0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Article |

A Randomized Placebo-Controlled Trial of Mebendazole for Halitosis FREE

Bahri Ermis, MD; Turan Aslan, MD; Levent Beder, MD; Murat Unalacak, MD
[+] Author Affiliations

From the Departments of Pediatrics (Dr Ermis), Infectious Diseases (Dr Aslan), Otorhinolaryngology (Dr Beder), and Family Medicine (Dr Unalacak), School of Medicine, Karaelmas University, Zonguldak, Turkey.


Arch Pediatr Adolesc Med. 2002;156(10):995-998. doi:10.1001/archpedi.156.10.995.
Text Size: A A A
Published online

Objective  To test whether mebendazole, an antiparasitic drug, would affect recovery from halitosis.

Design  We conducted a randomized, double-blind, placebo-controlled trial between April 1999 and September 2001.

Setting  A referral medical center.

Patients  One hundred sixty-two children aged 5 to 16 years whose parents complained about their chronic bad breath.

Interventions  Children were randomly assigned to receive mebendazole (n = 82) or placebo (n = 80).

Main Outcome Measure  Parents whose children had halitosis were evaluated for halitosis at 2 months of treatment by questionnaire. The microbiologist investigated the stool samples of children for parasitosis at the beginning of the trial and also at the end of the trial in children who were treated with mebendazole.

Results  Among those children who had evidence of parasites in stool samples at the beginning of the trial, 18 of 28 who were treated with mebendazole recovered from halitosis, compared with 2 of 24 who received placebo (relative risk [RR] for recovery, 7.7; 95% confidence interval [CI], 2.0-29.9). Among those who did not have stool parasites, 14 of 52 improved with mebendazole, compared with 10 of 48 taking placebo (RR, 1.3; 95% CI, 0.6-2.6). Mebendazole intake made a significant difference whether or not the children had parasites (P = .002).

Conclusions  Parasitosis should be considered as a possible cause of halitosis in the pediatric patient population. Mebendazole therapy seems to offer benefit to those children with parasites as a potential cause of their halitosis.

Figures in this Article

HALITOSIS (bad breath) is defined as a foul odor arising from a person's oral cavity or nasal passages.1 It is a common ailment in children and adults, and 50% to 60% of the general population has chronic halitosis.24 Most cases of halitosis may have oral causes.2,57 Besides the oral cavity problems, it is associated with chronic sinusitis, upper and lower respiratory tract diseases, various systemic diseases, and usage of certain drugs.1,69 Bad breath originating from gastrointestinal disorders is considered to be extremely rare.10 It was reported in 1941 that 19% of the children visiting an outpatient clinic at Children's Hospital of Boston (Boston, Mass) were infected with pinworms.11 Prevalence levels as high as 100% have been recorded for some parasites, especially Enterobius vermicularis in the United States and northwestern Europe.12 Using standard methods, the prevalence levels have been shown to be around 35% to 87% in Turkey.13,14 Although most of the children infested with parasites may be asymptomatic, others suffer from deficits in their physical, intellectual, and cognitive growth.15

We have no knowledge of medical literature reporting the relationship between halitosis and parasitosis. When a mother stated that the bad breath of her child, who was infested with E vermicularis, disappeared after antiparasitic treatment with mebendazole, we became suspicious that halitosis might be a consequence of parasitic infection and decided to see if a randomized trial with mebendazole could influence recovery from halitosis.

We conducted a randomized, double-blind, placebo-controlled trial. The Ethical Committee of Karaelmas University (Zonguldak, Turkey) approved the trial. Parents were informed, and their consent was obtained before enrollment.

PATIENTS AND SETTING

Children aged 5 to 16 years whose parents complained about their chronic bad breath were included in the trial. Participants were enrolled between April 1999 and September 2001 from the outpatient clinics of the Department of Pediatrics at the Research Hospital of Karaelmas University.

INCLUSION CRITERIA

When parents spontaneously reported bad breath in their children who were taken to outpatient clinics for various nonpathologic reasons (well-child care, growth follow-up, lack of appetite, etc), these children were included. The parents reported no recent acute infection.

EXCLUSION CRITERIA

A pediatrician, an otorhinolaryngologist, and a dentist examined all of the children. If needed, their pulmonary and/or Water view radiographs were taken. According to any suspicion of adenoiditis or sinusitis during the ear-nose-throat examination, endoscopic and tomographic investigations were done. Also, liver function tests (alanine aminotransferase and aspartate aminotransferase levels), serum urea nitrogen levels, creatinine levels, fasting blood glucose levels, uric acid levels, and hemograms were studied for all children.

RANDOMIZATION

A random-number table was used to generate random sequences of allocation, which were generated by a research coordinator. Numbered containers were used for allocation concealment. The investigators, who were blinded to the trial, were assigned participants to their treatment groups. The parents, investigators, and the research coordinator were unaware of the assigned treatment. Follow-up data collection and effectiveness of blinding were evaluated by questionnaire at the end of the trial.

We assumed a 30% difference in children who had parasites, and a 40% clinical success rate in the mebendazole group. To achieve 80% power with α = .05, we needed to enroll 29 children with parasites in each study group. The 58 children who had parasites were recruited from those 190 children with halitosis.

LABORATORY INVESTIGATIONS

Fresh stool specimens were submitted to the laboratory in sterile containers with tight-fitting lids, and these containers were then placed into plastic bags before transport. All fresh and liquid specimens were examined within 1 hour or 30 minutes of passage, respectively. Examination of 3 specimens collected every other day was considered the minimum necessary to perform an adequate ova and parasite evaluation (National Committee for Clinical Laboratory Standards, Wayne, Pa, unpublished data, 1993).

Direct wet mounts and iodine (1:5 dilution of Lugol iodine) staining of fresh stool specimens were examined microscopically for motile trophozoites or helminth larvae. We performed either a Faust zinc sulfate centrifugal flotation technique or the Richie technique of formalin-ether sedimentation to increase yield, in addition to direct wet mount examinations according to the standard procedures. For false-negative test results, attention must be paid to the recommended speed and time of centrifugation, as well as excessive amounts of fat content in feces.16

The eggs, or occasionally, the adult worms of the pinworm, E vermicularis, may be detected on examination of a clear adhesive cellophane tape pressed against the perianal region. Specimens were collected late at night, when the worms are most active, or first thing in the early morning before bathing or defecation, then evaluated by microscopic examination in the standard manner.

In children who had parasites, 37 were found in the first, 14 were found in the second, and 7 were found in the third stool samples to be positive for parasites. The parents were not informed about parasitosis during follow-up. The stool samples that had parasites were investigated once at the end of the trial in the mebendazole group.

TREATMENT

Children were randomly assigned to receive mebendazole (100 mg twice daily for 3 consecutive days) or placebo. Pills were administered by the parents and were taken on an empty stomach 30 minutes before meals.

EVALUATION OF TREATMENT RESPONSE

A clinical improvement was acknowledged if parents declared the disappearance or notable decrease of their children's bad breath. Clinical failure was defined as parents sustaining reports of bad breath in their children.

STATISTICAL ANALYSIS

The differences between groups were analyzed by using the Pearson χ2 test. A Mantel-Haenszel test was used for point estimates (risk ratios) and 95% confidence intervals (CIs).

Of the 190 children, 28 (6 also had parasites) were excluded from the trial: 8 had tonsillitis and/or adenoiditis, 6 had chronic sinusitis, 7 had dental problems, 1 had chronic persisting hepatitis, and 6 refused to participate in the trial. Of the 58 children who had parasites, 6 were not meeting eligibility criteria (refused to participate and/or had other etiological reasons for halitosis) and were excluded from the trial. One hundred sixty-two children met the eligibility criteria and were randomized as shown in Figure 1. Ten children were excluded from the trial during follow-up: 5 were lost to follow-up, 2 were excluded for unknown reasons, 2 had varicella, and 1 child was excluded for noncompliance (Figure 1). Follow-up interviews were successfully completed in 93% of children. The characteristics of the study group and the parasites detected in stool samples are presented in Table 1. Stool examinations revealed that 28 children (35%) in the mebendazole group had parasites vs 24 (33%) in the placebo group. Of the 28 children with parasites who were treated with mebendazole, 18 (64%) recovered from halitosis vs only 2 (8%) of the 24 children with parasites who received placebo (relative risk [RR] for recovery, 7.7; 95% CI, 2.0-29.9). Among those who did not have stool parasites, 14 of 52 improved with mebendazole, compared with 10 of 48 taking placebo (RR, 1.3; 95% CI, 0.6-2.6). Mebendazole intake made a significant difference whether or not the children had parasites (P = .002) (Table 2).

Place holder to copy figure label and caption

Participant flow diagram.

Graphic Jump Location
Table Graphic Jump LocationTable 1. Characteristics of Children and Parasites Detected on Stool Examination*
Table Graphic Jump LocationTable 2. Recovery From Halitosis in Children With or Without Parasites*

Those 18 children who had parasites and improved for halitosis with mebendazole therapy were also cleared of parasites following mebendazole intake at the end of the trial. Of the 10 children who had parasites but did not improve for halitosis with mebendazole therapy, 4 had E vermicularis, and 2 had Giardia lamblia in their stool samples at the end of the trial. Of the rest of those, 2 were cleared from Ascaris lumbricoides, and 2 were cleared from Taenia saginata.

Stool examinations revealed that 28 children (35%) in the mebendazole group had parasites vs 24 (33%) in the placebo group. Of the 28 children with parasites who were treated with mebendazole, 18 (64%) recovered from halitosis vs only 2 (8%) of the 24 children with parasites who received placebo (RR for recovery, 7.7; 95% CI, 2.0-29.9). In our preliminary trial, mebendazole treatment seemed to encourage recovery from bad breath. It seemed to work in children with evidence of parasitic infection. By a search of MEDLINE, we do not find any literature to date regarding a relationship between halitosis and parasitosis. There might be several possible explanations for parasitosis as the cause of halitosis. First, excess saliva secretion stimulated by parasites leads to stasis, which may be a more convenient environment for bacterial overgrowth, especially during sleeping.17 Second, pulmonary migrations of some parasites and their larvae (eg, A lumbricoides and Trichuris trichiura). Third, it is suggested that halitosis should be considered in the presence of an increased formation of intestinal gases.18

At usual recommended dosages (100-200 mg daily), mebendazole seems to cause minimal adverse effects. Adverse effects seem to occur more frequently when higher dosages are used, and they may be related to effects resulting from drug-induced killing of the parasites in some cases.19 Transient diarrhea, abdominal pain, nausea, vomiting, headache, tinnitus, and dizziness also have been occasionally reported during mebendazole therapy. Myelosuppression manifesting as neutropenia and/or thrombocytopenia has also been reported in patients receiving high-dose (30-50 mg/kg daily) mebendazole therapy for extraintestinal infections.19 However, international trials have shown that mebendazole is safe and effective in eradicating many parasites.15,20,21 Biddulph22 has reported that widespread use of mebendazole in less-developed countries indicates that it is probably safe for infants and children, except for children with blood dyscrasias, leukopenia, or liver diseases.

Limitations to our study design included the fact that some parents reported that a child's bad breath showed a notable decrease, but did not disappear, and we accepted this to be a positive response to treatment. It may have been better to develop some grading for the improvement, or to use more objective tests for the assessment of halitosis.

In this trial, we found an association between mebendazole therapy and the resolution of halitosis through the resolution of parasitosis. We think that mebendazole improved bad-smelling breath among children who were infected with parasites.

Accepted for publication May 10, 2002.

What This Study Adds

Halitosis is defined as a foul odor arising from a person's oral cavity or nasal passages. It is a common ailment in children and adults, and 50% to 60% of the general population suffers from chronic halitosis. In this trial, we have presented an association between mebendazole therapy and resolution of halitosis through the resolution of parasitosis.

Corresponding author: Bahri Ermis, MD, Department of Pediatrics, Yakutiye Research Hospital, Ataturk University, 25240, Erzurum, Turkey (e-mail: bahriermis@yahoo.com).

Goroll  AHMulley  AG Primary Care Medicine: Office Evaluation and Management of the Adult Patient. 4th ed Philadelphia, Pa Lippincott Williams & Wilkins2000;1119- 1120
Bollen  CMRompen  EHDemanez  JP Halitosis: a multidisciplinary problem. Rev Med Liege. 1999;5432- 36
Meninguad  JPBado  FFavre  EBertrand  JCGuilbert  F Halitosis in 1999. Rev Stomatol Chir Maxillofac. 1999;100240- 244
Scully  CPorter  SPGreenman  J What to do about halitosis. BMJ. 1994;308217- 218
Link to Article
Tonzetich  J Production and origin of oral malador: a review of mechanisms and methods of analysis. J Periodontol. 1997;4813- 20
Link to Article
Tonzetich  JMcBride  BC Characterization of volatile sulphur production by pathogenic and non-pathogenic strains of oral bacteroides. Arch Oral Biol. 1981;26963- 969
Link to Article
Spielman  AIBivona  PRifkin  BR Halitosis: a common oral problem. N Y State Dent J. 1996;6236- 42
Rosenfeld  RM Pilot study of outcomes in pediatric rhinosinusitis. Arch Otolaryngol Head Neck Surg. 1995;121729- 736
Link to Article
Amir  EShimonov  RRosenberg  M Halitosis in children. J Pediatr. 1999;134338- 343
Link to Article
Rosenberg  M Clinical assesment of bad breath: current concepts. J Am Dent Assoc. 1996;127475- 482
Link to Article
Weller  THSorenson  CW Enterobiasis: its incidence and symptomatology in a group of 505 children. N Engl J Med. 1941;224143- 146
Link to Article
Cook  GH Parasitic Disease in Clinical Practice.  London, England Springer Verlag1990;114- 116
Ozcelik  SErdemir  FSaygi  G Sivas'ta ilkokul cocuklarinda enuresis ve enterobiasis arasindaki iliskinin incelenmesi [Investigations for the relationship between enuresis and enterobiasis in primary school children in the middle part of Turkey]. Infeksiyon Dergisi. 1991;5281- 283
Yilmaz  HTurkdogan  MKBerktas  M Van yoresinde intestinal parazitler [Intestinal parasites in the eastern part of Turkey]. Gastroenteroloji. 1996;773
Katz  SLGershon  AAHotez  PJKatz  SLedGershon  AAedHotez  PJed Parasitic infections in temperate climates. Krugman's Infectious Diseases of Children 10th ed St Louis, Mo Mosby-Year Book1998;311- 325
Fritsche  TRSmith  JWHenry  JBed Clinical diagnosis and management by laboratory methods. Medical Parasitology 19th ed Philadelphia, Pa WB Saunders Co1996;1252- 1307
Toreci  KCetin  ETedAng  OedToreci  Ked Parazitler [Parasites]. Tibbi Parazitoloji [Medical Parasitology] 5th ed Istanbul, Turkey Publishing House of Istanbul Medical School1995;301- 310
Henker  JSchuster  FNissler  K A case report: successful treatment of gut-caused halitosis with a suspension of living non-pathogenic Escherichia coli bacteria. Eur J Pediatr. 2001;160592- 594
Link to Article
Levin  MHWeinstein  RAAxelrod  JL Severe, reversible neutropenia during high-dose mebendazole therapy for echinococcosis. JAMA. 1983;2492929- 2931
Link to Article
Muenning  PPallin  DSell  RLChan  MS The cost effectiveness of strategies for the treatment of intestinal parasites in immigrants. N Engl J Med. 1999;340773- 779
Link to Article
Not Available, Physicians' Desk Reference Electronic Library. Version 5.2 Montvale, NJ Medical Economics Co Inc2000;
Biddulph  J Mebendazole and albendazole for infants. Pediatr Infect Dis J. 1990;9373
Link to Article

Figures

Place holder to copy figure label and caption

Participant flow diagram.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Characteristics of Children and Parasites Detected on Stool Examination*
Table Graphic Jump LocationTable 2. Recovery From Halitosis in Children With or Without Parasites*

References

Goroll  AHMulley  AG Primary Care Medicine: Office Evaluation and Management of the Adult Patient. 4th ed Philadelphia, Pa Lippincott Williams & Wilkins2000;1119- 1120
Bollen  CMRompen  EHDemanez  JP Halitosis: a multidisciplinary problem. Rev Med Liege. 1999;5432- 36
Meninguad  JPBado  FFavre  EBertrand  JCGuilbert  F Halitosis in 1999. Rev Stomatol Chir Maxillofac. 1999;100240- 244
Scully  CPorter  SPGreenman  J What to do about halitosis. BMJ. 1994;308217- 218
Link to Article
Tonzetich  J Production and origin of oral malador: a review of mechanisms and methods of analysis. J Periodontol. 1997;4813- 20
Link to Article
Tonzetich  JMcBride  BC Characterization of volatile sulphur production by pathogenic and non-pathogenic strains of oral bacteroides. Arch Oral Biol. 1981;26963- 969
Link to Article
Spielman  AIBivona  PRifkin  BR Halitosis: a common oral problem. N Y State Dent J. 1996;6236- 42
Rosenfeld  RM Pilot study of outcomes in pediatric rhinosinusitis. Arch Otolaryngol Head Neck Surg. 1995;121729- 736
Link to Article
Amir  EShimonov  RRosenberg  M Halitosis in children. J Pediatr. 1999;134338- 343
Link to Article
Rosenberg  M Clinical assesment of bad breath: current concepts. J Am Dent Assoc. 1996;127475- 482
Link to Article
Weller  THSorenson  CW Enterobiasis: its incidence and symptomatology in a group of 505 children. N Engl J Med. 1941;224143- 146
Link to Article
Cook  GH Parasitic Disease in Clinical Practice.  London, England Springer Verlag1990;114- 116
Ozcelik  SErdemir  FSaygi  G Sivas'ta ilkokul cocuklarinda enuresis ve enterobiasis arasindaki iliskinin incelenmesi [Investigations for the relationship between enuresis and enterobiasis in primary school children in the middle part of Turkey]. Infeksiyon Dergisi. 1991;5281- 283
Yilmaz  HTurkdogan  MKBerktas  M Van yoresinde intestinal parazitler [Intestinal parasites in the eastern part of Turkey]. Gastroenteroloji. 1996;773
Katz  SLGershon  AAHotez  PJKatz  SLedGershon  AAedHotez  PJed Parasitic infections in temperate climates. Krugman's Infectious Diseases of Children 10th ed St Louis, Mo Mosby-Year Book1998;311- 325
Fritsche  TRSmith  JWHenry  JBed Clinical diagnosis and management by laboratory methods. Medical Parasitology 19th ed Philadelphia, Pa WB Saunders Co1996;1252- 1307
Toreci  KCetin  ETedAng  OedToreci  Ked Parazitler [Parasites]. Tibbi Parazitoloji [Medical Parasitology] 5th ed Istanbul, Turkey Publishing House of Istanbul Medical School1995;301- 310
Henker  JSchuster  FNissler  K A case report: successful treatment of gut-caused halitosis with a suspension of living non-pathogenic Escherichia coli bacteria. Eur J Pediatr. 2001;160592- 594
Link to Article
Levin  MHWeinstein  RAAxelrod  JL Severe, reversible neutropenia during high-dose mebendazole therapy for echinococcosis. JAMA. 1983;2492929- 2931
Link to Article
Muenning  PPallin  DSell  RLChan  MS The cost effectiveness of strategies for the treatment of intestinal parasites in immigrants. N Engl J Med. 1999;340773- 779
Link to Article
Not Available, Physicians' Desk Reference Electronic Library. Version 5.2 Montvale, NJ Medical Economics Co Inc2000;
Biddulph  J Mebendazole and albendazole for infants. Pediatr Infect Dis J. 1990;9373
Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Related Collections
PubMed Articles
A randomized placebo-controlled trial of mebendazole for halitosis. Arch Pediatr Adolesc Med 2002;156(10):995-8.