Niger J Paed 2013; 40 (1): 1 –5 REVIEW

Sadoh WE Need for a clinical decision rule for Sadoh AE the management of in Nigeria.

DOI:http://dx.doi.org/10.4314/njp.v40i1.1 Accepted: 26th May 2012 Abstract Pharyngitis is a common (CDR) which is a clinical tool that reason for presentation in the hospi- helps guide physicians in the man- ( ) Sadoh WE tal by children. Although viral aeti- agement of conditions such as Department of Child Health ology is the commonest, Group A pharyngitis, have been shown to be University of Benin/University of Streptococcus is the most important helpful in managing pharyngitis in Benin Teaching Hospital, Benin City, Nigeria. cause of and reason for antibiotic other countries. It reduces the num- E-mail: [email protected] treatment of pharyngitis. The fact ber of unnecessary antibiotic pre- Tel: +2348028809710 that GAS causes the non suppura- scriptions and has a high sensitivity tive sequalae of rheumatic and and specificity in distinguishing Sadoh AE acute glomerulonephritis perhaps GAS from non GAS pharyngitis. Institute of Child Health, drives the empirical antibiotic treat- Currently there are no guidelines or University of Benin, ment of most cases of pharyngitis. CDR for the management of Benin City, The unnecessary antibiotic treat- pharyngitis in Nigeria, there is an Nigeria. ment contributes to antibiotic resis- urgent need to derive, validate and tance, a major public health prob- implement a CDR to guide the lem. While it is desirable to do treatment of pharyngits. throat culture to guide the physi- cian’s management of each case, Keywords: Clinical decision rule, the required laboratory skill is un- pharyngitis, antibiotic resistance, available in most clinical settings in group A Streptococcus . Nigeria. A clinical decision rule

Introduction treatment with appropriate antibiotic prevents RF and thus RHD, encourages the prescription of antibiotic for Pharyngitis is a common cause of out-patient presenta- 1,2 the treatment of most cases of pharyngitis in the absence tion amongst children and adults. The commonest of laboratory confirmation of the causative agent. These cause of pharyngitis is viral. Bacterial causes are impor- unnecessary antibiotic prescriptions portend grave con- tant causes of pharyngitis as they may require treatment sequences for the nation as they cause antibiotic resis- with antibiotic. Three of the bacterial causes, group A β tance. Laboratory services are lacking in most clinical haemolytic Streptococcus (GAS) is the most common settings in Nigeria. Alternatives to laboratory services and most pathogenic bacterial aetiology because it 4 are clearly needed to facilitate the discrimination be- causes both suppurative and non suppurative sequalae. tween GAS and non GAS cases of pharyngitis to guide GAS contributes 15 – 30 % of cases of pharyngitis in 5 antibiotic prescription. The clinical decision rule (CDR) children and 5 – 20% in adults. GAS pharyngitis is is a cheap and efficient alternative where laboratory ser- transmitted by respiratory droplets and the incubation vices may be lacking. A CDR is a clinical tool often period is 24 to 72 hours.5 Children in crowded situations consisting of weighted clinical features, it assist clini- such as schools, and hostels are thus particularly vulner- cians with the diagnosis, prognosis and treatment of a able. given condition. The CDR is used in many clinical conditions one of which is in the management of The non suppurative sequalae of rheumatic fever (RF) pharyngitis. and rheumatic heart disease (RHD) are of major public health concern in developing countries where they are Clinical diagnosis of pharyngitis still prevalent and contribute the majority of the 16 mil- lion cases of RHD globally and the greater proportion of Clinical evaluation of cases of pharyngitis provides an the over 200,000 death attributable to RHD globally.6 opportunity to distinguish between viral and bacterial The prevalence of RHD in Nigeria is 0.07/1000 among aetiology. In viral cases, the children may present insidi- primary school children aged six to twelve years. 7RHD ously and often with coryza, conjunctivitis, , fever is responsible for 7 – 68% of all heart diseases in Nige- 10 8,9 and diarrhoea. Bacterial pharyngitis on the other hand ria. The age group 5 to 15 years is commonly affected. presents with sudden onset, fever, tender cervical ade- The fact that GAS pharyngitis results in RF and that its nopathy, presence of pharyngeal , sorethroat 2 and absence of cough. 1 In clinical practice the ability to visit medicine stores where antibiotics maybe procured discriminate GAS from non GAS using the aforemen- based on the purchasing power of the patients.This tioned clinical is possible in half of suboptimal treatment may contribute to resistance which the cases. 11 There may be overlap between features mak- is a major public health problem. 17 Also, the inadequate ing discrimination difficult, besides no one feature has treatment of pharyngitis may not prevent RF since the proven to have that discriminating ability between viral immunologic damage may still occur despite the relief and bacteria pharyngitis. However when the presence of the patient may have from the symptoms. The initiation multiple signs and symptoms are used as in CDR, the and sustenance of a programme using RADT will be diagnostic accuracy of making this clinical decision im- difficult in resource limited setting such as ours except it proves. is heavily subsidized.

Primary prevention of RF/RHD Antibiotic resistance

The importance of promptly and adequately treating A major consequence of indiscriminate antibiotic pre- GAS pharyngitis is the basis of primary prevention of scription for viral pharyngitis, is antibiotic resistance. RF. Primary prevention is being advocated as the way Other major contributors are incomplete or inadequate forward in reducing the burden of RHD in Africa. 12 Sec- dosing and antibiotic use among livestock globally.17 In ondary prevention strategy only, which involves the a study in Jos, Nigeria, 18 the prevalence of penicillin placement of the affected individual on penicillin pro- resistant Streptococcus pneumoniae was found to be phylaxis may not be enough to combat this scourge. 29.72%. The organisms were resistant to commonly used antimicrobials which included penicillin, ampicilin, Since primary prevention involves the identification of genticin, chloramphenicol erythromycin and ciproflox- the child with GAS pharyngitis for antibiotic treatment. acin. Streptococcus pneumoniae is responsible for more Laboratory backup will be needed to culture the throat than one third of under-fives’ deaths from . 19 swabs from affected children. The determination of the Acute respiratory infections in turn contributes 15% to Lancefield group of the β haemolytic streptococcus to under fives mortality in Nigeria. 20 The impact of un- ascertain if it is group A will also be required. This level checked antibiotic resistance to Streptococcal pneumo- of laboratory skills is absent in most health facilities in nia would be enormous on childhood mortality. Nigeria. Thus attending physicians may have difficulty in making a decision on whether to prescribe antibiotic In another study in Ibadan. 21 high rates of antimicrobial for pharyngitis or not in the absence of laboratory ser- resistance was noted in pathogens ranging from Staphy- vices. The option of commencing the most children with lococcus aureus to gram negative bacilli such as kleb- pharyngitis on antibiotic while awaiting laboratory result siella spp . They were again mostly resistant to common exposes them to inadequate antibiotic doses since the medicines such as amoxicillin/clavulanate, cefuroxine, medication will be stopped following a negative culture. genticin, penicillin and chloramphenicol. Physicians are The patient may all together not revisit the health facility known to prescribe a variety of medicines for children as would be requested by the physician especially when with pharyngitis. 13 When the common antibiotics fail, the child is getting better, compliance to medication may prescribers will resort to the more expensive and newer then become questionable. The physician in an attempt antibiotics. The cost of treatment becomes quite high to err on the side of caution often resort to prescribing resulting from cost of medicines and longer hospital antibiotic for all cases of pharyngitis. Sadoh et al 13 re- stay. Antibiotic resistance becomes a major contributor ported that 56.4 % of physicians surveyed in the mid to childhood morbidity and mortality. This doubtless Western part of Nigeria would prescribe antibiotic em- will place a huge financial and social burden on the af- pirically for all patients with pharyngitis. Perhaps simi- fected families and the Nation. Reducing the indiscrimi- lar antibiotic prescription pattern obtains in other parts nate antibiotic prescription for pharyngitis will thus of the country. ameliorate the pressure on antibiotic and reduce the chances of antibiotic resistance. In developed countries, rapid antigen detection test (RADT) for GAS is used in the place of full microbi- The use of clinical decision rule ological culture. 14 This has the advantage of providing rapid results and requires less expertise to perform. The To prevent the indiscriminate prescription of antibiotics use of RADT is however limited because the sensitivity for non GAS pharyngitis, the physician must be able to may not be as good as microbiological cultures. Thus distinguish bacterial from viral and non infective causes patients who are RADT negative maybe required to do of pharyngitis. In the absence of laboratory services, the culture.15 The newer ELISA, optical immunoassays and doctors may have to use a set of clinical signs and symp- assay employing the chemiluminiscent DNA probes toms as the basis for deciding whether to prescribe or have sensitivities upto 90 – 99 % compared with micro- not to prescribe antibiotic for a given case of pharyngi- biological culture and thus the requirement for microbi- tis, the so CDR. ological culture may not be needed. 16 These newer test kits are quite expensive and mark up the cost of treating The most popular and perhaps the earliest CDR was pharyngitis. This extra cost may prevent patients from derived by Centor et al 22 in 1980. It comprised the use of presenting in the health facilities preferring instead to four criteria; tender cervical adenopathy, fever, absence 3 of cough and pharyngeal exudates. The presence of all haemolytic Streptococcus were obtained respectively. 7,30 four was said to give a high probability of the GAS The difference in prevalence suggests the need to de- pharyngitis while the presence of two or three features velop and validate different CDRs in different parts of will necessitate the culturing of the throat swab or use of the country to crystallise a CDR that best capture the rapid antigen detection test. The Centor criteria was es- entire country for implementation. tablished for patients 15 years and above. It is good in identifying individuals with low risk for GAS pharyngi- The importance of clinical decision rule tis and reduces the proportion of unnecessary antibiotic prescription, having been validated by a number of stud- Once a CDR is established for the country, attending ies where high sensitivity and specificity results were physicians will be guided by it. This will enhance the obtained. 23,24 The modified Centor score by McIsaac et primary prevention strategy of RF/RHD in the country al 25 was validated in over 600 children and adults. 26 In as likely GAS pharyngitis will be adequately treated. addition to the four Centor criteria, age was included as This together with effective implementation of the sec- a criterion. The criteria are scored as shown in the table ondary prevention strategy and health educating the both 1. Patients <15 years were given an extra score of one the prescribers and the populace, will lead to reduction while in those between 15 and 44 years were scored in the burden of RF and RHD. There will be a reduction zero. A score of one was subtracted from those 45 years in the prescription of unnecessary antibiotics for and above. Decisions were taken based on the score ob- pharyngitis as has been shown in other studies. 26,28 This tained from evaluating the patients as shown in Table 1. will go a long way in reducing antibiotic resistance in The sensitivity and specificity of the modified Centor the country. clinical scoring system in identifying GAS was 85% and 92.1% respectively. Using the scoring tool resulted in Antibiotic treatment of pharyngitis 63.7% reduction in antibiotic prescription compared to the usual physician practice. It is also important that a clear first line medicine for the treatment of pharyngitis is established nationally. Tradi- tionally penicillin V is the drug of choice, however in a Table 1: Modified Centor score 25 study on physicians’ management of in Be- Criteria Points nin City; most doctors did not comply with the use of penicillin as first line medicine. A variety of medicines Absence of cough 1 were being prescribed for pharyngitis in children in- Tender and swollen cervical glands 1 stead. 13 This means that not only penicillin is exposed to Temperature >380C 1 resistance but other medicines and thus increasing the Tonsillar swelling or exudates 1 antibiotic resistance problem. Age 3 – 14 year 1 Because of the difficulty with compliance with a ten day 15 – 44 year 0 course of penicillin, the effectiveness of other alternative >45 years -1 medicines such as amoxylcillin and cefuroxine in ade- Cumulative score quately treating GAS pharyngitis have been demon- strated in other studies. 31,32 The issue of poor compliance Score 0 or 1 (low risk) no testing and no antibiotic with medication also contributes to antibiotic resistance, Score of 2 and 3 (medium risk) perform testing and give antibiotic if there are studies that have evaluated the efficacy of positive Score 4, (high risk), consider giving antibiotic empirically shorter duration and dosing of medicines used in the treatment of pharyngitis compared to standard treatment Since the Centor criteria, a number of CDRs have been regimen. 31,32 Single Benzathin penicillin injection has derived by other workers in both developing and devel- also been shown to be effective and is being used in oped world. 27,28 Joachim et al 27 working in Brazil pro- Brazil to enhance treatment compliance in cases of duced a scoring system which resulted in a 35% to 55% pharyngitis. 33 Single injection of penicillin maybe quite reduction in unnecessary antibiotic prescription while useful to ensure compliance to therapy in our setting for the one by Smeester et al 28 had a sensitivity of 92% and the children without penicillin allergy. Benzathin peni- resulted in a 31% to 38% reduction in antibiotic pre- cillin has continued to be efficacious in clinical settings. scription for culture negative pharyngitis. CDRs work best in the populations in which they are derived and in populations with similar GAS prevalence. Where the prevalence are different, they don’t not work well.29 It is thus important to develop a National CDR for Nigeria. Conclusion

There is a paucity of studies on agents causing pharyngi- Managing pharyngitis in children without laboratory tis in patients in Nigeria and no CDR has yet been de- backup is a common problem physicians are faced with rived for facilitating the management of pharyngitis in in most clinical settings across the nation. In order to Nigeria. The prevalence of GAS is different from locale prevent the occurrence of RF, alot of unnecessary antibi- to locale as shown in two studies from Benin City and otics are prescribed. This leads to antibiotic resistance Lagos where values of 0 % and 22.8% of the cases of β which is a growing global concern. 4 A wide variety of common medicines are involved. It is imperative to guide all prescribers in the absence of Periodic evaluation of the efficacy of current medicine a national CDR. Perhaps the modified Centor criteria be of choice is important in the face of antibiotic resistance recommended as guideline pending when a national and so guides prescribers as to the optimal medicine for CDR is established. The Integrated Management of the treatment of pharyngitis. The current situation in the Childhood Illnesses (IMCI) programme is a veritable country is that antibiotics are prescribed indiscriminately tool for cascading the process down to community ex- in the absence of guideline and the choices of antibiotics tension workers and allied health workers by incorporat- are left to the prescribers’ whim. This situation can only ing a guideline on treatment of pharyngitis in the IMCI be arrested if concerted efforts are made by the Ministry as has been done with the IMCI programme in Turkey.34 of Health through research to establish not only a CDR It is also important to educate the health community on in the management of pharyngitis but also the choice of appropriate antibiotic prescription and the dangers posed medicine to prescribe when the need arises. by indiscriminate antibiotic use.

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