On the association between soft drink consumption and Helicobacter pylori infection.
ABSTRACT The association between soft drink (SD) consumption and Helicobacter pylori infection remains unclear.
To examine the relationship between SD consumption and H. pylori infection.
A prospective study included individuals who were referred for an upper gastrointestinal endoscopic examination because chronic dyspepsia within a period of 1 year. In addition to determining daily SD consumption and the risk factors for H. pylori infection by asking all study participants to complete a standard questionnaire about their diet, daily eating and drinking habits, and their lifestyle before undergoing the endoscopic examination. H. pylori infection was established by a positive result of the rapid urease test and histology.
Of the 312 individuals who were referred for the endoscopic examination because chronic dyspepsia, 269 met the inclusion criteria. H. pylori infection was found in 164 (61%) of the 269 study participants, and, of these, 104/164 individuals were SD consumers with H. pylori infection versus 24/105 individuals without H. pylori infection (63 vs. 23%, respectively, P < 0.001). The results of the multiple logistic regression analysis showed that SD consumption (odds ratio = 4.0; 95% confidence interval = 3.19-5.82, P < 0.001), was associated with H. pylori infection.
SD consumption is associated with H. pylori infection in individuals with chronic dyspepsia.
- SourceAvailable from: Kathleen (Kathy) B Bamford[Show abstract] [Hide abstract]
ABSTRACT: Despite the widespread prevalence and serious clinical sequelae of infection with Helicobacter pylori, there have been few large population-based studies, using randomly selected subjects, examining the epidemiology of this infection. To examine the distribution and determinants of H. pylori infection in a developed country. Overall 4742 subjects, aged 12-64, from Northern Ireland were randomly selected. Helicobacter pylori specific IgG antibodies were measured by enzyme linked immunosorbent assay, using an acid-glycine extract antigen, in stored serum from subjects who had participated in three linked population-based surveys of cardiovascular risk factors performed in 1986 and 1987. The overall prevalence of H. pylori infection was 50.5%. Prevalence increased with age from 23.4% in 12-14 year olds to 72.7% in 60-64 year olds: chi 2 for trend 518, P < 10(-4). In subjects aged > or = 25, infection was more common in males (60.9%) than females (55.2%): chi 2 = 9.53, P < 0.01. This relation remained significant after adjusting for age, and measures of socioeconomic class: odds ratio (OR) for infection, male versus female was 1.19 (95% confidence interval [CI]: 1.02-1.40). Infection was associated with social class: the adjusted OR of infection in subjects from manual social classes relative to those from non-manual classes was 1.7 (95% CI: 1.47-1.98). Infection was significantly more common in current smokers and ex-smokers than in subjects who had never smoked: adjusted OR for infection, ex-smokers versus never smoked was 1.22 (95% CI: 1.01-1.49); for smokers of > or = 20/day versus never smoked OR = 1.33 (95% CI: 1.05-1.67). Infection was not associated with height in adult males but mean height in infected women was lower than in uninfected women after adjusting for age and socioeconomic status: difference in mean height (SE), -0.85 cm (0.32), P < 0.01. There was no demonstrable relationship between H. pylori infection and current alcohol intake. This study demonstrated a high prevalence of infection in a population from a developed country. Previously reported associations between H. pylori infection, age, sex, social class, and reduced height in females were confirmed and smoking was identified as a possible risk factor for H. pylori infection.International Journal of Epidemiology 08/1997; 26(4):880-7. · 6.98 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Intraluminal duodenal pH was recorded using a combined miniature electrode and logged digitally every 10 or 20 seconds for five hours (basal/meal/drink) in eight control subjects and 11 patients with duodenal ulcer (five on and off treatment with cimetidine). Over the whole test there were no significant differences in duodenal mean pH or log mean hydrogen ion activity (LMHa) between control subjects and patients with duodenal ulcer, but there were significantly longer periods of duodenal acidification (pH less than 4) and paradoxically more periods of duodenal alkalinisation (pH greater than 6) in the duodenal ulcer group compared with controls. After a meal duodenal mean pH and LMHa fell significantly in both controls and patients with duodenal ulcer, with more periods of duodenal acidification and alkalinisation in the duodenal ulcer group. An exogenous acid load (Coca-Cola) significantly increased the periods of duodenal acidification, and reduced alkalinisation, in both groups. Cimetidine significantly increased mean pH and LMHa and abolished the brief spikes of acidification in four of five patients with duodenal ulcer. Peak acid output (but not basal acid output) was significantly correlated with duodenal mean pH and LMHa but not with the periods of duodenal acidification. Smoking did not affect duodenal pH in either group.Gut 05/1984; 25(4):386-92. · 10.73 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: To investigate the effect of alcohol consumption on the risk of Helicobacter pylori infection, standardized questionnaires on drinking habits were used to interview 451 patients, whose H. pylori status was determined both by culture and serology. Reported alcohol consumption did not increase the risk of H. pylori infection (a 1.0 odds ratio, CI95 0.6-1.6). However, when the patients were divided into two age-groups, those under 35 years who reported to use alcohol seemed to have a slightly higher risk of H. pylori infection (a 3.3 odds ratio CI95 0.9-12.2) compared to those over 35 years (a 1.0 odds ratio, CI95 0.5-2.2). This phenomenon did not reach statistical significance. The type of alcohol consumed did not affect the age-adjusted risk of H. pylori infection. If pathologically defined chronic gastritis was found, the risk for H. pylori was high (a 26.7 odds ratio, CI95 12.1-59.0, for those under 35 years, and a 12.8 odds ratio, CI95 6.7-24.3, for those over 35 years of age.Digestion 02/1991; 50(2):92-8. · 1.94 Impact Factor
The association between vitamin D levels and recurrent group A streptococcal
tonsillopharyngitis in adults
William Nseira,b,e,*, Julnar Mograbia,b, Zuhair Abu-Rahmehc, Mahmud Mahamida,
Omar Abu-Elhejaa, Adel Shalatad
aDepartment of Internal Medicine, Infectious Disease Unit, Holy Family Hospital, POB 8, 16100, Nazareth, Israel
bInfectious Diseases Unit, Holy Family Hospital, Nazareth, Israel
cDepartment of Radiology, Holy Family Hospital, Nazareth, Israel
dDepartment of Pediatrics, Holy Family Hospital, Nazareth, Israel
eFaculty of Medicine on the Galilee, Bar-Ilan University, Safed, Israel
In the adult population, acute tonsillopharyngitis accounts for
1–2% of all visits to outpatient clinics, physician offices, and
emergency departments.1Approximately 5–17% of acute tonsillo-
pharyngitis cases are due to a bacterial infection, often to group A
b-hemolytic streptococci (GAS).2,3The 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.4–13
The association between vitamin D deficiency 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.14Recently, epidemiological studies have demonstrated a
correlation between vitamin D concentration and the incidence
of respiratory infections.15–18Moreover, scientific evidence
shows the important role of vitamin D in the immune
system.19,20The antimicrobial peptides (AMPs) defensin and
cathelicidin, which are the principal defense factors of the upper
respiratory tract (URT), are upregulated by vitamin D.21,22Aydin
et al. showed that vitamin D insufficiency was more prevalent in
children with recurrent tonsillitis than in healthy children.23
Despite the fact that such an association between vitamin D
deficiency 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 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) e735–e738
A R T I C L E
I N F O
Received 23 December 2011
Accepted 11 May 2012
Corresponding Editor: William Cameron,
Group A Streptococcus
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 identified 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 defined 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 significant 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 D among subjects
with recurrent GAS tonsillopharyngitis were significantly 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% confidence interval 1.51–1.76; p
Conclusions: Our findings indicate a link between vitamin D deficiency and the recurrence of GAS
? 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: +972 46508942; fax: +972 46508973.
E-mail address: email@example.com (W. Nseir).
Contents lists available at SciVerse ScienceDirect
International Journal of Infectious Diseases
jou r nal h o mep ag e: w ww .elsevier .co m /loc ate/ijid
1201-9712/$36.00 – see front matter ? 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
2. Materials and methods
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 were aged 18–60 years. The exclusion criteria were: (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).
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.24Recurrent
GAS tonsillopharyngitis was defined as three or more episodes of
GAS tonsillopharyngitis per year for a period of two consecutive
years. Obesity was defined as a BMI >30 kg/m2. For laboratory tests,
levels considered normal were: CRP 0–0.5 mg/l, serum iron 60–
180 mg/dl, serum creatinine 0.67–1.17 mg/dl, and serum calcium
8.1–10.4 mg/dl. The normal range for serum 25(OH) vitamin D levels
was considered to be 30–50 ng/ml; we defined vitamin D
insufficiency as levels of 25(OH) vitamin D <30 ng/ml and vitamin
D deficiency 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 Student’s 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 significance level of <0.05 was used in this test.
The medical charts of 173 adult patients with acute tonsillo-
pharyngitis were reviewed for the years 2007–2009. 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.
Demographic clinical, and some clinical laboratory data, cases vs. controls
Cases (n = 54)
Controls (n = 50)
Serum 25(OH) vitamin Da(ng/ml)
Serum 25(OH) vitamin D <20 ng/mla
41 ? 13
27 ? 4.4
0.7 ? 0.15
4.9 ? 3.3
11.5 ? 4.7
68 ? 31
9.2 ? 0.26
42 ? 12
28 ? 5
0.8 ? 0.14
2.8 ? 2.2
26 ? 7
67 ? 40
9.0 ? 1.16
SD, standard deviation; BMI, body mass index; CRP, C-reactive protein; NS, not significant.
aResults are mean ? SD, or n (%).
W. Nseir et al. / International Journal of Infectious Diseases 16 (2012) e735–e738
The most clear differences were seen in the mean levels of
serum CRP and 25(OH) vitamin D. Univariate analysis showed a
significant 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
To the best of our knowledge, this is the first study that has
investigated the association between vitamin D and recurrent GAS
tonsillopharyngitis in adults. Our findings indicate a link between
vitamin D deficiency and the recurrence of GAS tonsillopharyngi-
Vitamin D deficiency has been associated with several adverse
health consequences that include autoimmune diseases, cardio-
vascular diseases, and infections.25–27The results of epidemiologi-
cal studies have demonstrated the existence of a link between
vitamin D deficiency and the increased occurrence of pulmonary
tuberculosis and respiratory infections.28,29Recently we showed
an association between vitamin D insufficiency and the risk of
recurrent bacterial infections among adult patients with fatty
liver.30Aydin et al. showed that vitamin D insufficiency was more
prevalent in children with recurrent tonsillitis than in healthy
children.23Two double-blind randomized controlled trials of
vitamin D supplementation have shown that vitamin D reduces the
incidence of URT infection.31,32In contrast one randomized
controlled trial showed that there was no benefit of vitamin D
supplementation in decreasing the incidence of symptomatic URT
There is a growing epidemic of vitamin D deficiency, and its
consequences beyond bone health are still not well known.
However, early reports have linked it to cardiovascular conditions,
immune diseases, and infections.25–30,34,35The 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.36Gombart et al. proposed
that 1,25-dihydroxyvitamin D3 induces the expression of the
human cathelicidin antimicrobial peptide gene.37Thus 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.38–41
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.42–44Melbye 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 deficiency is
prevalent in children with recurrent tonsillitis and in children
undergoing adenotonsillectomy.46,47Low 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.48Elverland et al. showed a beneficial effect of
tonsillectomy and adenoidectomy on hemoglobin and iron
metabolism and found that iron deficiency was common among
children with recurrent tonsillitis and upper airway obstruction.49
In our study, we did not find 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 deficiency has become a common
finding in recent years and appropriate replacement may offer
immune and antimicrobial benefits. 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
Conflict of interest: No conflict of interest to declare.
1. Schappert SM. Ambulatory care visits to physician offices, hospital outpatient
departments, and emergency departments: United States, 1996. Vital Health
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;110:612–6.
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;1:1–7.
4. Eisen SA, Miller DK, Woodward RS, Spitznagel E, Przybeck TR. The effect of
prescribed daily dose frequency on patient medication compliance. Arch Intern
5. Breese BB, Disney FA, Talpey WB. Penicillin in streptococcal infections: total
dose and frequency of administration. Am J Dis Child 1965;110:125–30.
6. Khajavi A, Amirhakimi GH. The rachitic lung. Pulmonary findings in 30 infants
and children with malnutritional rickets. Clin Pediatr 1977;16:36–8.
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;10:126–30.
8. Pichichero ME, Disney FA, Talpey WB, Green JL, Francis AB, Roghmann KJ, et al.
Adverse and beneficial effects of immediate treatment of group A beta-hemo-
lytic streptococcal pharyngitis with penicillin. Pediatric Infect Dis J 1987;6:
9. Gerber MA, Randolph MF, Demeo KK, Kaplan EL. Lack of impact of early
antibiotic therapy for streptococcal pharyngitis on recurrence rates. J Pediatr
10. Pichichero ME, Casey JR. Systemic review of factors contributing to penicillin
treatment failure in Streptococcus pyogenes pharyngitis. Otolaryngol Head Neck
11. Kim KS, Kaplan EL. Association of penicillin tolerance with failure to eradicate
group A streptococci from patients with pharyngitis. J Pediatr 1985;107:681–4.
12. Grahn E, Holm SE, Roos K. Penicillin tolerance in beta-streptococci isolated from
patients with tonsillitis. Scand J Infect Dis 1987;19:421–6.
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;156:514–6.
14. Najada AS, Habashneh MS, Khader M. The frequency of nutritional rickets
among hospitalized infants and its relation to respiratory diseases. J Trop Pediatr
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
17. Grant WB. Variation in vitamin D production could possibly explain the
seasonality of childhood respiratory infections in Hawaii. Pediatr Infect Dis J
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:
19. Diamond G, Legarda D, Ryan LK. The innate immune response of the respiratory
epithelium. Immunol Rev 2000;173:2398–402.
Results of multiple logistic regression analysis of recurrent GAS tonsillopharyngitis
OR (95% CI)
CRP >3 mg/l
Serum 25(OH) vitamin D <20 ng/ml
1.15 (0. 21–6.38)
0.97 (0. 91–1.03)
GAS, group A Streptococcus; OR, odds ratio; CI, confidence interval; CRP, C-reactive
W. Nseir et al. / International Journal of Infectious Diseases 16 (2012) e735–e738
20. Medzhitov R, Janeway Jr C. Innate immune recognition: mechanisms and
pathways. Immunol Rev 2000;173:89–97.
21. Brogden KA. Antimicrobial peptides: pore formers or metabolic inhibitors in
bacteria? Nat Rev Microbiol 2005;3:238–50.
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
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;75:364–7.
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;35:113–25.
25. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–81.
26. Arnson Y, Amital H, Shoenfeld Y. Vitamin D and autoimmunity: new etiological
and therapeutic consideration. Ann Rheum Dis 2007;66:1137–42.
27. Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab 2010;95:
28. Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systemic
review and meta-analysis. Int J Epidemiol 2008;37:113–9.
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;86:714–7.
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
31. Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial
of vitamin D supplementation to prevent seasonal influenza A in school-
children. Am J Clin Nutr 2010;91:1255–60.
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
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:
34. Wallis DE, Penckofer S, Sizemore GW. The ‘‘sunshine deficit’’ and cardiovascular
disease. Circulation 2008;118:1476–85.
35. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-Hydroxyvitamin D and risk of
myocardial infarction in men. Arch Intern Med 2008;168:1174–80.
36. Bikle DD. Vitamin D and the immune system: role in protection against
bacterial infection. Curr Opin Nephrol Hypertens 2008;17:348–52.
37. Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide
(CAMP)gene is a direct targetof the vitamin D receptor and is stronglyup-regulated
in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J 2005;19:1067–77.
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;12:636–41.
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;173:2909–12.
40. Akbar NA, Zacharek MA. Vitamin D: immunomodulation of asthma, allergic
rhinitis, and chronic rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg 2011;19:
41. Bartley J. Vitamin D, innate immunity and upper respiratory tract infections. J
Laryngol Otol 2010;124:465–9.
42. Kaplan EL, Wannamaker LW. C-reactive protein in streptococcal pharyngitis.
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;12:70–6.
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;49:119–21.
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;62:521–5.
46. Busuttil A, Kerr AI, Logan RW. Iron deficiency in children undergoing adenoid-
tonsillectomy. J Laryngol Otol 1979;93:49–58.
47. Mira E, Benazzo M, Asti L, Marchi A, Spriano P, Losi R. Iron status in children
undergoing tonsillectomy and its short-term modification following surgery.
Acta Otolaryngol 1988;454:261–4.
48. Dallman PR. Iron deficiency and the immune response. Am J Clin Nutr 1987;46:
49. Elverland HH, Aasand G, Miljeteig H, Ulvik RJ. Effects of tonsillectomy and
adenoidectomy on hemoglobin and iron metabolism. Ind J Pediatr Otorhinolar-
W. Nseir et al. / International Journal of Infectious Diseases 16 (2012) e735–e738