32 - Symptom control at the end-of-life

Editors: Goldman, Ann; Hain, Richard; Liben, Stephen

Title: Oxford Textbook of Palliative Care for Children, 1st Edition

Copyright 2006 Oxford University Press, 2006 (Chapter 34: Danai Papadatou)

> Table of Contents > Section 3 - Symptom care > 30 - HIV/AIDS

30

HIV/AIDS

Debbie Norval

Bernadette O'Hare

Rodica Matusa

Introduction

The management of children with human immunodeficiency virus (HIV) or AIDS (acquired immunodeficiency syndrome) presents problems that are, in many ways, rather different from other life-limiting conditions. Even in adult palliative medicine, it has long been recognized that the needs of patients with HIV/AIDS present particular challenges that are quite distinct from the needs of patients with cancer. One author [1] observed that, in the United Kingdom, adult palliative care in HIV/AIDS differs from mainstream adult palliative medicine in four major ways:

  • It is a disease of the young rather than the elderly.

  • There may be multiple pathologies, so that cure and palliation may become indistinguishable earlier than in cancer.

  • Within a progressive and ultimately fatal syndrome, there may be curable components.

  • The patient is characteristically informed, vocal, and assertive.

It seems from this that palliative medicine in HIV/AIDS may have more in common with the speciality in children. Much of what is described here, could equally be said of many conditions that limit life in childhood. One principle in particular, seems common to HIV/AIDS and paediatric palliative medicine; the co-existence of conditions (such as chest infection) that impose a heavy symptom load, and which are themselves potentially curable, but occur within a relentlessly progressive condition. Treating these can contribute significantly, to good symptom management, so that within palliative care there are elements of a curative approach.

The clinical course of HIV/AIDS in children has been dramatically changed by the introduction of antiretroviral agents, where they are available. It has become for many, a chronic illness in which many acute curable components may occur. These include infections and, less commonly, malignancy.

This chapter will be in two sections. One, based largely on clinical experience from Africa, will consider the active management of HIV/AIDS itself and some of the curable components within it. The second, based on clinical experience from Romania, will consider common symptoms among children with HIV/AIDS and how they can be approached.

Management of HIV/AIDS: The African experience

Ninety-five per cent of children infected with human immunodeficiency virus (HIV) in Africa, will have acquired their infection by vertical transmission from mother to child (MTCT). Sexual abuse, transfusion of blood and related products, and other forms of horizontal transmission (expressed breast milk, rare nosocomial spread in nurseries) account for the remainder.

Perinatal HIV transmission in this population [2] can be reduced to 12%, but the infrastructure to make these interventions available to all does not exist. Nevirapine and HIV rapid testing has been made free to eligible countries as of 2000 and 2002 [3] and hopefully interventions will become more widely available.

There are 2.5 million children aged <15 years living with HIV/AIDS in sub-Saharan Africa. During 2003, there were 700,000 newly infected children and up to 540,000 died. One thousand five hundred children died each day as opposed to fewer than 100 per year in either USA or Europe [4]. In the absence of antiretroviral intervention or caesarian section, between 25 39% of infected African women transmit HIV to their offspring [5] but the number of children living with

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HIV/AIDS is lower than one would expect due their high mortality in early infancy.

In regions of high HIV prevalence, up to 50% of all admissions to regional and specialist paediatric hospitals are HIV-related. These children have a mortality rate at least three times, as high as, that of HIV-negative children.

The natural history of HIV-related disease in children with perinatal infection.

In the absence of anti-retroviral therapy (ART), survival of HIV-infected children is dependent on access to programmes providing comprehensive and intensive health care.

Prior to access to ART, fewer than 10% of vertically infected children in developed countries were likely to die before they were a year old, and median survival from the time of diagnosis was 38 months. Experience regarding the natural history of HIV/AIDS in developing countries, shows that 25% of children die before they are a year old [6] and 90%, by the time they are three years old [7]. This difference in mortality points to disparities in resources and access to care.

Early death is due to the common causes of morbidity and mortality among all children in developing countries. In children first diagnosed as HIV-positive under 6 months of age, a combination of diarrhoea, pneumonia, failure to thrive, and neurological abnormalities should alert tone to the possibility of rapidly progressive disease and death. Yet, as is suggested by the far lower annual death rates observed in developed countries, many early deaths are preventable. In both resource-rich and resource-poor scenarios, children may remain asymptomatic and without significant symptoms or signs for many years.

Features of HIV/AIDS

Table 30.1 describes signs, symptoms and investigations that are suggestive or diagnostic of HIV/AIDS in childhood.

Particular clinical issues include attention to nutrition and growth, prescription of anti-retroviral therapy where its is available, and management of diarrhoea, respiratory conditions, skin conditions, and fever that can all complicate HIV/AIDS itself. Prompt recognition and intervention of these intercur-rent problems can make a significant impact on the symptoms experienced by the child.

Growth

The majority of children who are diagnosed with HIV 1 infection in the first few years of life, grow poorly and may present with or continue to suffer from, varying degrees of failure to thrive. The mean birth weight and length of HIV-positive infants is less than that of HIV-negative infants [8]. The body mass index of HIV-infected infants is lower than that of uninfected children in the first 6 months of life, perhaps because their energy and nutrient requirements are higher than those of uninfected children [9]. HIV-infected infants continue to grow poorly, as reflected by a significant deficit in weight, length, and head circumference for age at 24 months of age [10].

Table 30.1 Signs, symptoms, and investigations in the diagnosis of HIV/AIDs in children

 

Classical disease complex suggesting HIV infection:

Failure to thrive

Recurrent or chronic diarrhoea

Pneumonitis in the first year of life

Oral candidiasis

Recurrent upper respiratory infections

Recurrent invasive infections (meningitis, septicaemia, osteitis, mastoiditis)

Unexplained anaemia or thrombocytopaenia

Tuberculosis

Severe herpes simplex stomatitis, herpes zoster or chicken pox

Physical signs commonly seen and suggestive of HIV infection. These clinical features are not specific, either in respect of making the diagnosis of HIV infection or in determining prognosis:

Malnutrition

Generalized lymphadenopathy

Hepatomegaly with or without splenomegaly

Severe papular acrodermatitis or papular urticaria

Unexplained encephalopathy

Chronic otorrhoea

Parotid gland enlargement

Digital clubbing

Rectovaginal or rectovesical fistula (an uncommon sign)

Diagnosis in a child suspected of having HIV/AIDS:

If the child is >18 months ELISA confirmed with Western Blot

If the child is <18 months HIV PCR is required as the antibodies may reflect his mother's status and not his own

While weight and length/height for age continue to fall below the normal growth percentiles, weight for length does not, and children may not appear wasted. The reason for the disproportionate short stature amongst HIV-positive children has yet to be established; indeed, the pathogenesis of poor growth in HIV/AIDS in general is poorly understood.

Failure to thrive in HIV-infected children is generally multifactorial. Poor growth may be the consequence of one or more of the following:

  • poverty-related malnutrition

  • malabsorbtion

  • recurrent or chronic diarrhoea

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  • the consequences of concurrent chronic infections

  • increased energy expenditure

  • the effects of HIV infection itself (6) HIV wasting syndrome

  • poor feeding related to recurrent and severe oral thrush, oesophagitis, encephalopathy, etc.

In a Rwandan prospective cohort study of infants born to HIV-positive mothers, mean weight, height and head circumference for age, were lower among HIV 1 infected infants than among HIV-negative infants [11].

Weight velocity is of prognostic utility in HIV-positive children. Those with significant deficits in weight velocity have a poorer prognosis, correlating with more rapid falls in CD4+ counts and higher viral loads [12]. Significantly, low weight for age prior to the onset of monotherapy with Zidovudine, or a failure to gain weight to the 25th percentile prior during the first 6 months of therapy, are significant predictors of early death [13].

Highly active anti-retroviral therapy (HAART) has a positive effect on the growth of HIV-infected children. Height and weight are favourably influenced in children in whom HAART reduce sviral load by at least 1.5 log or to less than 500 copies per ml and increases the CD4+ count [14]. The palliative effect of HAART for children, therefore, extends beyond an improvement in immune status and fewer intercurrent infections to better growth in respect of both height and stature.

Antiretroviral treatment

Goals of antiretroviral therapy

The goal of antiretroviral therapy for children is to decrease HIV-related morbidity and mortality.

  • The child's CD4 count should rise to near normal values for age and remain above the baseline count.

  • The child's viral load should become undetectable (<400 copies/ml) and remain undetectable on ARV therapy.

  • In some children, a suppressed though detectable viral load, with sustained elevation in CD4 count and absence of intercurrent and/or opportunistic infection, may be the best achievable goal.

Who should receive therapy?

In addition to medical criteria based on number of admissions and stage of disease, patients need to fulfil certain social criteria including:

  • an identifiable adult who is able to administer medication;

  • demonstrated reliability in adult caregiver that is, the adult has attended three or more scheduled visits to an HIV clinic. Immunization record up to date;

  • previous record of adherence to nutritional supplements/other chronic care regimens suchas TB drugs;

  • able to attend the antiretroviral centre on a regular basis (transport may need to be arranged for patients in rural areas or for those remote from the treatment site).

The decision to start antiretroviral therapy should be made on the basis of a multi disciplinary group that includes medical, nursing and counselling staff, as well as, the child's mother, and other main care giver.

Prophylaxis in HIV/AIDS

Pneumocystis carinii pneumonia prophylaxis

Cotrimazole is a potent preventer of PCP in children with HIV/AIDS. The dose of cotrimoxazole depends on the size of the child. Children less than 5 kg should receive a dose of 20/100 (trimethoprim/sulphamethoxazole (sulfa methoxazole) dose in mg) twice daily, those between 5 and 10 kg 40/200, and those over 10 kg 80/400.

An alternative, for those who are allergic to or cannot tolerate cotrimoxazole, is Dapsone 1 mg/kg/day.

Vitamins

Multivitamin supplements can reduce symptoms among poorly nourished children. If there is any evidence of poor nutrition, administer one tablet or 5 ml suspension of multivitamin preparation daily.

Vitamin A deficiency imposes a particular risk of corneal damage, including ulceration, so should be treated prophylactically. Administer 6 monthly (age 6 12 months: 100,000 IU, age 1 6 years: 200 000 IU). In symptomatic children, or those with corneal ulceration on staining, give 10 000 IU/kg for 3 days.

Vitamin A supplementation is also reported to be of benefit in preventing or reducing the severity of diarrhoea in vitamin deficient populations. There is no evidence that this intervention is of benefit in Vitamin A-replete populations [15], but it would seem to reduce the diarrhoea-related morbidity in malnourished children, with or without HIV/AIDS [16, 17]. Zinc supplementation (1 mg/kg/day elemental zinc) reduces the duration of acute and chronic diarrhoea [18].

Tuberculosis prophylaxis

Infants and children of mothers who have tuberculosis are at high risk of infection and disease. They should receive Isoniazid (INH)+ Pyrazinamide (PZA) and Rifampicin (Rif) as prophylaxis for a minimum of three months. Children under the age of five years with known exposure to tuberculosis,

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should receive INH + PZA + Rif for three months. Itis recommended that all HIV-positive children living in areas where pulmonary tuberculosis is highly prevalent, should receive INH prophylaxis at a dose of 5 mg/kg/day, once daily. However, there is currently a high level of resistance to INH and it may be necessary to consider prophylaxis with INH and Rifampicin together.

Ascaricides, (mebendazole)

Prophylactically, administer 3 monthly (age <5 years: 2 tablets (200 mg), age>5 years: 5 tablets (500 mg). Alternatively, use Albendazole suspension : >2 years : 400 mg (20 ml),<2 years or 10 kg : 200 mg (10 ml)

Diarrhoea

Diarrhoea and wasting are common features of HIV/AIDS in Africa [19]. It is associated with the common bacterial pathogens [46] encountered in HIV-negative children [20], but HIV infected children are more likely to be malnourished, to have prolonged diarrhoea, and to have co-morbid pneumonia than HIV-negative children.

Aetiology

Water-borne infection is a common source of enteric infection in developing countries, but there is no published account of benefit derived from interventions designed to improve water-related hygiene. Families that do not have tap water in their homes, tend to store water in buckets. Water is then dispensed from the reservoir bucket by dipping into it with a pitcher or a cup. Each dipping event is likely to contaminate the water in the bucket with whatever organisms the person is carrying on his/her hand at the time. In summer, it is likely that enteropathic organisms will flourish under these circumstances and that this form of water storage is a cause of bacterial diarrhoea. One prophylactic intervention would be to provide families with a 25 l, polyethylene water container with a spigot, so as to rule out contamination of water as described above. While this is intuitively an appropriate intervention, there is no trial-based evidence that it has positive effects.

Investigation

The nature of palliative care in children with HIV/AIDS means that, even aggressive investigation and management may be justified. For example, the acid-base state should be established in tachypnoeic children with acidotic breathing, and those with features suggesting shock. Serum electrolytes, including serum calcium should be measured, since malnourished children are frequently hypokalaemic, and because hypocalcaemia is relatively common in HIV-positive patients [21]. A full blood count should be performed, because anaemia and thrombocytopenia are relatively frequent complicating factors and should be taken into account in the management plan.

Stool specimens must be collected and delivered to the laboratory promptly and repeatedly if they remain negative in persistent diarrhoea. Antimicrobial therapy should be directed by the results of stool microscopy and culture.

Invasive investigation by sigmoidoscopy may be of value where a cause for colitis cannot be determined and in children with rectal fistulae [22] although, in the developing world, this is not usually provided. Bacterial overgrowth of the upper small bowel may be confirmed by aspiration of duodenal fluid by upper gastro-intestinal endoscopy.

Treatment

Patients presenting with diarrhoea may initially be managed as ambulatory patients provided they are not shocked (showing signs of intra-vascular dehydration) and do not have intractable vomiting. Either of these complications is an indication for admission and intravenous rehydration. Ambulatory care of diarrhoea in HIV-infected children includes a course of Metronidazole as treatment for presumed Giardia lamblia infestation, Albendazole for intestinal worms and microsporidium, and a supply of a packaged salt and electrolyte mixture for suspension in water. Mothers should be advised to return to the clinic if the child becomes drowsy or if vomiting prevents fluid retention. Be aware of treating for intestinal worms in a patient with acute diarrhoea as a worm bolus can result in an acute intestinal obstruction.

In children who are not shocked, but in whom hydration is felt to be necessary, oral rehydration is safe and efficient. Feeds should be introduced as soon as shock has resolved. In mal-nourished children with chronic diarrhoea, lactose intolerance is likely and the benefit of lactose-free milk should be assessed in management. Intravascular resuscitation may be indicated in children with shock.

Specific issues influencing management in African children

  • Clean water supplies may not be easily accessible. Families should be advised to drink more fluids than usual from the onset of diarrhoea

  • Oral rehydration solution:

    • 8 tsp sugar

    • 1 level tsp salt r

    • 1 litre boiled water

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    • Mix well and store covered in a cool place. Make a fresh solution every day

    • Water, unsweetened juice, weak tea, can be used as maintenance, but should not be used for rehydration

    • Rice water (see below)

    • Dilute maize/millet/sorghum pap

    • Maize-based ORS (see below)

  • Children should be encouraged to drink as much as possible. Often, they will not feel thirsty, so encourage them to keep a glass nearby and take small sips every five minutes. If the child is breast-feeding, this should continue, but more frequently than before (at least every 3 h).

  • Continue to eat. If children stop eating when they have diarrhoea, this can cause malnutrition, or make existing malnutrition, worse. Stopping oral feeds is unnecessary except in severe dehydration when it may be necessary for the carer to concentrate on rehydration for fourto six hours (50 100 ml/kg).

  • Prepare food, for example, porridge more watery than usual, so the child gets both nutrition and fluids.

  • Eat small amounts of nutritious and easily digestible food frequently.

  • After the diarrhoea has stopped, an extra meal each day for two weeks will help regain any weight lost during the illness.

  • Preparation of Rice-based Oral Rehydration Solution

    • Fistful of dry rice grain (25 g)

    • Wash and soak until soft

    • Grind to paste

    • Put 2 cups of water in pan and mix with paste

    • Heat and stir until bubbling

    • Use within 6 8 hrs

  • Preparation of Maize-based Oral Rehydration Solution

    • Add 50 g maize to l water

    • Cook for 5 8 min

    • Add 1 tsp salt once cooled

In addition to specific antimicrobial and antiviral therapy as indicated by stool culture, Bowies regimen may be tried although there is inadequate evidence that it is effective: Cholestyramine (colestyramine) 1 g 6 hourly 5 days and Gentamicin 50 mg/kg/day 4 hourly for 3 days given orally. Lactose-free milk. Small doses of oral morphine solution may be useful for intractable diarrhoea.

Management of skin conditions

Skin lesions (Table 30.2) are common in children with HIV/AIDS and may cause them great discomfort. When correctly diagnosed, they are often easily treated.

Table 30.2 Skin infections in HIV/AIDS

Common skin conditions in HIV-infected children

Herpes simplex

Seborrhoeic eczema

Tinea of the head and body

Fungal nail infections

Dry skin

Scabies

Drug hypersensitivity

Molluscum contageosum

Warts

Pruritic papular eruption of HIV

Varicella Zoster

Varicella (chicken pox)

Bacterial skin infections

Herpes simplex

Vesicles and erosions around the mouth and other mucocutaneous surfaces such as penis and vagina. Treat with Acyclovir 10 mg/kg/dose 5 times a day for 7 days. Topical and oral analgesia.

Seborrhoeic eczema

Seborrhoeic eczema occurs in the axillae, neck, groin and scalp. It may complicate fungal napkin dermatitis. A potent topical steroid (betamethasone valerate 0.1%) should be used as lotion in the hair and body folds. On the face, 1% hydro-cortisone lotion is appropriate. Secondary infection should be treated with flucloxacillin. Topical therapy should be followed-up with an anti-dandruff shampoo. Should the condition persist, an azole anti-fungal agent may be of benefit.

Tinea capitis

This may present as grey balding patches, as alopecia areata, as seborrhoeic dermatitis or as patches of hair loss with crusting and pustulation.

Clotrimazole cream should be used for localised infection and griseofulvin for extensive disease and involvement of the nails.

Fungal nail infections

Griseofulvin 10 mg/kg/day once each day with fat containing meal. Treat for 4 6 weeks.

Dry skin

Dry skin is a common complaint. Mothers should be encouraged to bathe children by first applying aqueous cream (UEA) and then rinsing this off in the bath, rather than to use soap. Petroleum Jelly should be avoided.

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Scabies

This may be confused with papular urticaria and the pruritic papular eruption of HIV. Finding a typical burrow will avoid confusion and the diagnosis may be confirmed by identifying mites in skin scrapings. Children who have raw lesions and those under 6 months of age, should be treated with 2% sulphur ointment, three times daily, for three days. Benzyl benzoate lotion stings on open lesions. However, Benzyl Benzoate can be used on infants if diluted and it is more effective than sulphur. All members of the household other than specified above, should be treated by the application of lotion to the whole body overnight and a repeat application after 72 h.

Prevention of scabies is also important and includes the use of heat in the form of the hot sun or ironing of linen and Tetmosol (Monosulfiram) soap for all family members.

Bacterial skin infections

Impetigo, folliculitis, furunculosis and abcesses are caused by Staphylococci and streptococci. Treat with Cloxacillin 25 mg/kg/dose, four times, each day (on an empty stomach) for 7 days or until healed. If severe, treat for two weeks initially. For recurrent problems, topical application of mupirocin 2% may be effective. Nasal irradication of bacteria using Mupirocin is also important.

Drug reactions

The number of medications they can be taking means that drug reactions are common in children with HIV/AIDS. Patients present with a generalised erythema and systemic signs within two to four weeks after starting a drug. Co-trimoxazole, phenytoin, carbamazepine, anti-tuberculous drugs, and importantly, non-nucleoside reverse transcriptase inhibitors are the most frequent causes. Stop therapy with the suspected drug. Use topical steroid ointment in the absence of secondary skin infection.

Molluscum contagiosum

Though often considered a trivial infection, molluscum causes significant morbidity through disfigurement (Figure 30.2) when lesions are extensive. Repeated application of liquid nitrogen or silver nitrate may be required, but this may not be effective and can result in spread. Lesions regress on anti-retroviral therapy. Molluscum contagiosum is often best left alone.

Warts

Warts may be large and extensive in the ano-genital region, particularly in babies and young children. Treatment is with podophyllin 25% applied weekly and washed off, after 4 h to prevent irritation. Lesions frequently recur, even after cautery or the application of liquid nitrogen. Other treatments include radiotherapy and, of course, antiretroviral therapy.

The pruritic papular eruption of HIV

This presents on the limbs and the trunk and may be the manifestation of several disorders. Papular urticaria in response to insect bite, folliculitis and a form of the Gianotti-Crosti syndrome [23], may contribute to the underlying pathology. Children suffer severe discomfort because of itching. Scratching leads to secondary impetigo. Symptoms are relieved by application of a potent topical steroid, treatment of secondary bacterial infection and a sedative anti-histamine, such as promethazine 25 mg at night.

Varicella (chicken pox)

In the child with HIV/AIDs, systematic varicella may be fatal. Symptomatic treatment with topical calamine lotion. IV Acyclovir 20 mg/kg/dose, five times, daily for seven days. If IV therapy is not available, use oral formulation.

Varicella zoster

Zoster eruptions are a cause of severe pain and carry a high mortality rate in severely immuno-compromised patients. Children with low CD4+ counts may have extensive mucocutaneous disease with persistent vesicle formation [24]. Treatment is according to the WHO approach [25], with analgesia by-the-ladder and by-the-clock (i.e. regularly around the clock to prevent recurrence of pain). The first step is often a paracetamol and codeine combination 6 hourly, a soothing topical anti-bacterial cream or calamine lotion and Aciclovir 20 mg/kg/dose 800 mg 5-hourly, for 7 days. The best response is obtained by starting Aciclovir within 72 h of the onset of symptoms. An evening dose of amitriptyline is recommended for post-herpetic neuralgia in Herpes Zoster.

Candidiasis

Cutaneous candidiasis is typically found in the nappy area, armpits or neck folds. Topical gentian violet 1% aqueous solution twice daily for 7 days or topical clotrimazole twice dailyfor 7 days.

Measles

Treat symptomatically. Ensure vitamin A has been administered within the last 3 months, if not, administer. If any signs of pneumonia, treat.

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Respiratory complications (see also Chapter 27, Respiratory symptoms)

Lower respiratory tract infections

A number of acute and chronic disease processes give rise to lower respiratory symptoms in children with HIV/AIDS. Chief amongst these symptoms are shortness of breath, cough and effort intolerance. The management of these symptoms depends on the underlying cause.

Pneumocystis carinii pneumonia (PCP) is common amongst HIV-infected children, not on chemoprophylaxis children, and may be the presenting illness in infants [26]. PCP presents in a non-specific fashion, with tachypnoea, fever, cough, and dyspnoea. The cough is non-productive and the chest may be clear to auscultation, except for scattered crepitations and rhonchi. Arterial oxygen saturation is low, measured by pulse oxymetry, or by blood gas analysis. The serum lactate dehydrogenase (LDH) concentration may be markedly elevated, although this is non-specific. The chest radiograph may show a diffuse interstitial infiltrate with batwing appearance, may be normal, or show features of concomitant chronic lung disease.

The organism is rarely isolated from children. Adequate sputum samples require broncho-alveolar lavage or sputum induction. Giemsa, modified silver methenamine, or toluidine blue staining of sputum or lung tissue will confirm the diagnosis.

A presumptive diagnosis based on symptoms, signs, hypoxaemia, a chest-suggestive radiograph and an elevated serum LDH, indicates a need for treatment. Intravenous co-tromoxazole at 10mg/kg of the trimethoprim base as a loading dose, followed by 20 mg/kg in four divided doses for three weeks, is the treatment of choice. Co-administration of prednisone 2 mg/kg for seven days followed by a 14 day tapering-dose-reduction over 14 days, is reported to improve survival [27].

Prophylaxis against PCP is indicated in infants from six weeks until one year of age. Children over the age of one year, should receive prophylaxis if their CD4+ counts fall below an absolute count of 500 per micro-litre or if the CD4+ cells count is less than 15 per cent of the total lymphocyte count. All children with prior PCP should receive life-long chemoprophylaxis. Cotrimoxazole is the chemo-prophylactic agent of choice and should be given at a dose of 5 mg/kg of the trimethoprim component. Guidelines for dosing vary between a single dose daily and a twice-daily dose on three days of the week. PCP prophylaxis may be discontinued in children over the age of one year with CD4+ counts over 15 per cent. Because co-trimoxazole is useful in preventing recurrent bacterial infections, it may be advisable to continue, regardless of CD4+ count, even in children with good immunological recovery on HAART. In the absence of CD4 monitoring, consider life-long prophylaxis.

HIV-positive children are at risk of recurrent severe bacterial pneumonia, presenting with fever, cough, intercostal recession and hypoxia that is mild relative to that associated with PCP. Streptococcus pneumoniae and Haemophilus influenzae are most frequently the causative agents. Blood culture is positive in 15 20 per cent of cases. Sputum microscopy will provide evidence of a preponderant organism and is more useful than culture, which will not distinguish between pathogenic and commensal organisms. A blood count is useful to determine oxygen carrying capacity in hypoxic patients, but the differential count is not sufficiently sensitive to distinguish between bacterial, viral, or mixed infections. The chest radiograph may show lobar, segmental, or broncho-pneumonic consolidation and is more useful in detecting complications of infection than in altering management.

Treatment of acute lower respiratory infection is in accordance with guidelines from Integrated Management of Childhood Illness [28]. Immunofluorescent staining of sputum or nasopharyngeal aspirate may identify viral agents of lower respiratory infection. The burden of disease due to respiratory syncytial virus (RSV), adenovirus influenza, and Para influenza viruses is increased in HIV-positive children. RSV infection in HIV-positivechildren is associated with increased morbidity and mortality [29].

Lymphoid interstitial pneumonitis

Between 16% and 50% of HIV-1 infected children, acquire lymphoid interstitial pneumonitis (LIP), most often in the second or third year of life [30]. In this age group, LIP is strongly associated with progression to AIDS and is listed in clinical category B in the clinical classification of HIV/AIDS in children under 13 years of age [31]. Although a lung biopsy is generally thought necessary to differentiate between LIP and infectious aetiologies [32], this procedure is rarely performed in children, and the diagnosis is generally made on clinical and radiological findings.

Children with LIP present, in their second and third years, with respiratory distress, radiological lung infiltrates and failure to thrive. Symptoms suggestive of small airways disease (air trapping, with or without reversible airways obstruction) and cough, may present long before any radiological abnormality [32]. Acute lower respiratory tract infections occur more frequently in LIP [30], a finding that confounds the analysis of symptoms associated with LIP and contributes to an understanding of the aetiology of both bronchiectasis

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and cor-pulmonale associated with LIP. Finger clubbing, parotid gland enlargement, and prominent generalised lymphadenopathy are commonly associated with LIP.

The classical chest radiograph in LIP has bilateral, predominantly lower zone reticular or reticulo-nodular opacities. While this pattern is also seen in miliary tuberculosis and Cytomegalovirus pneumonia, in LIP, it is indolent and does not respond to standard therapy for these conditions. In children, a resolution of this infiltrate has been correlated with a declining CD4+ count and advancing immunosuppression [33], although the association is not absolute. Resolution of the pulmonary infiltrate has also been observed in response to anti-retroviral therapy and to glucocorticoids.

There are no randomized, controlled clinical trials of glucocorticoids therapy in LIP, but case reports support this treatment, and also indicate a favourable response to single and multiple anti-retroviral drug regimens [34]. Indications for steroids in LIP include hypoxia and cor-pulmonale. Most patients with LIP and no access to anti-retroviral agents, die from infections related to immunosuppression and progressive pulmonary fibrosis. Cor-pulmonale and cardiac failure are frequently observed complications. While some studies have reported a shorter survival for children with LIP, other reports indicate a substantially better prognosis for these children compared with those who have other AIDS-defining conditions [35].

If a child does not have access to HAART, then pulsed steroid (2 mg/kg for 7 days, tailed to 5 mg daily over a month) offers appropriate palliative therapy for symptomatic LIP. If HAART is accessible, then triple therapy is the most appropriate and effective treatment.

Bronchiectasis

Children with AIDS and pulmonary disease, frequently, also have bronchiectasis; those who have LIP, also have recurrent or unresolved pneumonia and CD4+ counts below 100 per cubic millimetre [36]. This problem emerges particularly in children who, because of intensive and comprehensive management, survive for longer periods of time, and may occur in up to 15% of children with HIV and chronic chest illness [37].

The diagnosis of bronchiectasis in children is suggested by a history of recurrent, febrile, productive lower respiratory tract infections, recurrent signs of lower respiratory tract consolidation, and finger clubbing. Recurrent infections and increased work of breathing, contribute to failure to thrive. Plain chest radiography is not the gold standard for bronchiectasis, but recurrent consolidation in the same anatomical distribution, sometimes associated with lobar or segmental collapse is suggestive, in the presence of the other features mentioned above. In the absence of bronchograpy (where late films indicate poor clearance of radio-opaque dye), high-resolution computerised tomography is a convenient diagnostic aid [38]. Radioisotope ventilation perfusion scan is also useful in the diagnosis of bronchiectasis.

In some children, radiographic features of LIP coexist with persistent consolidation, and features suggestive of bronchiectasis. Since both these conditions may present with similar clinical histories, with recurrent infections and clinical findings such as finger clubbing, it is difficult to tease out features of individual pulmonary disease processes. Consequently, a substantial number of children are thought to have both these conditions concurrently.

In the absence of access to HAART, the palliative care of bronchiectasis in children with HIV/AIDS includes the use of antibiotics to treat acute bacterial super-infection of lower respiratory tract disease and a rotating antibiotic regimen as prophylaxis against progression of bronchietasis-related lung damage. Children also benefit from vigorous physiotherapy with dependent drainage, should damage be focused, in a particular and anatomical area. Bronchiectatic change in HIV/AIDS is generally diffuse and not amenable to surgery. Where it is localised, and if thoracic surgeons are amenable to operate on HIV positive children without access to HAART, surgery would be an appropriate element of the palliative management of bronchiectasis in such children. HAART does not reverse established bronchiectasis.

Cor-pulmonale

Cor-pulmonale is defined as hypertrophy of the right ventricle resulting from disease affecting the function and/or structure of the lung excepting causes related to primary left ventricular or congenital heart disease.

In children with HIV/AIDS, right ventricular hypertrophy is associated with recurrent pulmonary infections [37], and is observed in children with bronchiectasis and/or LIP. Chronic hypoxia, caused by interstitial pneumonitis or parenchymal lung disease, is likely to play a part in the pathogenesis of cor-pulmonale. A large proportion of children with a chronic cough and a persistent pulmonary infiltrates, have right ventricular hypertrophy and dilatation on echocardiography.

Cor-pulmonale responds to anti-failure therapy with diuretics and digoxin and these are appropriate in the palliative care of affected children who do not have access to HAART. Patients with chronic lung disease who are oxygen dependent, often spend protracted periods as in-patients. Home-oxygen can be arranged for children living in houses with electricity by means of an oxygen concentrator; or a supply of oxygen cylinders where there is no access to electricity.

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Experience in the effects of anti-retrovirals on children with cor-pulmonale, has reveale dunexpected and gratifying benefits in cardiac function. Children who have been oxygen dependent and on treatment with digoxin, diuretics, and alpha blockers have first been weaned off home-oxygen and subsequently off treatment of cardiac failure. The basis of therapeutic response is uncertain, but is likely to be the effect of anti-retrovirals at several sites: On retroviral myocarditis, on lymphoid interstitial pneumonitis, and possibly because with an improvement in immune function. On HAART, these children have fewer episodes of intercurrent lower respiratory tract infections, and fewer episodes of infection with associated increase in metabolic rate.

Tuberculosis in children with HIV/AIDS

Tuberculosis is a common opportunistic infection amongst children with HIV/AIDS. The risk of tuberculosis in HIV-infected individuals who have been exposed to tuberculosis, is approximately 10% per annum [39] and tuberculosis occurs with increasing frequency as patients become more immuno-suppressed [40]. Most frequently, the child acquires M tuberculosis infection from an adult. In the case of an HIV-positive child, this is usually, from an adult living in his home with HIV/AIDS and reactivation of tuberculosis. HIV-positive children in contact with tuberculosis should receive preventive therapy, regardless of whether the sputum smear is negative or positive in the index case.

Tuberculosis in an HIV-infected child, usually presents with prolonged fever, chronic cough, and a history of contact with an active case and weight loss. Some children present with less specific symptoms and an abnormal chest radiograph, that does not respond to antibiotics. Unusual presentations include extra-pulmonary disease with hepato-splenomegaly, lymphadenopathy, anaemia, and weight loss in children with more advanced immuno-suppression. It is difficult to distinguish this presentation from that of advanced HIV/AIDS itself [41], lymphoma, deep mycosis, or infection by atypical mycobacteria.

Children with HIV and M tuberculosis co-infection have a shorter life expectancy than children with HIV alone [42, 43], but respond to conventional anti-tuberculosis therapy both in the acute and the maintenance phase of the treatment.

Anti-retroviral, anti-fungal and anti-tuberculosis drugs interact with one another. 39 Ketoconazole and fluconazole inhibit the absorption of Rifampicin, which is a regular first-lineagent in the treatment of tuberculosis. Rifampicin in turn reduces the serum concentration ofthese anti-fungal agents and accelerates the metabolism of some Protease Inhibitors (PIs) andthe non-nucleoside reverse transcriptase inhibitor (NNRTI) Nevirapine. When a Rifampicin-containing regimen for tuberculosis and HAART are indicated simultaneously, the non-nucleoside reverse transcriptase inhibitor NNRTI Efavirenz or the PI Ritonavir may satisfactorily be combined with two nucleotide reverse transcriptase inhibitors.

Paradoxical reactions to HAART are defined as transient worsening of signs, and symptoms or the appearance of new signs, symptoms or radiographic features of tuberculosis that occur after the initiation of treatment. They are not a sign of treatment failure, but are thought to be a manifestation of an immune reaction to tubercle bacilli, previously inert because of immune suppression. Such paradoxical reactions are reported in up to 36% of patients starting treatment [44].

Immune reconstitution symptoms occur within days to weeks, after starting HAART [44]. Initiation of HAART within the first 2 months of starting anti-tuberculosis therapy is associated with an increased risk of a paradoxical reaction.

Common presenting signs include fever, enhanced adenopathy, serositis, cutaneous lesions, and new or expanding central nervous system lesions. Most patients who present paradoxical reactions have advanced HIV infection with CD4+ counts below 50 cells and very high viral loads [45]. Treatment includes non-steroidal anti-inflammatory agents and reassurance. High dose corticosteroids (prednisone 2 mg/kg for 7 10 days) are indicated in the case of lymphadenopathy with life-threatening airway compression.

Symptomatic pyrexia

Causes for fever in children with HIV/AIDs are many and varied. Management (Figure 30.1) will often require anti-infective treatment, which may need to be empirical if no specific cause can be found. HIV itself can be a cause of fever.

Symptoms in HIV/AIDS: The romanian experience

Between 1989 and 2004, there were 1800 children under the paediatric HIV/AIDS service based in Constanza, Romania. This cohort of children, unique in Europe, were infected as a result of blood transfusion or dirty needles, at a time when blood transfusion was often seen as a tonic to help children who were lethargic or failing to thrive. The stigma of the diagnosis was intolerable for some families, and many children continue to live in communal residential-respite facilities. While these are valuable providers of social and psychological support, living in close proximity can also encourage transmission of contagious diseases; and tuberculosis in particular is a common problem.

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Fig.30.1 Management of symptomatic pyrexia in children with HIV/AIDS.

In adults, the two main causes of symptom complications in HIV/AIDS are, malignancy and infection [46]. Our experience suggests that malignancy is much less often a problem in children. Of 1800 cases, only 20 have suffered from a malignancy (14 Kaposi's sarcoma, 4 NHL and 2 Burkitt's lymphoma). Infective problems (including tuberculosis, toxoplasmosis, CMV and zoster) seem to be equally common in children. Even here, there are differences in incidence; for example, pneumocystis carinii pneumonia is rather rare among our patients.

Antiretroviral agents were introduced in Romania in 1996. They have resulted in a dramatic change in the problems presented by children with HIV/AIDS. Many can live normal or near normal lives, but for others, the drugs themselves may have an impact. The occurrence of symptomatic infections remains relatively common and correlates closely with falls in CD4 count or rises in viral load.

This section will consider clusters of symptoms that can occur.

Conseque nces of poor nutrition

Even before the arrival of antiretroviral drugs, it was possible to observe a dramatic improvement in a child's general condition, simply by attention to good nutrition. Muscle wasting and weakness can lead to pain directly [1] or by causing osteoporosis. Poor skin quality and ulceration of skin or mouth can be sources of severe pain.

As children are surviving into teenage, poor nutritional status increasingly carries with it, the problems of self-image. Normal pubertal development can be delayed by poor nutrition and final adult height may be significantly reduced. Many children with HIV/AIDS in Romania attend normal schools and their classmates may be unaware of the diagnosis. Changes in appearance that mark them out as different, can carry great stigma.

The pain of muscle wasting is musculoskeletal in nature and may well respond to a non-steroidal anti-inflammatory drug. Currently, major opioids are not yet available for prescription to children in Romania, but where they are available they too, can be effective in managing pain.

Gastrointestinal symptoms

Appetite is often affected. Although many children lose their appetite, it is less well recognized, that others can develop a form of hyperphagia. Diarrhoea is also common, often with an infective aetiology (see above).

There are a number of potential gastrointestinal sources for pain. Candidiasis of the mouth and oesophagus, or colonising the entire bowel from mouth to anus, can cause considerable discomfort.

Painful stomatitis or frank mouth ulcers can occur, due often to CMV or anaerobic infections. Multiple infections are common.

Less commonly, abdominal pain can be caused by atypical infections such as mycobacterium avium intracellulare (MAI). The lymphadenopathy of MAI is particularly uncomfortable but will often respond well to straightforward measures such as simple analgesics or opioids. Where intestinal spasm is a cause for pain, adjuvants such as buscopan should be considered (see also Chapter 23, Gastrointestinal symptoms).

Otherwise, treatment is often that of the underlying condition. Specific approaches (see above) include antibiotics, antivirals and antifungals. Malignant conditions can and should be treated, where it is likely that the benefit of doing so will outweigh the burden. Lymphoma in childhood, even in HIV/AIDS, is often curable and the treatment can be well tolerated.

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Respirtory symptoms

Pneumocystis carinii pneumonia is relatively rare in children. Tuberculosis, on the other hand, is commonly seen. It is usually treatable but can spread to involve meninges, pericardium, liver, spleen, or to form cold abscesses.

TB meningitis, which is very difficult to treat, can also cause nausea and vomiting. Again, symptomatic treatment using appropriate antiemetics for centrally mediated emesis (see also Chapter 23, Gastrointestinal symptoms) should be accompanied by attempts to treat the underlying condition.

The dyspnoea associated with TB in children with HIV/AIDS does not tend to be painful. Rather, the child will become agitated and struggle for breath. There is an objective rise in respiratory rate. In our experience, excessive secretions are a relatively uncommon problem. Oxygen is rarely helpful, suggesting that most children are not hypoxaemic. The usual measures to relieve dyspnoea, may be of value. In addition, we have found good effect from short courses of steroids. This can be effective not only in TB, but in the dyspnoea associated with LIP (lymphocytic interstitial pneumonia), and pneumocystis pneumonia. The mechanism is presumably, reduction of interstitial oedema.

We have also used bronchodilators with some effect. Even in patients who are not asthmatic, there may be a reversible element to bronchospasm associated with pulmonary pathology.

Skin problems

Most problems with the skin are associated with infections and, again, symptomatic treatment should be combined with treatment of the underlying cause where this is possible.

Herpes, simplex and zoster are common and can cause considerable pain, pruritus or both. Approaches to pruritus are considered elsewhere in this book (see also Chapter 28, skin sypmtoms). The conditions can be recurrent over many years or even decades, and treatment with acyclovir seems to be progressively less effective over time.

Atypical tuberculosis, or other infections with anaerobes or staphyloccus aureus can cause cutaneous or subcutaneous infection. Cellulitis can be extremely painful, not only in the infected area but elsewhere in skin and joints. Staphylococcal infection in particular can cause a syndrome of severe myalgia.

Scabies is common among our children, due to a combination of close living contact and poor skin condition. Before the introduction of antiretrovirals, this was a particularly uncomfortable condition that could be very difficult to treat. Norwegian scabies (sc. norvegium) resulted in hyperkeratotic clusters that could be intensely pruritic and painful. Again, symptomatic treatment should be accompanied by management of the underlying condition.

Fig.30.2 Facial molluscum contagiosum in an 8-year old girl with HIV/AIDS (reproduced by kind permission of Children in Distress).

Molluscum contagiosum can present in children with HIV/AIDS as a widespread and disfiguring disease (Figure 30.2). Management is complicated by issues of self-image, and by problems associated with odour, as infections develop between the lesions. Management of odour, which is often caused by anaerobes, can include topical or systemic metronidazole.

Neuropsychiatric problems

At presentation, children with HIV/AIDS tend to be mildly developmentally delayed and to be mentally slower than their peers. The cause for this is unclear, and may not be related directly to infection with HIV/AIDS itself but to the poor social and family circumstances of the child at the time. Once children are well cared for, and their nutritional and emotional needs are met, there is often a rapid recovery. Some will go on to function normally. It appears therefore, that this syndrome of mild delay may be related more to circumstances, than to HIV/AIDS itself.

In our experience, 4 5% of children with HIV/AIDS will develop a syndrome analogous to the AIDS/dementia complex seen in adults. This may be characterized by lethargy, absent-mindedness or psychoretardation, or by seizures or

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pseudoseizures comprising repetitive movements and absences. It may be accompanied by dramatic loss of some skills including facial expression, speech, and recognition of family members.

Other than maintaining a safe and caring environment, there is little treatment available for this syndrome. Management of seizures is often difficult but is important for child and family.

Kaposi's sarcoma

Malignancies are less common in children with HIV/AIDS than in adults. Nevertheless, when they occur they can impose a heavy symptom load. Among our children, Kaposi's sarcoma was most common in the skin of the face, usually the nose or the ear, and then on the abdomen. The lesions themselves are tender, particularly the less superficial ones, but only mildly so.

Kaposi's sarcoma can develop or metastasise to meninges or lung. Pulmonary Kaposi's sarcoma is another cause for dyspnoea, and can cause significant haemoptysis.

Toxoplasmosis

Toxoplasmosis can occur at many sites, including intracerebral, ocular and pulmonary. Intracerebral and ocular toxoplasmosis can be very painful. Indeed, toxoplasmosis is the only condition other than cancer, for which major opioids can be prescribed in Romania. In our experience, pain is pulsatile and characterised by a relatively short response to morphine. The pain appears to be related to raised intracranial pressure and is particularly severe when the patient presents with visual disturbance.

Intracerebral toxoplasmosis can also cause nausea and vomiting, though this seems to be less of a problem than with TB or cryptococcal meningitis.

Our experience suggests that in contrast to tuberculosis and cryptococcosis which can be treated successfully even after recurring many times, toxoplasmosis becomes increasingly difficult to treat. This is particularly true of intracranial toxoplasmosis.

Cryptococcosis

Since the advent of antiretroviral drugs, generalized cryptococcosis or cryptococcal meningitis has become much rarer. Cryptococcosis is associated with severe headaches which seem to be made worse on movement, but can otherwise be of any type. Nausea and vomiting can be a major problem, leading to significant loss of weight. Torpor is another common symptom.

Management is, where possible, that of the underlying condition. This should be accompanied by careful attention to symptom management with appropriate analgesics and antiemetics.

Summary

In contrast with many other life-limiting conditions in childhood, in HIV/AIDS, the causes of pain and other symptoms themselves, are often a result of potentially curable conditions rather than directly to HIV/AIDS itself. In children, malignancy is relatively rare but infections are common. When it occurs, malignancy can cause significant symptoms. The main causes of pain in our experience, have been cerebral toxoplasmosis, cerebral lymphoma, cellulitis, visceral Kaposi's sarcoma and herpes zoster infection.

In parallel to curative approaches, the principles of good palliative care remain applicable to children with HIV/AIDS. Simple analgesia, opioids and appropriate adjuvants should be considered in the management of pain. Pain from zoster, for example, will often have a neuropathic component. Headache associated with lymphoma or toxoplasmosis may have an element of oedema, which can respond to short courses of sterioids or non-steroidal anti-inflammatory drugs, as well as, more usual measures. Other symptoms, such as nausea and vomiting, should be approached in the usual rational way, by considering the likely mechanism for the symptom.

It seems likely that children who have access to antiretroviral drugs will often survive into adulthood. The role of those working in paediatric palliative care, therefore, may be to ensure that a curative approach to intercurrent illness is always accompanied by a systematic approach to good symptom management.

References

1. Jennings, A. and George, R. HIV/AIDS, palliative care of HIV disease and AIDS. Themed Review Series. Progr Palliat Care 1996; 4:44 7 2.

2. Guay, L. et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet 1999;354(9181):795 802.

3. www.pmtctdonations.org/en/welcome.

4. UNAIDS, AIDS epidemic update: December 2003. www.unaids.org/en/resources/epidemiology/epidemicupdateslides.asp, 2003.

5. Dabis, F. et al. Estimating the rate of mother-to-child transmission of HIV. Report of a workshop on methodological issues Ghent (Belgium), 17 20 February 1992. The Working Group on Mother-to-Child Transmission of HIV. AIDS 1993;7(8):1139 48.

6. Bobat, R. et al. Mortality in a cohort of children born to HIV-1 infected women from Durban, South Africa. S Afr Med J 1999;89: 646 8.

7. Taha, T. et al. Morbidity among human immunodeficiency virus-1-infected and -uninfected African children. Pediatrics 2000; 106(6):E77.

P.481


8. Bulterys, M. et al. Maternal human immunodeficiency virus 1 infection and intrauterine growth: A prospective cohort study in Butare, Rwanda. Pediatr Inf Dis J 1994;13:94 100.

9. Agostoni, C. et al. Body mass index development during the first six months of life in infants born to human immunodeficiency virus-seropositive mothers. Acta Pediatr 1998;87:378 80.

10. McKinney, R., Robertson, W., et al. Effect of human immunodeficieny virus infection on the growth of young children. J Pediatr 1993;123:579 82.

11. Lepage, P. et al. Growth of human immunodeficiency type 1 infected and uninfected children: A prospective cohort study in Kigali, Rwanda, 1988 to 1993. Pediatr Infect Dis J 1996;15:479 85.

12. Carey, V., Yong, F.H., Frenkel, L.M., and McKinney, R.E. Pediatric AIDS prognosis using somatic growth velocity. AIDS 1998;12: 1361 9.

13. McKinney, R., Wilfert, C., et al. Growth as a prognostic indicator in children with human immunodeficiency virus infection treated with Zidovudine. J Pediatr 1994;125:728 33.

14. Verweel, G. et al. Treatment with highly active antiretroviral therapy in human immunodeficiency virus type-1-infected children is associated with a sustained effect on growth. Pediatrics 2002; 109(2):25.

15. Grotto, I. et al. Vitamin A supplementation and childhood morbidity from diarrhoea and respiratory infections: A meta-analysis. J Pediatr 2003;142:297 304.

16. Fawzi, W. et al. Vitamin A supplements and diarrhoeal and respiratory tract infections among children in Dar es Salaam, Tanzania. J Pediatr 2000;2003;137:142:660 7;297 304.

17. Barreto, M. et al. Effect of vitamin A supplementation on diarrhoea and acute lower respiratory tract infections in younger children in Brazil. Lancet 1994;344:228 31.

18. Baqui, A., Black, R., and Afeen, E. Effect of zinc supplementation started during diarrhoea on morbidity and motality in Bangladeshi children: Community randomised trial. BMJ 2002;325:1095.

19. Quinn, T. et al. AIDS in Africa: An epidemiological paradigm. Science 1986;234:955 63.

20. Johnson, S. et al. Effect of human immunodeficiency virus infection on episodes of diarrhoea among children in South Africa. Pediatr Inf Dis J 2000;19:972 9.

21. Kuehn, E. et al. Hypocalcaemia in HIV infection and AIDS. J Intern Med 1999;245:69 73.

22. Wiersma, R. HIV-positive African children with rectal fistulae. J Pediatr Surg 2003;38:62 4.

23. Blauvelt, A. and Turner, M. Gianotti-Crosti syndrome and human immunodeficiency virus infection. Arch Dermatol 1994;130:481 3.

24. Pediatrics, A.A.O. Varicella-zoster infections. In (25th edition) L. Pickering Red Book Elk Grove Village, IL: American Academy of Pediatrics;2000, p. 636.

25. World Health Organization, Guidelines for analgesic drug therapy. In Cancer Pain Relief and Palliative Care in Children. Geneva: WHO/IASP, 1998, pp. 24 8.

26. Pediatrics, A.A.O., Pneumocystis carinii infections. In L. Pickering, Red Book 25th edition, Elk Grove Village, IL: American Academy of Pediatrics 2000, pp. 460 5.

27. McLaughlin, G. et al. Effect of corticosteroid on survival of children with acquired immunodeficiency syndrome and Pneumocystis carinii-related respiratory failure. J Pediatr 1995;127:1007 8.

28. World Health Organisation. Cough or Difficult Breathing, in Management of the Child with a Serious Infection or Severe Malnutrition: Guidelines for Care at the First-Referral Level in Developing Countries. Geneva: WHO, 2000.

29. Mahdi, S. et al. Increased burden of respiratory viral associated severe lower respiratory tract infections in children with human immunodeficiency virus type-1. J Pediatr 2000;137:78 84.

30. Sharland, M., Gibb, D., and Holland, F. Respiratory morbidity from lymphocytic interstitial pneumonitis (LIP) in vertically acquired HIV infection. Arch Dis Child 1997;76:334 6.

31. Control, C.f.D. 1994 revised classification for immunodeficiency virus infection in children less than 13 years of age. Morb Mort Wkly Rep 1994;43:1 10.

32. Swigris, J. et al. Lymphoid interstitial pneumonia. Chest 2002;122: 2150 64.

33. Prosper, M. et al. Clinical significance of resolution of chest X-ray findings in HIV-infected children with lymphocytic interstitial pneumonitis (LIP). Pediatr Radiol 1995;25 (Suppl. 1):S243 6.

34. Bach, M. Zidovudine for lymphocytic interstitial pneumonia associated with AIDS (letter). Lancet 1987;2:796.

35. Tovo, P. et al. Prognostic significance of immunologic changes in 675 infants perinatally exposed to HIV infected individuals. Lancet 1992;339:702 9.

36. Sheikh, S. et al. Bronchiectasis in pediatric AIDS. Chest 1997;112: 1202 7.

37. Bannerman, C. and Chitsike, I. Cor pulmonale in children with human immunodeficiency virus infection. Ann Trop Paediatri 1995; 15:129 34.

38. Chang, A. et al. Non-CF bronchiectasis: Clinical and HRCT evaluation. Paed Pulmon 2003;35:477 83.

39. Africa, H.C.S.O.S. Guidelines for tuberculosis preventative therapy in HIV infection. South Afr Med J 2000;90:592 4.

40. Wood, R., Maartens, G., and Lombard, C. Risk factors for developing tuberculosis in HIV-1 infected adults from communities with a low or very high incidence of tuberculosis. J Acquir Immune Def Syndr Hum Retrovirol 2000;23:75 80.

41. Jeena, P. et al. Impact of HIV-1 co-infection on presentation and hospital-related mortality in children with culture proven pulmonary tuberculosis in Durban, South Africa. Int J Tuberc Lung Dis 2002;6:672 8.

42. Palme, I. et al. Impact of human immunodeficiency virus 1 infection on clinical presentation, treatment outcome and survival in a cohort of Ethiopian children with tuberculosis. Pediatr Infect Dis J 2002;21:1053 61.

43. Blusse van Oud-Alblas, H., van Vliet, M., and Kimpen, J. Immunodeficiency virus infection in children hospitalised with tuberculosis. Ann Trop Paediatr 2002;22:115 23.

44. Furrer, H. and Malinverni, R. Systemic inflammatory reaction after starting highly active antiretroviral therapy in AIDS patients treated for extrapulmonary tuberculosis. Am J Med 1999;106:371 2.

45. Narita, M. et al. Paradoxical worsening of tuberculosis following antiretroviral therapy in patients with AIDS. Am J Resp Crit Care Med 1998;158:157 61.

46. Winter, H. Gastrointestinal and nutritional problems in children with immunodeficiency and AIDS. In T. Chang, ed. Pediatr Clini N Am. 1996;43:573 90.



Oxford Textbook of Palliative Care for Children
Oxford Textbook of Palliative Care for Children (Liben, Oxford Textbook of Palliative Care for Children)
ISBN: 0198526539
EAN: 2147483647
Year: 2004
Pages: 47

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