Research Themes and Advances in Malaria Research Capacity Made by the Multilateral Initiative on Malaria

The Multilateral Initiative on Malaria was created after an international conference on malaria in Africa held in Dakar, Senegal, in early 1997. The main goal of the conference was to “strengthen and sustain, through collaborative research and training, the capability of malaria endemic countries in Africa to carry out research required to develop or improve tools for malaria control.” This conference marked the beginning of a new global focus on malaria research and capacity building three decades after a partially successful global malaria eradication program. In addition to promoting research on and institutional strengthening for malaria, the initiative was created to develop mechanisms and systems to facilitate timely communication of information to scientists working in Africa, enhance the capacity to conduct malaria collaborative/multi center research in Africa, and promote application of research results to address malaria control needs. This report summarizes the increased malaria research capacity and empowerment of African researchers facilitated by the Multilateral Initiative on Malaria through the Special Program for Research and Training in Tropical Disease Research at the World Health Organization.

Introduction

After a series of planning meetings to define goals and themes, the first International conference on malaria in Africa (the first Multilateral Initiative on Malaria [MIM] conference) was organized and held in Dakar, Senegal, in January 1997. The conference brought together malaria experts from 35 countries including 22 African countries and representatives from the major funding agencies for malaria research worldwide. Recognizing a worsening malaria situation in sub-Saharan Africa and the need to develop more effective tools and strategies to reverse the trend, the conference considered mechanisms needed in the short term to advance research on malaria in Africa. A major outcome of the conference was the recognition of a need to strengthen and sustain through collaborative research and training the capability of malaria-endemic countries in Africa to carry out research required to develop or improve tools for malaria control. Two major issues were identified: the development of mechanisms and systems to 1) facilitate timely communication of information to scientists working in Africa and 2) to enhance the capacity to conduct collaborative/multi-center research in Africa.¹ As a result, MIM was created with the aim to maximize scientific research and collaboration on malaria in Africa.² The primary goal was to address key areas of research needs and gaps in knowledge identified as being critical to the understanding and control of malaria in malaria-endemic countries in Africa. A follow-up conference was held in July 1997 to develop mechanisms for supporting this initiative.

Three decades after the partially successful global malaria eradication program from 1955 to the late 1960s,³ MIM became the watershed of a new global focus on malaria and was soon followed in 1998 by the Roll Back Malaria program.⁴ Since then, more malaria funding programs have come into existence. Although these programs have increased the aggregate resources available for malaria research and control,⁵ the resources fall short in comparison to the disease burden.⁶ Competition, duplication of activities, poor communication and lack of cohesion limit the impact of the additional resources that have became available within the past decade.⁷ There remains a clear and pressing need for a critical mass of researchers and institutions in Africa able to identify critical gaps in malaria control and manage high quality research programs to address these gaps.⁸

A Task Force on Malaria Research Capability Strengthening (RCS) in Africa was launched as part of MIM in the fall of 1997 with initial donations of more than US $2.5 million to the World Health Organization/Special Program for Research and Training in Tropical Disease Research (WHO/ TDR). The United Nations Children’s Fund/United Nations Development Program/World Bank/WHO TDR took the responsibility of managing this task force (MIM/TDR Task Force on RCS in Africa). The task force developed a competitive research grant award program to strengthen malaria research capacities of African scientists and institutions based in Africa.⁹ This program supports collaborative research and training between scientists in Africa and counterparts in Europe and North America, and promotes establishment of core multidisciplinary groups of African investigators and institutions undertaking high-quality research.¹⁰ Since 1998, the MIM/TDR RCS program has supported through 69 competitive grants for research and training 56 principal investigators from Africa working in 33 institutions located in 17 African countries (Table 1). Most grants involved collaboration with scientists and institutions across Europe and the United States and networking within Africa.

Table 1

Recipients of MIM/TDR research grants 1998–2007

There have been important reviews undertaken by the secretariat of the MIM. In 1998, a review of malaria research capacity in Africa was conducted by the Wellcome Trust.¹¹ The main objective of that review was to provide evidence to guide development of the initiative in Africa by identifying existing research capacity and centers of excellence, and to highlight those areas with great need of input. Ten years later, the overall level of malaria research capacity in Africa and the gaps and priorities beyond that provided in the report can only at best be extrapolated.

In 2002, the Fogarty International Center commissioned the first external review of MIM after five years.¹² The goal of the review was to provide perspective to program leadership, and insight on the activities of the MIM Secretariat for coordination of the various MIM components as the forthcoming secretariat planned for the future. The review noted important achievements: contribution to training of masters and doctoral students, improved communication and research collaboration with institutions in Europe and North America, and the novel approach of establishing networks between institutions within Africa. The report also identified challenges and made focused recommendations for redefined objectives and a new strategic plan for the next five years.

More recently, the MIM secretariat at the Karolinska Institute/Stockholm University hosting the Malaria Research and Development Alliance produced an “Assessment of Global Investment,”⁵ which provided the detailed information on disbursement of funds for malaria research and development.

This report is a summary of a recent review focused specifically on the MIM/TDR grant program. It describes research themes supported by the program and the role it has played in enhancing capacity building of African researchers and institutions to conduct high level research in malaria by looking at the research and training undertaken and outcomes, the capacity and networks built or enhanced, and the major scientific contributions of the research funded in the past 10 years with the resources available to the initiative. The detailed review will be published by WHO/TDR.

The information presented in this report was obtained through structured questionnaires, direct interviews with investigators and members of the MIM/TDR scientific review committee, visits to institutions funded by MIM/TDR, reports of investigators, and peer-reviewed publications. The choice of institutions visited took into account location and type of institution and area of research. Core information on the grants, related research capacity building activities, and the scientific review of proposals and reports were obtained from the TDR electronic database.

Funding

MIM/TDR research capacity strengthening grants are awarded on a competitive basis to support investigator initiated research within predefined malaria research priorities. The MIM/TDR grant program is funded through ear marked contributions and is separate from TDR malaria research grants. Funding for the program over a 10-year period is shown in Table 2. To date, an aggregate of $12.9 million has been expended on 69 research grants. The number of new projects funded and new grant disbursement per year are shown in Figures 1 and 2, respectively. The reduction in contribution to the MIM/TDR program over time has had a major impact on the size and number of projects funded over the period reviewed. However, with the modest resources provided through the MIM/TDR RCS grant program, a number of African institutions were able to improve their research capacity and infrastructures enough to attract other funding resources and international collaboration (Table 3).

Table 2

Donor contributions (US$) to the MIM/TDR malaria research capability strengthening program (1998–2007)

Figure 1

Trend in the new Multilateral Initiative on Malaria/ Special Program for Research and Training in Tropical Disease Research grant awards (1988–2007).

Figure 2

Trend in grant disbursement per year of funding.

Table 3

Other funding accessed by recipients of MIM/TDR research capability strengthening grants

Research Themes

Research priorities articulated by the Dakar conference in 1997, the WHO/TDR Scientific Working Group on Malaria 2003,¹³ and the Disease Control Priorities Project¹⁴ have guided the research focus of the MIM/TDR RCS program. Research supported since 1998 have been focused on the following subjects.

Pathogenesis and Immunology of Malaria.^15–53

Anemia, low birth weight, and cerebral malaria account for most of the malaria mortality in Africa. In most settings, there are co-infections with human immunodeficiency virus or other pathogens and these infections impact the clinical management of the patient. Better understanding of the pathogenesis and mechanisms of immune response to malaria may accelerate the development of new/better tools and approaches for prevention and case management of malaria. The goals of this research area are to provide better understanding of 1) the predisposition to severe forms of the disease (severe anemia, cerebral malaria, malaria in pregnancy), 2) to identify/ develop surrogate markers for protective immunity, and 3) to increase regional capacity for training in malaria immunology and pathogenesis. A total of 17 research grants were awarded in this area. The research focused mostly on basic immunology research on vaccines, immunopathogenesis of malaria in pregnancy, and severe anemia. Grants to investigators at the Hospital Albert Schweitzer in Gabon, the University of Ibadan in Nigeria, the University of Ghana, and the Universities of Buea and Yaounde in Cameroon have characterized the epidemiology of malaria and naturally acquired immunity to Plasmodium falciparum candidate vaccine antigens, produced new knowledge on genetic diversity of and antibody responses to merozoite surface protein 1–19, allelic polymorphisms and severe malaria anemia, immunologic responses to malaria infection in pregnancy, and most recently the mechanism of P. falciparum-infected erythrocyte recognition by natural killer cells. Investigators at the Institute of Primate Research in Kenya are currently developing an animal model for malaria in pregnancy, and investigators at the University of Nairobi are attempting to identify biologic markers of severe malaria in humans. The grants funded in pathogenesis and immunology of malaria are shown in Table 4.

Table 4

Grants funded in pathogenesis and immunology of malaria (1998–2007)

Malaria Vector Control: Mosquito Entomology, Epidemiology, and Insecticide Resistance.^54–62

Vector control is an important strategy for malaria control. However, the impact of malaria vector control has been limited not only because of inadequate implementation of existing interventions, but because of development and spread of vector resistance and limited knowledge of mosquito biology and ecology. The goal of MIM research in this area is to provide through global and regional partnerships knowledge needed for understanding vector biology and ecology, with a view to improve the current vector control methods, and to develop new vector control approaches. Sixteen grants focused on vector biology, ecology, or insecticide resistance were awarded to investigators at the Nigerian Institute for Medical Research in Lagos; the Kenyan Institute for Medical Research in Kisumu; the Center de Recherche Entomologique de Cotonou in Benin; the Center National de Recherche et de Formation sur le Paludisme in Ouagadougou, Burkina Faso; the Institut de Recherche en Science de la Santé/Center Muraz in Bobo-Dioulasso, Burkina Faso; the University of Dschang in Cameroon; the National Health Laboratory Services, National Institute for Communicable Diseases in Johannesburg, South Africa; the Institut Pierre Richet in Bouake, Côte d’Ivoire; and the University of Mali in Bamako. The projects have resulted in the characterization of insecticide resistance profile across Nigeria and re-establishing the capacity for molecular entomology and insecticide resistance monitoring in that country; establishment selection of a DDT-resistant Anopheles arabiensis colony in South Africa; new knowledge on An. funestus ecology and population structure; the spatial and temporal mating behavior of An. gambiae; and new knowledge on the role of agricultural practices on the selection of insecticide resistance in malaria vectors. The grants funded in malaria vector control (mosquito entomology, epidemiology and insecticide resistance) are shown in Table 5.

Table 5

Grants funded in malaria vector control: mosquito entomology, epidemiology and insecticide resistance

Chemotherapy of Malaria and Genetics of Antimalarial Drug Resistance.^63–92

Prompt access and appropriate treatment with effective antimalarial drugs is a principal strategy for malaria control. The goal of research in this area is to enhance the capacity of African scientists and institutions to generate, analyze, and collate new knowledge to enhance disease prevention and case management. A total of 18 research projects have been funded by MIM/TDR in this area to date. A network of MIM/TDR investigators from the Universities of Ibadan in Nigeria; Mali; Ghana; and Makerere in Uganda; and Med Biotech Laboratories in Kampala, Uganda; and the Ifakara Health Research and Development Center in Tanzania collaborated to provide efficacy data to inform national decisions on antimalarial treatment policy. The network also investigated the relevance of antimalarial drug blood levels, molecular markers of resistance, and in vitro susceptibility of isolates in the clinical outcome of antimalarial drug treatment and parasite resistance. This concept has evolved into a global collaboration, the World Antimalarial Resistance Network (WARN).^93–97

With the emergence and spread of drug-resistant malaria globally, artemisinin-based antimalarial combination therapies (ACTs) are now the recommended therapy for uncomplicated P. falciparum malaria.⁹⁸ Although ACTs are currently highly efficacious against malaria infections, human behavior impacts on effectiveness of treatment with these classes of drugs. Other MIM/TDR grants to investigators in Gabon, Mali, and Nigeria provided new knowledge on the genetics of chloroquine, mefloquine, or sulfadoxine-pyrimethamine resistance in P. falciparum. The grants funded in chemotherapy of malaria and genetics of antimalarial drug resistance are shown in Table 6.

Table 6

Grants funded in chemotherapy of malaria and genetics of antimalarial drug resistance

Research to Facilitate Malaria Control Interventions Including Introduction and Evaluation of New Strategies and Policies.^{99– 102}

The rational deployment and use of interventions, strategies, and policies necessary for effective malaria control, depends in part on changes in behavior and good surveillance/ follow-up systems in the household and community and in the health facility. The goal of the research in this area is the introduction and use of appropriate strategies and tools for malaria control at the peripheral level of care. Ten grants focused on sociocultural impacts, implementation and operational strategies for community/home-based management of malaria and prevention research have been awarded to researchers at the Universities of Ibadan; Nigeria-Nssuka; and Technology in Yola, Nigeria; Makerere University and the Ministry of Health in Uganda; the Kenya Medical Research Institute in Kilifi; the National Institute for Medical Research in Tanzania; the Tropical Disease Research Center in Ndola, Zambia; and The Institut Pierre Richet in Bouake, Côte d’Ivoire. Factors likely to influence appropriate treatment-seeking behavior in nomadic and rural communities are being identified and documented. The MIM/TDR in collaboration with the WHO Global Malaria Program is funding research that explores ways to promote appropriate use of ACTs by patients or care givers in Cameroon, Tanzania, and Uganda. These grants are focused on identifying the most effective channel for distributing antimalarials in rural communities for use in home management of malaria; exploring the use of antenatal services to enhance the use of insecticide-treated bed nets and intermittent preventive treatment during pregnancy; and generating relevant knowledge about the relative cost, effectiveness, and acceptability of rapid diagnostic tests compared with usual methods for diagnosing malaria (clinical and microscopic) in areas where ACTs are being deployed. The grants funded in research to facilitate malaria control interventions including introduction and evaluation of new strategies and policies are shown in Table 7.

Table 7

Grants funded in research to facilitate malaria control interventions including introduction and evaluation of new strategies and policies

Novel Malaria Control Tools from Natural Products.^{103– 113}

Two of the most important antimalarial medicines in current use, quinine and artemisinine derivatives, are natural products of plant origin. Pyrethroid insecticides are also of plant origin. Although plants are considered a veritable source of new antimalarial drugs, research and development of antimalarial drugs from natural products is expensive and a high-risk venture. MIM/TDR support in this area focused on two groups in Kenya (University of Nairobi and the International Center of Insect Physiology and Ecology working with Maseno Univeristy) and one in Nigeria (The University of Ibadan and the Univeristy of Port Harcourt). The group in Kenya identified and isolated eight essential oils from indigenous plants. These oils were shown to have mosquito-repellent activities better than N,N-diethyl-m-toluamide (DEET) and were larvicidal. The group in Nigeria investigated the value of traditional remedies in the treatment of malaria infections and documented a survey of the efficacy of herbal remedies used in communities in southwestern Nigeria. The grants funded in research on novel malaria control tools from natural products are shown in Table 8.

Table 8

Grants funded in research to facilitate malaria control interventions including introduction and evaluation of new strategies and policies

Conclusions

The MIM/TDR managed by WHO/TDR is considered good and important by investigators, heads of research and academic institutions, directors, members of research network coordinators, and trainees interviewed during this review. The program has been successful in addressing its aims and goals through its activities during the past decade. With a modest research budget of approximately $12.9 million over 10 years, the program has facilitated the capacity of African institutions and researchers to engage in collaborative research of high quality, attract additional research funding, contribute to new knowledge through high-quality scientific publications, and train the next generation of malaria researchers and program implementers. The challenges of malaria and health care in areas of Africa with high burdens of disease, especially sub-Saharan Africa, and the endemic shortage of qualified personnel underscore the necessity of sustained capacity building, encouragement of capacity use, and adequate and sustained support for African research institutions and indigenous researchers working in Africa.¹¹⁵ Adequate funding of this unique and important initiative and a renewed commitment to the major goal of the conference in Dakar are essential for relevant research and sustained effective malaria control in sub-Saharan Africa.

References

1.

Bruno JM, Feachem R, Godal T, Nchinda T, Ogilvie B, Mons B, Mshana R, Radda G, Samba E, Schwartz M, Varmus H, Diallo S, Doumbo O, Greenwood B, Kilama W, Miller LH, da Silva LP. The spirit of Dakar: a call for action on malaria. Nature. 1997;386:541. [PubMed: 9121571]

2.

Davies CS. The Multilateral Initiative on Malaria: coordination and co-operation in international malaria research. Parassitologia. 1999;41:497–500. [PubMed: 10697909]

3.

Scholtens RG, Kaiser RL, Langmuir AD. An epidemiologic examination of the strategy of malaria eradication. Int J Epidemiol. 1972;1:15–24. [PubMed: 4669175]

4.

Nabarro D. Roll Back Malaria. Parassitologia. 1999;41:501–504. [PubMed: 10697910]

5.

MARDA. Malaria R & D Alliance Assessment of Global Investment. 2005. [cited September 2007]. Available from http://www​.malariaalliance.org/.

6.

Shiffman J. Donor funding priorities for communicable disease control in the developing world. Health Policy Plan. 2006;21:411–420. [PubMed: 16984894]

7.

Alilio MS, Bygbjerg IBC, Breman JG. Are multilateral malaria research and control programs the most successful? Lesson from the past 100 years in Africa. Am J Trop Med Hyg. 2004;71:268–278. [PubMed: 15331847]

8.

Heddini A, Keusch GT, Davies CS. The multilateral initiative on malaria: past, present, and future. Am J Trop Med Hyg. 2004;71:279–282. [PubMed: 15331848]

9.

WHO/TDR. Multilateral perspective on malaria begins to take shape. TDR News Feb. 1998;1:12. [PubMed: 12348561]

10.

Zicker F. Strengthening capability for malaria research in Africa. Emerg Infect Dis. 2001;7:529–530. [PMC free article: PMC2631813] [PubMed: 11485647]

11.

Beattie P, Renshaw M, Davies CS. Strengthening Health Research in the Developing World. Malaria Research Capacity in Africa. London: The Trustee of the Wellcome Trust; 1999.

12.

Bockarie M, Bond E, Mutambu S, Nchinda T, Quakyi I, Rodriguez-Lopez M, Snow R. Review of the Multilateral Initiative on Malaria (MIM). 2002. [cited September 2007]. Available from http://www​.fic.nih.gov/about/plan/.

13.

WHO/TDR. Report of the Scientific Working Group on Malaria. 2003. [cited September 2007]. Available from www​.who.int/tdr/publications​/publications/malaria_swg.htm.

14.

Breman JG, Mills A, Snow RW, Mulligan J, Lengeler C, Mendis K, Sharp B, Morel C, Machesini P, White NJ, Steketee RW, Doumbo OK. Conquering malaria. Disease Control Priorities in Developing Countries. In: Jamison DT, Breman JG, Measham AR, Alleyne G, Claeson M, Evans DB, Jha P, Mills A, Musgrove P, editors. 2. New York: Oxford University Press; 2006. pp. 413–431.

15.

Akanmori BD, Kurtzhals JA, Goka BQ, Adabayeri V, Ofori MF, Nkrumah FK, Behr C, Hviid L. Distinct patterns of cytokine regulation in discrete clinical forms of Plasmodium falciparum malaria. Eur Cytokine Netw. 2000;11:113–118. [PubMed: 10705308]

16.

Ekala MT, Lekoulou F, Djikou S, Dubreuil G, Issifou S, Ntoumi F. Evaluation d’une méthode simple et rapide d’extraction de l’ADN de Plasmodium falciparum à partir de gouttes épaisses de patients gabonais. Bull Soc Pathol Exot. 2000;93:8–11. [PubMed: 10774484]

17.

Quaye IK, Ekuban FA, Goka BQ, Adabayeri V, Kurtzhals JA, Gyan B, Ankrah NA, Hviid L, Akanmori BD. Haptoglobin 1-1 is associated with susceptibility to severe Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg. 2000;94:216– 219. [PubMed: 10897372]

18.

Goka BQ, Kwarko H, Kurtzhals JA, Gyan B, Ofori-Adjei E, Ohene SA, Hviid L, Akanmori BD, Neequaye J. Complement binding to erythrocytes is associated with macrophage activation and reduced haemoglobin in Plasmodium falciparum malaria. Trans R Soc Trop Med Hyg. 2001;95:545–549. [PubMed: 11706671]

19.

Issifou S, Ndikou S, Sanni A, Lekoulou F, Ntoumi F. No influence of the transmission season on genetic diversity and complexity of infections in Plasmodium falciparum isolates from Benin. Afr J Med Med Sci. 2001;30:17–20. [PubMed: 14513933]

20.

Ntoumi F, Ngoundou-Landji J, Luty A, Dubreuil G, Millet P. Polymorphisme allélique du gène MSP-2 de Plasmodium falciparum analysé à partir d’échantillons sanguins d’enfants gabonais. Bull Soc Pathol Exot. 2001;94:183–187. [PubMed: 16579074]

21.

Ekala MT, Jouin H, Lekoulou F, Issifou S, Mercereau-Puijalon O, Ntoumi F. Plasmodium falciparum merozoite surface protein 1 (PfMSP1): genotyping and humoral responses to allele-specific variants. Acta Trop. 2002;81:33–46. [PubMed: 11755430]

22.

Ekala MT, Jouin H, Lekoulou F, Mercereau-Puijalon O, Ntoumi F. Allelic Family specific humoral responses to merozoite surface protein 2 (MSP2) in Gabonese residents with Plasmodium falciparum infections. Clin Exp Immunol. 2002;129:326– 331. [PMC free article: PMC1906438] [PubMed: 12165090]

23.

Gyan B, Goka B, Cvetkovic JT, Perlmann H, Lefvert AK, Akanmori B, Troye-Blomberg M. Polymorphisms in interleukin-1 and interleukin-1 receptor antagonist genes and malaria in Ghanaian children. Scand J Immunol. 2002;56:619–622. [PubMed: 12472674]

24.

Gyan B, Kurtzhals JA, Akanmori BD, Ofori M, Goka BQ, Hviid L, Behr C. Elevated levels of nitric oxide and low levels of haptoglobin are associated with severe malarial anaemia in African children. Acta Trop. 2002;83:133–140. [PubMed: 12088854]

25.

Kemp K, Akanmori BD, Adabayeri V, Goka BQ, Kurtzhals JA, Behr C, Hviid L. Cytokine production and apoptosis among T cells from patients under treatment for Plasmodium falciparum malaria. Clin Exp Immunol. 2002;127:151–157. [PMC free article: PMC1906283] [PubMed: 11882046]

26.

Ntoumi F, Ekala MT, Makuwa M, Lekoulou F, Mercereau-Puijalon O, Deloron P. Sickle cell trait carriage: imbalanced distribution of IgG subclass antibodies reactive to Plasmodium falciparum family-specific MSP2 peptides in serum samples from Gabonese children. Immunol Lett. 2002;84:9–16. [PubMed: 12161278]

27.

Nwuba RI, Sodeinde O, Anumudu CI, Omosun YO, Odaibo AB, Holder AA, Nwagwu M. The human immune response to Plasmodium falciparum includes both antibodies that inhibit merozoite surface protein 1 secondary processing and blocking antibodies. Infect Immun. 2002;70:5328–5331. [PMC free article: PMC128297] [PubMed: 12183594]

28.

Issifou S, Mavoungou E, Borrmann S, Bouyou-Akotet MK, Matsiegui PB, Kremsner PG, Ntoumi F. Severe malarial anemia associated with increased soluble Fas ligand (sFasL) concentration in Gabonese children. Eur Cytokine Netw. 2003;14:238–241. [PubMed: 14715416]

29.

Issifou S, Rogier C, Adjagba-Olakpo M, Chabi-Worou N, Ntoumi F. Complexity and genetic diversity of Plasmodium falciparum infections in young children living in urban areas of central and west Africa. Parasitol Res. 2003;90:423–428. [PubMed: 12759745]

30.

Mawili-Mboumba DP, Borrmann S, Cavanagh DR, McBride JS, Matsiegui PB, Missinou MA, Kremsner PG, Ntoumi F. Antibody responses to P. falciparum MSP-1 and the efficacy of amodiaquine in Gabonese children with falciparum malaria. J Infect Dis. 2003;187:1137–1141. [PubMed: 12660928]

31.

Anumudu CI, Okafor CM, Ngwumohaike V, Afolabi KA, Nwuba RI, Nwagwu M. Clinical manifestations and immune response to MSP 1(19) in severe paediatric malaria in Adeoyo state maternity hospital, Ibadan. Afr J Med Med Sci. 2004;33:57–63. [PubMed: 15490796]

32.

Gyan BA, Goka B, Cvetkovic JT, Kurtzhals JL, Adabayeri V, Perlmann H, Lefvert AK, Akanmori BD, Troye-Blomberg M. Allelic polymorphisms in the repeat and promoter regions of the interleukin-4 gene and malaria severity in Ghanaian children. Clin Exp Immunol. 2004;138:145–150. [PMC free article: PMC1809180] [PubMed: 15373917]

33.

Mayengue PI, Rieth H, Khattab A, Issifou S, Kremsner PG, Klinkert M, Ntoumi F. Submicroscopic Plasmodium falciparum infections and multiplicity of infection in matched peripheral, placental and umbilical cord blood samples from Gabonese women. Trop Med Int Health. 2004;9:949–958. [PubMed: 15361107]

34.

Akum AE, Kuoh AJ, Minang JT, Achimbom BM, Ahmadou MJ, Troye-Blomberg M. The effect of maternal, umbilical cord and placental malaria parasitaemia on the birthweight of newborns from south-western Cameroon. Acta Paediatr. 2005;94:917–923. [PubMed: 16188815]

35.

Akum AE, Minang JT, Kuoh AJ, Ahmadou MJ, Troye-Blomberg M. Plasmodium falciparum inhibitory capacities of paired maternal-cord sera from south-west province, Cameroon. J Trop Pediatr. 2005;51:182–190. [PubMed: 15855302]

36.

Achidi EA, Anchang JK, Minang JT, Ahmadou MJ, Troye-Blomberg M. Studies on Plasmodium falciparum isotypic antibodies and numbers of IL-4 and IFN-gamma secreting cells in paired maternal cord blood from south west Cameroon. Int J Infect Dis. 2005;9:159–169. [PubMed: 15840457]

37.

Achidi EA, Kuoh AJ, Minang JT, Ngum B, Achimbom BM, Motaze SC, Ahmadou MJ, Troye-Blomberg M. Malaria infection in pregnancy and its effects on haemoglobin levels in women from a malaria endemic area of Fako Division, South West Province, Cameroon. J Obstet Gynaecol. 2005;25:235–240. [PubMed: 16147724]

38.

Amodu OK, Adeyemo AA, Ayoola OO, Gbadegesin RA, Orimadegun AE, Akinsola AK, Olumese PE, Omotade OO. Genetic diversity of the msp-1 locus and symptomatic malaria in south-west Nigeria. Acta Trop. 2005;95:226–232. [PubMed: 16023985]

39.

Amodu OK, Gbadegesin RA, Ralph SA, Adeyemo AA, Brenchley PE, Ayoola OO, Orimadegun AE, Akinsola AK, Olumese PE, Omotade OO. Plasmodium falciparum malaria in south-west Nigerian children: is the polymorphism of ICAM-1 and E-selectin genes contributing to the clinical severity of malaria? Acta Trop. 2005;95:248–255. [PubMed: 16002039]

40.

Amodu OK, Olumese PE, Gbadegesin RA, Ayoola OO, Adeyemo AA. The influence of individual preventive measures on the clinical severity of malaria among Nigerian children. Acta Trop. 2006;97:370–372. [PubMed: 16438924]

41.

Boeuf P, Vigan-Womas I, Jublot D, Loizon S, Barale JC, Akanmori BD, Mercereau-Puijalon O, Behr C. CyProQuant-PCR: a real time RT-PCR technique for profiling human cytokines, based on external RNA standards, readily automatable for clinical use. BMC Immunol. 2005;6:5. [PMC free article: PMC555737] [PubMed: 15748278]

42.

Minang JT, Gyan BA, Anchang JK, Troye-Blomberg M, Perlmann H, Achidi EA. Haptoglobin phenotypes and malaria infection in pregnant women at delivery in western Cameroon. Acta Trop. 2004;90:107–114. [PubMed: 14739029]

43.

Ntoumi F, Flori L, Mayengue PI, Matondo Maya DW, Issifou S, Deloron P, Lell B, Kremsner PG, Rihet P. Influence of carriage of hemoglobin AS and the Fc gamma receptor IIa-R131 allele on levels of immunoglobulin G2 antibodies to Plasmodium falciparum merozoite antigens in Gabonese children. J Infect Dis. 2005;192:1975–1980. [PubMed: 16267770]

44.

Omosun YO, Anumudu CI, Adoro S, Odaibo AB, Sodeinde O, Holder AA, Nwagwu M, Nwuba RI. Variation in the relationship between anti-MSP-1(19) antibody response and age in children infected with Plasmodium falciparum during the dry and rainy seasons. Acta Trop. 2005;95:233–247. [PubMed: 16055071]

45.

Rasti N, Falk KI, Donati D, Gyan BA, Goka BQ, Troye-Blomberg M, Akanmori BD, Kurtzhals JA, Dodoo D, Consolini R, Linde A, Wahlgren M, Bejarano MT. Circulating epstein-barr virus in children living in malaria-endemic areas. Scand J Immunol. 2005;61:461–465. [PubMed: 15882438]

46.

Awandare GA, Goka B, Boeuf P, Tetteh JK, Kurtzhals JA, Behr C, Akanmori BD. Increased levels of inflammatory mediators in children with severe Plasmodium falciparum malaria with respiratory distress. J Infect Dis. 2006;194:1438–1446. [PubMed: 17054074]

47.

Haase R, Megnekou R, Lundquist M, Ofori MF, Hviid L, Staalsoe T. Plasmodium falciparum parasites expressing pregnancy-specific variant surface antigens adhere strongly to the choriocarcinoma cell line BeWo. Infect Immun. 2006;74:3035–3038. [PMC free article: PMC1459756] [PubMed: 16622246]

48.

Matondo Maya DW, Mavoungou E, Deloron P, Theisen M, Ntoumi F. Distribution of IgG subclass antibodies specific for Plasmodium falciparum glutamate-rich-protein molecule in sickle cell trait children with asymptomatic infections. Exp Parasitol. 2006;112:92–98. [PubMed: 16356497]

49.

Rindsjo E, Hulthen Varli I, Ofori MF, Lundquist M, Holmlund U, Papadogiannakis N, Scheynius A. Presence of IgE cells in human placenta is independent of malaria infection or chorioamnionitis. Clin Exp Immunol. 2006;144:204–211. [PMC free article: PMC1809662] [PubMed: 16634792]

50.

Achidi EA, Apinjoh TO, Titanji VP. Malaria parasitemia and systemic cytokine bias in pregnancy. Int J Gynaecol Obstet. 2007;97:15–20. [PubMed: 17331514]

51.

Mavoungou E, Held J, Mewono L, Kremsner PG. A Duffy binding-like domain is involved in the NKp30-mediated recognition of Plasmodium falciparum-parasitized erythrocytes by natural killer cells. J Infect Dis. 2007;195:1521–1531. [PubMed: 17436233]

52.

Mayengue PI, Kalmbach Y, Issifou S, Kremsner PG, Ntoumi F. No variation in the prevalence of point mutations in the Pfcrt and Pfmdr1 genes in isolates from Gabonese patients with uncomplicated or severe Plasmodium falciparum malaria. Parasitol Res. 2007;100:489–493. [PubMed: 17096149]

53.

Meraldi V, Nebie I, Tiono AB, Diallo D, Sanogo E, Theisen M, Druilhe P, Corradin G, Moret R, Sirima BS. Natural antibody response to Plasmodium falciparum Exp-1, MSP-3 and GLURP long synthetic peptides and association with protection. Parasite Immunol. 2004;26:265–272. [PubMed: 15541030]

54.

Collins FH, Kamau L, Ranson HA, Vulule JM. Molecular entomology and prospects for malaria control. Bull World Health Organ. 2000;78:1412–1423. [PMC free article: PMC2560650] [PubMed: 11196488]

55.

Dia I, Loucouarn L, Boccolini D, Constantini C, Fontenille D. Spatial and temporal variations of the chromosomal inversion polymorphism of Anopheles funestus in Senegal. Parasite. 2000;7:179–184. [PubMed: 11031753]

56.

Ranson H, Jensen B, Vulule JM, Wang X, Hemingway J, Collins FH. Identification of a point mutation in the voltage-gated sodium channel gene of Kenyan Anopheles gambiae associated with resistance to DDT and pyrethroids. Insect Mol Biol. 2000;9:491–497. [PubMed: 11029667]

57.

Sinkins SP, Hackett BJ, Costantini C, Vulule J, Ling YY, Collins FH, Besansky NJ. Isolation of polymorphic microsatellite loci from the malaria vector Anopheles funestus. Mol Ecol. 2000;9:490–492. [PubMed: 10736053]

58.

Weill M, Chandre F, Brengues C, Manguin S, Akogbeto M, Pasteur N, Guillet P, Raymond M. The kdr mutation occurs in the Mopti form of Anopheles gambiae s. through introgression. Insect Mol Biol. 2000;9:451–455. [PubMed: 11029663]

59.

Diabaté A, Brengues C, Baldet T, Dabire KR, Hougard JM, Akogbeto M, Kengne P, Simard F, Guillet P, Hemingway J, Chandre F. The spread of the Leu-Phe kdr mutation through Anopheles gambiae complex in Burkina Faso: genetic introgression and de novo phenomena. Trop Med Int Health. 2004;9:1267–1273. [PubMed: 15598258]

60.

Awolola TS, Oyewole IO, Amajoh CN, Idowu ET, Ajayi MB, Oduola A, Manafa OU, Ibrahim K, Koekemoer LL, Coetzee M. Distribution of the molecular forms of Anopheles gambiae and pyrethroid knock down resistance gene in Nigeria. Acta Trop. 2005;95:204–209. [PubMed: 16023989]

61.

Awolola TS, Oyewole IO, Koekemoer LL, Coetzee M. Identification of three members of the Anopheles funestus (Diptera: Culicidae) group and their role in malaria transmission in two ecological zones in Nigeria. Trans R Soc Trop Med Hyg. 2005;99:525–531. [PubMed: 15869772]

62.

Akogbeto MC, Djouaka RF, Kinde-Gazard DA. Screening of pesticide residues in soil and water samples from agricultural settings. Malar J. 2006;5:22–30. [PMC free article: PMC1513586] [PubMed: 16563153]

63.

Crawley J, Kokwaro G, Ouma D, Watkins W, Marsh K. Chloroquine is not a risk factor for seizure in childhood cerebral malaria. Trop Med Int Health. 2000;5:860–864. [PubMed: 11169275]

64.

Mberu EK, Mosobo M, Nzila MA, Kokwaro GO, Sibley C, Watkins WM. The changing pattern of in vitro response to pyrimethamine-sulfadoxine in Plasmodium falciparum field isolates from Kilifi, Kenya. Am J Trop Med Hyg. 2000;62:396–401. [PubMed: 11037785]

65.

Ogutu BR, Newton CR, Crawley J, Muchohi SN, Otieno GO, Edwards G, Marsh K, Kokwaro GO. Pharmacokinetics and anticonvulsant effects of diazepam in children with severe falciparum malaria and convulsions. Br J Clin Pharmacol. 2002;53:49 –57. [PMC free article: PMC1874558] [PubMed: 11849195]

66.

Ogutu BR, Newton CR, Muchohi SN, Otieno GO, Kokwaro GO. Phenytoin pharmacokinetics and clinical effects in African children following fosphenytoin and chloramphenicol coadministration. Br J Clin Pharmacol. 2002;54:635–642. [PMC free article: PMC1874507] [PubMed: 12492612]

67.

Oundo JO, Muli F, Kariuki S, Waiyaki PG, Iijima Y, Berkley J, Kokwaro G, Ngetsa CJ, Mwarumba S, Torto R, Lowe B. Association of non-typhi Salmonella with severe malaria in children in Kilifi on the Kenyan coast. E Afr Med J. 2002;79:633–638. [PubMed: 12678446]

68.

Barennes H, Sterlingot H, Nagot N, Meda H, Kabore M, Sanou M, Nacro B, Bouree P, Pussard E. Intrarectal pharmacokinetics of two formulations of quinine in children with falciparum malaria. Eur J Clin Pharmacol. 2003;58:649–652. [PubMed: 12610739]

69.

Djimdé AA, Doumbo OK, Traore O, Guindo AB, Kayentao K, Diourte Y, Niare-Doumbo S, Coulibaly D, Kone AK, Cissoko Y, Tekete M, Fofana B, Dicko A, Diallo DA, Wellems TE, Kwiatkowski D, Plowe CV. Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria. Am J Trop Med Hyg. 2003;69:558–563. [PubMed: 14695097]

70.

Kokwaro GO, Ogutu BR, Muchohi SN, Otieno GO, Newton CR. Pharmacokinetics and clinical effect of phenobarbital in children with severe falciparum malaria and convulsions. Br J Clin Pharmacol. 2003;56:453–457. [PMC free article: PMC1884365] [PubMed: 12968992]

71.

Nzila MA, Mberu KE, Bray P, Kokwaro G, Ward S, Watkins B, Winstanley P, Marsh K. Reversal of antifolate and chloroquine resistance by probenecid in Plasmodium falciparum. Antimicrob Agents Chemother. 2003;47:2108–2112. [PMC free article: PMC161864] [PubMed: 12821454]

72.

Muchohi SN, Kokwaro GO, Maitho TE, Munenge RW, Watkins WM, Edwards IG. Pharmacokinetics of phenytoin and fosphenytoin following intravenous and intramuscular administration. Eur J Pharmacokin Biopharm. 2002;27:83–89. [PubMed: 12064376]

73.

Ogutu BR, Newton CR, Muchohi SN, Otieno GO, Edwards G, Watkins WM, Kokwaro GO. Pharmacokinetics and clinical effects of phenytoin and fosphenytoin in children with severe malaria and status epilepticus. Br J Clin Pharmacol. 2003;56:112–119. [PMC free article: PMC1884335] [PubMed: 12848783]

74.

Thompson AH, Kokwaro GO, English M, Muchohi S, Mohammed S, Edwards IG. Population pharmacokinetics of intramuscular gentamicin administered to infants with suspected sepsis in Kenya. Br J Clin Pharmacol. 2003;56:25–31. [PMC free article: PMC1884322] [PubMed: 12848772]

75.

Gitau EN, Muchohi SN, Ogutu BR, Githiga IM, Kokwaro G. Selective and sensitive liquid chromatographic assay of amodiaquine and desethylamodiaquine in whole blood spotted on filter paper. J Chromatograph. 2004;799:173–177. [PubMed: 14659450]

76.

Mithwani S, Aarons L, Kokwaro GO, Majid O, Muchohi S, Edwards G, Mohamed S, Marsh K, Watkins W. Population pharmacokinetics of artemether and dihydroartemisinin following intramuscular administration to children with severe malaria. Br J Clin Pharmacol. 2004;57:148–152. [PMC free article: PMC1884434] [PubMed: 14748813]

77.

Nzila A, Kokwaro G, Winstanley P, Marsh K, Ward S. Can exploitation of the folate salvage pathway in Plasmodium falciparum be the saviour of sulfadoxine/pyrimethamine? Trends Parasitol. 2004;20:109–111. [PubMed: 16676416]

78.

Achidi EA, Ajua A, Kimbi HK, Sinju CM. In vivo efficacy study of quinine sulphate in the treatment of uncomplicated P. falciparum malaria in patients from southwestern Cameroon. East Afr Med J. 2005;82:181–185. [PubMed: 16122085]

79.

Akogun OB, John KK. Illness-related practices for the management of childhood malaria among the Bwatiye people of north-eastern Nigeria. Malar J. 2005;4:13. [PMC free article: PMC553996] [PubMed: 15723706]

80.

Koram KA, Abuaku B, Duah N, Quashie N. Comparative efficacy of antimalarial drugs including ACTs in the treatment of uncomplicated malaria among children under 5 years in Ghana. Acta Trop. 2005;95:194–203. [PubMed: 16054584]

81.

Mugittu K, Abdulla S, Falk N, Masanja H, Felger I, Mshinda H, Beck HP, Genton B. Efficacy of sulfadoxine-pyrimethamine in Tanzania after two years as first-line drug for uncomplicated malaria: assessment protocol and implication for treatment policy strategies. Malar J. 2005;4:55. [PMC free article: PMC1315332] [PubMed: 16297234]

82.

Sowunmi A, Fateye BA, Adedeji AA, Fehintola FA, Bamgboye AE, Babalola CP, Happi TC, Gbotosho GO. Effects of antifolates–co-trimoxazole and pyrimethamine-sulfadoxine–on gametocytes in children with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria. Mem Inst Oswaldo Cruz. 2005;100:451–455. [PubMed: 16113897]

83.

Sowunmi A, Fateye BA, Adedeji AA, Fehintola FA, Gbotosho GO, Happi TC, Tambo E, Oduola AM. Predictors of the failure of treatment with chloroquine in children with acute, uncomplicated, Plasmodium falciparum malaria, in an area with high and increasing incidences of chloroquine resistance. Ann Trop Med Parasitol. 2005;99:535–544. [PubMed: 16156966]

84.

Quashie NB, Duah NO, Abuaku B, Koram KA. The in-vitro susceptibilities of Ghanaian Plasmodium falciparum to antimalarial drugs. Ann Trop Med Parasitol. 2007;101:391–398. [PubMed: 17550644]

85.

Mawili-Mboumba DP, Ekala MT, Lekoulou F, Ntoumi F. Molecular analysis of DHFR and DHPS genes in P. falciparum clinical isolates from the Haut–Ogooue region in Gabon. Acta Trop. 2001;78:231–240. [PubMed: 11311186]

86.

Mawili-Mboumba D, Kun JFJ, Lell B, Kremsner PG, Ntoumi F. Pfmdr1 gene alleles and response to low dose mefloquine treatment in Gabonese patients. Antimicrob Agents Chemother. 2002;46:166–170. [PMC free article: PMC127001] [PubMed: 11751128]

87.

Mberu EK, Nzila AM, Nduati E, Ross A, Monks SM, Kokwaro GO, Watkins WM, Hopkins Sibley C. Plasmodium falciparum: in vitro activity of sulfadoxine and dapsone in field isolates from Kenya: point mutations in dihydropteroate synthase may not be the only determinants in sulfa resistance. Exp Parasitol. 2002;101:90–96. [PubMed: 12427462]

88.

Happi TC, Thomas SM, Gbotosho GO, Falade CO, Akinboye DO, Gerena L, Hudson T, Sowunmi A, Kyle DE, Milhous W, Wirth DF, Oduola AM. Point mutations in the pfcrt and pfmdr-1 genes of Plasmodium falciparum and clinical response to chloroquine, among malaria patients from Nigeria. Ann Trop Med Parasitol. 2003;97:439–451. [PubMed: 12930607]

89.

Ochong E, Nzila A, Kimani S, Kokwaro G, Mutabingwa T, Watkins W, Marsh K. Molecular monitoring of Leu-164 mutation of dihydrofolate reductase in highly sulfadoxine/ pyrimethamine-resistant area in Africa. Malar J. 2003;2:46. [PMC free article: PMC317348] [PubMed: 14675491]

90.

Mugittu K, Ndejembi M, Malisa A, Lemnge M, Premji Z, Mwita A, Nkya W, Kataraihya J, Abdulla S, Beck HP, Mshinda H. Therapeutic efficacy of sulfadoxine-pyrimethamine and prevalence of resistance markers in Tanzania prior to revision of malaria treatment policy: Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase mutations in monitoring in vivo resistance. Am J Trop Med Hyg. 2004;71:696– 702. [PubMed: 15642957]

91.

Happi CT, Gbotosho GO, Folarin OA, Akinboye DO, Yusuf BO, Ebong OO, Sowunmi A, Kyle DE, Milhous W, Wirth DF, Oduola AM. Polymorphisms in Plasmodium falciparum dhfr and dhps genes and age related in vivo sulfadoxine-pyrimethamine resistance in malaria-infected patients from Nigeria. Acta Trop. 2005;95:183–193. [PubMed: 16023986]

92.

Mayengue PI, Ndounga M, Davy MM, Tandou N, Ntoumi F. In vivo chloroquine resistance and prevalence of the pfcrt codon 76 mutation in Plasmodium falciparum isolates from the Republic of Congo. Acta Trop. 2005;95:219–225. [PubMed: 16002038]

93.

Sibley CH, Barnes KI, Plowe CV. The rationale and plan for creating a World Antimalarial Resistance Drug Network (WARN). Malar J. 2007;6:118. [PMC free article: PMC2000470] [PubMed: 17822531]

94.

Price RN, Dorsey G, Ashley EA, Barnes KI, Baird JK, d’Alessandro U, Guerin PJ, Laufer MK, Naidoo I, Nosten F, Olliaro P, Plowe CV, Ringwald P, Sibley CH, Stepniewska K, White NJ. World Antimalarial Resistance Network (WARN) I: clinical efficacy of antimalarial therapy. Malar J. 2007;6:119. [PMC free article: PMC2008205] [PubMed: 17822532]

95.

Bacon DJ, Jambou R, Fandeur T, Le Bras J, Wongsrichchanalai C, Fukuda MM, Ringwald P, Sibley CH, Kyle DE. World Antimalarial Resistance Network (WARN) II: in vitro antimalarial drug susceptibility. Malar J. 2007;6:120. [PMC free article: PMC2008206] [PubMed: 17822533]

96.

Plowe CV, Roper C, Barnwell JW, Happi CT, Joshi HH, Mbacham W, Meshnick SR, Mugittu K, Naidoo I, Price RN, Shafer RW, Sibley CH, Sutherland CJ, Zimmerman PA, Rosenthal PJ. World Antimalarial Resistance Network (WARN) III: molecular markers for drug resistant malaria. Malar J. 2007;6:121. [PMC free article: PMC2008207] [PubMed: 17822535]

97.

Barnes KI, Lindegardh N, Ogundahunsi O, Olliaro P, Plowe CV, Randrianarivelojosia M, Gbotosho GO, Watkins WM, Sibley CH, White NJ. World Antimalarial Resistance Network (WARN) IV: clinical pharmacology. Malar J. 2007;6:122. [PMC free article: PMC2014777] [PubMed: 17822537]

98.

World Health Organization. Guidelines for the Treatment of Malaria. Geneva: World Health Organization; 2006. Treatment of Uncomplicated P. falciparum malaria; pp. 16–40.

99.

Ajayi IO, Falade CO, Adeniyi JD, Bolaji MO. The role of patent medicine sellers in home management of childhood malaria: a situational anaysis of experience in rural Nigeria. Int Q Community Health Educ. 2003;21:271–281.

100.

Asa A, Adegbenro CA, Dare FO, Adeniyi JD, Osowole OS, Oladepo O. Enhancing treatment compliance in the home management of childhood malaria: the use of a participatory approach in ensuring intervention appropriateness. Int Q Community Health Educ. 2004;22:239–248.

101.

Falade CO, Osowole OS, Adeniyi JD, Oladepo O. Attitude of health care workers to the involvement of alternative healthcare providers in the home management of childhood malaria. Int Q Community Health Educ. 2004;23:169–180.

102.

Falade CO, Ogundiran MO, Bolaji MO, Ajayi IO, Akinboye DO, Oladepo O, Adeniyi JD, Oduola AM. The influence of cultural perception of causation, complications, and severity of childhood malaria on determinants of treatment and preventive pathways. Int Q Community Health Educ. 2005;24:347–363. [PubMed: 17686690]

103.

Ajaiyeoba EO, Abalogu UI, Krebs HC, And Oduola AMJ. In vivo antimalarial activities of Quassia amara and Quassia undulate plant extracts in mice. J Ethnopharmacol. 1999;67:321–325. [PubMed: 10617067]

104.

Barasa SS, Ndiege IO, Lwande W, Hassanali A. Repellent activities of stereoisomers of p-menthane-3,8-diols against Anopheles gambiae (Diptera: Culicidae). J Med Entomol. 2002;39:736–741. [PubMed: 12349856]

105.

Seyoum A, Kabiru EW, Lwande W, Killeen GF, Hassanali A, Knols BG. Repellency of live potted plants against Anopheles gambiae from human baits in semi-field experimental huts. Am J Trop Med Hyg. 2002;67:191–195. [PubMed: 12389946]

106.

Seyoum A, Killeen GF, Kabiru EW, Knols BG, Hassanali A. Field efficacy of thermally expelled or live potted repellent plants against African malaria vectors in western Kenya. Trop Med Int Health. 2003;8:1005–1011. [PubMed: 14629767]

107.

Seyoum A, Palsson K, Kung’a S, Kabiru EW, Lwande W, Killeen GF, Hassanali A, Knols BG. Traditional use of mosquito-repellent plants in western Kenya and their evaluation in semi-field experimental huts against Anopheles gambiae: ethnobotanical studies and application by thermal expulsion and direct burning. Trans R Soc Trop Med Hyg. 2002;96:225– 231. [PubMed: 12174767]

108.

Ajaiyeoba EO, Oladepo O, Fawole OI, Bolaji OM, Akinboye DO, Ogundahunsi OA, Falade CO, Gbotosho GO, Itiola OA, Happi TC, Ebong OO, Ononiwu IM, Osowole OS, Oduola OO, Ashidi JS, Oduola AM. Cultural categorization of febrile illnesses in correlation with herbal remedies used for treatment in southwestern Nigeria. J Ethnopharmacol. 2003;85:179–185. [PubMed: 12639738]

109.

Ndung’u M, Hassanali A, Hooper AM, Chhabra S, Miller TA, Paul RL, Torto B. Ring A-seco mosquito larvicidal limonoids from Turraea wakefieldii. Phytochemistry. 2003;64:817– 823. [PubMed: 14559274]

110.

Ajaiyeoba EO, Falade CO, Fawole OI, Akinboye DO, Gbotosho GO, Bolaji OM, Ashidi JS, Abiodun OO, Osowole OS, Itiola OA, Oladepo O, Sowunmi A, Oduola AM. Efficacy of herbal remedies used by herbalists in Oyo State Nigeria for treatment of Plasmodium falciparum infections: a survey and an observation. Afr J Med Med Sci. 2004;33:115–119. [PubMed: 15565927]

111.

Omolo MO, Okinyo D, Ndiege IO, Lwande W, Hassanali A. Repellency of essential oils of some Kenyan plants against Anopheles gambiae. Phytochemistry. 2004;65:2797–2802. [PubMed: 15474566]

112.

Odalo JO, Omolo MO, Malebo H, Angira J, Njeru PM, Ndiege IO, Hassanali A. Repellency of essential oils of some plants from the Kenyan coast against Anopheles gambiae. Acta Trop. 2005;95:210–218. [PubMed: 16018957]

113.

Omolo MO, Okinyo D, Ndiege IO, Lwande W, Hassanali A. Fumigant toxicity of the essential oils of some African plants against Anopheles gambiae sensu stricto. Phytomedicine. 2005;12:241–246. [PubMed: 15830848]

114.

Kleinschmidt I, Omumbo J, Briët O, van de Giesen N, Sogoba N, Kumasenu Mensah N, Windmeijer P, Moussa M, Teuscher T. An empirical malaria distribution map for west Africa. Trop Med Int Health. 2001;6:779–786. [PubMed: 11679126]

115.

Ntoumi F, Djimde AA, Mbacham W, Egwang T. The importance and future of malaria research in Africa. Am J Trop Med Hyg. 2004;71:iv. [PubMed: 15331851]

Authors’ addresses: Florence N. Nantulya, Chemin du Joran 7, VD1260, Nyon, Switzerland, E-mail: moc.oohay@orewmikan. Jane F. Kengeya-Kayondo and Olumide A. T. Ogundahunsi, Special Program for Research and Training in Tropical Diseases, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland, E-mails: tni.ohw@odnoyakayegnek and tni.ohw@oisnuhadnugo.