Fiebre tifoidea y paratifoidea

Synonyms: enteric fever

How common are typhoid and paratyphoid fevers? (Epidemiology)¹

Las fiebres tifoidea y paratifoidea son causadas por cepas relacionadas pero diferentes de Salmonella spp. Hay una considerable superposición en los síntomas, aunque la fiebre tifoidea es la enfermedad más grave y duradera, y es la que tiene más probabilidades de resultar en muerte si no se administra un tratamiento oportuno.

El nombre fiebre tifoidea significa 'semejante al tifus', y fue elegido debido a la aparición de síntomas neuropsiquiátricos en las tres enfermedades. Sin embargo, aunque puede haber cierta superposición de síntomas, tifus, y la condición relacionada tifus del matorral, are completely separate diseases.

Fiebre tifoidea

• Is caused by a Gram-negative organism Salmonella enterica subspecies enterica serovar Typhi (Salmonella typhi).

Paratyphoid fever

• Se divide en tres subtipos (A, B y C). La fiebre paratifoidea es causada por cualquiera de los tres serovares de Salmonella enterica subespecies enterica:

  • S. paratyphi A.

  • S. schottmuelleri (also called S. paratyphi B).

  • S. hirschfeldii (also called S. paratyphi C).

• Type A is the most common worldwide, although B predominates in Europe. Type C is rare, and is seen only in the Far East.^{1 2 3}

• The overall ratio of disease caused by S. typhi to that caused by S. paratyphi is about 10 to 1.⁴

Enteric fever affects only humans (who are the reservoir) and is spread through consumption of contaminated food and drink handled by people who shed the organism from stool or, less commonly, urine. It may also be acquired from ingesting water contaminated with sewage. Shellfish from water polluted by raw sewage and canned meat production with poor technique have also caused outbreaks. Food needs to be heavily contaminated for infection to occur - approximately 10⁵ hasta 10⁹ puede que se requieran células para causar enfermedad.¹

Global trends in prevalence

Typhoid fever has virtually disappeared in the developed world, but is still endemic in many developing countries. Most cases now occur in Africa and Asia. In Latin America, incidence has decreased with water and sanitation measures, but it remains a public health concern.^{4 5 6}

• The World Health Organization (WHO) estimates that globally 9 million people become ill from typhoid annually and about 110,000 people die. Poor sanitation and lack of clean drinking water in rural settings are significant causes. However, urbanisation, with overcrowding and inadequate water and sanitation systems, as well as climate change can further increase the global burden.⁷

• In the tropics, enteric fever tends to be more common during the hot dry seasons when the concentration of bacteria in rivers and streams increases, or in the rainy season if flooding distributes sewage to drinking water sources.^{8 9}

• En algunas áreas, la incidencia de fiebre tifoidea puede ser tan alta como 1,000 casos por cada 100,000 habitantes por año. En tales áreas, la fiebre tifoidea es predominantemente una enfermedad de los niños, y la excreción fecal de S. typhi durante y después de la infección es la principal fuente de la infección. En tales áreas, las infecciones suelen ser leves y autolimitadas. La enfermedad grave representa la 'punta del iceberg'.⁸

• In temperate countries, persistent carriers are a more important reservoir of infection.

• For travellers the highest attack rates are associated with visits to South Asia. Although Indonesia has a reported annual incidence up to 1%, the attack rate for travellers is low.

• In general, the mortality is low (<1%) where antibiotics are available, but in poorer areas, or in the context of natural disasters, war, migrations, large concentrated refugee populations, and other privations, the mortality may rise to 10-30%, despite antibiotic therapy.

• Typhoid tends to cluster in families, presumably reflecting a common source of the infection and is associated with poverty and poor housing.

• Un factor que complica la evaluación de la incidencia es que la epidemia de VIH y SIDA en África se ha asociado con un aumento concomitante de bacteriemia adquirida en la comunidad debido a no tifoidea Salmonella especies como S. typhimurium - una enfermedad que puede ser clínicamente indistinguible del tifus.⁴
  

Typhoid and paratyphoid fever in the UK¹

En 2023, 645 casos sintomáticos confirmados por laboratorio de S. typhi y S. paratyphi se reportaron en Inglaterra, Gales e Irlanda del Norte. De estos, el 63% fueron causados por S. Typhi, el 32% de los casos por S. Paratyphi A y el 4% por S. Paratyphi B.

Factores de riesgo¹

Aparte de la exposición al organismo, varios factores del huésped aumentan el riesgo de infección con Salmonella spp. al reducir la carga necesaria de organismos infecciosos. Estos incluyen:

• Disease-related or iatrogenic achlorhydria (antacids, H2-receptor antagonists, proton pump inhibitors), reduction in stomach acidity or gut pathology (surgery, inflammatory bowel disease, malignancy) and recent antibiotics increase the susceptibility to infection.

• Immunosuppression of any cause.

• Varias otras infecciones, notablemente la esquistosomiasis, la malaria, la histoplasmosis y la bartonelosis, están asociadas con un mayor riesgo de infección con Salmonella spp.

• Typhoid is more common, and more severe at the extremes of age. Neonatal typhoid, usually acquired from the mother, may follow a fulminant course often with meningitis.

• Patients with haemoglobinopathies, particularly sickle cell disease, are also at increased risk.

Período de incubación¹

• Esto depende de la dosis infecciosa ingerida - típicamente son 10-20 días para S. typhi (pero puede ser tan corto como tres días). Durante esta fase, el 10-20% de los pacientes tienen diarrea transitoria. Anteriormente se ha informado que el período de incubación para la paratifoidea es más corto (1-10 días). Sin embargo, los datos de vigilancia para Inglaterra, Gales e Irlanda del Norte 2007-2010 no mostraron diferencias significativas entre la fiebre tifoidea y la paratifoidea en el tiempo de aparición de los síntomas al llegar al Reino Unido.

• 96% of cases of enteric fever had an onset date within 28 days of return from travel.

• 91% had an onset date within 21 days.

Symptoms of typhoid fever^{8 10}

Typhoid is one of the most common febrile illnesses seen by practitioners in the developing world. Untreated, the illness usually lasts for three to four weeks, but may be longer. Symptoms vary from mild to severe and life-threatening.

The course of untreated typhoid fever is classically divided into four stages, each lasting about a week. This disease pattern is not commonly seen, with severe disease representing the 'tip of the iceberg' in typhoid, and with the advent of antibiotics altering the course of the disease. For descriptions of the untreated disease the literature relies on historical descriptive accounts by physicians such as Sir William Osler.

Week one

• Gradual rise in temperature, typically worse through the day, over the first 2-3 days, typically reaches 40°C (104°F).

• Dry cough.

• Relative bradycardia (Faget's sign): - the pulse is slower than would be expected from the degree of temperature.

• Malestar.

• Dolor de cabeza.

• Epistaxis in around a third.

• Dolor abdominal.

• Leukopenia with relative lymphocytosis.

• Los cultivos de sangre son positivos para S. typhi (o S. paratyphi).

• Widal's test is usually negative.

• In this bacteraemic phase it is possible to find bacteria in the reticuloendothelial tissues of the liver, spleen, bone marrow, and gallbladder and Peyer's patches in the terminal ileum. The gallbladder is infected via the liver and infected bile gives positive stool cultures and re-infects the bowel. Gallstones predispose to chronic biliary infection and long-term faecal carriage.

Week two

• During the second week the patient has a toxic appearance with apathy and sustained pyrexia.

• High fever around 40°C (104°F), often swinging.

• Malaise and weakness.

• Relative bradycardia, with dicrotic pulse wave.

• Confusional state, which gave typhoid the name of 'nervous fever'.

• Rose spots on the lower chest and abdomen - seen in around one third of white patients; difficult to see in darker skin. Rose spots are caused by bacterial emboli. They are crops of macules 2-4 mm in diameter that blanch on pressure.

• Lung base rhonchi.

• Abdominal distension with right lower quadrant tenderness and increased borborygmi.

• Diarrhoea, typically green, with a characteristic foul smell, often compared to pea soup.

• Constipation may also occur.

• Hepatosplenomegaly is common.

• Elevated liver transaminases.

• Positive Widal's test.

Week three

• By the third week there is considerable weight loss.

• Pyrexia persists and a toxic confusional state may occur.

• Marked abdominal distension develops and liquid, foul, green-yellow diarrhoea is common.

• The patient is weak with a weak pulse and raised respiratory rate.

• Crackles may develop over the lung bases.

• Death can occur at this stage from overwhelming toxaemia, myocarditis, intestinal haemorrhage, or perforation of the gut, usually at Peyer's patches.

• Complications which are most likely to develop at this stage include:

  • Intestinal haemorrhage due to bleeding from congested Peyer's patches.

  • Perforation of the distal ileum, frequently fatal. There may be little warning, and peritonitis is a common complication.

  • Encephalitis.

  • Neuropsychiatric symptoms: muttering, picking at clothes, confusion.

  • Metastatic abscesses.

  • Colecistitis.

  • Endocarditis.

  • Osteitis.

  • Dehydration is a significant risk.

  • One third develop a macular truncal rash.

  • Thrombocytopenia with risk of bleeding.

  • Eye complications may occur (usually only with associated systemic illness) including corneal ulcers, uveitis, abscesses (eyelid or orbit), vitreous or retinal haemorrhage, retinal detachment, optic neuritis, extraocular muscle palsies, and orbital thromboses.

Week four

• In the untreated patient the fourth week sees the fever, mental state and abdominal distension slowly improve over a few days, but intestinal complications may still occur. Convalescence is prolonged, and most relapses occur at this stage.

Carrier status

2-3% of patients infected with typhoid fever may have a low-grade infection. They may not develop any significant symptoms, and then become carriers of the disease.

Symptoms of paratyphoid fever

• Vague chills, sweating, headache, weakness, dry cough, anorexia, sore throat, dizziness, and muscle pains are frequently present before the onset of fever.

• Rising then persistent fever.

• Abdominal pain (in about a third of patients).

• Relative bradycardia.

• Hepatosplenomegaly.

• Rose spots (in about a third of patients).

• Constipation (more common than diarrhoea).

• Very rarely, neuropsychiatric symptoms.

• Very rarely, epileptiform seizures.

Diagnóstico diferencial⁴

The group of symptoms which most clearly suggests the diagnosis of typhoid fever is:

• Gradually increasing fever with evening exacerbation and morning remission.

• General malaise with headache.

• Furred tongue with red edges and tip.

• Epistaxis.

• Relatively slow pulse (possibly dicrotic).

• Abdominal distension with increased bowel sounds.

• Tenderness in the right iliac fossa on firm pressure.

• A roseolar eruption confined principally to the abdomen and chest.

• Esplenomegalia.

• Bronchial catarrh.

El diagnóstico diferencial de este grupo de síntomas dependerá del historial de viajes y puede incluir una amplia variedad de causas tropicales y no tropicales de fiebre y erupción. Siempre considere la coexistencia malaria o esquistosomiasis.

In patients with appropriate travel history malaria remains the most likely cause of febrile illness, although this does not rule out the presence of additional disease. A list of diagnoses to consider in the returning traveller with febrile illness, abdominal pain, neurological symptoms and rashes should include:

• Malaria.

• Amebiasis.

• Influenza.

• Tuberculosis.

• Tifus.

• Viral haemorrhagic fever - for example, Ebola.

• Dengue.

• Infección no tifoidea con Salmonella spp.

• Campylobacter.

• Colera.

• Tifus.

• Scrub typhus.

• Tuberculosis.

• Abdominal abscess.

• Yellow fever.

• African trypanosomiasis (sleeping sickness).

Investigaciones

Organism culture

Diagnosis is usually made by culture of the organism from faeces, urine or blood. Blood cultures are positive in 61% of cases. Bone marrow culture gives a higher yield, but is not often performed. Faeces, urine, or bile aspirate may be cultured, but a positive result may only indicate chronic faecal carriage rather than acute infection.¹¹

Serology

La prueba serológica tradicional es la prueba de Widal. Mide los anticuerpos aglutinantes contra los antígenos flagelares (H) y somáticos (O) de S. typhi. It is still used in developing countries because of its low cost, but is no longer considered a useful diagnostic tool to identify acute or recent infection. It has largely been replaced by newer serological methods such as standard immunoblotting and ELISA techniques.

Treatment for typhoid and paratyphoid fever

In non-endemic countries, patients presenting with symptoms suggestive of typhoid or paratyphoid fever are initially assessed in hospital where a firm diagnosis by blood culture or bone marrow culture can be made, and antibiotic sensitivities determined. Empiric antibiotic treatment is commenced depending on the likely source of the infection (country travelled to). Clinically unstable patients are admitted to hospital for IV treatment while those who are stable may be treated as outpatients.

General principles for the management of typhoid^{3 4 11}

• Rapid diagnosis e institución de un tratamiento antibiótico adecuado.

• Adequate nutrition - se debe continuar con una dieta blanda y de fácil digestión a menos que el paciente tenga distensión abdominal o íleo.

• Apoyo - descanso adecuado, rehidratación y corrección de alteraciones electrolíticas.

• Antipyretic therapy - según sea necesario.

• Higiene - los cuidadores deben ser meticulosos con el lavado de manos y la eliminación de heces y orina.

• Close attention to hand washing y limitación del contacto cercano con individuos susceptibles durante la fase aguda de la infección.

• Regular follow-up y monitoreo de complicaciones y recaídas clínicas (esto puede incluir la confirmación de la eliminación de heces en áreas no endémicas o en grupos de alto riesgo como manipuladores de alimentos.

• Antibióticos (ver abajo) - acortar el curso, reducir la tasa de complicaciones si se comienza temprano y reducir la mortalidad.¹²

• Esteroides - se han utilizado ocasionalmente en casos graves. Sin embargo, pueden inducir una recaída, por lo que generalmente no se recomiendan.

• Quirúrgico - si ocurre una perforación del intestino, será necesario cerrarla. El tratamiento solo con antibióticos fue favorecido en el pasado, pero se requiere un cierre simple y drenaje.

Antibiotic treatment of typhoid fever^{13 14 15 16 17}

• Ideal antibiotic treatment is safe and available in short courses of five days, causes resolution of fever within one week, renders blood and stool cultures sterile, and prevents relapse.

• Current national guidelines or local formularies should be consulted for the selection of antimicrobial based on regional susceptibility patterns.

• Drug resistance is a major problem. Older drugs such as chloramphenicol, ampicillin and trimethoprim have been replaced by fluoroquinolones, but these too have become less effective as resistance develops in South Asia and increasingly in Africa. Currently, extended spectrum cephalosporins, oral cefixime, parenteral ceftriaxone, and oral azithromycin are recommended options, with parenteral meropenem reserved as a last resort.

• The antibiotic is appropriately changed once sensitivities are available.

• Antibiotic treatment durations of 7-14 days or 5 days after fever resolution, whichever is longer, have traditionally been used. Patients on IV antibiotics can be switched to oral preparations as soon as clinically stable.¹¹

Uncomplicated typhoid fever

• Empirical treatment if infection is likely to have originated in Asia - azithromycin.

• Multiple-resistant - fluoroquinolone (5-7 days), or cefixime (7-14 days).

• Quinolone-resistant - azithromycin (7 days) or ceftriaxone (10-14 days).

• If the infection is likely to be from Africa, South America or Central America, fluoroquinolones (for example, ciprofloxacin) may still be used (5-7 days). Fewer than 4% of infections imported to the UK from Africa are resistant to fluoroquinolones.

Severe typhoid fever requiring parenteral treatment

• If the origin of infection is likely to be Asia - IV ceftriaxone.

• Fully sensitive - fluoroquinolone (such as ofloxacin) for 10-14 days.

• Multiple-resistant - fluoroquinolone (such as ofloxacin) for 10-14 days.

• Resistente a quinolonas - ceftriaxona o cefotaxima durante 10-14 días.

Complicaciones¹

• The two most common complications are haemorrhage (including disseminated intravascular coagulation) and perforation of the bowel. Before antibiotics, perforation had a mortality of around 75%.

• Jaundice may be due to hepatitis, cholangitis, cholecystitis, or haemolysis.

• Pancreatitis with acute kidney injury and hepatitis with hepatomegaly are rare.

• Toxic myocarditis occurs in 1-5% of patients (ECG changes may be present). It is a significant cause of death in endemic areas.

• Toxic confusional states and other neurological and psychiatric disturbances have been reported.

Chronic carriers of typhoid ¹¹

About 10% of people with the infection excrete the organism for up to 3 months after infection, and up to half of these may become long-term carriers (more than 1 year).¹⁸

One week following treatment, a stool culture is taken from asymptomatic patients to check that these infections have cleared. If the sample is positive, strict hygiene procedures need to be continued, and retreatment may be necessary. If the patient is in a 'risk group' (see 'Risk groups', below) re-treatment, exclusion, redeployment and bacteriological surveillance are needed until there have been three negative clearance faecal samples taken at least 48 hours apart.

• Ciprofloxacin 750 mg bd and norfloxacin 400 mg bd have both been effective in the past. This may remain effective treatment in cases where Africa or South America was the source of infection. Where the source is Southeast Asia, however, newer quinolones such as gatifloxacin, ampicillin, amoxicillin with probenecid or co-trimoxazole have been used.¹⁴ (Discutir con el microbiólogo.)

• Long-term urinary carriers should be assessed for urinary tract abnormalities, including schistosomiasis.

• In long-term faecal carriage, cholecystectomy is not very effective, as the liver is a reservoir.

Community containment and public health management¹

La estrecha colaboración entre el consultor de enfermedades infecciosas, el microbiólogo, el médico de salud pública y el médico general ayuda a prevenir la propagación de S. typhi y S. paratyphi a través de la comunidad. Todos los pacientes, portadores, compañeros de viaje y contactos deben adherirse a estrictas normas de higiene.

Exclusion or redeployment should be considered for those in risk groups who have had enteric fever for at least 48 hours after their symptoms subside. One week after completing their treatment, three samples taken from them 48 hours apart need to be negative before they are no longer considered to be at risk of passing on the infection.

Grupos de riesgo

En el Reino Unido, la gestión de la salud pública de S. typhi y S. paratyphi se centra en 'Grupos de riesgo' que se definen como:

• Any person of 'doubtful personal hygiene' o con instalaciones insatisfactorias de inodoro, lavado de manos o secado de manos en casa, trabajo o escuela.

• All children aged 5 years old or under que asisten a la escuela, preescolar, guardería u otros grupos de cuidado infantil o de atención.

• People whose work involves preparing or serving unwrapped food para ser servido crudo o no sometido a más calentamiento.

• Clinical, social care or nursery staff que trabajan con niños pequeños, ancianos u otras personas particularmente vulnerables, y cuyas actividades aumentan el riesgo de transferir infecciones por vía fecal-oral - por ejemplo, cuidando a un familiar crónicamente enfermo.

Exclusion/redeployment are not required of those not in the above risk groups, but strict standards of hygiene should be adhered to.

Casos documentados de S. typhi y S. paratyphi

En el Reino Unido, todos los casos de S. typhi y S. paratyphi - con un diagnóstico documentado basado en una muestra de sangre o heces tomada en el Reino Unido o en el extranjero - debe notificarse a la Unidad de Protección de la Salud (HPU). Aquellos que están en 'grupos de riesgo', mencionados anteriormente, deben ser excluidos mientras presenten síntomas y durante al menos 48 horas después de que los síntomas hayan desaparecido. La HPU les aconsejará sobre cualquier acción adicional necesaria y cuándo pueden regresar al trabajo.

Casos no documentados de S. typhi y S. paratyphi

Algunas personas pueden haber recibido un diagnóstico de fiebre tifoidea y haber sido tratadas en el extranjero, sin tener un diagnóstico documentado de cultivo de sangre. Si están asintomáticas al presentarse, se debe enviar una muestra de heces para su análisis a un laboratorio local.

They need not be excluded while they are waiting for the results unless they become symptomatic. If the result is positive, the HPU should be informed. If they are symptomatic at presentation, they should be treated appropriately, the HPU should be informed, and they should be excluded if they are in a 'risk group', above, until 48 hours after their symptoms have subsided.

Co-travellers

Es probable que los contactos asintomáticos que viajan junto a casos conocidos de fiebre tifoidea hayan estado expuestos a la misma fuente de fiebre tifoidea o paratifoidea que su compañero. Se debe enviar una muestra de heces para cultivo lo antes posible. Se les debe dar consejos estrictos de higiene, informarles sobre los síntomas y signos de estas infecciones, y aconsejarles que contacten a su médico de cabecera o al hospital si se sienten mal.

If they develop symptoms of typhoid or paratyphoid fever, they should be excluded, as above, and treated as necessary. If they remain asymptomatic, they need not be excluded while they are waiting for the results of their stool culture. If the stool culture is positive, the HPU should be notified. If they are in a high-risk group, they should be excluded until the HPU advises them that they can go back to work or school.

Non-travelling contacts

Household or sexual contacts of patients with enteric fever should be given hygiene advice and warned to contact their GP if they develop symptoms of the disease. They do not need a screening sample and do not need to be excluded unless they become unwell.

Pronóstico

In the days before antibiotics, mortality was 20%. The overall current mortality rate is less than 1% due to advances in treatment and the development of antibiotics. Early diagnosis and treatment avoids complications. In untreated patients, approximately 10% will relapse, and 4% will become chronic carriers.¹⁰

Today mortality is low (<1%); however, in the context of natural and man-made disasters and catastrophes, outbreak mortality rises back to 10-30%, despite antibiotic therapy.

A study of 581 patients hospitalised for typhoid in Vietnam in 2014 found that more severe disease occurred in about 15% including gastrointestinal bleeding (7%), hepatitis (5%), encephalopathy (3%), myocarditis (2%), intestinal perforation (1%), haemodynamic shock (1%) and death (0.5%).¹⁹

Factors associated with more severe disease were:

• Edad avanzada.

• Longer duration of illness.

• Infection with an organism only partially susceptible to ciprofloxacin.

Prevention of typhoid fever

• In countries in which typhoid is endemic, the most important action is attention to safe drinking water and disposal of sewage.

• Vacunación masiva con vacuna oral contra la fiebre tifoidea también es efectivo.

• Los viajeros a áreas endémicas también deben tomar precauciones con respecto a la higiene, pero deben recibir vacunación también (no hay vacuna para S. paratyphi A).

La Dra. Mary Lowth es una autora o la autora original de este folleto.