1. Introduction
In 2022, nearly half of the world’s population was still at risk of malaria. An estimated 249 million cases occurred and 608000 people died of malaria, 95% of the disease cases and 96% of deaths occur in WHO African Region [
1]. Angola ranked fifth and seventh among African countries in malaria cases and deaths, respectively [
1]. There are significant differences in the disease incidence across Angola provinces [
2]. In the country malaria burden is divided into three distinct zones: high transmission year-round in the north, mesoendemic in the center, and seasonal malaria (unstable) in the south [
3]. Malaria symptoms are non-specific, and clinical diagnostic relies mostly on the basis of fever or a history of fever. Severe malaria is defined as malaria with a significantly increased risk of death compared to others in the community with the illness (uncomplicated malaria) [
4,
5]. More than 90% of severe malaria cases are caused by
Plasmodium falciparum [
4]. The definition of severe malaria is based on clinical and laboratory findings, with some criteria including: impaired consciousness, prostration, acidosis, hypoglycaemia, severe anemia, renal impairment, jaundice, pulmonary oedema, significant bleeding, shock, and hyperparasitaemia [
4,
5].
In low endemic regions, such as Huíla province (capital city Lubango) [
2,
3], severe malaria is common in young adults. Lower exposure to the disease leads to a lower immunity, possibly making them more susceptible to sever malaria [
6,
7]. Despite the severity and impact of the disease, there are few published case studies of severe malaria in adults, particularly in lower endemic areas [
8,
9].
The purpose of this study was to describe the clinical aspects on admission and clinical outcome, of severe malaria patients admitted to Hospital Central Dr. António Agostinho Neto of Lubango (hereafter designated HCL), Angola at the departments of Intensive Care Unit (ICU), Infectiology (INF) and Internal Medicine (MED).
4. Discussion
This study provides an overview of the clinical characteristics observed in severe malaria patients at HCL (Lubango, Huíla province, Angola) during the peak months of January, February, and March in 2021 and 2022.
For the purpose of context, at that the Emergency Room (ER) of HCL mortality rate due to malaria rose 12.3% in 2022 as compared to the same period in the year 2021 (data relative to the first semester, according to HCL internal Official Report). These patients arrived at HCL ER in critical condition, exhibiting multiorgan failure and some of them requiring live saving hemodialysis. This surge in mortality has positioned malaria as the leading cause of death at the ER of HCL during the first half of 2022, surpassed only by stroke and pneumonia. Our study was conducted in order to shine some light to the profile of the patients arriving at the hospital and represents the first study of severe malaria systematic characterization in Angola (apart from one study with 101 patients; Antunes et al, 2020) [
12].
From 2020 to 2021, amidst the coronavirus 19 (COVID-19) pandemic, malaria emerged as the sixth leading cause of mortality among the hospitalized patients admitted to HCL. Furthermore, in 2021, it remains the primary cause for medical consultations, indicating a notable rise in the fatality rate compared to 2020 (increasing from 2% to 4%). According to HCL internal Official Report, the number of cases of malaria had a notable surge, rising from 1640 in 2021 to 2273 in 2022. This might be due to the constrained availability of healthcare services and the heightened level of fear within the population regarding seeking medical help [
13]. Also decreased income of the families, due to COVID-19 pandemic restrictions most probably led to increased challenges in covering health related costs [
14].
At HCL, the total number of severe malaria patients in 2022 almost tripled in comparison to 2021, a trend also registered in other studies from Africa [
15]. However at HCL, the mortality rate decreased substantially from 10.2% to 5.9% in 2022. Severe malaria usually has a mortality well over 5%, and therefore represents a > 50-fold increase in the risk of death [
5]. Many factors affecting the prognosis of
P. falciparum malaria have been identified [
16]. The SOFA a score that describes quantitively the degree of organ dysfunction/failure over time in patients, has become a common feature for the assessment of morbidity in critical illness [
17] including severe malaria [
12]. Increasing SOFA reflects severity of illness [
12,
18]. At ICU, as expected, most patients had multiorgan dysfunction, with a median SOFA of 11 (min. 4, max. 21) though in our study SOFA was not a predictor of mortality, corroborating what was previously reported from Luanda, Angola [
12]. We could not corroborate that SOFA is a good predictor of mortality at ICU [
19]. This cloud be due to low number of patients with negative outcome at the ICU and also the fact that 68% died within the first 48h after admission. Hence, we could not detect the predictive value of SOFA for 28-day mortality [
18,
19].
Mortality due to severe malaria varies substantially, as it depends on (among others) the host immunity, [
5].
P. falciparum malaria positivity rate tends to be higher during productive age [
10,
20] although the severity of the disease tends to be lower, due to higher antimalarial immunity [
6]. In our study the majority of the individuals afflicted by severe malaria were young adults (mean of 29.5 ± 13.6 years) closely mirroring that of the patients who died during the study period (28.9 ± 14.1 years). Recent literature suggests that severe and complicated malaria can occur in this population more frequently than previously thought [
8,
21]. These findings highlight the importance of a focused approach to studying the underlying causes behind this pattern. Although hyperparasitaemia (parasites/µL) is poor predictor of outcome [
5], it is established that high parasitaemia has a negative impact on the overall severity of illness particularly because of increased risk of severe anemia, as the disease progresses [
22]. After renal impairment, impaired consciousness, and jaundice, emerged in our study, as the most commonly observed clinical features overall. These findings align with other studies from sub-Saharan Africa [
8,
9,
21], demonstrating similarities in clinical presentations, with the exception of jaundice, which was notably common in our study.
Our overall findings indicate that in spit the number of fatalities decreased from 2021 to 2022, life threatening signs like renal impairment, jaundice and impaired conscience increased considerably (particularly among patients with a negative outcome). Several other studies have also identified these as prevailing clinical feature among patients with severe malaria [
23].
Among patients with renal impairment, jaundice was the second most common other complication seen in both years (27.3% in 2021 and 47.6% in 2022). Although jaundice has been associated with renal impartment in other studies [
8], the increased occurrence at HCL is nevertheless worrisome. The most common other complication among patients with renal impairment, was impaired conscience. Long-term effects, attributed to cerebral malaria (impaired conscience), are extensively studied in pediatric patients [
11,
24] and thought to be more frequent in children than in adults [
25,
26]. In fact in African children, severe malaria is the leading cause of acquired neurodisability [
27]. In adults studies of neurological sequelae with serial follow-up assessments are currently lacking. Our study was not designed to identify the cause of the increased number of patients presenting renal impairment and impaired conscience from 2021 to 2022, but it highlighted the need to understand the reason behind this increase in order to enable mitigation measures to be implemented at HCL. More so because an emerging link between acute renal impairment and the brain (neurologic deficits and neurocognitive sequelae) in severe malaria patients is gaining momentum [
28,
29,
30,
31,
32,
33]. Rapid diagnosis with timely blood transfusion, renal replacement therapy, and restrictive fluid therapy can improve survival in severe malaria [
34].
Thrombocytopenia is a common finding in adults with severe
P. falciparum malaria and has been presented as a potential predictor of poor outcome in
P. falciparum malaria [
35,
36]. In our study 82.2% of patients that survive and 75.6% of the ones that died, presented thrombocytopenia at addition. In both, the survival group and the diseased, platelets counts decreased as parasitaemia increased (p<0,0001 and p=0,0417 respectively), corroborating other findings [
35,
36,
37,
38]. Hence we agree that thrombocytopenia is a marker of disease severity in adults with
P. falciparum malaria, but has limited utility in prognostication, triage and management [
37].
The time-lapse from symptoms-onset to hospital admission (this data was self-reported and may not entirely reliable), showed an insignificant difference between 2021 (4.6±2.2 days) and 2022 (4.5±2.1 days). By itself, it seems insufficient to account for, or substantiate the increased severity of patients severity of illness, registered in 2022 when compared to 2021. For the same admission severity, outcomes in well-equipped intensive care units (ICUs) with well-trained staff, are better than in peripheral health centers [
39,
40]. Hence, we are inclined to attribute the reduction in mortality by half, during 2022, to a general improvement of the ICU conditions due to the recent hospital (HCL) infrastructure intervention.
This retrospective study is subject to limitations as it is a single-center study and as a result, the generalizability of our findings to other settings may be limited. Nevertheless, this study provides both a baseline and valuable (up to date) data on severe malaria in adult patients in a low transmission region. A well-designed cohort study with adult patients with serial follow-up assessments is needed.