Prospective study on severe malaria among in-patients at Bombo regional hospital, Tanga, north-eastern Tanzania

Malaria is the leading cause of morbidity and mortality affecting about 300-400 million people worldwide and accounts for about 1-2 million deaths every year. It is also the most prevalent tropical disease especially in sub-Saharan Africa [1, 2]. Major causes of malaria related deaths are severe anaemia and cerebral malaria [3‐8]. According to Annual report from Bombo regional hospital for the year 2000, clinically diagnosed malaria accounted for 59.9% of all admissions of which 21.6% had had the severe form of the disease. Anaemia contributed 18.6% of all admissions. There were 228 deaths reported in the paediatric ward of which 33.3% were due to anaemia that was most likely caused by malaria. Causes of severe malaria other than anaemia accounted for 30.7% of all reported deaths [9].

Due to their low acquired immune status, children below five years of age are the most affected by malaria in high transmission areas, whereas in low transmission areas all age groups are equally affected [10, 11]. Although health facility-based reports show that malaria is the leading cause for hospital attendance and admissions, several studies across Africa indicate that the disease is declining [12‐14]. This has also been found in two recently conducted studies at one health facility in the city of Tanga (Makorora Health Centre), where only 10% of patients screened in one study were positive for malaria parasites [15], and in the other study (Msangeni et al, unpublished) data collection activities had to be stopped after failure to obtain suitable candidates despite most of the patients having clinical symptoms suggestive of malaria.

Apart from these two studies which have shown very low malaria prevalence, there is still inadequate information on the epidemiology of laboratory confirmed malaria and the underlying associated risk factors. It was the objective of this study, therefore, to determine the malaria disease pattern and the proportion of malaria associated deaths in patients admitted at Bombo regional hospital. The study was conducted for a period of one year from October 2004 to September 2005 and involved prospective data collection from severe malaria cases admitted to Bombo hospital.

According to health facility statistics, malaria in Tanzania is the leading cause of morbidity and mortality. Ministry of Health data from 2003 show that around 30 per cent of all hospital admissions and 15 per cent of all hospital deaths in Tanzania are due to malaria [24]. Results obtained in our study show that just over half of the patients admitted in the 1 year period October 2004 to September 2005 were cases of malaria. A case of malaria requires the presence of parasites in the blood, supported by fever or history of fever. Reyburn [25] recorded almost similar findings in a study aimed at assessing the diagnosis and outcomes in patients admitted with a diagnosis of severe malaria in north-eastern Tanzania. In the case of fever in BS negative, infections other than malaria should be considered as has been documented by Berkley [26] in Kenyan children where various bacterial infections were found to be responsible for the majority of childhood deaths.

An interesting observation was that a considerable proportion of patients with negative blood smear for malaria parasites and without fever was also admitted as severe cases of malaria. The inclusion of afebrile/apyrexic patients and those with BS negative results for malaria parasites as severe malaria shows that malaria is over-reported in this health facility using clinical diagnosis as the principal method of diagnosis. This is likely to occur in most Sub-Saharan Africa and is facilitated through the syndromic approach, popularly termed as integrated management of childhood illness (IMCI) strategy [27], which is not a precise way of diagnosing diseases [28, 29]. Reyburn [25] had comparable findings where only 46.1% of the clinically examined patients had positive blood smears.

The high rate of cases with negative BS for malaria parasites found in our study could have been attributed to the inclusion of patients with acute febrile illnesses caused by aetiologies other than malaria. This is similar to what Njama-Meya [30] reported in a prospective cohort study of malaria treatment restricted to laboratory-confirmed cases in Ugandan children in which 32% of the febrile episodes were found positive for malaria. This means that majority (68%) of the episodes attended were caused by various other infections.

The proportion of cases with hypoglycaemia in our study was relatively lower than those reported in other areas of Sub-Sahara Africa. For instance, Taylor et al [31] in a study to find out the clinical associations and relationship to quinine dosage of hypoglycaemia in severe malaria in Malawi reported that 20% of children had hypoglycaemia before treatment. In another study that was conducted along the coastal areas of Kenya, English et al [32] reported almost similar proportion (16%) of hypoglycaemia in children on admission. So far, we cannot identify the reasons for the lower proportion of hypoglycaemia recorded in patients in our study.

Moreover, the low sensitivity of laboratory techniques used in diagnosing malaria could have played a part in the increase of BS negative results. Microscopy has some technical drawbacks that make it less sensitive than polymerase chain reaction (PCR) technique in the detection of malaria parasites [33]. It has been noted that considerable number of parasites are lost during the staining process [34‐36], leading to either incorrect estimates of parasite density or the smear being considered as negative in the case of scanty or low parasitaemia, usually in densities of < 50 parasites/μL of blood [37, 38]. Otherwise these children had infections in other body systems causing illnesses resembling severe malaria, e.g. septicaemia, pneumonia, urinary tract infection, HIV/AIDS and other viral infections.

According to the scores obtained with the Blantyre coma scale, it seems that cerebral malaria is a common manifestation of severe malaria among the under-fives in this area. It was observed that among the sick children assessed, 47.3% had altered consciousness indicative of cerebral involvement, and about one third of these had negative BS for malaria parasites. Considering the fact that a case definition of malaria requires the presence of asexual parasites in the blood[39, 40], it is most likely that the patients who had no parasitaemia could have other infections with cerebral manifestations mimicking cerebral malaria, like cerebrospinal meningitis [41]. The proportion of patients who had cerebral malaria (47.3%) was actually higher than that recorded by Pankoui Mfonkeu (20.2%) in Douala, Cameroon [42].

Furthermore, severe anaemia also appeared to be a problem that was significantly associated with malaria (p = 0.001). The trend showed that where there was an increase in the proportion of BS positive results for malaria parasites, there was a corresponding increase in the proportion of severe anaemia cases, and vice versa. This phenomenon was more marked in children below the age of five years who also happened to be the group with the highest proportion of BS positive for malaria parasites. In many malaria endemic countries anaemia has been reported to be the most common complication of falciparum malaria and one of the commonest causes of deaths in children [5, 43, 44]. The overall prevalence of malaria-related severe anaemia in our study was 14.6%, which was almost threefold less compared to 46.0% reported by Newton [45] in children along the coastal area of Kenya between 1989 and 1991 and, by Dzeing-Ella [21] in Gabon between 2000 and 2002, where prevalence of severe anaemia has been reported to be as high as 67.%. In general, the prevalence of malaria-related severe anaemia has a corresponding level with malaria endemicity, for instance, Font [46] found that malaria and anaemia were the main causes of referrals from rural health facilities to the district hospital of Kilombero in Tanzania. Effective malaria control interventions, particularly the country-wide use of insecticide treated bed nets [47, 48] might have been responsible for the decline in malaria prevalence recently reported in Tanzania [49], resulting in a parallel decrease in the level of severe anaemia recorded in our study. However, despite the possible association between malaria and anaemia, it is difficult to draw a strong conclusion of malaria being the sole cause and effect of anaemia due to its multi-factorial nature in the tropical environment [50].

It has been noted that patients reported various duration of illness. Some had been sick for periods as short as one day, whereas a number of them were unwell for almost 3 months. Duration of illness documented in adult patients (≥20 years) was noted to be significantly long among those with negative BS, indicating that some causes other than malaria, like HIV/AIDS, might have been responsible for the sickness in this age group.

Low death rates might have resulted from good access to health services for the majority of the patients living within the city (as has been evidenced by the fact that half of the patients already received some antimalarials even before coming to hospital). Prompt treatment by hospital staff due in part to over-diagnosis of malaria [25] played a role in the low rate of malaria-specific deaths. The use of quinine has proved to be very effective in reducing mortality in our study although recent report indicates that artesunate performs better [51].

Almost half of the patients enrolled in our study had a history of taking antimalarial drugs prior to admission. These patients most likely got their medicines either from low level health facilities before they were referred or they might have obtained the drugs over the counter, which is a common practice in Tanzania. Some studies conducted in the country show that over 71% of patients treat themselves even before consulting a health facility [52, 53].

The high proportion of fever cases in patients with BS negative results for malaria parasites poses the question as to what could be the actual cause of illness. There is a need to find out if malaria still continues to be the leading cause of morbidity and mortality in Tanzania and sub-Saharan Africa as is believed to be, particularly bearing in mind the impact of HIV/AIDS. Use of more specific RDT might also help. This would reduce the problem of over-diagnosis of malaria and bring about rational use of antimalarials and other relatively expensive drugs. We need to revisit the usefulness of IMCI in terms of its impact on disease over-diagnosis and over-prescription of drugs. Improvement of clinical and laboratory diagnosis of malaria is crucial for proper case management and reliable data collection in the changing epidemiological setting. Blood and urine culture tests could be an important component of management of febrile illnesses in general and cases of non malaria febrile illness in particular.