In malaria holoendemic areas with no laboratory facilities, anti-malarial treatment is recommended for all patients with fever or a history of fever [
15]. However, although fever is the characteristic sign of clinical malaria, many
P. falciparum infections in endemic areas do not present with elevated temperature [
16]. Studies in areas of high transmission have shown fever or a history of fever with asexual parasitaemia of any density, to have a sensitivity and specificity of 70.4% and 68.9%, respectively for diagnosis of malaria [
2]. Slide confirmation is also of limited utility in areas of intense transmission, as asymptomatic carriage of malaria parasites occurs frequently due to high tolerance to malaria parasites [
17,
18] and the detection of parasites in a blood film or antigens from afebrile individuals does not necessarily indicate clinical malaria [
16]. However the pattern of clinical malaria varies with the intensity of transmission, and in areas of low transmission, any
P. falciparum infection may be synonymous with a malaria episode due to lack of acquired immunity [
19,
20] and the sensitivity of diagnostic approaches may differ. In Thailand, an area of low transmission, a history of fever and headache without cough was found to have a sensitivity of 51% and a specificity of 72% for diagnosis of malaria among 1–15 year old children [
5]. However, other studies have shown that none of the reported symptoms were good predictors of malaria in an area of low malaria transmission in India [
6]. In the present study history of fever was commonly reported but was an unreliable indicator being neither associated with presence of parasitaemia nor with fulfilling the malaria case definition. Headache had the highest sensitivity (84.4%), followed by vomiting (59.2%), for diagnosis of clinical malaria. However, the specificity and positive predictive value of clinical signs and symptoms were generally low, and a reliable clinical algorithm appropriate for the diagnosis of malaria in a low transmission area could not be formulated. This could partly be due to restrictive case definition used in this study as patients with parasitaemia who were not febrile were not classified as malaria cases. This case definition was used because earlier studies in the area showed that only about 60% of asymptomatic parasitaemic individuals became symptomatic within 14 days of follow-up (unpublished data), indicating that probably malaria endemicity in this area could have changed from hypo to meso-endemic due to several factors including climatic changes. The predictive value of diagnostic tests and clinical algorithms is strongly dependent on disease prevalence, and the poor predictive values of individual symptoms observed in this study area reflects the low prevalence of parasitaemia and malaria in highland areas. In addition, fever or
"Omushwija" (the local term for fever in the study area) is a broad term meaning any febrile illness, which could include acute respiratory tract infections that were also common and the reason why more than 27.6 % of the patients had elevated temperature without parasitaemia. Similarly, other symptoms such as headache, rigors and joint pains may occur in other febrile illness making them non-specific for malaria. Severe anaemia was most frequently seen in children less than five years as previously observed [
21]. However, in our study Hb level was associated neither with parasitaemia nor with a malaria episode, indicating that malaria is not an important cause of anaemia in areas of low transmission as opposed to areas of high transmission [
23].
A presumptive diagnosis of malaria was made on 1627 patients but only 24.8% had a malaria episode according to the case definition, resulting in more than 75% of the patients receiving anti-malarial drugs unnecessarily. Only about 18% of the patients received antibiotics. Over diagnosis of malaria in sub-Saharan Africa is common [
2,
8]. By treating all febrile cases as malaria leads to over diagnosis of malaria and this may cause other infections to be under diagnosed and untreated leading to high morbidity and mortality. The presented data confirm the findings of others, and show that even in a highland area of low malaria transmission insufficient thought is given to alternative causes for fever. The overuse of anti-malarial treatments could be due to inadequate skills of peripheral health workers in diagnosing malaria, unreliability of signs and reported symptoms in making the diagnosis of malaria (as the present data suggest) and lack of a standard case definition for malaria in areas of low transmission. In view of the emerging resistance to the commonly available anti-malarial drugs and the recommended change in anti-malarial drug policy to introduce the more costly artemisinin combination therapy (ACT), identification and treatment of only malaria cases with antimalarials would prevent drug misuse and development of drug resistance. Information on the cost-effectiveness of various diagnostic tools and the treatment regimens putting into consideration diagnostic accuracy such as reductions in illness, death and drug resistance is needed to reduce over-diagnosis of malaria and misuse of more expensive drugs [
9]. Lack of expertise, maintenance of microscopes reagents, delays in results and inadequate quality control at peripheral health care facilities make microscopical diagnosis problematic [
3,
23] and RDTs are increasingly being used as alternative to microscopy in many malaria endemic areas [
10‐
12].The sensitivity of 65.5 % of the RDT used in this study was lower than what has been previously observed [
10], which could be due to unreliability of microscopy and RDTs especially in areas of low prevalence and parasite density like in this study area. We can not rule out the batch effect or storage conditions prior to purchase which could have compromised the reliability of the results Yet to improve diagnosis and treatment in populations with little or no immunity, a high-sensitivity diagnostic test is vital to ensure that malaria-infected patients do not go untreated.
The interpretation of the RDT by health workers during case detection could not have been influenced by haemoglobin level since it was not measured at community level or by blood slide readings which was done at later stage in Kampala. The health workers used presumptive diagnosis to treat all patients suspected to be having malaria with the recommended anti-malarial drugs in the national guidelines. The sensitivity of RDT could have been higher than what is observed in this study if more sensitive diagnostic tests such as polymerase chain reaction (PCR) had been used as the gold standard.
In the absence of more reliable malaria diagnosis, the current practice of treating all febrile infections with antimalarial drugs remains unavoidable in low transmission areas, despite increasing drug costs. Although RDTs are easy to use, require minimal expertise and no special equipment, the variability in sensitivity both within and between products calls for an urgent development of high quality, accurate, rapid and affordable diagnostic tools for malaria so that new anti-malarial drugs which are costly and associated with increased toxicity are targeted to people with definite malaria illness.