Typhoid fever and brucellosis

Typhoid and paratyphoid (enteric) fevers

Typhoid and paratyphoid fevers are systemic disease caused by infection with Salmonella typhi and S. paratyphi A and B which are a gram negative bacilli. After a few days of bacteraemia, the bacilli localize, mainly in the lymphoid tissue of the small intestine, resulting in typical lesions in the Peyer's patches and follicles.
These swell at first, then ulcerate and usually heal. After clinical recovery, about 5% of patients become chronic carriers; the bacilli may live in the gallbladder for months or years and pass intermittently in the stool and less commonly in the urine.

Routs of transmission.

The diseases are transmitted by the faecal-oral route, through contaminated water or food. The sources of infection are either asymptomatic fecal carrier or cases during disease or convalesce state.

Clinical features

The incubation period is about 10-14 days and the onset may be insidious. The temperature rises in a stepladder fashion for 4 or 5 days with malaise, increasing headache, drowsiness and aching in the limbs. Constipation may be present, although in children diarrhea and vomiting may be prominent early in the illness. The pulse is often slower than would be expected from the height of the temperature, i.e. a relative bradycardia.
At the end of the first week, a rash may appear on the upper abdomen and on the back as sparse, slightly raised, rose-red spots, which fade on pressure. It is usually visible only on white skin.
Cough and epistaxis occur. Around the 7th-10th day the spleen becomes palpable. Constipation is then succeeded by diarrhea and abdominal distension with tenderness. Bronchitis and delirium may develop. If untreated, by the end of the 2nd week the patient may be profoundly ill

Paratyphoid fever

The course tends to be shorter and milder than that of typhoid fever and the onset is often more abrupt with acute enteritis. The rash may be more abundant and the intestinal complications less frequent.
Complications
The Hemorrhage from, or a perforation of, the ulcerated Peyer's patches may occur at the end of the 2nd week or during the 3rd week of the illness. A drop in temperature to normal or subnormal levels may be falsely reassuring in patients with intestinal haemorrhage. Additional complications may involve almost any viscus or system because of the septicaemia present during the 1st week. Bone and joint infection is common in children with sickle-cell disease.

Investigations

1)-isolation or culturing of m.o.
Other than positive culture no specific laboratory test is diagnostic for enteric fever .the blood culture is positive in 90% during first weak of infection but the yeid of culture decrease with time to 50% at 3th weak. Also diagnosis based on positive culture of bone marrow 90% at 2th weak. stool culture positive during 2th-3th wk of infection.
2)- serological tests
The classical widal test given high rate of false positive and false negative results so this test is not diagnostic but when positive support the diagnosis of enteric fever.
Other blood finding leucopenia, thrombocytopenia and abnormal liver function test.

Differential diagnosis.

Malaria,
hepatitis,
typhus,
brucellosis,
visceral lishamansis,
amebic liver abscess
shigellosis.

Treatment

1)- first line drugs
Ciprofloxacin 500mg bid for 10 days.
Ofloxacin 10-15 mg/kg po bid for 2-3 days.
Ceftriaxone 1-2g i.v/im for 10-14 days.
1)-alternative drugs .
Azithromycin 1g po dialy for 5 days.
High dose of ciprofloxacin 20mg/kg for 10 days.
Prolong duration of oflaxocin 10 mg/kg for 7-10 days.
Chronic carriers are treated for 4 weeks with ciprofloxacin; cholecystectomy may be necessary

Brucellosis (undulant fever, malta fever, Mediterranean fever)

Brucellosis is an enzootic infection (i.e. endemic in animals). Although six species of Brucella Gram-negative spore forming bacilli are known, only four are important to humans:
B. melitensis with a reservoir (goats, sheep and camels in Europe, especially the Mediterranean basin, the Middle East, Africa, India, Central Asia and South America),
B. abortus (cattle, mainly in Africa, Asia and South America),
B. suis (pigs in South Asia)
B. canis (dogs).
B. melitensis causes the most severe disease; B. suis is often associated with abscess formation.

Routs of transmission

Infected animals may excrete Brucella spp. in their milk for prolonged periods and human infection is acquired by ether:
ingesting contaminated dairy products, uncooked meat or offal.
through abraded skin or via splashes and aerosols to the respiratory tract and conjunctiva due to contaminated by animal urine, faeces, vaginal discharge and uterine products.
High risk groups
1)-The farmers ,2)-veterinarians 3)-slaughter house workers 4)-laboratory personals

Clinical features

Brucella spp. are intracellular organisms that survive for long periods within the reticulo-endothelial system. This explains many of the clinical features, including the chronicity of disease and tendency to relapse even after antimicrobial therapy.
Asymptomatic or clinically unrecognized human brucellosis often occur in high risk groups and detected only by serological tests.
Acute illness after an incubation period of 10-14 days is characterized by a high swinging temperature, rigors, lethargy, headache, joint and muscle pains, and scrotal pain. Occasionally, there is delirium, abdominal pain and constipation. Physical signs are non-specific, e.g. enlarged lymph nodes. Enlargement of the spleen may lead to hypersplenism and thrombocytopenia
The chronic brucellosis or localized infection which occurs in about 30% of patients, is more likely if diagnosis and treatment are delayed.
.

Focal manifestations of brucellosis

Musculoskeletal
Suppurative arthritis; synovitis, bursitis
Osteomyelitis
Spinal spondylitis or sacro-iliitis
Paravertebral or psoas abscess
Central nervous system
Meningitis
Intracranial or subarachnoid haemorrhage
Stroke
Myelopathy
Radiculopathy
Cranial nerve palsies


Ocular
Uveitis
Retinal thrombophlebitis

Cardiac

Myocarditis
Endocarditis

Respiratory

Pneumonitis or abscesses
Hilar adenopathy
Abdominal
Splenic abscesses or calcification
Hepatitis
Genitourinary
Epididymo-orchitis
Haematological
Pancytopenia

Diagnosis

1)-culturing of m.o.
Definitive diagnosis of brucellosis depends on the isolation of the organism.
Blood cultures are positive in 75-80% of infections caused by B. melitensis and 50% of those caused by B. abortus.
Bone marrow culture should not be used routinely but may increase the diagnostic yield, particularly if antibiotics have been given before specimens are taken.
CSF culture in neurobrucellosis is positive in about 30% of cases. The laboratory should be alerted to a suspected diagnosis of brucellosis, as the organism has a propensity for infecting
2)-serological test.
Serum tests(rose bingal test) are also used to detect brucellosis antibodies. In endemic areas a single high titre of > 1/320 or a fourfold rise in titre is needed to support a diagnosis of acute infection. The test usually takes several weeks to become positive but should eventually detect 95% of acute infections.

Management

Aminoglycosides show synergistic activity with tetracyclines against brucellae; standard therapy in acute infection consists of
doxycycline 100 mg 12-hourly for 6 weeks, with streptomycin 1 g i.m. daily for the first 2 weeks. The relapse rate with this treatment is about 5%.
An alternative oral regimen consists of doxycycline 100 mg 12-hourly plus rifampicin 900 mg (15 mg/kg) daily for 6 weeks, but failure and relapse rates are higher, particularly with spondylitis. Rifampicin may antagonise doxycycline activity by reducing serum levels through enzyme induction.
Rifampicin and co-trimoxazole are potential agents to use in pregnancy.


Endocarditis is often treated with three active drugs, usually doxycycline, rifampicin and streptomycin, but surgery is often required.
Chronic illness or neurobrucellosis should be treated for a minimum of 3 months and many authorities would extend this to 6 months, depending upon the response