In Tanzania, as in most settings of sub-Saharan Africa, malaria is the first reported cause of attendance in health facilities. The National Bureau of Statistics estimates that a total of 16 million cases and 100,000 deaths (mainly in children) are due to malaria each year. In Dar es Salaam, the main city, approximately 3 million attendances are recorded, of which about one third are due to fever, mostly considered as presumptive malaria. Recent data show that transmission intensity is much lower in urban settings than in rural lowland areas. This is especially true for Dar es Salaam where only a small fraction of all fever episodes in children and adults are actually associated with Plasmodium parasitaemia. Clinical presentation of malaria is largely unspecific. No reliable clinical predictor that allows including or excluding the diagnosis of malaria has been identified. In this context, and in the absence of diagnostic test, WHO recommended in the past all fever episodes to be treated with antimalarials. Such blanket treatment leads first to substantial over-treatment with malaria drugs (in Dar es Salaam up to 95% of all treatments are unnecessary) and second to increased risk of missing alternative diagnoses with potentially fatal outcome. To address this issue of high public health relevance, we undertook a project called IMALDIA (Improving Malaria Diagnosis) aimed at improving the management of febrile patients in health facilities in Dar es Salaam, mainly through the implementation of Rapid Diagnostic Tests for malaria (mRDT). The project had 3 major components: (1) Evaluating the safety of withholding antimalarials in febrile children with a negative mRDT living in a moderate and a highly endemic area (2) Introducing laboratory diagnosis for malaria in the routine management of fever cases, using mRDT. The focus of this operational research was to document how feasible and effective the introduction of these tests is in the context of the routine management of fever cases. (3) Understanding the aetiologies of fever cases in children by screening a group of 1000 children with detailed clinical assessments and a range of laboratory tests in order to better identify the diversity of the causes of fever in small children living in an urban and a rural area. The overall aim of the IMALDIA project was to improve the diagnostic approach and management of fever cases in health facilities in Dar es Salaam, contribute to a more efficient and effective health sector, and help Tanzania on its way to reducing infant and child mortality.In a first step, we assessed the diagnostic performance of mRDT when used by health workers in routine practice. For this purpose, a quality assurance system both at central and peripheral level was set up. This system did not detect major problem and showed that the final result of mRDT by health workers was reliable. Summary X The purpose of the second step was to better estimate the pre-test probability of malaria in populations targeted by mRDT (febrile patients of all age groups attending a health facility of any type). To this end we undertook a systematic review of the studies giving the proportion of patients with associated P. falciparum parasitemia (PFPf) in Sub-Saharan Africa. We found that the median PFPf was 35%, and that it had decreased by half when comparing the period before with the period after the year 2000 (44% versus 22%). This relatively low pre-test probability nowadays is another reason to implement mRDT in Africa. In Dar es Salaam the PFPf was very low (below 10%) hence it was even more urgent to start using a reliable malaria test. Microscopy was available in almost all public health facilities of the city but its performance was extremely low, with an overall sensitivity of 71% and a specificity of only 47%. On the request of several Tanzanian stake-holders, in particular clinicians working routinely with patients, we assessed the safety of withholding antimalarials in children under five years with a negative malaria test. We did not observe any complication or death due to a missed diagnosis of malaria in our cohort of 1000 children, of which 60% were negative by mRDT. We concluded that the strategy of withholding antimalarials in negative children is safe and does not expose the child to an increased risk. The results of the systematic review coupled with the findings of the safety study led us to question the appropriateness of the previous WHO recommendation of treating all fevers with antimalarials in children less than five years living in highly endemic areas. WHO has now changed its policy, confirming that the IMALDIA findings were very relevant to the changed situation of many African countries, including Tanzania. The core of this thesis, and the main objective of the IMALDIA project, was to investigate the feasibility and value of implementing mRDT in the management of fever episodes in an urban malaria setting. Using 2 different designs and 2 independent data sources, we found a three quarter reduction in antimalarial consumption following RDT implementation. This massive reduction was due to the higher accuracy of routine mRDT compared to routine microscopy (that led to a dramatic reduction in the number of positive patients) and to the confidence of health workers in mRDT results (the proportion of negative patients treated with antimalarials dropped from 53% to 7%). The impact was maintained up to the end of the observation period (18 months). Not surprisingly, mRDT implementation increased the prescription of antibiotics by 50% and unfortunately did not have a major impact on the quality of the medical consultation. We took the opportunity of our near-to-program implementation of mRDT to perform a cost-saving analysis in a real situation and in a setting representative of many moderate endemic places in Africa. The conclusion was that costs can be saved on drugs, from both the provider and from the client’s perspective. For this reason, the overall expenditure for the patient was lower in health facilities using mRDT (by 0.31 USD per patient). However, the overall expenditure for the health Summary XI system was higher (by 1.31 USD per patient) when using mRDT instead of routine microscopy, mainly because of the relatively high price of the device. The aim of the last study was to explore the other causes of fever (beside malaria), in order to generate evidence for a revision of the existing clinical decision-charts for the management of patients, in particular the Integrated Management of Childhood Illness (IMCI). Half of the fever episodes in children were due to acute respiratory infections (ARI), of which 2/3 were probably of viral origin. Only 5% of all ARI were documented pneumonia. Gastroenteritis contributed to 9% of all fevers, of which at least 1/3 were due to a virus. In 1/5 of the children, no aetiology of high probability could be found but most of them recovered without treatment. Most of the children with acute fever thus do not need to receive an antibiotic. Based on these findings, we proposed a limited series of modifications to the IMCI chart and concluded that new point-of-care laboratory tests for the main infectious diseases are urgently needed. In conclusion, the IMALDIA project provided a deep insight into many aspects of the implementation of mRDT in near-to-programme conditions in Tanzania. Our findings show that the introduction of mRDT is safe, feasible and useful for the routine management of fever cases in all age groups and at all levels of the health system. Implementation at large scale will require flexibility on the part of the health care provider in order to be able to change his/her behaviour and a strong commitment of all persons involved. As malaria diagnosis is only one aspect of the management of patients presenting with fever, this will not solve all obstacles for making a proper differential diagnosis and prescribing the appropriate treatment for fever episodes. To really improve the quality of care it will be essential to develop new improved guidelines for clinicians. These decision charts should be based on the new available evidence and could include novel point-of-care tests for the key diseases, once these become availabl
In sub-Saharan Africa previous efforts to control malaria have proved less successful mostly
due to prolonged use of less efficacious mono-therapy drugs to which Plasmodium falciparum
has developed drug resistance. In most parts of malaria endemic regions chloroquine (CQ)
was found to be poorly effective for several decades but it was still being prescribed until
recently. In Tanzania, for instance, P.falciparum was already resistant to CQ in more than 60%
of all P. falciparum positive patients back in the late 80’s but was still used until when it was
possible to replace it by sulfadoxine-pyrimethamine (SP) in 2001. SP is anti-folate sulfa
based anti-malaria drug that was adopted as an interim first line drug by many malaria
endemic countries as there was no affordable immediate alternative to CQ. Elsewhere in sub-
Saharan Africa Zambia was the first African country to embrace policy change with efficacious
anti-malaria combination therapy using Artemisinin-based Combination Therapy (ACT) back in
2004 after support from global funds.
Until 1990, the past three decades have had a sustained global focus on malaria control
strategy with the aim of intensifying developing intervention tools. This was preceded by
specific eradication efforts of the 1940s, which were intensified in most parts of Southern
Europe and America. It was during this period that the global focus on malaria sustained a
great deal of change. In that same period therefore, the main focus was on technical issues
as well as research and development for new tools, that could lead to advances in drug and
vaccine development alongside vector control strategies. There were medium term gains
during this period but at the same time some challenges were recorded. Key among these
challenges was the fragmented global efforts, whereby there was total loss of a broad based
global focus to a joint strategy on the fight against malaria. This resulted in little global support
with no clear roadmap for developing states, mostly in Sub Saharan Africa, to establish
adequate health systems and primary health care for comprehensive malaria management.
These challenges resulted in to overuse of ant-malaria mono-therapies that were cheaply
available in most of these countries and led to development of parasite resistance to drugs
with far reaching consequences. Towards the mid of 1990s, the combination of a worsening
malaria situation and emerging positive technical developments led to renewed global focus
on malaria control. It is for the same reason that in 2000 the global head of states developed
a joint position to address the global disease burden most affecting developing countries as part of the Millennium Development Goals (MDG) of global programme on development to be
achieved by 2015. Two goals were developed to improved health for the Under Five (U5e.i,
MDG4 and MGD6. MGD4 sets target to reduce child mortality by two third by 2015 while
MGD6 aims at combating malaria and other major infectious diseases (HIV and TB) by year
2015 as compared to baseline 1990.
As the results of the launch of these global initiatives, a number of new strategies and tools
against malaria have been developed and existing ones sharpened to better address the
problem. Not later than beginning of last decade, Artemisinin-based Combination Therapy
(ACT) emerged as potential therapeutically efficacious proven tool to combat malaria. In the
face of growing anti-malarial drug resistance due to the use of mono-therapies, ACT has
placed itself as a novel treatment for malaria treatment. Use of insecticide Treated Mosquito
bed-Nets (ITN) has also been advocated. With the support of Global Health Partners, ITN
have been made available to the vulnerable persons within endemic communities. Support to
control malaria has exceeded 1000millionayearbutmalariastillexertsathreattotheU5andexpectantmothers.InTanzaniaACTasthefirstlineanti−malariadrugwasintroducedinlate2006,scaledforcountrywideusein2007.TheACTimplementationsinTanzaniabearsomesimilaritieswithapproachesinotherAfricancountriesbuttherearestillmajordifferences.TanzaniahasahomogenoushealthsystemthatfacilitatedtherolledoutofthemalariacontrolprogrammeaspartoftheprimaryHealthCare(PHC)system.ThiswasalsosupportedbytheevidencegeneratedfromtheNorth−Southresearchcollaborationsthatinformedpolicymakers.Governmentandnon−statecollaborationwithinTanzaniawaskeyininformingtheaboveprocess.InsomecasescrossboardercollaborationamongeconomicblocksofEastAfricaandSouthernAfricanDevelopmentCommunity(SADC)haveprovidedinsightsintothecontrolofmalariainthecontinent.SomeofthenovelimplementationtoolsdevelopedandtestedinTanzaniahavebeenappliedintherestofSub−Saharanmalariaendemicstatesandoftensupportedtheglobalcampaignagainstmalaria.InTanzania,politicalstabilityandpeaceforoverfourdecadeshasalsomadeiteasyforquickpolicychangeandscaleupofcontrolinterventionsusingACTthiscouldhavebeendifferentinneighboringnationslikeUganda,Sudan,MozambiqueandDemocraticrepublicofCongowhichhaveexperiencedcivilstrifeduringthisperiod.TanzaniahasemergedasoneofthefewAfricancountriesthatprovidedthegroundtotestsomeofthemostsuccessfulmalariacontrolinterventionsfortherestoftheworldtoup−scale.TheKilomberoRiverbasininIfakaraTanzaniaisaknowncradleformalariaendemicity.Severalnovelinterventionshavebeentestedforefficacyandthenevaluatedforimpactduringrolloutasprogrammes.MostfindingspresentedinthisthesishavebeenlargelyderivedfromtheIfakaraDemographicsurveillancesystemamongotherstudysitesinTanzania.ThisworkhasprovidedmajorinsightsintothepolicychangeforACTanditsimplementationatthenationalscale.TheaimofthePhDworkpresentedherewastocontributetoabetterunderstandingoftheimpactoftheACTintroductiononmalariamorbidityandmortalityinruralTanzaniaandtomonitoritslong−termsafetywhenusedatcountrywide.Availabilityofbaselineefficacyprofile,mobilizationofstakeholdersincludingparticipatingcommunitiesandpreparednessamongresearchersacceleratedpolicyimplementationinmostpartofTanzaniarightfromtheon−setofpolicyinception.FindingsfromtheInterdisciplinaryMonitoringProjectofAnti−malariaCombinationTherapy(IMPACT)andEastAfricanNetworkforMonitoringAnti−malariaTreatment(EANMAT)programmesasdescribedinthisthesishaveprovidedevidencethatinformedpolicy.Theinvivostudieshaveshownthatartemetherlumefantrine(AL)wasnearly100ChainReaction(PCR)inchildrenU5yearsintheyearspriorpolicychange.Wehavealsoshownthatinreallifesituationitispossibletobuildcomprehensiveresearchers−policymakers−pharmaceuticalindustrypartnershiptoimplementstrategiesformonitoringsafetyandproperuseofanti−malariadrugsasreportedintheprogrammeArtemether−LumefantrineInVulnerablepatients:ExploringhealthImpact(ALIVE).Wewereable,forthefirsttimeintheALIVEprojecttodescribeacomplianceofmorethan95forALinarandomizedstudyconductedatcommunitylevel.WehavereporttheestablishmentofapharmacovigilancesysteminaruralcommunitythatalsotestedforthefirsttimetheuseofmobilephonetechnologywithSMStoreportanti−malarialseriousadverseevents(SAE).TheALIVEprojectprovidedanassessmentoftheimpactofACTandothermalarialinterventionsonchildmortalityaswellasonmalariatransmission.Itdemonstratedthatforevery10parasitaemia[IRR=0.52;95underfivemortalitywhenadjustedforotherkeyfactors[IRR=0.89;95ALIVEalsoshowedtherelationshipofkeycontextualfactorswithmalariainterventionsandU5childmortality.Foodsecuritywasmajordeterminantofunderfivechildmortality;notablythericeyieldswasresponsiblefornearly36CI=0.54to0.75].Asfarasmalariatransmissionisconcerned,weobservedparallela65reductionofparasiteprevalenceinasymptomaticcommunitymembersofstudyareaascomparedtobaselinein2006beforeACTwasintroducedinthestudypopulation.Lastly,theseeffectsarelikelytobesustainablesincetheefficacyofAL,asevaluatedwithaninvivostudyconductedoneyearafterimplementationhasremainedabove96Kilomberovalleyinspiteofitswidescaleuse.Thefindingsofthisthesisattesttheimportanceofpolicychangeinmalariacontrolsupportedbyevidencegatheredfromoperationalresearches.Thelessonslearnedfromthisworkwillberelevanttosimilarinterventionslocallyandonaglobalscaleinmostmalariaaffectedcommunities.WehavealsolearntthatsafetyandcomplianceissuesofmedicinalproductsthataredeployedatlargescalesuchasACTshouldbemonitoredandmanagedbystrongpartnershipinvolvingtheMinistryofHealthanditallieddepartments,thepharmaceuticalindustrieswhenpossible,theresearchersandmostimportantlywithfullparticipationandsupportoflocalleadershipandcommunities.We,recommendthatthispartnershipgainsupportfromotherglobalhealthpartnerstoensuresafetyofdrugsthroughrigorousmonitoringofitsuseandlonglifespan.Capacitybuildingofmarketandpolicyimplementersisanothercriticalaspectthatshouldbegivenpriority.Wealsorecommendthatresourcesbemadeavailabletostrengthenthehealthsystem(humanresource,HealthInformationSystemandInfrastructure)inordertogainsustainedresultsinmalariacontrol.Thiswillfurthercreateenablingenvironmentandacriticalmassofscientistsandpublichealthexpertstospearheadanti−malariapolicyimplementationsproperlyandmonitoritontimelybasis.Asoutlinedinthiswork,asuccessfulcampaignagainstmalariacanberealizedthroughcombiningeffortsofresearchers,policymakers,globalhealthdevelopmentpartnersandcommunities.Thispartnershiphasleadtoreallifetimeachievementsrelatedprogrammes,suchasthe1940smalariaeliminationcampaigninSardiniaIslandofItaly.−−−−−−−−−−Zusammenfassung:InSubsahara−AfrikahabensichdiebisherigenBemu¨hungenzurBeka¨mpfungvonMalariaalswenigerfolgreicherwiesen,davorallemaufeineMono−Medikamente−Therapiegesetztwurde,gegenwelchePlasmodiumfalciparuminzwischenResistenzenentwickelthat.ObwohlsichChloroquin(CQ)indenletztenJahrzehntenindenmeistenMalariagebietenalsnurteilweisewirksamerwies,wurdeesnochbisvorkurzemeingesetzt.Bereitsindenspa¨ten1980erJahrenwurdenbeispielsweiseinTansaniainu¨ber60P.falciparum−positivenPatientenResistenzengegenu¨berCQfestgestellt.TrotzdemwurdeCQerstimJahre2001durchSulfadoxin−Pyrimethamin(SP)ersetzt.SPisteinMalaria−Medikament,dasinvielenMalaria−endemischenLa¨ndernalsZwischenlo¨sungeingefu¨hrtwurde,danochkeineerschwinglicheAlternativezuCQzurVerfu¨gungstand.EtwazurselbenZeiterlebteSambiaalserstesafrikanischesLandeinenPolitikwandelundfu¨hrte2004mithilfeglobalerFo¨rdermitteldieeffizientereArtemisinin−basedCombinationTherapy(ACT)ein.Zwischen1960und1990wurdederFokusaufeinenachhaltigeMalaria−Kontroll−Strategiegelegt,diezumZielhatte,dieInterventionsstrategienderEntwicklungsla¨nderzufo¨rdern.Vorangegangensindinden1940erJahrenspezifischeMaßnahmenzurAusrottung,wobeiderSchwerpunktauftechnischeFragensowieaufdieForschungundEntwicklungvonneuenWerkzeugengelegtwurde,diezuFortschritteninderMedikamenten−undImpfstoffentwicklung,sowieinderVektorkontrollstrategieha¨ttenfu¨hrensollen.EsgabmittelfristigeinigeErrungenschaften,gleichzeitigentstandenaberindiesemZeitraumauchneueHerausforderungen.EineHauptherausforderunglagindenglobalenBemu¨hungen,dieeinefokussierte,breitangelegteStrategiezurBeka¨mpfungvonMalariaerschwerte.DieswarauchderGrund,weshalbesdenLa¨ndernsu¨dlichderSaharanichtgelang,eineangemesseneGesundheitsversorgungaufzubauen.SiewarendeshalbimmernochvonveraltetenMono−Therapienabha¨ngig,diezwarindenmeistenLa¨ndernzugu¨nstigenPreisenzurVerfu¨gungstanden,aberwegenderenchronischenU¨berbeanspruchungzurEntwicklungvonResistenzenbeitrugen.Mitteder1990erJahrefu¨hrtedieverschlechterteSituationbezu¨glichMalariazusammenmitdensichabzeichnendenpositiventechnischenEntwicklungendazu,dassdieKontrollevonMalariawiederindenglobalenFokusru¨ckte.AusdemgleichenGrundversuchtenimJahr2000verschiedeneStaatschefseinegemeinsamePositionbezu¨glichderStrategiezurBeka¨mpfungderwichtigstenKrankheitenzufinden.ZweiZielewurdeninFormderMillenniumDevelopmentGoals(MDG)konkretformuliertundsolltenbis2015erreichtwerden.DasMGD4bestanddarindieKindersterblichkeitbezogenaufdasJahr1990umzweiDrittelzusenken,wa¨hrendMGD6daraufabzieltedieBeka¨mpfungvonMalariaundanderenschwerenInfektionskrankheiten(z.B.HIVundTB)bezu¨glichderSituationin1990deutlichzuverbessern.DieseglobalenInitiativenvermochteneinigebereitsbestehendenInterventionsstrategiengegenMalariazuverbessernundhalfenzurEntwicklungeinerReiheneuerInstrumenteundStrategienbei.ErstzuBeginndesletztenJahrzehntskamdie„Artemisinin−basedCombinationTherapy“(ACT)alseineAlternativezudenMono−Therapienauf,welchewegenderwachsendenResistenzimmermehranWirksamkeiteinbu¨sste.DesWeiterenwurdeauchfu¨rdenEinsatzvon„insecticidetreatedmosquitobed−nets“(ITNs)pla¨diert.DankderUnterstu¨tzungvonGlobalHealthPartnern,konntendieITNsnunfu¨rvieleinMalariaendemischenGebietenlebendePersonenzuga¨nglichgemachtwerden.Obwohlbisherja¨hrlichu¨ber1000MillionenUS für die Bekämpfung von Malaria ausgegeben wurden, stellt Malaria
weiterhin eine grosse Bedrohung vor allem für Kinder unter 5 Jahren und für schwangere
Frauen dar.
ACT wurde als Haupt-Malaria-Medikament in Tansania gegen Ende 2006 eingeführt und 2007
auf das ganze Land ausgeweitet. Die Realisierung dieses Projekts hatte einige Ähnlichkeiten
mit Ansätzen in anderen afrikanischen Ländern, jedoch gibt es nach wie vor grosse
Unterschiede. Das homogene Gesundheitssystem in Tansania im Allgemeinen und das
„Primary Health Care“ (PHC) System im Speziellen erleichterten die Realisierung dieser
Malaria-Programme erheblich. Auch die Erkenntnisse, die im Rahmen der Nord-Süd-
Forschungskooperationen gewonnen wurden, die Kollaborationen zwischen NGOs und der
Regierung, sowie die Bereitstellung der erforderlichen Nachweise durch die politischen
Entscheidungsträger, führten schliesslich zu einer erfolgreichen Umsetzung. Zusätzlich
ermöglichte die Zusammenarbeit zwischen den wirtschaftlichen Blöcken Ostafrikas und der
„Southern African Development Community“ (SADC) neue Einblicke in die
grenzüberschreitende Kontrolle von Malaria. Einige dieser in Tansania neu entwickelten und praxis-erprobten Instrumente wurden auch in
anderen Staaten südlich der Sahara angewandt und dabei oft von globalen anti-Malaria
Kampagnen unterstützt.
Die politische Stabilität und der Frieden in Tansania während mehr als vier Jahrzehnten haben
ein schnelles Umdenken in der Politik und die landesweite Ausdehnung der ACTKontrollstrategie
überhaupt erst ermöglicht. Viele benachbarte Länder wie Uganda, Sudan,
Mozambique und die Demokratische Republik Kongo erlebten im gleichen Zeitraum viele
Unruhen. Tansania hat sich als eines der wenigen afrikanischen Länder nicht gescheut sich
dem Rest der Welt für Grossversuche der heute erfolgreichsten Interventionen gegen Malaria
zur Verfügung zu stellen.
Der Kilombero River Basin in Ifakara Tansania wird als Wiege von Malaria bezeichnet. Etliche
neue Interventionen wurden auf ihre Wirksamkeit getestet und evaluiert. Die in dieser Arbeit
präsentierten Ergebnisse wurden hauptsächlich aus verschiedenen Studienzentren in
Tansania zusammengetragen, wobei der grösste Teil aus dem „Ifakara Demographic
Surveillance System“ stammt. Die vorliegende Arbeit gewährt Einblicke in das von Tansania
verfolgte Programm zur landesweiten Umsetzung der ACT.
Das Ziel der Doktorarbeit ist es, einen Beitrag zum besseren Verständnis der Auswirkungen,
welche die Einführung der ACT auf die Malaria Morbidität und Mortalität hatte, beizutragen
und die langfristige Sicherheit im landesweiten Einsatz zu überwachen.
Die erfolgreiche Einbindung der Akteure, insbesondere der teilnehmenden Communities,
sowie die grosse Bereitschaft unter den Forschern beschleunigten die Umsetzung der neuen
Richtlinien von Beginn an. Die auf Beweisen basierten Erkenntnisse, die aus dem
“Interdisciplinary Monitoring Project of anti-malaria Combination Therapy” (IMPACT) und dem
“East African Network for Monitoring anti-malaria Treatment” (EANMAT) gewonnen wurden,
werden in die Entwicklung von neuen Richtlinien einfliessen. Die in vivo Studien haben
gezeigt, dass Artemether-Lumefantrin (AL) nach Kontrolle der Reinfektion durch Polymase
Chain Reaction (PCR) bei Kindern unter fünf Jahren nahezu 100% wirksam war. Wir haben
ebenfalls bewiesen, dass es durch eine intensive Zusammenarbeit zwischen Forschung,
Politik und der pharmazeutischen Industrie möglich ist, auch unter Realbedingungen
Strategien für die Überwachung der Sicherheit und dem sachgemäßen Gebrauch von Antixviii Malaria-Medikamenten umzusetzen. Das „Exploring Health Impact“ Programm (ALIVE) war als
erstes Programm überhaupt in der Lage, in einem randomisierten Beurteilungsdesign auf
Community-Level eine Compliance von mehr als 95% zu einer komplexen 6 Dosen Therapie
von Artemether-Lumefantrin (AL) aufzuzeigen. In Kapitel 5 wird berichtet, dass „ALIVEpharmacovigilance“
afrikaweit die erste community-based Pharmakovigilanz-Studie ist, welche
auch die Verwendung von SMS als Überbringer von schweren Nebenwirkungen untersucht.
Das Projekt ALIVE gewährt sowohl einen Einblick in die Auswirkungen von ACT und anderen
Interventionen auf die Kindersterblichkeit und die Prävalenz. ALIVE hat gezeigt, dass eine
Erhöhung der ITN Abdeckung um 10% eine Verringerung von 48% jährlicher Malariabedingten
Parasitämie auf kommunaler Ebene erzielt [IRR=0.52; 95% CI=0.38 to 0.73]. Es
wurde ebenfalls gezeigt, dass im Vergleich zu der Zeit, als in erster Linie noch SP verwendet
wurde, ACT für ungefähr 11% der jährlichen Reduktion der Mortalität verantwortlich war, wenn
man für andere wichtige Faktoren stratifiziert [IRR = 0,89, 95% CI = 0,79 bis 1,0]. Des
Weiteren wurde beobachtet, dass die Erhöhung der Ernährungssicherheit, insbesondere der
Reiserträge, für fast 36% der Reduktion der jährlichen Mortalität von Kindern unter 5 Jahren
verantwortlich war [IRR = 0,64, 95% CI = 0,54 - 0,75]. Hinsichtlich der Übertragung von
Malaria wurde parallel eine Parasiten-Prävalenz Reduktion von 65% bei asymptomatischen
Community-Mitgliedern im DSS in Ifakara aufgezeichnet, im Vergleich zum Ausgangswert im
Jahr 2006 als ACT eingeführt wurde.
Darüber hinaus wurden diese Auswirkungen als nachhaltig beurteilt, da die Wirksamkeit von
AL, wie anhand einer in vivo Studie ein Jahr nach Umsetzung gezeigt, im Kilombero-Tal bei
über 96% liegt.
Die Ergebnisse dieser Arbeit unterstreichen die Bedeutung des politischen Wandels in der
Malariabekämpfung. Dazu gehört die Forschung als systematischer Weg, um das
Gesundheitssystem zu stärken und sich in der Malaria Bekämpfung innerhalb eines
endemischen Entwicklungslands zu engagieren. Die Erfahrungen aus dieser Arbeit werden
relevant sein für Malaria-betroffene Gebiete vor Ort und auf globaler Ebene. Wir haben auch
gelernt, dass die Sicherheit und Compliance von Arzneimitteln, die, wie ACT, im großen
Maßstab eingesetzt werden überwacht und verwaltet werden muss. Dabei sollten das
Gesundheitsministerium und verwandte Fachbereiche sowie die pharmazeutische Industrie
und Forschungspartner, als auch die örtliche Führung miteinbezogen werden. Wir empfehlen,
dass diese Partnerschaft von globalen Gesundheitsorganisationen unterstützt wird. Die rigorose Überwachung der ordnungsgemässen Verwendung von Medikamenten würde zu
einem besseren Verständnis betreffend der Fragen der Sicherheit von Arzneimitteln führen,
sowie deren Lebensdauer verlängern. Ein weiterer kritischer Aspekt, welcher den Vorrang
eingeräumt werden sollte, ist der Aufbau von Kapazitäten. Wir empfehlen, dass Ressourcen
zur Verfügung gestellt werden um das Gesundheitssystem in Malaria-endemischen Gebieten
zu stärken (human resources, Health Information und Infrastruktur), um nachhaltige
Ergebnisse in der Malariabekämpfung zu erreichen. Damit werden günstige
Rahmenbedingungen geschaffen um eine wirksame, regelmässig überwachte, Anti-Malaria-
Politik zu implementieren.
Wie in dieser Arbeit erläutert, kann eine erfolgreiche Kampagne gegen Malaria durch die
Bemühungen der Forscher, politischer Entscheidungsträger, globaler Entwicklungs-Partnern
und der lokalen Gemeinden realisiert werden. Eine solche Partnerschaft hat bereits Erfolge
erzielt, wie das Beispiel in den 1940er Jahren der Malari
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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