Typhoid

specific localization of the causative agent in intestine (small or

large, rectum, mesenterium)
removing the agent with feces or vomiting mass
can penetrate into a susceptible organism by next ways of transmission (watery, alimentary, contact-household)
various factors of transmission (foodstuff, water, hands, insects, toys, soil)
in intestine causative agent can be: in the lumen of intestine, intestinal epithelium, mucous membrane, lymphatic tissue of intestine

causative agent can constantly be in intestine (cholera, dysentery, some helminthic invasion) or temporarily,

penetration from intestine in blood and other tissue (ascariasis, amebiasis, strongyloidiasis, trichinosis, echinococcosis)

- in warm and/or rainy period of year

(in moderate climatic zones is more often registered during
summer or autumn);
- in countries with low socio-economic level of development;
- among people of risk-groups:
- age - children and the elderly,
- chronic GIT-pathology - patients with
gastritis, duodenitis, peptic ulcer, cholecystitis;
- profession - sanitary workers, plumbers, teachers,
medical personal;
- occupation – fishermen, water-rescuers,
veterinarians, animal trainers

fecal - oral mechanism of transmission caused by S. typhi,

characterized by lesions of lymphatic apparatus of the small intestine and bacteremia, development of severe intoxication, hepatosplenomegaly and roseola rash.
The name of the disease came from the word «typhos», meaning «smoke» or «fog».

The disease has been referred to by various names, often associated with symptoms, such as gastric fever, enteric fever, abdominal typhus, infantile remittant fever, slow fever, nervous fever, and pathogenic fever.

the writings of the ancient historian Thucydides, who suffered this

disease.

In 430 BC in Athens lost one-third of the population of Athens, including their leader Pericles.

- Some historians believe that English colony of Jamestown, Virginia, died from typhoid. Typhoid fever killed more than 6000 settlers in the New World between 1607 and 1624.

- During the American Civil War 81 360 Union soldiers died of typhoid or dysentery, more than died of battle wounds.

typhoid fever was Mary Mallon, also known as Typhoid Mary.

In 1907, she became the first carrier in the United States to be identified and traced. She was a cook in New York who is closely associated with 53 cases and 3 deaths.

Public health authorities told Mary to give up working as a cook or have her gall bladder removed, as she had a chronic infection that kept her active as a carrier of the disease.

Mary quit her job, but returned later under a false name. She was detained and quarantined after another typhoid outbreak.

She died of pneumonia after 26 years in quarantine.

known as Salmonella enterica serotype typhi (D),

parasitizing in the intestine and blood;
gram–negative enteric bacillus belongs to the family of Enterobacteriaceae;
motile due to peritrichous flagella;
facultative anaerobe that is susceptible to various antibiotics;
spores and capsules do not form; stable in the environment;
grows best at 37°C on ordinary medium, especially with the addition of bile;
releases endotoxin after destruction;

Salmonella typhus possesses 3 main antigenic factors:
1. - O, or somatic antigen,
2. - Vi, or encapsulated antigen,
3. - H, or flagellar antigen

releases within 3 months, chronic – more than 6 months

(the most dangerous in epidemiological terms). - patient discharges bacteria with feces, urine, saliva. (massive discharging starts from the 7th day of illness). Mechanism of transmission: – fecal-oral implemented by – water, - food, - contact-household ways. Sensitivity: - children, young people, elderly,
54% of typhoid fever cases involved males;
patients with immunodeficiency and chronic diseases of the gastrointestinal tract; After the disease develops persistent immunity. Characterized by seasonality (summer, autumn).

conditions are poor.

Typhoid fever is endemic in Asia, Africa,

Latin America, the Caribbean, and Oceania, but 80% of cases come from Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, or Vietnam.
Within those countries, typhoid fever is most common in underdeveloped areas.
Typhoid fever infects roughly 21.6 million people (incidence of 3.6 per 1,000 population) and kills an estimated 200,000 people every year

Annually in the world are ill 20 million persons from

which 800.000 died.

necessary infectious dose (107 - 109) and
condition of protective

barriers.

Incubation (14-17 days). 1-st week of contact with the agent. Clinic no.

2-nd phase
Primary regional infection

- Penetration into mucosa of the small intestine, - accumulation in the solitary follicles, - formation of primary foci of inflammation, - multiplication in mesenteric lymph. nodes, - development of lymphadenitis and lymphangitis.

Incubation. 2-nd week of contact with the agent. Clinic no.

number Salmonella enters the blood via the thoracic duct and

dies due to action of the bactericidal properties of blood releasing endotoxin.

- With the blood flow Salmonella penetrates into the parenchymal target organs (liver, spleen, bone marrow and skin), forming secondary foci of inflammation (granulomas)

Initial period
(1-st week of disease).
Development of intoxication syndrome (nonspecific symptom).

Climax period
(2-3-d week of the disease).
Appearance of the typical pathognomonic syndromes of illness (hepatosplenomegaly, pancytopenia, rash).

and immune complexes through the kidneys, bile duct and intestine.

The remaining bacteria are embedded in sensitized lymph. follicles, causing hyperergic inflammation with necrosis.

Production of specific antibodies,
Normalization of microcirculation and restore organ functions.

Climax period
(3-4-th week of the disease).
Pathognomonic symptoms persist.

The period of convalescence
(5-th week – early convalescence,
6-th – late convalescence). Gradual disappearance of the syndromes.

lymph follicles in the mucosa of the small intestine.
Cerebrum-like swelling

of lymphoid structures of the small intestine.

Formation of ulcers. In the center of the follicles are formed necrosis with green, gray, or yellow surface covered with fibrin.

Stage of “dirty” ulcers
(deep layers covered by fibrin)

Period of “clean” ulcers, purification of fibrin.
Healing of ulcers without scarring, deformation, but the pigmentation is gray-black in color.

complications

Specific
complications

week) – nonspesific syndroms:

- General intoxication;
- Cardio-vascular syndrome;
- Respiratory syndrome;
- Gastrointestinal syndrome;

Climax period – (2-3 weeks) – typical syndroms:
- Hepatosplenomegaly;
- Roseola rash;
- Status typhosus;
– nonspesific syndroms:
- General intoxication;
- Cardio-vascular syndrome;
- Respiratory syndrome;
- Abdominal syndrom;

4. Convalescence period – (2-3 weeks) – asthenovegetative syndrom

of 9-14 days. When the water route of infection -

up to 1 month. Clinical picture no.
Initial period characterized by:

1. Intoxication syndrome with acute (peak within 2-3 days)
or gradual beginning:
- fatigue, weakness, chills;
- headache, apathy;
- temperature rises gradually
to 38-39 °C
(by the 5-7-th day of illness);



- sleep disturbance;
- pale face and skin;

- decrease of blood pressure;







3. Respiratory syndrome:
hard breathing,
- diffuse dry rales ( as bronchitis),
- coughing;

4. Gastroenteric syndrome :
- loss of appetite or anorexia;
tongue is thickened, covered with gray – white fur
and imprints of teeth;
the mucous membrane of oropharynx is hyperemic,
tonsils can be increased;

at palpation ( ileitis);
- at percussion – is

a shortening of sound
in the right iliac area
(“+” Padalka – sign due to hyperplasia of the mesenteric lymph. nodes),

within 2-4 days of disease may be seen
diarrhea (stool is stinking with a sour
smell, up to 2 – 4 t/day, foamy, liquid,
greenish like pea soup.

enlargement of the spleen and liver
(at the end of 1st week),

the 2-d week of the disease and lasts an average

of 2-3 weeks)
Intoxication syndrome:
- headache is the most expressed, not relieved by drugs;

- insomnia, drowsiness;
- chills, weakness;
- photophobia;

- status typhosus - delayed mental reactions,
sometimes prostration, stupor condition
and coma, tremor of fingers, chin and
tongue;

- apathy, adynamia;

- temperature is febrile or hectic (39-40ºC), increases every day
for 1-2ºC during the week and lasts for about 2 weeks.

temperature not more then 1ºC,
The 1-st phase (3-4 days)

characterized by an increase of temperature. In the 2-d phase (1, 5-2-3 weeks) fever is continuous between morning and evening temperature marked a slight remission. The 3-d phase (amphibolitic) – is characterized by high ranges of the temperature curve. In the 4-th phase (5-8 days) and ing the temperature is reduced.

Botkin –wave-like - f. undulans - with sequential alternating 3-4-days episodes of febrile and subfebrile temperature. Daily fluctuations of temperature within 0,5-1ºC;

Kildushevsky – triangular - with a short (1 -2 days) stage of constantly high temperature and prolong (2-2,5 weeks) stage of decreasing;

There are 3 possible types of the temperature curve in the clinic:

and mucous membranes;
- tongue is dry enlarged with

teeth prints,
bright red, covered with brown fur (fuliginous);

- abdomen distended, rumbling,
painful palpation;

“+” Padalka and cross-Sternberg symptoms;
- Philippovich-symptom - icteric staining of the palms and feet – due to carotene skin hyperchromia (liver damage);
- obstipation;

but has a smooth edge; spleen is enlarged and painful;
-

clinic cholecystitis, pancreatitis, hepatitis.

the heart sizes;
- dull heart tones, systolic murmur at the

apex of the heart
( due to intoxication inhibition of the conducting system of myocardium).
6. Respiratory syndrome:
- hard breathing, diffuse dry rales;
sometimes bronchial pneumonia.

During this period, there are specific complications caused by pathogenic action of bacteria and its toxin.
Often develop:
intestinal bleeding – (1-2%) is observed on the 3-d week of illness
(due to damage of the blood vessel at the bottom of the ulcer). Has diffuse or
the capillary character;
perforative peritonitis – (0,5-1,5%) develops in 2-4 weeks
(due to perforation of ulcer in intestine);
- infectious-toxic shock – (0,5 – 0,7%) develops at the end of the initial period (due to the massive penetration of bacteria and their toxins in the blood).

the main method of laboratory
diagnosis

of typho-paratyphoid diseases, allows to select and
determine the type of pathogen.
Bacteriological research is subjected to blood (52—78%), urine (0,7—2,1%),
feces (11—19%) , bile and scraping of the rash, bone marrow, pus, sputum.

The time of selection of the material:
- 1-2-d week – the blood; - 2-3-d week – the urine, stool;
- during the whole of the disease – the duodenal contents.

Blood should be taken from the first days of sickness and whole period of the fever in volume of 5-10ml on a nutrient medium containing a bile
(Rappoport-medium).
The ratio between the blood and nutrition – 1:10
(because the blood has antibacterial properties
destroys the microbe).

Stool-, bile-, urin-culture can be obtained
on the nutrient medium called Ploskirev-medium.

the blood or antigens in
biosubstrate, should be performed by

paired serums method;
the diagnostic titer – increase of antibodies titer in 4 and more times.
- Vidal-test (reaction of agglutination) - detection of specific O – and
H- antibodies-agglutinins in the blood of the patient using the
appropriate antigens.
Positive results can be obtained with 8-9 days
of illness (titer 1:200);
- RIHA (reaction of indirect hemagglutination ) –
with erythrocyte O - , H - and Vi-antigens;
- RIF (reaction of immunofluorescence), RIA;

- ELISA, PCR of different samples

leukocytosis then leukopenia with a shift formula to the left

(4-5-th day), uneozinofilia, thrombocytopenia, lymphocytosis, tendency to anemia, increased ESR;


2. Urinalysis: signs of “toxic kidney” (proteinuria, microhematuria, casts);


3. Coprocytogram:
leukocytes
(90 % from them
monocytes);

changes in lungs (pneumonia).

2. Radiography of the abdomen - if

you suspect an intestinal perforation.

3. ECG, monitor heart activity - to diagnose myocarditis.

4. Spinal puncture - is performed when a positive meningeal signs,
suspicion for the development of meningitis.

5. Ultrasound of the abdomen - helps to determine the size of the liver and
spleen.

person or carrier,
using of unboiled water and contaminated

food);
- gradual onset with a classic temperature curve;
chills and sweating, hot dry pale skin;
bloating (mainly in the classic version);
- tenderness on palpation of the abdomen and positive Padalka-symptom;
presence of watery stool a yellowish or greenish color without
pathological admixtures, transforming into constipation;
- tongue with prints of teeth on lateral surfaces;
- enlarged liver and spleen;
- symptoms of intoxication (headache, sleep disturbance and weakness);
rash (roseola-like) on the skin of the abdomen and thorax on
the 8-9th day of illness;
- relative bradycardia.

%

- Perforation of intestinal wall - 0,5 -

1,5 %

- TISH - 0,5 - 0,7 %

- Relapses (are more often in 2-3 weeks) - 7-9%

Nonspecific:
pneumonia, osteomyelites, purulent arthritises,
abscesses, pyelonephrites, endophthalmias,
meningitises

- strict bed regime - up to 6-7-th day of

apyrexia;
- sitting position - from the 7-8-th day of apyrexia;
- allowed to walk - from the 10-11th day of normal
body-temperature;

2. Diet №4 - the entire febrile period and up to 7-8-th day of apyrexia.
Food must be mechanically and chemically sparing;





3. Specific therapy:
- antibiotics on the sensitivity of the microorganism (first choice);
- duration of a/b treatment – till 10-12-th days of normal body-
temperature;
- gradual dose reduction.

Allowed Contraindicated

- in mild and moderate severity (without vomiting)

0,5-1,0 g × 4 t/d (daily dose - 2-4g);
- parenteral (i/m or i/v) – in severe cases and vomiting
1-2 g × 2 t/d (daily dose - 2-4g);
On the 2nd day of normalization of body temperature the dose is reduced gradually and should be given per os in 0,5 g × 4 t/d 10 days of apyrexia.
2. Ampicillinum:
(effect is slower than of chloramphenicol, but relapse is less often)
- per os or parenteral (i/m) – 1-1,5 g × 4 t/d;
3. Ciprofloxacin:
- per os - 0,5 g × 4 t/d;
4. Trimethaprim – sulphamethoxazole:
- per os - 0,960 g × 2 t/d;
5. Alternative remedies: ceftriaxone - 2 g/day, ofloxacin - 0,8 g/day,
azitromicin - 0,25-0,5 g/day, cefoxim - 0,4 g/day.

For the treatment of a carrier:
- ampicillinum in a dose 40-50 mg/kg per os 4 t/d within 4 - 6 weeks
(efficiency 80 %).

IV);
- sufficient hydration (PO or IV);
-

hemostatic therapy (intestinal bleeding);
- glucocorticoids (ТISH);
- antioxidants;
- antiferment drugs;
- probiotics, eubiotics.
Symptomatic therapy:
- analgetics, antipyretics, antiemetics;

Rules of discharging the patient out from the hospital:
Discharge the patient from the hospital is possible on 21-st day of normal
temperature, but not before the 4-th week of illness.

1. Clinical recovery;
2. 2 negative copro- and urine-cultures (5, 10 day of normal temperature);
4. 1 negative bile-culture (12-14-th day of normal temperature)

relapse appears in 20-25 %

The vaccines do not form

a complete protection, but should be used:

- at close family contact with patient or carrier;

- during outbreaks of T.F.

- before visiting the areas endemic on T.F.

Basic preventive measures:

- keeping of rules of personal hygiene;

- control of cooking and storage of nutrition;

- registration, treatment and discharge from work carriers of S.t;

- careful clearing of the drynking water;

- desinfection of the sewers;

- constant medical control for decreed risk groups in population