Am. J. Trop. Med. Hyg., 76(1), 2007, pp. 7–11 Copyright © 2007 by The American Society of Tropical Medicine and Hygiene

EFFECT OF ARTEMISININ-BASED TREATMENT POLICY ON CONSUMPTION PATTERN OF ANTIMALARIALS OLUGBENGA A. MOKUOLU, EMMANUEL O. OKORO,* SUSAN O. AYETORO, AND AMOS A. ADEWARA Directorate of Clinical Services and Training, University of Ilorin Teaching Hospital, Ilorin, Nigeria; Committee for Safety and Efficacy of Medicines and Medical Devices, University of Ilorin Teaching Hospital, Ilorin, Nigeria; Department of Statistics, University of Ilorin, Ilorin, Nigeria

Abstract. The purpose of this study was to observe the effect of the 2004 national artemisinin-based malaria treatment policy on consumption pattern of antimalarials. The study was undertaken at the University of Ilorin Teaching Hospital (UITH), Nigeria. Prescription and sales data at our pharmacy outlets were gathered from January to December 2004 and compared with similar data for 2005 after policy introduction in January 2005. Total consumption of antimalarials in 2004 was 23,404 doses, made up of artemisinin-containing medications (ACMs; 18.5%); sulphadoxinepyrimethamine (SP; 7.1%); chloroquine (CQ; 72.85%); and quinine (QUI; 1.6%), compared with 26,383 doses in 2005, made up of ACMs (50.00%); SP (22.7%); CQ (27.3%); and QUI (0%). Z-tests indicate that these differences in proportions were significant (P < 0.001) for ACMs and SP (increased) and decreased for CQ and QUI. The comparative retail price per dose of these medications was in the order: ACMs > QUI > SP > CQ. These data show increased use of antimalarials, with ACMs overtaking CQ as the dominant antimalarial class purchased from the pharmacies operated by the hospital in the first year of policy implementation. This suggests that cost alone may not be the overriding determinant of specific antimalarial consumption. fee-for-service basis because of poorly developed nature of the lower levels of health care services in our catchment area, which is also poorly industrialized.9 Services are offered in two designated locations in a city (Ilorin) and two rural settings (Esie, 60 km east of Ilorin; Ihima, ∼360 km northeast of Ilorin). Available services at these locations were General Hospital wing, Ilorin (Medicine and subspecialties, Surgery and subspecialties, Pediatrics and Family Medicine); Maternity wing Ilorin (Obstetrics and Gynecology; and Neonatology); comprehensive health centers at Ihima and Esie, both dedicated to Primary Health Care. The majority of the population we serve are either low level civil servants, petty traders, or subsistent farmers. Most users of our facility have little or no formal education (∼56% illiteracy level) and live on a dollar or less per day.10–12 The few rich opt for either private clinics/hospitals or use the family executive care program of the hospital where charges are higher. Drug supply. The drug supply to the hospital is always through the Drug Revolving Fund (DRF) scheme, which is a management strategy to ensure that the majority of users of our services have access to a sustainable supply of safe, effective, and affordable drugs to meet their health care needs. This scheme was adopted to overcome the inability of public health facilities to meet their drug demands that usually results from limited budgetary allocation from government and high drug prices.13,14 The hospital central drugs store acquires needed drugs and monitor stock level. At critical levels, the DRF committee replenishes the stock through a competitive tendering process. Retail prices are set in such a way as to recover cost with a profit margin of ∼5%. Prices are fixed to make our drugs more competitive than are obtainable at our competitor private pharmacies and clinics/hospitals. The scheme is self-accounting and runs outside the main hospital account. Drug prescription is limited to doctors, without which the pharmacy does not dispense any medication, including all antimalarials. Data collection. The hospital operates a DRF scheme, and drugs are centrally supplied from the drug store located in General Hospital wing to each of the pharmacy outlets in the four service areas. Supplies are usually made monthly based on prescription pattern and sales data.

INTRODUCTION Malaria is the most common reason most individuals fall ill in Nigeria, and current figures suggest that at least one half of the estimated 130 million people living in the country will have one or more malaria attacks annually.1 Sadly, the increasing resistance of Plasmodium falciparum to widely available and cheap antimalarial drugs is making the treatment of this condition difficult. More recently, nationwide surveillance data1 on efficacy clearly showed that chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) are no longer viable therapeutic options for the effective treatment of malaria. Based on this information, and the increasingly devastating impact of malaria on public health, artemisinin-containing combination therapies (ACMs) were recommended in November 2004 and formally adopted nationally as first-line treatment of uncomplicated malaria in January 2005.1 Specifically, artemether-lumefantrine is the recommended ACM, but artesunate-amodiaquine and other ACMs are also available in the country. The problem, however, is that ACMs are expensive, costing far more than both CQ and SP combined. These concerns1–7 have prompted fears that given the essential drug nature of antimalarials, affordability could be inimical to effective policy implementation. In this center, however, the difficulty of treating malaria with older drugs prompted us to simultaneously adopt this policy in January 2005, and this report concerns its impact on consumption pattern of antimalarials. MATERIALS AND METHODS Setting. The University Teaching Hospital is located in central Nigeria, where the vegetation is Guinea Savannah. Malaria is endemic, transmission occurring all year round with upsurge in the rainy season of June to September.8 Our facility, although a medical school affiliated tertiary hospital, also offers primary and secondary health care services on a

* Address correspondence to Emmanuel O. Okoro, Department of Medicine, University of Ilorin, PMB 1515 Ilorin, Kwara State, Nigeria. E-mail: [email protected]

7

8

MOKUOLU AND OTHERS

Essentially, to observe the effect of introducing the 2004 national artemisinin-based malaria treatment policy on consumption pattern of antimalarial drugs, prescription and sales data were gathered monthly from January to December 2004 and compared with similar data for 2005 after policy introduction in January 2005. Data analysis. ␹2 test was used to test for association between years and the type of antimalarial drug groups consumed. Within each drug group, ␹2 test was also used to test the association between the years and the specific drugs consumed. Also, a Z-test was used to test for differences between the amounts of a particular drug group consumed as a proportion of the total antimalarial drugs used in each of the 2 years. Differences were considered statistically significant if P < 0.05 except as otherwise stated. RESULTS Between groups. The results summarized in Table 1 and Figure 1 show a significant association between drug groups consumed and years (␹2 ⳱ 11,171.71, df ⳱ 3, P < 0.001). Specifically, CQ was the dominant antimalarial consumed in 2004, whereas ACM was the dominant antimalarial type used in 2005, being 72.9% and 50.0%, respectively, of total antimalarial consumption in 2004 and 2005 (Figure 1). Z-test for proportion indicates that the quantity of ACMs used as a total of antimalarials consumed in 2005 (50.0%) was significantly (Z-value ⳱ 87.35, P < 0.001) higher than in 2004 (18.5%). Similar patterns held true for SP (22.7% versus 7.1%; Z-value ⳱ −37.88, P < 0.001), but was reversed for CQ (Z-value ⳱ 141.94, P < 0.001; i.e., consumption of CQ was lower in 2005 compared with 2004, being 72.85% versus 27.30% for 2004 and 2005 respectively). In contrast, the quantity of QUI consumed in 2005 was zero compared with 1.6% of total doses of antimalarial used in 2004, and these proportions were significantly different from each other (Z-value ⳱ 3.53; P ⱕ 0.001). Overall, the quantity of antimalarials consumed in 2005 increased by ∼13% of that of 2004 (Table 1). This is also

reflected in the comparative sizes of the pie charts shown in Figure 1. Within groups. 1) ACMS: The quantity of ACMs (drugs 1–9; Table 1) consumed in 2005 increased to 13,191 doses from 4,325 doses in 2004, representing a > 300% increase in use. This increase was across board except for artesunate plus mefloquine tablet (Artequine), which decreased significantly in 2005 compared with 2004. (Table 1). Of note, the largest increase in consumption of ACMs was in artemether + lumefantrine tab (Coartem) and in the use of artesunate injection (Table 1). Strikingly, in 2004, ACMs such as artemether + lumefantrine tab (Coartem) constituted 20.16% of ACMs consumed in that year (4,325 doses) and this increased to 25.30% of 13,191 doses of ACMs consumed in 2005. Of note, artemether + lumefantrine tablets (Coartem), which is the most expensive of the three artemisine combinations, was the most consumed in both years, with a > 380% increase in the quantity used in 2005 (Table 1). 2) SP: Although there was a significant increase in the use of SP as a total of antimalarials consumed in 2005 (Figure 1), this was largely because of increased consumption of the tablet form. Specifically, there was a significant increase (␹2 ⳱ 545, df ⳱ 1, P < 0.001) in the proportion of SP tablets consumed as opposed to SP syrup, which decreased significantly (93.46% versus 6.54% compared with 90.78% versus 9.22% for 2005 and 2004, respectively). 3) CQ: Despite overall reduction in CQ use in 2005 (Figure 1), the proportion of CQ injections used (Table 1) as a total of CQ consumed in 2005 increased significantly (␹2 = 4,526.6, df ⳱ 1, P < 0.001), while the use of tablets decreased significantly (Table 1; i.e., 81.94% versus 18.06 in 2005, with 58.94% versus 41.06% in 2004). 4) Quinine: The data contained in Table 1 and Figure 1 show that QUI powder was not used in both years, whereas no quinine tablets were consumed in 2005 versus 369 doses in 2004.

TABLE 1 Antimalarials consumption by year and purchase price per dose Statistics Drugs

2004 [n (%)]

2005 [n (%)]

z-value

P

Price/dose

Artesunate tablets × 8 Dihydro-artemisinin tablets × 8 Dihydro-artemisinin syr. (bottle) Artesunate syrup (bottle) Artesunate inj. (ampoules) Artesunate supp. Artesunate + amodiaquine (larimal) tab × 24 *Artether + lumefantrine tab (Coartem) × 24 Artesunate + mefloquine tab (artequine) × 6 Pyrimethamine + sulphadoxine tab × 3 Pyrimethamine + sulphadoxine (bottle) Chloroquine tablets × 1,000 Chloroquine injection × amp Quinine tablets × 500 Quinine powder Total (doses)

805 (3.44) 1,910 (8.16) 20 (0.088) 30 (0.13) 553 (2.36) 0 (0) 0 (0) 872 (3.73) 135 (0.58) 1,507 (6.44) 153 (0.65) 7,000 (29.91) 10,050 (42.94) 369 (1.58) 0 (0) 23,404

1,105 (4.19) 3,000 (11.37) 615 (2.33) 885 (3.35) 3,389 (12.84) 20 (0.08) 800 (3.03) 3,337 (12.65) 40 (0.15) 5,600 (21.23) 392 (1.49) 1,300 (4.93) 5,900 (22.36) 0 (0) 0 (0) 26,383

− 1.70 − 7.54 − 5.04 − 7.27 − 24.37 0.17 − 6.82 20.81 0.95 − 35.63 − 1.87 61.06 55.69 3.53 –

0.08 < 0.001* < 0.001* < 0.001* < 0.001* 0.86 < 0.001* < 0.001* 0.34 < 0.001* 0.06 < 0.001* < 0.001* < 0.001* –

N 300:00 N 390:00 N 475:00 N 540:00 N 270:00 N 880 N 620:00 N 935:00 N 800:00 N 20:00 N 82:00 N 15:00 N 4:20/ampoule N 420:00 N 250–350:00 –

Numbers in bracket are percentages of the total consumption for that year. National minimum wage is N 7,500, average family size is 6. * Indicates significant difference at P shown. N, Naira, ∼ 125 ⳱ 1 US dollar.

9

ARTEMISININ TREATMENT AND ANTIMALARIAL CONSUMPTION

DISCUSSION

FIGURE 1. Pie charts showing consumption pattern by drug group.

In interpreting the results shown in the preceding section, a number of issues must be clarified upfront. First, the data represent sales figure of all antimalarials at the pharmacy outlet operated by this hospital where all medication are dispensed only on prescription unlike the case in the wider community where chloroquine and SP can be purchased over the counter. Second, because of the tertiary and medical school affiliated nature of this center, there was a high level of awareness and the desirability to switch over to ACMs even before its formal adoption (see 2004 data in Tables 1 and 2). Consequently, and to that extent, prescription on which sales were based would seem skewed toward or based on implementation of the new policy. Nevertheless, these data showed a 3-fold upsurge in the use of ACMs over the 2004 figure. Effectively, ACMs replaced chloroquine and SP as the most commonly used antimalarial (Figure 1). These observations are probably an underestimate of actual trends as 1) the hospital remained closed throughout January 2005 caused by a strike action and 2) stocks were unavailable for some artemisinin derivatives: artesunate tablets, dihydro-artemisinin tablets; artesunate syrup; artesunate injection (ampoules); artesunate + amodiaquine (larimal) tablets for 2, 1, 1, 1, and 2 months, respectively, because of supply problems. These findings are encouraging and could suggest that for users of our facilities in the period under observation, affordability was less of a factor in the acceptability of ACMs as the preferred treatment of malaria, contrary to initial fears.1–7 On the strength of this finding and the retail prices (without subsidy) shown in Tables 1 and 2, these observations could indicate that the availability of ACMs is probably sustainable on the basis of the DRF scheme. This observation is intriguing within the context of Nigeria, where the majority of users of public health facilities such as ours either belong to the lowor middle-income groups,9–12 and there are huge price differentials between ACMs and the older classes of antimalarials (Table 2). Nevertheless, our data add to a growing body of evidence12,15–17 that shows that, in several communities in West Africa, users of government-operated health care facilities are willing to pay more if services available are considered important and effective.

TABLE 2 Comparative price (N) and annual expenditure by consumers Drugs

Price/dose

Total drug cost 2004

Total drug cost 2005

Artesunate tablets × 8 Dihydro-artemisinin tablets × 8 Dihydro-artemisinin syr. (bottle) Artesunate syrup (bottle) Artesunate inj. (ampoules) Artesunate supp. Artesunate + amodiaquine (larima) tab × 24 *Artether + lumefantrine tab (Coartem) × 24 Artesunate + mefloquine tab (Artequine) × 6 Pyrimethamine + sulphadoxine tab × 3 Pyrimethamine + sulphadoxine (bottle) Chloroquine tablets × 1,000 Chloroquine injection × amp Quinine tablets × 500 Quinine powder Total (cost)

N 300:00 N 390:00 N 475:00 N540:00 N 270:00 N 880 N 620:00 N 935:00 N 800:00 N 20:00 N 82:00 N 15:00 N 4:20/ampoule N 420:00 N 250–350:00 –

241,500 744,900 9,500 16,200 143,910 0 0 789,160 30,140 108,000 12,546 105,000 42,210 154,980 0 2,398,046

331,500 1,170,000 292,125 477,900 915,030 17,600 496,000 3,019,985 112,000 32,000 32,144 19,500 24,780 0 0 6,940,564

10

MOKUOLU AND OTHERS

Specifically, for the first time and to the best of our knowledge, these results confirm recent suspicion18–20 that some families living in areas of Africa with high malaria resistance to CQ and SP may be willing to pay more for the more effective artemisinin-based therapies, but this time at their full market value (Tables 1 and 2). Even more surprisingly, the most expensive of the three ACMs studied (artemetherlumefantrine) was the most consumed. Clearly this consumption pattern especially in 2004 followed the relative order of their effectiveness against CQ-resistant malaria in West Africa,1–3,5 thus reinforcing previous observations22 that, besides cost, effectiveness of treatment may be a major determinant of use of health care services in some parts of Nigeria. However, it is important to put these observations in perspective: 1) our data pertains to the first year of policy implementation only; 2) these results relates only to one tertiary center in the formal sector, 3) there was some experience in the use of ACMs as first-line treatment of uncomplicated malaria before adoption of the new policy, as indicated in Table 1. The latter probably reflects the increased awareness of the inadequacy of CQ and SP and the influence of promotional activities on prescribers.23 For these reasons, the generalization of our findings to other settings remains unknown. Apart from the foregoing, there are a number of other issues relevant to this discussion. First, although the preferential use of artemisinin derivatives alone compared with combination therapies (Table 1) in 2004 declined substantially and reversed in 2005, it nevertheless persists in 2005. Because this study was non-discriminating in stratifying who bought prescribed antimalarials in our pharmacies, this could suggest that cost remains an issue in the choice of antimalarials offered to some individuals. This view is reinforced by the preferential use of chloroquine injections over tablets (Table 1) and probably reflects the strong belief in the superior efficacy of injections over oral medications. The practice of initiating parenteral treatment in the presence of vomiting or food refusal, particularly in children, may have also contributed to this observation. In the light of the foregoing, the use of age-specific prepackaged ACMs could further reduce unit cost and improve access to vulnerable groups while at the same time discouraging the use of artemisinin monotherapy, which could trigger the development and spread of ACM-resistant malaria.23–25 For this latter to succeed, a global campaign to end the production of single artemisinin drugs would be needed. Second, use of artesunate injection (Table 1), which is usually reserved for the treatment of severe malaria, showed > 500% increased consumption rate over the 2004 figure. Concomitantly, quinine use was either scanty or non-existent in both years, thereby suggesting that artesunate injection may have virtually replaced quinine as the preferred treatment of severe malaria in this facility. Despite this observation and a recent report26 from Asia indicating that artesunate may be superior to quinine in saving lives in severe malaria, it is important to remember that, in Africa, quinine remains a recommended and rescue treatment of this life-threatening condition.1,5 Third, the apparent success of this policy implementation was associated with increased antimalarial consumption (Table 1; Figure 1). This was unexpected, especially because most of the increases were in ACMs and SP consumption (Figure 1). The exact reasons for this are not entirely clear

from this study. However, there are a number of plausible explanations for these observations: 1) increased public awareness of the ineffectiveness of chloroquine for malaria treatment and the new treatment policy from sustained public enlightenment by African Union and governments, national agencies, and other stakeholders; 2) unlike chloroquine, which is obtainable over the counter outside this hospital and can be used at home without prescription, ACMs were prescription-only medication in 2005 and remain so. Therefore, increased use of our facility for the sole purpose of accessing ACMs because of our favorable pricing policy over those of our competitors may have contributed to the observed upsurge; 3) our adoption of SP for intermittent preventive therapy (IPT) against malaria in pregnancy administered as directly observed therapy (DOT) in antenatal care in 2005 as part of the new policy may have resulted in the increased consumption of SP herein reported. Regardless of the foregoing, this finding may also indicate a possible failure of other intervention measures in malaria control strategy1,5,7,27 and certainly represents an increase in economic burden (Table 2). Global Fund and other developmental partners aim to provide cheap ACMs through subsidy,1,7,19 but this was still being expected at the time of these observations. It is too early to know whether such effort is sustainable or even desirable in the first place given past experience with subsidies.15–18 In this regard, it may be possible to further reduce direct cost to families by fine-tuning the existing policy. For example, the 2004 treatment guidelines is anchored on the national surveillance data on efficacy of CQ, SP, and two ACMs (artemether + lumefantrine and artesunate + amodiaquine) conducted in 2002 and 2004, respectively, in children < 5 years old with uncomplicated malaria. While many mathematical models1,6 predict with ∼95% certainty the cost-effectiveness of switching to ACMs in areas of high CQ and SP resistance, such as Nigeria, these predictions were often based on data in children and pregnant women. These two groups are particularly vulnerable to the adverse health consequences of uncomplicated malaria, which can rapidly progress and become fatal if not promptly and properly treated.2–5,25,28,29 This is not often so in non-pregnant adults and older children who usually possess some immunity against malaria in endemic areas of high transmission such as Nigeria.2,5,25 Consequently, to extrapolate treatment recommendations based on data in such groups to the larger population as the new policy seems to have done could trigger unnecessary drug cost, where cheaper alternatives may suffice.4 Therefore, efficacy and effectiveness studies are needed to define the appropriate drug treatment of uncomplicated malaria in the non-pregnant adult population. In summary, these data showed a leap in the consumption of ACMs as the preferred medication for the treatment of uncomplicated malaria in the first year of policy change. Considering the huge price differentials involved, this finding could suggest that drug cost alone may not be the dominant factor in specific antimalarial purchase and could signal that availability of ACMS is sustainable through the drug revolving fund scheme. Received February 2, 2006. Accepted for publication August 15, 2006.

ARTEMISININ TREATMENT AND ANTIMALARIAL CONSUMPTION

Acknowledgments: The authors thank our A. T. Orunmuyi, MBBS, for help in preparing the typescript. O.A.M. is a member of the training Sub Committee of the National Transition Committee on the 2004 artemisinin-based treatment policy of Nigeria since March 2005. A preliminary communication of part of our data was presented to Paediatrics Association of Nigeria in Jos, Nigeria in January 2006. This work is dedicated to the memory of Olukoye Ransome-Kuti, FWACP, and to Soludo Charles, PhD. The American Society of Tropical Medicine and Hygiene (ASTMH) assisted with publication expenses. Authors’ addresses: Olugbenga A. Mokuolu, Directorate of Clinical Services and Training, University of Ilorin Teaching Hospital, PMB 1459, Ilorin, Kwara State, Nigeria. Emmanuel O. Okoro, Department of Medicine, University of Ilorin, PMB 1515 Ilorin, Kwara State, Nigeria, E-mail: [email protected]. Susan O. Ayetoro, Committee for Safety and Efficacy of Medicines and Medical Devices, University of Ilorin Teaching Hospital, PMB 1459, Ilorin, Kwara State, Nigeria. Amos A. Adewara, Department of Statistics, University of Ilorin, PMB 1515, Ilorin, Kwara State, Nigeria. Disclaimer: No authors have any financial or other affiliations to any of the entities involved in the manufacturing or supply of antimalarial drugs.

REFERENCES 1. Federal Ministry of Health, 2004. National Antimalarial Treatment Policy. Abuja, Nigeria: Federal Ministry of Health. 2. Falade C, Makanga M, Premji Z, Ortmann CE, Stockmeyer M, de Palacios PI, 2005. Efficacy and safety of artemetherlumefantrine (Coartem ®) tablets (six-dose regimen) in African Infants and children with acute uncomplicated falciparum malaria. Trans Roy Soc Trop Med 99: 459–467. 3. Adjuik M, Aquamey P, Babiker A, Borrmann S, Brasseur P, Cisse M, Cobelens F, Diallo S, Faucher JF, Garner P, Gikunda S, Kremsner PG, Krishna S, Lell B, Loolpapit M, Matsiegui PB, Missinou MA, Musanza J, Ntoumi F, Olliaro P, Osimbo P, Rezbach P, Some E, Taylor WR, 2002. Amodiaquineartesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: A randomized multicentre trial. Lancet 359: 1365–1372. 4. Pitmang SL, Thatcher TD, Madaki JKA, Egah DZ, Fischer PR, 2005. Comparison of sulphadoxine-pyrimethamine with and without chloroquine for uncomplicated malaria in Nigeria. Am J Trop Med Hyg 721: 263–266. 5. Mutabingwa TM, Anthony D, Heller A, Hallet R, Ahmed J, Drakeley C, Greenwood, BM, 2005. Amodiaquine alone, amodiaquine + sulphadoxine-pyrimethamine, amodiaquine + artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomized effectiveness trials. Lancet 365: 1474–1480. 6. Coleman PG, Morel C, Shillcutt S, Goodman C, Mills AJ, 2004. A threshold analysis of the cost effectiveness of artemisininbased combination therapies in sub-Saharan Africa. Am J Trop Med 71 (Suppl): 196–204. 7. Whitty CJM, Allah R, Wiseman V, Ochola S, Nakyanzi-Mugisha MV, Vohhm B, Mwita M, Miaka C, Oloo A, Premji Z, Burgess C, Mutabingwa TK, 2004. Averting a malaria disaster in Africa; where does the buck stop? Bull WHO 82: 381–384. 8. Salako LAS, Ajayi FO, Sowunmi A, Walker O, 1990. Malaria in Nigeria: A revisit. Ann Trop Med Parasitol 84: 435–445. 9. Ologe FE, Okoro EO, Oyejola BA, 2006. Environmental noise levels in Nigeria a report. J Occupat Environl Hygiene 3: 19–21. 10. Okoro EO, Adeyemi MI, 1999. Physical stature of three groups of adolescent children in Ilorin metropolis. Nigerian Med Pract 37: 62–66. 11. Okoro EO, Adeyemi AD, Oyejola BA. Quality of diabetic care in Nigeria 2002. J Diabetes Complications 16: 159–164.

11

12. Okoro EO, Adewara AA, David AE, 2005. Quality of diabetic care in Nigeria a patient satisfaction survey. Diabetes Int. 13: 21–23. 13. Adenika FB, 1992. Concept of Essential Drugs and National Drug Policies. Adenika FB, ed. Essential Drugs Management. 1st edition. Ibadan, Nigeria: Shaneson C. I. Limited, 9–80. 14. Midala TAS, Lege–Oguntoynbo L, Mustapha A, Abdu-Aguye I, Bangudu AB, 1991. Preliminary reports on quality assurance testing of chloroquine tablets in northern Nigeria. West Afr J Pharmacol Drug Res 10: 25–31. 15. Martey JO, Djan S, Twum E, Browne EN, Opoku SA, 1995. Utilization of maternal health services in Ejisu district, Ghana. West Afr. Health. 14: 24–28. 16. Kanoute AC, 1998. Consumer power comes to Africa. Afr Health 20: 19–20. 17. Evarard M, 1998. Essential drugs for the poor and vulnerable. Afr Health 20: 22–23. 18. Wiseman V, Onwuejekwe O, Matovu F, Mutanbingwa TK, Whitty CJM, 2005. Differences in willingness to pay for artemisinin-based combinations or monotherapy: experiences from the united republic of Tanzania. Bull WHO 83: 845–852. 19. Onwujekwe O, 2004. Criterion and content validity of a novel structured haggling contingent valuation question format versus the bidding game and binary with follow-up format. Soc Sci Med 58: 525–537. 20. Onwujekwe O, Uzochukwu B, Shu E, Ibeh C, Okonkwo P, 2004. Is combination therapy for malaria based on user fees worthwhile and equitable to consumers? Assessment of cost and willingness to pay in South East Nigeria. Acta Trop 19: 101– 105. 21. Igun UA, 1987. Why we seek treatment here: Retail pharmacy and clinical practice in Maiduguri, Nigeria. Ann Borno 4: 203– 215. 22. Okoro EO, Davies AE, 2001. Sponsorship of education programmes in Nigerian Medical and Pharmacy Schools by pharmaceutical companies: Possible risk implications for public health. Ethics Med 17: 52–60. 23. Fehintola FA, Adedeji AA, Ganiyu AA, Tambo E, Salako BL, 2005. Efficacy of artesunate plus cotrimixazole and artesunatepyrimethamine-sulphadoxine combination in the treatment of Plasmodium hyperparasitaemia Niger. Del Med J 46: 83–87. 24. Von Seidlein L, Bojang K, Jones P, Jaffar S, Pinder M, Obaro S, Doherty T, Haywood M, Snounou G, Gemperli B, Gathmann I, Royce C, McAdam K, Greenwood B, 1998. A randomized controlled trial of artemether/ benflumetol, a new antimalarial, and pyrimethamine/sulphadoxine in the treatment of uncomplicated falciparum malaria in African children. Am J Trop Med Hyg 5815: 638–643. 25. Borrmann S, Adenike AA, Missinou MA, Binder RK, Issifou S, Schindler A, Matsiegui PB, Kun JF, Krishna S, Lell B, Kremsner PG, 2003. Short course artesunate treatment of uncomplicated Plasmodium falciparum malaria in Gabon. Antimicrob Agents Chemotherap 47: 901–904. 26. Dondrop A, Nosten F, Stepniewska K, Day N, White N, South East Asian Quinine Artesunate Trial (SEQUAMAT) Group, 2005. Artesunate versus quinine for treatment of severe falciparum malaria: a randomized trial. Lancet 366: 717–725. 27. Attaran A, Barnes KI, Curtis C, d’Alessandro U, Fanello CI, Galinski MR, Kokwaro G, Looaressuwan S, Makanga M, Mutabingwa TK, Talisuna A, Trape JF, Watkins WM, 2004. WHO, the global fund and medical malpractice in malaria treatment. Lancet 363: 237–240. 28. Menendez C, 1999. Priority areas of current research on malaria during pregnancy. Annals. Trop Med Parasit. 93: 571–574. 29. Parise ME, Lewis LS, Ayisi JG, Nahlen BL, Slutsker L, Muga R, Shariff SK, Hill J, Steketee RW, 2003. A rapid assessment approach for public health decision making related to the prevention of malaria during pregnancy. Bull WHO 18: 316–321.