Globalisation of Hib vaccination--how far are we? - Lancet

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http://www.thelancet.com/journal/vol365/iss9453/full/llan.365.9453.analysis_

and_interpretation.31789.1

Globalisation of Hib vaccination--how far are we?

In Asia, the introduction of Haemophilus influenzae type b (Hib) vaccine

into routine immunisation programmes has been hampered mainly by the high

cost of the vaccine and the scarcity of population-based frequency data to

verify the burden of Hib disease.1 In today's Lancet, Bradford Gessner and

colleagues examine the contentious issue of using Hib vaccine in Asia. They

did a double-blind randomised community trial in Lombok, Indonesia, to

assess the vaccine's ability to protect against Hib meningitis and

pneumonia. More than 55 000 children less than 2 years of age were enrolled

to receive the Hib vaccine or diphtheria, pertussis, and tetanus (DPT)

vaccine. The authors found an unexpectedly high absolute reduction of

vaccine-preventable Hib meningitis. The rate, up to 158 cases per 100 000

person-years, is one of the highest rates of Hib meningitis ever documented.

The researchers recommend adding Hib vaccination to the course of routine

infant immunisations because of the high rate of Hib meningitis and

improvements in morbidity and mortality associated with Hib vaccine use. The

only statistically significant endpoint the vaccine achieved for pneumonia

was the prevention of 1561 cases of clinically defined pneumonia per 100 000

person-years.

The trial's methodology allowed Gessner and colleagues to measure the burden

of Hib meningitis more accurately, since it measured the absolute rather

than relative reduction of Hib invasive disease, also known as a probe

trial. By counting all cases confirmed by microbiology and not just the more

sensitive meningitis outcomes, they found the rate of Hib meningitis in

Indonesia to be underestimated. This evidence is valuable for addressing

future guidelines to assess the burden of Hib disease worldwide. A

disappointing finding was the vaccine's inability to reduce the rate of

pneumonia as defined by lung alveolar consolidation (primary outcome): the

point estimates were less than zero for both the percentage of effectiveness

and the rate of pneumonia. That finding does not accord with previous

findings. It has been 8 years since the Gambia probe trial2 used radiology

to provide the first solid evidence of the effectiveness of Hib vaccination

in reducing childhood pneumonia. After the trial in The Gambia, a

retrospective cohort study in Chile3 and a case-control study in Brazil4

also confirmed the impact of Hib vaccination on pneumonia defined by

radiology. Results from case-control studies in Bangladesh5 and Colombia6

will add more evidence supporting the benefit of Hib vaccination.

Although Gessner and colleagues discussed the possible causes of their

negative findings for pneumonia in detail, room remains for additional

comment. The investigators' active surveillance increased the rate of early

detection of pneumonia. Among the 3171 children admitted to hospitals with

pneumonia from whom chest radiographs were obtained, about 40% of the films

had no radiological infiltrate, suggesting that in some cases the disease

was detected before it progressed sufficiently to be identified

radiologically. Therefore most of the outcomes were described as non-severe

pneumonia. Whether the randomisation process succeeded in properly

distributing the patients without radiological infiltrate among the Hib

vaccination and control groups could be critical to the authors'

conclusions. Also, the extensive use of antimicrobial drugs and their prompt

administration in the outpatient setting could have masked the radiological

image. Finally, there is a high local frequency of respiratory syncytial

virus in severe lower-respiratory-tract infection.8 That variable,

respiratory syncytial virus, could explain the vaccine's poor performance

compared with previous studies because respiratory syncytial virus has

previously been associated with alveolar consolidation.9

One could also argue that because effectiveness studies are done under

unique field conditions and influenced by the performance of local health

services, findings about how well preventive interventions work in a trial

setting are location-dependent and should not be assumed to apply to other

regions. However, effectiveness studies on Hib vaccination in separate

countries under distinct epidemiological scenarios have been in accord,

except for the Lombok trial (figure). How do we translate the evidence

gathered from Hib vaccine trials into public-health policies? Are the

results of Hib vaccination on pneumonia still inconclusive? Do we need to

spend more time and resources on additional regional probe studies? Can we

afford to postpone introducing the vaccine while we wait to gather more

evidence about the rate of Hib pneumonia or meningitis or both? Are

less-developed countries not using the Hib vaccine because it is too

expensive or difficult to deliver?

Figure: Evidence-based vaccination effectiveness on Hib radiological

pneumonia in infants7

WHO

How much evidence is sufficient for policy makers? Hib continues to be a

major cause of invasive childhood diseases, especially meningitis and

pneumonia, in countries where the Hib conjugate vaccine is routinely

unavailable. It is time to globalise Hib vaccination to protect the people

in less-developed countries that are vulnerable to Hib invasive diseases. It

is time to move forward from further studies to allocate resources to

procure and use the vaccine.

*Ana Lucia S Sgambatti de Andrade, Celina M Turchi Martelli

Departamento de Saúde Coletiva, Universidade Federal de Goiás.

S Universitário, Goiânia, 74605-050, Brasil

ana@...

We declare that we have no conflict of interest.

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