Gram negative rods related to animal sources (Zoonotic organisms)

Last updated: November 12, 2024

Briefly describe Brucellosis
- Brucellosis is a zoonotic disease. Brucella abortus (Cattle), Brucella melitensisi (Sheep goat and cattle), Brucella suis (pigs), Brucella canis (dogs). Brucella abortus is more common in prevalence. Tissues affected in animals include mammary glands (ease of transmission), epididymis and seminal vesicles (sterility), uterus and placenta (abortions). Brucella sheds ni urine, stool, and POCs (Products of Conception – placenta, amniotic fluid) remain viable in the environment for ≥ 40 days.
- Brucella is a gram negative coccobacili (may imitate hemophilus), non-encapsulated, no motile, non spore forming. They are oxidase catalse, and urease positive but non-lactose fermenters. Difficult to culture but use of castaneda bottle or biphasic culture media for up to 6 weeks. Automated culture systems may take up to 7 days.
- Epidemiology
  - Global distribution, increasing number of cases. Expansion of animal rearing without adequate education. Consumption of “health” foods and travel to endemic areas.
Outline the causative agents of Brucellosis Cause Brucellosis/ undulant fever/ Mediterranean fever/ Malta fever
1. Brucella arbotus- cattle
2. Brucella suis- swine
3. Brucella melitensis- goats/ sheep
4. Brucella canis- dogs
5. Brucella bovis- goats/ sheep(no evidence it affects man)
Outline the characteristics of Brucella
1. GN coccobacilli occurring singly, in chains or in groups.
2. Non motile, non sporing, non capsulated
3. Strict aerobes, grow very slowly (fastidious) on blood agar
4. Facultative intracellular pathogens
5. Do not ferment CHOs
6. Difficult to culture- Castaneda bottle or biphasic culture media for up to 6 weeks
Briefly describe the pathogenesis and transmission of Brucellosis
- Ingestion of contaminated unpasteurized products (milk), Ingestion of raw meat, bone marrow, liver, direct contact with infected animals, inhalaton (meat processing factories, lab workers), entry through cut woumds or breaks)
- At risk individuals
  - Livestock farmers, pastoralists, abattori workers, vets (Trans-placental transmission), consumers of unpasteurized animal products
- Enters host → not picked up by TLRs (some eukaryotic cell membrane feaatures) → access intraepithelial spaces (immune avoidance) → triggers phagocytosis by macrophages 0> Inhibit macrophage MPO and phagolysosome → trafficked by macrophages to RES (Liver sinusoids, spleen, BM, Lymph nodes) → Multiply in the ER of macrophages → Formation of granulomas (important clinical feature of disease persistence)
- Erythritol – alcohol based compound that is highly nutritious for brucella, found in placentla tissue
Outline the clinical features of Brucellosis
- Incubation 1-3 weeks to months
- Undulating fevers, drenching, worse in the late afternoon or evening. Can pesist for weeks, months, or years
- Associated myalgia, headache, joint (spine) pain and anorexia
- Weight loss – directly proportaionl to duration of illness
- Enlarged RES Splenomegaly > lymphadenpathy or hepatomegaly
- Other organs involved – Lung, bone, brain, heart, GUT
What are the complications of Brucellosis
- MSK disease localization and complications
- CVS omplications
- Pulmonary manifestation (Rare)
- Genitourinary disease
- Neurobrucellosis
- Pregnancy related complications (abortion not common in humans
- Dermatological findings
- Vaccine related complications (splash effect to conjuctiva when injecting animals)
Outline the clinical features, treatment, and prevention of Brucellosis
- Culture: Blood, bone marrow
- Serology: Tube agglutination that measures Abs against smooth LPS
  - Non-endemic dz → titres higher than 1:160 + clinical features
  - Endemic dz → titres higher than 1:320 + clinical features
  - Potential cross creacton with IgM of francisella, salmonella urbana, yersinia enterocolita serotype O9, Vibrio cholerae, Alpha cleverlandensis, and some other bacteria
- PCR
- Imaging
  - Spinal radiography: Sacroiliitis, Spondylitis
  - Ultrasonography: Heart
  - Radionuclide scintigraphy
  - CT scan
- Biopsy
- Treatment
  - Monotherapy associated with high relapse rates (40%)
  - Doxycycine with either rifampicin for at least 5 weeks
  - Doxycycline with streptomycin
- Prevention
  - Vaccination, Pasteurization, Changing cultural dietary habit
Briefly describe the transmission of Yersinia pestis
1. Sylvatic (enzootic)phase: in forest infections of rodents, squirrels, rabbits, field rats.
2. Urban plague: transmission of the bacteria among urban rats with the rat flea as the vector. Also domestic cats infected by eating infected rodents. Pets may bring infected fleas into the home
3. Human to human:
a) inhalation- through respiratory droplets of secretions of infected persons b) flea bite- from infected humans with bacilli in their blood to susceptible ones.
What are the laboratory features of Yersinia pestis Specimens: fluid or material aspirated from buboes/ other tissues; sputum, blood
1. Gram stain: GN coccobacilli, demonstrate bipolar staining with Giemsa, Wayons or Methylene Blue
2. Culture:
- Cefsulodin, Irgasan,Novobiacin (CIN) agar– selective for Yersinia and Aeromonas spp. Bull’s eye appearance
- SBA, MacConkey agar: autolyses after 2-3 days on Mac, pink but not a LF. On SBA small transparent colonies that enlarge wit prolonged incubation
1. Biochemical tests: catalase positive. Oxidase, citrate and indole negative
2. Motility test- non motile at 18-22°C
3. Direct immunofluorescence
4. Serological tests: complement fixation + hemagglutination
5. Dipstick Ag: immunochromatography test for buboe aspirates and sputum

Reference Intervals ›

Biochemistry

ACTH	P: <80 ng/L
ALT	P: 5–35 U/L
Albumin	P: 35–50 g/L
Aldosterone	P: 100–500 pmol/L
Alk. phosphatase	P: 30–130 U/L
α-Amylase	P: 0–180 IU/dL
α-Fetoprotein	S: <10 kU/L
Angiotensin II	P: 5–35 pmol/L
ADH	P: 0.9–4.6 pmol/L
AST	P: 5–35 U/L
Bicarbonate	P: 24–30 mmol/L
Bilirubin	P: 3–17 μmol/L
BNP	P: <50 ng/L
CRP	P: <10 mg/L
Calcitonin	P: <0.1 mcg/L
Calcium (ionized)	P: 1.0–1.25 mmol/L
Calcium (total)	P: 2.12–2.60 mmol/L
Chloride	P: 95–105 mmol/L
Cholesterol	P: <5.0 mmol/L
VLDL	P: 0.128–0.645 mmol/L
LDL	P: <2.0 mmol/L
HDL	P: 0.9–1.93 mmol/L
Cortisol AM	P: 450–700 nmol/L
Cortisol Midnight	P: 80–280 nmol/L
CK ♂	P: 25–195 U/L
CK ♀	P: 25–170 U/L
Creatinine	P: 70–100 μmol/L
Ferritin	P: 12–200 mcg/L
Folate	S: 2.1 mcg/L
FSH	P: 2–8 U/L ♂; >25 menopause
GGT ♂	P: 11–51 U/L
GGT ♀	P: 7–33 U/L
Glucose (fasting)	P: 3.5–5.5 mmol/L
Growth hormone	P: <20 mu/L
HbA1C (DCCT)	B: 4–6%
HbA1C (IFCC)	B: 20–42 mmol/mol
Iron ♂	S: 14–31 μmol/L
Iron ♀	S: 11–30 μmol/L
Lactate (venous)	P: 0.6–2.4 mmol/L
Lactate (arterial)	P: 0.6–1.8 mmol/L
LDH	P: 70–250 U/L
LH	P: 3–16 U/L
Magnesium	P: 0.75–1.05 mmol/L
Osmolality	P: 278–305 mosmol/kg
PTH	P: 0.8–8.5 pmol/L
Potassium	P: 3.5–5.3 mmol/L
Prolactin ♂	P: <450 U/L
Prolactin ♀	P: <600 U/L
PSA	P: 0–4 mcg/mL
Protein (total)	P: 60–80 g/L
Red cell folate	B: 0.36–1.44 μmol/L
Renin (erect)	P: 2.8–4.5 pmol/mL/h
Renin (recumbent)	P: 1.1–2.7 pmol/mL/h
Sodium	P: 135–145 mmol/L
TBG	P: 7–17 mg/L
TSH	P: 0.5–4.2 mU/L
T4	P: 70–140 nmol/L
Free T4	P: 9–22 pmol/L
TIBC	S: 54–75 μmol/L
Triglycerides	P: 0.50–2.3 mmol/L
T3	P: 1.2–3.0 nmol/L
Troponin T	P: <0.1 mcg/L
Urate ♂	P: 210–480 μmol/L
Urate ♀	P: 150–390 μmol/L
Urea	P: 2.5–6.7 mmol/L
Vitamin B12	S: 0.13–0.68 nmol/L
Vitamin D	S: 50 nmol/L

Arterial Blood Gases

pH	7.35–7.45
PaCO₂	4.7–6.0 kPa
PaO₂	>10.6 kPa
Base excess	±2 mmol/L

Urine

Cortisol (free)	<280 nmol/24h
Hydroxyindole acetic acid	16–73 μmol/24h
Hydroxymethylmandelic acid	16–48 μmol/24h
Metanephrines	0.03–0.69 μmol/mmol cr.
Osmolality	350–1000 mosmol/kg
17-Oxogenic steroids ♂	28–30 μmol/24h
17-Oxogenic steroids ♀	21–66 μmol/24h
17-Oxosteroids ♂	17–76 μmol/24h
17-Oxosteroids ♀	14–59 μmol/24h
Phosphate (inorganic)	15–50 mmol/24h
Potassium	14–120 mmol/24h
Protein	<150 mg/24h
Protein/creatinine ratio	<3 mg/mmol
Sodium	100–250 mmol/24h

Haematology

WCC	4.0–11.0 ×10⁹/L
RBC ♂	4.5–6.5 ×10¹²/L
RBC ♀	3.9–5.6 ×10¹²/L
Hb ♂	130–180 g/L
Hb ♀	115–160 g/L
PCV ♂	0.4–0.54 L/L
PCV ♀	0.37–0.47 L/L
MCV	76–96 fL
MCH	27–32 pg
MCHC	300–360 g/L
RDW	11.6–14.6%
Neutrophils	2.0–7.5 ×10⁹/L (40–75%)
Lymphocytes	1.0–4.5 ×10⁹/L (20–45%)
Eosinophils	0.04–0.44 ×10⁹/L (1–6%)
Basophils	0–0.10 ×10⁹/L (0–1%)
Monocytes	0.2–0.8 ×10⁹/L (2–10%)
Platelets	150–400 ×10⁹/L
Reticulocytes	0.8–2.0% / 25–100 ×10⁹/L
Prothrombin time	10–14 s
APTT	35–45 s

Paediatric

Pulse Rate (bpm)
Neonate	140–160
Infant <1yr	120–140
1–5 years	110–130
5–12 years	80–120
>12 years	70–100
Respiratory Rate (tachypnoea)
0–2 months	≥60/min
2–12 months	≥50/min
1–5 years	≥40/min
>5 years	≥30/min
Blood Pressure (mmHg)
Term	65/45
1 year	75/50
4 years	85/60
8 years	95/65
10 years	100/70
Weight Formulas
3–12 months	(a + 9)/2 kg
1–6 years	2a + 8 kg
>6 years	(7a − 5)/2 kg
Haemoglobin (g/dL)
Term newborn	13–20
1 month	11–18
2 months	10–15
1–2 years	10–13
>2 years	11–14
MUAC (6 months–5 years)
Obese	>17.5 cm
Normal	13.5–17.4 cm
At risk	12.5–13.4 cm
Moderate malnutrition	11.5–12.4 cm
Severe malnutrition	<11.5 cm
Developmental Milestones
Social smile	1.5 months
Head control	4 months
Sits unsupported	7 months
Crawls	10 months
Stands unsupported	10–12 months
Walks	12–13 months
Talks	18 months
CSF WBC (/mm³)
Term newborn	0–25
>2 weeks	0–5

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