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MEASLES IN CHILDREN WITH HIV INFECTION Presentators : Jonathan Toman Lumbantobing (090100187) Ferdinando M. Baeha (090100243) Lisa Setiawaty (090100333) Day, Date Supervisor CHAPTER 1 INTRODUCTION 1.1. Background Measles is an acute viral disease caused by a virus in the family Paramyxovirus, genus Morbilli 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 of immunodeficiency 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 : Tuesday, March 26th 2013 : dr. HJ. RITA EVALINA RUSLI, SpA (K)

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 HIVseropositive 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.

CHAPTER 2 LITERATURE REVIEW 2.1. Measles 2.1.1. Definition Measles is an acute viral illness caused by a virus in the family of Paramyxovirus, 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 genus Morbillivirus 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

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

effects. 2.1.5 Clinical Signs and Symptoms High fever and lethargy are prominent. Sneezing, eyelid edema, tearing, copious coryza, 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

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

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 Next Day 50.000 IU 100.000 IU 200.000 IU 2-4 weeks late (if eye signs) 50.000 IU 100.000 IU 200.000 IU Diagnosis Infants < 6 Months 50.000 IU Infants aged 6-11 100.000 IU Months Children aged >12 200.000 IU months 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 <5 yr of age (especially <1 yr of age) and those >20 yr of age. In developing countries, higher casefatality rates have been associated with crowding, which is possibly attributable to a larger inoculum dose following household exposure. Severe malnutrition in children results in suboptimal immune response and higher morbidity and mortality with measles infection. Low serum retinol levels in children with measles have been shown to be associated with higher measles morbidity and mortality in developing countries and in the United States.

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 <3% of children with measles. Encephalitis following measles has been a long-associated complication, often with an unfavorable outcome. Rates of 1-311,000 cases of measles have been reported, with greater numbers occurring in adolescents and adults than in preschool or school-aged children. This is a postinfectious immunologically mediated process rather than due to a direct effect by the virus. Clinical onset begins during the exanthem and presents with seizures (56%), lethargy (46%), coma (28%), and irritability (26%). Findings in cerebrospinal fluid include lymphocytic pleocyosis in 85% and elevated protein concentration. Approximately 15% of patients die, and 20-40% suffer long-term sequelae, including mental retardation. motor disabilities. and deafness. Measles encephalitis in immunocompromised patients results from direct damage to the brain by the virus. Subacute measles encephalitis presents 1-10 mo following measles in immunocompromised patients, particularly those with AIDS, lymphoreticular malignancies,

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 college campus 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, and pancreatitis 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 definition and 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 mononuclear leukocytes. Symptomatic CNS involvement occurs in 10-30% of infected individuals, but CSF pleocytosis has been found in 4060% 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 resolve in 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 1020% 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 0.55.0/100,000 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 <'I3 of cases the orchitis is bilateral. Atrophy of the testes may occur, but sterility is rare even with bilateral involvement. Oophoritis is uncommon in postpubertal females but maycause severe pain and when on the right side it may be confusedwith appendicitis. 3. Pancreatitis. Pancreatitis may occur in mumps with or without parotid involvement. Severe disease is rare, but fever, epigastric pain, and vomiting are suggestive. Epidemiologic studies have suggested that mumps may be associated with the subsequent development of diabetes mellitus, but a causal link has not been established. 4. Cardiac Involvement. Myocarditis has been reported 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 subSaharan Africa is infected with HIV; these individuals represent 64% of the world's HIVinfected 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 antigendriven 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 Hematopoietic T-cells (CD4+ OR CD 8+)

Cell Macrophages/monocytes Dendritic cells Fetal thymocytes and thymic epithelium B-cells NK cells Megakaryotic cells Stem cells Microglia Capillary endothelial cells Astrocytes Oligodendrocytes

Central Nervous

Large Intestine Other

Columnar epithelium 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 the infection and seem to help in the continued suppression of viral replication during clinical

20

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 (GMCSF), 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.

21

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 than adults 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 Likely to be evidence of Highly suggestive for HIV Suggestive infection Esophageal candidiasis Herpes zoster Invassivesamonella infection Pneumocystis pneumonia Extrapulmonary cryptococcosis Kaposi sarcoma infection Recurrent infection jirovecii thrush Parotid enlagement Generalized lymphadenopathy Hepatosplenomegaly Persistent orrecurrent fever Neurologic dysfunction for HIV HIV infection but common in both HIV-infected and uninfected children severe bacterial Otitis media- persistent or recurrent persistent or recurrent Severe Pneumonia Tuberculosis Failure to thrive

Persistent or recurrent oral Diarrhea

22

sPersistent dermatitis 2.3.6 Diagnostic

generalized

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 HIV rapid test HIV ELISA (also called EIA) Western blot Virologic HIV-1 DNA PCR HIV-1 RNA PCR (viral load) 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,

23

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 HIVinfected 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 CLINICAL STAGE 1 Asymptomatic Persistent.generalized lymphadenopathy CLINICAL STAGE 2 Unexplained persistent hepatosplenomegaly Papular pruritic eruptions Extensive wart virus infection Children greater than 15 years old and adults CLINICAL STAGE 1 Asymptomatic Persistent.generalized lymphadenopathy CLINICAL STAGE 2 Unexplained moderate weight loss (<10% of presumed or measured body weight)

24

Extensive molluscum contagiosum Fungal nail infections Recurrent oral ulcerations Unexplained persistent parotid enlargement Lineal gingival erythema Herpes zoster infections (otitis media, otorrhoea, sinusitis or tonsillitis) CLINICAL STAGE 3 adequately responding to standard therapy more) intermittent or constant, for longer than one month) of life) Oral hairy leukoplakia periodontitis Lymph node tuberculosis Pulmonary tuberculosis Severe recurrent bacterial pneumonia Symptomatic lymphoid pneumonitis including brochiectasis Unexplained anaemia neutropaenia (<0.5 x 109 per litre) and or chronic thrombocytopaenia (<50 x 109 per litre)

Recurrent

respiratory

tract

infections

(sinusitis, tonsillitis, otitis media and pharyngitis) Herpes zoster Angular cheilitis Recurrent oral ulceration Seborrhoeic dermatitis Fungal nail infections CLINICAL STAGE 3 presumed or measured body weight) than one month intermittent or constant, for longer than on month) Oral hairy leukoplakia Pulmonary tuberculosis (such as infection, pneumonia, empyema, pyomyositis, bone or joint meningitis or bacteraemia) Acute necrotizing ulcerative stomatitis, Unexplained anaemia (<8 g/dl), interstitial gingivitis or periodontitis

Recurrent or chronic upper respiratory tract Papular pruritic eruptions

Unexplained moderate malnutrition not Unexplained severe weight loss (>10% of

Unexplained persistent diarrhea (14 days or Unexplained chronic diarrhea for no longer Unexplained persistent fever (above 37.5C Unexplained persistent fever (above 37.5C

Persistent oral candidiasis (after 6-8 weeks Persistent oral candidiasis

Acute necrotizing ulcerative gingivitis or Severe bacterial infections

Chronic HIV-associated lung disease neutropaenia (<0.5 x 109 per litre) and/or chronic thrombocytopaenia (<50 (<8g/dl), x 109 per litre)

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CLINICAL STAGE 4 severe malnutrition not responding to standard therapy Pneumocystis pneumonia as empyema, pyomyositis, excluding pneumonia) or cutaneous of more site) Extrapulmonary tuberculosis Kaposi sarcoma trachea, bronchi or lungs) (after one month of life) HIV encephalopathy cytomegalovirus infection older than one month meningitis) Disseminated endemic (extrapulmonary histoplasmosis, coccidiomycosis) Chronic cryptosporidiosis Chronic isosporiasis Disseminated mycobacterial infection Cerebral or B-cell non-Hodgkin lymphoma

CLINICAL STAGE 4 Pneumocystis pneumonia Recurrent severe bacterial pneumonia Chronic herpes simplex infection (orolabial, of more than one months duration or visceral Oesophageal candidiasis (or candidiasis of lungs) Kaposis sarcoma Cytomegalovirus infection (retinitis or infection of other organs) HIV encephalopathy meningitis Disseminated non-tuberculous Progressive multifocal leukoencephalopathy Chronic isosporiasis histoplasmosis or mycosis coccidiomycosis) Recurrent septicaemia (including nontyphoidal Salmonella) Lymphoma (cerebral or B-cell nonHodgkin) non-tuberculous Invasive cervical carcinoma Atypical disseminated leishmaniasis Symptomatic HIV-associated nephropathy

Unexplained severe wasting, stunting or HIV waste syndrome

Recurrent severe bacterial infections (such genital or anorectal bone or joint infection or meningitis but at any site) Chronic herpes simplex infection (orolabial trachea, bronchi or than one months duration or visceral at any Extrapulmonary tuberculosis

Oesophageal candidiasis (or candidiasis of Central nervous system toxoplasmosis Central nervous system toxoplasmosis Extrapulmonary cryptococcosis including

Cytomegalovirus infection: retinitis or mycobacterial infection affecting another organ, with onset at age Chronic cryptosporidiosis Extrapulmonary cryptococcosis (including Disseminated mycosis (extrapulmonary

26

Progressive

multifocal or symptomatic HIV-associated cardiomyopathy

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).

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 <11 months (% 12-35 months 36-59 months >5 months CD4+) >500 years (% immunodeficiency CD4+) None or not >35 (% CD4+) >30 (% CD4+) >25

significant Mild 30-35 25-30 20-25 350-499 Advanced 25-29 20-24 15-19 200-349 Severe <25 <20 <15 <200 or <15% Source: World Health Organization, Antiretroviral Therapy of HIV Infection in Infants and Children in Resource-Limited Settings: Towards Universal Access - Recommendations for a Public Health Approach, August 7, 2006. 2.3.7.1 Clinical Latency/Asymptomatic Disease (Clinical Stage 1) Although patients recently infected with HIV usually experience a clinically latent period of years between HIV infection and clinical signs and symptoms of AIDS, evidence of HIV replication and host immune system destruction exists from the onset of infection. Early during this time, referred to as Clinical Stage 1 , the immune system produces antibodies in

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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

28

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 <12 months 1 - <5 years Criteria Reccomendation Regardless of clinical symptoms, Treat immune status, or viral load AIDS or significant HIV-related Treat symptoms1 CD4 <25%, regardless of symptoms or HIV RNA level2 Asymptomatic or mild symptoms CD4 25% HIV RNA >100,OOO copies/mL Asymptomatic or mild symptoms3 CD4 25% 5 years HIV RNA <100,000 copies/mL AIDS or significant HIV-related Treat symptoms1 CD4 <350 cells/mm3 Asymptomatic or mild symptoms and CD4 350 cells/mm and HIV RNA 100,000 copies/mL Asymptomatic or mild symptoms3 and 4 CD4 350 cells/mm] and HIV RNA <100,000 copies/mL Fixed-dose formulations for children became available in late 2005; they include d4T/3TC/NVP in different strengths, although they are not yet approved by stringent regulatory authorities. FDC of standard first and second line ARV regimens are urgently neededfor younger children. Defer Treat Consider Defer Consider Treat

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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 <100 cells/L. Cell-to-cell transmission of CMV results in tissue necrosis in association with nonspecific inflammation. Transient episodes of CMV viremia can also occur. Although the clinical significance of viremia is uncertain, such episodes probably result in dissemination of CMV to other organs (eg, the retina), thereby setting the stage for subsequent end-organ disease. 2.3.10.3Malnutrition Malnutrition is a common complication of human immunodeficiency virus (HIV) infection and plays a significant and independent role in its morbidity and mortality. Malnutrition was one of the earliest complications of acquired immunodeficiency syndrome (AIDS) to be recognized. Unexplained weight loss is one of the most common initial AIDSdefining diagnoses to be reported to public health authorities. Malnutrition associated with HIV infection has far-reaching ramifications not only for the patient, but also for the health care system and society in general. Many patients become too debilitated to work steadily and come to rely on public or other assistance. Weight loss often is the initiating event in a vicious cycle of increased fatigue and decreased physical activity, including the ability to prepare and consume food. The burden of providing custodial services as well as specialized nutritional support has strained health care resources and confounds attempts to provide streamlined and cost-efficient health care. Malnutrition also was found to increase the rate of complications during hospitalization in other diseases. This generally results in further medical intervention that may include expensive diagnostic and therapeutic measures. The increase in expenditure adds to the overall economic burden of providing health care. To this amount must be added the cost of lost wages and a decreased level of contribution to society by affected individuals. 2.3.10.4 Tuberculosis Tuberculosis (TB) and HIV have been closely linked since the emergence of AIDS. Worldwide, TB is the most common opportunistic infection affecting HIV-seropositive

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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 of secondary 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) 4,001-50,000 50,001- 100,000 100,001- 500,000 500,001-1,000,00 1,000,000

: 24% : 28% : 15% : 40% : 40% : 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 Age Sex Date of Admission

:MSS : 7 years 6 month : Female : March, 11th 2013

Chief Complaint History

: Fever : 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 From 9 months to 1,5 years : milk only : milk with soft rice From 6 months to 9 months : milk with rice porridge From 1,5 years until now : Family food History of Growth and Development Sitting Crawling Standing : 5 months : 8 months : 10 months

Walking: 18 months History of previous illness History of previous medications : HIV/AIDS : 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 Complete Blood Count Hemoglobin Hematocrite Erithrocyte Leucocyte Platelet MCV MCH MCHC RDW MPV PCT PDW LED Diftel Neutrofil Value 12,00 gr% 35,2% 4,21 x 106 /mm3 6,07 x 103 /mm3 235.000 /mm3 83,6 fl 28,50 pg 34,1 gr% 13,6 % 9,2 fL 0,22% 10,3 fL 25 mm/hour 66,00 % Normal Value 12,0 14,4 gr% 36 42% 4,75 4,85 x 106 /mm3 4,5 13,5 /mm3 150000 450000 /mm3 75 87 fl 25 31 pg 33 35 gr% 11,6 14,8 % 7,0-10,2 fL <20 mm/hour 37-80%

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Limfosit Monosit Eosinofil Basofil Neutrofil Absolut Limfosit Absolut Monosit Absolut Eosinofil Absolut Basofil Absolut

26,90 % 6,90 % 0,00 % 0,200 % 4,01 x 103 /L 1,63 x 103 /L 0,42 x 103 /L 0,00 x 103 /L 0,01 x 103 /L

20-40 % 2-8 % 1-6 % 0-1 % 2,4 7,3 x 103 /L 1,7 5,1 x 103 /L 0,2 -0,6 x 103 /L 0,10 0,30 x 103 /L 0 0,1 x 103 /L

Laboratory Findings: Parameters Carbohydrate Metabolism Blood Glucose ad random Renal Function Test Ureum Creatinine Electrolytes Natrium (Na) Kalium (K) Chloride 9(Cl) Differential Diagnosis: Dengue fever + AIDS Thypoid fever + AIDS Tonsilofaringitis + AIDS Morbili + AIDS Morbili + Mumps + AIDS Value 88,60 mg/dL 19,90 mg/dL 0,55 mg/dL 127 mEq/L 4,0 mEq/L 99 mEq/L Normal Value < 200 < 50 0,39 0,73 135 155 3,6 5,5 96 106

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 Neck Thorax Abdomen Conjunctiva palpebra inferior anemic (-). Light reflex (+)/(+). Isochoric pupil. Ear-nose-mouth within normal limit. Lymph node enlargement (-). Simetris fusiformis. Retraction (-). HR: 124 bpm, reguler. Murmur (-). RR: 30 x/i, regular. Breath sound: vesicular. Additional sound(-) Soepel, 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 (+). Laboratory Findings: Parameters Complete Blood Count Hemoglobin Hematocrite Erithrocyte Leucocyte Platelet LED Diftel Neutrofil Limfosit Monosit Eosinofil Basofil Laboratory Findings: Value 12,00 gr% 35,2% 4,21 x 106 /mm3 6,07 x 103 /mm3 235.000 /mm3 25 mm/hour 66,00 % 26,90 % 6,90 % 0,00 % 0,200 % Normal Value 12,0 14,4 gr% 36 42% 4,75 4,85 x 106 /mm3 4,5 13,5 /mm3 150000 450000 /mm3 <20 mm/hour 37-80% 20-40 % 2-8 % 1-6 % 0-1 %

41

Parameters Carbohydrate Metabolism Blood Glucose ad random Renal Function Test Ureum Creatinine Electrolytes Natrium (Na) Kalium (K) Chloride 9(Cl) A P dengue fever Thyfoid fever

Value 88,60 mg/dL 19,90 mg/dL 0,55 mg/dL 127 mEq/L 4,0 mEq/L 99 mEq/L

Normal Value < 200 < 50 0,39 0,73 135 155 3,6 5,5 96 106

AIDS

- Tonsilofaringitis 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 Diet M II 1400 kkal dengan 36 gr proteins

March 12th 2013 S Fever (-/+), cough (+). O Sens: CM, Temp: 37,3-38oC. Anemic (+). Icteric (-). Cyanosis (-). Body weight: 18 kg, Body length: 110 cm. Head Neck Thorax Abdomen Conjunctiva palpebra inferior anemic (+). Light reflex (+)/(+). Isochoric pupil. Ear-nose-mouth within normal limit. Lymph node enlargement (-). Simetris fusiformis. Retraction (-). HR: 126 bpm, reguler. Murmur (-). RR: 24 26 x/i, regular. Breath sound: vesicular. Additional sound(-) Soepel, peristaltic were within normal limit. Liver palpable 3 cm under right arcus costa. The surface is flat. The is blunt edge. Firm boundaries . Tenderness (-). Turgor back normally. Extremities Pulse 126 x/i, regular, adequate p/v, warm, CRT < 3. Rumple leed (+). A P dengue fever Thyfoid fever

AIDS

- Tonsilofaringitis Management:

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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

- Diet M II 1400 kkal dengan 36 gr proteins March 13th 2013 S Fever (-), cough (+) O Sens: CM, Temp: 37,4oC. Anemic (-). Icteric (-). Cyanosis (-). Body weight: 18 kg, Body length: 110 cm. Head Neck Thorax Abdomen Conjunctiva palpebra inferior anemic (-). Light reflex (+)/(+). Isochoric pupil. Mouth oral trush (+). Ear-nose within normal limit. Lymph node enlargement (-). Simetris fusiformis. Retraction (-). HR: 124 bpm, reguler. Murmur (-). RR: 28 x/i, regular. Breath sound: vesicular. Additional sound(-) Soepel, 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 126 x/i, regular, adequate p/v, warm, CRT < 3. A P Dengue fever Thyfoid fever Tonsilofaringitis

AIDS

- Mobili 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 Diet M II 1400 kkal dengan 36 gr proteins

March 14th 2013 S Fever (-), cough (-), diarhea (-), red rash (+) O Sens: CM, Temp: 37oC. Anemic (-). Icteric (-). Cyanosis (-). Body weight: 18 kg, Body length: 110 cm. Head Conjunctiva palpebra inferior anemic (-). Light reflex (+)/(+). Isochoric pupil. Mouth oral thrush (+). Ear-nose within normal limit. Face red rush Neck Thorax (+). Lymph node enlargement (-). Simetris fusiformis. Retraction (-). HR: 110 bpm, reguler. Murmur (-). RR: 22 x/i, regular. Breath sound: vesicular. Additional sound(-). Red

43

Abdomen

rush (+). Soepel, 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. Red rush (+) Extremities Pulse 110 x/i, regular, adequate p/v, warm, CRT < 3. Red rush (+). A P Dengue fever Thyfoid fever Tonsilofaringitis

AIDS

- Mobili / measles (Infection and Tropical Medicine) 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 Diet M II 1400 kkal dengan 36 gr proteins 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 (-). Body weight: 18 kg, Body length: 110 cm. Head Conjunctiva palpebra inferior anemic (-). Light reflex (+)/(+). Isochoric pupil. Mouth oral thrush (+). Ear-nose within normal limit. Face red rush Neck Thorax (+). Lymph node enlargement (-). Simetris fusiformis. Retraction (-). HR: 112 bpm, reguler. Murmur (-). RR: 24 x/i, regular. Breath sound: vesicular. Additional sound(-). Red Abdomen rush (+). Soepel, 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. Red rush (+) Extremities Pulse 112 x/i, regular, adequate p/v, warm, CRT < 3. Red rush (+). A P Mobili / measles (Infection and Tropical Medicine) + 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)

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Paracetamol 3 x 250 mg Diet M II 1400 kkal dengan 36 gr proteins

April 16th 2012 S Fever (+), cough (-), diarhea (-), red rash (+) O Sens: CM, Temp: 38oC. Anemic (-). Icteric (-).Cyanosis (-). Body weight: 18 kg, Body length: 110 cm. Head Conjunctiva palpebra inferior anemic (-). Light reflex (+)/(+). Isochoric pupil. Mouth oral thrush (+). Ear-nose within normal limit. Face red rush Neck Thorax (+). Lymph node enlargement (-). Simetris fusiformis. Retraction (-). HR: 120 bpm, reguler. Murmur (-). RR: 20 x/i, regular. Breath sound: vesicular. Additional sound(-). Red Abdomen rush (+). Soepel, 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. Red rush (+) Extremities Pulse 120 x/i, regular, adequate p/v, warm, CRT < 3. Red rush (+). A P Mobili / measles (Infection and Tropical Medicine) + candidiasis oral + AIDS Caries dentis 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 Diet M II 1400 kkal dengan 36 gr proteins 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 (+) O Sens: CM, Temp: 37oC. Anemic (-). Icteric (-).Cyanosis (-). Body weight: 18 kg, Body length: 110 cm. Head Conjunctiva palpebra inferior anemic (-). Light reflex (+)/(+). Isochoric pupil. Mouth oral thrush (+). Ear-nose within normal limit. Face red rush

45

Neck Thorax

(+). Lymph node enlargement (-). Simetris fusiformis. Retraction (-). HR: 108 bpm, reguler. Murmur (-). RR: 24 x/i, regular. Breath sound: vesicular. Additional sound(-). Red rush (+). Soepel, peristaltic were within normal limit. Liver palpable 3 cm under right arcus costa. The surface is flat. The is blunt edge. Firm bounderies.

Abdomen

Tenderness (-). Turgor back normally. Red rush (+) Extremities Pulse 108 x/i, regular, adequate p/v, warm, CRT < 3. Red rush (+). A P Mobili / measles (Infection and Tropical Medicine) + candidiasis oral + AIDS Caries dentis 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 Diet M II 1400 kkal dengan 36 gr proteins D4TFDC junior 1,5 tablets morning; 1 tablet night, 11th days Candistatin drop 4 x 1 cc Keep oral hygiene

April 18th 2012 Fever (+), cough (-), diarhea (-), red rash (+) Sens: CM, Temp: 37,8oC. Anemic (-). Icteric (-).Cyanosis (-). Body weight: 18 kg, Body length: 110 cm. Head Conjunctiva palpebra inferior anemic (-). Light reflex (+)/(+). Isochoric pupil. Mouth oral thrush (+). Ear-nose within normal limit. Face black Neck Thorax rush (+). Swelling of cheek (+). Lymph node enlargement (-). Looks swelling (+). Pain of tenderness (+) Simetris fusiformis. Retraction (-). HR: 110 bpm, reguler. Murmur (-). RR: 24 x/i, regular. Breath sound: vesicular. Additional sound(-). Abdomen Black rush (+). Soepel, 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. 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

46

Caries dentis 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 Diet M II 1400 kkal dengan 36 gr proteins D4TFDC junior 1,5 tablets morning; 1 tablet night, 11th days Candistatin drop 4 x 1 cc Keep oral hygiene

April 19th 2012 Fever (+), cough (-), diarhea (-), red rash (+) Sens: CM, Temp: 37,7oC. Anemic (-). Icteric (-).Cyanosis (-). Body weight: 18 kg, Body length: 110 cm. Head Conjunctiva palpebra inferior anemic (-). Light reflex (+)/(+). Isochoric pupil. Mouth oral thrush (+). Ear-nose within normal limit. Face black Neck Thorax rush (+). Swelling of cheek (+). Lymph node enlargement (-). Looks swelling (+). Pain of tenderness (+) Simetris fusiformis. Retraction (-). HR: 90 bpm, reguler. Murmur (-). RR: 25 x/i, regular. Breath sound: vesicular. Additional sound(-). Abdomen Black rush (+). Soepel, 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. Black rush (+) Extremities Pulse 90 x/i, regular, adequate p/v, warm, CRT < 3. Black rush (+). Laboratory Findings: Parameters Complete Blood Count Hemoglobin Hematocrite Erithrocyte Leucocyte Platelet MCV MCH MCHC RDW MPV PCT Value 10,50 gr% 31,3% 3,78 x 106 /mm3 2,81 x 103 /mm3 197.000 /mm3 82,8 fl 27,80 pg 33,5 gr% 14,2 % 9,8 fL 0,19% Normal Value 12,0 14,4 gr% 36 42% 4,75 4,85 x 106 /mm3 4,5 13,5 /mm3 150000 450000 /mm3 75 87 fl 25 31 pg 33 35 gr% 11,6 14,8 % 7,0-10,2 fL

47

PDW Diftel Neutrofil Limfosit Monosit Eosinofil Basofil Neutrofil Absolut Limfosit Absolut Monosit Absolut Eosinofil Absolut Basofil Absolut

11,3 fL 48,00 % 35,60 % 14,90 % 1,10 % 0,400 % 1,35 x 103 /L 1,00 x 103 /L 0,42 x 103 /L 0,03 x 103 /L 0,01 x 103 /L 37-80% 20-40 % 2-8 % 1-6 % 0-1 % 2,4 7,3 x 103 /L 1,7 5,1 x 103 /L 0,2 -0,6 x 103 /L 0,10 0,30 x 103 /L 0 0,1 x 103 /L

Laboratory Findings: Parameters Imunnoserology Autoimunne CRP Qualitative Another test Procalcitonin Value Positive 0,86 ng/mL < 0,050 < 0,5 ng/mL low risk of septic shock >2,0 ng/mL high risk of septic shock Mobili / measles (Infection and Tropical Medicine) + candidiasis oral + mumps + AIDS Caries dentis Management: Diagnostic Planning: T3 / T4 / TSH Blood culture 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 Diet M II 1400 kkal dengan 36 gr proteins D4TFDC junior 1,5 tablets morning; 1 tablet night, 11th days Candistatin drop 4 x 1 cc Keep oral hygiene Normal Value

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Septic work up

CHAPTER 4 DISCUSSION AND SUMMARY 4.1. Discussion MS 7-year-old female was admitted to RSUP HAM diagnosed with Measles and HIV infection. Her parents has been diagnosed with HIV infection. This patient has been diagnosed with HIV infection before and CD4 count has been made with 199 cells/mm 3 and has been given ARV (Anti Retroviral) for 1 week before he was hospitalized in RSUP HAM. This patient also diagnosed with measles based on clinical finding such fever for 3 days and had rash after the fever started, the rash itself begin from head then to the trunk. Patient also diagnosed with mumps virus infection based on clinical signs such as fever, headache, and parotid gland swelling. For the therapy, the patient has been given Ceftriaxone 1gr/12hr intravenous, paracetamol 3 x 200mg orally, Vitamin A 1x200.000 IU, Nystatin drop 1x4cc, and D4T FDC junior 1 tab in the morning and 1 tab in the night administered orally. Based on Nelson Texbook of Paediatrics 19th edition, treatment for therapy in immunocompetent patient with measles and mumps is entirely supportive, there is no specific antiviral.

49

Antipyretics for fever, bed rest, and maintenance of an adequate fluid intake are indicated. In this case, paracetamol used as antipyretics administered 10-15mg/kgBW orally. Vitamin A is effective for the treatment of measles and can result in a reduction in morbidity and mortality. WHO recommends administration of once daily doses of 200 000 IU of vitamin A for 2 consecutive days to all children aged 12 months or older who have measles.
16

For

immunocompromised patients, supportive therapy also given. In this patient Nystatin oral drop also given to treat the oral candiasis. Based on 2009 CDC guidelines, Nystatin is given 4-6 mL orally 4 times daily or 1-2 x 200.000 IU flavored pasilles oral 4-5 times daily for 7-14 days. Patient is treated with Anti Retroviral (ARV) called D4T FDC junior which consists of 12 mg Stavudine, 60 mg Lamivudine, and 100mg Nevirapine each tablet. Based on 2007 WHO Guidelines, the dosage of Stavudine is 1 mg/kg per dosage twice daily, Lamivudine is 4 mg/kg per dosage twice daily and Nevirapine is 150-200 mg/m2 twice daily.17

4.2. Summary This paper reports a case of a 7 years 6 month female diagnosed with HIV infection with measles and mumps Infection . A comprehensive treatment with antiretoviral therapy and spesific medication for his oppurtinistic infection has been given to this patient. Monitoring CD4 and other metabolites had been done to this patient as a part of comprehensive treatment.

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DAFTAR PUSTAKA 1. Kutty, Preeta, et.al., Measles, in VPD Surveillance Manual, 5th Ed., 2011,p. 1-16 2. Ikatan Dokter Anak Indonesia, Campak, In Buku Ajar Infeksi dan Pediatri Tropis,2010, Bagian Ilmu Kesehatan Anak FKUI, 2002, p.109-118 3. World Health Organization. Strategic Vision. World Health Organization. Available at http://www.who.int/hiv/pub/mtct/strategic_vision.pdf 4. De Moraes-Pinto, Maria Isabel Interaction between HIV and Measles in Pediatrics Available from http://www.medscape.com/viewarticle/754870 5. Moss, William J., et.al Prospective Study of Measles in Hospitalized, Human Immunodeficiency Virus (HIV)Infected and HIVUninfected Children in Zambia. Clinical Infectious Diseases 2002; 35 p:18996 6. Maldonado, Yvonne A. Rubeola Virus in Principles and Practice of Pediatric Infectious Disease, 3th Edition, 2008;

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7. Cherry, James D. Measles Virus in Textbook of Pediatric Infectious Disease, 6th Edition, 2009 8. Maldonado, Yvonne. Measles in Nelson Textbook of Pediatric. 19th Edition. 2011 9. World Health Organization. Preferred antiretroviral medicines for treating and preventing HIV infection in younger children. 2007.