{"id":431,"date":"2015-01-22T09:00:54","date_gmt":"2015-01-22T09:00:54","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=431"},"modified":"2018-10-05T11:13:01","modified_gmt":"2018-10-05T11:13:01","slug":"comparative-study-on-the-efficacy-of-sulfadoxine-pyrimethamine-amodiaquine-and-amodiaquine-sulfadoxine-pyrimethamine-combination-in-the-treatment-of-acute-uncomplicated-malaria-in-enugu-state-nig","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol1no2\/comparative-study-on-the-efficacy-of-sulfadoxine-pyrimethamine-amodiaquine-and-amodiaquine-sulfadoxine-pyrimethamine-combination-in-the-treatment-of-acute-uncomplicated-malaria-in-enugu-state-nig\/","title":{"rendered":"Comparative Study on the Efficacy of Sulfadoxine- Pyrimethamine, Amodiaquine and Amodiaquine + Sulfadoxine-Pyrimethamine Combination in the Treatment of Acute Uncomplicated Malaria in Enugu State, Nigeria."},"content":{"rendered":"

Introduction<\/strong><\/p>\n

It has been shown that artemisinin-based combination therapy (ACT) could improve therapeutic effectiveness, reduce gametocyte carriage and delay the emergence and spread of drug resistant parasite.1<\/sup>\u00a0 It is noteworthy, that despite the recent change in national malaria drug policy in favour of artemisinin-based combination therapy (ACT) in Nigeria, the non-ACT regimens still remain the commonest antimalarial drugs widely prescribed as a result of low cost and availability.2<\/sup>\u00a0 There is, therefore, the need for continuous monitoring and evaluation of the efficacy of these combination therapies in the management of acute uncomplicated P.falciparum<\/em> malaria.\u00a0 This study attempts to evaluate the current status in respect of clinical and therapeutic efficacy of\u00a0\u00a0\u00a0\u00a0\u00a0 non-ACT (AQ + SP) and ACT (AT + AQ) in the treatment of acute uncomplicated P.falciparum<\/em> malaria among under five children in Enugu State, Nigeria.<\/p>\n

Patients and Methods<\/strong><\/p>\n

Patients (n = 120) enrolled in this study were selected by stratified random sampling from children with clinically characterized uncomplicated malaria aged 6 to 59 months (M:F = 1:1.32) who presented at Amafor primary healthcare facility, Ugbakwa; a rural farming population with high endemicity of malaria\u00a0 transmission, under the Asu Nkanu Local Health Authority of Enugu State.\u00a0 They presented with a history of fever in the preceding 24 to 48 hours or axillary temperature ><\/u> 37.5o<\/sup>C and parasitemia > 2000 asexual forms\/mL of blood.\u00a0 Patients with concomitant illness, intense vomiting, recent history of convulsion, lethargic or unconscious state and sickle cell anaemia were excluded.\u00a0 Ethical clearance was obtained and informed consent of the parent or guardian for each child was sought.\u00a0 The patients were subsequently assigned randomly to any of the drug treatment groups: AQ + SP or AT + AQ.\u00a0 Thus, 60 patients were allotted to each treatment group.\u00a0 Drug dosages were computed using the weight of the patients.\u00a0 AQ was given at a dose of 10mg\/kg daily for 3 days and SP at 25mg\/kg as single dose on Day 0.\u00a0 AT was given at a dose of 2mg\/kg twice daily on Day 0, and 1mg\/kg twice daily for the next 4 days.\u00a0 Drugs were administered orally by direct observation and monitored by the clinician to ensure they were not vomited.\u00a0 Drugs were re-administered within 1 hour following initial vomiting but withdrawn from the study with another episode of vomiting. Patients were followed up for 2 weeks after treatment.\u00a0 Evaluation of response carried out on days 1,2,3,7 and 14 according to WHO criteria1<\/sup>.\u00a0 Data obtained were statistically analyzed using Student t<\/em>-test and presented in tabular form.<\/p>\n

Results<\/strong><\/p>\n

Table 1, clearly depicted the therapeutic response of patients in both\u00a0\u00a0\u00a0 AQ + SP and AT + AQ combinations.\u00a0 In the AQ + SP treatment group, mean Fever Clearance Time (FCT) of 28.3+<\/u>2.3 hours was not significantly different (P>0.05) from 25.4+<\/u>2.3 hours reported for AT + AQ combination therapy.\u00a0 Similarly mean Parasite Clearance Time (PCT) of 3.5+<\/u>0.15 days in ACT (AT + AQ) did not differ significantly from 3.7+<\/u>0.15 days reported in non\u2013ACT (AQ + SP).\u00a0 Interestingly, there was no reported treatment failure in both combinations, with a radical cure rate of 100% reported for both ACT and non-ACT.\u00a0 It was also noted as shown in tables 2 and 3, that there was no statistically significant difference (P>0.05) in the haematocrit and axillary temperature of patients both at initial presentation, Day 0 and post-treatment, Day 14 in both AQ + SP and AT + AQ combination therapies.<\/p>\n

Table 1:\u00a0\u00a0 Therapeutic Response of Patients in the <\/strong>Various Treatment Groups.<\/strong>\u00a0<\/strong><\/p>\n\n\n\n\n\n\n
<\/td>\nAQ + SP<\/strong><\/p>\n

(Mean+<\/u>SEM)<\/strong><\/td>\n

AT + AQ<\/strong><\/p>\n

(Mean+<\/u>SEM)<\/strong><\/p>\n

\u00a0<\/strong><\/td>\n

P<\/em><\/strong>-Value<\/strong><\/td>\n<\/tr>\n
 <\/p>\n

Fever Clearance Time (Hours)<\/p>\n

 <\/td>\n

 <\/p>\n

28.3+<\/u>2.3<\/td>\n

 <\/p>\n

25.4+<\/u>2.3<\/td>\n

 <\/p>\n

>0.05<\/td>\n<\/tr>\n

 <\/p>\n

Parasite Clearance Time (Days)<\/p>\n

 <\/td>\n

 <\/p>\n

3.7+<\/u>0.15<\/td>\n

 <\/p>\n

3.5+<\/u>0.15<\/td>\n

 <\/p>\n

>0.05<\/p>\n

 <\/td>\n<\/tr>\n

 <\/p>\n

Radical Cure Rate (%)<\/p>\n

 <\/td>\n

 <\/p>\n

100+<\/u>0.0<\/td>\n

 <\/p>\n

100+<\/u>0.0<\/td>\n

 <\/p>\n

>0.05<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Table 2:\u00a0\u00a0 Pre and Post- Treatment Haematocrit and\u00a0<\/strong>Axillary Temperature Of Patients in the <\/strong>Aq + Sp (Non-Act) Treatment Group.<\/strong><\/p>\n\n\n\n\n\n
<\/td>\n\u00a0<\/strong><\/p>\n

Pre-Treatment, DO<\/strong><\/p>\n

\u00a0<\/strong><\/td>\n

\u00a0<\/strong><\/p>\n

Post-Treatment, D14<\/strong><\/td>\n

\u00a0<\/em><\/strong><\/p>\n

P<\/em><\/strong>-Value<\/strong><\/td>\n<\/tr>\n

 <\/p>\n

Haematocrit (%)<\/p>\n

 <\/td>\n

 <\/p>\n

28.9+<\/u>2.5<\/td>\n

 <\/p>\n

30.1+<\/u>2.5<\/td>\n

 <\/p>\n

>0.05<\/td>\n<\/tr>\n

 <\/p>\n

Axillary Temperature (o<\/sup>C)<\/p>\n

 <\/td>\n

 <\/p>\n

39.1+<\/u>1.6<\/td>\n

 <\/p>\n

37.0+<\/u>1.5<\/td>\n

 <\/p>\n

>0.05<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Table 3:\u00a0\u00a0 Pre and Post-Treatment Haematocrit and\u00a0<\/strong>Axillary Temperature of Patientsi in the \u00a0At + Aq (Act) Treatment Group<\/strong><\/p>\n\n\n\n\n\n
<\/td>\n\u00a0<\/strong><\/p>\n

Pre-Treatment, DO<\/strong><\/p>\n

\u00a0<\/strong><\/td>\n

\u00a0<\/strong><\/p>\n

Post-Treatment, D14<\/strong><\/td>\n

\u00a0<\/em><\/strong><\/p>\n

P<\/em><\/strong>-Value<\/strong><\/td>\n<\/tr>\n

 <\/p>\n

Haematocrit (%)<\/p>\n

 <\/td>\n

 <\/p>\n

29.0+<\/u>2.5<\/td>\n

 <\/p>\n

30.8+<\/u>2.5<\/td>\n

 <\/p>\n

>0.05<\/td>\n<\/tr>\n

 <\/p>\n

Axillary Temperature (o<\/sup>C)<\/p>\n

 <\/td>\n

 <\/p>\n

38.6+<\/u>1.6<\/td>\n

 <\/p>\n

37.2+<\/u>1.5<\/td>\n

 <\/p>\n

>0.05<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Discussion<\/strong><\/p>\n

The non-ACT regimen AQ + SP in this study has been demonstrated to be quite effective in the treatment of uncomplicated P.falciparum<\/em> malaria with a radical cure rate recorded as 100%.\u00a0 This study also revealed as shown in table 1, that there was no statistically significant difference (P>0.05) in the various criteria used to assess therapeutic response between AQ + SP and AT + AQ combinations.\u00a0 Amodiaquine, a 4-aminoquinoline and effective blood schizonticide, is useful in areas where there is low-grade chloroquine resistance but recrudescence is not uncommon3<\/sup>.\u00a0 The AQ + SP combination was shown to be more effective than ACT for the treatment of uncomplicated malaria in Burkina Faso4<\/sup>.\u00a0 Although SP is still relatively effective in most areas in Africa, resistance is increasing and could potentially develop as it has in Asia, to render the drug useless in the near future5<\/sup>.\u00a0 The use of AQ + SP combination could also slow down development of parasite resistance to the individual drugs, increasing the life-span of each of them as an effective anti-malarial drug6<\/sup>.\u00a0 In the AT + AQ combination (ACT), a cure rate of 100% was also recorded in this study.\u00a0 Artesunate (AT) is a water soluble analog of artemisinin, a sesquiterpene lactone endpoperoxide.\u00a0 It is a very rapidly acting blood schizonticide.\u00a0 Its antimalarial activity results from the production of free radicals following the iron-catalyzed cleavage of the endoperoxide bridge in the parasite.\u00a0 The enhanced, cumulative blood schizonticidal effect of AT + AQ combination, therefore, is very beneficial in ensuring rapid fever clearance and relief of symptoms.\u00a0 Notwithstanding, the effectiveness and good therapeutic response of AT + AQ combination reported in this study, as evidenced by exceptionally high cure rate and no treatment failures; high cost and non-availability have seriously limited the effective use of ACT7<\/sup>.\u00a0 The change in treatment policy in Nigeria to ACT without adequate sensitization and education of medical personnel may pose some difficulties that could lead to high morbidity and mortality8<\/sup>.\u00a0 A resultant increase in resistance of P.falciparum<\/em> to these new combinations may also arise since transition into an alternative compound may take some years before they are accepted and put into proper use9<\/sup>. Current World Health Organisation (WHO) recommendations have focused on the use of combination antimalarial therapy, particularly artemisinin-based combination therapy (ACT)10,11<\/sup>.\u00a0 However, several control programmes in Africa have switched to non-ACT, for example AQ + SP12<\/sup>.\u00a0 In conclusion, the AQ + SP combination (non-ACT) is strongly recommended as a cost effective and therapeutic alternative to ACT, for the treatment of acute uncomplicated P.falciparum <\/em>malaria especially in under five children in Enugu State, Nigeria.<\/p>\n

References<\/strong><\/p>\n

    \n
  1. WHO \u2013 World Health Organization. (2006) Guidelines for the treatment of malaria. WHO Press, Geneva.<\/em><\/li>\n
  2. Ogungbamigbe T., Ogunro P., Elemile P., Egbewale B., Olowu O., and Abiodun O. (2005). Presentation patterns of antimalarial drugs among medical practitioners in Osogbo metropolis, South-West, Nigeria.\u00a0 Trop Med Health.<\/em> 33: 201 \u2013 208.<\/li>\n
  3. Olliaro P. and Mussano P. (1997). Amodiaquine for the treatment of malaria.\u00a0 Infectious diseases module of the cochrane database of systematic reviews.\u00a0 BMJ Publishing.<\/em><\/li>\n
  4. Zongo I., Dorsey G., Rouamba N., Tinto H., Dokomajilar C., Guiguemde R.T., Rosenthal P.D. and Ouedraogo J.B. (2007). Artemether-lumefantrine versus amodiaquine plus sulfadoxine-pyrimethamine for uncomplicated falciparum<\/em> malaria in Burkina Faso: a randomized non-inferiority trial.\u00a0 Lancet.<\/em> 369: 491 \u2013 498.<\/li>\n
  5. Trigg J.K., Mbwana H., Chambo O., Hills E., Watkins W. and Curtis C.F. (1997). Resistance to sulfadoxine-pyrmethamine in falciparum<\/em> in 12 Villages in North East Tanzania and a test of Chloroproguanil\/dapsone.\u00a0 Acta Tropica.<\/em> 63:185 \u2013 189.<\/li>\n
  6. Kremsner P.G., Luty A.J.F and Granninger W. (1997).\u00a0 Combination chemotherapy for falciparum<\/em> malaria.\u00a0 Parasitology Today<\/em>. 13: 167 \u2013 168.<\/li>\n
  7. Yeung S., Pongtavornpinyo W., Hastings I.M., Mills A.J and White N.J. (2004). Antimalarial drug resistance, artermisinin-based combination therapy and the contribution of modeling to elucidating policy choices.\u00a0 Am J. Trop Med Hyg.<\/em> 71: 179 \u2013 186.<\/li>\n
  8. Ogungbameigbe T.O., Ojurongbe O., Ogunro P.S., Okanlawon B.M. and Kolawole S.O. (2005) Chloroquine resistant Plasmodium falciparum<\/em> malaria in Osogbo Nigeria: efficacy of amodiaquine + sulfadoxine-pyrimethamine and chloroquine + chlorpheniramine for treatment.\u00a0 Mem Inst Oswaldo Cruz.<\/em> 103 (1): 79 \u2013 84.<\/li>\n
  9. Shretta R., Omumbo J., Rapuoda B. and Snow R.N. (2000). Using evidence to change antimalarial drug policy in Kenya. Trop Med Int Health.<\/em> 5:755 \u2013 764.<\/li>\n<\/ol>\n

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