Burden of pneumonia among HIV-infected children

[Guest guest]

Can the burden of pneumonia among HIV-infected children be reduced?

Prakash Mohan Jeena (a)

Of the approximately 2.1 million children who are infected with human

immunodeficiency virus type 1 (HIV-1),1 more than 80% will develop a

respiratory illness sometime during the course of their disease.2

The prevalence of HIV-1 infection among African children admitted for

very severe pneumonia (under the WHO case definition) varies from 55%

to 65% and is associated with a case fatality rate of 20% to 34%;

three- to six-times higher than children who are not infected with

HIV.3,4

In infancy, pneumonia caused by Pneumocystis jiroveci is often the

first HIV/AIDS indicator disease that prompts HIV testing and,

consequently, early antiretroviral treatment for those infected.5

Approximately 2 million children less than 5 years of age die of

pneumonia each year in countries with a high prevalence of HIV. The

standard case management guidelines for pneumonia recommended by WHO

for use in areas with low HIV burdens are less effective in areas

where HIV burdens are high.6

Modifications to these guidelines have been suggested, but their use,

as reported in a recently published study of children with very

severe pneumonia, resulted in a 45% treatment failure rate among HIV-

infected infants in tertiary care settings.4 Polymicrobial infections

with Staphylococcus aureus, nontyphoidal Salmonella spp. and other

Gram-negative pathogens, Mycobacterium tuberculosis, P. jiroveci,

cytomegalovirus and other viruses were commonly seen among the

treatment failures and carried a greater than 10-fold risk of a

poorer outcome.

Randomized controlled studies of alternative antimicrobial agents

that are active against some of the pathogens identified among these

treatment failures are urgently required.

A second major challenge for standard case management in the HIV era

is to develop a management guideline to care for the largest group of

HIV-affected children: HIV-exposed but HIV-uninfected children, who

are at increased risk of acquiring pneumonia. Such children, who live

in close contact with HIV-infected persons who persistently harbour a

multitude of different pathogens, are at higher risk of pneumonia

treatment failure than HIV-unexposed control children; however, the

risk of an adverse outcome is lower than for HIV-infected children.7

Studies on the impact of pneumonia on HIV-exposed but HIV-uninfected

children are essential.

The other major intervention to reduce pneumonia-related morbidity

and mortality among HIV-infected children requires the implementation

of preventive strategies. Routine immunizations against Streptococcus

pneumoniae, Haemophilus influenzae and varicella are safe and

effective in HIV-infected children, even though their primary

immunological response is inferior and they experience faster decay

in immunological memory. Despite the lower efficacy of the conjugate

pneumococcal (65% versus 83%) and H. influenzae type b vaccines (55%

versus 91%) against invasive disease in HIV-infected and HIV-

uninfected control children, respectively, introduction of these

vaccines would considerably reduce the 1.6 million pneumococcal and

300 000 H. influenzae deaths that occur each year.8–10

Other preventive strategies, such as the provision of co-trimoxazole

prophylaxis against bacterial and P. jiroveci infections, improvement

in the provision of prevention of mother-to-child transmission

(PMTCT) interventions and early use of highly active antiretroviral

therapy (HAART) require urgent scaling-up. In a randomized controlled

study of co-trimoxazole prophylaxis versus placebo in HIV-infected

older Zambian children, a significant reduction in the hazards ratio

for death of 0.57 (95% confidence interval: 0.43–0.77) was seen in

the treated group.11

Although there is undoubted benefit in providing co-trimoxazole

prophylaxis to HIV-infected children, its widespread implementation

does carry risks such as development of resistance to a drug used for

treating P. jiroveci pneumonia.

This needs to be studied urgently as ineffective treatment of these

conditions could increase mortality substantially. The effective

implementation of PMTCT programmes, involving at least dual

antiretroviral therapy and effective nutritional advice, will help to

reduce to less than 4% the incidence of transmission of HIV to

newborns and infants.12

Such a reduction is likely to have a significant impact on cutting

the prevalence of pneumonia among HIV-infected children. Furthermore,

use of HAART with HIV-infected children has been associated with a

fourfold reduction in the rate of opportunistic infections and a

threefold reduction in hospitalizations.13

The role of nutritional inventions, such as exclusive breastfeeding

and zinc supplements, in the prevention of pneumonia among HIV-

infected children needs to be explored more thoroughly.

In conclusion, significant attention has to be paid to revising the

standard case management guidelines for HIV-infected children with

pneumonia through properly conducted randomized controlled studies.

The implementation of preventative strategies that include co-

trimoxazole prophylaxis, pneumococcal and H. influenzae type b

vaccinations, PMTCT programmes and early introduction of HAART carry

the greatest immediate hope for helping these children. There is a

need to rapidly scale up these measures globally.

References

1. UNAIDS epidemic update: special report on HIV/AIDS: December

2007. Geneva: UNAIDS/WHO; 2007. Available from:

http://whqlibdoc.who.int/unaids/2007/9789291736218_eng.pdf [accessed

on 3 April 2008].

2. UNAIDS epidemic update: December 2005. Geneva: UNAIDS/WHO;

2005. Available from:

http://www.unaids.org/epi/2005/doc/EPIupdate2005_pdf_en/epi-

update2005_en.pdf [accessed on 3 April 2008].

3. Nathoo KJ, Gondo M, Gwanzura L, Mhlanga BR, Mavetera T, Mason

PR. Fatal Pneumocystis carinii pneumonia in HIV seropositive infants

in Harare, Zimbabwe. Trans R Soc Trop Med Hyg 2001; 95: 37-9 doi:

10.1016/S0035-9203(01)90325-6 pmid: 11280062.

4. McNally LM, Jeena PM, Gajee K, Thula SA, Sturm AW, Cassol S,

et al., et al. Effect of age, polymicrobial disease and maternal HIV

status on treatment response and cause of severe pneumonia in South

African children: a prospective descriptive study. Lancet 2007; 369:

1440-51 doi: 10.1016/S0140-6736(07)60670-9 pmid: 17467514.

5. Graham SM, Mtitimila EI, Kamanga HS, Walsh AL, Hart CA,

Molyneux ME. The clinical presentation and outcome of Pneumocystis

carinii pneumonia in Malawian children. Lancet 2000; 355: 369-73 doi:

10.1016/S0140-6736(98)11074-7 pmid: 10665557.

6. Jeena P, Thea DM, Macleod MB. the APPIS Group. Failure of

standard antimicrobial therapy in children aged 3-59 months with mild

or asymptomatic HIV infection and severe pneumonia. Bull World Health

Organ 2006; 84: 269-75 pmid: 16628299.

7. Jeena PM, Minkara AK, Corr P, Bassa F, McNally LM, Coovadia

HM, et al., et al. Impact of HIV-1 status on the radiological

presentation and clinical outcome of children with WHO defined

community-acquired severe pneumonia. Arch Dis Child 2007; 92: 976-9

doi: 10.1136/adc.2006.104406 pmid: 17595201.

8. Klugman KP, Madhi SA, Huebner RE, Kohberger R, Mbelle N,

Pierce N. for the vaccine trialists group. A trial of a 9valent

pneumococcal conjugate vaccine in children with and without HIV

infection. N Engl J Med 2003; 349: 1341-8 doi: 10.1056/NEJMoa035060

pmid: 14523142.

9. Madhi SA, sen K, Khoosal M, Huebner RE, Mbelle N,

Mothupi R, et al., et al. Reduced effectiveness of Haemophilus

influenzae type b conjugate vaccine in children with a high

prevalence of human immunodeficiency virus type 1 infection. Pediatr

Infect Dis J 2002; 21: 315-21 doi: 10.1097/00006454-200204000-00011

pmid: 12075763.

10. Centers for Disease Control and Prevention. Vaccine

preventable deaths and the Global Immunization Vision and Strategy,

2006-2015. MMWR Morb Mortal Wkly Rep 2006; 55: 511-5 pmid: 16691182.

11. Chintu C, Bhat GJ, AS, Mulenga V, Sinyinza F, Lishimpi

K, et al., et al. Co-trimoxazole prophylaxis against opportunistic

infections in HIV infected Zambian children CHAP: a double blind

placebo trial. Lancet 2004; 364: 1865-71 doi: 10.1016/S0140-6736(04)

17442-4 pmid: 15555666.

12. Lallemant M, Jourdain G, Le Coeur S, JY, Ngo-Giang-Huong

N, Koetsawang S, et al., et al. Single dose perinatal nevirapine plus

standard zidovudine to prevent mother-to-child transmission of HIV-1

in Thailand. N Engl J Med 2004; 351: 217-28 doi: 10.1056/NEJMoa033500

pmid: 15247338.

13. Nesheim SR, Kapogiannis BG, Soe MM, Sulivan KM, Abrams E,

Farley J, et al., et al. Trends in opportunistic infections in the

pre- and post-highly active antiretroviral therapy eras among HIV-

infected children in the Perinatal AIDS Collaborative Transmission

Study, 1986-2004. Pediatrics 2007; 120: 100-9 doi: 10.1542/peds.2006-

2052 pmid: 17606567.

Affiliations

a. Department of Paediatrics and Child Health, University of Kwazulu-

Natal, Private bag X1, Congella, Durban 4013, South Africa.

doi: 10.2471/BLT.08.053223

WHO Bulletin. Volume 86, Number 5, May 2008, 321-416

http://www.who.int/bulletin/volumes/86/5/en/index.html