Tropical Medicine and International Health

doi:10.1111/j.1365-3156.2010.02578.x

volume 15 no 10 pp 11481155 october 2010

Effects of vitamin D supplementation to children diagnosed with

pneumonia in Kabul: a randomised controlled trial
Semira Manaseki-Holland1, Ghulam Qader1, Mohammad Isaq Masher2, Jane Bruce3, M. Zulf Mughal4,
Daniel Chandramohan3 and Gijs Walraven5
1
2
3
4
5

Aga Khan Health Services, Kabul, Afghanistan

Kabul Medical University, Kabul, Afghanistan
London School of Hygiene and Tropical Medicine, London, UK
Department of Paediatric Medicine, Royal Manchester Childrens Hospital, Manchester, UK
Secretariat of His Highness the Aga Khan, Gouvieux, France

Summary

objectives To determine whether (i) supplementation of oral 100 000 iu of vitamin D3

(cholecalciferol) along with antibiotics will reduce the duration of illness in children with pneumonia; (ii)
supplementation will reduce the risk of repeat episodes.
methods Double-blind individually randomised placebo-controlled trial in an inner-city hospital in
Kabul, of 453 children aged 136 months, diagnosed with non-severe or severe pneumonia at the
outpatient clinic. Children with rickets, other concurrent severe diseases, very severe pneumonia or
wheeze, were excluded. Children were given vitamin D3 or placebo drops additional to routine pneumonia treatment.
results Two hundred and twenty-four children received vitamin D3; and 229 received placebo.
There was no significant difference in the mean number of days to recovery between the vitamin D3
(4.74 days; SD 2.22) and placebo arms (4.98 days; SD 2.89; P = 0.17). The risk of a repeat episode
of pneumonia within 90 days of supplementation was lower in the intervention (92 204; 45%) than the
placebo group [122 211; (58%; relative risk 0.78; 95% CI 0.64, 0.94; P = 0.01]. Children in the
vitamin D3 group survived longer without experiencing a repeat episode (72 days vs. 59 days; HR 0.71;
95% CI 0.530.95; P = 0.02).
conclusion A single high-dose oral vitamin D3 supplementation to young children along with antibiotic treatment for pneumonia could reduce the occurrence of repeat episodes of pneumonia.
keywords pneumonia, infants, children, vitamin D supplementation, Afghanistan

Introduction
Pneumonia is the leading cause of childhood mortality,
accounting for 19% of the 10.6 million deaths that occur
each year (Bryce et al. 2005). Three hospital-based case
control studies from Ethiopia (Muhe et al. 1997) and India
(Rehman 1994; Wayse et al. 2004) suggest that vitamin D
deficiency may substantially increase the risk of severe
pneumonia among children younger than five. In the study
in Ethiopia, 42% of hospitalised pneumonia cases had
rickets, compared to 4% of children admitted for other
reasons (controls); the odds of having vitamin D deficiency
were 13.4 times higher in pneumonia cases (95% CI 81,
24.2; P < 0.001) than in the control group (Muhe et al.
1997). In a study in India (Wayse et al. 2004), prevalence
of subclinical vitamin D deficiency (serum concentrations
of 25-hydroxyvitamin D3 < 22.5 nmol l) was higher in
1148

patients with pneumonia than in healthy children attending

clinic for immunisation (80% vs. 31%; P < 0.001). High
rates of vitamin D deficiency and rickets have also been
found among children admitted to hospital for pneumonia,
ranging from 43% in Tehran (Salimpour 1975) and
Kuwait (Lubani et al. 1989) to 50% in Yemen and Jordan
(Najada & Habashneh 2004).
Vitamin D plays a crucial role in calcium and phosphorous homeostasis, and it is also important for skeletal
mineralisation. Its deficiency causes rickets in children and
osteomalacia in adults. Vitamin D also plays an important
role in modulating the innate immune response against
infections (White 2008). In vitro studies have shown that
1,25-dihydroxyvitamin D3, the active metabolite of vitamin D, is important for promoting and regulating immune
responses (Rockett et al. 1998; Cantorna 2000; Pichler
et al. 2002). Subclinical vitamin D deficiency has been

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S. Manaseki-Holland et al. Vitamin D supplement during childhood pneumonia

associated with an increased risk of tuberculosis in adults

through modification of polymorphisms in the vitamin D
receptor (VDR) (Wilkinson et al. 2000).
In children, serum concentrations of 25-vitamin D
[25(OH)D] <20 ng ml (Misra et al. 2008) are considered
to be a suboptimal index of vitamin D status, and
concentrations <12 ng ml (Pettifor 2000) are often associated with rickets. Prevalence of vitamin D deficiency is
very high in Afghanistan. In the winter of 2005, the median
serum concentration of 25(OH) D was 5 ng ml (range
225 ng ml) among 108 children aged 648 months in
Kabul; 73% had concentrations <8 ng ml, a level considered to be significantly deficient (Manaseki-Holland et al.
2008). Thus, we undertook a randomised controlled trial
(RCT) in Kabul to assess the effects of vitamin D3
supplementation to children seen at a hospital for treatment of pneumonia. We hypothesised that supplementation of 100 000 iu of vitamin D3 (Cholecalciferol), along
with antibiotic treatment, will shorten the duration of
illness in children with pneumonia and reduce the risk of
repeat episodes of pneumonia, over the next 3 months.

Methods
Ethics
The study was approved by the Ethics and Review Board of
the Ministry of Public Health of Afghanistan. Thumbprint or signature consent was obtained from one of the
childs parents at outpatients if the child met the study
criteria and after either the parent read the Dari consent
form or it was explained to him her by the doctor.
Study sites and sample population
The trial was conducted at Maywand Hospital, which
serves the central city districts of Kabul that constitute the
socio-economically deprived population of Kabul, many of
whom live in high-walled mud houses. All children
between 1 week and 3 years of age from this population
diagnosed clinically with pneumonia (Box 1) at the local
Maywand Teaching Hospital were eligible for inclusion in
the trial. Children who had clinical signs of rickets or were
known to have received high-dose vitamin D treatment in
the past 3 months (one child) had severe vomiting (one
child) or pronounced wheeze (10 children) were excluded
from the study. (Children who developed wheeze after
enrolment were not excluded.) Thirteen children with very
severe pneumonias and nine children with other severe
illnesses (meningitis, heart or renal disorders, measles,
severe malnutrition and suspected tuberculosis) were also
excluded. Finally, one child from a family that was likely to

2010 Blackwell Publishing Ltd

migrate out of the study area within 3 months was

excluded from the trial.
Randomisation and allocation of study groups
The children were individually randomised into intervention or placebo groups using a random number sequence
generated in an Excel spreadsheet with no restrictions, and
460 placebo and 100 000 iu of vitamin D3 (Cholecalciferol; Sinochem Ningbo Laboratory, China; quality certified
by Ministry of Health of Pakistan) doses in 1 ml of olive oil
were individually packaged into sealed 2-ml plastic syringes at the Department of Pharmacy, Aga Khan University
Hospital, Karachi [Joint Commission International
Accreditation of Hospitals (JCIA) accredited], Pakistan,
and labelled with an unique ID number (only office aware
of randomisation codes) and stored in manufacturers
recommended conditions in a dry, cool environment for 2
8 weeks (depending on the date of recruitment). Placebo
(containing olive oil alone) and vitamin D syringes looked
the same and the contents tasted the same. None of the
investigators, staff in Kabul and caretakers of children,
were aware of the study groups. Three paediatricians well
trained in the standard operating procedures of the trial
enrolled children from 9th December 2006 to 10th
February 2007. Children were treated with antibiotic
according to the national pneumonia treatment protocol
[based upon Integrated Management of Childhood illnesses (IMCI) guidelines] and after obtained consent from
parents, children were given either vitamin D3 or placebo
orally by the blinded doctors choosing the next syringe
with a randomisation code. On random questioning of
staff and parents, there were no indications at any stage
that families or doctors knew which child may have
received placebo or vitamin. As there was only one
administration of the intervention, there were no deviations from protocol.
Follow-up
Study children were given an ID card to facilitate follow-up
at home and revisits to the local study hospital. The
children were followed daily, up to 10 days, either at the
study hospital by paediatricians or at home by medical
doctors if discharged to assess the resolution of signs and
symptoms of the first episode of pneumonia. Thereafter,
the children were followed fortnightly up to 90 days
(ending mid-May 2007) by trained female medical doctors
to assess any illness and to refer to the study hospital if
necessary. All doctors involved were trained in IMCI and
examination of the study signs and symptoms and their
work in the clinics or follow-up were monitored through
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S. Manaseki-Holland et al. Vitamin D supplement during childhood pneumonia

random observations by a supervisor on weekly basis. The

families were encouraged to come to the study hospital for
any illnesses of the child, and the treatment was free of
charge to children during the study period.
Outcome measures
Severity of pneumonia was categorised using WHOs IMCI
criteria (Box 1). Absence of pronounced wheeze was added
to define pneumonia because wheeze could be caused by
viral infections and would reduce the specificity of the
diagnosis of pneumonia. Respiratory rate was measured
twice for one full minute using stopwatches, and axillary
temperature was measured twice using electronic thermometers (Thermoval Classic, Paul Hartmann AG,
Germany).
Box 1 Definitions of outcomes
Pneumonia: (i) Age-specific tachypnoea (>60 min if
<2 months; >50 min if 211 months; >40 if 12
24 months) and (ii) absence of wheeze (with or without
fever).
Severe pneumonia: above-mentioned criteria of pneumonia plus chest indrawing (World Health Organisation, 1995).
Very severe pneumonia: criteria of pneumonia plus at
least one of the danger signs (central cyanosis, sever
respiratory distress [head nodding, nasal flaring,
grunting], inability to drink, convulsions, vomiting)
(World Health Organisation, 1995).
Fever: Axillary temperature >37.50 C (age 1 week
3 months) or >38.0 C (223 months).
Recovery: For two consecutive days, respiratory rate
<40 min, no danger signs or subcostal recession, and
no fever.
Failure to treat: No reduction in the resting respiratory
rate over a 72 h period compared to that detected at
enrolment after allowing for a variability of
5 breaths min of the baseline respiratory rate
(Brooks et al. 2004, 2005).
Repeat episodes of pneumonia: An episode of pneumonia 14 days after the last day of illness of the
previous episode of pneumonia.
Sample size and statistical analysis
To detect a 20% difference in the mean duration of
pneumonia between the vitamin D arm and placebo arm
[5 days vs. 6 days (SD 2)] allowing Type I error of 5% and
Type II error of 10%, 137 per group (274 total) were
required. Allowing for 37% failure of response to the
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treatment regime and loss to follow-up during the

3 months, 450 were to be recruited (453 children were
actually enrolled).
Given the short period of the study follow-up and single
intervention, there was no stopping rule or interim analyses. All children randomised were included in the analysis
on an intention-to-treat basis unless the outcome measures
were missing (n = 2) or reported to have recovered or lost
within 24 h (n = 22). Mean time to recovery for the
episode of pneumonia at recruitment was compared for the
vitamin D group and placebo group.
For the repeat episodes of pneumonia, the aforementioned 24 children were excluded from analysis as were
those lost to follow-up before 10 days post-treatment
(n = 14). Time at risk of repeat episodes of pneumonia was
calculated from day 11 post-treatment with vitamin D or
placebo from the index episode of pneumonia at recruitment to the date of the first or only new episode of
pneumonia, for those who experienced a new episode, or
the last day of follow-up within the 90-day follow-up
period for those who did not have a new episode. There
were four children in intervention and four in the placebo
arms whose index recovery time was after 10 days and up
to 14 days.
KaplanMeier plots and log-rank tests were used to
compare the time to recover from the index episode of
pneumonia between the vitamin D and placebo groups.
Incidence rates of pneumonia were calculated by dividing
the number of new episodes of pneumonia by total time at
risk for all children. Hazard ratios with 95% CIs were
obtained with Cox proportional-hazards models to measure time to repeat episodes between treatment groups. The
potential confounding of baseline characteristics on treatment effect was also assessed.
Results
Three children died during the 90-day follow-up
(Figure 1). No adverse events related to vitamin D3 were
observed. The number of children lost to follow-up during
the first 10 days of post-treatment follow-up was small and
similar between the two groups (Figure 1). There was no
statistically significant difference in any of the baseline
characteristics between the groups (Table 1).
The mean number of days to recovery from the index
episode of pneumonia was the same for both the vitamin
D group and the placebo group [4.74 (SD 2.22) vs. 4.98
(SD 2.89); P = 0.17] (Table 2). The risk of children having
a repeat episode of pneumonia during the 90-day posttreatment period was significantly lower in the vitamin D
group than in the placebo group (RR 0.78; 95% CI 0.64,
0.94, P = 0.01) (Table 3). Children in the vitamin D

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S. Manaseki-Holland et al. Vitamin D supplement during childhood pneumonia

Assessed for
eligibility (n = 503)

Excluded (n = 49)
Not meeting
inclusion
criteria (n = 35)
Refused to
participate (n = 14)

Randomized (n = 453)

Allocated to and received

vitamin D (n = 224)

Allocated to and received

placebo (n = 229)

Recovered/lost within 24 h
(n = 12)

Recovered/lost within 24 h
(n = 10)

Date of recovery not recorded

(n = 1)

Date of recovery not recorded

(n = 1)

Lost to follow-up within 10

days of recruitment (n = 7)

Lost to follow-up within 10

days of recruitment (n = 7)

Included in the analysis

of repeat episodes of
pneumonia (n = 204 )

Included in the analysis

of repeat episodes of
pneumonia (n = 211)

2 Died

1 Died

Figure 1 Trial profile.

group survived without experiencing a repeat episode of

pneumonia for a longer period than children in the
placebo group, for the first or only episode of pneumonia
(HR 0.71; 95% CI 0.530.95, P = 0.02) (Table 3, Figure 2). There was no confounding effect of baseline
measures on risk of repeat pneumonia or time to repeat
episode.
Discussion
The result of this RCT has shown for the first time that
vitamin D supplementation, along with antibiotic treatment, significantly reduces new episodes of pneumonia
over a 90-day period. However, this trial did not find any
evidence for improved prognosis of the index episode of
pneumonia by vitamin D supplementation along with
antibiotic treatment. The numbers of severe repeat episodes or more than two repeat episodes did not seem
different between the groups, but the study was underpowered to detect the effect of allocation on this outcome.

2010 Blackwell Publishing Ltd

From these results, we conclude that a high-dose supplementation of vitamin D may not immediately influence the
recovery from a pneumonia case. Nevertheless, occurrence
of pneumonia is a risk factor for the next episode
(Lehmann et al. 1991), and children experiencing an
episode of pneumonia are likely at a higher risk of repeat
pneumonia because of underlying conditions, their socioeconomic or environmental risk factors (Behrman et al.
2003). Thus, preventing repeat episodes of pneumonia
would likely improve their health outcomes and the overall
burden of disease and deaths from pneumonia.
This was a randomised, well-conducted trial in a
population at high risk of vitamin D deficiency. Study
outcomes were ascertained by experienced doctors and the
loss to follow-up was minimal. One possible source of
imprecision in our study is the lack of x-ray confirmation
of cases of pneumonia. However, the use of IMCI clinical
definitions is comparable with other trials with pneumonia
as an outcome in children (World Health Organisation,
1995; Banajeh 1998).
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Table 1 Background and recruitment illness characteristics of

study children at enrolment
Vitamin D
group
N = 225

Placebo
group
N = 229

Background characteristics
Mean age in months (SD)
13.18 (9.1) 13.19 (9.2)
Male (%)
130 (57.8)
127 (55.6)
Female (%)
94 (41.8)
102 (44.5)
Missing data
1
0
Never breast fed (%)
28 (12.4)
24 (10.5)
Mean age in months
14.38 (7.0) 14.51 (8.0)
at weaning (SD)
Maternal age
<20 years (%)
12 (5.3)
4 (1.7)
2034 years (%)
184 (81.8)
192 (83.8)
>34 years (%)
27 (12.0)
30 (13.1)
Missing data
1
2
Maternal education
None (%)
180 (80.0)
195 (85.1)
Primary (%)
16 (7.1)
14 (6.1)
Secondary or above (%)
22 (9.8)
20 (8.7)
Missing data
7
0
Mean number persons sleeping in 4.53 (2.3)
4.78 (2.4)
the same room with the child (SD)
Recruitment illness characteristics
Severity of pneumonia
(very severe excluded)
Pneumonia
185 (82.6)
192 (83.8)*
Severe pneumonia
39 (17.4)
35 (15.3)
Mean RR (SD)
61 (8.9)
61 (8.3)
Mean temperature (SD)
38.3 (1.2)
38.3 (0.9)
*Treatment group 211 analysed; placebo 218 analysed.

Distinction of viral causes of pneumonia was impossible

in this study, but the exclusion of cases with wheeze
reduced the chances of including viral respiratory diseases
in the index cases. Misclassification of other causes of
raised respiratory rate as pneumonia would be distributed
equally between the two groups and therefore unlikely to
bias the observed reduction in the incidence of repeat
episodes of pneumonia.
A few children may have received treatment from health
care providers other than the study doctors, such as private
medical practitioners, for repeat pneumonia cases. How-

ever, the under reporting of cases would be similar between

the two groups because the socio-economic characteristics
were comparable. The high risk nature of this study
population [a socioeconomically deprived population
known to have a high rate of vitamin D deficiency
(Manaseki-Holland et al. 2008)] means that generalisability of these findings may be limited to those children of
similar age with high risk and especially to children who
had an episode of pneumonia.
Furthermore, it was not possible to conduct quality
control of the vitamin D3 preparation because testing of
such samples was too costly and technically difficult for the
resources available to this study; a measurement of vitamin
D level in the serum achieved as the result of this
supplementation (to ensure adequate supplementation or
excessively high blood levels) was also not possible; these
are the weaknesses of our study. Side effects were not
detected, though the number of children and the length of
follow-up involved in this study could only detect gross,
common and early adverse effects.
Although this is the first trial demonstrating the
preventive effect of vitamin D supplementation upon
pneumonia infection, it is in harmony with findings that
vitamin D can enhance the immune function. The exact
mechanisms at this stage can be speculated. There is
increasing evidence suggesting that 1,25-dihydroxy vitamin D (1,25(OH)2 D, the biologically active metabolite of
vitamin D acting via the VDR, plays an important role in
the human innate immune system (Bikle 2008; White
2008). Innate immunity is responsible for host defence
against infections through rapid production of antimicrobial proteins (AMPs) such as cathelicidin, after activation
of toll like receptors (TLRs) which are responsible for
recognition of pathogens in human macrophages, monocytes and epithelial cells. Activation of TLRs also results
in increased expression of the lalpha-hydroxylase enzyme
(CYP27B1) (Liu et al. 2006) responsible for local conversion of 25 hydroxyvitamin D to 1,25(OH)2 D. This
local synthesis of 1,25 (OH)2D further enhances the
expression of cathelicidin, thereby potentiating the hosts
innate immunity against microbes. These investigators
also observed that the induction of TLR-mediated induction of cathelicidin mRNA was blunted in African

Table 2 Outcomes of the index episode of pneumonia by treatment in intention-to-treat analysis

Outcomes

Vitamin D group
N = 224*

Placebo group
N = 229*

P value

Recovered within 24 h of admission or date of recovery not recorded

Mean number of days to recovery* (SD)

13 (6%)
4.74 (2.22)

11 (5%)
4.98 (2.89)

0.68
0.2

*Treatment group 211 analysed; placebo 218 analysed.

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Table 3 Risk of repeat episodes of pneumonia during 90 days post recovery from the index episode of pneumonia in intention-to-treat
analysis

Outcomes
Children with at least one episode
of repeat simple or severe pneumonia
Children with at least one episode
of severe pneumonia
Children with two or more episodes
of repeat simple or severe pneumonia
Children with at least two episodes
of severe pneumonia
Median time to 1st repeat episode
Incidence of at least one episode
repeat pneumonia

Vitamin D
N = 204

Placebo
N = 211

Risk ratio (95% CI)

P value

92 (45%)

122 (58%)

0.78 (0.64, 0.94)

0.01

23 (11%)

22 (10%)

1.04 (0.77, 1.41)

0.8

26 (13%)

19 (9%)

1.4 (0.81, 2.48)

0.2

2 (1%)

2 (1%)

1.1 (0.15, 7.57)

0.8

72 days
7 per 1000
child days

59 days
10 per 1000
child days

Americans, who had low serum concentration of

25(OH)D, the substrate necessary for local 1,25(OH)2 D
synthesis. Addition of exogenous 25(OH)D to African
American sera restored the induction of cathelicidin
mRNA.
Altogether the results of these in vitro studies provide a
scientific basis for the observations of increased susceptibility to infections in vitamin D-deficient individuals. They
also provide an explanation for results for our trial which
was undertaken among the children in whom we have
previously reported profound and widespread vitamin D
deficiency (Manaseki-Holland et al. 2008).
In spite of close monitoring, we observed no side effects
from this supplementation. Although vitamin D overload is
a theoretical possibility, it can be minimised by using clear
guidelines for supplementation and 100 000 iu of vitamin
D provide the best protection against vitamin D deficiency
and no overload in high-risk 09 month infants with

Proportion of children

1.00

Placebo
Vitamin D

0.75

0.50

0.25

0.00
0

30
60
Time since recruitment (days)

Number at risk (no of episodes)

Placebo 211
(52)
156
Vitamin D 204
(37)
162

(45)
(35)

104
121

90

(19)
(15)

Figure 2 Proportion of children free of a repeat episode of

pneumonia up to post-treatment day 90.

2010 Blackwell Publishing Ltd

0
0

Hazard ratio: 0.71

(0.54, 0.94)

0.06
0.02

normal baseline ranges of vitamin D (Zeghoud et al.

1994). There are no known noticeable side effects from this
supplementation. Single intramuscular injection of three
times this dose (300 000 iu) was safe and effective in
treating nutritional rickets in 6 to 30-month-old children
residing in lower socioeconomic regions of sunny Istanbul
(Kutluk et al. 2002). Higher than recommended doses of
daily supplementation of vitamin D (5001000 iu day,
adding up to 120 000 iu over 3 months) plus additional
vitamin D fortified milk does not induce an overload
(Vervel et al. 1997) in infants starting with normal ranges
of vitamin D, even when supplementation continued
during the summer (in France) and mothers who had
antenatal vitamin D supplementation (Zeghoud et al.
1997). Thus, the evidence suggests that the proposed
dosing regime is safe and effective.
We used one 3-monthly high-dose since in a pragmatic
setting, it was more likely to enable compliance than a
daily dose and was effective at maintaining the serum
vitamin D level in normal ranges for 23 months in other
French high-risk infant populations (Vervel et al. 1997).
Although it is possible that a higher dose of supplementation may have lasted longer and been more effective in
highly deficient individuals, this study was pragmatic, and
as many hospitals in developing countries that have a
population with high vitamin D deficiency did not have the
possibility to test individuals for vitamin D status before
supplementation. In this case, and given the lack of
published evidence for safety of higher doses in infants, we
could not justify giving higher doses to young children
from the community diagnosed with pneumonia.
Conclusions
This RCT has demonstrated that a 100 000 iu supplementation of vitamin D3 can reduce the recurrence of
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S. Manaseki-Holland et al. Vitamin D supplement during childhood pneumonia

pneumonias in the children living in areas with high

vitamin D deficiency. In this target population of children
with high vitamin D deficiency, future supplementation to
patients at the time of pneumonia diagnosis would be
advisable. Similar vitamin D supplementation to cases of
pneumonia is easily implementable in developing countries
with childhood vitamin D deficiency. Given the extent of
such deficiency in sunny and poor countries (Salimpour
1975; Elidrissy et al. 1984; Garabedian & Ben-Mekhbi
1991; Ghai & Koul 1991; Zhao 1991; Ozgur et al. 1996;
Akpede et al. 2001; Kutluk et al. 2002; Nutrition Research
Center of Public Health Institute, Ministry of Health,
2003; Wayse et al. 2004), vitamin D supplementation may
be significant for reducing this killer disease of childhood.
However, these findings need to be confirmed in larger
trials and diverse settings, and effects of supplementation
upon less high-risk groups and other infectious diseases
need to be investigated to assess the full potential of this
intervention to improve child health globally.
Acknowledgements
We acknowledge the families who took part in this study.
We further thank Dr Abdul Malik Faize who assisted in
recruitment, training and management of the project, all
the project field staff, in particular Drs Abdul Rasheed
Mansoor, Sayed Mujahid Hashimi and Ahmad Fayaz
Iqbal, who recruited and clinically followed up the
children and the 10 female field workers of the study.
Support and guidance of Drs Alawi from the Ministry of
Public Health of Afghanistan and Dr Kohdamani, the
Director of the Maywand Hospital, were invaluable. We
are grateful to Dr Latif Sheikh and his Pharmacy Department colleagues at the Aga Khan University Hospital
Karachi who provided the randomised labelled syringe
samples of vitamin D and placebo and to Prof Zulfiqar
Bhutta for his coordination and facilitation of this
arrangement. The study was generously funded by the
New Zealand Aid Cooperation.

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Corresponding Author Semira Manaseki-Holland, C O Public Health, Epidemiology and Biostatistics, University of Birmingham,
Edgbaston, Birmingham B15 2TT, UK. Tel.: +93 79 941 0124; E-mail: manaseki@yahoo.org, semira.manasekiholland@akdn.org

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