measles in hiv infection children fix

7/30/2019 Measles in HIV Infection Children FIX

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MEASLES IN CHILDREN WITH HIV INFECTION

Presentators : Jonathan Toman Lumbantobing (090100187)

Ferdinando M. Baeha (090100243)

Lisa Setiawaty (090100333)

Day, Date : Tuesday, March 26th 2013

Supervisor : dr. HJ. RITA EVALINA RUSLI, SpA (K)

CHAPTER 1

INTRODUCTION

1.1. Background

Measles is an acute viral disease caused by a virus in the family Paramyxovirus,

genusMorbilli virus. Measles is characterized by a prodromal symptoms, such as fever and

malaise, cough, coryza, and conjunctivitis, followed by a maculopapular rash. 1 Measles is

very infectious, can infect others since the first day of prodromal state until the fourth day

after the rashes appeared. The infection spread by droplet. 2 In Indonesia, the prevalence of

measles since 1999 until 2002 was stil high about 3000-4000 per year, and the frequency of

phenomenal outbreak of measles increased from 23 to 174 per year. But the case fatality rate

has been decreased from 5.5 % to 1.2 %. The most infected person is children under 12

months, followed by 1-4 and 5-14 years old.3

Human Immunodeficiency virus (HIV) has been a major threat since the past 30

years, after the first infection was identified during 1981, the number of children infected

with HIV has increased dramatically in developing countries as the number of HIV-infected

women of childbearing age has risen.4

Infections by measles virus and by HIV are known to cause a state ofimmunodeficiency in the host. Measles virus leads to a transient immunodeficiency with

depression of cellular mediated immunity. Because measles vaccine is a live attenuated

strain, a similar although much less intense state of temporary immunodeficiency is expected

in the weeks following measles vaccination. By contrast, natural HIV infection leads to a

progressive state of immunodeficiency. Efforts to overcome or postpone HIV effects on the

immune system are mainly composed of the use of antiretroviral schemes to control HIV

infection. Much progress has been made in this area of research so that today HIV-infected

individuals can lead almost normal lives for prolonged periods.5


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Measles in persons coinfected with HIV has been reported to be unusual in its

presentation and frequently fatal. Few studies have investigated measles morbidity and

mortality in HIV-infected children in sub-Saharan Africa, where both infections are endemic.

In Zaire (now the Democratic Republic of Congo), the case-fatality rates among HIV-

seropositive and HIV-seronegative children hospitalized with measles were similar (31% vs.

28%) [11]. In Zambia, the measles case-fatality rate among HIV-seropositive children aged

959 months was significantly higher (28%). 6

1.2. Objective

The aim of this study is to explore more about the theoritical aspects of measles in

children with HIV infection, and to integrate the theory and application of measles in

children with HIV infection case in daily life.


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CHAPTER 2

LITERATURE REVIEW

2.1. Measles

2.1.1. Definition

Measles is an acute viral illness caused by a virus in the family ofParamyxovirus,

genus Morbillivirus.1 The virus is transmitted from person to person through coughing

sneezing. The disease characterized by :

a. a generalized, reddish (eritematous), blotchy (maculopapular) rash

b. a history of fever usually above 380C

c. at least one of the following- cough, runny nose, or red eyes

d. In addition, children with measles frequently exhibit a dislike of brightlight

(photophobia) and often have a sore red mouth.4

The average incubation period for measles is 14 days, with a range of 7-21 days.

Persons with measles are usually considered infectious from 4 days before until 4 days after

oneset of rash.

2.1.2. Etiology

Measles virus is a member of the genusMorbillivirus in the family Paramyxoviridae.4

It is 100-200 nm in diameter, with a core of single stranded RNA, and is closely related to the

rinderpest and canine distemper viruses. Two membrane enbelope porteins are important in

pathogenesis. They are the F (fusion) protein, which is responsible for fusion of virus amd

host cell membranes, viral penetration, and hemolysis, and the H (Hemaglutinin) protein ,

which is responsible for adsorption of virus to cells.7

There is only onle antigenic type if measles virus. Although studies have documented

change in the H glycoprotein, these changes do not appear to be epidemiologically important.

Measles virus is rapidly inactivated by heat, light, acidic pH, ether, amdtrypsin. It has a short

survival time in the air or on objects and surfaces.7

In cell cultures, measles virus causes a distinct cytopathic effect : the formation of

multinucleated syncytia. Containing numerous nucle of fused cells. This effect corresponds

the pathological process observed in infected tissues, including skin rash and Kopliks spots.8


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2.1.3. Epidemiology

In Indonesia, according to the Family Health Survey, measles is in the fifth place of

ten common illness in children (0.7 %) and the fifth place of ten common illness in chldren

age 1-4 years (0.77%).2

Recent estimates (2001) from WHO indicate that about 30 million cases and 700.00

deaths occur annually in developing countries. In these countries, measles is one of the

leading causes of childhood deaths, most of which follow complications such as pneumonia,

diarrhoea, and malnutrition. Actual numbers of children affected by measles may be much

higher-health workers often identify a childhood illness as simply pneumonia or

diarrhoea and may not realize that the illness is, in fact, a complication of measles .6

In countries where immunization rate are low, virtually all unimmunized children will

have been infected with measles by the age of 5 years. About half the cases occur in children

below one year, the age group in which most deaths. In more developed and industrialized

countries measles is now a disease of older children and young adults, who are unimmunized

or in whom primary immunization has failed. At particularly high risk of measles are te urban

poor, who live in areas where immunization coverage is low and where overcrowding AIDS

transmission. Special efforts are needed to reach these children with immunization and other

health services.6

2.1.4. Pathogenesis

Measles consists of 4 phases: incubation period, prodromal illness,

exanthematous phase, and recovery. During incubation, measles virus

migrates to regional lymph nodes. A primary viremia ensues that

disseminates the virus to the reticuloendothelial system. A secondary

viremia spreads virus to body surfaces. The prodromal illness begins

following the secondary viremia and is associated with epithelial necrosis

and giant cell formation in body tissues. Cells are killed by cell-to-cell

plasma membrane fusion associated with viral replication that occurs in

many body tissues, including cells of the central nervous system (CNS).

Virus shedding begins in the prodromal phase. With onset of the rash,

antibody production begins and viral replication and symptoms begin to

subside. Measles virus also infects CD4+ T cells, resulting in suppression

of the Thl immune response and a multitude of other immunosuppressive


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effects.

2.1.5 Clinical Signs and Symptoms

High fever and lethargy are prominent. Sneezing, eyelid edema, tearing, copiouscoryza, photophobia, and harsh cough ensue and worsen. Koplik spots are white macular

lesions on the buccal mucosa, typically opposite the lower molars. These are almost

pathognomonic forrubeola, although they may be absent.

A discrete maculopapular rash begins when the respiratory symptoms are maximal

and spreads quickly over the face and trunk, coalescing to a bright red. As it involves the

extremities, it fades from the face and is completely gone within 6 days; fine desquamation

may occur. Fever peaks when the rash appears and usually falls 23 days thereafter.

2.1.6 Laboratory Finding and Diagnosis

Laboratory abnormalities during measles infection include leukopenia and marked

lymphopenia. Serologic tests that can be used to establish the diagnosis include complement

fixation, hemagglutination inhibition, and enzyme immunoassays. Although neutralizing

antibody assays are more sensitive than the other tests in diagnosing previous infection,

performance is expensive and time-consuming. Antibody levels begin to rise 1 to 3 days after

the onset of rash and peak 2 to 4 weeks later. A fourfold or greater rise in antibody titer from

paired sera or a single elevated immunoglobulin (Ig) M level is indicative of recent infection.

IgM antibody is usually detectable 1 to 2 days after the onset of rash and persists for 30 to 60

days.Measles virus can sometimes be isolated from blood, urine, and nasopharyngeal

secretions, but isolation is difficult, and serology is the preferred diagnostic method.

Detection of measles virus antigen in respiratory epithelial cells or tissue by

immunofluorescent methods and detection of viral genome by polymerase chain reaction

have also been described.

The differential diagnosis of measles includes rubella, enteroviral infection, exanthem

subitum, and adenovirus, EpsteinBarr virus, and streptococcal infections. Infection caused

by Mycoplasma pneumoniae, hypersensitivity to drugs, and Kawasaki disease can be

confused with measles.

2.1.7 Treatment


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No specific therapy is indicated for measles infection. Although ribavirin is active

against measles virus in vitro and has been used to treat immunocompromised patients with

measles pneumonia and encephalitis, it has not been evaluated in controlled clinical trials and

is not licensed for the treatment of measles.

But there are four major points of the management of all measles cases :

a. relieve common symptoms such as fever, cough, blocked nose, conjunctivitis and

sore mouth.

i. Fever

1. Give paracetamol if the child is very uncomfortable or feels very hot

2. Take blankets or clothes off the child

3. Continue breastfeeding; if weaned, continue feeding and ensure the

child drinks plenty

4. Bring the child back if the fever persists for more than 4 days- this may

be an indication of a secondary infection

ii. Cough : if there is cough but there is no rapid breathing, suggest the

mother to give a soothing remedy, such as tea with lemon and honey or a

simpe cough linctus

iii. Blocked nose: if the nose is blocked and makes feeding difficult, advise

the mother to use a weak solution of saline nose drops given using a

moistened wick of clean cloth before feeding

iv. Conjunctivitis : if the child has a clear watery discharge from the eye,

advise the mother not to do anything special. If the eyes are sticky

because of pus, advise regular cleaning with cotton swabs and apply

tetracycline eye ointment three times a day. The cotton swabs should be

boilde in water and allowed to cool before use.

v. Sore mouth. Rinse the mouth with clean water as often as possible, but at

least for times a day. Advise frequent sips of clean water.

b. Provide nutritional support and promote breastfeeding


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c. Provide vitamin A

d. Inform the mother about the illness and what to expect in the next few days

i. Tell the mother about measles and that, even after the recovery, the child is

at increased risk of developing other infections and malnutrition. Advise

the mother that the child should attend the clinic regularly for health

checks and growth monitoring. The first follow up visit should be abou14

days after the measles illness starts and thereafter ay least once a month for

a minimum period of six months

ii. Advise the mmoher to bring any other unimmunized children for

immunization at once. Immunizig susceptible children within 72 hours of

exposure may prevent the disease from occuring in contacts.

iii. Advise he mother to bring the child back immediately if the childs

condition worsen.

Table 1. Vitamin A Dosage

Age Immediately on

Diagnosis

Next Day 2-4 weeks late (if eye

signs)Infants < 6 Months 50.000 IU 50.000 IU 50.000 IU

Infants aged 6-11

Months

100.000 IU 100.000 IU 100.000 IU

Children aged >12

months

200.000 IU 200.000 IU 200.000 IU

2.1.8 Complication

Complications of measles are largely attributable to the pathogenic effects of the virus

on the respiratory tract and immune system . There are several factors that make

complications more likely. Morbidity and mortality from measles are greatest in patients


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Measles infection lowers serum retinol, so subclinical cases of hyporetinolemia may be made

symptomatic during measles. Measles infection in immunocompromised persons is

associated with increased morbidity and mortality. Pneumonitis occurs in 58% of patients

with malignancy infected with measles, and encephalitis occurs in 20%. Pneumonia is the

most common cause of death in measles. It

may manifest as giant cell pneumonia caused directly by the viral infection or as

superimposed bacterial infection. The most common bacterial pathogens are S. pneumoniae,

H. influenzae, and S. aureus. Following severe measles pneumonia, the final common

pathway to a fatal outcome is often the development of bronchiolitis obliterans. Croup,

tracheitis, and bronchiolitis are common complications in infants and toddlers with measles.

The clinical severity of these complications frequently requires intubation and ventilatory

support until the infection resolves. Acute otitis media is the most common complication of

measles and was of particularly high incidence during the epidemic of the late 1980s and

early 1990s because of the relatively young age of affected children. Sinusitis and mastoiditis

also occur as complications. Viral and/or bacterial tracheitis are seen and can be life

threatening. Retropharyngeal abscess has also been reported. Measles infection is known to

suppress skin test responsiveness to purified tuberculin antigen. There may be an increased

rate of activation of pulmonary tuberculoses in populations of individuals infected with

Mycobacterium tuberculosis. Diarrhea and vomiting are common symptoms associated with

acute measles, and the gastrointestinal tract has diffuse giant cell formation in the epithelium.

Dehydration is a common consequence, especially in young infants and children.

Appendicitis may occur due to obstruction of the appendiceal lumen by lymphoid

hyperplasia. Febrile seizures occur in


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and immunosuppression. Signs and symptoms include seizures, myoclonus, stupor, and

coma. In addition to intracellular inclusions, abundant viral nucleocapsids and viral antigen

are seen in brain tissue. Progressive disease and death almost always occurs. A severe form

of measles rarely seen now is hemorrhagic or "black measles." It presented with a

hemorrhagic skin eruption and was often fatal. Keratitis, appearing as multiple punctate

epithelial foci, resolved with recovery from the infection. Thrombocytopenia sometimes

occurred following measles. Myocarditis is a rare complication. Miscellaneous bacterial

infections have been reported, including bacteremia, cellulitis, and toxic shock syndrome.

Measles during pregnancy has been associated with high maternal morbidity, fetal wastage

and stillbirths, and congenital malformations in 3% of live born infants. 3

2.1.9 Prevention

Patients shed measles virus from 7 days after exposure to 4-6 days

after the onset of rash. Exposure of susceptible individuals to measles

patlents should be avoided during this period. In hospttals, standard and

airborne precautions should be observed for this period.

Immunocompromised patients with measles will shed for the duration of

the illness, and isolationshould be maintained throughout.3

2.2 Mumps

2.2.1 Definition

Mumps is an acute infection illness that caused by a virus with a

characteristic of parotid swelling and tenderness3

2.2.2 Etiology

Mumps virus is in the family Paramyxoviridae and the genus

Rubulavirus. It is a single-stranded pleomorphic RNA virus encapsulated

in a lipoprotein envelope and possessing 7structural proteins. Two surface

glycoproteins, HN (hemagglutinin-neuraminidase) and F (fusion), mediate

absorption of the virus to host cells and penetration into cells,

respectively. Both stimulate production of protective antibodies. Mumps

virus exists as a single immunotype, and humans are the only natural


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host.3

2.2.3 Epidemiology

In the United States, the reported incidence of mumps declined after

the introduction of mumps vaccine in 1967 and the recommendation for

its routine use in 1977. After expanded recommendations for a 2-dose

measles, mumps, and rubella (MMR) vaccine schedule for measles control

in 1989, mumps cases declined further.During 2001 to 2003, fewer than

300 mumps cases were reported each year a 99% decline from the 185

691 cases reported in 1968 Following a first case of mumps on a collegecampus in eastern Iowa in December 2005, outbreaks in 8 states and >

2600 cases ensued. The virus strain was related to a genotype found in a

large outbreak in the United Kingdom in 2003. The age group most

affected (38% of cases) was young adults 18 to 24 years of age, many of

whom were college students, and then individuals a decade younger and

older. Parotitis was reported in the majority of individuals; complications

of orchitis, meningitis, encephalitis, deafness, oophoritis, mastitis, andpancreatitis were also reported. Endemic mumps infections are most

common in winter and early spring. Although rates of infection are similar

in males and females, males are more likely to have complications.3

2.2.4 Pathogenesis

Mumps virus targets the salivary glands, central nervous system

(CNS), pancreas, testes, and, to a lesser extent, thyroid, ovaries, heart,

kidneys, liver, and joint synovia. Following infection, initial viral replication

occurs in the epithelium of the upper respiratory tract. Infection spreads

to the adjacent lymph nodes by the lymphatic drainage, and viremia

ensues, spreading the virus to targeted tissues. Mumps virus causes

necrosis of infected cells and is associated with a lymphocytic

inflammatory infiltrate. Salivary gland ducts are lined with necrotic

epithelium, and the interstitium is infiltrated with lymphocytes. Swelling of


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tissue within the testes may result in focal ischemic infarcts. The

cerebrospinal fluid (CSF) frequently contains mononuclear pleocytosis,

even in individuals without clinical signs of meningitis.3

2.2.5 Clinical Signs and Symptoms

One-third of patients with mumps infection have subclinical or mild

respiratory disease. The most common manifestation is parotid swelling,

which is usually unilateral at the onset of illness, later becoming bilateral

in 70% of cases. Prodromal symptoms, including headache, vague

abdominal discomfort, and loss of appetite, typically precede the parotid

swelling by 12 to 24 hours. Earache on the side of parotid involvement

and discomfort with eating or drinking acidic food are common

complaints. Parotid pain is most pronounced during the first few days of

swelling. The swollen parotid gland lifts the earlobe upward and outward,

and the angle of the mandible is obscured the opening of the Stensen

duct on the buccal mucosa is edematous and erythematous. Trismus

(spasm of the masticatory muscles) can occur. Other salivary glands such

as the submandibular and sublingual glands may also be involved.

Presternal edema can be notable. Morbilliform rash has been reported in

association with mumps infection. Systemic symptoms, including fever,

usually resolve within 3 to 5 days, and the parotid swelling subsides within

7 to 10 days. Adolescents and adults have more severe disease than

young children. For purposes of surveillance, the Council of State and

Territorial Epidemiologists (CSTE) has established a case definition of

mumps infection based on clinical and laboratory criteria. The clinical case

definition of mumps is an illness with acute onset of unilateral or bilateral

swelling of the parotid or other salivary gland lasting more than 2 days

and without other apparent cause. Laboratory criteria for diagnosis

include a positive IgM antibody test for mumps, a significant rise in IgG

titers in acute and convalescent serum, isolation of mumps virus by

culture or detection by reverse transcriptase (RT)-PCR. A confirmed case

is one that is laboratory confirmed or meets the clinical case definitionand is linked to a confirmed or probable case of mumps.26 Studies have


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shown that failure to use a strict case definition or confirmatory laboratory

testing can lead to an overestimation of the number of cases of mumps in

a population.3

2.2.6 Diagnosis and Differential Diagnosis

When mumps was highly prevalent, the diagnosis could be made

based on history of exposure to mumps infection, an appropriate

incubation period, and development of typical

clinical findings. Confirmation of the presence of parotiditis could be made

with demonstration of an elevated amylase level. Leukopenia with a

relative lymphocytosis was a common finding. Today, in patients with

parotiditis of >2 days of unknown cause, a specific diagnosis of mumps

should be confirmed or ruled out by virologic or serologic means. This may

be accomplished by isolation of the virus in cell culture, detection of viral

antigen by direct immunofluorescence, or identification of nucleic acid by

reverse transcriptase polymerase chain reaction. Virus can be isolated

from upper respiratory tract secretions, CSF, or urine during the acute

illness. Serologic testing is usually a more convenient and available mode

of diagnosis. A significant increase in serum mumps immunoglobulin G

(IgG) antibody between acute and convalescent serum specimens by

complement fixation, neutralization hemagglutination, or enzyme

immunoassay (EIA) tests establish the diagnosis. However, IgG antibody

tests may cross react with antibodies to parainfluenza virus. More

commonly, an EIA for mumps IgM antibody is used to identify recent

infection. Skin testing for mumps is neither sensitive nor specific and

should not be used.

Parotid swelling may be caused by many other infections and

noninfectious conditions. Viruses that have been shown to cause parotitis

include parainfluenza 1 and 3, influenza A, cytomegalovirus, Epstein-Barr

virus, enteroviruses, lymphocytic choriomeningitis virus, and HIV. Purulent

parotitis, usually caused by Staphylococcus aureus, is unilateral,

extremely tender, and associated with an elevated white blood cell count,and may have purulent drainage from the Stensen duct. Submandibular or


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anterior cervical adenitis due to a variety of pathogens may also be

confused with parotitis. Other noninfectious causes of parotid swelling

include obstruction of the Stensen duct, collagen vascular diseases such

as Sjogren syndrome, systemic lupus erythematosis, and tumor.

3

2.2.7 Treatment

Mumps is a self limited diseases. Conservative therapy is given such

as adequate hydration and nutrition to reduce the morbidityand to help

healing process. Paracetamol can be used to reduce the pain due to

parotid swelling.

2.2.8 Complication

The most common complications of mumps are meningitis, with or

without encephalitis, and gonadal involvement. Uncommon complications

include conjunctivitis, optic neuritis, pneumonia, nephritis, pancreatitis,

and thrombocytopenia. Maternal infection with mumps during the 1st

trimester of pregnancy results in increased fetal wastage. No fetal

malformations have been associated with intrauterine mumps infection.

However, perinatal mumps disease has been reported in infants born to

mothers who acquired mumps late in gestation.

1. Meningitis and Meningoencephalitis. Mumps virus is

neurotropic and is thought to enter the CNS via the choroid

plexus and infect the choroidal epithelium and ependymal cells,

both of which can be found in CSF along with mononuclearleukocytes. Symptomatic CNS involvement occurs in 10-30% of

infected individuals, but CSF pleocytosis has been found in 40-

60% of patients with mumps parotitis. The meningoencephalitis

may occur before, along with, or following the parotitis. It most

commonly will present 5 days after the parotitis. Clinical findings

vary with age. Infants and young children will have fever,

malaise, and lethargy, while older children, adolescents, and

adults will complain of headache and demonstrate meningeal


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signs. In 1 series in children with mumps with meningeal

involvement, findings were fever in 94%, vomiting in 84%,

headache in 47%, parotitisin 47%, neck stiffness in 71%, lethargy

in 69%, and seizures in 18%. In typical cases, symptoms resolvein 7-10 days. CSF in mumps meningitis has a white blood cell

pleocytosis of 200-600/mm3 with a predominance of

lymphocytes. The glucose is normal in most patients, but a

moderate hypoglycorrhachia (20-40 mg/dL) may be seen in 10-

20% of patients. Protein is normal or mildly elevated. Less

common CNS complications of mumps include transverse

myelitis, aqueductal stenosis, and facial palsy. Sensorineural

hearing loss is rare but has been estimated to occur in 0.5-

5.0/100,000 cases of mumps. There is some evidence that it is

more likely in patients with meningoencephalitis.

2. Orchitis and Oophoritis. In adolescent and adult males,

epidymoorchitis is 2nd only to parotitis as a common finding in

mumps. Involvement in prepubescent male children is extremely

rare, but following puberty it occurs in 30-40% of males. It begins

within days following onset of parotitis in the majority of cases

and is associated with moderate to high fever, chills, and

exquisite pain and swelling of the testes. In


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mumps, and molecular studies have identified mumps virus in

heart tissue taken from patients with endocardia1 fibroelastosis.

5. Arthritis. Arthralgia, monoarthritis, and migratory polyarthritis

have been reported in mumps. It is seen with or without

parotitisand usually occurs within 3 weeks of onset of parotid

swelling. It is generally mild and self-limited.

6. Thyroiditis. Thyroiditis is rare following mumps. It has not

beenreported without parotitis and may occur weeks following

theacute infection. Most cases resolve, but some become

relapsing and result in hypothyroidism.

2.2.9 Prevention

Immunization with the live mumps vaccine is the primary mode of

prevention used in the United States. It is given as part of the MMR 2 dose

vaccine schedule, at 12-15 mo of age for the 1st dose and 4-6 yr of age

for the 2nd dose. If not given at 4-6 yr, the 2nd dose should be given

before children enter puberty. Antibody develops in 95% of vaccinees

after 1 dose. One study showed vaccine effectiveness of 88% for 2 doses

of MMR vaccine compared with 64% for a single dose. Immunity appears

to be long lasting, with existing serologic and epidemiologic evidence

indicating protection for >25 yr. As a live-virus vaccine, MMR should not

be administered to pregnant women or severely immunodeficient or

immunosuppressed individuals. HIV-infected patients not severely

immunocompromised may receive the vaccine since the risk for severe

infection with mumps outweighs the risk for serious reaction to the

vaccine. Individuals with anaphylactoid reactions to egg or neomycin may

be at risk for immediate-type hypersensitivity reactions to the vaccine.

Persons with other types of reactions to egg or reactions to other


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components of the vaccine are not restricted from receiving the vaccine.

2.3 Human Immunodeficiency Virus (HIV)

2.3.1. Definition

Human immunodeficiency virus in an infection that affects the cells of the immune

system, including helper T lymphocytes (CD4 lymphocytes), monocytes and macrophages.

The functions ofthese cells are diminished by HIV infection, with profound affects towards

both humoral and cell-mediated immunity. In the absence of treatment, HIV infection causes

deterioation of the immune system, leading to conditions that is known as acquired

immunodeficiency syndrome (AIDS), and severe complications due to vulnerability towards

infections.

2.3.2. Etiology

HIV infectino is caused by a complex member of the Lentivirus genus of the

Retroviridae family. HIV-1 is the most common cause of HIV infection in the South east

Asia. HIV-2 disease progresses more slowly than HIV-1 disease, and HIV-2 is less

transmissible than HIV-1

HIV-1 subtypes differ by geographic region. HIV-1 non-B subtypes are the most

dominant is South east Asia and Africa. The high transmission rate from these countries to

Europe has increased the diversity of subtypes in Europe. In United States however, HIV-1 B

subtypes are the most dominant types.

Vertical transmission of HIV from mother to child is the main route by which

childhood HIV infection is acquired, and the risk of this perinatal acquisition is 25%.

2.3.3. Epidemiology

The World health organization estimates that approximately 2.5 million children were

living with HIV infection as of 2009. In 2009 alone, 370,000 children were newly infected.

This is a drop of 24 % from 5 years earlier.

About 0.9% of cases of HIV infection occur in children younger than 1 years old and

1.4% in children younger than 4 years. Incidence peaks in those whose age group are

within20-29years old.


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According to the national survey, the percentage of cases caused by mother to baby

transmission as a risk factor is 2.7 %. This figure has decreased more than 40% from the past

respective years since 1991.

The WHO estimates that over 33 million individuals are infected with HIV

worldwide, and 90% of them are in developing countries. HIV has infected 4.4 million

children and has resulted in the deaths of 3.2 million. Each day, 1800 childrenthe vast

majority newbornsare infected with HIV. Approximately 7% of the population in sub-

Saharan Africa is infected with HIV; these individuals represent 64% of the world's HIV-

infected population. Furthermore, 76% of all women infected with HIV live in this region.

Although the annual number of new HIV infections has been steadily declining since

the late 1990s, the epidemics in Eastern Europe and in Central Asia continue to grow; the

number of people living with HIV in these regions reached an estimated 1.6 million in 2005

an increase of almost 20-fold in less than 10 years.2The overwhelming majority of these

people living with HIV are young; 75% of infections reported between 2000 and 2004 were

in people younger than 30 years. In Western Europe, the corresponding percentage was 33%.

The magnitude of the AIDS epidemic in Asia is significant. The seroprevalence rate

in pregnant women is already 2%, and the vertical transmission rate is 24% without

breastfeeding. Indian mothers infected with HIV routinely breastfeed and have transmission

rates as high as 48%.

Globally, children outside the United States are not faring as well. Every day, 1400

children become HIV positive and 1000 children die of HIV-related causes. An estimated 2.5

million children worldwide younger than 15 years are living with HIV/AIDS. In sub-Saharan

Africa alone, 1.9 million children are living with HIV/AIDS and more than 60% of all new

HIV infections occur in women, infants, or young children. As of 2007, 90% of the newly

infected children are infants who acquire HIV from their infected mothers. Alarmingly, 90%

of babies who acquire the disease from infected mothers are found in sub-Saharan Africa.

The prevalence of HIV infection among undernourished children has been estimated to be as

high as 25%.

In 2004, more than half a million children younger than 15 years died from

HIV/AIDS. In 2006, this number decreased to 380,000. In 2002, HIV/AIDS was the seventh

leading cause of mortality in children in developing countries. The disease progresses rapidly

in approximately 10-20% of children who are infected, and they die of AIDS by age 4 years,

whereas 80-90% survive to a mean age of 9-10 years.


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A 2006 South African study estimated that HIV/AIDS is the single largest cause of

infant and childhood deaths in rural South Africa.HIV/AIDS is now responsible for 332,000

child deaths in sub-Saharan Africa, almost 8% of all child deaths in the region.3

The results of one study noted that pneumonia and malnutrition are highly prevalent

and are significantly associated with high rates of mortality among hospitalized, HIV-infected

or HIV-exposed children in sub-Saharan Africa. Other independent predictors of death were

septicemia, Kaposi sarcoma, meningitis, and esophageal candidiasis for HIV-infected

children; and meningitis and severe anemia for inpatients exposed to HIV. These results

stress the importance of expediently establishing therapeutic strategies in African pediatric

hospitals.4

2.3.4. Pathogenesis and Pathophysiology

The pathogenesis of HIV is basically a struggle between HIV replication and the

immune responses of the patient, via cell-mediated and immune-mediated reactions. The HIV

viral burden directly and indirectly mediates CD4+ T-cell destruction.

When the mucosa serves as the portal of entry for the HIV, the first cells to be

infected are the dendritic cells. These cells are in charge of collecting and processing antigens

introduced from the periphery and transporting them to the lymphoid tissue. The HIV does

not infect the dendritic cell but it binds to its DC-SIGN surface molecule, which allows the

virus to survive until it reaches the lymphatic tissue. In the lymph node, the HIV selectively

binds to cells expressing CD4 molecules on their surface, primarily helper T lymphocytes

(CD4 cells) and cells of the monocyte-macrophage lineage.

Another cells such as microglia, astrocytes, oligodendroglia, and placental tissue

containing villous Hofbauer cells, may also be infected by HIV. Usually, CD4 lymphocytes,

recruited to respond to viral antigen, migrate to the lymph nodes where they become

activated and proliferate, making them highly susceptible to HIV infection. This antigen-

driven migration and accumulation of CD4 cells within the lymphoid tissue may contribute to

the generalized lymphadenopathy characteristic of the acute retroviral syndrome in adults and

adolescents. When the HIV replication reaches a threshold (usually within 36 wk from the

time of infection), a burst of plasma viremia occurs. This intense viremia cause flulike

symptoms (i.e., fever, rash, lymphadenopathy, and arthralgia) in 5070% of infected adults.

With establishment of a cellular and humoral immune response within 24 mo, the viral load

in the blood declines substantially, and patients enter a phase characterized by a lack of

symptoms and a return of CD4 cells to only moderately decreased levels.


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Table 2. Cells Infected by HIV

System Cell

Hematopoietic T-cells (CD4+ OR CD 8+) Macrophages/monocytes Dendritic cells

Fetal thymocytes and thymic epithelium

B-cells

NK cells

Megakaryotic cells

Stem cells

Central Nervous Microglia Capillary endothelial cells

Astrocytes

Oligodendrocytes

Large Intestine Columnar epithelium

Other Kupfer cells (liver

Synovial cells

Placental tophoblast cells

Adapted from Levy L.A. Microbiological Reviews, 57:183-289, March 1993

These cells may be destroyed by multiple mechanisms: HIV-mediated single cell

killing, formation of multinucleated giant cells of infected and uninfected CD4 cells (syncytia

formation), virus-specific immune responses, superantigen-mediated activation of T cells

(rendering them more susceptible to infection with HIV), and programmed cell death

(apoptosis). Viral replication in monocytes, which can be infected productively yet resist

killing, explains their role as reservoirs of HIV and as effectors of tissue damage in organs

such as the brain.

Cell-mediated and humoral responses occur early in the infection. The CD8 T cells

play an important role in containing the infection. HIV-specific cytotoxic T lymphocytes

(CTLs) develop against both the structural (i.e., ENV, POL, GAG) and regulatory (e.g., tat)

viral proteins. The CTL cells appear at the end of the acute retroviral infection as the viral

replication is controlled. The CTL cells control the infection by killing HIV-infected cells

before new viruses are produced and by secreting potent antiviral factors that compete with

the virus for its receptors (e.g., CCR5). Neutralizing antibodies appear later during theinfection and seem to help in the continued suppression of viral replication during clinical


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latency. There are at least two possible mechanisms that control the steady-state viral load

level during the chronic clinical latency. One mechanism may be the limited availability of

activated CD4 cells which prevent further increase in viral load due to a set point (i.e.,

controlled) replication. The other mechanism, the immune-control, suggests that the

development of active immune response (whose magnitude is controlled by the amount of the

viral antigen) limits the viral replication at a steady state. There is no general consensus about

which of these two mechanisms is more important. The CD4cell limitation mechanism

accounts for the effect of antiretroviral therapy, whereas the immune-control mechanism

emphasizes the importance of immune-modulation treatment (e.g., cytokines, vaccines) to

increase the efficiency of the immune response, which, in turn, slows the disease progression.

A group of cytokines, such as tumor necrosis factor (TNF), TNF, interleukin 1

(IL-1), IL-3, IL-6, interferon-, granulocyte-macrophage colony-stimulating factor (GM-

CSF), and macrophage colony-stimulating factor, play an integral role in upregulating HIV

expression from a state of quiescent infection to active viral replication. Other cytokines such

as interferon (INF), INF-, and transforming growth factor D exert a suppressive effect on

HIV replication. The interactions among these cytokines influence the concentration of viral

particles in the tissues. Plasma concentrations of cytokines need not be elevated for them to

exert their effect, because they are produced and act locally in the tissues. Thus, even during

states of apparent immunologic quiescence, the complex interaction of cytokines sustains a

constant level of viral expression, particularly in the lymph nodes.

Commonly the phenotypic HIV isolated during the clinical latency period grows

slowly in culture and produces low titers of reverse transcriptase. These isolates are called

nonsyncytium-inducing (NSI) viruses, which use CCR5 as their co-receptor. By the late

stages of the clinical latency, the isolated virus is phenotypically different. It grows rapidly

and to high titers in culture and it uses CXCR4 as its co-receptor. These isolates are called

syncytium-inducing (SI) viruses. The switch from NSI to SI increases the capacity of the

virus to replicate, to infect a broader range of target cells (CXCR4 is more widely expressed

on resting and activated immune cells), and to kill T cells more rapidly and efficiently. As a

result, the clinical latency phase is over and progression toward AIDS is noted. The

progression of disease is related temporally to the gradual disruption of lymph node

architecture and degeneration of the follicular dendritic cell network with loss of its ability to

trap HIV particles. This frees the virus to recirculate, producing high levels of viremia and an

increased disappearance of CD4 T cells during the later stages of disease.


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HIV-infected children have changes in the immune system that are similar to those in

HIV-infected adults. CD4 cell depletion may be less dramatic because infants normally have

a relative lymphocytosis. Lymphopenia is relatively rare in perinatally infected children and

is usually only seen in older children or those with end-stage disease.

2.3.5 Clinical Manifestations

The clinical manifestations of HIV infection vary widely among infants, children, and

adolescents. In most infants, physical examination at birth is normal. Initial symptoms may

be subtle, such as lymphadenopathy and hepatosplenomegaly, or nonspecific, such as failure

to thrive, chronic or recurrent diarrhea, interstitial pneumonia, or oral thrush, and may be

distinguishable only by their persistence. Symptoms found more commonly in children thanadults with HIV infection include recurrent bacterial infections, chronic parotid swelling,

lymphocytic interstitial pneumonitis (LIP), and early onset of progressive neurologic

deterioration.

Table 3. Clinical Finding Suggestive for HIV

Highly suggestive for HIV

infection

Suggestive for HIV

infection

Likely to be evidence of

HIV infection but common

in both HIV-infected and

uninfected children

Esophageal candidiasis

Herpes zoster

Invassivesamonella infection

Pneumocystis jirovecii

pneumonia

Extrapulmonary

cryptococcosis

Kaposi sarcoma

Recurrent severe bacterial

infection

Persistent or recurrent oral

thrush

Parotid enlagement

Generalized

lymphadenopathy

Hepatosplenomegaly

Persistent orrecurrent fever

Neurologic dysfunction

Otitis media- persistent or

recurrent

Diarrhea persistent or

recurrent

Severe Pneumonia

Tuberculosis

Failure to thrive


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sPersistent generalized

dermatitis

2.3.6 Diagnostic

There are several laboratory tests to diagnose hiv infection. It can be devided into antibody

and virologic test. HIV rapid test, HIV ELISA and Western Blot are kind of serologic test.

HIV-1 RNA PCR. HIV-1 RNA PCR, another important virologic test, is commonly used to

monitor response to HIV treatment.

Table 4. Common HIV Diagnostic Tests

Antibody Virologic

HIV rapid test HIV-1 DNA PCR

HIV ELISA (also called EIA) HIV-1 RNA PCR (viral load)

Western blot Ultrasensitive p24 antigen

assay test

HIV culture

2.3.6.1 Antibody Test

Antibody test is used to diagnose HIV infection. This category of test includes HIV

rapid tests, ELISA, and Western blot. Antibody tests can detect the antibodies that are

produced during the immune response to HIV. Like most lab tests, they can yield

falsenegative and false-positive results. False-negative tests occur when HIV-infected

individuals do not produce detectable antibodies, such as during the early, acute phase of the

infection (the preantibody, or window, period) and the very late stages of infection (when

immune suppression is severe and antibodies are no longer being produced in response to

HIV infection).Usually, individuals produce antibodies within 6 weeks of infection, and

almost all infected individuals have detectable antibodies by 12 weeks postinfection.

The other primary cause of false-negative antibody tests is severe

immunosuppression. During the very late stages of HIV-infection, antibody levels can fall so

far as to become undetectable. When a false negative is suspected in the presence of severe

clinical symptoms, further testing is required. One of the most important diagnostic

limitations of antibody tests occurs in infants younger than 18 months. During pregnancy,


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HIV-infected mothers passively transfer immunoglobulin G HIV antibody to the infant

through the placenta.

2.3.6.2 Virologic Tests

HIV-1 RNA PCR. HIV-1 RNA PCR, another important virologic test, is commonly

used to monitor response to HIV treatment. Whereas DNA PCR is a qualitative test providing

positive or negative results, RNA PCR tests are quantitative and indicate how much HIV is in

the blood. For this reason, RNA PCR is also known as the viral loadmand represents the

number of copies of HIV per milliliter. RNA PCR is also an accurate method of HIV

diagnosis in young infants (>10,000 copies/mL is considered diagnostic). RNA PCR

sensitivity and specificity are similar to those of DNA PCR in this group (nearly 100% by 6

weeks of age for exposed, nonbreast-feeding infants).

Ultrasensitive p24 antigen assay. Another laboratory test that directly detects HIV in

the bloodstream is the p24 antigen test. The antigen p24 is a major core protein of HIV that

can be found either free in the bloodstream of HIV-infected people or bound to anti-p24

antibody.

2.3.7 Clinical Staging On HIV Infection

Clinical staging is for use where HIV infection has been confirmed (i.e. serological

and/or virological evidence of HIV infection). It is informative for assessment at baseline or

entry into HIV care and can also be used to guide decisions on when to start CPT in HIV-

infected children and other HIV-related interventions, including when to start, switch or stop

ART in HIV-infected children, particularlyin situations where CD4 is not available.

Table 5. Clinical Stage On HIV Infection

Children less than 15 years old Children greater than 15 years old and adults

CLINICAL STAGE 1

Asymptomatic

Persistent.generalized lymphadenopathy

CLINICAL STAGE 1

Asymptomatic

Persistent.generalized lymphadenopathy

CLINICAL STAGE 2

Unexplained persistent hepatosplenomegaly

Papular pruritic eruptions

Extensive wart virus infection

CLINICAL STAGE 2

Unexplained moderate weight loss (


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Extensive molluscum contagiosum

Fungal nail infections

Recurrent oral ulcerations

Unexplained persistent parotid enlargement

Lineal gingival erythema

Herpes zoster

Recurrent or chronic upper respiratory tract

infections (otitis media,

otorrhoea, sinusitis or tonsillitis)

Recurrent respiratory tract infections

(sinusitis, tonsillitis, otitis

media and pharyngitis)

Herpes zoster

Angular cheilitis

Recurrent oral ulceration

Papular pruritic eruptions

Seborrhoeic dermatitis

Fungal nail infections

CLINICAL STAGE 3

Unexplained moderate malnutrition not

adequately responding to

standard therapy

Unexplained persistent diarrhea (14 days or

more)

Unexplained persistent fever (above 37.5C

intermittent or

constant, for longer than one month)

Persistent oral candidiasis (after 6-8 weeks

of life)

Oral hairy leukoplakia

Acute necrotizing ulcerative gingivitis or

periodontitis

Lymph node tuberculosis

Pulmonary tuberculosis

Severe recurrent bacterial pneumonia Symptomatic lymphoid interstitial

pneumonitis

Chronic HIV-associated lung disease

including brochiectasis

Unexplained anaemia (


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CLINICAL STAGE 4

Unexplained severe wasting, stunting or

severe malnutrition not

responding to standard therapy

Pneumocystis pneumonia

Recurrent severe bacterial infections (such

as empyema, pyomyositis,

bone or joint infection or meningitis but

excluding pneumonia)

Chronic herpes simplex infection (orolabial

or cutaneous of more

than one months duration or visceral at any

site)

Extrapulmonary tuberculosis

Kaposi sarcoma

Oesophageal candidiasis (or candidiasis of

trachea, bronchi or lungs)

Central nervous system toxoplasmosis

(after one month of life)

HIV encephalopathy

Cytomegalovirus infection: retinitis or

cytomegalovirus infection

affecting another organ, with onset at age

older than one month

Extrapulmonary cryptococcosis (including

meningitis)

Disseminated endemic mycosis

(extrapulmonary histoplasmosis,

coccidiomycosis)

Chronic cryptosporidiosis

Chronic isosporiasis

Disseminated non-tuberculous

mycobacterial infection

Cerebral or B-cell non-Hodgkin lymphoma

CLINICAL STAGE 4

HIV waste syndrome

Pneumocystis pneumonia

Recurrent severe bacterial pneumonia

Chronic herpes simplex infection (orolabial,

genital or anorectal

of more than one months duration or visceral

at any site)

Oesophageal candidiasis (or candidiasis of

trachea, bronchi or

lungs)

Extrapulmonary tuberculosis

Kaposis sarcoma

Cytomegalovirus infection (retinitis or

infection of other organs)

Central nervous system toxoplasmosis

HIV encephalopathy

Extrapulmonary cryptococcosis including

meningitis

Disseminated non-tuberculous

mycobacterial infection

Progressive multifocal leukoencephalopathy

Chronic cryptosporidiosis

Chronic isosporiasis

Disseminated mycosis (extrapulmonary

histoplasmosis or

coccidiomycosis)

Recurrent septicaemia (including non-

typhoidal Salmonella)

Lymphoma (cerebral or B-cell non-

Hodgkin)

Invasive cervical carcinoma

Atypical disseminated leishmaniasis

Symptomatic HIV-associated nephropathy


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Progressive multifocal

leukoencephalopathy

Symptomatic HIV-associated nephropathy

or HIV-associated

cardiomyopathy

Some additional specific conditions can also

be included in regional classifications

(such as reactivation of American

trypanosomiasis [meningoencephalitis

and/or myocarditis] in the WHO Region of

the Americas, penicilliosis in Asia

and HIV-associated rectovaginal fistula in

Africa).

or symptomatic

HIV-associated cardiomyopathy

Source: WHO case definitions of HIV for surveillance and revised clinical staging and

immunological classification of HIV-related disease in adults and children, 2007. Available

at http://www.who.int/hiv/pub/guidelines/en/.

Table. 6. Stage of HIV Infection Base on CD4+ Count

HIV-associated

immunodeficiency

5 years

months (%

CD4+)

None or not

significant

>35 >30 >25 >500

Mild 30-35 25-30 20-25 350-499

Advanced 25-29 20-24 15-19 200-349

Severe


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an attempt to protect itself from HIV. This is when the viral set point is established. The

viral load of the set point can be used to predict how quickly disease progression will occur.

People with higher viral load set points tend to exhibit more rapid disease progression than

those with lower viral load set points. During latency, HIV-infected patients may or may not

have signs and symptoms of HIV infection though persistent lymphadenopathy is common.

In HIVinfected adults, this phase may last 810 years. The HIV enzyme-linked

immunosorbent assay and Western blot or immunofluorescence assay will be positive. The

CD4+ count is greater than 500 cells/L in children over 5 years of age.

2.3.7.2. Clinical Stage 2

HIV-infected people may appear to be healthy for years, and then minor signs and symptoms

of HIV infection begin to appear. They may develop candidiasis, lymphadenopathy,

molluscom contagiosum, persistent hepatosplenomegaly, popular pruritic eruptions, herpes

zoster, and/or peripheral neuropathy. The viral load increases, and the CD4+ count falls is

between 350-499/ uL in children older than 5 years. Once patients are in this stage they

remain in stage 2. They can be reassigned stage 3 or 4 if a condition from one of those

occurs, but they cannot be reassigned to Clinical Stage 1 or 2 if they become asymptomatic.

2.3.7.3 Clinical Stage 3

HIV-infected patients with weakened immune systems can develop life-threatening

infections. The development of cryptosporidiosis, pulmonary and lymph node tuberculosis,

wasting, persistent fever (longer than one month), persistent candidasis, recurrent bacterial

pneumonia, and other opportunistic infections is common. These patients may be wasting, or

losing weight. Their viral load continues to increase, and the CD4+ count falls to less than

200-349 cells/L in children older than 5 years.

2.3.7.4 Clinical Stage 4

Patients with advanced HIV disease, or AIDS, can continue to develop new

opportunistic infections, such as Pneumocystis jirovecii pneumonia (formerly Pneumocystis

carinii pneumonia), cytomegalovirus infection, toxoplasmosis, Mycobacterium avium

complex, cryptococcal meningitis, progressive multifocal leukoencephalopathy, Kaposi


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sarcoma and other infections that commonly occur with a severely depressed immune system.

The viral load is very high, and the CD4+ count is less than 200 cells/L in children older

than 5 years. At this point in the disease course death can be imminent.

2..3.8 Treatment

Table 7. Indications for initiation of antiretroviral therapy in children infected

with human immunodeficiency virus (HIV)

Age Criteria Reccomendation


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The preferred option when choosing a first-line regimen for infants and children is

two nucleoside reverse transcriptase inhibitors (NRTIs) plus one non-nucleoside reverse

transcriptase inhibitor (NNRTI). These drugs prevent HIV replication by inhibition of the

action of reverse transcriptase, the enzyme that HIV uses to make a DNA copy of its RNA.

Regimen of 2 NRTI plus 1 NNRTI:

AZT b + 3TCc + NVPd/ EFVe

d4T b + 3TCc + NVPd /EFVe

ABC + 3TCc + NVPd/ EFVe

In addition, they preserve a potent new class (i.e. protease inhibitors [PIs]) for the

second line. The disadvantages include different half-lives, the fact that a single mutation is

associated with resistance to some drugs (e.g. lamivudine [3TC], NNRTIs), and, in respect of

the NNRTIs, a single mutation can induce resistance to all currently available drugs in the

class.

Active components of these regimens may include a thymidine analogue NRTI (i.e.

stavudine [d4T], zidovudine [AZT]) or a guanosine analogue NRTI (i.e. abacavir [ABC]),

combined with a cytidine analogue NRTI, (i.e. lamivudine [3TC] or emtricitabine [FTC]) and

an NNRTI (i.e. efavirenz [EFV] or nevirapine [NVP])

A caveat is that EFV is not currently recommended for use in children under 3 years

of age because of a lack of appropriate dosing information, although these matters are under

study. For such children, consequently, NVP is the recommended NNRTI. Additional

concerns about NNRTIs as components of first-line regimens relate to their use in

adolescents , these include the teratogenic potential of EFV in the first trimester of pregnancy

and the hepatotoxicity of NVP in adolescent girls with CD4 absolute cell counts >250/mm3.The available data on infants and children indicate a very low incidence of severe

hepatotoxicity for NVP without association with CD4 count.

2.3.9 Education

Educating parents regarding the importance of compliance with prescribed

medications and health care visits is a major challenge. Patients should be educated regarding

the transmission of HIV. Increasing their awareness of the mechanism and consequences of


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HIV transmission is important. Safe social interactions that do not expose people to an

increased risk for HIV transmission should also be emphasized.

2.3.10 Complication

Many people living with human immunodeficiency virus (HIV)/AIDS acquire

diseases that also affect otherwise healthy people. In such cases, HIV-infected patients may

have a more severe disease course than uninfected people or may develop symptoms that

uninfected people do not. However, HIV-infected people are also susceptible to opportunistic

infections (OIs), which are infections caused by organisms that in a healthy. Not only OIs,

HIV also can cause malnutrition and wasting syndromes to the patient. Therere several case

that usually found in HIV infection:

2.3.10.1Hepatitis

Hepatitis C virus (HCV) is a significant public health concern; it affects 3.9 million persons

in the United States and an estimated 170 million persons worldwide. Those persons with

repeated exposure to blood or blood products are at risk for both HIV and HCV infection. An

estimated 60%90% of persons with hemophilia and 50%90% of injection drug users who

have HIV are coinfected with hepatitis C. Currently, injection drug users account for 60% of

the persons with newly acquired cases of HCV infection in the United States, as well as 22%

of AIDS cases in men and 42% of AIDS cases in women. Therefore, coinfection with HIV

and HCV will be an increasing problem in the coming years.

As the life expectancy of patients with HIV improves, the clinical impact of HCV as a

comorbid condition may be increasingly noticed. Patients with HIV need to be evaluated for

HCV infection, and HCV should be defined as an opportunistic infection in patients with

HIV.

2.3.10.2 Cytomegalovirus

CMV, a beta-herpesvirus, is the major cause of non-Epstein-Barr virus infectious

mononucleosis in the general population and an important pathogen in immunocompromised

hosts, including patients with AIDS, neonates, and transplant recipients. The risk of exposure

to CMV increases with age, and serologic evidence of prior infection can be detected in

approximately 60% of the general adult population in the United States. Asymptomatic

excretion of CMV in saliva, respiratory secretions, urine, and semen is common and explains


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the increasing risk of exposure over time. As with other herpesviruses, CMV remains latent

in the infected host throughout life and rarely reactivates to cause clinical illness except in

immunocompromised individuals.

In patients with AIDS, progressive loss of immune function, and, in particular, loss of

cell-mediated immunity, permits CMV reactivation and replication to begin; asymptomatic

excretion of CMV in urine can be detected in approximately 50% of HIV-infected individuals

with a CD4 lymphocyte count


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individuals, and it remains the most common cause of death in patients with AIDS. HIV

infection has contributed to a significant increase in the worldwide incidence of TB. By

producing a progressive decline in cell-mediated immunity, HIV alters the pathogenesis of

TB, greatly increasing the risk of disease from TB in HIV-coinfected individuals and leading

to more frequent extrapulmonary involvement, atypical radiographic manifestations, and

paucibacillary disease, which can impede timely diagnosis. Although HIV-related TB is both

treatable and preventable, incidence continues to climb in developing nations wherein HIV

infection and TB are endemic and resources are limited. Interactions between HIV and TB

medications, overlapping medication toxicities, and immune reconstitution inflammatory

syndrome (IRIS) complicate the cotreatment of HIV and TB.

2.3.10.5 Toxoplasmosis

Toxoplasmosis is the leading cause of focal central nervous system (CNS) disease in

AIDS. CNS toxoplasmosis in HIV-infected patients is usually a complication of the late

phase of the disease. Typically, lesions are found in the brain and their effects dominate the

clinical presentation. Rarely, intraspinal lesions need to be considered in the differential

diagnosis of myelopathy. The decision to treat a patient for CNS toxoplasmosis is usually

empiric. Primary therapy is followed by long-term suppressive therapy, which is continued

until antiretroviral therapy can raise CD4+ counts above 200 cells/L. Prognosis is guarded.

Patients may relapse because of noncompliance or increasing dose requirements.

2.3.10.6 Pneumocystis Carinii Pneumonia

Pneumocystis carinii pneumonia (PCP) is an opportunistic infection that occurs in

immunosuppressed populations, primarily patients with advanced human immunodeficiency

virus infection. The classic presentation of nonproductive cough, shortness of breath, fever,

bilateral interstitial infiltrates and hypoxemia does not always appear. Diagnostic methods of

choice include sputum induction and bronchoalveolar lavage. The drug of choice for

treatment and prophylaxis is trimethoprim-sulfamethoxazole, but alternatives are often

needed because of adverse effects or, less commonly, treatment failure. Adjunctive

corticosteroid therapy improves survival in moderate to severe cases. Complications such as

pneumothorax and respiratory failure portend poorer survival. Prophylaxis dramatically

lowers the risk of disease in susceptible populations. Although PCP has declined in incidence


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in the developed world as a result of prophylaxis and effective antiretroviral therapy, its

diagnosis and treatment remain challenging.

2.3.11 Prognosis

Although HIV infection is usually deadly in children, especially in developing

countries, the development of new antiretroviral drugs is promising. The lack of access to

antiretroviral agents by children in developing countries is of particular concern.

The nutritional status of the child and the diligence with which viral replication is

controlled are paramount in determining the outcome of most children with HIV disease.

Aggressive treatment of opportunistic infections prevents the more deleterious effects ofsecondary disease from progressing and further weakening the patient. The social setting and

the stressors to which children are exposed have also been linked to the progression of the

disease.

Hematologic disturbances, such as anemia, thrombocytopenia, and neutropenia,

increase the risk of complications and death. Resolution of anemia improves the prognosis,

and treatment of anemia with erythropoietin improves survival. Neutropenia significantly

increases the risk of bacterial infection, and treatment of neutropenia with granulocyte

colony-stimulating factor substantially decreases the risk of bacteremia and death.

Infection with Mycobacteriumavium complex (MAC) hastens death, especially in

patients with coexisting anemia (defined as a hematocrit < 25%).

The following factors are associated with rapidly progressive disease in infants:

Advanced maternal disease

High maternal viral load

Low maternal CD4+ count

Prematurity

In utero transmission

High viral load in the first 2 months of life

Lack of neutralizing antibodies

Presence of p24 antigen

AIDS-defining illnesses

Early cytomegalovirus (CMV) infection


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Early neurologic disease

Failure to thrive

Early-onset diarrhea

Each logarithmic decrease in the viral load after the start of therapy decreases the risk of

progression by 54%.

Baseline CD4+ T-lymphocyte percentage and associated intermediate-term risk of death

in HIV-infected children is as follows:

< 5%: 97%

5-9%: 76%

10-14%: 43%

15-19%: 44%

20-24%: 25%

25-29%: 31%

30-34%: 10%

35%: 33%

Baseline HIV RNA copy number (copies/mL) and associated intermediate-term risk for

death in HIV-infected children is as follows:

Undetectable ( 4,000) : 24%

4,001-50,000 : 28%

50,001- 100,000 : 15%

100,001- 500,000 : 40%

500,001-1,000,00 : 40%

1,000,000 : 71%

The natural progression of vertically acquired HIV infection appears to have a trimodal

distribution. Approximately 15% of children have rapidly progressive disease, and the

remainder has either a chronic progressive course or an infection pattern typical of that

observed in adults. Mean survival is about 10 years.

In resource-poor nations, the progression to death is accelerated. In some instances, close

to 45-90% of HIV-infected children died by the age of 3 years. However, among children and

adolescents, the start of combination therapy including protease inhibitors reduces the


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intermediate-term risk of death by an estimated 67%. Also, host genetics play an important

role in HIV-1related disease progression and neurologic impairment

Combination antiretroviral treatment, available in resources settings since 1996, has

forestalled disease progression for over 15 years in many individuals. The full duration of the

favorable outcome of therapy is not yet defined, and it is not known whether adverse effects

from the medications will affect mortality or limit their use. Plasma viremia and age adjusted

CD4 lymphocyte counts are used to assess the risk of progression and response to

antiretroviral treatment. With the introduction of HAART, mortality rates for HIV infected

children in the United States declined 80% between 1994 and 1999. Many children, infected

from birth, are entering adolescence and young adulthood.

With recognition of the longer survival time in most infected children, this disease is

now approached as a chronic, rather than acute terminal, illness. The complexity of

antiretroviral drug therapy requires care from a provider with HIV expertise. Primary case

physicians are encouraged to participate in the care of HIV infected children in collaboration

with centers staffed by personnel with expertise in pediatric HIV issues.


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CHAPTER 3

CASE REPORT

Name : M S S

Age : 7 years 6 month

Sex : Female

Date of Admission : March, 11th 2013

Chief Complaint : Fever

History : This problem has already been occurring to this patient for three

days. This fever type continual and didnt down after use drug fever. Vomitting occurring to

this patient for two days, frequency more than 3/days, the volume of vomitting is 30ml.

Vomitting everything eat and drink. Phlegm cough occuring to 3 days. No history of diahrea,

and pain swallowing.


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This patient usually control in posyansus and allergy imunology departement. OS has been

given ARV therapy on one week. OS already check CD4 two weeks ago is 199. Her mother

and father is HIV/AIDS positive and had been therapy of ARV

Feeding History

From birth to 6 months : milk only

From 6 months to 9 months : milk with rice porridge

From 9 months to 1,5 years : milk with soft rice

From 1,5 years until now : Family food

History of Growth and Development

Sitting : 5 monthsCrawling : 8 months

Standing : 10 months

Walking: 18 months

History of previous illness : HIV/AIDS

History of previous medications : ARV

Physical Examination

Generalized status

Body weight: 18 kg, Body length: 118 cm,

Body weight in 50th percentile according to age: 24 kg

Body length in 50th percentile according to age: 125 cm

Body weight in 50th percentile according to body length: 18 kg

BW/BL: 18/24 x 100% = 75%

BW/age: 110/125 x 100% = 88%

BL/age : 18/18 x 100% = 100%

Presens status

Consciousness: Compos Mentis

Body temperature: 39,5oC.

Anemic (+). Icteric (-). Cyanosis (-). Edema (+). Dyspnea (-).


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Localized status

Head:

Isochoric pupil. Inferior palpebra conjunctiva pale (+/+). Icteric sclera (-). Light reflex (+/+).

Ear and nose were within normal limit.

Neck:

Lymph node enlargement (-).

Thorax:

Symmetrical fusiformis. Chest retraction (-).

HR: 120 bpm, regular, murmur (-).

RR: 32x/i, reguler, ronchi (-).

Abdomen:

Soepel, peristaltic were within normal limit. Liver palpable 3 cm under right arcus costa. The

surface is flat. The is blunt edge. Dull pain(-), normal turgor,

Extremities:

Pulse 120x/i, regular, adequate pressure and volume, warm, CRT < 3. BP: 110/60 mmHg.

Rumple leed (-).

Laboratory Findings:

Parameters Value Normal Value

Complete Blood Count

Hemoglobin 12,00 gr% 12,0 14,4 gr%

Hematocrite 35,2% 36 42%

Erithrocyte 4,21 x 106

/mm3

4,75 4,85 x 106

/mm3

Leucocyte 6,07 x 103 /mm3 4,5 13,5 /mm3

Platelet 235.000 /mm3 150000 450000 /mm3

MCV 83,6 fl 75 87 fl

MCH 28,50 pg 25 31 pg

MCHC 34,1 gr% 33 35 gr%

RDW 13,6 % 11,6 14,8 %

MPV 9,2 fL 7,0-10,2 fL

PCT 0,22%

PDW 10,3 fL

LED 25 mm/hour


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Limfosit 26,90 % 20-40 %

Monosit 6,90 % 2-8 %

Eosinofil 0,00 % 1-6 %

Basofil 0,200 % 0-1 %

Neutrofil Absolut 4,01 x 103 /L 2,4 7,3 x 103 /L

Limfosit Absolut 1,63 x 103 /L 1,7 5,1 x 103 /LMonosit Absolut 0,42 x 103 /L 0,2 -0,6 x 103 /L

Eosinofil Absolut 0,00 x 103 /L 0,10 0,30 x 103 /L

Basofil Absolut 0,01 x 103 /L 0 0,1 x 103 /L

Laboratory Findings:Parameters Value Normal Value

Carbohydrate Metabolism

Blood Glucose ad random 88,60 mg/dL < 200

Renal Function Test

Ureum 19,90 mg/dL < 50

Creatinine 0,55 mg/dL 0,39 0,73

Electrolytes

Natrium (Na) 127 mEq/L 135 155

Kalium (K) 4,0 mEq/L 3,6 5,5

Chloride 9(Cl) 99 mEq/L 96 106

Differential Diagnosis:

- Dengue fever + AIDS

- Thypoid fever + AIDS

- Tonsilofaringitis + AIDS

- Morbili + AIDS

- Morbili + Mumps + AIDS

Working Diagnosis:

- Morbili + Mumps + AIDS

Management:

- IVFD D5% NaCl 0,45% 20 gtt/i micro

- Ceftriaxone injection 1 gr / 12 hours/ iv/ in 20 cc NaCl 0,9% in 20 minutes (Skin-test)- Paracetamol 3 x 250 mg


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- Diet M II 1400 kkal dengan 36 gr proteins

- D4TFDC junior 1,5 tablets morning; 1 tablet night, start at March, 5th 2013

- Vitamin A 1 x 200000 IU, single dose

- Nistatin drop 4 x 1 cc

FOLLOW UP

March 11th 2013

S Fever

O Sens: CM, Temp: 40,3. Anemic (-). Icteric (-). Cyanosis (-).

Body weight: 18 kg, Body length: 110 cm.

Head Conjunctiva palpebra inferior anemic (-). Light reflex (+)/(+). Isochoric

pupil. Ear-nose-mouth within normal limit.

Neck Lymph node enlargement (-).

Thorax Simetris fusiformis. Retraction (-). HR: 124 bpm, reguler. Murmur

(-). RR: 30 x/i, regular. Breath sound: vesicular. Additional sound(-)

AbdomenSoepel, peristaltic were within normal limit. Liver palpable 3 cm under

right arcus costa. The surface is flat. The is blunt edge. Firm bounderies.

Tenderness (-). Turgor back normally.

Extremities Pulse 124 x/i, regular, adequate p/v, warm, CRT < 3. Rumple Leed (+).






Erithrocyte 4,21 x 106 /mm3 4,75 4,85 x 106 /mm3

Leucocyte 6,07 x 103 /mm3 4,5 13,5 /mm3

Platelet 235.000 /mm3 150000 450000 /mm3

LED 25 mm/hour


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Carbohydrate Metabolism

Blood Glucose ad random 88,60 mg/dL < 200

Renal Function Test

Ureum 19,90 mg/dL < 50

Creatinine 0,55 mg/dL 0,39 0,73Electrolytes

Natrium (Na) 127 mEq/L 135 155

Kalium (K) 4,0 mEq/L 3,6 5,5

Chloride 9(Cl) 99 mEq/L 96 106

A - dengue fever

- Thyfoid fever

- Tonsilofaringitis

P Management:- IVFD D5% NaCl 0,45% 20 gtt/i micro

- Ceftriaxone injection 1 gr / 12 hours/ iv/ in 20 cc NaCl 0,9% in 20 minutes (Skin-test)

- Paracetamol 3 x 250 mg


March 12th 2013

S Fever (-/+), cough (+).

O Sens: CM, Temp: 37,3-38

o

C. Anemic (+). Icteric (-). Cyanosis (-).Body weight: 18 kg, Body length: 110 cm.

Head Conjunctiva palpebra inferior anemic (+). Light reflex (+)/(+). Isochoric

pupil. Ear-nose-mouth within normal limit.



(-). RR: 24 26 x/i, regular. Breath sound: vesicular. Additional sound(-)

AbdomenSoepel, peristaltic were within normal limit. Liver palpable 3 cm under

right arcus costa. The surface is flat. The is blunt edge. Firm boundaries.


Extremities Pulse 126 x/i, regular, adequate p/v, warm, CRT < 3. Rumple leed (+).

A - dengue fever

- Thyfoid fever

- Tonsilofaringitis

P Management:

+

AIDS+

AIDS


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March 13th 2013

S Fever (-), cough (+)

O Sens: CM, Temp: 37,4oC. Anemic (-). Icteric (-). Cyanosis (-).



pupil. Mouth oral trush (+). Ear-nose within normal limit.



(-). RR: 28 x/i, regular. Breath sound: vesicular. Additional sound(-)Abdomen Soepel, peristaltic were within normal limit. Liver palpable 3 cm under



Extremities Pulse 126 x/i, regular, adequate p/v, warm, CRT < 3.

A - Dengue fever

- Thyfoid fever

- Tonsilofaringitis

- Mobili

P Management:





March 14th 2013S Fever (-), cough (-), diarhea (-), red rash (+)

O Sens: CM, Temp: 37oC. Anemic (-). Icteric (-). Cyanosis (-).



pupil. Mouth oral thrush (+). Ear-nose within normal limit. Face red rush

(+).



(-). RR: 22 x/i, regular. Breath sound: vesicular. Additional sound(-). Red

AIDS+


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rush (+).

Abdomen Soepel, peristaltic were within normal limit. Liver palpable 3 cm under


Tenderness (-). Turgor back normally. Red rush (+)

Extremities Pulse 110 x/i, regular, adequate p/v, warm, CRT < 3. Red rush (+).

A - Dengue fever

- Thyfoid fever

- Tonsilofaringitis

- Mobili / measles (Infection and Tropical Medicine)

P Management:





- Vitamin A 1 x 200000 IU, single dose

April 15th 2012

S Fever (-), cough (-), diarhea (-), red rash (+)

O Sens: CM, Temp: 37oC. Anemic (-). Icteric (-).Cyanosis (-).




(+).




rush (+).





A Mobili / measles (Infection and Tropical Medicine) + AIDS

P Management:



AIDS+


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April 16

th

2012S Fever (+), cough (-), diarhea (-), red rash (+)





(+).




rush (+).





A Mobili / measles (Infection and Tropical Medicine) + candidiasis oral + AIDS

Caries dentisP Management:





- D4TFDC junior 1,5 tablets morning; 1 tablet night, 10th days

- Candistatin drop 4 x 1 cc

- Nistatin drop

- Keep oral hygiene

April 17th 2012

S Fever (-), cough (-), diarhea (-), red rash (+)






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(+).




rush (+).Abdomen Soepel, peristaltic were within normal limit. Liver palpable 3 cm under




A Mobili / measles (Infection and Tropical Medicine) + candidiasis oral + AIDS

Caries dentis

P Management:







- Keep oral hygiene

April 18th 2012

Fever (+), cough (-), diarhea (-), red rash (+)

Sens: CM, Temp: 37,8oC. Anemic (-). Icteric (-).Cyanosis (-).



pupil. Mouth oral thrush (+). Ear-nose within normal limit. Face black

rush (+). Swelling of cheek (+).

Neck Lymph node enlargement (-). Looks swelling (+). Pain of tenderness (+)Thorax Simetris fusiformis. Retraction (-). HR: 110 bpm, reguler. Murmur

(-). RR: 24 x/i, regular. Breath sound: vesicular. Additional sound(-).

Black rush (+).



Tenderness (-). Turgor back normally. Black rush (+)

Extremities Pulse 110 x/i, regular, adequate p/v, warm, CRT < 3. Black rush (+).

Mobili / measles (Infection and Tropical Medicine) + candidiasis oral + mumps + AIDS


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Caries dentis

Management:







- Keep oral hygiene

April 19th 2012

Fever (+), cough (-), diarhea (-), red rash (+)Sens: CM, Temp: 37,7oC. Anemic (-). Icteric (-).Cyanosis (-).



pupil. Mouth oral thrush (+). Ear-nose within normal limit. Face black

rush (+). Swelling of cheek (+).

Neck Lymph node enlargement (-). Looks swelling (+). Pain of tenderness (+)


(-). RR: 25 x/i, regular. Breath sound: vesicular. Additional sound(-).Black rush (+).



Tenderness (-). Turgor back normally. Black rush (+)

Extremities Pulse 90 x/i, regular, adequate p/v, warm, CRT < 3. Black rush (+).






Erithrocyte 3,78 x 106 /mm3 4,75 4,85 x 106 /mm3

Leucocyte 2,81 x 103 /mm3 4,5 13,5 /mm3

Platelet 197.000 /mm3 150000 450000 /mm3

MCV 82,8 fl 75 87 fl

MCH 27,80 pg 25 31 pg

MCHC 33,5 gr% 33 35 gr%

RDW 14,2 % 11,6 14,8 %

MPV 9,8 fL 7,0-10,2 fLPCT 0,19%


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PDW 11,3 fL

Diftel

Neutrofil 48,00 % 37-80%

Limfosit 35,60 % 20-40 %

Monosit 14,90 % 2-8 %

Eosinofil 1,10 % 1-6 %Basofil 0,400 % 0-1 %

Neutrofil Absolut 1,35 x 103 /L 2,4 7,3

measles in hiv infection children fix

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