Abstract

Background: Malaria, which is a parasite vector-borne disease, is one of the most significant health threats in tropical regions, despite the availability of individual treatment and chemoprophylaxis. Malaria chemoprophylaxis and chemotherapy remain a major area of research, and new drug molecules are constantly being developed. However, this study was aimed to investigate the synergistic effect of ciprofloxacin 500mg and artesunate 60mg for malaria in infected blood samples.

Methods: This study employed an experimental design. A total of 25 participants gave their consent and were enrolled in this study. Blood samples of malaria positive patients were collected and invitro testing was done to determine the synergistic effect of ciprofloxacin and artesunate from the 6th of march to the 11th of march.

Results: Results shows that ciprofloxacin at 50mg/ml, 5mg/ml, 0.5mg/ml, 0.005mg/ml and 0.1mg/ml has no effect on both the number and shape of malaria parasites while artesunate at 6mg/ml and 0.6mg/ml has an effect on the parasitemia level reduction of the malaria parasites with a p value of <.001, and as concentration dropped to 0.06mg/ml, 0.006mg/ml and 0.012mg/ml its effect on malaria parasites decreases implying that this drug at its lowest concentration produces no significant change in malaria parasites.

The combined effects of ciprofloxacin and artesunate at (6mg/ml/50mh/ml), (0.6mg/ml/5mg/ml), (0.06mg/ml/0.05mg/ml) respectively has a significant effect on malaria parasites with a p value of <.001 which is less than 005 significance level with a 95% confidence and thus implies that these drug combinations have a positive effect on malaria parasites which means that the alternative hypothesis should be accepted and the null hypothesis rejected.

Conclusion: Ciprofloxacin enhances the antimalarial activity of artesunate against malaria parasites in infected blood samples in-vitro and this is beneficial in the management and treatment of malaria parasite. Key words: Malaria, parasitemia level, ciprofloxacin, artesunate and synergistic.

CHAPTER ONE

INTRODUCTION

1.1 Background

Malaria is the most widespread endemic disease in Cameroon. Plasmodium falciparum is the predominant malaria parasite species, female anopheles mosquitoe is the primary vector responsible for transmission (WHO,2021).

The Government of Cameroon has made the fight against malaria a priority, with a highlight in the country’s Health Sector Strategy, and the adoption of the High Burden High Impact stratification exercise in the National Malaria Strategic Plan (Malaria operational plan,2022). Cameroon’s current National Strategic Plan (NSP) for malaria control covers the period 2019–2023 and is the fifth iteration of a national strategy.

Overall, Cameroon is among the 15 highest burden malaria countries, with 2.9% of all global malaria cases and deaths, and 2.4% of malaria deaths in 2020, this represents the 3rd highest number of malaria cases in Central Africa (12.6% of cases in 2020) (WHO,2021). Suspected malaria cases caused 30% of all medical consultations, and 21 % of visits to health facilities resulted in a diagnosis of laboratory-confirmed malaria. (WHO,2021).

National statistics from 2015 note that in health facilities, 19% of deaths were attributed to malaria, and 48 % of all hospital admissions were due to the suspicion of severe malaria.  Between 2017 and 2020, case numbers increased by 3.8%, from 250 to 260 per 1000 of the population at risk (Malaria operational plan,2022) Mortality rates increased slightly by 0.8% in the same period, from 0.55 to 0.56 per 1000 of the population at risk.

Less than 30% of children who reported having fever were tested for malaria. (Malaria operational plan,2022); Under the High Burden High Impact (HBHI) approach, a malaria risk stratification was developed by combining prevalence, incidence, and all-cause mortality rates. Based on this criterion, the country’s 189 health districts are classified into: very high risk (21percent), high risk (31 percent), medium risk (27 percent), and low risk (21percent).

The very high risk and health districts are distributed throughout almost all of the country’s regions, but with a high concentration in the East, Adamawa, Central and South regions. Medium risk and low risk districts are concentrated in the Far North, Northwest and West regions. (Global fund,2022).

Previous studies have revealed on the use of antibiotics for malaria chemoprophylaxis and treatment. The type of antibiotic used defined any compound that has been used to treat bacterial infections and their analogues developed were active against Plasmodium falciparum. Two families, tetracyclines and macrolides and their derivatives, have been the focus of many studies in the past 30 years and were previously described in two reviews (Gaillard et al.,2016).

However, other antibiotics against malaria parasites could be developed in the future. The use of antibiotics as anti-malarial drugs has been described. Some of the antibiotic drugs used against Plasmodium falciparum include co-trimoxazole, quinolones, ketolides, fusidic acid and thiopeptide. Quinolones are synthetic compounds mostly used as antibiotics for their bactericidal properties.

However limited studies have been done to investigate its effect on plasmodium. Quinolones contain the 4-oxo-1,4-dihydroquinoline skeleton. The first antibacterial quinolone, nalidixic acid, was discovered as a by-product during the synthesis of chloroquine. The quinolone scaffold is present in the structure of compounds that display anti-malarial activity, probably by targeting the gyrase enzyme of the parasites, a type II topo-isomerase (Dubar et al., 2011). However, in Plasmodium falciparum there is evidence for off-target toxicity, particularly for ciprofloxacin (Tang et al.,2015).

The main quinolones used as antibiotics are fluoroquinolones. Their anti-malarial activity has been documented (Beteck et al.,2014). Norfloxacin, ofloxacin, pefloxacin and trovafloxacin displayed low in vitro anti-malarial activity in the micromolar range against Plasmodium falciparum (20– >100 µM). Many studies have shown that ciprofloxacin displayed the best in vitro anti-malarial activity within the first 48h. Prolonged exposure of parasites to ciprofloxacin increased its anti-malarial activity.

1.2 Statement of Problem

Malaria treatment and resistance has been a call for concern, despite the new development in malaria therapies, death rate as a result of malaria still remain high in Cameroon. However, choosing the right dosage for malaria treatment has been a challenge to medical practitioners due to lack of potent and affordable drug for malaria treatment and different malaria drugs are been adulterated in the market of which some do not meet the WHO standards.

So, the use of antimalarial drugs as combination instead of monotherapy has been in practice to increase the efficacy of drug and to delay the emergency of drug resistant parasites and thus ACTs has been most widely and effectively used for malaria treatment.

Recently, resistance to ACT has been reported in southeast Asia increasing the global alarm for malaria treatment and control (Ashley et al., 2014). Therefore, there is a need for the formulation of new antimalarials to overcome this resistance and to better malaria treatment and improve treatment outcome.

This study therefore has been designed to investigate the synergistic effect of ciprofloxacin and artesunate for malaria in infected blood samples. If the combine effect is greater and effective, further studies would be carried out concerning this drug development and prescription practices using ciprofloxacin for malaria therapy will be employed.

1.4 Research Questions

1. What is the in-vitro effect of ciprofloxacin 500mg on the blood film of individuals infected with malaria?
2. What is the in-vitro effect of Artesunate 60mg on the blood film of individuals infected with malaria?
3. How is the synergistic effect of ciprofloxacin 500mg and artesunate 60mg on the blood film of individuals infected with malaria?

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