Introduction
Immunodeficiency in children refers to a group of disorders in which components of the immune system are absent, defective, or functionally impaired, resulting in increased susceptibility to infections, poor response to treatment, unusual infection patterns, and immune dysregulation. These conditions may be primary (genetic) or secondary (acquired). Early recognition is essential because timely diagnosis and treatment can prevent severe morbidity and mortality, especially in low- and middle-income settings such as Ghana and West Africa, where infectious disease burden is already high.
Classification of Immunodeficiency
Immunodeficiencies are broadly classified as:
Primary Immunodeficiency Disorders (PIDs)
Genetically determined, usually presenting in infancy or early childhood. Over 450 PIDs have been described, grouped into: - Combined immunodeficiencies
(e.g., Severe Combined Immunodeficiency—SCID) - Predominantly antibody deficiencies
(e.g., X-linked agammaglobulinemia, CVID) - Phagocytic defects
(e.g., Chronic Granulomatous Disease) - Complement deficiencies - Immune dysregulation disorders - Innate immune defects
Secondary (Acquired) Immunodeficiency
More common globally, especially in sub-Saharan Africa. Causes include:
- HIV infection (most common)
- Severe malnutrition (major contributor to immunosuppression in children)
- Malignancy
- Immunosuppressive drugs
- Protein-losing enteropathy or nephrotic syndrome
- Chronic renal or liver disease
Epidemiology
True prevalence of PIDs in Ghana and West Africa is unknown due to:
- Limited diagnostic capacity (genetic testing, flow cytometry)
- Misdiagnosis as recurrent infections without further evaluation
- High competing burden of infectious diseases masking underlying immune defects
However, increased awareness has led to rising recognition of conditions like SCID and agammaglobulinemia.
Secondary immunodeficiencies are far more common, particularly due to:
- HIV
- Severe acute malnutrition
- Sickle cell disease
- Tuberculosis
- Chemotherapy-related immunosuppression
Normal Immune Development in Children
Understanding immunodeficiency requires familiarity with the developing immune system:
- Newborns rely on maternal IgG transferred transplacentally.
- Endogenous IgG production rises after 3–6 months.
- IgA and IgM levels are low in infancy, predisposing young children to respiratory and gastrointestinal infections.
- Complement system matures over the first few years of life.
- T-cell immunity is robust at birth but may be impaired by prematurity or congenital defects.
This developmental process explains why certain age groups show characteristic vulnerability patterns.
Clinical Features of Immunodeficiency
Children with immunodeficiency may present with varied symptoms, but several “warning signs” should raise suspicion.
Recurrent Infections
- ≥4 ear infections in one year
- ≥2 serious sinus infections in one year
- ≥2 pneumonias in one year
- Persistent diarrhoea
- Infections with unusual or opportunistic organisms (e.g., Pneumocystis jirovecii)
Severe, Persistent, or Unusual Presentations
- Severe sepsis or meningitis
- Failure to thrive
- Delayed wound healing
- Poor response to standard antibiotics
- Deep-seated infections (liver abscess, osteomyelitis)
- Persistent oral thrush or fungal skin infections
Non-infectious Manifestations
- Autoimmune cytopenias
- Eczema (e.g., Wiskott–Aldrich syndrome)
- Lymphoproliferation
- Chronic diarrhoea ± malabsorption
Common Primary Immunodeficiencies in Children
Severe Combined Immunodeficiency (SCID)
- Absence of T-cell immunity, with or without B/NK cell defects
- Presents in early infancy:
- Recurrent or severe infections
- Persistent diarrhoea
- Failure to thrive
- Fatal without immune reconstitution (HSCT)
X-linked Agammaglobulinemia (XLA)
- Mutation in BTK gene → absent B cells
- Recurrent respiratory infections starting after 6 months
- Low IgG, IgA, and IgM
Common Variable Immune Deficiency (CVID)
- Later childhood onset
- Low IgG and IgA, recurrent sinopulmonary infections
- Risk of autoimmunity
Chronic Granulomatous Disease (CGD)
- Phagocytic defect due to NADPH oxidase deficiency
- Recurrent abscesses, lymphadenitis, osteomyelitis
- Catalase-positive organisms (e.g., Staph aureus)
Complement Deficiencies
- Recurrent meningococcal or pneumococcal infections
- Terminal complement defects → Neisseria infections
Secondary Immunodeficiency: Context of Ghana and West Africa
HIV Infection
- Most common cause of immunodeficiency in children
- Presents with:
- Opportunistic infections
- Failure to thrive
- Lymphadenopathy
- Chronic diarrhoea
- Diagnosis via PCR in infants and serology after 18 months
Severe Acute Malnutrition (SAM)
- Suppresses both innate and adaptive immunity
- Increased risk of pneumonia, sepsis, skin infections
- Restoring nutrition is essential for immune recovery
Sickle Cell Disease (SCD)
- Functional asplenia → susceptibility to encapsulated organisms (e.g., Strep pneumoniae, H. influenzae)
- Need for routine prophylaxis
Tuberculosis and Chronic Diseases
- TB leads to chronic immune exhaustion
- Renal and liver failure also impact immunity
Investigations
Evaluation depends on the suspected type of immunodeficiency.
First-line Tests (available in many Ghanaian hospitals)
- Complete blood count with differential
- ESR/CRP
- HIV test
- Blood film for parasites (if indicated)
- Chest X-ray
- Serum immunoglobulin levels (IgG, IgA, IgM)
- Culture studies for recurrent infections
Second-line Tests (limited availability)
- Lymphocyte subset analysis (CD3, CD4, CD8, CD19, NK cells)
- Specific antibody titers (response to vaccines)
- Complement levels (CH50, C3, C4)
- Neutrophil oxidative burst test (for CGD)
- Genetic testing (send-out)
In many West African settings, diagnosis is often clinical plus basic laboratory support due to cost and availability constraints.
Management
Treat Acute Infections Promptly
- Early, aggressive antibiotics for bacterial infections
- Antifungals or antivirals as needed
Long-term Management Strategies
Immunoglobulin replacement therapy
For antibody deficiencies (XLA, CVID)
Prophylactic antibiotics
e.g., Cotrimoxazole prophylaxis for HIV-exposed/infected infants or SCID
Stem cell transplantation
Curative option for SCID and some PIDs (availability limited in West Africa)
Nutritional rehabilitation
Essential for children with SAM
Vaccination considerations
- Avoid live vaccines in severe T-cell immunodeficiency
- Prioritize pneumococcal, Hib, and meningococcal vaccines
- Ensure annual influenza vaccination where available
Family Screening
- Important for hereditary conditions
- Genetic counselling (where available)
Complications
- Recurrent lung infections → bronchiectasis
- Growth failure
- Chronic diarrhoea and malabsorption
- Autoimmune diseases
- Increased risk of lymphoma (e.g., CVID)
Prognosis
Varies widely:
- Early diagnosis → excellent outcomes in many PIDs
- Delayed diagnosis → high morbidity, irreversible organ damage
- Secondary immunodeficiency often improves with treatment of underlying cause (e.g., nutritional recovery, ART in HIV)
Resource constraints in West Africa impact prognosis, making early suspicion vital.
Summary
Immunodeficiency in children represents a spectrum of disorders that increase susceptibility to infections and immune dysregulation. Primary immunodeficiencies, though less common, are serious and often present early. Secondary causes, notably HIV and malnutrition, are far more prevalent in Ghana and West Africa. Early diagnosis through careful clinical assessment, basic laboratory tests, and timely management—including prompt treatment of infections, immunoglobulin replacement where indicated, and supportive care—is essential to improving outcomes.
Further Reading
- Nelson Textbook of Paediatrics – Immunodeficiency Chapters
- WHO Guidelines on HIV and Paediatric Care
- Jeffrey Modell Foundation: Warning Signs of Primary Immunodeficiency
- African Society for Immunodeficiencies (ASID) Resources