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WSN 80 (2017) 116-142 EISSN 2392-2192

Efficacy of Rectal Artesunate on Parasitaemia and Febrile Condition of Children of , South-Western

O. A. Agbeyangi1, S. O. Sam-Wobo1,*, U. F. Ekpo1, O. A. Akinloye2,

and C. F. Mafiana3

1Parasitology Unit, Department of Biological Sc., University of Agriculture, Nigeria 2Department of Biochemistry, University of Agriculture, Abeokuta Nigeria 3Executive Secretary Office, National University Commission, Abuja, Nigeria

*E-mail address: [email protected]

ABSTRACT Efficacy of Rectal Artesunate on parasitaemia and febrile condition of children was assessed in 905 children below the age of 5 years. Grid systematic method was employed in selecting sixteen study centres from 8 Local Government Areas of Ogun State. Ethical approvals were obtained in addition to interactive sessions with parents of the children and PHCs medical practitioners. Body weight and temperature were taken and drug was administered at a dose of 5 to 10mg/kg of the body weight per rectum at 0 hour, 24 hours and 48 hours. Efficacy of treatment was monitored by analysing blood samples taken at 0 hour, 24 hours and 48 hours for Malaria Parasites Count (MPC/µl), parasitized red blood cells (PRBC). Data obtained were analyzed using SPSS version 20 to assess association with p-value of < 0.05. A significant (p < 0.05) difference was observed between malaria parasites prevalence at 0 hour, 24 hours and 48 hours. Also a baseline mean malaria parasite density (MPC/µl) of 3,320/μl was observed at 0 hour and a reduction in mean MPC/µl of 1,230/μl and 420/μl at 24 hours and 48 hours respectively with a significant (p < 0.05) difference between MPC/µl at 0 hour, 24 hours and 48 hours. Baseline mean parasitized red blood cells (PRBC) of 4.2 % was observed at 0 hour with reduction in mean PRBC of 2.4 % and 1.1 % at 24 and 48 hours respectively with a significant (p < 0.05) difference between PRBC at 0 hour, 24 hours and 48 hours. Fever Subsidence Ratio between 0 hour, 24 hours and 48 hours were 1.4:1.1. Rectal artesunate is highly effective and well tolerated antimalarial suppository for pre-referral and parenteral therapy. World Scientific News 80 (2017) 116-142

Keywords: Efficacy, Pre-Referral, Parasitaemia, Febrile Condition, Rectal Artesunates, Malaria, Children, Ogun State, South-Western Nigeria

1. INTRODUCTION

Malaria is a feverish illness caused by mosquito-borne unicellular obligate intracellular protozoan parasites of the genus Plasmodium. Malaria as a major causes of deaths in the tropical area of the world (WHO, 2012; Kotepui et al., 2014), Malaria is endemic throughout most of the tropics. Of the approximately 3.4 billion people worldwide who are exposed annually, 1.2 billion are at high risk; World Health Organization (WHO) states that more than 207 million developed symptomatic malaria in 2012 (WHO, 2012). P. falciparum is by a considerable margin the most important cause of morbidity and mortality in tropical countries. Malaria constitutes a serious public health problem in Nigeria and the most vulnerable groups being children aged zero to five years and pregnant women. Since malaria is a serious public health problem in under five year’s children, and is accompanied with vomiting which make it difficult for oral drug administration, World Health Organization (WHO) introduce artemisinin also known as Qinghaosu (Chinese) and its derivatives; are a group of drugs that possess the most rapid action of all current drugs against P. falciparum malaria. It comes in water soluble form (Artesunate) and fat soluble form (Artemether) that facilitate absorption across the rectal mucosa (Bar-Zeev and White, 2006). Artemisinin derivatives were recognised as having powerful antimalarial activity and a variety of formulations have since been developed and these drugs form the basis of current antimalarial treatment policy in most countries in the world. Rectal preparations have the advantage of being easy to administer in rural areas, therefore it is anticipated that rectal administration of an artemisinin derivative in remote settings might "buy time" by halting or slowing the progress of disease while a patient is being transported to a health-care facility equipped to provide definitive treatment (Bar-Zeev and White, 2006; TDR, 2008). Therefore, it can be administered by non-medical persons, especially in rural peripheral settings at different levels of health care (community or health facility), compare with oral, intravenous and intramuscular administration of drugs (TDR, 2008). Risk of mortality is usually highest within the first 48 h after onset of severe symptoms that is within one cycle of the blood stage infection. Many patients die either before reaching hospital or immediately thereafter (Dondorp et al., 2005). These deaths can be avoided by a single inexpensive artesunate suppository at the time of referral (Gomes et al., 2008). Rectal artesunate had been proved safe and efficacious for adults (Awad et al., 2003; Bar-Zeev and White 2006), in children with non severe infections from Africa (Krishna, et al., 2001), South East Asia (Pengsaa et al., 2005; Inthavilay et al., 2010), South America (Gomez-Landires, 1996), Papua New Guinea (Karunajeewa et al., 2003; 2006) and Nigeria (Sam-Wobo et al., 2012). Results from a variety of clinical studies have indicated that artesunate suppositories can be used for initial emergency and curative treatment in uncomplicated (Karunajeewa et al., 2003; Karunajeewa et al., 2004), moderate (Krishna et al., 2001), severe (Gomes et al.,

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2009), and cerebral malaria (Aceng et al., 2005). In light of these considerations, rectal administration of artesunate suppositories for the treatment of malaria has been accepted as active anti-malaria drug (Hinton et al., 2007; Karunajeewa et al., 2007).

2. MATERIALS AND METHODS Study Areas The study was conducted in Ogun State, Nigeria; a Tropical Rain Forest Zone, lies approximately between Longitude 2°31’ W and 4°31’ E, and Latitude 6°31’ S and 8° N, its bounded in the south partly by the Atlantic Ocean, and sharing common boundaries with Oyo, Osun, Ondo, States and Republic of (Plate 5).The state is made up of three Senatorial Zones i.e. Ogun Central, Ogun East and Ogun West) and four Geo-Political Zones (GPZs) i.e. -Awori, Egba, Ijebu and Remo) with five main ethnic groups namely, Egba, Ijebu, Egbado, Awori and Egun. The main occupations are Farming, Textile production (tie and dye), Fishing, Trading, Civil Servant, Public Servant and Pottering. It has an area of 16,980.55 Square Kilometres (km2) of the 196,000 km2 land area of the South-West Zone of the 192,803.07 km2 of the Southern Nigeria in overall land area of 937,052.16 km2 of Nigeria. It has a population of 3,751,140, (1,864,907 Males and 1,886,233 Females) (NPC, 2010).

Selection of Study Sites Grid Systematic Method was employed in selecting sixteen (16) study centres which comprised two Primary Health Centres (PHCs) from each eight Local Government Areas (LGA) namely, Ado-Odo-Ota (ADT), Imeko-Afon (IMA), (EWK), (ODD), Ijebu-East (IJE), Ijebu-North (IJN), (ODG) and Remo-North (RMN). GIS instrument was used to obtained co-ordinates of the PHCs and map was drawn using ArcGIS 9.3 software (Figure 1).

Consent and Ethical Approvals Ethical approval was obtained from Ethics Committee of Department of Biological Sciences, and Federal Medical Centre Idi-Aba Abeokuta, Ogun State, Nigeria. Permission for study was obtained from Ogun State Ministry of Health and Local Government Service Commission, Abeokuta Ogun State, Nigeria. A Certificate of approval was obtained from National Agency for Food and Drug Administration and Control (NAFDAC) for import permission for the Plasmotrim-50/200 mg (produced by Acino Pharma Ltd Dornacherstrasse 114/ch-4147 Aesch Switzerland) used for the study and multi-centre clinical trial permission to carry out the research.

Determination of Sample Size From the 2014 immunization data obtained from Ogun State Ministry of Health, 905 children were sampled (Table 1). This was calculated using formula by Kothari (2005).

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Figure 1. Map of Ogun State Showing the Selected LGAs and their PHCs Used for the Study.

Inclusion Criteria The inclusion signs/features for selecting children for this study are: • Children from 1 month to 5 years • Temperature ≥ 37.5 °C, • Feverish condition, • Nausea, • Repeated vomiting • Unable to eat or drink (or suck, in the case of infants). • General weakness • No history of watery stools, diarrhoea and anal disease.

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Blood Collection and Examination Pre-treatment blood samples were collected (0 hour) from each child that met the inclusion criteria and at 24 and 48 hours during treatment to determine Malaria Parasite Count (MPC) and Percent Parasitized Red Blood Cells (PPRBC as described by Flegg et al. (2013). Venous blood was collected from antecubital vein of the children at enrolment to provide blood for the haematological investigations. 2 ml of venous blood of the children was collected using sterile needle and syringes, as described by Carter and Lema (1993); Cheesbrough (2009) and WHO (2010). Blood collected was transferred immediately into a labeled Ethylene-Diamine-Tetra-Acetate Acid (EDTA) bottle and mixed gently by inverting the stopper tube several time to prevent blood from clotting and kept at temperature of 4-8 °C and transferred to laboratory within 2-3 days of collection (Cheesbrough, 2009). Examination of thin and thick film for parasites count was done as described by Cheesbrough (2005). The degree of parasitaemia was determined by counting parasite against white blood cells (WBC), to give the approximate number of the parasite per ml of blood (Epidi et al., 2008). Using oil immersion ×100 objective, WBC was counted in the thick film and at the same time the number of parasites (asexual) in each field was counted. The stained thin blood film was placed on microscope stage, and examined with x100 oil immersion objective lens. The number of parasitized RBC (excluding gametocytes) in at least 5 fields from thin blood film at 0, 24 and 48 hours respectively were counted

Data Analysis The obtained result from blood analysis and the questionnaire were entered in MS excel (MS Excel 2007) and analyzed using SPSS version 20 (IBM SPSS Incorporation). Frequencies and percentages were used to compare number of participants associated with a study variable. Averages and 95% confidence interval (CI) were used for summarizing of results. Pearson’s Chi-square test, Pearson’s R and Spearman correlation (r) were used to test for an association. A p-value of < 0.05 was regarded as significant association between the variables.

3. RESULT Demographic Data of Studied Group Of a total of 905 participated children, 52.0% (471/905) were male and 48.0% (434/905) were female, and 25.4% (230/905), 44.6% (404/905) and 29.9% (271/905) were between the age group 1-11 months, 12-35 months and 36-59 months respectively with means of 21±1.236 months, 21.7% (196/905), 45.5% (412/905), 25.5% (231/905) and 7.3% (66/905) children were between body weight (BW) group 1-9.9kg, 10-19.9kg, 20-29.9kg and ≥30kg respectively with means of 17.5±0.672kg (Figure 2). Pearson’s Chi-square analysis (χ2) of variance at 95% confidence interval (CI) showed that there was no significant difference in distribution of sex across the study area (p = 0.601). However, there was a significant difference in distribution of age and body weight across the study area (p = 0.010 and p = 0.002).

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Participated children N=905

Age Sex Body Weight Month(s) (Kg)

Male- N= 471 1-11- N=230 1-9.9- N=196 (52.0%) (25.4%) (21.7%)

Female- N=434 12-35- N=404 10-19.9- N=412 (48.0%) (44.6%) (45.5%)

36-59- N=271 20-29.9- N=231 (29.9%) (25.5%)

>30- N=66 (7.3%)

Figure 2. Distribution of Demographic Characteristics of the Participants in the Study Areas

Baseline Prevalence of Malaria Parasites before Treatment (0 Hour) and Reduction in Intensity during Treatment (24 And 48 Hours) Before treatment (0 hour), an overall baseline malaria parasites prevalence of 98.5 % (891/905) was observed among participated children. During 24 hours of treatment a reduction in intensity of malaria parasites was observed, 77.1% (687/891) of the children were still infected with malaria parasites. While during 48 hours of treatment, 50.2% (345/687) of the children were still infected with malaria parasites (Table 2) There was a significant (p = 0.002 and p = 0.001) difference between malaria parasites prevalence at 0 hour, 24 and 48 hours during treatment.

Cumulative Malaria Parasites Prevalence and Reduction in Intensity during Treatment (24 And 48 Hours) across the LGAs Result from Figure 3 showed cumulative prevalence and reduction in intensity across the LGAs revealed that children from Odeda (99.1%), Ado-Odo-Otta (99.1%), Remo-North

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(99.1%) and Ijebu-East (99.1%) were more infected when compare with other LGAs before treatment, while children from Imeko-Afon (97.3%, 107/110) were least infected with malaria parasites. During 24 and 48 hours of treatment, reduction in malaria parasites intensity observed across all the LGAs with more reduction observed in Ewekoro LGA (69.4%, 68/98 and 44.9%, 44/98). There was a significant (p = 0.022 and p = 0.014) difference between malaria parasites intensity at 0 hour, 24 and 48 hours during treatment across the LGAs.

Figure 3. Cumulative Malaria Parasites Prevalence and Reduction in Intensity during Treatment (24 And 48 Hours) across the Local Government Areas

Cumulative Malaria Parasites Prevalence and Reduction in Intensity during Treatment (24 And 48 Hours) across the Geo-Political Zones (GPZs) Result from Figure 4 showed cumulative prevalence and reduction in intensity across the GPZs. The highest baseline malaria parasites prevalence was observed in Ijebu GPZ (98.7%, 227/230) before treatment (0 hour). During 24 and 48 hours of treatment, cumulative highest reduction in malaria parasites intensity observed in Egba GPZ (74.4%, 154/207 and 46.8%, 72/154). There was a significant (p = 0.028 and p = 0.017) difference in malaria parasites intensity at 0 hour and 24 and 48 hours during treatment across the GPZs.

Cumulative Malaria Parasites Prevalence and Reduction in Intensity in relation to Sex, Age and Body Weight during Treatment (24 and 48 Hours) Result in Figure 5 on cumulative malaria parasites prevalence in relation to sex, age and body weight before treatment (0 hour) showed that 98.5% male and 98.4% female were

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infected before treatment. Reduction in intensity observed in both genders during 24 and 48 hours, with no significant (p = 0.287) difference in malaria parasites intensity among sexes. Age group 12-35 months were more infected before treatment (98.5%). More reduction was observed in children of age group 36-59 months (74.1%) and 1-11 months (47.9%) during 24 and 48 hours respectively with a significant (p = 0.034) difference in malaria parasites intensity among age groups. Children of body weight group 10-19.9kg were more infected before treatment (98.8%). And during treatment (24 and 48hours), reduction in malaria parasites intensity was observed in children of body weight group >30kg (72.5% and 42.1%) with a significant (p = 0.011) difference in malaria parasites intensity among body weight groups.

Figure 4. Cumulative Malaria Parasites Prevalence and Reduction in Intensity during Treatment (24 and 48 hours) across all the GPZs

Comparative Malaria Parasites Prevalence and Reduction in Intensity in Relation to Sex during Treatment (24 and 48 Hours) across the Local Government Areas Result from Figure 6 showed comparative malaria parasites prevalence and reduction in intensity in relation to sex across the LGAs, it revealed that male children were more infected with malaria parasites in Ewekoro (100%), Odeda (100%), Ado-Odo-Otta (100%), and Ijebu-

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North (100%) LGAs while female children were more infected Imeko-Afon (98.0%), Odogbolu (98.7%), Remo-North (100%) and Ijebu-East (100%) LGAs before treatment (0 hour). There was no significant (p = 0.143) difference in malaria parasites intensity among sexes. Reduction in malaria parasites intensity was observed during 24 hours of treatment, with more reduction among male and female children in Ijebu-East (67.8% and 76.3%) and Odogbolu (71.2% and 51.4%) LGAs respectively when compare with other LGAs. During 48 hours of treatment, more significant reduction was observed in malaria parasites intensity among male and female children in Ewekoro (41.5% and 42.6%) and Ijebu-North (50.7% and 41.2%) LGAs respectively when compare with other LGAs.

Figure 5. Cumulative Sex, Age and Body Weight in Relation to Malaria Parasites Prevalence and Reduction in Intensity during Treatment (24 And 48 Hours).

Comparative Malaria Parasites Prevalence and Reduction in Intensity in Relation to Age during Treatment (24 and 48 Hours) across the Local Government Areas Table 3 showed comparative malaria parasites prevalence and reduction in intensity in relation to age across the LGAs, children of age group 1-11 months were more infected with malaria parasites in Odeda (100%), Ado-Odo-Otta (100%), Ijebu-North (100%) and Ijebu- East (100%) LGAs and children of age group 12-35 months were more infected in Ewekoro (100%), Ado-Odo-Otta (100%) and Remo-North (100%) LGAs while children of age group 36-59 months were more infected in Odeda (100%), Odogbolu (100%), Remo-North (100%) and Ijebu-East (100%) LGAs before treatment (0 hour). There was a significant (p = 0.038) difference in malaria parasites prevalence among ages across the LGAs. During 24 hours of treatment, significant reduction in malaria parasites intensity among children of age group 1-11 months, 12-35 months and 36-59 months in Ijebu-East (60.9%),

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Odogbolu (62.5%) and Imeko-Afon (46.7%) LGAs respectively when compare with other LGAs. During 48 hours of treatment, more significant reduction in malaria parasites among children of age group 1-11 months, 12-35 months and 36-59 months observed in Odeda (34.8%), Odogbolu (37.5%) and Ewekoro (29.6%) LGAs respectively when compare with other LGAs.

Figure 6. Comparative Malaria Parasites Prevalence and Reduction in Intensity in Relation to Sex during Treatment (24 and 48 Hours) across the LGAs

Efficacy of Rectal Artesunate on Parasitaemia and Body Temparature among the Study Groups

Impact of Rectal Artesunate on Malaria Parasites Count per micro litre (MPC/µL) during 24 Hours and 48 Hours of Treatment across the LGAs Result from Table 4 on efficacy of rectal artesunate on parasitaemia showed that children had high baseline density of Malaria Parasites Count per micro litre (MPC/µl) before treatment (0 hour) with more children observed with moderate parasitaemia (1001-4999/µl) (57.3%, 518/905) and 1.6% (14/905) had no infection with mean of parasite density of 3,320/μl. There was a decrease in parasitaemia (MPC/µl) during 24 hours (PC24) of treatment, 22.9% (204/891) children presented no infection (0/µl) and more with low parasiteaemia (<1000/µl) (42.5%, 379/891) when compare with basiline parasitaemia at 0 hour. The mean parasite density was 1,230/μl. Parasite Reduction Ratio [PRR] between 0 hour and 24 hours was 4.4 (891/204). More significant decrease in parasitaemia (MPC/µl) was observed during 48 hours of treatment with 49.8% (342/687) children presented no infection (0/µl). The mean

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parasite density was 420/μl. PRR between 24 hours and 48 hours was 3.7 (891/240) and PRR between 0 hour and 48 hours was 1.4 (891/648). Pearson’s Chi-square (χ2) analysis showed that there was a significant (p = 0.001 and p = 0.000) reduction in baseline parasitaemia (MPC/µl) during 24 and 48 hours of treatment across the studied LGAs.

Impact of Rectal Artesunate on Percent Parasitized Red Blood Cells (PRBC) during 24 Hours and 48 Hours of Treatment across the LGAs More children with low (≤5%) and moderate (≤14.9) PRBC (64.2%, 580/905 and 23.1%, 209/905) was observed before treatment (0 hour) with mean of 4.2%. A decrease in PRBC was observed during treatment (24 hours) with 13.1% (117/891) and 4.4% (39/891) children still had moderate (≤14.9) and high/severe (≥15.0) PRBC respectively with mean of 2.4%. More significant decrease in PRBC was observed during 48 hours of treatment with 1.0% (7/687) children still had moderate (≤14.9) PRBC and no children presented high/severe (≥15.0) PRBC (Mean = 1.1%) (Table 5). There was a significant (p = 0.005 and p = 0.002) reduction in baseline PRBC during 24 and 48 hours of treatment across studied LGAs.

Impact of Rectal Artesunate on Body Temperature (0C) during 24 and 48 hours of Treatment across the LGAs Result from Table 6 on examination of body temperature revealed higher body temperature among children under study before treatment (0 hour), more children was observed with moderate body temperature group 37.5-38.4 °C (85.7%) and, 0.8% (7/905) had normal (36.5-37.4) body temperature. During 24 hours of treatment, more children presented normal body temperature (36.5-37.4 °C) (72.6%, 657/905). Also during 48hours, 88.6% (802/905) children presented normal body temperature (36.5-37.4 °C). Fever Subsidence Ratio (FSR) between 0 hour and 24 hours was 1.4 (905/664), while FSR between 0 hour and 48 hours was 1.1 (905/809). There was a significant (p = 0.004 and p = 0.001) reduction in baseline body temperature during 24 and 48 hours of treatment across the LGAs.

4. DISCUSSION AND CONCLUSIONS

There was an unequal representation of participants from the four GPZs may be due to rate of exposure to mosquitoe bites because male children played around than the females. Similar results were reported by Sam-Wobo et al. (2012) Mogaji et al. (2013) and Olasukanmi et al. (2013) among children in some LGAs of Ogun State. The high cumulative pre-treatment (0 hour) baseline prevalence of malaria parasites observed in under five year’s children in this study may be due to selection criteria used, since children with symptom of malaria disease and baseline body temperature ≥37.5°C or history of fever during the 24 hours before recruitment were recruited. And this study was conducted at the onset of raining season till the end of raining season (March-October, 2014) in the rural communities of Ogun State. This period has been marked as high malaria parasites transmission due to exposure to mosquitoe bite and other factors may also contribute to susceptibility (Agbolade et al., 2008). Earlier reports by Olasehinde et al. (2010), Adesola (2012) and Sam-Wobo et al. (2012) showed high prevalence of malaria parasites in other

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studied LGAs of Ogun State, while prevalence of malaria parasites obtained by Olasunkanmi et al. (2013) and Mogaji et al. (2013) in children of LGAs of Ogun State are lower than observed baseline prevalence. And also higher than results obtained on children from neighbouring states of Ogun State by Dada-Adegbole et al. (2013) and Ajayi et al. (2015) in . An overall difference in gender in relation to malaria parasites prevalence observed corresponding with sex in relation to malaria parasites prevalence reported in children of Ogun State by Adesola et al. (2012) and Sam-Wobo et al. (2012), while Mogaji et al. (2013) and Olasunkanmi et al. (2013) reported reverse sex-malaria parasites prevalence that female counterpart are more infected than male in children of Ogun State. In other parts of the country, reports from Oladehinde et al. (2012), Dada-Adegbola et al. (2013) and Okoli et al. (2013) also revealed that males harboured malaria parasites than females while Jonathan and Agbolade (2012) reported a reverse prevalence. However, no scientific evidence to prove that susceptibility to malaria is gender based (Okonko et al., 2012; Olasunkanmi et al., 2013). In other parts of Nigeria, similar prevalence had also been reported by Ekong et al. (2013) in Cross River State, Modi and Borke (2013) in Edo State and Okoli et al. (2013) in Jos, Plataeu State. Similar prevalence had also been reported in West Africa countries, Ghana (Adu-Gyasi et al., 2012), Cameroon (Takem et al., 2010; Achidi et al., 2012) and Cote dIvoire (Knoublanch et al., 2014; Hurlimann et al., 2014) and other parts of Africa (Alemu et al., 2014; Jean Claude et al., 2014), and as well as other parts of the world (Bhutta et al., 2014; Smitt and Whittaker, 2014). Post treatment reduction in intensity of parasitaemia observed in children across the LGAs was as a result of chemotherapeutic properties of rectal artesunate [Artemisia annua (Qinghaosu or the Sweet Wormwood)] in reducing the level of parasitaemia in children as described by Meier zu Biesen (2010). Since it contain artesunate which is the synthetic hemisuccinate ester of its active metabolite dihydroartemisinin (DHA) and this effectiveness had been reported in previous studies by Miller and Su (2011), Morris et al. (2011), Youyuo (2011) and Flegg et al. (2013). Similar overall post treatment reduction in intensity in relation to sex observed in this study had been reported by Morris et al. (2011), post treatment reduction in intensity in relation age and body weight indicated that rectal artesunate effectiveness is independent of age or body weight. This was corresponding with results obtained from previous study on rectal artesunate in children by Dondop et al. (2005) and Karunajeewa et al. (2006). The high baseline parasitaemia (MPC/µl) observed before treatment (0 hour) showed that children in rural communities of Ogun State harboured high parasitaemia and prone to malaria parasites transmission due to exposure to mosquitoe bites. This result was in line with results obtained by Adesola (2012), Sam-Wobo et al. (2012), Olasunkanmi et al. (2013) and Sam-Wobo and Asiwaju (2014) in under five years children of Ogun State. A significant drop in the level of baseline parasitaemia (MPC/µl) observed after treatment (24 hours) indicated that rectal artesunate is effective in reducing the level of parasitaemia within 12-24hours of insertion since it has potential for an intrarectal preparation across the rectal mucosa (Bar-Zeev and White, 2006). The increase in parasites clearance observed during 48 hours post treatment indicated that rectal artesunate can be instituted as parenteral therapy and this had also be reported by Nwani et al. (2004) in patients of health facility in Ihiala, in Anambra State, Nigeria that rectal artesunate is a suitable alternative therapy to parenteral antimalarias in the management

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of acute severe malaria in patients who cannot take the drug orally and are also living in places where it is difficult to have access to well-structured health facilities. Related reports had also been reported in other parts of the world in children treated with rectal artesunate (Dondorp et al., 2005; Bar-Zeev and White, 2006). Also the significant drop in PRBC during treatment (24 and 48hours) observed was in line with current results obtained by researchers on efficacy of rectal artesunate in children of Nigeria (Sam-Wobo et al., 2012), Ghana (Krishna, 2006; Agbenyega, 2008), Tanzania (Warsame et al., 2007), Zambia (Kaona and Tuba, 2005), and other parts of the world (Grobusch, 2009; Flegg et al., 2013). The efficacy of rectal artesunate may be as a result of its chemotherepeutic content artesunate which have shown to have superior reduction in parasitaemia in children than other parenteral antimalaria drugs used for malaria treatment (Hirji and Premji, 2011; Miller and Su, 2011; Morris et al., 2011; Flegg et al., 2013). However, a high baseline body temperature observed among children under study before treatment (0 hour) was a manifestation of febrile condition in children of rural communities of Ogun State due to high percent of malaria parasites harboured and this was in line with previous results obtained on febrile condition of children of Ogun State by Ukwaja et al. (2011), Olasunkanmi et al. (2013) and Sam-Wobo et al. (2012), and in other parts of Nigeria (Okoli et al., 2013; Erhabor et al., 2014; Ajayi et al., 2015). The reduction in febrile condition as a result of treatment with rectal artesunate and was in line with result obtained by Sam-Wobo et al. (2012) in children of Abeokuta treated with rectal artesunate. And this was related with results obtained by Agbenyega, (2008), Gomes et al. (2008) and Hendriksen et al. (2013).

References

[1] Aceng, J.R., Byarugaba, J.S. and Tumwine, J.K. 2005. Rectal Artemether versus Intravenous Quinine for the Treatment of Cerebral Malaria in Children in Uganda: Randomized Clinical Trial. British Medical Journal, 330(7487): 334-340. [2] Adesola, A.H. 2012. Challenges of Malaria Control in Peri-Urban Communities of High Endemicity. Research Journal of Environmental and Earth Sciences, 4(9): 844-849. [3] Adu-Gyasi, D., Adams, M., Amoako. S., Mahama, E., Nsoh, M., Amenga-Etego, S.B., Asante, K.P., Newton, S. and Owusu, S. 2012. Estimating Malaria Parasite Density: Assumed White Blood Cell Count of 10,000/µl of Blood is appropriate measure in Central Ghana. Malaria Journal, 11: 238. [4] Agbenyega, T. 2008. Efficacy and safety of rectal Artesunate in paediatric patients -a randomized controlled study (Ghana). TDR Annual Report. [5] Agbolade, J.M., Akintola, O.B., Agu, N.C., Raufu, T. and Johnson, O. 2008. Protection Practices against Mosquito among Students of a Tertiary Institution in Southwest Nigeria. World Applied Sciences Journal, 5(1): 25-28. [6] Ajayi, I.O., Afonne, C., Dada-Adegbola, H. and Falade, C.O. 2015. Prevalence of Asymptomatic Malaria and Intestinal Helminthiasis Co-infection among Children Living in Selected Rural Communities in Ibadan Nigeria. American Journal of Epidemiology and Infectious Disease, 3(1): 15-20.

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[7] Awad, M.I., Alkadru, A.M.Y., Behrens, R.H., Baraka, O.Z. and Eltayeb, I.B. 2003. Descriptive Study on the Efficacy and Safety of Artesunate Suppository in Combination with other Anti-Malarias in the Treatment of Severe Malaria in Sudan. American Journal of Tropical Medicine and Hygiene. 63: 153-158. [8] Bar-Zeev, N. and White, N.J. 2006. Evidence behind the WHO Guidelines: Hospital Care for Children: Efficacy and Safety of Artemisinin Derivatives in Children with Malaria. Journal of Tropical Pediatrics, 52(2): 78-82. [9] Carter, J.Y. and Lema, O.E. 1993. Practical Laboratory Manual for Health Centers in Eastern African. African Medical and Research Foundation, Nairobi, Kenya. 87-143. [10] Cheesbrough, M. 2009. Parasitological Tests. Part 1: District Laboratory Practice in Tropical Countries, 2nd ed. Cambridge: Cambridge University Press, pp. 178-309. [11] Dada-Adegbola, H.O., Oluwatoba, O.A. and Falade, C.O. 2013. Asymptomatic Malaria and Intestinal Helminth Co-Infection among Children in a Rural Community in Southwest Nigeria. MWJ, 4: 18 [12] Dondorp, A., Nosten, F., Stepniewska, K., Day, N. and White N.J. 2005. Artesunate versus Quinine for Treatment of Severe Malaria: A Randomized Trial. Lancet. 366: 717-725. [13] Ekong, U., Oyo-Ita, A., Odey, F., Effa, E., Esu, E., Oduwole, O., Chibuzor, M. and Meremikwu, M. 2013. Management of Uncomplicated Malaria in Under-fives in Private and Public Health Facilities in South-Eastern Nigeria: A Clinical Audit of Current Practices. Malaria Research and Treatment, 6. [14] Erhabor, O., Mohammad, H.J., Ahmed, H.M. andEzimah, A.C.U. 2014. Effect of Plasmodium Parasitaemia on some Haematological Parameters in Children Living in Sokoto, North Western, Nigeria. International Journal of Clinical Medicine Research, 1(2): 57-64. [15] Flegg, J.A., Guérin, P.J., Nosten, F., Ashley, E.A., Phyo, A.P., Dondorp, A.M., Fairhurst, R.M., Socheat, D., Borrmann, S., Björkman, A., Mårtensson, A., Mayxay, M., Newton, P.N., Bethell, D., Se, Y., Noedl, H., Diakite, M., Djimde, A.A., Hien, T.T. White, N. J. and Stepniewska, K. 2013. Optimal Sampling Designs for Estimation of P. falciparum Clearance Rates in Patients Treated with Artemisinin Derivatives. Malaria Journal, 12: 411. [16] Gomes, M., Ribeiro, I., Warsame, M., Karunajeewa, H. and Petzold, M. 2008. Rectal Artemisinins for Malaria: A Review of Efficacy and Safety from Individual Patient Data in Clinical Studies. Bio Medical Central, 8: 39 [17] Gomes, M.F., Faiz, M.A. and Gyapong G.O. 2009. Pre-Referral Rectal Artesunate to Prevent Death and Disability in Severe Malaria: A Placebo-Controlled Trial. Lancet, 373: 557-566. [18] Gomez, L.E.A. 1996. Efficacy of Artesunate Suppository Followed by Oral Mefloquine in the Treatment of Severe Falciparum Malaria in Endemic Areas where Resistance to Chloroquine Exists in Ecuador. Japanese Journal of Tropical Medicine and Hygine, 24(suppl 1): 17-24.

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[19] Grobusch, M. 2009. Early Rectal Artesunate Administration: A Life-Saver in Remote Areas. Ingental connect Future Microbiology, 4: 397-400 [20] Hendriksen, I.C., Mtove, G., Kent, A., Gesase, S., Reyburn, H. and Lemnge, M.M. 2013. Population Pharmacokinetics of Intramuscular Artesunate in African Children with Severemalaria: Implications for a Practical Dosing Regimen. Clinical and Pharmacological Theory, 93(5): 443-50. [21] Hinton, R.L., Auwun, A., Pongua, G., Davis, T.M.E, Karunajeewa, H.A. and Reeder, J.C. 2007. Caregivers’ Acceptance of Using Artesunate Suppositories for Treating Childhood Malaria in Papua New Guinea. American Journal of Tropical Medicine and Hygiene, 76: 634-640. [22] Hirji, K.F., and Premji, Z.G. 2011. Pre-Referral Rectal Artesunate in Severe Malaria: Flawed Trial. Trials, 12: 188. [23] Hsu, E. 2010. Qing hao… (Herbal Artemisiae annuae) in the Chinese Materia Medica, in Elisabeth Hsu and Stephen Harris, eds., Plants, Health and Healing: On the Interface of Ethnobotany and Medical Anthropology, Berghahan Books, Oxford and New York, 83-120. [24] Hürlimann, E., Houngbedji, C.A., N’Dri, P.B., Bänninger, D., Coulibaly, J.T., Yap, P., Silué, K.D., N’Goran, E.K., Raso, G. and Utzinger, J. 2014. Effect of Deworming on School-Aged Children’s Physical Fitness, Cognition and Clinical Parameters in a Malaria-Helminth Co-Endemic Area of Côte d’Ivoire. BMC Infectious Diseases, 14: 411. [25] Inthavilay, S., Franchard, T., Meimei, Y., Ashley, E.A. and Barennes, H. 2010. Knowledge and Acceptability of the Rectal Treatment Route in Laos and Its Application for Pre-Referral Emergency Malaria Treatment. Malaria Journal, 9: 342. [26] Jonathan, K.A. and Agbolade O.M. 2012. Plasmodium and Loa Loa Infections among Secondary School Teachers and Students, and Ante-Natal Out-Patients in Area, South-Western Nigeria. International Research Journal of Microbiology 3(7): 253-257. [27] Kaona, F. A. and Tuba, M. 2005. A Qualitative Study to Identify Community Structures for Management of Severe Malaria: A Basis for Introducing Rectal Artesunate in the Under Five Years Children in Nakonde District of Zambia. BMC Public Health, 5(1): 28. [28] Karunajeewa, H.A., Ilett, K.F., Dufall, K., Kemiki, A., Bockarie, M., Alpers, M.P., Barrett, P.H., Vicini, P. and Davis T.M. 2004. Disposition of Artesunate and DihydroArtemisinin after Administration of Artesunate Suppositories in Children from Papua New Guinea with Uncomplicated Malaria. Antimicrobial Agent of Chemotherapy, 48: 2966-2972. [29] Karunajeewa, H.A., Kemiki, A., Alpers, M.P., Lorry, K., Batty, K.T., Ilett, K.F., and Davis T.M. 2003. Safety and Therapeutic Efficacy of Artesunate Suppositories for Treatment of Malaria in Children in Papua New Guinea. Pediatric Infectious Diseases Journal, 22: 251-256.

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[30] Karunajeewa, H.A., Manninig, L., Mueller, I.., Ilett, K.F. and Davis, T.M.E. 2007. Rectal Administration of Artemisinin Derivatives for the Treatment of Malaria. JAMA, 297: 2381-2390. [31] Karunajeewa, H.A., Reeder, J., Lorry, K., Dabod, E., Hamzah, J., PAge-Sharp, M., Chiswell, G.M., Ilett, K.F. and Davis, T.M. 2006. Artesunate Suppositories versus Intramuscular Artemether for Treatment of Severe Malaria in Children in Papua New Guinea. Antimicrobial Agents Chemotherapy, 50: 968-974. [32] Kassile, T. 2012. Prevention and Management of Malaria in Under-Five Children in Tanzania: A Review. Tanzania Journal of Health Research, 14: 14. [33] Knoblauch, A.M, Mirko, S., Winkler, C.A., Mark, J.D., Milka, O., Raoul, M.Y., Pokou, A.Y. and Jürg, U. 2014. The Epidemiology of Malaria and Anaemia in the Bonikro Mining Area, Central Côte d’Ivoire. Malaria Journal, 13: 194. [34] Kotepui, M., Bhukdee, P., Nuoil, P., Chaowanee, C. and Suwit, D. 2014. Effect of Malarial Infection on Haematological Parameters in Population near Thailand-Myanmar Border. Malaria Journal, 13: 218. [35] Kothari, C.R. 2005. Research Methodology: Methods and Techniques, Second Edition, New Age International Publishers, Washington DC. [36] Krishna, S., Planche, T., Agbenyega, T., Woodrow, C., Agranoff, D., Bedu-Addo, G., Owusu-Ofori, A., Appiah, J., Ramanathan, S., Mansor, S., Navaratnam, V. 2001. Bioavailability and preliminary clinical efficacy of intrarectal Artesunate in Ghanaian children with moderate malaria. Antimicrobial Agents Chemotherapy. 45: 509-516. [37] Meier zu Biesen, C. 2010. The Rise to Prominence of Artemisia annua L.-The Transformation of a Chinese Plant to a Global Pharmaceutical. African Sociological Review, 14(2): 24-46. [38] Miller, L.H. and Su, X. 2011. Artemisinin: Discovery from the Chinese Herbal Garden. Cell, 146: 855-858. [39] Mogaji, H.O., Adeniran, A.A., Awoyale, A.K., Oluwole, A.S. and Ekpo, U.F. 2013. Baseline Study of Malaria Infection in Four Rural Communities of Ogun State. Asian Journal of Biological Science, 6(6): 300-305. [40] Mordi, R.M., and Borke, M.E. 2013. The Prevalence of Malaria in Edo State Nigeria Journal of Microbiology Research, 1(2): 18-23. [41] Morris, C.A., Stephan, D., Borghini-Fuhrer, I., Jung, D., Chang-Sik, S. and Lawrence, F. 2011. Review of the Clinical Pharmacokinetics of Artesunate and Its Active Metabolite Dihydro Artemisinin Following Intravenous, Intramuscular, Oral or Rectal Administration. Malaria Journal, 10: 263. [42] Nwani, P.O., Unekwe, P.C., Oguejiofor, O.C. 2004. The Efficacy of Artesunate Suppositories [Plasmotrim 200 Rectocap (R)] in the Treatment of Adults with Acute Malaria. Journal of Medical Research and Technology, 1(2): 42-49. [43] Okoli, C. A. Okolo, S. N., Collins. J. C. 2013. P. falciparum Infection among Neonates in the North Central Region of Nigeria. Journal of Infectious Diseases of Developing Countries, 7(5): 265-371.

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[44] Okonko, I.O., Adejuwon, A.O., Okerentungba, P.O. and Frank-Peterside, N. 2012. P. falciparum and HIV- 1/2 Coinfection among Children Presenting at the Out-Patient Clinic of Oni Memorial Children Hospital in Ibadan, Southwestern Nigeria. Nature and Science, 10(8): 94-100. [45] Olasehinde, G., Ajayi, A.A., Taiwo, S.O., Adekeye, B.T. and Adeyeba, O.A. 2010. Prevalence and Management of falciparum Malaria among Infants and Children in Ota, Ogun State, South Western Nigeria. African Journal Clinical Experiment in Microbiology, 11(3): 199-163. [46] Olasunkanmi, O.I., Akingbade, O.A., Akinjinmi, A.A., Okerentugba, P.O., Onajobi, I.B.and Okonko, I.O. 2013. Prevalence of Malaria Plasmodium among Children in Abeokuta, Nigeria. Academic Arena, 5(10): 44-47 [47] Rutebemberwa, E., Pariyo, G., Peterson, S., Tomson, G. and Kallander, K. 2009. Utilization of Public or Private Health Care Providers by Febrile Children after User Fee Removal in Uganda. Malaria Journal, 8. [48] Sam-Wobo, S.O. and Asiwaju R.T. 2014. Status of falciparum Malaria in Some Granite Mining Communities of Odeda Local Government Area, Ogun State, Nigeria. Research Journal in Engineering and Applied Sciences, 3(1): 34-37. [49] Sam-Wobo, S.O., Agbeyangi, O.A., Ekpo, U.F. Akinloye, O.A., Mafiana, C.F. and Adeleke, M.A. 2012. Rectal Artesunate, their Utilization and Parental Perception in the Management of Malaria in Children from Abeokuta, South-Western Nigeria. Journal of Vector-Borne and Zoonotic Diseases, 12(2): 151-155. [50] Simba, D.O., Kakoko, D.C., Warsame, M., Premji, Z., Gomes, M.F., Tomson, G. and Johansson E. 2010. Understanding Caretakers’ Dilemma in Deciding Whether or Not to Adhere with Referral Advice after Pre-Referral Treatment with Rectal Artesunate. Malaria Journal, 9: 123. [51] Takem, Ebako, N., Achidi, E.M. and Ndumbe, P.M. 2010. An Update of Malaria Infection and Anaemia in Adults in Buea, Cameroon, BMC Research Notes, 3: 121. [52] TDR, 2008. Efficacy and safety of rectal Artesunate as emergency treatment in children with severe malaria who are unable to take oral medication, and development of appropriate strategies for its use. Annual report. [53] Ukwaja, K.N., Aina, O.B. and Talabi. A. A. 2011. Clinical Overlap Between Malaria and Pneumonia: Can Malaria Rapid Diagnostic Test Play a Role? Journal of Infection of Developing Countries, 5(3): 199-203. [54] Warsame, M., Kimbute, O., Machinda, Z., Ruddy, P., Melkisedick, M., Peto, T., Ribeiro, I., Kitua, A., Tomson, G. and Gomes, M. 2007. Recognition, Perceptions and Treatment Practices for Severe Malaria in Rural Tanzania: Implications for Accessing Rectal Artesunate as a Pre-Referral. Plos One, 2: e149. [55] World Health Organization. 2001a. Tropical Disease Research, Progress 1999-2000. Special Programme for Research and Training in Tropical Diseases, 15th programme report. TDR/GEN/01.5.

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[56] World Health Organization. 2007. Artemisinin-Based Suppositories in the Management of Severe Malaria (Rectal Artemisinin). Report of an Informal Consultation, Global malaria Programme, Geneva. WHO/H.T.M/MAL, 1118: 1-16. [57] World Health Organization. 2010. Basic Malaria Microscopy. Part 1. Learner’s Guide. 2nd ed. Geneva: WHO; 2010. [58] World Health Organization. 2012. WHO handbook for guideline development. (http://www.who.int/about/licensing/copyright_form/en/index.html)

( Received 17 June 2017; accepted 15 July 2017 )

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Table 1. 2014 Immunization Data of under Five Years Children, Calculated Sample Size, Parents of ≤5 Years Treated, Interviewed Health Workers and Interviewed Patent Medicine Vendors

Pop. of <5 Local Pop. of Years Sample ≤5 Years Selected PHCs Governments Communities Children in Size Treated PHCs

Alapoti. 19023 3804 74 130 Ado-Odo Ota

Ado-odo 1. 23888 4778 56

Imeko. 18577 3715 62 110 Imeko-Afon

Ilara. 13033 2607 48

Itori. 9735 1947 50 Ewekoro 100 Elere-Adubi. 7815 1563 50

Ilugun. 16173 3235 64 Odeda 110 Alabata. 12889 2578 46

Odoladalepo 15696 3139 56 Ijebu-East 110 Tonigbo. 8080 1616 54

Obada. 39273 7855 64 Ijebu North 120 Ibipe. 32500 6500 56

Ososa. 14868 2974 52 Odogbolu 115 Mobalufon. 25163 5032 63

Ipara 8809 1762 59 Remo-North 110 Ajana 3856 771 51

Total 16 269378 52876 905 905

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Table 2. Overall Baseline Malaria Parasites Prevalence and Reduction in Intensity during Treatment (24 And 48 Hours).

Parameters F (%)

NE 905 Prevalence 0 hour NI% 891(98.5)

NE 891 24 hours (p = 0.002) NI% 687(77.1) Intensity NE 687 48 hours (p = 0.001) NI% 345(50.2)

F-Frequency, NE-Number examine, and NI-Number infected.

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Table 3. Comparative Malaria Parasites Prevalence and Reduction in Intensity in Relation to Age during Treatment (24 and 48 Hours) across LGAs

Age-Malaria Parasites Age-Malaria Parasites Prevalence Reduction in Intensity

0 hour (%) 24 hours (%) 48 hours (%)

Parameters

35 Month(s) 35 Month(s) 59 Month(s) 35 Month(s) 59 Month(s) 35 Month(s) 59

11 Month(s) 11 Month(s) 11 Month(s) 11

------

- - -

1 1 1

12 36 12 36 12 36

75

100

96.4 96.3 64.4 51.9 39.3 51.1 29.6

EWK

98

100 100

ODD

69.6 82.4 77.8 34.8 47.1 52.8

IMA

97.1 98.3 93.8 74.3 74.6 46.7 48.6 47.5 31.3

100 100

ADT

97.4 75.9 77.9 73.7 58.6 52.4 55.3

= 0.038) =

LGAs

p

(

95

100

ODG

97.8 78.3 62.5 62.1 56.5 37.5 51.7

1

100 100

94.4 72.2 81.8 81. 38.9 58.2 62.2

RMN

75 75

IJN

100

98.1 87.5 82.7 39.3 48.1 48.4

IJE

100 100

97.4 60.9 76.9 85.4 43.5 43.6 58.3

EWK-Ewekoro, ODD-Odeda, IMA-Imeko-Afon, ADT-Ado-Odo-Ota, ODG-Odogbolu, RMN-Remo-North, IJN-Ijebu-North and IJE-Ijebu-East

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Table 4. Impact of Rectal Artesunate on MPC/µL during 24 Hours and 48 Hours of Treatment across the LGAs

Local Government Areas TOTAL Parameter EWK ODD IMA ADT ODG RMN IJN IJE F (%)

F (%) F (%) F (%) F (%) F (%) F (%) F (%) F (%)

MPC/µL (Parasitaemia) 0 Hour

No Infection (0)

(1.7)

2(2.0) 1(0.9) 3(2.7) 1(0.8) 3(2.6) 1(1.8) 2 1(0.9)

14(1.6)

Low (<1000)

9(8.2)

44(44.0) 17(15.5) 41(37.3) 39(30.0) 41(35.6) 25(20.8) 18(16.4)

234(25.9)

Moderate (1001-

4999)

40(40.0) 81(73.6) 48(43.6) 64(49.2) 52(45.2) 83(74.5) 76(63.3) 75(68.2)

519(57.3)

High/Severe

(≥5000)

19(6.9)

14(14.0) 11(10.0) 18(16.4) 26(20.0) 14(12.7) 17(14.2) 16(14.5) 138(15.2)

MPC/µL (Parasitaemia) 24 Hours p = 0.001

No Infection (0)

30(30.6) 23(21.1) 27(25.2) 29(22.5) 30(26.8) 20(18.4) 22(18.6) 23(21.1)

204(22.9)

)

Low (<1000)

35(35.7) 45(41.3) 45(42.1) 50(38.8 43(38.4) 54(49.5) 62(52.6) 45(41.3)

379(42.5)

Moderate (1001-

4999)

24(24.5) 37(33.9) 25(22.4) 39(30.2) 30(26.8) 31(28.4) 27(22.9) 34(31.2)

247(27.7)

High/Severe

(≥5000) 9(8.0

9(9.2) 4(3.7) 4(3.7) 7(5.9) 7(6.4)

10(9.3) 11(8.5) 61(6.9)

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MPC/µl (Parasitaemia) 48 Hours p = 0.000

No Infection (0)

36(52.9) 46(53.4) 41(51.3) 48(48.0) 37(45.1) 40(44.9) 51(53.1) 43(50.0)

342(49.8)

Low (<1000) 2.6)

26(38.2) 28(3 35(43.8) 46(46.0) 45(54.9) 36(40.5) 45(46.9) 32(37.2)

293(41.7)

Moderate (1001- 0(0)

4999) 0(0)

6(8.8) 4(5.0) 4(4.0)

49(7.1)

12(14.0) 13(14.6) 10(11.6)

High/Severe

0(0) 0(0) 0(0) 0(0) 0(0)

(≥5000) 0(0)0

2(2.0) 1(1.2) 3(0.4)

F- Frequency, EWK-Ewekoro, ODD-Odeda, IMA-Imeko-Afon, ADT-Ado-Odo-Ota, ODG-Odogbolu, RMN-Remo-North, IJN-Ijebu-North and IJE-Ijebu-East.

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Table 5. Impact of Rectal Artesunate on PRBC during 24 and 48 hours of Treatment across the LGAs.

Local Government Areas

TOTAL Parameter EWK ODD IMA ADT ODG RMN IJN IJE F (%)

F (%) F (%) F (%) F (%) F (%) F (%) F (%) F (%)

PPRBC (%) 0 Hour

No Infection (0)

2(2.0) 1(0.9) 3(2.7) 1(0.8) 3(2.6) 1(1.8) 2(1.7) 1(0.9)

14(1.6)

Low (≤5)

67(67.0) 73(66.4) 65(59.1) 84(64.6) 70(60.9) 69(62.7) 75(62.5) 77(70.0)

580(64.2)

Moderate (≤14.9)

21(20.0) 25(22.7) 29(26.4) 30(23.1) 25(21.7) 28(25.5) 29(24.2) 22(20.0)

209(23.1)

High/Severe

(≥15.0) 10.0)

10(9.1)

10(10.0) 11(10.0) 13(11.8) 15(11.5) 17(14.8) 11( 14(11.7) 101(11.1)

PPRBC (%) 24 Hour p = 0.005

No Infection (0)

30(30.6) 23(21.1) 27(25.2) 29(22.5) 30(26.8) 20(18.4) 22(18.6) 23(21.1)

204(22.9)

)

Low (≤5)

49(40.0) 72(66.1) 60(56.1) 73(56.6) 62(55.4) 69(63.3) 73(60.9) 73(67.0)

531(59.6

Moderate (≤14.9)

10(9.2)

14(14.3) 11(10.1) 17(15.9) 18(14.0) 13(11.6) 16(14.7) 18(15.3)

117(13.1)

High/Severe

(≥15.0)

5(5.1) 3(2.7) 3(2.8) 9(6.9) 7(6.2) 4(3.6) 5(4.2) 3(2.7) 39(4.4)

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PPRBC (%) 48 Hour p = 0.002

No Infection (0)

36(52.9) 46(53.4) 41(51.3) 48(48.0) 37(45.1) 40(44.9) 51(53.1) 43(50.0)

342(49.8)

Low (≤5)

32(47.1) 40(46.6) 39(48.7) 51(51.0) 45(54.9) 45(50.6) 45(46.9) 41(47.7)

338(49.2)

Moderate (≤14.9)

0(0) 0(0) 0(0) 0(0) 0(0)

1(1.0) 4(4.5) 2(2.3) 7(1.0)

High/Severe

0)

0( 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) (≥15.0) 0(0)

F- Frequency, EWK-Ewekoro, ODD-Odeda, IMA-Imeko-Afon, ADT-Ado-Odo-Ota, ODG-Odogbolu, RMN-Remo-North, IJN-Ijebu-North and IJE-Ijebu-East.

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Table 6. Impact of Rectal Artesunate on Body Temperature (°C) during 24 and 48 hours of Treatment across the LGAs

Local Government Areas

TOTAL Parameters EWK ODD IMA ADT ODG RMN IJN IJE F (%)

F (%) F (%) F (%) F (%) F (%) F (%) F (%) F (%)

Body Temperature ( °C) 0 Hour

Low

(0)

0 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) 0(0)

(35.5-36.4) 0(0)

Normal

0(0) 0(0)

(36.5-37.4) 0(0)

1(1.0) 1(0.8) 1(0.9) 2(1.7) 2(1.8) 7(0.8)

Moderate

(37.5-38.4)

81(81.0) 94(85.5) 94(85.5) 99(90.0) 88(80.0)

104(80.0) 108(93.9) 108(90.0) 776(85.7)

High

(>38.5)

6(14.5)

7(6.1)

10(9.1) 10(8.3)

18(18.0) 16(14.5) 1 25(19.2) 20(18.2) 122(13.5)

Body Temperature ( °C) 24 Hours p = 0.004

Low 0(0)

(35.5-36.4) 0(0)

3(3.0) 1(0.9) 3(2.3) 1(0.9) 1(0.9) 1(0.8)

10(1.1)

Normal

(36.5-37.4)

70(70.0) 78(70.9) 64(58.2) 91(70.0) 90(78.2) 85(77.3) 97(80.8) 82(74.5)

657(72.6)

Moderate

(37.5-38.4)

27(27.0) 31(28.2) 44(40.0) 35(26.9) 23(20.0) 24(21.8) 20(16.7) 28(25.5) 232(25.6)

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High

0(0) 0(0)

(>38.5) 0(0)

1(0.9) 1(0.9) 1(0.8) 1(0.9) 2(1.6) 6(0.7)

Body Temperature ( °C) 48 Hours p = 0.001

Low (

35.5-36.4) 0(0)

3(3.0) 1(0.9) 3(2.7) 1(0.9) 2(1.7) 2(1.8)

31(3.4)

19(14.6)

Normal

36.5-37.4)

85(85.0) 99(90.0) 95(73.1) 99(90.0)

104(94.6) 105(91.3) 105(95.5) 110(91.7) 802(88.6)

Moderate (37.5- .6)

38.4)

4(3.6) 8(7.3) 9(7.8) 4(3.6) 8(6 7(6.4)

67(7.4)

12(12.0) 15(11.4)

High (>38.5)

0(0) 0(0) 0(0) 0(0)

1(0.9) 1(0.8) 1(0.9) 2(1.8) 5(0.6)

F- Frequency, EWK-Ewekoro, ODD-Odeda, IMA-Imeko-Afon, ADT-Ado-Odo-Ota, ODG-Odogbolu, RMN-Remo-North, IJN-Ijebu-North and IJE-Ijebu-East.

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