STEPTRACKERIMMUNOLOGY + INFECTIOUS DISEASE | IMMUNODEFICIENCY | HIGH-YIELD REVIEW

Approach to Recurrent Infection

The kind of organism, the site and the age at onset point to the broken arm of immunity before any test is ordered — then a short, ordered workup confirms it.

FOCUS ON
Organism → defect: encapsulated bacteria (sinus, ear, lung) → antibody, early complement, spleen; Neisseria → C5–C9, properdin; viruses, fungi, Pneumocystis, mycobacteria → T cells; S aureus, gram-negatives, Aspergillus abscesses → neutrophils; catalase ⁺ → CGD; disseminated mycobacteria/Salmonella → IL-12/IFN-γ. Timing: first months → T-cell/combined (no maternal help); after 6 months → antibody; any age → complement, phagocyte. Workup: CBC with differential and smear → quantitative IgG/IgA/IgM ± IgE and vaccine titers → lymphocyte subsets (flow) → CH50/AH50 → DHR → HIV test. Always exclude secondary causes first: HIV, malnutrition, steroids/biologics, chemotherapy, diabetes, nephrotic syndrome, asplenia, aging.
INFECTION PATTERN
LIKELY DEFECT
FIRST TESTS
EXAMPLES
Recurrent sinusitis, otitis, pneumonia with encapsulated bacteria
Antibody (B cell)
IgG, IgA, IgM; vaccine titers; B-cell count
XLA, CVID, IgA deficiency
Severe pneumococcal sepsis
Asplenia, C3, antibody, MyD88/IRAK4
Smear (Howell-Jolly), ultrasound, CH50, Ig
Sickle cell, splenectomy
Recurrent Neisseria
Terminal complement, properdin
CH50, AH50
C5–C9 deficiency, eculizumab
Thrush, Pneumocystis, severe viral infections, failure to thrive in infancy
T cells / combined
Lymphocyte count and subsets, TRECs, HIV test
SCID, DiGeorge, HIV
Disseminated mycobacteria, Salmonella
IL-12/IFN-γ axis
Specialized cytokine-pathway tests
IFN-γR, IL-12Rβ1 defects
Skin and organ abscesses, catalase ⁺ organisms, Aspergillus
Neutrophil killing
DHR test
CGD
Infections without pus, high WBC, delayed cord separation
Neutrophil adhesion
CD18 flow
LAD 1
Cold staphylococcal abscesses, eczema, ↑ IgE
Th17 / STAT3
IgE, genetic testing
Hyper-IgE syndrome
Chronic Candida of skin, nails, mouth
Th17 / AIRE
Endocrine screen
CMC, APS-1
Recurrent herpes, severe varicella, CMV
NK cells, T cells
NK count/function
NK deficiency, GATA2
Enteroviral meningoencephalitis, Giardia
Antibody
Ig levels
XLA
Secondary immunodeficiency
Acquired
HIV test, glucose, albumin, medication review
Steroids, chemo, biologics, malnutrition, diabetes, nephrotic syndrome, CLL, myeloma
Warning signs in children
Any primary defect
Refer to immunology
≥ 2 pneumonias/year, need for IV antibiotics, deep abscesses, failure to thrive, family history

Mechanism — timing tells the arm

Birth–3 monthsT-cell/combined defects show early
→
3–6 monthsMaternal IgG still protects
→
After 6 monthsAntibody defects appear

Complement and phagocyte defects can appear at any age; LAD shows at birth with delayed cord separation.

Defect → organism map

DEFECT
BACTERIA
VIRUSES / FUNGI / OTHER
B cell
Encapsulated
Enteroviruses, Giardia
T cell
Intracellular (Listeria, mycobacteria)
CMV, VZV, Candida, Pneumocystis
Neutrophil
S aureus, gram-negatives
Candida, Aspergillus
Complement
Encapsulated, Neisseria
—
Spleen
Encapsulated, Capnocytophaga
Babesia, malaria

How it's tested

COMMON CONFUSIONRecurrent pneumococcal infections can come from antibody, complement or spleen defects — a peripheral smear (Howell-Jolly bodies) quickly flags asplenia.
THE TRAPBefore labeling a primary immunodeficiency in an adult, test for HIV and review drugs — secondary causes are far more common.
YOUR APPROACHOrganism type → site → age at onset → extra-immune clues → ordered tests (CBC → Ig → flow → complement → DHR) → defect.

If you see… think…

Recurrent encapsulated sinopulmonary infections after 6 months → antibody defect
Opportunistic infections in the first months of life → T-cell or combined defect
Repeated meningococcal disease → terminal complement
Liver abscess from S aureus in a child → CGD
Howell-Jolly bodies with pneumococcal sepsis → asplenia
Disseminated NTM in a non-HIV patient → IFN-γ/IL-12 axis (or anti-IFN-γ autoantibodies)
First test when an adult has unusual infections → HIV
Most common primary immunodeficiency → selective IgA deficiency
Most common symptomatic primary antibody defect in adults → CVID
Screening complement test for classical pathway → CH50