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1.
Proc Natl Acad Sci U S A ; 116(38): 19077-19082, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31484771

RESUMO

Serum amyloid A (SAA) proteins are strongly induced in the liver by systemic infection and in the intestine by bacterial colonization. In infected mice, SAA proteins circulate in association with the vitamin A derivative retinol, suggesting that SAAs transport retinol during infection. Here we illuminate a structural basis for the retinol-SAA interaction. In the bloodstream of infected mice, most SAA is complexed with high-density lipoprotein (HDL). However, we found that the majority of the circulating retinol was associated with the small fraction of SAA proteins that circulate without binding to HDL, thus identifying free SAA as the predominant retinol-binding form in vivo. We then determined the crystal structure of retinol-bound mouse SAA3 at a resolution of 2.2 Å. Retinol-bound SAA3 formed a novel asymmetric trimeric assembly that was generated by the hydrophobic packing of the conserved amphipathic helices α1 and α3. This hydrophobic packing created a retinol-binding pocket in the center of the trimer, which was confirmed by mutagenesis studies. Together, these findings illuminate the molecular basis for retinol transport by SAA proteins during infection.


Assuntos
Salmonella typhimurium/metabolismo , Proteína Amiloide A Sérica/química , Proteína Amiloide A Sérica/metabolismo , Febre Tifoide/metabolismo , Vitamina A/metabolismo , Vitaminas/metabolismo , Animais , Cristalografia por Raios X , Camundongos , Camundongos Knockout , Modelos Moleculares , Mutação , Conformação Proteica , Proteína Amiloide A Sérica/genética , Febre Tifoide/virologia
3.
J Infect Chemother ; 22(11): 770-773, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27297635

RESUMO

Re-emerging multidrug-resistant typhoid fever is becoming a worldwide threat, especially in East Africa. At the beginning of 2015, an outbreak of typhoid fever started in the capital city of Uganda, and 1940 suspected cases were reported by 5 March 2015. In this report, we describe a case of typhoid fever caused by a MDR strain with HIV infection and hemoglobin S-syndrome thalassemia in an Ugandan from Kampala City. It is essential to consider MDR strains of Salmonella enterica serovar Typhi infections, including fluoroquinolone-resistant strains, in patients from Africa and Southeast Asia.


Assuntos
Febre Tifoide/diagnóstico , Febre Tifoide/epidemiologia , Adulto , Surtos de Doenças , Farmacorresistência Bacteriana Múltipla , Feminino , Infecções por HIV/microbiologia , Humanos , Salmonella typhi/isolamento & purificação , Febre Tifoide/microbiologia , Febre Tifoide/virologia , Uganda/epidemiologia
4.
Travel Med Infect Dis ; 12(2): 143-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24201038

RESUMO

BACKGROUND: In Greece the number of international travellers has increased significantly the past decade. AIM: To study the impact of international travels on the epidemiology of hepatitis A and enteric fever in Greece. METHODS: We studied cases of hepatitis A and enteric fever notified through the National Surveillance System from January 1, 2004 through December 31, 2011. RESULTS: A total of 921 cases of hepatitis A and 106 cases of enteric fever were notified; of them, 88 (9.5%) and 46 (43.4%) were travel-associated, respectively. Travellers returning from Eastern Europe and the Middle East accounted for most imported cases of hepatitis A (37 (43.5%) and 14 (16.5%) cases, respectively). The Indian subcontinent was the prevalent area of acquisition of travel-associated enteric fever, followed by the Middle East (35 (83.3%) and 4 (9.5%) cases, respectively). Foreign-born travellers accounted for 43 (48.8%) and 39 (86.6%) cases of travel-associated hepatitis A and enteric fever, respectively. Children <15 years accounted for 65.1% of hepatitis A cases and 7.7% among foreign-born travellers. Greek Roma accounted for 270 (29.3%) of all hepatitis A cases notified. CONCLUSIONS: International travels have a significant impact on the epidemiology of enteric fever in Greece, affecting mainly foreign travellers. Hepatitis A carries a significant burden of morbidity among Greek travellers and children of foreign nationality. There is a need to improve travel medicine services for travellers travelling to developing countries.


Assuntos
Hepatite A/epidemiologia , Hepatite A/microbiologia , Viagem/estatística & dados numéricos , Febre Tifoide/epidemiologia , Febre Tifoide/virologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Grécia/epidemiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Medicina de Viagem , Adulto Jovem
5.
Travel Med Infect Dis ; 7(5): 291-5, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19747664

RESUMO

International travelers are at increased risk of acquiring infectious diseases. These risks are even greater for individuals visiting resource-poor tropical regions and for immunocompromised travelers, including those with HIV infection. We reviewed ten years of consultative charts from the International Health Clinic at the Ottawa Hospital General Campus to describe travel risks and preventative measures for international travelers infected with HIV. A total of 100 patients infected with HIV (63 male, 37 female; mean age 42.2 years) were referred to the clinic prior to international travel. More than half (57%) were born in countries endemic for tropical diseases. Overall the median HIV viral load (VL) was <50 copies/ml (i.e. undetectable) and the median CD4 count was 440 cells/microL (IQR=285-630). The most common destination regions were sub-Saharan Africa (55 patients) and the Caribbean (14 patients). Endemic-born patients took longer trips than Canadian-born travelers (mean 45.2 vs. 22.7 days, p<0.05), were more likely to travel to visit friends and relatives (80.7% vs. 4.7%, p<0.05), and frequented regions with higher risks of malaria and other infectious tropical diseases. Endemic-born travelers infected with HIV stay abroad longer and are more likely to visit malarious regions than their Canadian-born counterparts. More research is needed to ensure the best preventive care of these special needs travelers.


Assuntos
Infecções por HIV/epidemiologia , Viagem/estatística & dados numéricos , Adulto , Estudos Transversais , Doenças Endêmicas , Feminino , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Humanos , Malária/epidemiologia , Malária/virologia , Masculino , Meningite/epidemiologia , Meningite/virologia , Estudos Retrospectivos , Fatores de Risco , Febre Tifoide/epidemiologia , Febre Tifoide/virologia , Febre Amarela/epidemiologia , Febre Amarela/virologia
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