales de SFP esta etiología.

Introduction: Infections are the most frequent etiology of prolonged febrile illness (PFI). Although enteric fevers are a possible cause, their prevalence has significantly diminished in Uruguay, due to improved socio-sanitary conditions. Objective: To communicate the case of an adolescent with a currently exceptional etiology of PFI. Clinical case: 14 years old, healthy, suburban area. Two days prior to admission the patient has pain in upper hemi abdomen. Adds mild holocranial headache and occasional vomiting. 5 days prior to admission axilary temperature of 40°C, one daily peak, without other symptoms. Normal lower digestive and urinary transit. Physical examination: lucid, good general aspect, pain at deep palpation in epigastrium. No peritoneal irritation. Rest is normal. Laboratory: leukocytes 5200 mm3, C-reactive protein 71.4mg/dL, blood culture shows no growth. Abdominal sonogram, thoracic X-ray and echocardiogram are normal. Negative serology for Epstein Barr Virus, Cytomegalovirus and Bartonella henselae. Normal urine, urine culture with no growth. Fever persists, adds evanescent macropapular exanthema in on the trunk, without other symptoms. On the 7th day in hospital a new blood culture shows Salmonella Typhi sensitive to ampicillin, which he receives for 14 days. Good evolution. Discussion: Typhoid fever is an acute, life-threatening, infectious disease. Socioeconomic conditions are determinant in its transmission. Blood culture sensitivity is greater during the first week of the disease, that is why it must occasionally be repeated. Its unspecific clinical manifestations and low incidence make this etiology not be usually suspected in our surroundings. It is therefore important to increase our suspicion and to consider it amongst differential diagnosis in PFI.

Introdução: As infecções representam a etiologia mais frequente da síndrome febril prolongada (SFP). Embora as febres entéricas sejam uma causa possível, no Uruguai sua prevalência diminuiu significativamente com a melhoria das condições sociossanitárias. Objetivo: Relatar o caso de um adolescente com etiologia atualmente excepcional de SFP. Caso clínico 14 anos, saudável, zona suburbana. Começa 2 semanas antes da admissão com dor no abdome superior. Adiciona dor de cabeça holocraniana leve e vômitos ocasionais. 5 dias antes da admissão febre 40°C axilar, pico diário, sem outros sintomas. Trânsito digestivo inferior e trânsito urinário normais. Exame físico: lúcido, bom aspecto geral, abdome doloroso à palpação profunda no epigástrio. Sem irritação peritoneal. Resto normal. Análise: Leucócitos 5200mm3, proteína C reativa 71,4mg/dL, hemocultura sem desenvolvimento. Ultrassonografia abdominal, radiografia de tórax e ecocardiograma foram normais. As sorologias para vírus Epstein Barr, Citomegalovírus e Bartonella henselae foram negativas. Urina normal, urocultura sem desenvolvimento. Persiste com febre, acrescenta erupção macropapular evanescente no tronco, sem outros sintomas. No 7º dia de internação, nova hemocultura: Salmonella Typhi sensível à ampicilina, que recebeu por 14 dias. Boa evolução. Discussão: A febre tifóide é uma doença infecciosa aguda, potencialmente fatal. As condições socioeconômicas são decisivas na sua transmissão. A sensibilidade da hemocultura é maior durante a primeira semana da doença, por isso às vezes é necessário repeti-la. Suas manifestações clínicas inespecíficas e baixa incidência fazem com que essa etiologia não seja usualmente suspeitada em nosso meio. Portanto, é importante aumentar o índice de suspeição e considerar essa etiologia entre os diagnósticos diferenciais da SFP.

Extensively Drug-Resistant Typhoid Fever in the United States.

Cases of extensively drug-resistant (XDR) typhoid fever have been reported in the United States among patients who did not travel internationally. Clinicians should consider if and where the patient traveled when selecting empiric treatment for typhoid fever. XDR typhoid fever should be treated with a carbapenem, azithromycin, or both.

Tracking the Emergence of Azithromycin Resistance in Multiple Genotypes of Typhoidal Salmonella.

The rising prevalence of antimicrobial resistance in Salmonella enterica serovars Typhi and Paratyphi A, causative agents of typhoid and paratyphoid, have led to fears of untreatable infections. Of specific concern is the emerging resistance against azithromycin, the only remaining oral drug to treat extensively drug resistant (XDR) typhoid. Since the first report of azithromycin resistance from Bangladesh in 2019, cases have been reported from Nepal, India, and Pakistan. The genetic basis of this resistance is a single point mutation in the efflux pump AcrB (R717Q/L). Here, we report 38 additional cases of azithromycin-resistant (AzmR) Salmonella Typhi and Paratyphi A isolated in Bangladesh between 2016 and 2018. Using genomic analysis of 56 AzmR isolates from South Asia with AcrB-R717Q/L, we confirm that this mutation has spontaneously emerged in different Salmonella Typhi and Paratyphi A genotypes. The largest cluster of AzmR Typhi belonged to genotype 4.3.1.1; Bayesian analysis predicts the mutation to have emerged sometime in 2010. A travel-related Typhi isolate with AcrB-R717Q belonging to 4.3.1.1 was isolated in the United Kingdom, increasing fears of global spread. For real-time detection of AcrB-R717Q/L, we developed an extraction-free, rapid, and low-cost mismatch amplification mutation assay (MAMA). Validation of MAMA using 113 AzmR and non-AzmR isolates yielded >98% specificity and sensitivity versus phenotypic and whole-genome sequencing assays currently used for azithromycin resistance detection. With increasing azithromycin use, AcrB-R717Q/L is likely to be acquired by XDR strains. The proposed tool for active detection and surveillance of this mutation may detect pan-oral drug resistance early, giving us a window to intervene.IMPORTANCE In the early 1900s, with mortality of ∼30%, typhoid and paratyphoid ravaged parts of the world; with improved water, sanitation, and hygiene in resource-rich countries and the advent of antimicrobials, mortality dwindled to <1%. Today, the burden rests disproportionately on South Asia, where the primary means for combatting the disease is antimicrobials. However, prevalence of antimicrobial resistance is rising and, in 2016, an extensively drug resistant Typhi strain triggered an ongoing outbreak in Pakistan, leaving only one oral drug, azithromycin, to treat it. Since the description of emergence of azithromycin resistance, conferred by a point mutation in acrB (AcrB-R717Q/L) in 2019, there have been increasing numbers of reports. Using genomics and Bayesian analysis, we illustrate that this mutation emerged in approximately 2010 and has spontaneously arisen multiple times. Emergence of pan-oral drug resistant Salmonella Typhi is imminent. We developed a low-cost, rapid PCR tool to facilitate real-time detection and prevention policies.