Typhoid Fever and Septicaemia

Septicaemias and Typhoid Fever

• Definition of Septicaemia: Presence or multiplication of bacteria with/without toxins in the blood stream, leading to clinical manifestations – systemic illness.
• Bacteraemia: Presence of bacteria in the blood stream without clinical manifestations, usually transient.
• Typhoid Fever (TF): Acute febrile systemic illness caused by Salmonella enterica serotype typhi, formerly known as Salmonella typhi.

Aetiological Agent of Typhoid Fever

• Salmonella typhi: A Gram-negative bacillus, member of the family Enterobacteriaceae.
• Properties: Motile, produces hydrogen sulphide (H2S), making colonies black.

Mode of Transmission of Typhoid Fever

• Oral transmission: Via food or beverages handled by an often asymptomatic carrier, shedding bacteria through stool or urine.
• Hand-to-mouth transmission: After using a contaminated toilet and neglecting hand hygiene.
• Oral transmission: Via sewage-contaminated water or shellfish.

Epidemiology of Typhoid Fever

• Disease of the poor: Associated with poor environmental sanitation, poor water supply, poor personal hygiene, and poor waste disposal.
• Common in rural areas and urban slums: High prevalence in under-developed/developing countries of Africa and Asia.
• More common in children and young adults: Than in older patients.

Pathogenesis of Typhoid Fever

• Faeco-oral route: Ingestion of contaminated food or water, survival of bacteria in the stomach, and multiplication in the small intestine (terminal ileum).
• Infection of Peyer's patches: Adherence of S. typhi to epithelium, induction of macrophages, and subsequent multiplication in the lymphatic system.
• Bacteraemia and systemic infection: Breaking out into the bloodstream, infecting the rest of the body, and inducing clinical manifestations.

Clinical Manifestations of Typhoid Fever

• Incubation period: 3-30 days, depending on inoculum size and host defense.
• Classical onset: Daily remittent fever pattern, with temperature variation, chills, headache, and malaise.
• Intestinal manifestations: Constipation, diarrhoea, and abdominal tenderness.
• Fever: Prolonged and persistent in untreated patients.

Laboratory Diagnosis of Typhoid Fever

• Gold standard: Isolation of the organism in pure culture from clinical specimens.
• Microbiological tests: Blood culture, urine culture, and stool culture.
• Widal test: An agglutination reaction, detecting antibodies against S. typhi.

Treatment and Prevention of Typhoid Fever

• Supportive treatment: Rehydration, correction of electrolytes imbalance, and nutrition.
• Definitive treatment: Antimicrobial therapy, using 3rd and 4th generation cephalosporins or fluoroquinolones.
• Prevention and control: Based on WASH strategy, including provision of potable water, sanitation, and personal hygiene.

Mycobacterial Infections

• Definition: Infections caused by pathogenic mycobacterial species.
• Classification: Divided into two categories: obligate and opportunistic mycobacterial species.
• Obligate mycobacterial species: Always cause disease, e.g., M. tuberculosis, M. leprae, and M. ulcerans.
• Opportunistic mycobacterial species: Cause disease when immunity is low, e.g., M. kansasii, M. simiae, and M. avium complex.

Characteristics of Mycobacterial Species

• Acid-fastness: Retain the color of the initial stain when stained with Zeihl-Neelsen reagents.
• Growth rate: Slow-growing, requiring long periods of incubation.
• Temperature of growth: Grow best at 35-37°C.
• Pigment production: Divided into three classes: scotochromogen, photochromogen, and non-chromogen.

Tuberculosis (TB)

• Definition: Chronic inflammatory granulomatous infection with central area of caseation necrosis.
• Aetiology: Caused by Mycobacterium tuberculosis complex (MTBC), including M. tuberculosis, M. bovis, and M. africanum.
• Epidemiology and burden: TB is a major public health problem, closely related to poverty, overcrowding, and malnutrition.

Pathogenesis of TB

• Primary infection: Inhalation of infected droplets, affecting the apical portion of the lungs.
• Ghon focus: Formation of chronic inflammatory granulomatous lesions.
• Latency and reactivation: Healing of primary infection, followed by reactivation of latency phase to active TB lesion.

Manifestations of TB

• Pulmonary TB: Fever, weight loss, chronic cough, haemoptysis, night sweats, and finger clubbing.
• Extra-pulmonary forms: TB meningitis, renal TB, disseminated TB, etc.

Management of TB

• DOTS strategy: Directly observed treatment, short course, using a combination of antibiotics.

Laboratory Diagnosis of TB

• Smear microscopy: Acid-fast staining, using Ziehl-Neelsen or auramine staining.
• Culture: Isolation of the organism from clinical specimens, using solid or liquid media.
• Growth-based detection: Using automated BACTEC MGIT 960 TB system.
• Line probe assay (LPA): Rapid detection of MTBC and drug resistance.
• Gene Xpert/Rif: Point of care diagnostic tool.### TB Diagnosis and Treatment
• PCR-based machine used for rapid diagnosis of TB, especially in HIV co-infected patients
• Detects rifampicin resistance, which is an indicator of MDR-TB in about 90% of cases
• DOTS (Directly Observed Treatment, Short-course) centers and ART clinics must collaborate
• Treatment divided into two phases:
  • Initial phase: combination therapy for 2 months based on DOTS (Isoniazid, Rifampicin, Ethambutol, Pyrazinamide) to render patient non-infectious
  • Continuation phase: use of Isoniazid and Rifampicin for additional 6 months to kill remnant bacilli and prevent relapse or development of resistant strains

Complications of TB

• Development of resistant strains: MDR-TB, XDR-TB, and TDR-TB
  • MDR-TB: resistant to Isoniazid and Rifampicin
  • XDR-TB: resistant to MDR-TB and second-line drugs, quinolone, and injectable antibiotics
  • TDR-TB: resistant to all known anti-TB drugs
• Miliary TB

Prevention and Control of TB

• Good and well-ventilated housing
• Well-balanced nutrition
• Immunization at birth with BCG (Bacille Calmette-Guérin)
• Adequate treatment of infectious cases

Leprosy

• Chronic infectious disease caused by Mycobacterium leprae
• Mainly affects skin, peripheral nerves, mucosa of the upper respiratory tract, and eyes
• Two forms: Tuberculoid leprosy and Lepromatous leprosy
• Transmitted via droplets from the nose and mouth during close and frequent contacts with untreated cases

Pathology of Leprosy

• Two extremes of cases: Tuberculoid leprosy (good cell-mediated immunity, few bacterial loads, and unaffected nerves) and Lepromatous leprosy (low cell-mediated immunity, heavy bacterial load, and affected nerves)

Diagnosis of Leprosy

• Diagnosis made clinically, although laboratory testing can be important in some cases
• Health workers trained to diagnose leprosy based on finding at least one of three cardinal signs:
  • One or more hypo-pigmented, anaesthetic skin patches
  • One or more thickened peripheral nerves
  • A positive skin smear
• Most accurate way to diagnose leprosy is tissue biopsy
• Development of new diagnostic tests for leprosy is a global research priority

Treatment of Leprosy

• A blend of drugs known as Multi-Drug Therapy (MDT) is effective in killing all known strains of leprosy bacteria
• MDT given to patients for 6 months to 2 years, depending on the severity and progression of the disease

Buruli Ulcer

• Caused by Mycobacterium ulcerans
• Presents as ulcers at the extremities, especially feet
• Mainly seen in areas with poor environmental sanitation

Streptococci

• Gram-positive spherical bacteria that form pairs or chains during growth
• Catalase negative, non-sporing, non-motile, and facultative anaerobes
• Complex nutritional requirements (blood or serum enriched media)

Classifications of Streptococci

• Alpha-hemolytic (incomplete lysis of RBCs with reduction of Hb and formation of green pigment around bacterial growth)
• Beta-hemolytic (complete disruption of RBCs with clearing of blood around bacterial growth)
• Non-hemolytic (some are non-hemolytic)

Streptococcus pyogenes

• Consists of Lancefield group A Streptococci
• Associated with infections in man and causes a wide range of suppurative infections in the respiratory tract, skin, and life-threatening soft tissue infections
• Associated with non-suppurative sequelae due to adverse immunological reactions

Virulence Factors of Streptococcus pyogenes

• Adhesion: interactions with F-proteins and fibronectin of the host tissue mediate adherence and internalization of the bacteria
• M Protein: appears as hair-like projections of the streptococcal cell wall, anti-phagocytic, and immunogenic
• Capsules: some strains form a capsule composed of hyaluronic acid
• Toxins and enzymes: streptokinase, deoxyribonucleases, hyaluronidase, and streptococcal pyrogenic exotoxins (SPEs)

Pathogenic Pathways of Streptococcus pyogenes

• The organism enters via the respiratory tract and/or skin breach
• Non-invasive infections: pharyngitis, scarlet fever, and skin infections
• Invasive soft tissue infections: necrotizing fasciitis, streptococcal toxic shock syndrome, and bacteremia
• Non-suppurative sequelae: rheumatic fever and acute glomerulonephritis

Laboratory Diagnosis of Streptococcus pyogenes

• Specimens collection: sputum, CSF, blood, synovial fluid, and laryngeal swab
• Gram stain: gram-positive cocci in chains
• Culture on standard laboratory media: growth is inhibited by bacitracin
• Pharyngitis: rapid antigen detection test (RADT) is specific for Streptococcus pyogenes and immunologically detects group A carbohydrate antigen

Identification of Streptococcus pyogenes

• Catalase test: Streptococcus pyogenes is catalase negative
• Bacitracin sensitivity test: Streptococcus pyogenes is sensitive to bacitracin

Treatment of Streptococcus pyogenes

• Penicillin G, Penicillin V, and Penicillinase-resistant penicillin
• Following rheumatic fever: patients are placed on continuous prophylactic antibiotics to prevent repeat strep throat infection
• For invasive S.pyogenes infections: consider adding Clindamycin

Other Streptococci

• Streptococcus agalactiae (Group B): β-hemolytic, and part of normal vaginal flora and lower GIT in 5-30% of women
• Streptococcus C and G: share some virulence properties with Streptococcus pyogenes
• Enterococci: group D Streptococci, normal colonists of human large intestine, and cause opportunistic urinary, wound, and skin infections
• Viridans Group: large complex group, normal residents of the gums and teeth, oral cavity, and also found in nasopharynx, genital tract, and skin### Bacitracin Disk Test
• Inoculate Blood Agar Plate (BAP) with a heavy suspension of the tested organism
• Apply a Bacitracin disk (0.04 U) to the inoculated BAP
• The presence of a zone of inhibition around the disk indicates susceptibility to Bacitracin

CAMP Test

• Group B streptococci (S.agalactiae) produce an extracellular protein called CAMP factor
• CAMP factor acts synergistically with staphylococcal β-lysin to cause lysis of Red Blood Cells (RBCs)
• The test involves streaking the Streptococcus to be tested and Staphylococcus aureus perpendicular to each other, with a 3-5 mm distance between the two streaks
• A positive result appears as an arrowhead-shaped zone of complete hemolysis
• S.agalactiae is CAMP test positive, while non-group B streptococci are negative

Optochin Susceptibility Test

• The Optochin (OP) test is a presumptive test used to identify Streptococcus pneumoniae (S.pneumoniae)
• S.pneumoniae is inhibited by the Optochin reagent