Audit of Failure Rate of Sulfadoxine/Pyrimethamine

Auditof failurerate of sulfadoxine/pyrimethamine combinedwith chloroquine to treatfalciparum malariaat singlefourteen-day follow-up. VaughanWilliams,CH Summary-i\ BSc,MBBS, DCH, Objective. MFamMed(Natal) To assessthe failure rate of the presentfirst line treatmentregime for MosvoldHospital, lngwavuma, uncomplicatedfalciparum malaria of sulfadoxine/pyrimethaminecombined KwaZulu-Natal,South Africa with chloroquine. Memberof Subcommitteefor Design. Chemoprophylaxisand Therapy A before-afterstudyl of the NationalMalariaAdvisory Group Setting. La Cock, C Ndumo Clinic,Ingwavuma District, South Africa, October 2000 StudyGroup.55 patientspresenting to Ndumo clinicwith uncomplicated MedicalTechnologist, KwaZulu- malariaand malariatrophozoites visible on thin film. NatalLaboratory Services at Department of ::".i..":d Main outcome measures: Health,Jozini Trophozoitecount on thick film at day14. Henry, GFf Results. MBBS,DRCOG, MRCGP l5 out of 37 patientswho returnedfor follow-upstill had trophozoites MosvoldHospital, Ingwavuma on thick film.Symptoms of most patientsat day0 and day l4 were mild, Ross,AJ parasitecounts before and after treatment were low, and trophozoites MB,ChB,DCh, MFamMed were atypical. (MEDUNSA) Conclusions. MedicalSuperintendent, There appearsto be an unacceptablyhigh day 14 failure rate with the MosvoldHospital, Ingwavuma combinationof sulfadoxine/pyrimethamineand chloroguine.Themildness Correspondence to: of symptoms,low parasite counts and atypicaltrophozoites suggest VaughanWilliams immunityto falciparummalaria amongst the local population.With few e-mail:[email protected] antimalarialsto chosefrom, the difficultquestion as to future treatment of uncomplicatedmalaria arises. Keywords Falciparummalaria, chloroquine, sulfadoxine,pyrimethami ne SA FomPrad 2002,25(3): 4-7 .wlntroductionre Programme used SP alone to treat of those who returned. In the both self-presenting patients(passive absenceof immediatelyavailable new In 1988 sulfadoxine/pyrimethaminecases) and cases detected through first line anti-malarial drugs for (SP) officially replaced chloroquine active surveillance.From Januaryto uncomplicatedmalaria, SP combined (CQ) as first-linetreatment in malaria April 2000 an in vivo study' of the with CQ was adopted as first line control in South Africa because of efficacy of SP conducted by the treatment for uncomplicatedmalaria concerns about chloroquine resist- National Malaria Research Pro- th roughout KwaZulu-Natal. ance'. In northern KwaZulu-Natal gramme at Ndumo Clinic,Ingwavuma medicalofficers at Mosvold,Manguzi, District, KwaZulu-Natal,South Africa, There have been few studies of SP Bethesdaand Mseleni hospitalsused showed failure of SP treatment in ac combined with CQ. In a Cochrane SP combined with CQ because of least6 |.2% patientsby the end of 28 reviewo Mclntosh concluded that in perceived benefit of chloroquine, days.The 14 dayfailure rate was 50% areaswhere chloroquineis still effec- whereas the Malaria Control of recruited (63/ 125),but 73%(63186) tive, chloroquine in combinationwith SP may make people feel better faster Defence Force. In 1995,in South limited laboratory facilities.Applying and improve sustainedparasite clear- Africa, there were 5 992 notified the guidelinesin the form of a single ance. Bojang et als, in a trial of SP cases of malariat whereas from 14 day follow-up of a sample of alone versusSP with CQ in Gambian Januaryto May 2000 there were 36 patients was chosen as a quick and children,found SP with CQ to be 717 notifiedmalaria cases'.With such simple audit of the of the regime of more effective symptomatically, but largenumbers of patientsbeing treat- SP and CQ combined,deviating little no differencein parasitecure rate. ed, an audit of the failurerate of the from routine management. There has been a dramatic increasein treatment regime was desirable.A malaria incidence in KwaZulu-Natal WHO protocol' for assessmentof The interval between date of infec- and South Africa since 1996. For therapeutic efficacy of antimalarial tion with plasmodiumfalciparum and example,at Ndumo clinic,Ingwavuma drugs requiresfollow-up of patients the time when parasites are District, South Africa, (a satellite clinic on at leastdays 0,1,2,3,7 and l4.This detectable in the blood (the pre- of Mosvold Hospital, covering an area requires substantialresources, and patent period) is 9- l0 daysro.This with the highestincidence of malaria preventingpatients dropping out is meansthat there is an increasingpos- in South Africa), cases detected difficult. Department of Health sibility that parasitespresent after day increasedfrom 637 in 1995,to 2 972 Guidelines'recommend that a follow- 14 may be due to reinfection rather in 1998, and 17 420 in 1999. From up blood smear be taken after 2-3 than drug resistance.After 14 days Januaryto May 2000 alone, 21 352 weeks.This hasnot beenimplement- techniquessuch as polymerasechain cases were detected at the clinic, ed routinelyin northern KwaZulu- reaction are needed to distinguish requiringthe aid of the SouthAfrican Natal,due to numbersof patientsand between resistant malariaand reinfection. A blood film at day fourteen would be expected to provide useful Table l: ClassificationofTherapeutic Responses information regarding the combined early treatment failure (ETF) and late Earlytreatment failure Patientdevelops one of the following conditions treatment failure (LTF),as well as the (ErF) duringthe first three daysof follow-up: proportion of patients showing ade- . Developmentof dangersigns or severemalaria quate clinical response (ACR) to the on Day |, Day 2 or Day 3, in the presenceof therapeutic regime (see table l). parasitaemia; . Axillary temperature>37.5"C on Day 2 with par- Study Population and Methods asitaemia>Day0count; Pre-study calculation of sample . Axillary temperature> 37.5"C on Day 3 in the size presenceof parasitaemia; Samplesize was calculatedaccording . Parasitaemiaon Day 3 > 25 % of count on Day 0. to statistical considerations in a World Health Organisation protocol' Latetreatment failure Patientdevelops one of the followingconditions usinga system calledthe Double Lot (LrF) duringthe follow-up period from Day 4 to Day 14 Quality Assurance method.This sys- . Developmentof dangersings or severemalaria in tem is designedto allow identification the presenceof parasitaemiaon any day from of communities in which prevalence Day 4 to Day 14,without previouslymeeting any of resistance is above a critical level, of the criteria of earlytreatment failure; with small sample sizes.Taking a 25% . Axillary temperature> 37.5'C in the presenceof failure rate to be definitely unaccept- parasitaemiaon any day from Day 4 to Day 14, able, but l0% or less definitely acceptable,a samplesize of 42 is suf- without previouslymeeting any of the criteria of ficient to detect a 25% failure rate early treatment failure. with a probability of 0.05 of erroneously concludinga failure rate of Adequateclinical respons, Patientshows one of the followingconditions less than l0% (type I error), whilst (AcR) duringthe follow-upperiod (up to day l4): being 80% sure of not erroneously . Absenceof parasitaemiaon Day l4 irrespective concfuding there to be a 25% failure of axillarytemperature, previously without meet- rate when it is really less than l0% ing any of the criteria of early or late treatment (type 2 error). Using this method and failure; applying the given thresholds, 5 or . Axillary temperature< 37.5"C irrespectiveof the less treatment failures could be con- presenceof parasitaemia,without previously sidered acceptable,but more than 5 meetingany of the criteria of early or late treat- would be unacceptable.To allow for ment failure. drop-outs,55 patients were invited to return for follow-up. In October 2000, over six working were more likely to have visible para- water, air-dried and observed with days, 89 self-presenting patients at sites on thin film, so there was a l00x oil objective. Malaria parasites Ndumo clinic,diagnosed as suffering selection tendency to invite those were counted in conjunction with malaria by positive immunochromo- with more strongly positive rapid 300 white cells.The number of para- graphic test (KAT-Quick Malaria tests.Thickand thin blood films were siteswas multipliedby 25 to estimate RapidTest for Plasmodiumfalciparum taken,and thin films read immediately the number of parasites per - Cape Biotech (Pty) Ltd ), were after staining.Thick films required 24 microlitre of blood. Patients were asked if they would be prepared to hours to dry and so could not be given the usual adult treatment for return for a two week check. read immediately.Only those who uncomplicated malaria at Ndumo Patientswere assessedby a medical were thin film positive were asked to Clinic,whichis givenin tablell. officer,and those with severe or com- return for repeat blood smears at plicated malaria, pregnant women, two weeks,to ensure that a compari- All patients were told to return patients aged under | 6 years and son of parasite counts could be immediately should their condition patients treated for malaria during made. deteriorate. the previous two weeks were excluded from the audit.Children under l6 The films were examinedby a med- The Medical Superintendent of were excluded so that all patients ical technologistfrom KwaZulu-Natal Mosvold Hospital acceptedthe study could receive exactly the same laboratory services.Thin films were as an audit of current, practice regime for simplicity, while other air-dried,fixed with methanol,stained through the application

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