CHAPTER I 1. Introduction Haemophilus influenzae is a cause of bacterial infections that are often severe, particularly among infants.

It was first described by Pfeiffer in 1892. During an outbreak of influenza he found the bacteria in sputum of patients and proposed a causal association between this bacterium and the clinical syndrome known as influenza. The organism was given the name Haemophilus by Winslow, et al. in 1920. It was not until 1933 that Smith, et al. established that influenza was caused by a virus and that H. influenzae was a cause of secondary infection.In the 1930s, Margaret Pittman demonstrated that H. influenzae could be isolated in encapsulated and unencapsulated forms. She identified six capsular types (af), and observed that virtually all isolates from cerebrospinal fluid (CSF) and blood were of the capsular type b. Before the introduction of effective vaccines, H. influenzaetype b (Hib) was the leading cause of bacterial meningitis and other invasive bacterial disease among children younger than 5 years of age; approximately one in 200 children in this age group developed invasive Hib disease. Nearly all Hib infections occurred among children younger than 5 years of age, and approximately two-thirds of all cases occurred among children younger than 18 months of age.

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CHAPTER II 1. Haemophilus influenzae Haemophilus influenzae is a gram-negative coccobacillus. It is generally aerobic but can grow as a facultative anaerobe. In vitro growth requires accessory growth factors, including X factor (hemin) and V factor (nicotinamide adenine dinucleotide [NAD]).Chocolate agar media are used for isolation. H. influenzaewill generally not grow on blood agar, which lacks NAD.The outermost structure of H. influenzae is composed of polyribosyl-ribitolphosphate (PRP), a polysaccharide that is responsible for virulence and immunity. Six antigenically and biochemically distinct capsular polysaccharide serotypes have been described; these are designated types a through f. In the prevaccine era, type b organisms accounted for 95% of all strains that caused invasive disease. 2. Pathogenesis The organism enters the body through the nasopharynx. Organisms colonize the nasopharynx and may remain only transiently or for several months in the absence of symptoms (asymptomatic carrier). In the prevaccine era, Hib could be 88isolated from the nasopharynx of 0.5%3% of normal infants and children but was not common in adults. Nontypeable (unencapsulated) strains are also frequent inhabitants of the human respiratory tract.In some persons, the organism causes an invasive infection. The exact mode of invasion to the bloodstream is unknown. Antecedent viral or mycoplasma infection of the upper respiratory tract may be a contributing factor. The bacteria spread in the bloodstream to distant sites in the body. Meninges are especially likely to be affected.The most striking feature of Hib disease is age-dependent susceptibility. Hib disease is not common beyond 5 years of age. Passive protection of some infants is provided by transplacentally acquired maternal IgG antibodies and breastfeeding during the first 6 months of life. In the prevaccine era peak attack rates occurred at 67 months of age, declining thereafter. The presumed reason for this age distribution is the acquisition of immunity to Hib with increasing age.Antibodies to Hib capsular polysaccharide are protective. The precise level of antibody required for protection against invasive disease is not clearly established. However, a titer of 1 g/mL 3 weeks post vaccination correlated with protection in studies following vaccination with

unconjugatedpurifiedpolyribosyl-ribitol-phosphate (PRP) vaccine and suggested long-term protection from invasive disease.Acquisition of both anticapsular and serum bactericidal antibody is inversely related to the age-specific incidence of Hib disease.In the prevaccine
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era, most children acquired immunity by 56 years of age through asymptomatic infection by Hib bacteria. Since only a relatively small proportion of children carry Hib at any time, it has been postulated that exposure to organisms that share common antigenic structures with the capsule of Hib (so-called cross-reacting organisms) may also stimulate the development of anticapsular antibodies against Hib. Natural exposure to Hib also induces antibodies to outer membrane proteins, lipopolysaccharides, and other antigens on the surface of the bacterium.The genetic constitution of the host may also be important in susceptibility to infection with Hib. Risk for Hib disease has been associated with a number of genetic markers, but the mechanism of these associations is unknown. No single genetic relationship regulating susceptibility or immune responses to polysaccharide antigens has yet been convincingly demonstrated. 3. Clinical Features Invasive disease caused by H. influenzae type b can affect many organ systems. The most common types of invasive disease are meningitis, epiglottitis, pneumonia, arthritis, and cellulitis.Meningitis is infection of the membranes covering the brain and is the most common clinical manifestation of invasive Hib disease, accounting for 50%65% of cases in the prevaccine era. Hallmarks of Hib meningitis are fever, decreased mental status, and stiff neck (these symptoms also occur with meningitis caused by other bacteria). Hearing impairment or other neurologic sequelae occur in 15%30% of survivors. The case-fatality rate is 2%5%, despite appropriate antimicrobial therapy.Epiglottitis is an infection and swelling of the epiglottis, the tissue in the throat that covers and protects the larynx during swallowing. Epiglottitis may cause life-threatening airway obstruction.Septic arthritis (joint infection), cellulitis (rapidly progressing skin infection which usually involves face, head, or neck), and pneumonia (which can be mild focal or severe empyema) are common manifestations of invasive disease.Osteomyelitis (bone infection) and pericarditis (infection of the sac covering the heart) are less common forms of invasive disease. Otitis media and acute bronchitis due to H. influenzae are generally caused by nontypeable strains. Hib strains account for only 5%10% of H. influenzae causing otitis media.Nontypeable

(unencapsulated) strains may cause invasive disease but are generally less virulent than encapsulated strains. Nontypeable strains are rare causes of serious infection among children but are a common cause of ear infections in children and bronchitis in adults.

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4. Laboratory Diagnosis A Gram stain of an infected body fluid may demonstrate small gram-negative coccobacilli suggestive of invasive Haemophilus disease. CSF, blood, pleural fluid, joint fluid, and middle ear aspirates should be cultured on appropriate media. A positive culture for H. influenzae establishes the diagnosis. All isolates of H. influenzae should be serotyped. This is an extremely important laboratory procedure that should be performed on every isolate of H. influenzae, especially those obtained from children younger than 15 years of age. This test determines whether an isolate is type b, which is the only type that is potentially vaccine preventable. Serotyping 90 is usually done by either the state health department laboratory or a reference laboratory. Antigen detection may be used as an adjunct to culture, particularly in diagnosing H. influenzae infection in patients who have been partially treated with antimicrobial agents, in which case the organism may not be viable on culture. Two tests are available. Latex agglutination is a rapid, sensitive, and specific method to detect Hib capsular polysaccharide antigen in CSF, but a negative test does not exclude the diagnosis, and falsepositive tests have been reported. Antigen testing of serum and urine is not recommended. Counterimmunoelectrophoresis is similar to latex agglutination but is less sensitive, takes longer, and is more difficult to perform. 5. Medical Management Hospitalization is generally required for invasive Hib disease. Antimicrobial therapy with an effective thirdgeneration cephalosporin (cefotaxime or ceftriaxone), or chloramphenicol in combination with ampicillin should be begun immediately. The treatment course is usually 10 days. Ampicillin-resistant strains of Hib are now common throughout the United States. Children with life-threatening illness in which Hib may be the etiologic agent should not receive ampicillin alone as initial empiric therapy. 6. Epidemiology Occurrence Hib disease occurs worldwide. Reservoir Humans (asymptomatic carriers) are the only known reservoir. Hib does not survive in the environment on inanimate surfaces.
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Transmission The primary mode of Hib transmission is presumably by respiratory droplet spread, although firm evidence for this mechanism is lacking. Temporal Pattern Several studies in the prevaccine era described a bimodal seasonal pattern in the United States, with one peak during September through December and a second peak during March through May. The reason for this bimodal pattern is not known.Haemophilus influenzae type b Communicability The contagious potential of invasive Hib disease is considered to be limited. However, certain circumstances, particularly close contact with a case-patient (e.g., household, child care, or institutional setting) can lead to outbreaks or direct secondary transmission of the disease. 7. Secular Trends in the United States H. influenzae infections became nationally reportable in 1991. Serotype-specific reporting continues to be incomplete. Before the availability of national reporting data, several areas conducted active surveillance for H. influenzae disease, which allowed estimates of disease nationwide. In the early 1980s, it was estimated that about 20,000 cases occurred annually in the United States, primarily among children younger than 5 years of age (4050 cases per 100,000 population). The incidence of invasive Hib disease began to decline dramatically in the late 1980s, coincident with licensure of conjugate Hib vaccines, and has declined by more than 99% compared with the prevaccine era. From 1996 through 2000, an average of 1,247 invasive H. influenzae infections per year were reported to CDC in all age groups (range 1,1621,398 per year). Of these, an average of 272 (approximately 22%) per year were among children younger than 5 years of age. Serotype was known for 76% of the invasive cases in this age group. Three-hundred forty-one (average of 68 cases per year) were due to type b.There is evidence that Hib vaccines decrease the rate of carriage of Hib among vaccinated children, thereby decreasing the chance that unvaccinated children will be exposed. Incidence is strikingly age-dependent. In the prevaccine era, up to 60% of invasive disease occurred before age 12 months, with a peak occurrence among children 611 months
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of age. Children 60 months of age and older account for less than 10% of invasive disease.In 19982000, approximately 44% of children younger than 5 years of age with confirmed invasive Hib disease were younger than 6 months of age and too young to have completed a three-dose primary vaccination series. Fifty-six percent were age 6 months or older and were eligible to have completed the primary vaccination series. Of these age-eligible children, 68% were either incompletely vaccinated (fewer than 3 doses) or their vaccination status was unknown. Thirty-two percent of children aged 659 months with confirmed type b disease had received three or more doses of Hib vaccine, including 22 who had received a booster dose 14 or more days before onset of their illness. The cause of Hib vaccine failure in these children is not known.92In 2009, among children younger than 5 years of age, 35 cases of invasive disease due to Hib were reported in the United States. In addition, another 178 cases caused by unknown H. influenzae serotypes were reported, so the actual number of Hib cases could be between 35 and 213. Most cases were among unvaccinated or incompletely vaccinated children.Risk factors for Hib disease include exposure factors and host factors that increase the likelihood of exposure to Hib. Exposure factors include household crowding, large household size, child care attendance, low socioeconomic status, low parental education levels, and school-aged siblings. Host factors include race/ethnicity (elevated risk among African Americans, Hispanics, Native Americanspossibly confounded by socioeconomic variables that are associated with both race/ethnicity and Hib disease), chronic disease (e.g., sickle cell anemia, antibody deficiency syndromes, malignancies, especially during chemotherapy), and possibly gender (risk is higher for males).Protective factors(effect limited to infants younger than 6 months of age) include breastfeeding and passively acquired maternal antibody.Secondary Hib disease is defined as illness occurring 160 days following contact with an ill child, and accounts for less than 5% of all invasive Hib disease. Among household contacts, six studies have found a secondary attack rate of 0.3% in the month following onset of the index case, which is about 600-fold higher than the risk for the general population. Attack rates varied substantially with age, from 3.7% among children 2 years of age and younger to 0% among contacts 6 years of age and older. In these household contacts, 64% of secondary cases occurred within the first week (excluding the first 24 hours) of disease onset in the index patient, 20% during the second week, and 16% during the third and fourth weeks.Data are conflicting regarding the risk of secondary transmission among child care contacts. Secondary attack rates have varied from 0% to as high as 2.7%. Most studies seem to suggest that child care contacts are at relatively low risk for secondary transmission of Hib disease particularly if contacts are age-appropriately vaccinated.
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8. Haemophilus influenzae type b Vaccines Characteristics A pure polysaccharide vaccine (HbPV) was licensed in the United States in 1985. The vaccine was not effective in children younger than 18 months of age. Estimates of efficacy in older children varied widely, from 88% to -69% (anegative efficacy implies greater disease risk for vaccinees Haemophilus influenzae type b than nonvaccinees). HbPV was used until 1988 but is no longer available in the United States. The characteristics of the Hib polysaccharide were similar to other polysaccharide vaccines (e.g., pneumococcal, meningococcal). The response to the vaccine was typical of a T-independent antigen, most notably an age-dependent immune response, and poor immunogenicity in children 2 years of age and younger. In addition, no boost in antibody titer was observed with repeated doses, the antibody that was produced was relatively low-affinity IgM, and switching to IgG production was minimal.

9. Haemophilus influenzae type b Polysaccharide Protein Conjugate Vaccines Conjugation is the process of chemically bonding a polysaccharide (a somewhat ineffective antigen) to a protein carrier, which is a more effective antigen. This process changes the polysaccharide from a T-independent to a T-dependent antigen and greatly improves immunogenicity, particularly in young children. In addition, repeat doses of Hib conjugate vaccines elicit booster responses and allow maturation of class-specific immunity with predominance of IgG antibody. The Hib conjugates also cause carrier priming and elicit antibody to useful carrier protein.The first Hib conjugate vaccine (PRP-D, ProHIBIT) was licensed in December 1987. PRP-D is no longer available in the United States. HibTITER (HbOC) is also no longer available.Two conjugate Hib vaccines are licensed for use in infants as young as 6 weeks of age (see below). A third Hib vaccine (Hiberix) is approved only for the last dose of the Hib schedule among children 12 months and older. The vaccines utilize different carrier proteins. Two combination vaccines that contain Hib conjugate vaccine are also available.

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Haemophilus influenzae type b Conjugate Vaccines Vaccine PRP-T (ActHIB) PRP-T (Hiberix) PRP-OMP (PedvaxHIB) Protein Tetanus toxoid Tetanus toxoid Meningococcal group B outer membrane protein Carrier Manufacturer sanofi pasteur GSK Merck

10. Immunogenicity and Vaccine Efficacy Hib conjugate vaccines licensed for use in infants are highly immunogenic. More than 95% of infants will develop protective antibody levels after a primary series of two or three doses. Clinical efficacy has been estimated at 95% to 100%. Invasive Hib disease in a completely vaccinated infant is uncommon.Haemophilus influenzae type b Conjugate VaccinesVaccine Protein Carrier Manufacturer PRP-T (ActHIB) Tetanus toxoid sanofi pasteurPRP-T (Hiberix) Tetanus toxoid GSK PRP-OMP (PedvaxHIB) Meningococcal group B outer membrane protein Merck94 Hib vaccine is immunogenic in patients with increased risk for invasive disease, such as those with sickle-cell disease, leukemia, or human immunodeficiency virus (HIV) infection, and those who have had a splenectomy. However, in persons with HIV infection, immunogenicity varies with stage of infection and degree of immunocompromise. Efficacy studies have not been performed in populations with increased risk of invasive disease. 11. Vaccination Schedule and Use All infants, including those born prematurely, should receive a primary series of conjugate Hib vaccine (separate or in combination), beginning at 2 months of age. The number of doses in the primary series depends on the type of vaccine used. A primary series of PRP-OMP (PedvaxHIB) vaccine is two doses; PRP-T (ActHIB) requires a three-dose primary series (see table below). A booster is recommended at 1215 months regardless of which vaccine is used for the primary series.

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ACIP-Recommended Haemophilus influenzae type b (Hib) Routine Vaccine Schedule Vaccine PRP-T* PRP-OMP
age and older.

2 Months Dose 1 Dose 1

4 Months Dose 2 Dose 2

6 Months Dose 3

1215 Months Booster Booster

*Hiberix brand PRP-T vaccine is approved only for the last dose of the Hib series among children 12 months of

The recommended interval between primary series doses is 8 weeks, with a minimum interval of 4 weeks. At least 8 weeks should separate the booster dose from the previous (second or third) dose. Hib vaccines may be given simultaneously with all other vaccines. Limited data suggest that Hib conjugate vaccines given before 6 weeks of age may induce immunologic tolerance to subsequent doses of Hib vaccine. A dose given before 6 weeks of age may reduce the response to subsequent doses. As a result, Hib vaccines, including combination vaccines that contain Hib conjugate, should never be given to a child younger than 6 weeks of age.With the exception of Hiberix, the conjugate Hib vaccines licensed for use in infants are interchangeable. A series that includes vaccine of more than one type will induce a protective antibody level. If a child receives different brands of Hib vaccine at 2 and 4 months of age, a third dose of either brand should be administered at 6 months of age to complete the primary series. Either vaccine may be used for the booster dose, regardless of what was administered in the primary series. Unvaccinated children 7 months of age and older may not require a full series of three or four doses. The number of doses a child needs to complete the series depends on the childs current age. Detailed Vaccination Schedule for Haemophilus influenzae type b Conjugate Vaccines Vaccine PRP-T (ActHIB) Age at 1st Dose (Months) 26 711 1214 1559 PRP-OMP (PedvaxHIB) 26 711 1214 3 doses, 2 months apart 2 doses, 2 months apart 1 dose 1 dose 2 doses, 2 months apart 2 doses, 2 months apart 1 dose 1215 months* 1215 months* 2 months later 1215 months* 1215 months* 2 months later Primary Series Booster

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1559
age and older *At least 2 months after previous dose

1 dose

Hiberix brand PRP-T vaccine is approved only for the last dose of the Hib series among children 12 months of

11.1 PRP-T (ActHIB) Previously unvaccinated infants aged 2 through 6 months should receive three doses of vaccine administered 2 months apart, followed by a booster dose at age 1215 months, administered at least 2 months after the last dose. Unvaccinated children aged 7 through 11 months should receive two doses of vaccine 2 months apart, followed by a booster dose at age 1215 months, administered at least 2 months after the last dose. Unvaccinated children aged 12 through 14 months should receive one dose of vaccine followed by a booster at least 2 months later. Any previously unvaccinated child aged 15 through 59 months should receive a single dose of vaccine. 11.2 PRP-OMP (PedvaxHIB) Unvaccinated children aged 2 through 11 months should receive two doses of vaccine 2 months apart, followed by a booster dose at 1215 months of age, at least 2 months after the last dose. Unvaccinated children aged 12 through 14 months should receive one dose of vaccine followed by a booster at least 2 months later. Any previously unvaccinated child 15 through 59 months of age should receive a single dose of vaccine.Children with a lapsed Hib immunization series (i.e., children who have received one or more doses of Hib-containing vaccine but are not up-to-date for their age) may not need all the remaining doses of a threeor four-dose series. Vaccination of children with a lapsed schedule is addressed in the catchup schedule, published annually with the childhood vaccination schedule. Hib invasive disease does not always result in development of protective anti-PRP antibody levels. Children younger than 24 months of age who develop invasive Hib disease should be considered susceptible and should receive Hib vaccine. Vaccination of these children should start as soon as possible during the convalescent phase of the illness. The schedule should be completed as recommended for the child's age. 11.3 Vaccination of Older Children and Adults In general, Hib vaccination of persons older than 59 months of age is not recommended. The majority of older children are immune to Hib, probably from asymptomatic infection as
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infants. However, some older children and adults are at increased risk for invasive Hib disease and may be vaccinated if they were not vaccinated in childhood. These include those with functional or anatomic asplenia (e.g., sickle cell disease, postsplenectomy), immunodeficiency (in particular, persons with IgG2 subclass deficiency),

immunosuppression from cancer chemotherapy, infection with HIV, and receipt of a hematopoietic stem cell transplant (HSCT). Previously unvaccinated persons older than 59 months of age with one of these high-risk conditions should be given at least one pediatric dose of any Hib conjugate vaccine. 11.4 Combination Vaccines Two combination vaccines that contain H. influenzae type b are available in the United StatesDTaP-IPV-Hib (Pentacel, sanofi pasteur) and hepatitis BHib (Comvax, Merck). A third combination, TriHiBit, is no longer available in the U.S. 11.5 Comvax Comvax (Merck) is a combination hepatitis BHib vaccine, licensed in October 1996. The vaccine contains a standard dose of PRP-OMP (PedvaxHIB), and 5 mcg (pediatric dose) of Mercks hepatitis B vaccine. Comvax is licensed for use when either or both antigens are indicated. However, because of the potential of immune tolerance to the Hib antigen, Comvax should not be used in infants younger than 6 weeks of age (i.e., the birth dose of hepatitis B, or a dose at 1 month of age, if the infant is on a 0-1-6-month schedule). Comvax is not licensed for infants whose mothers are known to be hepatitis B surface antigen positive (i.e., acute or chronic infection with hepatitis B virus). However, the vaccine contains the same dose of Mercks hepatitis B vaccine recommended for these infants, so response to the hepatitis B component of Comvax should be adequate. The Advisory Committee on Immunization Practices (ACIP) has approved off-label use of Comvax in children whose mother is HBsAg positive or whose HBsAg status is unknown. Recommendations for spacing and timing of Comvax are the same as those for the individual antigens. In particular, the third dose must be given at 12 months of age or older and at least 2 months after the second dose, as recommended for PRP-OMP. 11.6 Pentacel Pentacel (sanofi pasteur) is a combination vaccine that contains lyophilized Hib (ActHIB) vaccine that is reconstituted with a liquid DTaP-IPV solution. The vaccine was licensed by
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FDA in June 2008. Pentacel is licensed by FDA for doses 1 through 4 of the DTaP series among children 6 weeks through 4 years of age. Pentacel should not be used for the fifth dose of the DTaP series, or for children 5 years or older regardless of the number of prior doses of the component vaccines. The DTaP-IPV solution is licensed only for use as the diluent for the lyophilized Hib component and should not be used separately. If the DTaP-IPV solution is inadvertently administered without being used to reconstitute the Hib component the DTaP and IPV doses can be counted as valid. However, PRP-T (ActHib) must be reconstituted only with the DTaP-IPV diluent supplied in the Pentacel package, or with a specific 0.4% sodium chloride ActHib diluent. If DTaP-IPV diluent is not available then the provider must contact the manufacturer (sanofi pasteur) to obtain the ActHib diluent. Any dose of ActHib reconstituted with a diluent other than DTaP-IPV or specific ActHib diluent should not be counted as valid and must be repeated. 11.7 Contraindications and Precautions to Vaccination Vaccination with Hib conjugate vaccine is contraindicated for persons known to have experienced a severe allergic reaction (anaphylaxis) to a vaccine component or following a prior dose of that vaccine. Vaccination should be delayed for children with moderate or severe acute illnesses. Minor illnesses (e.g., mild upper respiratory infection) are not contraindications to vaccination. Hib conjugate vaccines are contraindicated for children younger than 6 weeks of age because of the potential for development of immunologic tolerance.Contraindications and precautions for the use of Pentacel and Comvax are the same as those for its individual component vaccines (i.e., DTaP, Hib, IPV, and hepatitis B). 11.8 Adverse Reactions Following Vaccination Adverse reaction following Hib conjugate vaccines are not common. Swelling, redness, or pain have been reported in 5%30% of recipients and usually resolve within 1224 hours. Systemic reactions such as fever and irritability are infrequent. Serious adverse reactions are rare. All serious adverse events that occur after receipt of any vaccine should be reported to the Vaccine Adverse Event Reporting System (VAERS)

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11.9 Vaccine Storage and Handling All Hib conjugate vaccines should be shipped in insulated containers to prevent freezing. Unreconstituted or liquid vaccine should be stored at refrigerator temperature (35o46oF [2o 8oC]). Hib vaccine must not be frozen. ActHIB should be used within 24 hours of reconstitution. 12. Surveillance and Reporting of Hib Disease Invasive Hib disease is a reportable condition in most states. All healthcare personnel should report any case of invasive Hib disease to local and state health departments.

Bacterial Meningitis
1. Definition Bacterial meningitis is usually severe. While most people with meningitis recover, it can cause serious complications, such as brain damage, hearing loss, or learning disabilities. There are several pathogens (types of germs) that can cause bacterial meningitis. Some of the leading causes of bacterial meningitis in the United States include Haemophilus influenzae (most often caused by type b, Hib), Streptococcus pneumoniae, group B Streptococcus, Listeria monocytogenes, and Neisseria meningitidis. 2. Causes Common causes of bacterial meningitis vary by age group:
Age Group Newborns Infants and Children Adolescents and Young Adults Older Adults Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes Causes Group B Streptococcus, Escherichia coli, Listeria monocytogenes Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b Neisseria meningitidis, Streptococcus pneumoniae

3. Risk Factors Factors that can increase your risk of bacterial meningitis include:
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Age
o

Infants are at higher risk for bacterial meningitis than people in other age groups. However, people of any age are at risk. See the table above for which pathogens more commonly affect which age groups.

Community setting
o

Infectious diseases tend to spread more quickly where larger groups of people gather together. College students living in dormitories and military personnel are at increased risk for meningococcal meningitis.

Certain medical conditions

o

There are certain diseases, medications, and surgical procedures that may weaken the immune system or increase risk of meningitis in other ways.

Working with meningitis-causing pathogens

o

Microbiologists who are routinely exposed to meningitis-causing pathogens are at increased risk.

Travel
o

Travelers to the meningitis belt in sub-Saharan Africa may be at risk for meningococcal meningitis, particularly during the dry season. Also at risk for meningococcal meningitis are travelers to Mecca during the annual Hajj and Umrah pilgrimage.

4. Transmission The germs that cause bacterial meningitis can be contagious. Some bacteria can spread through the exchange of respiratory and throat secretions (e.g., kissing). Fortunately, most of the bacteria that cause meningitis are not as contagious as diseases like the common cold or the flu. Also, the bacteria are not spread by casual contact or by simply breathing the air where a person with meningitis has been. Other meningitis-causing bacteria are not spread person-to-person, but can cause disease because the person has certain risk factors (such as a weak immune system or head trauma). Unlike other bacterial causes of meningitis, you can get Listeria monocytogenes by eating contaminated food.
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Sometimes the bacteria that cause meningitis spread to other people. This usually happens when there is close or long contact with a sick person in the same household or daycare center, or if they had direct contact with a patient's oral secretions (such as a boyfriend or girlfriend). People who qualify as close contacts of a person with meningococcal or Haemophilus influenzaetype b (Hib) meningitis are at higher risk of getting disease and may need antibiotics (see Prevention). Close contacts of a person with meningitis caused by other bacteria, such asStreptococcus pneumoniae, do not need antibiotics. Tell your doctor if you think you have been exposed to someone with meningitis. Healthy people can carry the bacteria in their nose or throat without getting sick. Rarely, these bacteria can invade the body and cause disease. Most people who carry the bacteria never become sick. 5. Signs & Symptoms Meningitis infection may show up in a person by a sudden onset of fever, headache, and stiff neck. It will often have other symptoms, such as

Nausea Vomiting Increased sensitivity to light (photophobia) Altered mental status (confusion)

The symptoms of bacterial meningitis can appear quickly or over several days. Typically they develop within 3-7 days after exposure. Babies younger than one month old are at a higher risk for severe infections, like meningitis, than older children. In newborns and infants, the classic symptoms of fever, headache, and neck stiffness may be absent or difficult to notice. The infant may appear to be slow or inactive (lack of alertness), irritable, vomiting or feeding poorly. In young infants, doctors may look for a bulging fontanelle (soft spot on infants head) or abnormal reflexes, which can also be signs of meningitis. If you think your infant has any of these symptoms, call the doctor or clinic right away. Later symptoms of bacterial meningitis can be very severe (e.g., seizures, coma). For this reason, anyone who thinks they may have meningitis should see a doctor as soon as possible.
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6. Diagnosis If meningitis is suspected, samples of blood or cerebrospinal fluid (near the spinal cord) are collected and sent to the laboratory for testing. It is important to know the specific cause of meningitis because that helps doctors understand how to treat the disease, and possibly how bad it will get. In the case of bacterial meningitis, antibiotics can help prevent severe illness and reduce the spread of infection from person to person. If bacteria are present, they can often be grown (cultured). Growing the bacteria in the laboratory is important for confirming the presence of bacteria, identifying the specific type of bacteria that is causing the infection, and deciding which antibiotic will work best. Other tests can sometimes find and identify the bacteria if the cultures do not. 7. Treatment Bacterial meningitis can be treated effectively with antibiotics. It is important that treatment be started as soon as possible. Appropriate antibiotic treatment of the most common types of bacterial meningitis should reduce the risk of dying from meningitis to below 15%, although the risk remains higher among young infants and the elderly. 8. Prevention The most effective way to protect you and your child against certain types of bacterial meningitis is to complete the recommended vaccine schedule. There are vaccines for three types of bacteria that can cause meningitis: Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), and Haemophilus influenzae type b (Hib). Antibiotics may be recommended for close contacts of people with meningococcal meningitis. Antibiotics may also be recommended for the entire family if a family member develops severe Hib infection and theres a high risk person in the house. This is to decrease the risk of spreading disease to a high risk person, since they are at increased risk for severe disease. Your doctor or local health department will tell you if theres a high risk person in your house and antibiotics are needed. Maintaining healthy habits, like not smoking and avoiding cigarette smoke, getting plenty of rest, and not coming into close contact with people who are sick, can also help. This is especially important for young infants, the elderly, or for those with a weakened immune system, since they are at increased risk for severe disease.Antibiotics may be recommended
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for close contacts of people with meningococcal meningitis. Antibiotics may also be recommended for the entire family if a family member develops severe Hib infection and theres a high risk person in the house. This is to decrease the risk of spreading disease to a high risk person, since they are at increased risk for severe disease. Your doctor or local health department will tell you if theres a high risk person in your house and antibiotics are needed. Maintaining healthy habits, like not smoking and avoiding cigarette smoke, getting plenty of rest, and not coming into close contact with people who are sick, can also help. This is especially important for young infants, the elderly, or for those with a weakened immune system, since they are at increased risk for severe disease.

Pneumonia
1. Definition Pneumonia is an inflammation of the lungs caused by infection. Bacteria, viruses, fungi or parasites can cause pneumonia. Pneumonia is a particular concern if you're older than 65 or have a chronic illness or weak immune system. It can also occur in young, healthy people. Pneumonia can range in seriousness from mild to life-threatening. Pneumonia often is a complication of another condition, such as the flu. Antibiotics can treat most common forms of bacterial pneumonias, but antibiotic-resistant strains are a growing problem. The best approach is to try to prevent infection. 2. Signs and symptoms Pneumonia can occur at any age, although it is more common in younger children. Pneumonia accounts for 13% of all infectious illnesses in infants younger than 2 years.Newborns with pneumonia commonly present with poor feeding and irritability, as well as tachypnea, retractions, grunting, and hypoxemia. Infections with group B Streptococcus, Listeria monocytogenes, or gram-negative rods (eg, Escherichia coli, Klebsiella pneumoniae) are common causes of bacterial pneumonia. Group B streptococci infections are most often transmitted to the fetus in utero. The most commonly isolated virus is respiratory syncytial virus (RSV).Cough is the most common symptom of pneumonia in infants, along with tachypnea, retractions, and hypoxemia. These may be accompanied by congestion, fever,
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irritability, and decreased feeding. Streptococcus pneumoniae is by far the most common bacterial pathogen in infants aged 1-3 months. Adolescents experience similar symptoms to younger children. They may have other constitutional symptoms, such as headache, pleuritic chest pain, and vague abdominal pain. Vomiting, diarrhea, pharyngitis, and otalgia/otitis are also common in this age group. Mycoplasma pneumoniae is the most frequent cause of pneumonia among older children and adolescents. 3. Diagnosis The signs and symptoms of pneumonia are often nonspecific and widely vary based on the patients age and the infectious organisms involved. Observing the childs respiratory effort during a physical exam is an important first step in diagnosing pneumonia. The World Health Organization (WHO) respiratory rate thresholds for identifying children with pneumonia are as follows: Children younger than 2 months: Greater than or equal to 60 breaths/min Children aged 2-11 months: Greater than or equal to 50 breaths/min Children aged 12-59 months: Greater than or equal to 40 breaths/min

Assessment of oxygen saturation by pulse oximetry should be performed early in the evaluation when respiratory symptoms are present. Cyanosis may be present in severe cases. Capnography may be useful in the evaluation of children with potential respiratory compromise. Other diagnostic tests may include the following: Auscultation by stethoscope Cultures Serology Complete blood cell count (CBC) Chest radiography Ultrasonography

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New data show that point-of-care ultrasonography accurately diagnoses most cases of pneumonia in children and young adults. Ultrasonography may eventually replace x-rays for diagnosis. 4. Management Initial priorities in children with pneumonia include the identification and treatment of respiratory distress, hypoxemia, and hypercarbia. Grunting, flaring, severe tachypnea, and retractions should prompt immediate respiratory support. Children who are in severe respiratory distress should undergo tracheal intubation if they are unable to maintain oxygenation or have decreasing levels of consciousness. Increased respiratory support requirements such as increased inhaled oxygen concentration, positive pressure ventilation, or CPAP are commonly required before recovery begins. 5. Antibiotics The majority of children diagnosed with pneumonia in the outpatient setting are treated with oral antibiotics. High-dose amoxicillin is used as a first-line agent for children with uncomplicated community-acquired pneumonia. Second- or third-generation cephalosporins and macrolide antibiotics such as azithromycin are acceptable alternatives. Combination therapy (ampicillin and either gentamicin or cefotaxime) is typically used in the initial treatment of newborns and young infants.Hospitalized patients are usually treated with an advanced-generation intravenous cephalosporin, often in combination with a macrolide. Children who are toxic appearing should receive antibiotic therapy that includes vancomycin (particularly in areas where penicillin-resistant pneumococci and methicillin-resistant S aureus [MRSA] are prevalent) along with a second- or third-generation cephalosporin. 6. Vaccines Aside from avoiding infectious contacts (difficult for many families who use daycare facilities), vaccination is the primary mode of prevention. Influenza vaccine is recommended for children aged 6 months and older. The pneumococcal conjugate vaccine (PCV13) is recommended for all children younger than 59 months old. The 23-valent polysaccharide vaccine (PPVSV) is recommended for children 24 months or older who are at high risk of pneumococcal disease.

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Epiglottitis
1. Definition Epiglottitis is a severe bacterial infection of the epiglottis, which can block the windpipe, obstructing air flow. Epiglottitis is caused by a bacterial infection. Typical symptoms include a sudden sore throat, a high fever, irritability, anxiety, and difficulties in swallowing and breathing. The diagnosis is based on symptoms and an x-ray of the neck. Vaccination can help prevent this infection. The child is hospitalized, measures are taken to keep the airway open, and antibiotics are given to eliminate the infection. The epiglottis is a small flap of tissue that closes the entrance to the voice box (larynx) and windpipe (trachea) during swallowing. In the past, epiglottitis was most common among children 2 to 5 years old and was usually caused by the bacterium Haemophilus influenzae type b. Now that most children are vaccinated against Haemophilus influenzae type b, the disease is quite rare and is more common among adults (see Throat Disorders: Epiglottitis). In adults, it is typically caused by Streptococcus pneumoniae, other streptococci, and staphylococci. Children with epiglottitis often have bacteria in the bloodstream (bacteremia), which sometimes spreads the infection to the lungs, the joints, the tissues covering the brain (meninges), the sac around the heart, or the tissue beneath the skin. 2. Symptoms The infection usually begins suddenly and progresses rapidly. A previously healthy child develops a sore throat and often a high fever. The child may be irritable and anxious. Difficulties in swallowing and breathing are common. The child usually drools, breathes rapidly, and makes a loud noise while inhaling (called stridor). The difficulty in breathing often causes the child to lean forward while stretching the neck backward to try to increase the amount of air reaching the lungs. Labored breathing may lead to a buildup of carbon dioxide and low oxygen levels in the bloodstream, causing agitation and confusion followed by sluggishness (lethargy). The swollen epiglottis makes coughing up mucus difficult.

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Epiglottitis can quickly become fatal because swelling of the infected tissue may block the airway and cut off breathing. 3. Diagnosis Epiglottitis is an emergency, and a child is hospitalized immediately when a doctor suspects it. If the child does not have all of the typical symptoms of epiglottitis and does not appear seriously ill, the doctor sometimes takes an x-ray of the neck, which can show an enlarged epiglottis. The doctor does not hold the child down or use a tongue depressor to look in the throat. These manipulations may cause throat spasm and complete airway blockage in a child with epiglottitis. Epiglottitis

*On the left, an endoscopic view of the throat shows almost complete blockage of the airway (arrow). This finding is typical of epiglottitis. On the right, the airway has been opened (arrow) after insertion and removal of an endotracheal tube, although some redness and blood remain.

If an enlarged epiglottis is seen on x-ray or the child appears seriously ill, doctors examine the child under anesthesia in the operating room. The doctor inserts a thin flexible tube (laryngoscope) into the throat to directly view the larynx. 4. Prevention Prevention of epiglottitis is better than treatment. Prevention is achieved by ensuring that all children receive the Haemophilus influenzae type b and Streptococcus pneumoniae conjugate vaccines.

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5. Treatment If the examination shows epiglottitis or triggers throat spasm, the doctor inserts a plastic tube (endotracheal tube) into the airway to keep it open. If the airway is too swollen to allow placement of an endotracheal tube, the doctor cuts an opening through the front of the neck (tracheostomy) and inserts the tube. This tube is left in place for several days until the swelling of the epiglottis goes down. The child also receives antibiotics, such as ceftriaxone or ampicillin-sulbactam. Once the child's airway is opened, the prognosis is good.

Septic Arthritis
1.Definition Infectious arthritis (septic arthritis) is infection in the fluid and tissues of a joint usually caused by bacteria, but sometimes caused by viruses or fungi.

Bacteria or sometimes viruses or fungi may spread through the bloodstream or from nearby infected tissue to a joint, causing infection.

Pain, swelling, and fever usually develop within hours or a couple of days. Joint fluid is withdrawn in a needle and tested. Antibiotics are begun immediately.

People at risk of infectious arthritis include those who have abnormal joints because of arthritis (including rheumatoid arthritis, osteoarthritis, or arthritis from injury) who develop an infection that reaches the bloodstream. For example, an older person with pneumonia and sepsis (a bloodstream infection) may fall and injure a wrist. Bleeding into the injured wrist may then result in infectious arthritis. Infecting organisms, mainly bacteria, usually reach the joint through the bloodstream, but a joint can be infected directly if it is contaminated during surgery or by an injection or an injury. Different bacteria can infect a joint, but the bacteria most likely to cause infection depend on a person's age. Staphylococci and bacteria known as gram-negative bacilli most often infect infants and young children, whereas gonococci (bacteria that cause gonorrhea), staphylococci, and streptococci

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most often infect older children and adults. Occasionally, spirochetes (a type of bacteria), such as those that cause Lyme disease and syphilis, can infect joints. Virusessuch as the human immunodeficiency virus (HIV), parvoviruses, and those that cause rubella, mumps, and hepatitis Bcan infect joints in people of any age. A slowly developing chronic infectious arthritis is most often caused by Mycobacterium tuberculosis(the main cause of tuberculosis) or fungi. 2. Symptoms Infants usually have fever and pain and tend to be fussy. Generally, infants do not move the infected joint because moving or touching it is painful. Young children with knee or hip infections may refuse to walk. In older children and adults, symptoms usually begin over hours to a few days. The infected joint usually becomes red and warm, and moving or touching it is very painful. Fluid collects in the infected joint, causing it to swell and stiffen. Symptoms also include fever and chills. Less dramatic symptoms (such as less pain and a lower fever) usually occur in people with chronic infectious arthritis that is caused by mycobacteria or fungi. Infectious Arthritis

*An abnormal magnetic resonance image (MRI) reveals extensive damage to the bones in the knee (arrows). In this case, this finding is a result of an infectious arthritis caused by tuberculosis.

The joints most commonly infected are the knee, shoulder, wrist, hip, elbow, and the joints of the fingers. Most bacterial, fungal, and mycobacterial infections affect only one joint or, occasionally, several joints. For example, the bacteria that cause Lyme disease most often
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infect knee joints. Gonococcal bacteria and viruses can infect a few or many joints at the same time. 3. Diagnosis Usually, a sample of joint fluid is removed with a needle as soon as possible. It is examined for white blood cells and tested for bacteria and other organisms. The laboratory can almost always grow and identify the infecting bacteria from the joint fluid, unless the person has recently taken antibiotics. However, the bacteria that cause gonorrhea, Lyme disease, and syphilis are difficult to recover from joint fluid. If bacteria do grow in culture, the laboratory then tests which antibiotics would be effective.A doctor usually orders blood tests because bacteria from joint infections often appear in the bloodstream. Sputum, spinal fluid, and urine may also be tested for bacteria to help determine the source of infection. 4. Prognosis and Treatment Because an infected joint can be destroyed within days or sometimes within hours without prompt treatment, antibiotics must be started as soon as an infection is suspected, even before the laboratory has identified the infecting organism. Antibiotics that kill the most likely bacteria are given until the infecting organism is identified, usually within 48 hours of testing the joint fluid. Antibiotics are given by vein (intravenously) at first, to ensure that enough of the drug reaches the infected joint. If the antibiotics are effective against the infecting bacteria, improvement usually occurs within 48 hours. As soon as the doctor receives the laboratory results, the antibiotic may be changed depending on the sensitivity of the particular bacteria to specific antibiotics. The doctor often removes pus with a needle to prevent its accumulation, because accumulated pus may damage a joint. If drainage with a needle is difficult (as with a hip joint) or unsuccessful, arthroscopy (a procedure using a small scope to view the interior of the joint directlysee Diagnosis of Musculoskeletal Disorders: Arthroscopy) or surgery may be needed to drain the joint. Sometimes a tube is left in place to drain the pus. Splinting the joint (to keep it from moving) can help ease pain at first, but physical therapy is also needed to prevent stiffness and permanent loss of function. Infections caused by fungi are treated with antifungal drugs. Infections caused by mycobacteria are treated with a combination of antibiotics. Infections caused by viruses

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usually get better without treatmentonly acetaminophen or a nonsteroidal antiinflammatory drug (NSAID) is needed for pain and fever.

Cellulitis
1. Definition

Cellulitis is a spreading bacterial infection of the skin and the tissues immediately beneath the skin.

Redness, pain, and tenderness are felt over an area of skin, and some people have a fever, chills, and other more serious symptoms.

Antibiotics are needed to treat the infection.

Cellulitis may be caused by many different bacteria. The most common are those of the Streptococcus species. Streptococci spread rapidly in the skin because they produce enzymes that hinder the ability of the tissue to confine the infection. Staphylococcus bacteria can also cause cellulitis, as can many other bacteria, especially after bites by humans or animals or after injuries in water or dirt. Bacteria usually enter through small breaks in the epidermis that result from scrapes, punctures, burns, and skin disorders. Areas of the skin that become swollen with fluid (edema) are especially vulnerable. Cellulitis is more common in people with poor blood circulation (chronic venous insufficiency). However, cellulitis can also occur in skin that is not obviously injured. 2. Symptoms Cellulitis most commonly develops on the legs but may occur anywhere. The first symptoms are redness, pain, and tenderness over an area of skin. These symptoms are caused both by the bacteria themselves and by the body's attempts to fight the infection. The infected skin becomes hot and swollen and may look slightly pitted, like an orange peel. Fluid-filled blisters, which may be small (vesicles) or large (bullae), sometimes appear on the infected skin. The borders of the affected area are not distinct, except in a form of cellulitis called erysipelas.

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Cellulitis

Most people with cellulitis feel only mildly ill, but some may have a fever, chills, rapid heart rate, headache, low blood pressure, and confusion. As the infection spreads, nearby lymph nodes may become enlarged and tender (lymphadenitis), and the lymphatic vessels may become inflamed (lymphangitis see Bacterial Skin Infections: Lymphangitis). Sometimes, bacteria spread through the blood (bacteremiasee Bacteremia, Sepsis, and Septic Shock: Bacteremia), which can cause more serious illness.When cellulitis affects the same site repeatedly, especially the leg, lymphatic vessels may be damaged, causing permanent swelling of the affected tissue. 3. Diagnosis and Treatment A doctor usually diagnoses cellulitis based on its appearance and symptoms. Laboratory identification of the bacteria from blood, pus, or tissue specimens usually is not necessary unless a person is seriously ill or the infection is not responding to drug therapy. Sometimes, doctors need to perform tests to differentiate cellulitis from a blood clot in the deep veins of the leg (deep vein thrombosissee Venous Disorders: Deep Vein Thrombosis (DVT)), because the symptoms of these disorders are similar.Prompt treatment with antibiotics can prevent the infection from spreading rapidly and reaching the blood and internal organs. Antibiotics that are effective against both streptococci and staphylococci (such as dicloxacillin or cephalexin) are used. People with mild cellulitis may take antibiotics by mouth. Those with rapidly spreading cellulitis, high fever, or other evidence of serious infection often receive intravenous antibiotics (suchas oxacillin or nafcillin). Also, the affected part of the body, when possible, is kept immobile and elevated to help reduce swelling. Cool, wet dressings applied to the infected area may relieve discomfort. Symptoms of cellulitis usually disappear after a few days of antibiotic therapy. However, symptoms often get worse before they get better probably because, with the death of the bacteria, substances that cause tissue damage are released. When this occurs, the body continues to react even though the bacteria are dead.

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Antibiotics are continued for 10 days or longer even though the symptoms may disappear earlier.

References
1. American Academy of Pediatrics. Haemophilus influenzae 2. infections. In: Pickering L, Baker C, Kimberlin D, Long S, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics, 2009:31421. 3. Bisgard KM, Kao A, Leake J, et al. Haemophilus influenzae invasive disease in the United States, 19941995: near disappearance of a vaccine-preventable childhood disease. Emerg Infect Dis 1998;4:22937. 4. CDC. Haemophilus b conjugate vaccines for prevention of Haemophilus influenzae type b disease among infants and children two months of age and older: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1991;40(No. RR-1):17. 5. CDC. Progress toward elimination of Haemophilus influenzaetype b disease among infants and childrenUnited States, 19982000. MMWR 2002;51:23437. 6. CDC. Haemophilus influenzae invasive disease among children aged <5 years California, 19901996. MMWR 1998;47:73740. 7. CDC. Licensure of a Haemophilus influenzae Type b (Hib) Vaccine (Hiberix) and Updated Recommendations for Use of Hib Vaccine. MMWR 2009;58:1008-9.Decker MD, Edwards KM. Haemophilus influenzae type b vaccines: history, choice and comparisons. Pediatr Infect Dis J 1998;17:S11316. 8. Orenstein WA, Hadler S, Wharton M. Trends in vaccinepreventable diseases. Semin Pediatr Infect Dis 1997;8:2333. 9. Boggs W. Point-of-Care Ultrasound Diagnoses Pneumonia in Children. Medscape Medical News. December 10, 2012. Available at

http://www.medscape.com/viewarticle/775961. Accessed January 9, 2013. 10. Shah VP, Tunik MG, Tsung JW. Prospective Evaluation of Point-of-Care Ultrasonography for the Diagnosis of Pneumonia in Children and Young Adults. Arch Pediatr Adolesc Med. Dec 10 2012;1-7. [Medline].

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11. Metinko AP. Neonatal pulmonary host defense mechanisms. In: Polin RA, Fox WW, eds. Fetal and Neonatal Physiology. 3rd ed. Philadelphia, Pa: WB Saunders Co; 2004:1620-73. 12. Barnett ED, Klein JO. Bacterial infections of the respiratory tract. In: Remington JS, Klein JO, eds.Infectious Diseases of the Fetus and Newborn Infant. 6th ed. Philadelphia, Pa: Elsevier Saunders Co; 2006:297-317. 13. Goldenberg DL, Cohen AS. Acute infectious arthritis. A review of patients with nongonococcal joint infections (with emphasis on therapy and prognosis). Am J Med. Mar 1976;60(3):369-77. [Medline]. 14. Ross JJ, Shamsuddin H. Sternoclavicular septic arthritis: review of 180 cases. Medicine (Baltimore). May 2004;83(3):139-48. [Medline]. 15. Del Pozo JL, Patel R. Clinical practice. Infection associated with prosthetic joints. N Engl J Med. Aug 20 2009;361(8):787-94. [Medline]. [Full Text].

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