Gorączka tyfoidowa – Rokowania, prognozy i postęp choroby

Gorączka tyfoidowa
Rokowania, prognozy i postęp choroby

Gorączka tyfoidowa, wywołana głównie przez Salmonella enterica serotyp typhi, pozostaje poważnym zagrożeniem zdrowotnym, szczególnie w regionach o ograniczonym dostępie do diagnostyki i leczenia. Wskaźnik śmiertelności u hospitalizowanych pacjentów wynosi średnio 4,2%, z wyraźnymi różnicami geograficznymi: 0,9% w Azji, 5,4% w Afryce, 7,2% w Oceanii, 6,7% w obu Amerykach oraz 1,0% w Europie. Bez leczenia choroba może trwać od 4 do 8 tygodni, a powikłania występują u około 26% przypadków, obejmując perforację jelita (mediana śmiertelności 15,5%), krwawienia z przewodu pokarmowego oraz powikłania neurologiczne, takie jak encefalopatia. Czynniki wpływające na rokowanie to wiek (najwyższe ryzyko u niemowląt i osób starszych), stan odżywienia, płeć, czas do rozpoczęcia leczenia oraz region geograficzny. Wczesne wdrożenie antybiotykoterapii skraca czas hospitalizacji do mediany 6 dni i obniża śmiertelność do 0,2%.

Prognoza gorączki tyfoidowej

Śmiertelność w gorączce tyfoidowej
Czas trwania choroby i powikłania
Czynniki prognostyczne
Leczenie a rokowanie
Antybiotykooporność a rokowanie
Nosicielstwo po przebytej chorobie
Czynniki środowiskowe a prognoza
Zapobieganie a rokowanie
Kolejne rozdziały

Prognoza gorączki tyfoidowej

Gorączka tyfoidowa (dur brzuszny) to potencjalnie śmiertelna, wieloukładowa infekcja wywołana głównie przez bakterię Salmonella enterica serotyp typhi, a w mniejszym stopniu przez serotypy paratyphi A, B i C. Rokowanie w tej chorobie zależy od wielu czynników, w tym czasu wdrożenia odpowiedniego leczenia, wieku pacjenta, występowania chorób współistniejących oraz regionu geograficznego.¹²

Śmiertelność w gorączce tyfoidowej

Wskaźniki śmiertelności w gorączce tyfoidowej uległy znacznemu obniżeniu na przestrzeni lat. W erze przed wprowadzeniem antybiotyków śmiertelność wynosiła od 10% do 30%, natomiast obecnie wśród pacjentów, którzy otrzymują wczesne leczenie, spadła ona do poziomu poniżej 1%.³⁴ Ogólny współczynnik śmiertelności szacuje się na około 4,2% w przypadkach hospitalizowanych bez interwencji chirurgicznej, przy czym wartość ta znacznie różni się w zależności od regionu geograficznego:⁵⁶

0,9% w Azji
5,4% w Afryce
7,2% w Oceanii
6,7% w obu Amerykach
1,0% w Europie

⁷

Wśród przypadków poza szpitalami globalny współczynnik śmiertelności wynosi około 0,2%.⁸ Według Cleveland Clinic, spośród milionów osób z diagnozą gorączki tyfoidowej rocznie, około 1-2% przypadków kończy się zgonem przy zastosowaniu nowoczesnych metod leczenia.⁹

Czas trwania choroby i powikłania

Bez leczenia gorączka tyfoidowa może trwać od 4 do 8 tygodni.¹⁰ Badania pokazują, że około 26% potwierdzonych laboratoryjnie przypadków gorączki tyfoidowej, głównie hospitalizowanych, doświadcza powikłań.¹¹ Powikłania zwykle pojawiają się 2-3 tygodnie po wystąpieniu pierwszych objawów choroby i ich częstość zależy od wieku, płci, istniejących wcześniej schorzeń oraz regionu geograficznego.¹²

Do najpoważniejszych powikłań należą:¹³¹⁴

Perforacja jelita – szczególnie groźna, z medianą śmiertelności na poziomie 15,5% (zakres 6,7-24,1%) w badaniach chirurgicznych; w Afryce śmiertelność z powodu perforacji jelita sięga 20%
Krwawienie z przewodu pokarmowego
Powikłania neurologiczne (encefalopatia) – mogą prowadzić do majaczenia, otępienia, a nawet śpiączki
Długotrwałe lub trwałe powikłania neuropsychiatryczne u osób, które przeżyły nieleczoną chorobę

¹⁵¹⁶¹⁷

Otępienie, śpiączka lub wstrząs wskazują na ciężki przebieg choroby i złe rokowanie.¹⁸ Powikłania występują głównie u pacjentów nieleczonych lub u których leczenie zostało opóźnione.¹⁹

Czynniki prognostyczne

Na rokowanie w gorączce tyfoidowej wpływa wiele czynników:²⁰²¹

Wiek pacjenta – najwyższe ryzyko śmiertelności dotyczy niemowląt i osób starszych
Stan odżywienia – pacjenci niedożywieni mają gorsze rokowanie
Płeć – stosunek mężczyzn do kobiet wśród przypadków wynosi około 1,36, co sugeruje, że mężczyźni mogą być bardziej podatni na zakażenie lub częściej zgłaszają się do leczenia
Czas do rozpoczęcia leczenia – opóźnienie w uzyskaniu opieki koreluje ze zwiększoną śmiertelnością, szczególnie w Azji
Region geograficzny – Afryka wykazuje wyższy wskaźnik śmiertelności w porównaniu z Azją
Dostęp do diagnostyki i leczenia – posiew krwi pozostaje złotym standardem diagnostycznym, ale jego dostępność jest ograniczona w wielu krajach rozwijających się

²²²³

Leczenie a rokowanie

Przy odpowiednim i szybkim leczeniu antybiotykami, gorączka tyfoidowa zwykle staje się krótkotrwałą chorobą gorączkową wymagającą mediany 6 dni hospitalizacji. Prawidłowo leczona ma niewiele długotrwałych następstw i ryzyko śmiertelności wynoszące 0,2%.²⁴

Po rozpoczęciu antybiotykoterapii objawy zaczynają ustępować już po kilku dniach. Ważne jest, aby ukończyć pełną terapię antybiotykową zgodnie z zaleceniami, nawet jeśli pacjent zaczyna czuć się lepiej.²⁵ Przy szybkim leczeniu zmniejsza się prawdopodobieństwo wystąpienia ciężkich powikłań.²⁶

W przypadku powikłań neurologicznych, badania wykazały, że kortykosteroidy mogą być skuteczne w łagodzeniu zaburzeń bariery krew-mózg, co uzasadnia ich stosowanie w leczeniu powikłań neurologicznych gorączki tyfoidowej.²⁷

Antybiotykooporność a rokowanie

Rosnąca oporność na antybiotyki stanowi poważne zagrożenie dla skutecznej kontroli gorączki tyfoidowej i wpływa na rokowanie.²⁸ Globalne Konsorcjum Genomiki Duru (Global Typhoid Genomics Consortium) odnotowuje następujące trendy w zakresie oporności:²⁹³⁰

Niewrażliwość na ciprofloksacynę (1 determinant oporności) jest szeroko rozpowszechniona geograficznie i obejmuje różne genotypy
Wysoki poziom oporności na ciprofloksacynę (3 determinanty) osiąga 20% częstości występowania w Południowej Azji
Skrajnie lekooporne (XDR) szczepy duru stały się dominujące w Pakistanie (70% w 2020 r.), ale nie rozprzestrzeniły się jeszcze w innych regionach

³¹³²

Wprowadzenie nowych antybiotyków do leczenia gorączki tyfoidowej zawsze było ściśle powiązane z rozwojem oporności, począwszy od rozpowszechnionej oporności na chloramfenikol na początku lat 70-tych XX wieku. Pojawienie się szczepów wielolekoopornych (MDR) doprowadziło do powszechnego stosowania fluorochinolonów (głównie ciprofloksacyny) jako terapii pierwszego rzutu.³³³⁴

Problem oporności na fluorochinolony spowodował zwiększone stosowanie cefalosporyn trzeciej generacji (takich jak ceftriakson i cefiksym) lub azytromycyny (w łagodniejszych przypadkach). Obecnie istnieje pilna potrzeba śledzenia pojawiania się i rozprzestrzeniania szczepów opornych na antybiotyki, zarówno w celu kierowania terapią empiryczną, jak i wdrażania interwencji zapobiegawczych, takich jak szczepionki koniugowane przeciwko durowi (TCV) oraz infrastruktura wodno-sanitarna.³⁵³⁶

Nosicielstwo po przebytej chorobie

W przeciwieństwie do większości innych chorób, pacjent może pozostać zakaźny nawet po ustąpieniu objawów gorączki tyfoidowej. Około 5% osób, które wyzdrowiały z gorączki tyfoidowej, pozostaje nosicielami przez rok lub dłużej. Stan ten określa się jako długotrwałe nosicielstwo. Istotne jest, aby po wyzdrowieniu przeprowadzić badania kontrolne w celu wykluczenia możliwości przenoszenia zakażenia na inne osoby.³⁷

Czynniki środowiskowe a prognoza

Badania wykazały istotne związki pomiędzy czynnikami środowiskowymi a występowaniem i przebiegiem gorączki tyfoidowej:³⁸³⁹

Istnieje przestrzenny związek między zbiornikami wodnymi a występowaniem przypadków gorączki tyfoidowej
Analiza czasowa związku między przypadkami a czynnikami hydro-meteorologicznymi wykazała, że liczba zgłaszanych przypadków wzrasta wraz ze wzrostem temperatury, opadów i poziomów rzek

⁴⁰

Czynniki te mogą wpływać na rokowanie poprzez zwiększenie ekspozycji na patogen i utrudnienie kontroli epidemiologicznej, szczególnie w rejonach o ograniczonym dostępie do czystej wody i odpowiednich warunków sanitarnych.

Zapobieganie a rokowanie

W kontekście rosnącej oporności na antybiotyki, zapobieganie staje się kluczowym elementem wpływającym na rokowanie. Szczepionki koniugowane przeciwko durowi (TCV) oraz poprawa infrastruktury wodno-sanitarnej (WASH) są uznawane za kluczowe interwencje, które mogą zapobiec znacznej zachorowalności i śmiertelności związanej z durem brzusznym.⁴¹⁴²

Globalne Konsorcjum Genomiki Duru zachęca do ciągłego udostępniania danych i współpracy w celu monitorowania pojawiania się i globalnego rozprzestrzeniania się opornych szczepów S. Typhi oraz informowania o decyzjach dotyczących wprowadzania szczepionek koniugowanych przeciwko durowi i innych strategii zapobiegania i kontroli.⁴³

Kolejne rozdziały

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Materiały źródłowe

#1 Typhoid Fever: Background, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/231135-overview
Typhoid fever, or enteric fever, is a potentially fatal multisystemic infection produced primarily by Salmonella enterica serotype typhi and to a lesser extent Salmonella enterica serotypes and paratyphi A, B, and C. […] Untreated typhoid fever may progress to delirium, obtundation, intestinal hemorrhage, bowel perforation, and death within 1 month of onset. Survivors may be left with long-term or permanent neuropsychiatric complications. […] With prompt and appropriate antibiotic therapy, typhoid fever is typically a short-term febrile illness requiring a median of 6 days of hospitalization. Treated, it has few long-term sequelae and a 0.2% risk of mortality. […] Untreated typhoid fever is a life-threatening illness of several weeks’ duration with long-term morbidity often involving the central nervous system. The case fatality rate in the United States in the pre-antibiotic era was 9%-13%.
#2 Clinical and Epidemiological Features of Typhoid Fever in Pemba, Zanzibar: Assessment of the Performance of the WHO Case Definitions | PLOS One
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0051823
Typhoid fever prevalence rates on Pemba are high and its clinical signs and symptoms are non-specific. […] The sensitivity of the Widal test is low and the WHO case definition performed better than the Widal test. […] A sensitivity of more than 80% for the WHO case definition of suspected typhoid cases was superior to the sensitivity of the Widal test and superior to the sensitivity of other rapid diagnostics tests such as Tubex at the cost of poor specificity below 40%. […] The WHO case definition for suspected cases performed better than the Widal test, however with a high rate of false positive results. […] Blood culture remains the gold standard for typhoid fever diagnosis, but its usage is limited by the lack of equipment, funds and experience of laboratory technicians in many developing countries.
#3 Typhoid Fever – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK557513/
Enteric fever can result in serious complications and death, particularly if antibiotics are delayed or inadequate. The overall case-fatality rate for S Typhi infection has fallen drastically from 10% to 30% in the pre-antibiotic era to less than 1% in patients who receive early treatment today. The overall pooled case fatality rate is an estimated 4.2% in non-surgical hospital sites and varies significantly across regions: 0.9% in Asia, 5.4% in Africa, 7.2% in Oceania, 6.7% in the Americas, and 1% in Europe. Among cases in global non-hospital sites, the estimate is 0.2%. […] Complications usually occur 2 to 3 weeks after the onset of illness. In a 2020 global systematic review and meta-analysis of typhoid fever complications, 26% of lab-confirmed, predominantly hospitalized cases of typhoid experienced a complication. Reviews completed in 2018 and 2019 found similar results. The frequency of specific complications depends on age, sex, pre-existing medical conditions, and geographic region.
#4 Typhoid Fever: Background, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/231135-overview
Typhoid fever, or enteric fever, is a potentially fatal multisystemic infection produced primarily by Salmonella enterica serotype typhi and to a lesser extent Salmonella enterica serotypes and paratyphi A, B, and C. […] Untreated typhoid fever may progress to delirium, obtundation, intestinal hemorrhage, bowel perforation, and death within 1 month of onset. Survivors may be left with long-term or permanent neuropsychiatric complications. […] With prompt and appropriate antibiotic therapy, typhoid fever is typically a short-term febrile illness requiring a median of 6 days of hospitalization. Treated, it has few long-term sequelae and a 0.2% risk of mortality. […] Untreated typhoid fever is a life-threatening illness of several weeks’ duration with long-term morbidity often involving the central nervous system. The case fatality rate in the United States in the pre-antibiotic era was 9%-13%.
#5 Typhoid Fever – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK557513/
Enteric fever can result in serious complications and death, particularly if antibiotics are delayed or inadequate. The overall case-fatality rate for S Typhi infection has fallen drastically from 10% to 30% in the pre-antibiotic era to less than 1% in patients who receive early treatment today. The overall pooled case fatality rate is an estimated 4.2% in non-surgical hospital sites and varies significantly across regions: 0.9% in Asia, 5.4% in Africa, 7.2% in Oceania, 6.7% in the Americas, and 1% in Europe. Among cases in global non-hospital sites, the estimate is 0.2%. […] Complications usually occur 2 to 3 weeks after the onset of illness. In a 2020 global systematic review and meta-analysis of typhoid fever complications, 26% of lab-confirmed, predominantly hospitalized cases of typhoid experienced a complication. Reviews completed in 2018 and 2019 found similar results. The frequency of specific complications depends on age, sex, pre-existing medical conditions, and geographic region.
#6 Complications and mortality of typhoid fever: A global systematic review and meta-analysis
https://pmc.ncbi.nlm.nih.gov/articles/PMC7754788/
The pooled CFR estimate (95% CI; heterogeneity I2) among 79 studies reporting on mortality of confirmed typhoid fever was 2.0% (1.4-2.8%; 83.9%). […] The pooled CFR estimates for the Asia, Africa, Oceania, the Americas, and Europe regions were 0.9% (0.6-1.3%; 63.4%), 5.4% (2.7-8.9%; 83.4%), 7.2% (0.0-20.4%; 97.2%), 6.7% (0.0-19.9%; 94.4%), and 1.0% (0.0-6.8%; incalculable), respectively. […] Among hospital-based non-surgical studies, the CFR of typhoid fever was significantly higher in Africa compared to Asia. […] Intestinal perforation was a common complication and an important contributor to typhoid mortality, especially in African studies where one in five patients with TIP died.
#7 Complications and mortality of typhoid fever: A global systematic review and meta-analysis
https://pmc.ncbi.nlm.nih.gov/articles/PMC7754788/
The pooled CFR estimate (95% CI; heterogeneity I2) among 79 studies reporting on mortality of confirmed typhoid fever was 2.0% (1.4-2.8%; 83.9%). […] The pooled CFR estimates for the Asia, Africa, Oceania, the Americas, and Europe regions were 0.9% (0.6-1.3%; 63.4%), 5.4% (2.7-8.9%; 83.4%), 7.2% (0.0-20.4%; 97.2%), 6.7% (0.0-19.9%; 94.4%), and 1.0% (0.0-6.8%; incalculable), respectively. […] Among hospital-based non-surgical studies, the CFR of typhoid fever was significantly higher in Africa compared to Asia. […] Intestinal perforation was a common complication and an important contributor to typhoid mortality, especially in African studies where one in five patients with TIP died.
#8 Typhoid Fever – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK557513/
Enteric fever can result in serious complications and death, particularly if antibiotics are delayed or inadequate. The overall case-fatality rate for S Typhi infection has fallen drastically from 10% to 30% in the pre-antibiotic era to less than 1% in patients who receive early treatment today. The overall pooled case fatality rate is an estimated 4.2% in non-surgical hospital sites and varies significantly across regions: 0.9% in Asia, 5.4% in Africa, 7.2% in Oceania, 6.7% in the Americas, and 1% in Europe. Among cases in global non-hospital sites, the estimate is 0.2%. […] Complications usually occur 2 to 3 weeks after the onset of illness. In a 2020 global systematic review and meta-analysis of typhoid fever complications, 26% of lab-confirmed, predominantly hospitalized cases of typhoid experienced a complication. Reviews completed in 2018 and 2019 found similar results. The frequency of specific complications depends on age, sex, pre-existing medical conditions, and geographic region.
#9 Typhoid Fever: Causes, Symptoms & Treatment
https://my.clevelandclinic.org/health/diseases/17730-typhoid-fever
Depending on how soon you’re treated for typhoid, you can feel better in as little as a few days after starting antibiotics. It’s important to finish all of your medications as directed, even if you start to feel better. You may still be contagious for a long time after your symptoms go away. […] Typhoid fever can be very serious. If you get treated as soon as possible, you’re less likely to have severe complications. […] Typhoid can be fatal if not treated quickly. But with modern medicines, most people survive and fully recover. Out of the millions of people diagnosed with typhoid fever each year, about 1% to 2% of cases are fatal. […] Yes, unlike most other illnesses, you can still be contagious with typhoid even when you no longer have symptoms. About 5% of people who have recovered from typhoid fever are still contagious a year later or longer. This is called a long-term carrier. It’s important to be tested after you feel better to make sure you can’t give typhoid to someone else.
#10 Prognosis of Typhoid Fever | Hospital ClÃnic Barcelona
https://www.clinicbarcelona.org/en/assistance/diseases/typhoid-fever/progression-of-the-disease
The disease lasts for 4-8 weeks in patients who receive no treatment. By taking antibiotics that control Salmonella, the symptoms begin to subside a few days after treatment. […] In rare cases, there can be serious complications such as intestinal perforation or digestive bleeding. […] There is currently a growing problem with resistance to antibiotic treatments that are normally used for this disease, which can hinder treatment and worsen development.
#11 Typhoid Fever – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK557513/
Enteric fever can result in serious complications and death, particularly if antibiotics are delayed or inadequate. The overall case-fatality rate for S Typhi infection has fallen drastically from 10% to 30% in the pre-antibiotic era to less than 1% in patients who receive early treatment today. The overall pooled case fatality rate is an estimated 4.2% in non-surgical hospital sites and varies significantly across regions: 0.9% in Asia, 5.4% in Africa, 7.2% in Oceania, 6.7% in the Americas, and 1% in Europe. Among cases in global non-hospital sites, the estimate is 0.2%. […] Complications usually occur 2 to 3 weeks after the onset of illness. In a 2020 global systematic review and meta-analysis of typhoid fever complications, 26% of lab-confirmed, predominantly hospitalized cases of typhoid experienced a complication. Reviews completed in 2018 and 2019 found similar results. The frequency of specific complications depends on age, sex, pre-existing medical conditions, and geographic region.
#12 Typhoid Fever – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK557513/
Enteric fever can result in serious complications and death, particularly if antibiotics are delayed or inadequate. The overall case-fatality rate for S Typhi infection has fallen drastically from 10% to 30% in the pre-antibiotic era to less than 1% in patients who receive early treatment today. The overall pooled case fatality rate is an estimated 4.2% in non-surgical hospital sites and varies significantly across regions: 0.9% in Asia, 5.4% in Africa, 7.2% in Oceania, 6.7% in the Americas, and 1% in Europe. Among cases in global non-hospital sites, the estimate is 0.2%. […] Complications usually occur 2 to 3 weeks after the onset of illness. In a 2020 global systematic review and meta-analysis of typhoid fever complications, 26% of lab-confirmed, predominantly hospitalized cases of typhoid experienced a complication. Reviews completed in 2018 and 2019 found similar results. The frequency of specific complications depends on age, sex, pre-existing medical conditions, and geographic region.
#13 Prognosis of Typhoid Fever | Hospital ClÃnic Barcelona
https://www.clinicbarcelona.org/en/assistance/diseases/typhoid-fever/progression-of-the-disease
The disease lasts for 4-8 weeks in patients who receive no treatment. By taking antibiotics that control Salmonella, the symptoms begin to subside a few days after treatment. […] In rare cases, there can be serious complications such as intestinal perforation or digestive bleeding. […] There is currently a growing problem with resistance to antibiotic treatments that are normally used for this disease, which can hinder treatment and worsen development.
#14 Typhoid Fever: Background, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/231135-overview
Typhoid fever, or enteric fever, is a potentially fatal multisystemic infection produced primarily by Salmonella enterica serotype typhi and to a lesser extent Salmonella enterica serotypes and paratyphi A, B, and C. […] Untreated typhoid fever may progress to delirium, obtundation, intestinal hemorrhage, bowel perforation, and death within 1 month of onset. Survivors may be left with long-term or permanent neuropsychiatric complications. […] With prompt and appropriate antibiotic therapy, typhoid fever is typically a short-term febrile illness requiring a median of 6 days of hospitalization. Treated, it has few long-term sequelae and a 0.2% risk of mortality. […] Untreated typhoid fever is a life-threatening illness of several weeks’ duration with long-term morbidity often involving the central nervous system. The case fatality rate in the United States in the pre-antibiotic era was 9%-13%.
#15 Complications and mortality of typhoid fever: A global systematic review and meta-analysis
https://pmc.ncbi.nlm.nih.gov/articles/PMC7754788/
Complications and death are considerable among hospitalized patients with typhoid fever. […] Case fatality ratio of typhoid fever was higher in Africa compared to Asia. […] Among studies in Africa, 20% of patients with typhoid intestinal perforation died. […] Delays in care were correlated with increased typhoid case fatality ratio in Asia. […] Our findings identify considerable typhoid-associated illness and death that could be averted with prevention measures, including typhoid conjugate vaccine introduction. […] The pooled CFR estimate among non-surgical patients was 0.9% for the Asia region and 5.4% for the Africa region. […] Among surgical studies, the median CFR of TIP was 15.5% (6.7-24.1%) per study. […] The median CFR of TIP across the 36 studies was 15.5% (6.7-24.1%).
#16 Complications and mortality of typhoid fever: A global systematic review and meta-analysis
https://pmc.ncbi.nlm.nih.gov/articles/PMC7754788/
The pooled CFR estimate (95% CI; heterogeneity I2) among 79 studies reporting on mortality of confirmed typhoid fever was 2.0% (1.4-2.8%; 83.9%). […] The pooled CFR estimates for the Asia, Africa, Oceania, the Americas, and Europe regions were 0.9% (0.6-1.3%; 63.4%), 5.4% (2.7-8.9%; 83.4%), 7.2% (0.0-20.4%; 97.2%), 6.7% (0.0-19.9%; 94.4%), and 1.0% (0.0-6.8%; incalculable), respectively. […] Among hospital-based non-surgical studies, the CFR of typhoid fever was significantly higher in Africa compared to Asia. […] Intestinal perforation was a common complication and an important contributor to typhoid mortality, especially in African studies where one in five patients with TIP died.
#17 Typhoid toxin causes neuropathology by disrupting the bloodâbrain barrier | Nature Microbiology
https://www.nature.com/articles/s41564-025-02000-z
Typhoid fever, primarily caused by Salmonella Typhi, can result in severe life-threatening complications such as encephalopathy. […] We demonstrate that corticosteroids are effective at mitigating BBB disruption in vivo, supporting their use for managing typhoid fever neurological complications. […] Our data reveal mechanistic insight into how typhoid toxin causes encephalopathy and suggest targeted therapeutic interventions to alleviate the severe neurological manifestations of typhoid fever.
#18 Typhoid Fever – Infectious Diseases – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/infectious-diseases/gram-negative-bacilli/typhoid-fever
Without antibiotics, the case fatality rate is about 10 to 15%. With prompt therapy, the case fatality rate is 1% (1). Most deaths occur in people who are undernourished, infants, and older adults. […] Stupor, coma, or shock reflects severe disease and a poor prognosis. […] Complications occur mainly in patients who are untreated or in whom treatment is delayed.
#19 Typhoid Fever – Infectious Diseases – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/infectious-diseases/gram-negative-bacilli/typhoid-fever
Without antibiotics, the case fatality rate is about 10 to 15%. With prompt therapy, the case fatality rate is 1% (1). Most deaths occur in people who are undernourished, infants, and older adults. […] Stupor, coma, or shock reflects severe disease and a poor prognosis. […] Complications occur mainly in patients who are untreated or in whom treatment is delayed.
#20 Typhoid Fever – Infectious Diseases – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/infectious-diseases/gram-negative-bacilli/typhoid-fever
Without antibiotics, the case fatality rate is about 10 to 15%. With prompt therapy, the case fatality rate is 1% (1). Most deaths occur in people who are undernourished, infants, and older adults. […] Stupor, coma, or shock reflects severe disease and a poor prognosis. […] Complications occur mainly in patients who are untreated or in whom treatment is delayed.
#21 Typhoid Fever and Its Association with Environmental Factors in the Dhaka Metropolitan Area of Bangladesh: A Spatial and Time-Series Approach | PLOS Neglected Tropical Diseases
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001998
Typhoid fever is a major cause of death worldwide with a major part of the disease burden in developing regions such as the Indian sub-continent. […] The aims of the study were: (i) to analyse the epidemiology of cases from 2005 to 2009; (ii) to identify spatial patterns of infection based on two spatial hypotheses; and (iii) to determine the hydro-climatological factors associated with typhoid prevalence. […] The male-female ratio of typhoid cases was found to be 1.36, suggesting that in this population males are either more susceptible to typhoid, or more likely to present for hospital treatment, than females. […] The median age of the typhoid cases was 14 years. Out of the 4,355 typhoid cases reported during the study period, 35 people died. […] The comparison of global and local regression models indicated that GWR outperformed OLS model in terms of AICc and coefficient of determination (R2).
#22 Complications and mortality of typhoid fever: A global systematic review and meta-analysis
https://pmc.ncbi.nlm.nih.gov/articles/PMC7754788/
Complications and death are considerable among hospitalized patients with typhoid fever. […] Case fatality ratio of typhoid fever was higher in Africa compared to Asia. […] Among studies in Africa, 20% of patients with typhoid intestinal perforation died. […] Delays in care were correlated with increased typhoid case fatality ratio in Asia. […] Our findings identify considerable typhoid-associated illness and death that could be averted with prevention measures, including typhoid conjugate vaccine introduction. […] The pooled CFR estimate among non-surgical patients was 0.9% for the Asia region and 5.4% for the Africa region. […] Among surgical studies, the median CFR of TIP was 15.5% (6.7-24.1%) per study. […] The median CFR of TIP across the 36 studies was 15.5% (6.7-24.1%).
#23 Clinical and Epidemiological Features of Typhoid Fever in Pemba, Zanzibar: Assessment of the Performance of the WHO Case Definitions | PLOS One
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0051823
Typhoid fever prevalence rates on Pemba are high and its clinical signs and symptoms are non-specific. […] The sensitivity of the Widal test is low and the WHO case definition performed better than the Widal test. […] A sensitivity of more than 80% for the WHO case definition of suspected typhoid cases was superior to the sensitivity of the Widal test and superior to the sensitivity of other rapid diagnostics tests such as Tubex at the cost of poor specificity below 40%. […] The WHO case definition for suspected cases performed better than the Widal test, however with a high rate of false positive results. […] Blood culture remains the gold standard for typhoid fever diagnosis, but its usage is limited by the lack of equipment, funds and experience of laboratory technicians in many developing countries.
#24 Typhoid Fever: Background, Pathophysiology, Epidemiology
https://emedicine.medscape.com/article/231135-overview
Typhoid fever, or enteric fever, is a potentially fatal multisystemic infection produced primarily by Salmonella enterica serotype typhi and to a lesser extent Salmonella enterica serotypes and paratyphi A, B, and C. […] Untreated typhoid fever may progress to delirium, obtundation, intestinal hemorrhage, bowel perforation, and death within 1 month of onset. Survivors may be left with long-term or permanent neuropsychiatric complications. […] With prompt and appropriate antibiotic therapy, typhoid fever is typically a short-term febrile illness requiring a median of 6 days of hospitalization. Treated, it has few long-term sequelae and a 0.2% risk of mortality. […] Untreated typhoid fever is a life-threatening illness of several weeks’ duration with long-term morbidity often involving the central nervous system. The case fatality rate in the United States in the pre-antibiotic era was 9%-13%.
#25 Typhoid Fever: Causes, Symptoms & Treatment
https://my.clevelandclinic.org/health/diseases/17730-typhoid-fever
Depending on how soon you’re treated for typhoid, you can feel better in as little as a few days after starting antibiotics. It’s important to finish all of your medications as directed, even if you start to feel better. You may still be contagious for a long time after your symptoms go away. […] Typhoid fever can be very serious. If you get treated as soon as possible, you’re less likely to have severe complications. […] Typhoid can be fatal if not treated quickly. But with modern medicines, most people survive and fully recover. Out of the millions of people diagnosed with typhoid fever each year, about 1% to 2% of cases are fatal. […] Yes, unlike most other illnesses, you can still be contagious with typhoid even when you no longer have symptoms. About 5% of people who have recovered from typhoid fever are still contagious a year later or longer. This is called a long-term carrier. It’s important to be tested after you feel better to make sure you can’t give typhoid to someone else.
#26 Typhoid Fever: Causes, Symptoms & Treatment
https://my.clevelandclinic.org/health/diseases/17730-typhoid-fever
Depending on how soon you’re treated for typhoid, you can feel better in as little as a few days after starting antibiotics. It’s important to finish all of your medications as directed, even if you start to feel better. You may still be contagious for a long time after your symptoms go away. […] Typhoid fever can be very serious. If you get treated as soon as possible, you’re less likely to have severe complications. […] Typhoid can be fatal if not treated quickly. But with modern medicines, most people survive and fully recover. Out of the millions of people diagnosed with typhoid fever each year, about 1% to 2% of cases are fatal. […] Yes, unlike most other illnesses, you can still be contagious with typhoid even when you no longer have symptoms. About 5% of people who have recovered from typhoid fever are still contagious a year later or longer. This is called a long-term carrier. It’s important to be tested after you feel better to make sure you can’t give typhoid to someone else.
#27 Typhoid toxin causes neuropathology by disrupting the bloodâbrain barrier | Nature Microbiology
https://www.nature.com/articles/s41564-025-02000-z
Typhoid fever, primarily caused by Salmonella Typhi, can result in severe life-threatening complications such as encephalopathy. […] We demonstrate that corticosteroids are effective at mitigating BBB disruption in vivo, supporting their use for managing typhoid fever neurological complications. […] Our data reveal mechanistic insight into how typhoid toxin causes encephalopathy and suggest targeted therapeutic interventions to alleviate the severe neurological manifestations of typhoid fever.
#28 Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes | eLife
https://elifesciences.org/articles/85867
The increasing prevalence of AMR poses a major threat to effective typhoid fever control. […] The challenge of fluoroquinolone non-susceptible typhoid was met with increased therapeutic use of third-generation cephalosporins (such as ceftriaxone and cefixime) or azithromycin (for non-severe disease). […] The accumulation of resistance to almost all therapeutic options means that there is an urgent need to track the emergence and spread of AMR Typhi, both to guide empiric therapy to prevent treatment failure, and to direct the deployment of preventative interventions like typhoid conjugate vaccines (TCVs) and WASH infrastructure. […] The introduction of new antimicrobials to treat typhoid fever has been closely followed by the development of resistance, beginning with widespread chloramphenicol resistance in the early 1970s.
#29 Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes | eLife
https://elifesciences.org/articles/85867
The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. […] The data indicate that ciprofloxacin non-susceptibility (1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (3 determinants) reaching 20% prevalence in South Asia. […] Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. […] The consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies.
#30 Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes | eLife
https://elifesciences.org/articles/85867
The increasing prevalence of AMR poses a major threat to effective typhoid fever control. […] The challenge of fluoroquinolone non-susceptible typhoid was met with increased therapeutic use of third-generation cephalosporins (such as ceftriaxone and cefixime) or azithromycin (for non-severe disease). […] The accumulation of resistance to almost all therapeutic options means that there is an urgent need to track the emergence and spread of AMR Typhi, both to guide empiric therapy to prevent treatment failure, and to direct the deployment of preventative interventions like typhoid conjugate vaccines (TCVs) and WASH infrastructure. […] The introduction of new antimicrobials to treat typhoid fever has been closely followed by the development of resistance, beginning with widespread chloramphenicol resistance in the early 1970s.
#31 Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes | eLife
https://elifesciences.org/articles/85867
The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. […] The data indicate that ciprofloxacin non-susceptibility (1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (3 determinants) reaching 20% prevalence in South Asia. […] Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. […] The consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies.
#32 Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes | eLife
https://elifesciences.org/articles/85867
The emergence of MDR Typhi led to widespread use of fluoroquinolones (mainly ciprofloxacin) as first-line therapy in typhoid fever treatment. […] The XDR clone harbours a common combination of chromosomal AMR determinants (integrated MDR transposon plus single QRDR mutation, GyrA-83) but has also acquired an IncY-type plasmid carrying resistance genes. […] The accumulation of resistance to almost all therapeutic options means that there is an urgent need to track the emergence and spread of AMR Typhi, both to guide empiric therapy to prevent treatment failure, and to direct the deployment of preventative interventions like typhoid conjugate vaccines (TCVs) and WASH infrastructure.
#33 Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes | eLife
https://elifesciences.org/articles/85867
The increasing prevalence of AMR poses a major threat to effective typhoid fever control. […] The challenge of fluoroquinolone non-susceptible typhoid was met with increased therapeutic use of third-generation cephalosporins (such as ceftriaxone and cefixime) or azithromycin (for non-severe disease). […] The accumulation of resistance to almost all therapeutic options means that there is an urgent need to track the emergence and spread of AMR Typhi, both to guide empiric therapy to prevent treatment failure, and to direct the deployment of preventative interventions like typhoid conjugate vaccines (TCVs) and WASH infrastructure. […] The introduction of new antimicrobials to treat typhoid fever has been closely followed by the development of resistance, beginning with widespread chloramphenicol resistance in the early 1970s.
#34 Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes | eLife
https://elifesciences.org/articles/85867
The emergence of MDR Typhi led to widespread use of fluoroquinolones (mainly ciprofloxacin) as first-line therapy in typhoid fever treatment. […] The XDR clone harbours a common combination of chromosomal AMR determinants (integrated MDR transposon plus single QRDR mutation, GyrA-83) but has also acquired an IncY-type plasmid carrying resistance genes. […] The accumulation of resistance to almost all therapeutic options means that there is an urgent need to track the emergence and spread of AMR Typhi, both to guide empiric therapy to prevent treatment failure, and to direct the deployment of preventative interventions like typhoid conjugate vaccines (TCVs) and WASH infrastructure.
#35 Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes | eLife
https://elifesciences.org/articles/85867
The increasing prevalence of AMR poses a major threat to effective typhoid fever control. […] The challenge of fluoroquinolone non-susceptible typhoid was met with increased therapeutic use of third-generation cephalosporins (such as ceftriaxone and cefixime) or azithromycin (for non-severe disease). […] The accumulation of resistance to almost all therapeutic options means that there is an urgent need to track the emergence and spread of AMR Typhi, both to guide empiric therapy to prevent treatment failure, and to direct the deployment of preventative interventions like typhoid conjugate vaccines (TCVs) and WASH infrastructure. […] The introduction of new antimicrobials to treat typhoid fever has been closely followed by the development of resistance, beginning with widespread chloramphenicol resistance in the early 1970s.
#36 Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes | eLife
https://elifesciences.org/articles/85867
The emergence of MDR Typhi led to widespread use of fluoroquinolones (mainly ciprofloxacin) as first-line therapy in typhoid fever treatment. […] The XDR clone harbours a common combination of chromosomal AMR determinants (integrated MDR transposon plus single QRDR mutation, GyrA-83) but has also acquired an IncY-type plasmid carrying resistance genes. […] The accumulation of resistance to almost all therapeutic options means that there is an urgent need to track the emergence and spread of AMR Typhi, both to guide empiric therapy to prevent treatment failure, and to direct the deployment of preventative interventions like typhoid conjugate vaccines (TCVs) and WASH infrastructure.
#37 Typhoid Fever: Causes, Symptoms & Treatment
https://my.clevelandclinic.org/health/diseases/17730-typhoid-fever
Depending on how soon you’re treated for typhoid, you can feel better in as little as a few days after starting antibiotics. It’s important to finish all of your medications as directed, even if you start to feel better. You may still be contagious for a long time after your symptoms go away. […] Typhoid fever can be very serious. If you get treated as soon as possible, you’re less likely to have severe complications. […] Typhoid can be fatal if not treated quickly. But with modern medicines, most people survive and fully recover. Out of the millions of people diagnosed with typhoid fever each year, about 1% to 2% of cases are fatal. […] Yes, unlike most other illnesses, you can still be contagious with typhoid even when you no longer have symptoms. About 5% of people who have recovered from typhoid fever are still contagious a year later or longer. This is called a long-term carrier. It’s important to be tested after you feel better to make sure you can’t give typhoid to someone else.
#38 Typhoid Fever and Its Association with Environmental Factors in the Dhaka Metropolitan Area of Bangladesh: A Spatial and Time-Series Approach | PLOS Neglected Tropical Diseases
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001998
Typhoid fever is a major cause of death worldwide with a major part of the disease burden in developing regions such as the Indian sub-continent. […] The aims of the study were: (i) to analyse the epidemiology of cases from 2005 to 2009; (ii) to identify spatial patterns of infection based on two spatial hypotheses; and (iii) to determine the hydro-climatological factors associated with typhoid prevalence. […] The male-female ratio of typhoid cases was found to be 1.36, suggesting that in this population males are either more susceptible to typhoid, or more likely to present for hospital treatment, than females. […] The median age of the typhoid cases was 14 years. Out of the 4,355 typhoid cases reported during the study period, 35 people died. […] The comparison of global and local regression models indicated that GWR outperformed OLS model in terms of AICc and coefficient of determination (R2).
#39 Typhoid Fever and Its Association with Environmental Factors in the Dhaka Metropolitan Area of Bangladesh: A Spatial and Time-Series Approach | PLOS Neglected Tropical Diseases
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001998
The spatial association between water bodies and the incidences of typhoid showed significant relationships. […] The temporal analysis of the relationship between typhoid cases and hydro-meteorological factors revealed that the number of reported cases was amplified by increases in temperature, rainfall and river levels.
#40 Typhoid Fever and Its Association with Environmental Factors in the Dhaka Metropolitan Area of Bangladesh: A Spatial and Time-Series Approach | PLOS Neglected Tropical Diseases
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001998
The spatial association between water bodies and the incidences of typhoid showed significant relationships. […] The temporal analysis of the relationship between typhoid cases and hydro-meteorological factors revealed that the number of reported cases was amplified by increases in temperature, rainfall and river levels.
#41 Complications and mortality of typhoid fever: A global systematic review and meta-analysis
https://pmc.ncbi.nlm.nih.gov/articles/PMC7754788/
Complications and death are considerable among hospitalized patients with typhoid fever. […] Case fatality ratio of typhoid fever was higher in Africa compared to Asia. […] Among studies in Africa, 20% of patients with typhoid intestinal perforation died. […] Delays in care were correlated with increased typhoid case fatality ratio in Asia. […] Our findings identify considerable typhoid-associated illness and death that could be averted with prevention measures, including typhoid conjugate vaccine introduction. […] The pooled CFR estimate among non-surgical patients was 0.9% for the Asia region and 5.4% for the Africa region. […] Among surgical studies, the median CFR of TIP was 15.5% (6.7-24.1%) per study. […] The median CFR of TIP across the 36 studies was 15.5% (6.7-24.1%).
#42 Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes | eLife
https://elifesciences.org/articles/85867
The increasing prevalence of AMR poses a major threat to effective typhoid fever control. […] The challenge of fluoroquinolone non-susceptible typhoid was met with increased therapeutic use of third-generation cephalosporins (such as ceftriaxone and cefixime) or azithromycin (for non-severe disease). […] The accumulation of resistance to almost all therapeutic options means that there is an urgent need to track the emergence and spread of AMR Typhi, both to guide empiric therapy to prevent treatment failure, and to direct the deployment of preventative interventions like typhoid conjugate vaccines (TCVs) and WASH infrastructure. […] The introduction of new antimicrobials to treat typhoid fever has been closely followed by the development of resistance, beginning with widespread chloramphenicol resistance in the early 1970s.
#43 Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes | eLife
https://elifesciences.org/articles/85867
The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. […] The data indicate that ciprofloxacin non-susceptibility (1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (3 determinants) reaching 20% prevalence in South Asia. […] Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. […] The consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies.