Predictors of antibiotics co-prescription with antimalarials for patients presenting with fever in rural Tanzania

Malaria remains a public health problem in Africa. It is estimated to claim about 1 million deaths and over 400 million malaria cases worldwide each year, with 90% of these deaths occurring in sub Saharan Africa [1]. In Tanzania malaria has been reported as the leading cause of death and account for 40% of all outpatient attendances in health facilities [2]. Assessment of clinical symptoms is the common method of diagnosing patient’s conditions in the country, with most cases of fever being presumed to be malaria. Few health facilities are equipped with basic laboratory services or use rapid diagnostic test to provide confirmatory diagnoses of malaria; that has resulted into misdiagnosis or over diagnosis of malaria. A study conducted in Muhimbili National hospital showed 87% of patients who received antimalarial treatment with a diagnosis of severe malaria did not have detectable parasitemia, resulting in over-treatment of malaria and neglecting other potentially life threatening conditions [2].

Fever has been used as a major clinical symptom for malaria [3], Now reports show that malaria has been declining [4], while fever remains a major complaint in many outpatients clinical settings [5]. This high prevalence of fever may still be presumed as malaria, hence a need to strengthen confirmation of malaria in order to target use of antimalarial drugs to confirmed cases only. The Tanzania National Guideline for diagnosis and treatment of malaria states that, “a careful assessment of a patient with suspected malaria is essential in order to differentiate between uncomplicated and severe disease. Eventually, laboratory investigations are done to complement clinical diagnosis. In health care facilities without laboratory services, diagnosis is based only on signs and symptoms” [6]. Malaria treatment in Tanzania is mainly based on clinical judgment in the majority of health facilities, especially lower level facilities. Most of the health facilities lack laboratory diagnostic capacity for malaria and hence most of the reported malaria cases are clinically diagnosed. According to NMCP, up to early 2009, 83% of health facilities in Tanzania had no laboratory diagnostic capacity for malaria. In addition, there is a problem of inaccurate malaria microscopic diagnosis and hence misdiagnosis of patients and over use of ACT [7].

Microscopic examination of Giemsa-stained blood films remains a cornerstone of malaria diagnosis throughout Tanzania, but is only available at hospitals and some health centers. Historically, more than 5,000 of the lowest-level facilities (dispensaries and some health centers) had no laboratory diagnostic capacity, leaving health care workers at more than 90% of facilities to diagnose malaria on the basis of clinical signs and symptoms alone. According to the recent WHO guidelines, all suspected malaria cases should be parasitological confirmed prior to treatment, including children under five. NMCP’s policy has changed from presumptive treatment to confirmatory parasitological diagnosis. The NMCP objective is to increase the percentage of laboratory-confirmed malaria cases in public health facilities from a baseline of 20% to 80%. It is clear from numerous assessments that the quality of malaria microscopy is very poor at almost all levels of the health system. Phased rollout of RDTs began in April 2009, starting in areas of low/moderate transmission and expanded to areas of stable/high transmission. Currently, laboratory confirmation is happening in only 20% of the suspected cases and there is no system for laboratory quality assurance and quality control [8‐11]. Over-diagnosis of malaria can lead to inappropriate management of other causes of fever, unnecessarily usage of antimalarials, increasing the burden of malaria treatment cost, drug resistance and unsafe treatment, or prolongation of illness and death [12‐15]. Antibiotic resistance is increasingly becoming a public health problem [13]. Improvement in antibiotics prescription will reduce chances of bacterial resistance and minimize hospital costs. In hospitals, currently the costs for antibiotics accounts for more than 30% of hospital budgets, and about one third to a half of all hospitalized patients receive an antibiotic [14]. It is necessary, therefore, to define and assess the prescription patterns in order to address the problem of irrational prescribing habits, and understand types of drugs commonly co-prescribed with antimalarials [15, 16]. The World Health Organization (WHO) discourages the use of large number of drugs per encounter and irrational co-prescription of drugs with Artemisinin based Combination Therapy (ACT) [9]. The assessment of drug utilisation is important for both clinical and economic reasons.

Several factors influences prescribing behaviour of clinicians, therefore, to improve prescription behaviour, it is necessary to understand predictors of those behaviours [17, 18]. This paper highlights the prescription patterns and assesses the predictors of antibiotics co-prescription with artemether-lumefantrine (AL), the first line recommended antimalarial drug in Tanzania. The study was conducted within 8 government health facilities found in two Health and Demographic Surveillance Systems sites that presented with fever or history of fever and treated with AL.

The INDEPTH Effectiveness and Safety Studies of Anti-malarial Drugs in Africa (INESS) is an exciting new platform that aims to enable African researchers to carry out large Phase IV trials [19]. INDEPTH Network Effectiveness and Safety Studies of Antimalarial Drugs in Africa platform (INESS) operates in two HDSSs in Rufiji District, Coast Region, and in Kilombero and Ulanga Districts, around the town of Ifakara, Morogoro Region, Tanzania. More explanations about the INESS platform is further explained by Masanja [20].

Presumptive treatment is still practiced in rural areas of Tanzania, as evident in this study where 56% of patients attending to government health facilities were treated with AL without parasitological confirmation. This might be due to the WHO’s integrated management of childhood illness (IMCI) strategy [16]. The IMCI strategy, allows children under five years to be presumptively treated on malaria [11]. Regardless of the cost effectiveness of IMCI as explained in [25], there is a need to revise strategies for malaria treatment for children under five for improved malaria treatment outcomes and observation of other fever caused diseases. As Okebe and colleagues and Winskill et al.[26, 27] suggested, children aged 5–15 have higher odds of having malaria than those under five, and this might be due to more focus on under five and causes disease burden to shift to higher age. The Tanzanian National Guidelines for diagnosis and treatment of malaria (2006) stress the use of parasitological confirmation to supplement on clinical symptoms of malaria, and allows for presumptive treatment only when facilities have no laboratory or malaria rapid diagnostic test [6].

Findings from this study shows that presumptive treatment was done for all age groups; under five and those above 5 years. Similar results of presumptive treatment for malaria patients above 5 years was fund in study done in Kenya [16]. Presumptive treatment is commonly due to lack of laboratory expertise and stock-out of mRDT. The practice is commonly done in high transmission areas like the study area [28]. This study shows 20% of patients who were treated with AL were negative, this might be due to poor training of laboratory technicians and poor slides management which leads to mistrust of results and hence clinicians dispensing AL basing on clinical symptoms [27]. Also reported that in some cases clinicians tends to use “mind lines” instead of guidelines when it comes to malaria treatment [29].

The mean number of drugs prescribed was 2.4 drugs per patient per encounter, which is above the WHO guidelines on rational use of drugs with reference values of (1.6-1.8) drugs per encounter [30]. Since all patients received AL then there was a mean of 1.4 drugs co-prescribed with AL observed in rural settings of Tanzania. The study had more children, and number of drugs per encounter seems lower as compared to 3.2 per encounter reported for children in Uganda [31]. Patient receiving the least number of drugs were the one who received AL alone and maximum number of drugs prescribed was 7 drugs per encounter. The number of drugs prescribed was relatively high as compared to 2.1 per person per encounter reported in previous study in Kilombero District (an area included in this study) [32].

Analgesics were commonly prescribed class of drugs as more than 50% of patients prescribed AL were co-prescribed it with Analgesics. This is a common practice to clinicians and reported in other countries such as Sudan [33] and Yemen [34]. History of fever or presenting fever suggested the use of these Analgesics [35], even though the mean temperature did not suggest that as per WHO guidelines [12]. There is a good reason for prescribing analgesics with AL for patients presenting with fever, as they might need medicines to manage fever while continuing with antimalarial treatment.

The study indicates that antibiotics were co-prescribed for 20% of encounters which is less compared to 30.8% observed in Ghana [36]. Antibiotics are associated with some adverse reactions [36] and hence need to be used with great care to reduce those reactions. Other classes of drugs were co-prescribed with AL but in lower rates of less that 5% includes micronutrients supplements, antihelminths, antihistamines and antipsychotics.

Furthermore this study assessed the predictors of antibiotics co-prescription. Predictors found to be associated with the risk of being co-prescribed of other drugs with AL were age group and type of diagnosis (positive, negative and not tested). Children aged less than five years were more likely to be co-prescribed with antibiotics than those aged 5 years and more (Table 2). Similar findings were reported by Torvi et al. in [17]. This might be due to paediatrics being in high risk to suffer from recurrent infections of other systems such as the respiratory tract and gastrointestinal system as seen from Figure 1 that cough was a major symptom after fever and headache [37].

Patients with fever who had negative results on malaria, due to lack of laboratory services, clinicians tend to deal with all possibilities by giving antimalarial if fever was due to malaria and antibiotics if fever was caused by bacterial infection or analgesics for fever itself. A similar observation was done in Zanzibar as those with clinical diagnosis were more likely to be co-prescribed with antibiotics as compared to those with malaria rapid diagnosis tests (mRDT). Those who were not tested were presumptively treated and IMCI guidelines were used for children under five years [38]. For patients positive tested with malaria co prescription was given when deemed necessary as clinicians were almost certain of patient’s problem. For those not tested, co prescription was done basing on clinical symptoms and clinicians used their knowledge at best to assess the need for the co-prescription [38].

Fever is still the main complain regardless malaria decline. Presumptive treatment is still practised. When a child is having fever and tested malaria negative clinicians tends to give more drugs including atimalarial to cure for all possibilities.