Annals of Tropical Paediatrics (2000) 20, 223–226

A retrospective review of paediatric lymph nodetuberculosis in Port Moresby, Papua New Guinea

P. McMASTER, N. EZEILO & J. D. VINCE

Division of Paediatrics, Clinical Sciences Department, Port Moresby General Hospital, Papua NewGuinea

(Accepted March 2000)

Summary The study aimed to examine the perception that the relapse rate following standard short-course chemotherapy in children with lymph node tuberculosis is greater than in similarly treated childrenwith pulmonary tuberculosis (TB). The treatment records, clinical data and results of investigations of 427children treated for lymph node TB between 1989 and 1996 were analysed. The results and role ofinvestigations are discussed. The relapse rate was compared with that of 892 children treated for pulmonaryTB during the same period. The documented relapse rate for lymph node TB was 2.8% compared with0.6% in pulmonary TB. This highly signi� cant difference led to a prospective study of outcome of lymphnode TB treatment in Port Moresby.

Introduction

The short-course chemotherapy recom-mended by the World Health Organization(WHO) is endorsed by many authorities in-cluding the British Thoracic Society, theAmerican Thoracic Society, the Centers forDisease Control (CDC) in Atlanta, the Amer-ican Academy of Pediatrics and the CanadianPediatric Society.1–4 However, scienti� c dataon which to base this recommendation are notreadily available. A literature survey usingMedline and Paperchase produced little infor-mation. The only publication found dealingexclusively with paediatric lymph node TBwas a study in which streptomycin was used5

and this is not currently recommended byWHO for uncomplicated lymph node TB.1 A

standard clinical text on TB states that 5% ofadults with lymph node TB are estimated tohave palpable glands at the end of treatment,but that these rarely cause further trouble.6

One report from India suggests that 9months therapy is insuf� cient for lymph nodedisease. Sixty of 82 (74.3%) adults treatedwith rifampicin, isoniazid and ethambutol for9 months showed complete disappearance ofthe lymph nodes, but this increased to 70 of82 (87.2%) when the treatment was continuedfor 1 year.7 Another study suggests that thereis no further evidence of relapse during follow-up of those with residual nodes.8 Other litera-ture relates to lymph node TB in the contextof HIV infection, but this is not the issuediscussed in this study.9

In a British Thoracic Society study, three of51 adults who completed 6 months of treat-ment with currently recommended drugs(pyrazinamide (Z), isoniazid (H) and ri-fampicin (R), Z2H6R6) were judged to have

Reprint requests to: Dr Paddy McMaster, Departmentof Infectious Diseases, The New Children’s Hospital,PO Box 3515, Parramatta, NSW 2124, Australia.Fax: 1 61 29 845 3421; e-mail: Paddy McMaster@compuserve.com

ISSN 0272-4936 print/ISSN 1465-3281/online/00/030223-04 Ó 2000 The Liverpool School of Tropical MedicineCarfax Publishing

224 P. McMaster et al.

relapsed, although none of the biopsies waspositive for TB.2

In the paediatric TB clinic at Port MoresbyGeneral Hospital (PMGH), about 700 chil-dren less than 12 years of age are commencedon TB treatment each year. A substantial pro-portion of these have nodal TB. In Biddulph’sprevious study of 639 children enrolled at thesame clinic, 110 (17%) were classi� ed as hav-ing peripheral lymph node TB.10

In Port Moresby, the current short-courseregimen for children with lymph node TB orsputum/gastric aspirate-negative, pulmonaryTB is daily pyrazinamide (Z), isoniazid (H)and rifampicin (R) for 2 months, followed bytwice-weekly isoniazid (H) and rifampicin (R)for 4 months (2HRZ/4H2R2). WHO recom-mends 2HRZ/4H3R3 but states that 2HRZ/4H2R2 is acceptable.1 Senior medical staffworking in the clinic had the impression thatthe relapse rate following this regimen washigher in children with nodal TB than in thosewith pulmonary TB, and the study was under-taken to examine this perception.

Methods

A retrospective study was conducted in thepaediatric TB clinic and ward of Port MoresbyGeneral Hospital, Papua New Guinea. Datawere collected from the paediatric TB regis-ters. On discharge from the ward or on start-ing treatment in clinic, the followinginformation is entered in the register: name,address, age, diagnosis, weight, BCG immu-nization status, chest X-ray (CXR) � ndings,� ne needle aspiration biopsy (FNAB)/sputum/gastric aspirate, Mantoux or other investiga-tion results, date of starting treatment, familyscreening and if previously commenced ontreatment and whether it was completed. Ateach review (usually monthly) a record is keptof compliance, weight and clinical status. TheMantoux was performed using 10 IU humantuberculin and read as positive if the indura-tion was of more than 10 mm diameter, irre-spective of BCG history. A CXR was notperformed on every child but only if deemednecessary by the paediatrician seeing the pa-

tient. FNAB was performed using a 25 Frenchgauge needle without sedation, anaesthetic oranalgesia.

Generally, � ne needle aspiration biopsy(FNAB) was done only when resistant organ-isms were suspected or to rule out malignancywhen the diagnosis was in doubt. WhilstFNAB was easily organized, results were oftendif� cult to obtain. When the FNAB was in-conclusive and there were ‘worrying’ featuressuch as lymphadenopathy in multiple sites, abiopsy of the lymph node was obtained. Thiswas much more dif� cult to organize as therewas little theatre time for anything as electiveas this. The presence of granulomata orcaseating necrosis was taken as positive forTB. Fite Faraco (modi� ed Ziehl Neelsenstain) was used for AFB. The specimens havebeen cultured on liquid broth medium (Bactec12 B) since 1994, and prior to this on Lowen-stein–Jensen medium. Identi� cation of my-cobacterium and antimycobacterial drugsensitivity testing were routine during onlypart of the study period.

The study period was from 1 August 1989to 31 December 1996. The children enrolledin the study are those recorded as having onlylymph node TB. Those with a diagnosis oflymph node and other forms of TB were ex-cluded. However, those whose chest X-rayswere consistent with TB but with a primarydiagnosis of lymph node TB were included.Relapse is de� ned as a patient requiring asecond course of TB chemotherapy for en-largement of lymph nodes associated withother symptoms of TB (such as pyrexia, anor-exia, etc.) after having completed a 6-monthcourse, with apparent resolution of symptomsand signs of active TB. The comparison groupwas children with pulmonary TB enrolled overthe same period. Children with extra-pul-monary TB in sites other than lymph nodesalone were excluded from both groups. Thedata were analysed on Epi Info version 6.02.

Results

Of the 427 children who started TB treat-ment, our records con� rm completion of

Lymph node tuberculosis in PNG 225

treatment in only 207 (48%). There is anequal sex ratio for presentation of lymph nodeTB and for completion of treatment. Elevenchildren with lymph node TB were recordedas having had no BCG (3.4% of those forwhom BCG immunization status wasrecorded).

Fine needle aspiration biopsy (FNAB) wasperformed in 122 children, although only 65results were recorded. Of those, 59 (90%)were positive—de� ned as the presence of ep-ithelioid cells or granulomata suggestive of tu-berculosis on histology or positive culture.Eighteen excision biopsies were performedand of the 15 results available, 13 were posi-tive (by the same histological or microbiologi-cal criteria). AFBs in FNAB or biopsy weredetected far less frequently with only � ve posi-tive results from all specimens. All specimenswere cultured for TB but no results are avail-able.

Fifteen (3.5%) of 427 children diagnosed ashaving lymph node TB were restarted ontreatment. Of the 207 who completed treat-ment, � ve (2.4%) relapsed. A lymph nodebiopsy taken from one of them on restartingtreatment was histologically positive for TB.Fifteen of 220 (6.8%) children with incom-plete records restarted treatment.

During the same period, 892 cases of pul-monary TB (with no record of associated per-ipheral lymphadenopathy or any otherextra-pulmonary site) were documented ashaving completed treatment by the same cri-teria as the TB lymph node patients. Of these,� ve relapsed, giving a relapse rate of 0.56%.This is highly signi� cantly different from theincidence of relapse in lymph node TB ( v 2

test, p 5 0.0001).

Discussion

The results of this study lend support to theclinical impression that there is a higher re-lapse rate in children with lymph node TBthan in those with pulmonary TB. Thesigni� cance of this retrospective study is obvi-ously limited by large omissions in record-keeping. However, it does reveal a number of

important issues in the management of lymphnode TB in children.

There are issues concerning the diagnosis oflymph node TB. Our diagnoses were primarilyclinical. Lymphadenopathy in children, partic-ularly in developing countries, is common. Asa general rule, TB was suspected when a cervi-cal lymph node was of more than 1 cm diam-eter, an axillary node more than 1.5 cm and aninguinal node more than 2 cm, and whenthere was no response to a course of antibi-otics. Almost all diagnoses were made by staffat consultant level with considerable experi-ence of TB.

The very high positive diagnostic rate of theFNAB and excision biopsies supports the ac-curacy of clinical diagnoses. There was norecord of any patient with clinically diagnosedlymph node TB subsequently being shown tohave malignant disease. No problems associ-ated with FNAB such as tracking and scarringwere recorded.

The pick-up rate of acid- and alcohol-fastbacilli (AAFB) staining was low. The micro-biology department at PMGH has very rarelyidenti� ed atypical mycobacteria (personalcommunication).

Although Mantoux testing can be very use-ful in diagnosing TB, interpretation of resultsin developing countries is fraught withdif� culty. Tuberculin strengths and prepara-tions may vary, and potency is reduced withstorage, particularly if the preparation is notkept cool. Severely malnourished children arelikely to have negative Mantoux tests despiteheavy infection. Interpretation is madedif� cult by a high BCG vaccination rate ininfancy and in situations where there is a veryhigh rate of primary infection among theyoung population. Nevertheless, in a well-nourished child with lymphadenopathy, apositive Mantoux test is useful supporting evi-dence.

It is recognized that lymph nodes occasion-ally enlarge after treatment has been com-pleted. It is thought that this represents animmunological reaction to tubercular proteinrather than relapse. Even during therapy,lymph nodes may increase in size, become

226 P. McMaster et al.

� uctuant and suppurate. This makes thede� nition of relapse somewhat dif� cult but,for the purposes of the study, relapse wasdiagnosed when enlargement of glands wasassociated with other symptoms of TB(pyrexia, anorexia, etc.) after cessation oftreatment and apparent resolution of symp-toms and signs of active TB. Lymph nodespersisting but not enlarging after treatmentwere not regarded as indicating relapse.Nevertheless, the question remains as towhether patients who still have lymph nodesafter 6 months of treatment have an increasedrelapse rate compared with those whose glandenlargement has resolved.

The prevalence of HIV infection in childrenduring the study period was very low: only 31PNG children had been diagnosed as HIV-positive after 18 months of age by the end ofthe study period. None of these was in thestudy population. There is no doubt, however,that with the rapidly escalating epidemic ofsexually transmitted HIV infection in PNG,the diagnosis of TB lymphadenopathy is likelyto become even more complex than it is atpresent.

The present study raises the possibility thatthe recommended standard 6 months short-course anti-TB chemotherapy may be in-suf� cient in childhood lymph node TB. Aprospective study with improved follow-up isneeded before � rm conclusions can be drawn.In a prospective study, diagnosis before start-ing treatment and of possible relapse shouldbe con� rmed histologically or microbiologi-

cally. A prospective study may also help ident-ify causal factors in those who relapse. Such aprospective study is currently in progress atPMGH.

References

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2 Campbell IA, Ormerod LP, Friend JAR, JenkinsPA, Prescott RJ. Six-months versus nine-monthschemotherapy for tuberculosis of lymph nodes:� nal results. Respir Med 1993; 87:621–3.

3 American Thoracic Society. Treatment of tubercu-losis and tuberculosis infection in adults and chil-dren. Am J Respir Crit Care Med 1994;149:1359–74.

4 Canadian Paediatric Society, Infectious Diseasesand Immunization Committee. Short course ther-apy for tuberculosis in infants and children. CanMed Assoc J 1994; 150:1233–9.

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