Rectal Artesunates,Their Utilization,and Parental Perception in the Management of Malaria in Children from Abeokuta,Southwestern Nigeria

Abstract

Utilization, efficacy, perception, and acceptability of rectal artesunates for treatment of malaria were assessed in 264 children below 5 years attending two tertiary health facilities in Abeokuta, Nigeria. The children systematically selected were 136 from State Hospital Ijaye and 128 from Federal Medical Centre (FMC), Idi-Aba. Body weights and vital statistics of the children were measured; and blood samples were collected before and 24 h after administration of the rectal artesunates (Plasmotrim-50/200 mg Artesunate) to evaluate the efficacy of the suppository. The first dose of rectal artesunate suppository was administered at a dose of 5–10 mg/kg of body weight per rectum. Giemsa thin and thick films were employed to determine parasite species, malaria parasite count/μL (MPC/μL), and percentage of parasitized red blood cells (PPRBCs). Data were analyzed using SPSS version 16.0. Plasmodium falciparum was the malaria parasite identified by blood examination, with a pretreatment prevalence of 98.9%. Male children had higher infection rate (55%) than females (45%), and infection among age groups and weight groups varied. Chi-square analysis revealed a significant difference between weight and malaria parasite count (p<0.05). Post-treatment analysis after 24 h showed that prevalence dropped by 73%, with females having higher crash rate (77%) than males (69%) but with no statistical difference (p>0.05) among the sexes. Chi-square analysis of pre- and post-treatment revealed a significant difference between MPC/μL and PPRBC at p<0.05. This confirmed the efficacy of rectal artesunate in reducing the parasite density (parasitaemia) within 24 h of treatment. On acceptability, 99.60% of parents accepted to use the suppository. However, 87.1% of parents preferred its usage, as it is easy to administer with no adverse effects when administered on their children. If health officials increase more public knowledge on the use of rectal artesunates, the high mortality now experienced in children under 5 years due to malaria disease would be greatly reduced.

Introduction

M alaria, caused by a protozoan parasite of genus Plasmodium, is transmitted via the bites of infected mosquitoes. In the human body, the parasites multiply in the liver and then infect red blood cells. Symptoms of malaria include fever, headache, vomiting, muscles and joint aches, tiredness, nausea, lassitude, perspiration, anorexia, fatigue, and abdominal discomfort and usually appear between 10 and 15 days after the mosquito bite. If not treated, malaria can quickly become life-threatening by disrupting the blood supply to vital organs. In many parts of the world, the parasites have developed resistance to a number of malaria medicines. There are presently five Plasmodium species that infect humans and these are P. falciparum, P. vivax, P. ovale, P. malariae (WHO 2000, 2001), and P. knowlesi (Wong et al. 2010).

Malaria is a major cause of morbidity and mortality in endemic areas, particularly in children under 5 years of age in sub-Saharan Africa; therefore, it is vital that treatment starts within 24 h of the onset of symptoms, to prevent progression to severe malaria or death. However, in most malaria-endemic areas, accesses to curative and diagnostic services are limited. Distance to healthcare facilities had been observed to be a key determinant of high mortality rate (CDC 2009, Gomes et al. 2009), and mortality is currently estimated at over a million people per year, probably because of increasing resistance to antimalarial drugs (USAID 2009).

Malaria, a serious public health problem in children under 5 years is often accompanied with vomiting, which make it difficult for oral drug administration. This difficulty for prompt oral drug management necessitated research studies by WHO, which introduced the rectal treatment of malaria through the use of suppositories (WHO 2001, 2006). Suppositories are solid or semisolid medicinal substances placed in the rectum or vagina and left to dissolve gradually or melt. Suppository has potential for an intrarectal preparation, which can be oil or water soluble, facilitating absorption across the rectal mucosa, and can be instituted when circumstances prevent oral and parenteral therapy (Looareesuwan et al. 1996, 1997, Awad et al. 2003, Bar-Zeev and White 2006). It can be administered by nonmedical persons, especially in rural peripheral settings at different levels of healthcare (community or health facility), when compared with oral, intravenous, and intramuscular administration of drugs (WHO 2007, TDR 2008).

The treatment guidelines drawn up by WHO emphasize that the user follows up treatment of severe malaria with a complete course of an effective artemisinin-based combination therapy (WHO 2005). In light of these considerations, rectal administration of artesunate suppositories for the treatment of malaria has been accepted as active antimalaria drug (Hinton et al. 2007, Karunajeewa et al. 2007). Hinton et al. (2007) had inferred that community-based intervention using artemisinin-derived suppositories may potentially reduce malaria-related childhood mortality, but acceptability and utilization to rectal administration are required to inform effective deployment strategies. In view of the positive use of rectal suppositories in other parts of Africa, the study was conducted to determine the utilization, efficacy, and parental perfection of rectal suppositories in the management of childhood malaria in children admitted into tertiary health facilities in Abeokuta, Nigeria.

Materials and Methods

Study area

The study areas are two tertiary health facilities, namely FMC, Idi-Aba, and General Hospital Ijaye, all located in Abeokuta, the capital city of Ogun State. Ogun State in 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. The two health facilities are government-owned institutions and are highly patronized by the residents of Abeokuta, with a population of about 1 million people that are predominantly Yoruba-speaking people. Their main occupations are farming, local textile (tie and dye) industry trading, and pottering.

Ethical consent

Written consent was obtained from the State Ministry of Health, the ethical boards of the health facilities used, and their medical staff. The parents also gave consent for their children to participate in the study.

Study timeline and sample size

The study was conducted from September 2008 to February 2009, with a total of 264 children participating from the two tertiary health centers. One hundred twenty eight were from FMC, Idi-Aba, and 136 were from General Hospital Ijaye, Abeokuta. Systematic sampling method was employed in selecting the children for the study.

Clinical procedures

All children under 5 years (1–60 months) with clinical features of malaria (WHO 2001) were eligible for recruitment. Body weight and vital statistics were measured before and after the treatment of malaria using rectal artesunate drugs (Plasmotrim-50/200 mg Artesunate Antimalarial, Rectocap, produced by Mepha Ltd. Bausch-Basel, Switzerland). Following manufacturer's direction, the first dose of rectal artesunate suppository was administered at a dose of 5–10 mg/kg of body weight per rectum by the medical doctors, nurses, and the research team.

Each child was observed for 1 h after dosing, and if the suppository was expelled out, the same dose is readministered and the observation continues. All children were assessed comprehensively after 24 h for ability to tolerate oral medication and ability to eat, drink, and move normally in addition to vital statistics.

Collection and examination of samples

Venous bloods of the children were collected using sterile needle and syringes, as described by Carter and Lema (1993). Blood collected was transferred into EDTA bottles to prevent blood from clotting before examination. Giemsa's staining technique employing both thick and thin films as described by Cheesbrough (1998) was employed to determine malaria parasite species. Malaria parasite densities before treatment (0 h) and after treatment (24 h) with rectal artesunate suppository were determined by counting the number of parasites against white blood cells in a thick blood film to give approximate number of parasites per mL of blood.

Efficacy

Efficacy was determined by looking at the level of parasite density (parasitaemia) in the blood of the children after 24 h of administration of rectal artesunate. The time to return to normal status is also noted by observing the relationship between the parasite count and percentage of parasitized red blood cell count of the blood sample collected from each child before treatment (0 h) and after treatment (24 h).

Acceptability

Acceptability and side effects of rectal artesunate suppositories for the management/treatment of malaria in children less than 5 years were determined through the use of structured questionnaires to parents presenting their children for malaria treatment. Information obtained included demographic data and knowledge on use of artesunate drugs.

Data analysis

The data from the questionnaires were entered and analyzed using Epi info (CDC, Atlanta, GA) version 6.0 into percentiles. The data from blood sample analysis prior to administration of artesunate suppository (0 h) and after administration (24 h) for parasite density and reduction of parasitemia after treatment were obtained. Analyses of the relationship between the variables and for significance were done using SPSS for windows (SPSS, Inc., Chicago, IL) version 16.0.

Results

Prevalence of malaria parasite before and after treatment

The cumulative pretreatment prevalence for Plasmodium parasite, as shown in Table 1, from the two health facilities was 98.9%. Prevalence in males (99%) was slightly higher than in females (98%), with varied prevalence among the age groups and body weights.

Table 1.

Prevalence of Plasmodium Parasite by Sex, Age, and Body Weight of Children Before and After Treatment with Rectal Artesunate

	State Hospital, Ijaye, Abeokuta			FMC, Idi-aba, Abeokuta			Total
Parameter	No. of examined	No. of infected before treatment (%)	No. of infected after treatment (%)	No. of examined	No. of infected before treatment (%)	No. of infected after treatment (%)	No. of examined	No. of infected before treatment (%)	No. of infected after treatment (%)
Sex
Male	75	75 (100)	21 (28)	70	69 (99)	22 (31)	145	144 (99)	43 (30)
Female	61	59 (97)	13 (21)	58	58 (100)	12 (21)	119	117 (98)	25 (21)
Age groups (months)
1–12	39	39 (100)	12 (31)	58	58 (100)	15 (26)	97	97 (100)	27 (28)
13–24	31	31 (100)	6 (19)	23	23 (100)	7 (30)	54	54 (100)	13 (24)
25–36	23	22 (96)	7 (30)	24	24 (100)	10 (42)	47	46 (98)	17 (36)
37–48	19	18 (95)	2 (11)	14	13 (93)	0 (0)	33	31 (94)	2 (6)
49–60	24	24 (100)	7 (29)	9	9 (100)	2 (22)	33	33 (100)	9 (27)
Body weight (kg)
1–10	72	70 (97)	21 (29)	61	61 (100)	16 (26)	133	131 (98)	37 (28)
10.1–20	41	41 (100)	6 (15)	37	36 (97)	11 (30)	78	77 (99)	17 (22)
20.1–30	17	17 (100)	6 (35)	23	23 (100)	6 (26)	40	40 (100)	12 (30)
>30	6	6 (100)	1 (17)	7	7 (100)	1 (14)	13	13 (100)	2 (15)
Overall prevalence	136	134 (98.5)	34 (25.0)	128	127 (99.2)	34 (26.6)	264	261 (98.9)	68 (25.8)

FMC, Federal Medical Centre.

The results after 24 h of treatment showed a great drop in prevalence by about 73%, with only 68 children having one or more parasite cells in their blood samples. Female children had lower cumulative infection status of 21% than males (30%). Chi-square analysis revealed no significant difference in infection status among the sexes (p>0.05). Assessing the relationship between the frequency distribution of cases having parasites in different body weight groups (Table 1), chi-square analysis revealed a significant relationship (p<0.05) in that parasite counts were observed to vary in children within different body weight groups.

Efficacy

Assessing efficacy of the artesunate suppository, Table 2 showed that in over 74% of the children, no parasite cell was observed in blood samples collected after 24 h of treatment for both malaria parasite count/μL (MPC/μL) and percentage of parasitized red blood cells (PPRBCs). The results also showed that the rectal suppository greatly reduced the parasite load as none to a few cells were observed in MPC/μL counts above 501 cells. The study also observed a drop in temperature values after treatment to between 3°C and 37°C, as against 37°C–40°C before administration of drug (Table 2). This drop is highly significant considering that fever (increase in temperature) is a symptom of malaria.

Table 2.

Impact of The Artesunate Suppository Before and After Treatment (24 h) on The Parameters Measured

	State Hospital, Ijaye, Abeokuta		FMC, Idi-aba, Abeokuta
Parameters	% No. observed before treatment	% No. observed after treatment	% No. observed before treatment	% No. observed after treatment
MPC/μL
0	1	75	1	74
1–500	83	25	78	24
501–1000	12	0	16	2
1001–1500	4	0	5	0
PPRBCs
0	1	75	1	74
1–5.0	37	18	54	21
5.1–10.0	34	6	26	2
10.1–15.0	15	1	11	2
>15.0	13	0	8	1
Temperature (°C)
36.0–36.9	2	32	0	19
37.0–37.9	27	58	11	74
38.0–38.9	51	10	60	7
>39.0	20	0	29	0

MPC/μL, mean parasite count/μL; PPRBCs, percentage of parasitized red blood cells.

Acceptability

The responses on the acceptability of the rectal artesunate by the parents are summarized in Table 3. The analysis of data showed that the majority of the parents had never used rectal artesunate to treat malaria (97%). The acceptability of rectal artesunate showed that it is easy to use (87%) and the majority of the parents felt satisfied using it (99%). On the safety and effectiveness of rectal artesunate, 98% admitted that it is safe and also effective (99%). Persistence high body temperature was the common complication experienced by few of the children (3.80%), but most of the children did not show any complication or adverse effects (94%). In age utilization of rectal artesunate, statistical analysis showed no significant difference between those who had used rectal artesunate and those who had not used any rectal artesunate (p>0.05). Also, rectal artesunate was acceptable to all ages as almost all felt satisfied.

Table 3.

Summary on the Acceptability of Rectal Artesunate

S. No.	Parameter	State hospital (%)	FMC (%)
1	Have you had malaria before?
	Yes	88.1	89.4
	No	11.9	10.6
2	How do you prevent malaria?
	Use herbs	5.1	4.0
	Visits hospital	63.2	61.9
	Visit traditional birth home	0.0	0.8
	Self-medication	7.4	0.0
	Use herbs+visit hospital	15.4	25.4
	Use herbs+visit traditional	0.7	0.0
	Use herbs+self-medication	1.5	0.8
	Use herbs+visit hosp.+visit traditional	0.0	4.8
	Visit hospital+self-medication	6.6	2.4
3	Usage of Artesunate suppository drug before
	Yes	4.4	0.0
	No	95.6	100.0
4	Do you feel satisfied using it?
	Yes	100.0	99.2
	No	0.0	0.8
5	Does the use of rectal artesunate prove effective after usage?
	Yes	100.0	99.2
	No	0.0	0.8
6	Do you experience any form of complication?
	Yes	1.5	0.8
	No	98.5	99.2

Discussion

The high prevalence of malaria in children below 5 years is consistent with previous observations that children under 5 years and pregnant women were the most vulnerable groups to malaria (Ojo et al. 2005, Idowu et al. 2008). The high pretreatment prevalence confirms that malaria is still an endemic disease as earlier observed by Mbanugo and Ejini (2000), Sowunmi et al. (2000), Awad et al. (2003), Barnes et al. (2004), Krishna et al. (2006), Warsame et al. (2007), Agbenyega (2008), Idowu et al. (2008), CDC (2009), and Gomes et al. (2009).

The great reduction in infection levels with respect to MPC/μL and PPRBCs and the drop in temperature showed that rectal artesunate is effective in the management and treatment of malaria infection in children under 5 years because of reduction in parasitaemia within 24 h of treatment. The results confirm observations by Awad et al. (2003), Gomez et al. (2003), Karunnajeewa et al. (2003), Barnes et al. (2004), Bar-Zeev and White (2006), Krishna (2006), Agbenyega (2008), Gomes et al. (2008), and TDR (2008) on the efficacy of rectal artesunate in children.

The preference of most parents to visit hospital as well as use of herbs for the treatment of malaria may not be associated with financial constrains or poor primary health facilities but may be premised on their beliefs that herbs are good remedies for treating infections as earlier posited by Idowu et al. (2008) and Sam-Wobo et al. (2008).

The responses on the acceptability of rectal artesunate by the parents of the children showed that rectal artesunate was well accepted despite social problems associated with suppository drugs. The parents believed that rectal artesunate is highly effective and a good antimalarial suppository, as it shows a greater reduction in the level of parasitaemia. They affirm that rectal artesunate is safe and well tolerated for the management and treatment of falciparum malaria as earlier reported by researchers (Looareesuwan et al. 1996, Bar-Zeev and White 2006). The acceptability of rectal artesunate by the parents is based on the easy way of using it, that is, it can be administered by nonmedical person.

The high acceptability of rectal artesunate is remarkable and showed that good knowledge and awareness will increase its usage. Therefore, health education should be intensified by government health institutions and development partners for the general public to be aware of the easily usable drug for managing childhood malaria and reducing mortality.

Footnotes

Acknowledgment

The authors appreciate the support of management and staff of the hospitals and the cooperation of parents, guardians, and the children during the study.

Disclosure Statement

No competing financial interests exist.

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