The association between vitamin D levels and recurrent group A streptococcal

tonsillopharyngitis in adults
William Nseir
a,b,e,
*, Julnar Mograbi
a,b
, Zuhair Abu-Rahmeh
c
, Mahmud Mahamid
a
,
Omar Abu-Elheja
a
, Adel Shalata
d
a
Department of Internal Medicine, Infectious Disease Unit, Holy Family Hospital, POB 8, 16100, Nazareth, Israel
b
Infectious Diseases Unit, Holy Family Hospital, Nazareth, Israel
c
Department of Radiology, Holy Family Hospital, Nazareth, Israel
d
Department of Pediatrics, Holy Family Hospital, Nazareth, Israel
e
Faculty of Medicine on the Galilee, Bar-Ilan University, Safed, Israel
1. Introduction
In the adult population, acute tonsillopharyngitis accounts for
12% of all visits to outpatient clinics, physician ofces, and
emergency departments.
1
Approximately 517% of acute tonsillo-
pharyngitis cases are due to a bacterial infection, often to group A
b-hemolytic streptococci (GAS).
2,3
The recurrence of clinical
tonsillopharyngitis in adults represents a medical problem as
well as an economic burden. Several factors have been considered
to explain the recurrence of tonsillopharyngitis. These include low
patient compliance, short duration of antibiotic treatment, low
absorption of antibiotic, frequent exposure (family/peers), bacte-
rial tolerance, and other unknown reasons.
413
The association between vitamin D deciency and the
susceptibility to infections of the respiratory tract has been
suggested for many years. Children with nutritional rickets have
developed rachitic lung due to infections of the respiratory
tract.
14
Recently, epidemiological studies have demonstrated a
correlation between vitamin D concentration and the incidence
of respiratory infections.
1518
Moreover, scientic evidence
shows the important role of vitamin D in the immune
system.
19,20
The antimicrobial peptides (AMPs) defensin and
cathelicidin, which are the principal defense factors of the upper
respiratory tract (URT), are upregulated by vitamin D.
21,22
Aydin
et al. showed that vitamin D insufciency was more prevalent in
children with recurrent tonsillitis than in healthy children.
23
Despite the fact that such an association between vitamin D
deciency and the susceptibility to infections of the respiratory
tract has been suggested for many years, to the best of our
knowledge no such evidence-based study had been undertaken
in adults.
In this study we aimed to look for a possible association
between serum 25-hydroxy (25(OH)) vitamin D levels and
recurrent GAS tonsillopharyngitis in adults.
International Journal of Infectious Diseases 16 (2012) e735e738
A R T I C L E I N F O
Article history:
Received 23 December 2011
Accepted 11 May 2012
Corresponding Editor: William Cameron,
Ottawa, Canada
Keywords:
Recurrent tonsillopharyngitis
Group A Streptococcus
Vitamin D
Adults
S U M M A R Y
Objectives: To determine the association between recurrent group A streptococcal (GAS) tonsillophar-
yngitis and serum 25-hydroxy (25(OH)) vitamin D among adult subjects.
Methods: Adult patients with tonsillopharyngitis between January 2007 and December 2009 were
reviewed and identied retrospectively. Cases with a medical history of recurrent GAS tonsillophar-
yngitis were compared to age- and gender-matched individuals without a medical history of GAS
tonsillopharyngitis. Recurrent tonsillopharyngitis was dened as three or more episodes of GAS
tonsillopharyngitis per year for a period of two consecutive years.
Results: Fifty-four cases with recurrent GAS tonsillopharyngitis and 50 controls were enrolled. There
were no signicant differences between cases and controls with regard to mean age (41 13 vs. 42 12
years; p = 0.7) and male gender (55% vs. 54%; p = 0.6). Mean serum levels of 25(OH) vitamin Damong subjects
with recurrent GAS tonsillopharyngitis were signicantly lower from the controls (11.5 ng/ml 4.7 vs. 26
ng/ml 7; p = 0.001). Multiple regression analysis showed that a serum 25(OH) vitamin D level <20 ng/ml
was associated with recurrent GAS tonsillopharyngitis (odds ratio 1.62, 95% condence interval 1.511.76; p
< 0.001).
Conclusions: Our ndings indicate a link between vitamin D deciency and the recurrence of GAS
tonsillopharyngitis.
2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: +972 46508942; fax: +972 46508973.
E-mail address: w.nseir@yahoo.com (W. Nseir).
Contents lists available at SciVerse ScienceDirect
International Journal of Infectious Diseases
j our nal h o mepag e: w ww. el sevi er . co m / l ocat e/ i j i d
1201-9712/$36.00 see front matter 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ijid.2012.05.1036
2. Materials and methods
2.1. Subjects
This study included adult patients with recurrent tonsillophar-
yngitis who were followed-up at the Infectious Diseases Unit of the
Holy Family Hospital (HFH), a 150-bed primary care hospital in
Nazareth, Israel. We included all individuals with recurrent
tonsillopharyngitis who were followed-up between 2007 and 2009
and who wereaged1860years. The exclusioncriteriawere: (1) non-
GAS tonsillopharyngitis, (2) pregnancy, and (3) individuals with:
renal failure (creatinine clearance rate <35 ml/min), a malignancy
with life expectancy less than 1 year, an HIV infection, splenectomy,
low compliance or low adherence with antibiotic use, connective
tissue diseases, organ transplant, chronic use of corticosteroid
therapy, vitamin D supplementation, and substance abusers.
The control group included 50 healthy individuals without a
medical history of GAS tonsillopharyngitis who were enrolled
randomly from the Medicine Clinic, HFH. The members of this
group were matched with the study patients for age 4 years and
gender, and were subject to the same exclusion criteria as the study
patient group. For each case of recurrent GAS tonsillopharyngitis we
selected one comparator case (1:1). The study was reviewed and
approved by the local ethics committee of the FHF, Nazareth.
2.2. Study design
A retrospective study was carried out to examine the
association between serum 25(OH) vitamin D levels and recurrent
GAS tonsillopharyngitis in adults. The following were compared
between the groups of subjects with and without GAS tonsillo-
pharyngitis: age, gender, body mass index (BMI), serum iron, C-
reactive protein (CRP), diabetes mellitus, and serum levels of
25(OH) vitamin D.
Information concerning medical conditions, drug therapy, and
the results of laboratory tests were extracted from the medical
charts of each subject in both groups. (In general, every patient
who visits the Infectious Diseases Unit or Medicine Clinic
completes a standard questionnaire at every visit concerning
his/her medical condition, anthropometric information, dietary
habits, smoking, drug therapy, family history of different diseases,
and systemic bacterial infections.)
2.3. Sampling and measures
Laboratory tests were performed within 4 days from the
beginning of the tonsillopharyngitis symptoms and included
serum CRP levels, creatinine, serum calcium, and serum iron,
and a complete blood count. Serum 25(OH) vitamin D levels were
measured in the winter and summer seasons (twice a year) for all
patients visiting our units. Serum 25(OH) vitamin D levels were
measured using a commercial enzyme immunoassay (EIA) kit
(IMM, Bensheim, Germany).
2.4. Denitions
Tonsillopharyngitis was diagnosed by clinical signs of fever,
tonsillar swelling and/or exudates, enlarged and/or tender anterior
cervical lymph nodes, without rhinorrhea and cough, and a positive
throat culture for GAS or positive rapid GAS antigen test.
24
Recurrent
GAS tonsillopharyngitis was dened as three or more episodes of
GAS tonsillopharyngitis per year for a period of two consecutive
years. Obesity was dened as a BMI >30 kg/m
2
. For laboratory tests,
levels considered normal were: CRP 00.5 mg/l, serum iron 60
180 mg/dl, serum creatinine 0.671.17 mg/dl, and serum calcium
8.110.4 mg/dl. The normal range for serum 25(OH) vitamin D levels
was considered to be 3050 ng/ml; we dened vitamin D
insufciency as levels of 25(OH) vitamin D <30 ng/ml and vitamin
D deciency as levels of 25(OH) vitamin D <20 ng/ml.
2.5. Statistical analysis
Data were analyzed using SPSS version 19 (IBM SPSS, Chicago,
IL, USA). Continuous variables are expressed as the mean stan-
standard deviation. The Chi-square test was used to test differences in
categorical variables between the cases and controls, and analysis of
variance (ANOVA) or the Students t-test was used for comparisons of
continuous variables. Spearman rank correlation and univariate
regression analysis were used to determine the strength of the
relationship between the risk factors for recurrent GAS tonsillophar-
yngitis, namely age, gender, BMI, diabetes mellitus, creatinine, serum
CRP, serum 25(OH) vitamin D, serum iron, and serum calcium. A
multiple logistic regression analysis was done to determine the
association between the different risk factors for recurrent GAS
tonsillopharyngitis. A signicance level of <0.05 was used in this test.
3. Results
The medical charts of 173 adult patients with acute tonsillo-
pharyngitis were reviewed for the years 20072009. Forty-two
patients were excluded because of: malignancy (n = 11), taking
immunosuppressant drugs (n = 7), renal failure with creatinine
clearance <35 ml/min (n = 9), pregnancy (n = 6), connective tissue
disease (n = 4), low compliance (n = 3), and vitamin D supplemen-
tation (n = 2). One hundred and thirty-one patients with acute
tonsillopharyngitis were assessed and a further 77 were excluded
because of non-GAS tonsillopharyngitis or no recurrent GAS
tonsillopharyngitis. Finally 54 patients with recurrent GAS
tonsillopharyngitis were included in the study. Table 1 sum-
marizes the differences between the cases and controls.
Table 1
Demographic clinical, and some clinical laboratory data, cases vs. controls
Characteristic Cases (n = 54) Controls (n = 50) p-Value
Age
a
(years) 41 13 42 12 NS
Male sex 30 (55%) 27 (54%) NS
BMI
a
(kg/m
2
) 27 4.4 28 5 NS
Diabetes mellitus 7 (13%) 6 (12%) NS
Creatinine
a
(mg/dl) 0.7 0.15 0.8 0.14 NS
Serum CRP
a
(mg/l) 4.9 3.3 2.8 2.2 0.001
Serum 25(OH) vitamin D
a
(ng/ml) 11.5 4.7 26 7 0.001
Serum 25(OH) vitamin D <20 ng/ml
a
50 (92%) 4 (8%) 0.001
Serum iron
a
(mg/dl) 68 31 67 40 NS
Serum calcium
a
(mg/dl) 9.2 0.26 9.0 1.16 NS
Smoking 8 (15%) 11 (22%) NS
SD, standard deviation; BMI, body mass index; CRP, C-reactive protein; NS, not signicant.
a
Results are mean SD, or n (%).
W. Nseir et al. / International Journal of Infectious Diseases 16 (2012) e735e738 e736
The most clear differences were seen in the mean levels of
serum CRP and 25(OH) vitamin D. Univariate analysis showed a
signicant association between male gender, CRP, and serum
25(OH) vitamin D. Table 2 shows the results of the multiple logistic
regression analysis for identifying risk factors for recurrent GAS
tonsillopharyngitis after adjusting for the confounders of BMI,
diabetes mellitus, serum iron levels, serum creatinine, and serum
calcium. The analysis showed that serum CRP >3 mg/l and serum
25(OH) vitamin D <20 ng/ml were associated with recurrent GAS
tonsillopharyngitis.
4. Discussion
To the best of our knowledge, this is the rst study that has
investigated the association between vitamin D and recurrent GAS
tonsillopharyngitis in adults. Our ndings indicate a link between
vitamin D deciency and the recurrence of GAS tonsillopharyngi-
tis.
Vitamin D deciency has been associated with several adverse
health consequences that include autoimmune diseases, cardio-
vascular diseases, and infections.
2527
The results of epidemiologi-
cal studies have demonstrated the existence of a link between
vitamin D deciency and the increased occurrence of pulmonary
tuberculosis and respiratory infections.
28,29
Recently we showed
an association between vitamin D insufciency and the risk of
recurrent bacterial infections among adult patients with fatty
liver.
30
Aydin et al. showed that vitamin D insufciency was more
prevalent in children with recurrent tonsillitis than in healthy
children.
23
Two double-blind randomized controlled trials of
vitamin D supplementation have shown that vitamin D reduces the
incidence of URT infection.
31,32
In contrast one randomized
controlled trial showed that there was no benet of vitamin D
supplementation in decreasing the incidence of symptomatic URT
infections.
33
There is a growing epidemic of vitamin D deciency, and its
consequences beyond bone health are still not well known.
However, early reports have linked it to cardiovascular conditions,
immune diseases, and infections.
2530,34,35
The role of vitamin D as
an antimicrobial agent acting through multiple mechanisms is
becoming increasingly recognized. Bikle reviewed the potential
boost to innate immunity by vitamin D.
36
Gombart et al. proposed
that 1,25-dihydroxyvitamin D3 induces the expression of the
human cathelicidin antimicrobial peptide gene.
37
Thus vitamin D
has an important role in the production of both cathelicidin and
defensins, AMPs that provide a natural defense against potential
pathogens, especially in URT infections.
3841
In our study, we found that CRP levels were higher in patients
with recurrent GAS tonsillopharyngitis than in the comparator
group, and levels >3 mg/l were found to be associated with
recurrent tonsillopharyngitis. The CRP value is usually elevated in
patients with GAS tonsillopharyngitis and the CRP test has also
been shown to be useful in differentiating GAS tonsillopharyngitis
from other kinds of throat infection.
4244
Melbye et al. showed that
a periodic CRP measurement is an effective tool for monitoring
patients with GAS tonsillopharyngitis during antibiotic therapy.
45
Previous studies have demonstrated that iron deciency is
prevalent in children with recurrent tonsillitis and in children
undergoing adenotonsillectomy.
46,47
Low serum iron levels have
been associated with abnormalities in the cell-mediated response
as well as a decreased ability of phagocytic cells to kill certain types
of bacteria.
48
Elverland et al. showed a benecial effect of
tonsillectomy and adenoidectomy on hemoglobin and iron
metabolism and found that iron deciency was common among
children with recurrent tonsillitis and upper airway obstruction.
49
In our study, we did not nd any correlation between serum iron
levels and recurrent tonsillopharyngitis in adults.
We conclude that recurrent GAS tonsillopharyngitis in adults
could be related to vitamin D levels. Data from epidemiological
studies indicate that vitamin D deciency has become a common
nding in recent years and appropriate replacement may offer
immune and antimicrobial benets. Because measurement of
vitamin D levels is easily done and vitamin D supplements are
readily obtainable and inexpensive, further studies are needed to
assess whether this represents a causal association and whether
vitamin D replacement therapy can prevent the recurrence of GAS
tonsillopharyngitis.
Conict of interest: No conict of interest to declare.
References
1. Schappert SM. Ambulatory care visits to physician ofces, hospital outpatient
departments, and emergency departments: United States, 1996. Vital Health
Stat 1998;13(134):137.
2. Houvinen P, Lahtonen R, Ziegler T, Meurman O, Hakkarainen K, Miettinen A,
et al. Pharyngitis in adults: the presence and coexistence of viruses and bacterial
organisms. Ann Intern Med 1989;110:6126.
3. Komaroff AL, Pass TM, Aronson MD, Ervin CT, Cretin S, Winickoff RN, et al. The
prediction of streptococcal pharyngitis in adults. J Gen Intern Med 1986;1:17.
4. Eisen SA, Miller DK, Woodward RS, Spitznagel E, Przybeck TR. The effect of
prescribed daily dose frequency on patient medication compliance. Arch Intern
Med 1990;150:18814.
5. Breese BB, Disney FA, Talpey WB. Penicillin in streptococcal infections: total
dose and frequency of administration. Am J Dis Child 1965;110:12530.
6. Khajavi A, Amirhakimi GH. The rachitic lung. Pulmonary ndings in 30 infants
and children with malnutritional rickets. Clin Pediatr 1977;16:368.
7. el-Daher NT, Hijazi SS, Rawashdeh NM, al-Khalil IA, Abu-Ektaish FM, Abdel-Latif
DI. Immediate vs. delayed treatment of group A beta-hemolytic streptococcal
pharyngitis with penicillin V. Pediatr Infect Dis J 1991;10:12630.
8. Pichichero ME, Disney FA, Talpey WB, Green JL, Francis AB, Roghmann KJ, et al.
Adverse and benecial effects of immediate treatment of group A beta-hemo-
lytic streptococcal pharyngitis with penicillin. Pediatric Infect Dis J 1987;6:
63543.
9. Gerber MA, Randolph MF, Demeo KK, Kaplan EL. Lack of impact of early
antibiotic therapy for streptococcal pharyngitis on recurrence rates. J Pediatr
1990;117:8538.
10. Pichichero ME, Casey JR. Systemic review of factors contributing to penicillin
treatment failure in Streptococcus pyogenes pharyngitis. Otolaryngol Head Neck
Surg 2007;137:8517.
11. Kim KS, Kaplan EL. Association of penicillin tolerance with failure to eradicate
group A streptococci from patients with pharyngitis. J Pediatr 1985;107:6814.
12. Grahn E, Holm SE, Roos K. Penicillin tolerance in beta-streptococci isolated from
patients with tonsillitis. Scand J Infect Dis 1987;19:4216.
13. Dagan R, Ferne M, Sheinis M, Alkan M, Katzenelson E. An epidemic of penicillin-
tolerant group A streptococcal pharyngitis in children living in closed commu-
nity: mass treatment with erythromycin. J Infect Dis 1987;156:5146.
14. Najada AS, Habashneh MS, Khader M. The frequency of nutritional rickets
among hospitalized infants and its relation to respiratory diseases. J Trop Pediatr
2004;50:3648.
15. Sabetta JR, DePetrillo P, Cipriani RJ, Smardin J, Burns LA, Landry ML. Serum 25-
hydroxyvitamin D and the incidence of acute viral respiratory tract infections in
healthy adults. PLoS One 2010;14:1108.
16. Berry DJ, Hesketh K, Power C, Hypponen E. Vitamin D status has a linear
association with seasonal infections and lung function in British adults. Br J
Nutr 2011;106:143340.
17. Grant WB. Variation in vitamin D production could possibly explain the
seasonality of childhood respiratory infections in Hawaii. Pediatr Infect Dis J
2008;27:853.
18. Ginde AA, Mansbach JM, Camargo Jr CA. Association between serum 25-
hydroxyvitamin D level and upper respiratory tract infection in the Third
National Health and Nutrition Examination Survey. Arch Intern Med 2009;169:
38490.
19. Diamond G, Legarda D, Ryan LK. The innate immune response of the respiratory
epithelium. Immunol Rev 2000;173:2398402.
Table 2
Results of multiple logistic regression analysis of recurrent GAS tonsillopharyngitis
Variable OR (95% CI) p-Value
Male gender 1.15 (0. 216.38) 0.86
Age 0.97 (0. 911.03) 0.35
CRP >3 mg/l 1.57 (1.132.19) 0.007
Serum 25(OH) vitamin D <20 ng/ml 1.62 (1.511.76) 0.001
GAS, group A Streptococcus; OR, odds ratio; CI, condence interval; CRP, C-reactive
protein.
W. Nseir et al. / International Journal of Infectious Diseases 16 (2012) e735e738 e737
20. Medzhitov R, Janeway Jr C. Innate immune recognition: mechanisms and
pathways. Immunol Rev 2000;173:8997.
21. Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in
bacteria? Nat Rev Microbiol 2005;3:23850.
22. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor
triggering of a vitamin D-mediated human antimicrobial response. Science
2006;311:17703.
23. Aydin S, Aslan I, Yildiz I, Agachan B, Toptas B, Toprak S, et al. Vitamin D levels in
children with recurrent tonsillitis. Int J Pediatr Otorhinolaryngol 2011;75:3647.
24. Bisno AL, Gerber MA, Gwaltney Jr JM, Kaplan EL, Schwartz RH. Practice guide-
lines for the diagnosis and management of group A streptococcal pharyngitis.
Clin Infect Dis 2002;35:11325.
25. Holick MF. Vitamin D deciency. N Engl J Med 2007;357:26681.
26. Arnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: new etiological
and therapeutic consideration. Ann Rheum Dis 2007;66:113742.
27. Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab 2010;95:
4718.
28. Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systemic
review and meta-analysis. Int J Epidemiol 2008;37:1139.
29. Laaksi I, Ruohola JP, Touhimaa P, Auvinen A, Haataja R, Pihlajamaki H, et al. An
association of serum vitamin D concentration < 40 nmol/L with acute respira-
tory tract infection in young Finnish men. Am J Clin Nutr 2007;86:7147.
30. Nseir W, Taha H, Khateeb J, Grosovski M, Assy N. Fatty liver is associated with
recurrent bacterial infections independent of metabolic syndrome. Dig Dis Sci
2011;56:332834.
31. Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial
of vitamin D supplementation to prevent seasonal inuenza A in school-
children. Am J Clin Nutr 2010;91:125560.
32. Laaksi I, Ruohola JP, Mattila V, Auvinen A, Ylikomi T, Pihlajamaki H. Vitamin D
supplementation for the prevention of acute respiratory tract infection: a
randomized double-blinded trial amongst young Finnish men. J Infect Dis
2010;202:80914.
33. Li-Ng M, Aloia JF, Pollack S, Cunha BA, Mikhail M, Yeh J, et al. A randomized
controlled trial of vitamin D3 supplementation for the prevention of symp-
tomatic upper respiratory tract infections. Epidemiol Infect 2009;137:
1396404.
34. Wallis DE, Penckofer S, Sizemore GW. The sunshine decit and cardiovascular
disease. Circulation 2008;118:147685.
35. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-Hydroxyvitamin D and risk of
myocardial infarction in men. Arch Intern Med 2008;168:117480.
36. Bikle DD. Vitamin D and the immune system: role in protection against
bacterial infection. Curr Opin Nephrol Hypertens 2008;17:34852.
37. Gombart AF, Borregaard N, Koefer HP. Human cathelicidin antimicrobial peptide
(CAMP) geneis a direct target of the vitamin D receptor and is stronglyup-regulated
in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J 2005;19:106777.
38. Chromek M, Slamova Z, Bergman P, Kovacs L, Podracka L, Ehren I, et al. The
antimicrobial peptide cathelicidin protects the urinary tract against invasive
bacterial infection. Nat Med 2006;12:63641.
39. Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, et al. Cutting edge:
1,25-dihydroxyvitamin D3 is a direct inducer for antimicrobial peptide gene
expression. J Immunol 2004;173:290912.
40. Akbar NA, Zacharek MA. Vitamin D: immunomodulation of asthma, allergic
rhinitis, and chronic rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg 2011;19:
2248.
41. Bartley J. Vitamin D, innate immunity and upper respiratory tract infections. J
Laryngol Otol 2010;124:4659.
42. Kaplan EL, Wannamaker LW. C-reactive protein in streptococcal pharyngitis.
Pediatrics 1977;60:2832.
43. Hjortdahl P, Melbye H. Does near-to-patient testing contribute to the diagnosis
of streptococcal pharyngitis in adults? Scand J Prim Health Care 1994;12:706.
44. Gulich MS, Matschiner A, Gluck R, Zeitler HP. Improving diagnostic accuracy of
bacterial pharyngitis by near patient measurement of C-reactive protein (CRP).
Br J Gen Pract 1999;49:11921.
45. Melbye H, Bjorkheim MK, Leinan T. Daily reduction in C-reactive protein values,
symptoms, signs and temperature in group-A streptococcal pharyngitis treated
with antibiotics. Scand J Clin Lab Invest 2002;62:5215.
46. Busuttil A, Kerr AI, Logan RW. Iron deciency in children undergoing adenoid-
tonsillectomy. J Laryngol Otol 1979;93:4958.
47. Mira E, Benazzo M, Asti L, Marchi A, Spriano P, Losi R. Iron status in children
undergoing tonsillectomy and its short-term modication following surgery.
Acta Otolaryngol 1988;454:2614.
48. Dallman PR. Iron deciency and the immune response. Am J Clin Nutr 1987;46:
32934.
49. Elverland HH, Aasand G, Miljeteig H, Ulvik RJ. Effects of tonsillectomy and
adenoidectomy on hemoglobin and iron metabolism. Ind J Pediatr Otorhinolar-
yngol 2004;68:41923.
W. Nseir et al. / International Journal of Infectious Diseases 16 (2012) e735e738 e738