In fact, the extent of zinc deficiency in a
population is often estimated by the prevalence of stunting among these
settings [2]. Zinc affects both non-specific and specific immune
function at a variety of levels. In terms of nonspecific immunity, zinc
affects the integrity of epithelial barrier, and function of neutrophils,
natural killer cells, monocytes and macrophages [3,4]. Therefore, zinc
conceptually promises to offer a beneficial impact on prevention,
control and treatment of infections. Based on evidence from several
randomized controlled trials and meta-analyses the World Health
Organization (WHO) and the United Nations Children’s Fund recommended
zinc supplementation for up to 2 weeks for management of acute diarrhea
[5]. Similarly, several studies evaluated the effect of zinc
supplementation in reducing the frequency and severity of respiratory
infections children. Variable results have been reported from a series
of meta-analyses that evaluated the role of zinc in prevention of
pneumonia. Two meta-analyses in 1999 and 2007 reported a beneficial
effect in preventing pneumonia in children [6,7]. Subsequently, in 2008,
Roth, et al. [8] evaluated the burden of ALRI attributed to zinc
deficiency and concluded that zinc supplementation to young children
prevented about one-quarter of ALRI cases, which could translate into
reduction in infant mortality. Another meta-analysis of ten trials [9]
concluded a reduction in incidence of ALRI defined by a specific
definition but no effect on ALRI based on caregiver report. This finding
was supported by a Cochrane review of 6 studies in 2010 [10] but
mitigated in the same year by another review which included eleven
studies with robust methodology and consistent definition of pneumonia
[11].
In this issue, Malik, et al. [12],
reported a double blind randomized controlled trial to evaluate whether
zinc prophylaxis for a short duration had any role in reducing the
morbidity due to ARIs in 272 apparently healthy infants of 6-11 months
of age from two urban resettlement communities in Delhi, India. Nearly
40% of the population were wasted or stunted, more so in the placebo
group. They reported an overall absence of effect on the incidence of
acute respiratory infections (ARIs). There was a differential impact on
acute upper respiratory infections (AURTI) and acute lower respiratory
tract infection (ALRTI). A slight but insignificant increase in
incidence of AURTI but a reduction in incidence of ALRTI by 62% was
observed. These results need to be interpreted with caution. The sample
size was powered to observe a 20% reduction in an overall estimated ARIs
episodes of 5.5 episodes per child-year. The observed AURI and ALRTI
episodes in the study were a mean of 7.2 and 1 per child-year
respectively. So this study is largely underpowered to observe a
difference in ALRTI. A significant decrease of 15% in days of ARI and
12% in duration of an episode of ARI were perhaps contributed largely by
upper respiratory tract episodes which were 7 times more frequent than
ALRTI.
The reported efficacy of zinc therapy for pneumonia,
although encouraging, needs to be considered in the light of several
caveats. Previously conducted meta-analyses report significant
heterogeneity of estimated benefit across studies. This may occur due to
differences in host factors such as age, nutritional status, urban or
rural residency, and environmental exposures. The responses of
supplementation may also differ with viral, bacterial or allergic
etiology. Variability in zinc salts used, the dose, the frequency,
duration of supplementation and how the outcome of pneumonia is defined
or monitored can also contribute largely to the heterogeneous impact.
Whether and to what extent these factors might modify and tailor the
beneficial effect of zinc is still unclear. Finally the most recent
meta-analysis by Mayo-Wilson, et al. [13] of 80 randomized trials
with 205 401 participants found no effect of zinc supplementation
despite a possibly synergistic co-intervention of vitamin A on incidence
or prevalence of respiratory infections and a small but non-significant
effect on all-cause mortality. In conclusion, despite convincing
biological rationale exists for the role of zinc in reducing incidence
of infections – especially in malnourished children – the prophylactic
role of zinc to prevent pneumonia in children is unresolved. It is of
foremost importance to understand the predictors of zinc efficacy to
identify the populations most likely to benefit from supplementation. It
appears both intuitive and scientific that even if found to be
prophylactically efficacious, programmatic decisions on the prophylactic
use of zinc supplementation will need to address additional issues like
safety, acceptability, adherence, cost and effectiveness.
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Lawn JE, et al. Global, regional, and national causes of child
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Fontaine O, Hotz C. Conclusions of the joint WHO/UNICEF/IAEA/IZiNCG
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4. Fraker PJ, King LE, Laakko T, Vollmer TL. The
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5. WHO/UNICEF. Clinical Management of Acute Diarrhea. Geneva,
World Health Organization, 2004.
6. Bhutta ZA, Black RE, Brown KH, Gardner JM, Gore S,
Hidayat A, et al. Prevention of diarrhea and pneumonia by zinc
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9. Roth DE, Richard SA, Black RE.
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10. Lassi ZS, Haider BA, Bhutta ZA. Zinc
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months to 59 months. Cochrane Database Syst Rev. 2010;12:CD005978.
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