C ONCLUSIONES P ARCIALES

The diagnosis and treatment of TB in the HIV infected child has several challenges which shall be outlined in this section.

Diagnosis

Chronic symptoms

HIV infected children frequently have recurrent or persistent HIV-related illnesses and consequently the chronic symptoms suggestive of TB (chronic cough, persistent fever, weight loss or poor weight gain) are frequently present in the HIV infected child as part of HIV disease itself, and could suggest TB or many other underlying HIV-related diseases.

Physical sign:

Due to their deteriorating immunity, HIV infected children with pneumonia or meningitis frequently respond poorly to antibiotic therapy, as such, this sign may suggest TB, but may also suggest many other pathogenic infections.

Tuberculin Skin Test (TST)

Due to poor cell mediated immunity, HIV infected children with advancing disease may have poor immune response to tuberculin antigen, therefore have negative TST test even in the presence of active TB infection.

Suggestive Radiology: HIV infected children frequently present with atypical radiological pictures even in the presence of PTB, such as more widespread disease, absence of lung opacities due to their inability to mount a good inflammatory response to existing micro-organisms.

Microbiologic Confirmation of TB infection

HIV infected children may have pauci-bacillary disease, therefore making it difficult to identify mycobacteria from their various body specimens.

Because of the above reasons, TB may be over-diagnosed in these children due to high frequency of symptoms and signs suggestive of TB that they may present with.

However TB may also be missed due to atypical presentation, anergic TST and negative bacteriologic tests.

In approaching diagnosis of TB in an HIV infected child, one should use the same approach as outlined above – microbiologic diagnosis, and /or clinical diagnosis by evaluating for suggestive symptoms, signs, radiology and positive TST. One must have a higher index of suspicion in these children.

Treatment of Tuberculosis in the HIV infected Child

Several factors must be considering when planning treatment of TB in the HIV infected child as follows:

149

Child will require anti-TB drugs as well as antiretroviral drugs (6 drugs), consideration to timing of initiation of both therapies, and selection of drugs with consideration of drug interactions.

Consideration of adverse effects of drugs

Severely immuno-suppressed children may have severe forms of TB slower response to anti-TB therapy, therefore may require more aggressive therapy

Timing of Initiation of Therapy

Scenario A: TB develops in child not yet on ART

In this scenario, anti-TB therapy should be initiated immediately the diagnosis of TB is made, in accordance with treatment guidelines as outlined earlier in this chapter.

Antiretroviral therapy should be initiated soon after, within the next 2-8 weeks.

This allows for initial containment of TB bacillary load as well as identification and management of any early adverse reactions during the first weeks of anti-TB therapy before introducing the ARV drugs.

Scenario B: If child develops TB while on ART In this scenario, one must evaluate as follows:

1. Is this TB that was incubating at time of ART initiation, or immune reconstitution inflammatory syndrome (IRIS)? TB is likely if:

TB develops < 6mths after ART initiation

No other evidence of CD4 decline or clinical progression (Viral load remains controlled – if assay available)

In this scenario, give standard anti-TB therapy, however, care should be taken to ensure that ARV drugs used are compatible with the anti-TB drugs.

2. Is this ARV treatment failure? This is likely if:

TB develops > 6mths after ART initiation

Evidence of CD4 decline or clinical progression (other stage 3-4 defining illness) (Viral load increase - where assay available)

In this scenario, anti-TB therapy should be initiated, however ARV therapy should be re-evaluated by HIV specialist to identify reason for failure of ARV regimen, and plan how to proceed regarding the patients ART (meanwhile the patient should continue with their existing ART regimen alongside the anti-TB therapy)

Selection of antiretroviral therapy regimen

Rifampicin, an enzyme inducer, may induce rapid metabolism of non-nucleoside reverse transcriptase inhibitors (most affected is nevirapine) and most protease inhibitors (most affected is lopinavir). In general therefore, one should avoid combining rifampicin with nevirapine or with lopinavir. If these are the only drugs available, possible approaches include:

increase the dose of nevirapine by 30% during the period of anti-TB therapy (monitor closely for NVP adverse effects), or boost lopinavir with additional ritonavir to achieve LPV: r in 1:1.

150 Acceptable ART regimens for use with rifampicin:

Two NRTI drugs + efavirenz (age above 3 years)

Two NRTI drugs + ritonavir boosted lopinavir, with supplemental ritonavir to provide LPV: r at ratio of 1:1

Two NRTI drugs + nevirapine (age below 3 years where LPV/r + r option not feasible) Vitamin B6 supplementation: HIV infected children frequently are malnourished, and care should be taken to give them concurrent vitamin B 10mg once daily during the period they are on isoniazid, to reduce risk of neurotoxic adverse effects of INH.

Prevention of Tuberculosis in Children

Diagnosis of paediatric TB is difficult and treatment of diagnosed cases involves meticulous calculation of optimum doses and several months of follow-up. Treatment default and poor compliance are therefore major challenges in the treatment and control of TB.

Prevention of infection is therefore the most realistic way to control the TB epidemic and should form the basis of all TB control programmes. Preventive measures take different forms:

1. Prevention of infection:

Prevent contact with individuals likely to have sputum-positive pulmonary TB.

Prompt diagnosis and treatment of suspected cases of pulmonary TB using appropriate combination therapy.

Contact tracing and treatment.

2. Prevention of drug resistance:

Promotion of the DOTS policy to avoid default and non-compliance Improve surveillance to detect multi-drug resistant (MDR) TB Ensure proper dosage calculation based on patient’s body weight 3. Reduce vulnerability of children to developing TB:

Improve nutritional status of children

BCG vaccination of all infants at birth (protects children from severe forms of TB)

Isoniazid prophylactic therapy to children exposed to open TB especially HIV infected children, and children under five years.

Prevention of mother-to-child HIV infection 4. Health education:

Ensure that all people (especially community leaders) understand The epidemiological importance of TB

The common symptoms and signs of TB The importance of completion of therapy

151 REFERENCES

Global tuberculosis control - surveillance, planning, financing. WHO Report 2008.

Geneva, World Health Organization.

http://www.who.int/tb/publications/global_report/2008.

Guidance for national tuberculosis programmes on the management of tuberculosis in children. WHO 2006. Geneva, World Health Organization. WHO/HTM/TB/2006.371.

Jeena PM, Pillay P, Pillay T and Coovadia HM. Impact of HIV-1 co-infection on presentation and hospital related mortality in children with culture proved pulmonary tuberculosis in Durban, South Africa. Int J Tuberc Lung Dis 2002;6:672-678.

Mukadi YD, Wiktor SZ, Coulibaly IM et al Impact of HIV infection on the development and clinical presentation and outcome of tuberculosis among children in Cote d’Ivoire.

AIDS 1997;11:1151-1158.

La Porte CJ, Colbers EP, Bertz R, Voncken DS, Wikstrom K, Boeree MJ, Koopmans PP, Hekster YA, Burger DM. Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers. Antimicrob Agents Chemother. 2004 May;48(5):1553-60.

Madhi SA, Huebner RE, Doedens L, Aduc T, Wesley D, and Cooper PA. HIV-1 co-infection in children hospitalised with tuberculosis in South Africa. Int J Tuberc Lung Dis 2000:448-454.

Niemi M, Backman JT, Fromm MF, Neuvonen PJ, Kivisto KT. Pharmacokinetic interactions with rifampicin: clinical relevance. Clin Pharmacokinet. 2003;42(9):819-50.

152 CHAPTER 12 MALARIA IN CHILDREN

Amos Odiit, Sarah Kiguli, Samuel Ayaya, Esther D. Mwaikambo

INTRODUCTION

It has been estimated that 90% of the African population live in malarious zones and malaria is a direct cause of approximately 12% of all deaths of African children below five years of age. Malaria is, therefore a threat to child survival and development. It is a major cause of foetal loss and low birth-weight (LBW) particularly in primiparous mothers. The risk of severe malaria is greatest during pregnancy, early puerperium, early childhood and in individuals where malaria coexists with other infections, stress or chronic diseases and in individuals with little or no immunity to malaria.

Over the last 10 years, management of malaria has been bogged down by high resistance of P. Falciparum to choroquine, sulphadoxine-pyrimethamine. Currently, artemesinin containing combinations are recommended at Primary Health Care level.

Protein energy malnutrition (PEM), anaemia and malaria often coexist and aggravate each other. The effect of malaria, starting from pregnancy (anaemia, LBW and abortion), infancy (anaemia and death) and young children can result in:-

Sapping the energy and growth in children Poor education and stunted growth in children Low work output

Reduced or slow economic development

Therefore, control of malaria as an integral part of Primary Health Care (PHC) is very important for a health community

OBJECTIVES

At the end of this chapter, the student should be able to:- Explain the transmission of malaria

Explain the epidemiology of malaria and measure the extent of the problem in your community

Explain the pathophysiology of malaria in children including:- - The clinical features of uncomplicated and complicated malaria.

- Diagnose uncomplicated and complicated malaria Enumerate complications of malaria in children Treat uncomplicated and severe attacks of malaria Identify and treat drug resistant malaria

List methods of control and prevention of malaria

153 LEARNING ACTIVITIES

During your paediatric rotation, make a clinical diagnosis of malaria and confirm it by laboratory investigations

During your paediatric rotation, note the number of children admitted with malaria and the major complications.

During your community assignment, estimate the frequency of malaria in schools based on the frequency of anemia, hepato-splenomegaly and positive blood smear;

During your community assignment, determine the availability and common use of antimalarial drugs.