ABSTRACT
Objective: The study was carried out to describe the antimalarial drug prescribing practice in pediatrics in the University of Nigeria Teaching Hospital, Enugu. The specific objectives were to determine: the cases that were diagnosed based on laboratory investigation; the specific antimalarial drugs prescribed for the treatment of uncomplicated malaria cases between 2003-2011; the changes- if any- in the prescription pattern of the prescribers following the introduction of the Treatment Guidelines and the level of their compliance to the guidelines
Method: The patients’ medical charts were assessed. The exclusion criteria were patients with uncomplicated malaria below 6 months of age and above 5 years of age, and patients with special disease conditions like HIV. Inclusion criterion was patients with uncomplicated malaria between the ages of 6 months and 5 years. A total of 3034 prescriptions were collected for data extraction and analysis. With the use of a modified WHO prescribing indicator form, these data were collected; demographic data, clinical presentations (symptoms), laboratory investigation and the specific antimalarial drugs prescribed. Data were grouped into two; the pre-policy period (2003-2005) and the post-policy period (2006-2011), and then analysed using Excel spreadsheet and SPSS.14.0 software for descriptive and inferential statistics respectively.
Results: The results of the study showed that the number of malaria cases that were diagnosed based on positive malaria parasite test were 4.8% of 2765 patients diagnosed of malaria. Artemether-Lumefantrine combination was the most prescribed antimalarial drug with 45.4%. It was 2% of the prescriptions in the pre-policy period and 63.3% in the post-policy period. Although there was a significant increase in the prescription of ACT in the post-policy period (32.6%), the compliance to the Antimalarial treatment guideline (ATG) was low (23.8%).
Conclusion: This study revealed an increase in the prescription of Artemisinin-based combination therapy after the introduction of the National Antimalarial Treatment Guideline. Nevertheless, prescribers did not adhere strictly to the guideline. Many of the Artemisinin-based combination therapy prescribed were not the recommended ones. There was a high incidence of empirical diagnosis/treatment of malaria as opposed to parasitological/confirmatory diagnosis/treatment. Among the WHO drug use indicators, there was still a lot of room for improvement in the prescription of drugs in generics by prescribers. CHAPTER ONE
INTRODUCTION
- BACKGROUND OF THE STUDY
Malaria is a global public health problem and remains one of the major killers in many parts of the world, especially in the endemic countries. In Europe malaria was particularly present in the Mediterranean basin and Eastern regions, including the European Russia. From the mid nineteenth Century forward the process of regression of malaria started in North-Western European countries, as England and Holland, where the improvement of the health services in urban and rural areas progressed rapidly and resulted in a better control of the anopheline mosquitoes population. Throughout the first half of the 20th Century, malaria in Europe underwent a continual reduction, thanks to a combination of improved economic situation and control measures regularly implemented. In 1955 the WHO launched the Global Malaria Eradication program, a worldwide campaign for the eradication of malaria based on the use of DDT and other insecticides with residual activity applied inside the housing against vector Anopheles mosquitoes and on the use of antimalarial drugs for the elimination of plasmodia in humans. The campaign brought, toward the end of the 1960s, the eradication of malaria in all developed countries where malaria was endemic (Mediterranean countries, many regions of the tropics, etc.) and produced the interruption of malaria transmission in most areas of the tropical Asia and Latin America like in Brazil the number of cases decreased from 6 million to 37,000 (Majori, 2012)
By the mid-20th century, malaria was eliminated as a major health problem in many parts of the world. For instance at the end of world war II a massive malaria control program based on DDT (Dichloro Diphenyl Trichloroethane) spraying was carried out in Italy (Wikipedia,2014). Malaria also was eliminated in the United States of America by the use of DDT in the National Malaria Eradication Program from 1947-1952. Complete eradication of A.gambiae from northeast Brazil and thus from the New world was achieved in 1940 by meticulous application of Paris Green to breeding places and Pyrethrum spray-killing to adult resting places (Parmakelis et al, 2008). But then at the close of the 20th Century, malaria remained endemic in more than 100 countries throughout the tropical and subtropical zones, including large areas of central and south America, Hispanics (Haiti and the Dominican Republic), Africa, the middle East, the Indian subcontinent, southeast Asia and Oceania.
In 1969, the WHO abandoned the strategy of the eradication and replaced it with control strategy in order to reduce the morbidity and mortality. In 1992, WHO drew up a new strategy with emphasis on early diagnosis and immediate treatment in the context of programs managed by the basic health care system. Many countries such as Thailand, China, Brazil, Solomon Islands, Philippines, Vietnam, obtained good results in terms of control. Even though the estimated incidence of malaria globally has reduced by 17% since 2000 and malaria-specific mortality rate by 26%, (Majori, 2012), for many others, and especially for those in sub-Saharan Africa, the malaria situation is still critical. There were an estimated 216 million episodes of malaria and 655,000 malaria deaths in 2010, of which 91% were in Sub-Saharan Africa.
In Africa, an estimated 300-500 million cases of malaria occur each year resulting in approximately one million deaths. In many parts of sub-Saharan Africa, it is still the largest contributor to the burden of disease and premature death (WHO, 1996; Dillip et al, 2009), constituting the highest percentage (91%) of the 881,000 people who die of malaria every year, while children under 5 years of age make up 85% (EDCTP, 2011). To be precise, more than half of all estimated malaria cases occur in just five African countries: Nigeria, Democratic Republic of Congo, Ethiopia, United Republic of Tanzania and Kenya (WHO, 2008). In fact among death due to malaria occurring in Africa more than 90% are in under-five children that results in brain damage (Maslove, 2009). Children suffer mostly from malaria and in absolute terms malaria kills 3000 children below 5 years old daily, constitutes 25% of child mortality in Africa and 25-30% in Nigeria (Adesanmi, 2011). In young children, malaria can progress from a mild to severe case within 24 hours after the onset of symptoms. Prompt diagnosis and timely malaria treatment within 24 hours after onset of first symptoms can reduce illness progression to severe stages and, therefore, decrease mortality (Getahun, 2010).
During the past decades, numerous large-scale initiatives have been undertaken with the goal of reducing or eradicating the burden of malaria in the developing world. To mention but a few of such projects: the organization ‘Malaria no more’ set a public goal of eliminating malaria from Africa by 2015. The Global Fund to Fight AIDS, Tuberculosis and Malaria has distributed 230 million insecticide treated nets intended to stop mosquito-borne transmission of malaria. President’s Malaria Initiatives (PMI), PATH malaria Vaccine Initiative, Harvard Malaria Initiative etc. However, the ambitious goals set by these programmes for reducing the burden of malaria in the near future appear unlikely to be met (Attaran, 2004). And even though effective treatment exists, it must be administered promptly and timely by trained personnel in order to be effective, thus, most malaria deaths can be prevented when clinical cases are promptly diagnosed and effectively treated. Major factors affecting the outcome of the diseases are health-seeking behaviour and socio-economic status, which determine access to health services (WHO, 1996 (b); Getahun et al, 2010) that is why most deaths occur at the community level, outside health institutions.
Nigeria is one of the areas of high stable transmission, morbidity and mortality are highest in young children especially 6 months and above, in whom acquired protective immunity is insufficient to protect against severe disease. Those with high peripheral parasitaemia (>4-5% infected erythrocytes) are at increased risk of severe malaria and death (Crawley et al, 2010). Until recently, in areas of high malaria transmission like Nigeria, malaria treatment has been mainly on clinical diagnosis because malaria was considered one of the commonest causes of fever with a high mortality rate. Now it has been made obvious that causes of fever can range from non serious viral infections to serious life threatening conditions, thus making it impossible to base the diagnosis of malaria solely on the clinical presentation. Improper diagnosis poses the risk of overtreatment with anti-malarial drugs and under treatment of non-malarial causes of fever. Therefore for optimal treatment and to save lives, an accurate diagnosis is essential (FMOH, 2011). In line with WHO recommendation of diagnosis in all age groups before administration of appropriate treatment for malaria, Nigeria has provided guidelines on parasite-based diagnosis which is imperative to achieve targeted treatment and accurate estimation of true malaria cases (FMOH, 2011). This entails making use of proper laboratory tools to confirm the presence of the malaria parasite in the patient.
Growing resistance to conventional anti-malarial drugs and the associated resurgence in infection rates and malaria-related morbidity and mortality, particularly in sub-Saharan Africa (Bassat et al, 2011), has led to a paradigm shift in treatment strategies. Since 2004, the World Health Organization (WHO) recommends treatment with artemisinin-based combination therapy (ACT) (WHO, 2010), and ACT has been adopted as first-line treatment for uncomplicated Plasmodium falciparum malaria in virtually all African countries. The WHO had published guidelines in 2005- edited in 2010- to provide global evidence-based recommendation on the treatment of malaria. It contains information on the treatment of uncomplicated malaria and severe malaria. In the 2005 edition, the WHO recommended presumptive treatment of malaria using ACTs where the availability and use of laboratories are limited. However, recently in the 2010 edition the guideline places emphasis on testing for malaria with RDTs or microscopy before treating while reaffirming the use of ACTs. Following the indications of the WHO, Nigeria changed the first-line therapy for uncomplicated Plasmodium falciparum malaria from Chloroquine to artemisinin-based combination therapy (ACT) in 2005 (Ajayi, 2009). This combination reduces the risk of development of further resistance (Sinclair, 2009). The rationale for using ACT is based on the concept that the artemisinin will substantially and rapidly reduce even multidrug-resistant P. falciparum parasitaemia, leaving the residual parasite to be killed by high concentrations of the partner drug. In this way, the probability of the development of de novo resistance is greatly reduced (Sirima et al, 2009). ACT also reduces gametocyte carriage and infectivity. Artemether-lumefantrine (AL), the first fixed-dose ACT to be prequalified by the WHO, has consistently shown PCR-corrected cure rates > 95% against this species, with prompt resolution of parasitaemia and fever, rapid gametocyte clearance and good tolerance in populations of adults and children even when administered unsupervised (Bassat et al, 2011).
Malaria is a preventable, treatable and curable infection. Several Non-governmental organizations in collaboration with the government have made drugs and other interventions for its prevention and treatment widely available. Many of these are easy to apply and are affordable and accessible, yet Nigeria continues to suffer under the severe disease and economic burden brought upon it by malaria.
- STATEMENT OF THE PROBLEM
The degree of morbidity and mortality due to malaria infection is highest in young children especially between 6 months and five years. This is because the acquired protective immunity in this group is usually insufficient to protect against severe disease, mostly in areas of high stable transmission. Malaria, as a killer disease, accounts for 60% of outpatient visits and 30% of hospitalizations among children under five years of age in Nigeria (US Embassy, 2011). It is estimated that about 50% of the population in Nigeria experience at least one episode yearly while the under-five children have up to 2-4 attacks of malaria annually (FMOH, 2005).
Key to reducing the morbidity and mortality from malaria is the prompt delivery of effective drug treatment to sick children. In fact, more than 50% of deaths from severe childhood illnesses including malaria occur within 24 hr of hospital admission (Crawley, 2010). Early identification and treatment of children at highest risk of death are therefore of great importance. Increased resistance of the parasite to the existing antimalarial drugs militates against the proper treatment of this infection. The WHO had therefore recommended some treatment guidelines to combat multidrug resistance and to prevent its further development. It is a well known fact that antimalarial drug resistance accounts for the failure to control malaria in many areas of the tropical world and the consequent increasing global mortality. In fact the growing risk of resistance against many effective antimalarial drugs is one threat to the international ambition to eliminate malaria death by 2015 (EDCTP, 2011).
In view of this panorama, it is necessary to study the antimalarial drug prescribing practice in pediatrics in a teaching hospital in order to determine the quality of the treatments given and whether they comply with the recommended treatment guidelines.
