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«THE KILOMBERO VALLEY, TANZANIA INAUGURAL-DISSERTATION Zur Erlangung der Würde eines Doktors der Philosophie vorgelegt der ...»

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Erlangung der Würde eines Doktors der Philosophie

vorgelegt der

Philosophisch-Naturwissenschaftlichen Fakultät der

Universität Basel


Salim Mohammed Khamis Abdulla


Zanzibar - Tansania

Basel, November 2000

Genehmigt von der Philosophisch-Naturwissenschaftlichen Fakultät der Universität Basel auf Antrag der Herren Prof. Dr M. Tanner, PD Dr. C. Lengeler and PD Dr Tom Smith Basel, den 7. November 2000 Prof. Dr. Andreas Zuberbühler Dekan Dedicated to my family Table of contents Page Acknowledgements i Summary iv Zusammenfassung vi List of tables ix List of figures xi


CHAPTER 1 2 Introduction: 2 Burden of malaria disease 2 Malaria control strategies 6 Malaria prevention strategies in Tanzania 6 ITNs in Tanzania 7 ITNs implementation strategy 9 Impact of ITNs under programme conditions 10 Treatment of uncomplicated malaria in Tanzania 11 Evaluation of the control tools and programmes: 13 Summary 14 Reference 15 CHAPTER 2 21 Goal and objectives 21 CHAPTER 3 22 Design And Methods 22 Study area and population 22 Social marketing and distribution of nets 22 Demographic surveillance 23 Passive case detection at idete dispensary 23 Case-control study 24 Cross-sectional surveys 25 Mapping of houses in Idete 26 ® Clinical trial of Co-artem 26 Interview and clinical procedures 27 Assessment of parasi

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Acknowledgements I like to thank the children and guardians of the Kilombero valley for their patience and willingness to participate in the repeated surveys, the village leadership for consenting to have these studies be carried in their administrative areas, helping us in informing the villagers about the studies and facilitating the implementation of the surveys. I am indebted to the Health facility staff of the dispensaries and health Centres in the Ulanga and Kilombero district for assisting us in managing sick children identified in surveys and giving them proper advice. I send special thanks to the staff of the Idete dispensary and the St Francis Designated District Hospital for helping me to implement the facility based studies; Drs. Pascal Mbena and Fred Lwila the district medical Officers for assisting in administrative procedures that were required to get community consent and approval for the conduct of the studies at district level; and Dr. Patience Kibatala for assisting in getting the approval from the St Francis Hospital Governing board and giving useful advice for the conduct of the clinical trial.

This work would not have been possible without the endless efforts of the Ifakara Health Research and Development Centre (IHRDC) - Demographic Surveillance System team who had worked overtime and walked with me the length and breadth of the vast study area t o implement the surveys. I am especially grateful to Jensen Charles, Eric Mahundu and Patrick Rangimoto who assisted in conduct of the Idete studies. Thanks to members of laboratory and data units of the IHRDC for tolerating my huge demands and producing high quality data. I gratefully acknowledge the contribution of many fellow scientists at IHRDC, whom during the last five years helped to shape what I now know and think. This work would have not been possible without the assistance of the support staff of IHRDC who arranged for equipment, supplies, logistics and the happy ambience for doing the work. I am very grateful for the friendship, support and advice I received from Dr. Hassan Mshinda the Director of the IHRDC.

This work is a collaborative effort of many people from the IHRDC and the Swiss tropical Institute. I am grateful to Oscar Mukasa for spending many weekends working on this data. My sincere thanks also to Rose Nathan, Hadji Mponda, Nassor Kikumbih, Happiness Minja, Tanya

–  –  –

Marchant, Adiel Mushi for suggesting solutions for many practical problems encountered in doing this work, facilitating the conduct of the studies and harmonising the studies with the overall activities of the KINET project. My special thanks go to Joanna Schellenberg my local supervisor, who encouraged and introduced me into doing this work, supervised all the work in the field and gave valuable advice and support to complete the work.

My sincere thanks go to Dr. Christian Lengeler my main supervisor, who gave me the privilege of being one of his students and whose guidance, support and confidence enabled me to complete this work. Prof. Marcel Tanner the Director of Swiss Tropical Institute (STI), for always being there with valuable advice and making possible all the studies carried out. I thank Dr. Tom Smith for tolerating and smiling at my frequent disturbance and helping me out with the analysis of the data. Dr. Penelope Vounatsou and Armin Gemperli for introducing me to spatial statistics and Dr. Christoph Hatz for the support and guidance in conducting the clinical trial. Thanks to Drs. Hans Peter Beck, Ingrid Felger and Andrea Irion for enabling my eye to get a glimpse of the molecular world. I am grateful to professors Thierry Freyvogel, Mitchell Weiss and Dr Brigit Obrist for showing interest in my work and their encouragement. My special thanks also go to Frank Krönke and Felix Heckendorn for their support in German translations and friendship. My experience at the STI has been made memorable by the support and friendship of many other colleagues who work or study at the Institute. I thank Owusu Agyei, Jurg Utzinger, Regula Leuwenbeger, Zuwu Tu, Ivo Muller, Harshad Keval, Sebastian Molineux, Lea Knop, Margaret Gyampong and others for sharing a few jokes when the going was tough, Christine Walliser, Elida Keller, Cornelia Naumann, Jennifer Jenkins, Heidi Immler, Simon Roelly, Urs Hodel and others for accommodating my various requests and making my stay in Basel enjoyable.

I am very grateful to Dr. Robert Mull for his friendship and being like a second father to me. I also thank Dr. Catherine Royce, Ms. Nosipho Mtombeni, Ms. Insa Gathmann, Ms. Sybille Blum, Mr.

Daniel Marthe from CIBA/Novartis Pharma. I acknowledge the contribution of Drs. Alex Mwita and Renata Mandike f om the National Malaria Control Programme, Ritha Njau from WHO r country office and Dr. Don DeSavigny in the many discussions that shaped our ideas on malaria control policy issues. I would also like to thank our other collaborators, friends and colleagues from the Ministry of Health, National Institute of Medical Research, Muhimbili University College

–  –  –

of Health Sciences, TEHIP and AMMP projects, the London School of Hygiene and Tropical Medicine, CDC, WHO-Tanzania office and WHO-AFRO.

Lastly, I sincerely thank my extended family for enduring my long absence from home and for their support and encouragement.

Financial support was provided by the Swiss Agency for Development and Co-operation and the Government of Tanzania.

–  –  –

Summary Malaria is major public health problem in Tanzania and increasing trends have been observed in the last two decades. A significant consequence of repeated malaria infections in high transmission areas is anaemia in very young children. The control of malaria in Tanzania includes both preventive and curative strategies. On the preventive side insecticide treated bed nets (ITNs) are a promising tool. ITNs have been shown to be effective in reducing malaria morbidity and mortality in controlled trials. Large-scale implementation of the technology is currently being initiated in many African countries. We report the impact of a large social marketing programme of ITNs on malaria morbidity through a series of studies, in a population of about 55,000 people in Tanzania.

The ITNs social marketing programme resulted in a rapid increase in any net ownership (from 58 to 83%) and an increase in ITNs ownership (from 10 to 61%) in children under two years of age within 2 years of implementation. As a result the overall mean haemoglobin levels increased (from 8.0 to 8.9 g/dl) in the study children during the successive surveys. The prevalence of anaemia in the study population decreased from 49% to 26%. Comparison between children with ITNs and those without nets showed that ITNs had a protective efficacy of 63% (95% CI: 38 to 77) on the prevalence of parasitaemia, and 63% (95% CI: 27 to 82) on anaemia (haemoglobin ≤ 8 g/dl). These results endorse the wide scale implementation of

ITNs in Tanzania.

ITNs can only reduce the risk of malaria dis ease but cannot eliminate it. Hence, appropriate effective treatment is required. Chloroquine is a cheap and safe antimalarial and it was until recently the first line drug of choice in the National Malaria Treatment Policy. Resistance to chloroquine has been reported with increasing frequency in Tanzania and has been linked to the increasing admissions with severe disease in hospitals. A comparative randomised, open clinical trial of chloroquine against Co-artem ® (fixed combination of Artemether + Benflumetol) an alternative new antimalarial, showed seven-day parasitological cure rates of 94% for Co-artem® and only 35% for chloroquine. Generally, Co-artem® showed a superior clearance rate, successfully cleared higher parasite densities and suppressed new infections


over a longer period of time. Furthermore, Co-artem® suppressed more effectively gametocytes in these children, indicating a potential benefit for reducing malaria transmission.

The unacceptably high chloroquine failure rates call for an urgent review of the National Malaria Treatment Guidelines.

The decision to change the first line antimalarial and the choice of a new drug depend on a number of factors that include the clinical, epidemiological and social-economical factors, as well as the health infrastructure. Considering all of these dimensions, sulphadoxinepyrimenthamine (SP) was identified as a good interim replacement for chloroquine. Further Phase IV evaluation of Co -artem® and other combination therapy regimens are required before considering their inclusion in the national treatment policy. Much work is also needed to identify suitable compounds to be used for home management of malaria, within the national treatment guidelines.

Experience gained with these studies gives a description of the different methodologies and tools that can be used to evaluate different components of the National Malaria Control Programme. For example, it was difficult to assess the impact of the ITNs programme using the case-control approach. Repeated cross-sectional assessments were found to be more suitable for assessing the impact of ITNs under programme conditions, especially on malariarelated anaemia in this area of high transmission. Specific indicators for programme evaluation may need to be identified for specific interventions. These may be different from the ones used in randomised controlled trials. The use of molecular markers for monitoring and evaluation of antimalarial intervention programmes illustrate the need to develop and validate novel tools and approaches for programme evaluation.

Better malaria control is expected by combining ITNs and an effective antimalarial, especially combination therapy. The evaluation, implementation, and monitoring of all these control activities requires a partnership between researchers, policy makers, health managers, in close collaboration with other stakeholders in the public and private domain, including the beneficiaries - the community.

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Zusammenfassung Malaria ist ein schwerwiegendes öffentliches Gesundheitsproblem in Tansania. In den vergangenen 20 Jahren hat sich ein Trend zunehmender Ausbreitung der Krankheit beobachten lassen. Eine symptomatische Hauptfolge wiederholter Malariainfektionen in Gebieten mit hohen Übertragungsraten ist Anämie in Kleinkindern. Die Malariakontrolle in Tansania umfasst sowohl präventive als auch kurative Strategien. Auf der Seite der Prävention haben sich insektizidimprägnierte Bettnetze (IIB) als vielversprechendes Instrument erwiesen. In ‚kontrollierten Versuchen’ zeigte die Verwendung von IIB eine effektive Reduzierung malariabedingter Morbidität und Mortalität. Ein erweiterter Einsatz dieser präventiven Massnahme findet derzeit in zahlreichen afrikanischen Ländern statt.

Die vorliegende Arbeit zeigt die Wirkung eines grossangelegten sozialen Marketingprogramms für IIB auf Malaria Morbidität auf. Eine Serie von Studien in einer Population von 55'000 Menschen wurden hierfür durchgeführt.

Das soziale Marketingprogramm in Tansania für imprägnierte Bettnetze hatte in einem Zeitraum von 2 Jahren eine rapide Steigerung des Besitzes von Mückennetzen bei Erwachsenen (von 58 % auf 83 %) und der Nutzung bei Kindern unter zwei Jahren Lebensalter zur Folge. Als Konsequenz hieraus stieg der Gesamtmittelwert des Hämoglobinlevels (von 8,0 g/dl auf 8,9 g/dl). Die Prävalenz für Anämie sank in der Untersuchungspopulation von 45 % auf 26 %. Vergleiche zwischen Kindern, die mit und ohne imprägnierte Netze schliefen, zeigten eine Schutzwirkung der imprägnierten Netze von 63 % (95 % CI: 38 bis 77) in bezug auf die Prävalenz von Parasitämie, und 63 % (95 % CI: 27 bis 82 %) bezüglich der Anämieprävalenz (Hämoglobin 8 g/dl). Diese Ergebnisse unterstützen eine Befürwortung einer grossräumigen Einführung insektizidimprägnierter Bettnetze in Tansania.

Imprägnierte Bettnetze können jedoch das Risiko an Malaria zu erkranken nur reduzieren, nicht völlig aufheben. Folglich ist eine effektive Behandlung ebenso notwendig wie die Prävention. Chloroquine war lange Zeit ein kostengünstiges und sicher wirkendes Antimalariamedikament und es war bis vor kurzem das Medikament der Wahl in der nationalen Politik der Malariabehandlung. Es ist jedoch in Tansania mit zunehmender


Häufigkeit von Chloroquineresistenzen berichtet worden und es wurde ein Zusammenhang zwischen Spitalkonsultationen mit schwerer Malaria und Chloroquineresistenzen festgestellt.

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