Brucellosis in Children
Introduction to Brucellosis in Children
Brucellosis is a zoonotic infection caused by bacteria of the genus Brucella. It is one of the most common zoonotic infections worldwide, with a significant impact on both animal and human health. In children, brucellosis can present unique challenges due to its nonspecific symptoms and potential for complications.
The disease is also known as "undulant fever," "Malta fever," or "Mediterranean fever," reflecting its historical prevalence in certain regions. However, it is now recognized as a global health concern, particularly in developing countries where animal husbandry practices and consumption of unpasteurized dairy products are common.
Understanding brucellosis in pediatric populations is crucial for healthcare providers, as early diagnosis and appropriate treatment can significantly improve outcomes and prevent chronic complications.
Etiology of Brucellosis
Brucellosis is caused by gram-negative coccobacilli belonging to the genus Brucella. The most common species affecting humans are:
- B. melitensis: Primarily associated with goats and sheep
- B. abortus: Mainly found in cattle
- B. suis: Primarily affects pigs
- B. canis: Associated with dogs
In children, B. melitensis is the most frequently isolated species, often due to the consumption of unpasteurized dairy products from infected goats or sheep. The bacteria are facultative intracellular pathogens, capable of surviving and replicating within host cells, particularly macrophages.
Transmission to children typically occurs through:
- Ingestion of contaminated animal products (especially unpasteurized milk and dairy)
- Direct contact with infected animals or their tissues
- Inhalation of contaminated aerosols (less common)
- Vertical transmission from mother to fetus (rare)
Epidemiology of Brucellosis in Children
Brucellosis is considered one of the most widespread zoonoses globally, with more than 500,000 new cases reported annually. The epidemiology of brucellosis in children closely follows that of adults, with some notable differences:
- Geographic Distribution: Endemic in the Mediterranean basin, Middle East, Central and South America, and parts of Asia and Africa. Sporadic cases occur worldwide due to travel and importation of animal products.
- Age Distribution: While it can affect all ages, studies show a bimodal distribution with peaks in children aged 5-14 years and adults aged 25-64 years.
- Gender: In endemic areas, male children may be more affected due to increased exposure through agricultural activities.
- Seasonality: Often shows a peak incidence in spring and summer, coinciding with animal breeding seasons and increased production of dairy products.
- Risk Factors in Children:
- Living in rural or farming communities
- Consumption of unpasteurized dairy products
- Participation in animal husbandry activities
- Living in households with infected family members
In many endemic regions, children account for 20-30% of all brucellosis cases, highlighting the importance of considering this diagnosis in pediatric populations from or traveling to high-risk areas.
Pathophysiology of Brucellosis
The pathophysiology of brucellosis in children is similar to that in adults, but the developing immune system of children can influence the course and manifestations of the disease.
- Entry and Dissemination:
- Brucella organisms enter the body through mucous membranes or abraded skin.
- They are phagocytosed by macrophages and transported to regional lymph nodes.
- Bacteria survive intracellularly by inhibiting phagosome-lysosome fusion.
- Systemic Spread:
- Organisms disseminate hematogenously to various organs, particularly those rich in reticuloendothelial cells (liver, spleen, bone marrow).
- Formation of granulomas in affected tissues is a hallmark of the disease.
- Immune Response:
- Cell-mediated immunity plays a crucial role in controlling the infection.
- T-lymphocytes activate macrophages to kill intracellular bacteria.
- Humoral immunity produces antibodies, but their protective role is limited.
- Chronic Infection:
- Persistence of bacteria within macrophages can lead to chronic or relapsing infection.
- Chronic granulomatous inflammation can cause tissue damage in various organs.
In children, the developing immune system may result in a more rapid progression of the disease or atypical presentations. The ability of Brucella to evade host immune responses contributes to the chronic nature of the infection and the potential for relapses, which can be particularly challenging in pediatric patients.
Clinical Manifestations of Brucellosis in Children
The clinical presentation of brucellosis in children can be highly variable, ranging from asymptomatic infections to severe, multisystem disease. The incubation period is typically 2-4 weeks but can range from 1 week to several months.
General Symptoms
- Fever: Often undulant or intermittent
- Fatigue and malaise
- Sweating, especially at night
- Weight loss and anorexia
- Headache
- Myalgia and arthralgia
Organ-Specific Manifestations
- Musculoskeletal:
- Arthritis (monoarticular or polyarticular)
- Sacroiliitis
- Osteomyelitis
- Spondylitis (rare in children)
- Gastrointestinal:
- Hepatomegaly and splenomegaly
- Abdominal pain
- Nausea and vomiting
- Diarrhea
- Hematological:
- Anemia
- Leukopenia or leukocytosis
- Thrombocytopenia
- Neurological:
- Meningitis or meningoencephalitis
- Brain abscess (rare)
- Peripheral neuropathy
- Cardiovascular:
- Endocarditis (rare in children but serious)
- Myocarditis
- Genitourinary:
- Orchitis or epididymo-orchitis in adolescent males
- Pyelonephritis
- Respiratory:
- Bronchitis
- Pneumonia
- Pleural effusion
- Cutaneous:
- Rashes (maculopapular, petechial, or purpuric)
- Erythema nodosum
Special Considerations in Children
- Children may present with more acute and febrile forms of the disease compared to adults.
- Monoarthritis of large joints (hip, knee) is more common in children than in adults.
- Neurological complications, though rare, can be more severe in children.
- The clinical picture can be nonspecific, leading to delays in diagnosis.
The chronic form of brucellosis, defined as symptoms persisting for more than 12 months, is less common in children compared to adults but can occur, especially if the initial infection is not adequately treated.
Diagnosis of Brucellosis in Children
Diagnosing brucellosis in children can be challenging due to the nonspecific nature of symptoms and the variable clinical presentation. A combination of clinical suspicion, epidemiological history, and laboratory tests is crucial for accurate diagnosis.
Clinical Suspicion
- Consider brucellosis in children with:
- Prolonged fever of unknown origin
- Relevant epidemiological history (travel, animal contact, consumption of unpasteurized dairy)
- Musculoskeletal complaints
- Hepatosplenomegaly
Laboratory Diagnosis
- Blood Culture:
- Gold standard for diagnosis
- Sensitivity varies (15-70%) depending on disease stage and prior antibiotic use
- May require prolonged incubation (up to 30 days)
- Automated blood culture systems have improved detection rates
- Serology:
- Rose Bengal Test (RBT): Rapid screening test
- Standard Tube Agglutination Test (SAT): Titer ≥1:160 is considered positive in endemic areas
- ELISA: More sensitive and specific, especially for detecting IgM and IgG antibodies
- Coombs' test: Useful for detecting incomplete antibodies in chronic cases
- Molecular Techniques:
- PCR: High sensitivity and specificity, especially useful in early stages or culture-negative cases
- Can be performed on blood, synovial fluid, or tissue samples
- Other Laboratory Findings:
- Complete Blood Count: May show anemia, leukopenia, or thrombocytopenia
- Liver Function Tests: Elevated transaminases are common
- Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP): Usually elevated
Imaging Studies
- Ultrasonography: Useful for evaluating hepatosplenomegaly or abscesses
- X-rays: For assessing bone and joint involvement
- MRI or CT: May be necessary for evaluating complex osteoarticular or neurobrucellosis cases
Diagnostic Challenges in Children
- Lower sensitivity of serological tests in early stages of infection
- Difficulty in obtaining adequate blood volume for cultures in young children
- Nonspecific symptoms mimicking other common childhood illnesses
- Need for age-appropriate reference ranges for serological tests
A definitive diagnosis of brucellosis requires either isolation of Brucella spp. from clinical specimens or a combination of compatible clinical presentation with positive serological tests. In children, a high index of suspicion and thorough evaluation are crucial for timely diagnosis and appropriate management.
Treatment of Brucellosis in Children
The treatment of brucellosis in children aims to control symptoms, prevent complications, and reduce the risk of relapse. The approach involves combination antibiotic therapy for an extended period.
General Principles
- Combination therapy is essential to prevent relapses
- Duration of treatment depends on disease severity and complications
- Close monitoring for side effects and treatment adherence is crucial
Antibiotic Regimens
- Uncomplicated Brucellosis in Children ≥8 years:
- Doxycycline (2-4 mg/kg/day in two divided doses, max 200 mg/day) for 6 weeks
- PLUS
- Gentamicin (5-7 mg/kg/day IM or IV) for the first 5-7 days
- OR
- Rifampin (15-20 mg/kg/day, max 600-900 mg/day) for 6 weeks
- Children <8 years or when tetracyclines are contraindicated:
- Trimethoprim-sulfamethoxazole (TMP-SMX) (TMP 6-8 mg/kg/day, SMX 30-40 mg/kg/day in two divided doses) for 6 weeks
- PLUS
- Rifampin (15-20 mg/kg/day, max 600-900 mg/day) for 6 weeks
- Alternative Regimens:
- Ciprofloxacin (20-30 mg/kg/day in two divided doses, max 1.5 g/day) can be used in combination with rifampin in adolescents
- Azithromycin has shown promise in some studies but is not a first-line option
Treatment of Complicated Brucellosis
- Neurobrucellosis:
- Triple therapy with doxycycline, rifampin, and ceftriaxone or TMP-SMX
- Treatment duration: 3-6 months or longer, based on clinical and CSF response
- Endocarditis:
- Combination of doxycycline, rifampin, and gentamicin
- Duration: At least 6 weeks, often longer
- Surgical intervention may be necessary
- Osteoarticular Involvement:
- Standard regimens for 8-12 weeks
- Surgical drainage may be required for abscesses or septic arthritis
Monitoring and Follow-up
- Regular clinical assessment during treatment
- Monitor for adverse effects of antibiotics
- Follow-up blood tests, including complete blood count and liver function tests
- Serological tests may be used to monitor response, but titers can remain positive for months
- Long-term follow-up (6-12 months) to detect relapses
Special Considerations in Pediatric Treatment
- Adjust dosages based on weight and age
- Consider palatability and formulation of medications to ensure compliance
- Educate parents and children about the importance of completing the full course of antibiotics
- Be aware of potential long-term effects of certain antibiotics (e.g., tetracycline dental staining in young children)
Treatment success depends on early diagnosis, appropriate antibiotic selection, and adherence to the prolonged treatment regimen. Relapses can occur in 5-15% of cases, often due to inadequate treatment duration or poor compliance. In such cases, re-treatment with a different antibiotic combination may be necessary.
Prevention of Brucellosis in Children
Preventing brucellosis in children involves a combination of public health measures, education, and personal precautions, especially in endemic areas.
Public Health Measures
- Animal vaccination programs to control brucellosis in livestock
- Regular testing and culling of infected animals
- Strict regulations on the production and sale of dairy products
- Implementation of pasteurization processes for milk and dairy products
Personal and Family Precautions
- Avoid consumption of unpasteurized dairy products, including milk, cheese, and ice cream
- Practice proper hygiene when handling animals, especially during birthing or butchering
- Wear protective clothing (gloves, masks) when working with potentially infected animals or their products
- Proper cooking of meat, especially in endemic areas
Education and Awareness
- Educate children, parents, and communities about the risks of brucellosis and modes of transmission
- Promote awareness in schools, especially in rural and agricultural communities
- Train healthcare providers to recognize and promptly diagnose brucellosis in children
Occupational Safety
- Implement safety measures in high-risk occupations (e.g., farmers, veterinarians, abattoir workers)
- Provide appropriate personal protective equipment in occupational settings
- Regular health check-ups for individuals in high-risk occupations
Travel Precautions
- Advise families traveling to endemic areas about the risks of brucellosis
- Recommend avoiding consumption of unpasteurized dairy products during travel
- Consider post-travel screening for children with prolonged febrile illness after visiting endemic regions
Vaccination
- Currently, no human vaccine is available for widespread use
- Research is ongoing for the development of safe and effective human vaccines
Prevention strategies should be tailored to the local epidemiology and cultural practices. In endemic areas, a multisectoral approach involving public health, veterinary services, and education sectors is crucial for effective brucellosis control and prevention in pediatric populations.
Prognosis of Brucellosis in Children
The prognosis of brucellosis in children is generally favorable with appropriate and timely treatment. However, several factors can influence the outcome.
Factors Affecting Prognosis
- Early diagnosis and initiation of treatment
- Adherence to the full course of antibiotic therapy
- Presence of complications or focal disease
- Age of the child (younger children may have more severe disease)
- Underlying health conditions
- Brucella species involved (B. melitensis tends to cause more severe disease)
Outcomes
- Uncomplicated Cases:
- Most children with uncomplicated brucellosis recover completely with appropriate treatment
- Symptoms typically improve within 3-7 days of starting antibiotics
- Full recovery is expected within 6-12 weeks
- Complicated Cases:
- Recovery may be prolonged in cases with focal complications
- Neurobrucellosis can lead to long-term neurological sequelae in some cases
- Osteoarticular involvement may require extended treatment and rehabilitation
- Relapses:
- Occur in approximately 5-15% of treated cases
- Most relapses happen within 6 months of completing treatment
- Usually respond well to re-treatment with a different antibiotic combination
- Mortality:
- Mortality is rare in children with access to appropriate medical care
- Endocarditis, although rare, carries the highest mortality risk
Long-term Follow-up
- Regular follow-up for at least 6-12 months after treatment completion
- Monitor for signs of relapse or persistent symptoms
- Assess for potential long-term complications, especially in cases of neurobrucellosis or osteoarticular involvement
- Provide support for children who may have missed school or experienced developmental delays due to prolonged illness
Quality of Life
- Most children return to normal activities and school performance after recovery
- Some may experience fatigue or nonspecific symptoms for several months
- Psychological support may be beneficial, especially for children with prolonged or complicated disease courses
Overall, with proper diagnosis and treatment, the majority of children with brucellosis have an excellent prognosis. However, the potential for relapses and the risk of complications underscore the importance of complete treatment, careful follow-up, and ongoing awareness of the disease in endemic areas.
Brucellosis in Children
- Question: What is the causative agent of brucellosis? Answer: Bacteria of the genus Brucella, primarily B. melitensis, B. abortus, and B. suis
- Question: Which age group of children is most commonly affected by brucellosis? Answer: School-aged children and adolescents
- Question: What is the primary mode of transmission of brucellosis to children? Answer: Consumption of unpasteurized dairy products from infected animals
- Question: Which of the following is NOT a common symptom of brucellosis in children? Answer: Skin rash
- Question: What is the gold standard diagnostic test for brucellosis? Answer: Blood culture
- Question: Which antibiotic combination is commonly used to treat brucellosis in children? Answer: Doxycycline and rifampin
- Question: What is the typical duration of antibiotic treatment for uncomplicated brucellosis in children? Answer: 6 weeks
- Question: Which organ system is most commonly affected in focal brucellosis in children? Answer: Musculoskeletal system
- Question: What is the most frequent complication of brucellosis in children? Answer: Arthritis
- Question: Which laboratory finding is characteristic of brucellosis? Answer: Relative lymphocytosis
- Question: What is the incubation period for brucellosis? Answer: 1 to 3 weeks, but can range from 5 days to several months
- Question: Which of the following professions puts children at higher risk for brucellosis? Answer: Children of livestock farmers or veterinarians
- Question: What is the common name for brucellosis? Answer: Undulant fever or Malta fever
- Question: Which imaging modality is most useful in diagnosing osteoarticular complications of brucellosis? Answer: Magnetic Resonance Imaging (MRI)
- Question: What is the mortality rate of brucellosis in children with proper treatment? Answer: Less than 1%
- Question: Which of the following is NOT a typical feature of brucellosis in children? Answer: Rapid onset of symptoms
- Question: What is the most common cause of treatment failure in pediatric brucellosis? Answer: Poor compliance with the long-term antibiotic regimen
- Question: Which serological test is commonly used for initial screening of brucellosis? Answer: Rose Bengal test
- Question: What is the recommended antibiotic for treating brucellosis in children under 8 years old? Answer: Trimethoprim-sulfamethoxazole
- Question: Which of the following is a potential long-term complication of brucellosis in children? Answer: Chronic fatigue syndrome
- Question: What is the typical pattern of fever in brucellosis? Answer: Undulant or intermittent fever
- Question: Which laboratory test can help differentiate acute from chronic brucellosis? Answer: IgM and IgG antibody titers
- Question: What is the most common site of focal infection in neurobrucellosis? Answer: Meninges
- Question: Which of the following is NOT a typical symptom of brucellosis in infants? Answer: Productive cough
- Question: What is the primary preventive measure against brucellosis in children? Answer: Pasteurization of milk and dairy products
- Question: Which Brucella species is most commonly associated with human infections worldwide? Answer: Brucella melitensis
- Question: What is the recommended duration of follow-up for children treated for brucellosis? Answer: At least 6 months after completion of treatment
- Question: Which of the following is a potential ocular complication of brucellosis in children? Answer: Uveitis
- Question: What is the most common hematological finding in children with brucellosis? Answer: Anemia
- Question: Which vaccine is available for preventing brucellosis in children? Answer: There is no licensed vaccine for human use
