Thrombocytopenia Due to Plasmodium falciparum Infection and Its Association with Clinical Symptoms, Wad Medani Teaching Hospital, Sudan
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Background: Malaria is an endemic disease in Sudan, particularly in Gezira State. Malaria causes a significant decrease in the number of platelets in patients. This deficiency can be studied by considering clinical symptoms and parasite levels. This is a study of thrombocytopenia due to Plasmodium falciparum infection and its association with clinical symptoms in Gezira State, Sudan.
Methods: A cross-sectional hospital-based study was conducted at Wad Medani Teaching Hospital among Plasmodium falciparum-infected partic- ipants. Malaria was examined using thick and thin blood film of Giemsa staining preparations. Platelet count, WBC count, and hemoglobin level were measured by an automated blood analyzer (Sysmex). Parasitemia levels were calculated according to plus criteria as (+), (++), (+++), and (++++).
Results: In total, 200 Plasmodium falciparum patients were enrolled. The most commonly observed malaria symptoms were fever, headache, and vomiting, with rates of 94 (188/200), 76% (152/200), and 60.5% (121/200), respectively. In most cases, 80.5% (161/200) were categorized as level (+) of parasitemia. Regarding the hematological investigations, decreased hemoglobin levels were detected in 22% (44/200) cases. Leucopenia and leucocytosis were reported in 8% (16/200) and 20% (40/200) of patients, respectively. Thrombocytopenia was observed among 51% (102/200) of studied patients and categorized as mild 29.5 (59/200), moderate 14% (28/200), and severe 7.5% (15/200). Thrombocytopenia was significantly associated with joint pain (0.016) and skin pallor (0.030). Also, platelet count was significantly associated with TWBCs (p = 0.001) count, while no association was observed between platelet count and degree of parasitemia.
Conclusion: Despite the frequency of low platelet counts due to Plasmodium falciparum malaria in the current study, there were no severe consequences for patients, such as bleeding. The significant association between thrombo- cytopenia and malaria symptoms, such as joint pain and skin pallor, can be studied in more detail.
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Introduction
Malaria is an acute life-threatening parasitic infection caused by plasmodium species and transmitted by an infected mosquito bite. The infection is transmitted in extended parts of the tropics, especially Africa [1]. Malaria is curable and preventable. Nevertheless, malaria recorded a high death rate [2]. Strains of the Plasmodium falciparum are responsible for the severe and complicated forms of malaria, especially with the delay in the diagnosis [3]. In Sudan, malaria continues to pose a serious threat to public health. The illness is more common in rural regions because of environmental variables like high transmission rates from mosquito breeding sites and seasonal rains. The situation has been made worse by the persistent dogmatic unrest and the changing environment, which has increased the malaria incidence and transmission season. Moreover, the incidence of malaria infection in Sudan accounted for more than 50% of countries in the Eastern Mediterranean region [4]. Moreover, the complex and unstable conditions that Sudan has faced since 2018 have undoubtedly contributed to creating ideal conditions for the spread of malaria [5], [6].
The impact of malaria on the human body can be observed in short-term and long-term effects. Short-term effects include the destruction of red blood cells (RBC), liver dysfunction, splenomegaly, and systemic inflammation due to the cytokine storm. In contrast, long-term effects lead to chronic anemia, immune suppression, and recurrent fever. In addition to the hematological changes in red blood cells, plasmodium species can affect white blood cells (WBCs) and platelets. Some studies have reported decreased white blood cell counts due to malaria infection in children and immunocompromised adults [7]. However, severe malaria is accompanied by increased white blood cell counts [8]. Thrombocytopenia, or a low platelet count, is a frequently observed complication of malaria [9]. Several mechanisms resulting from malaria infection lead to either the destruction or consumption of platelets, decreasing their number. Destruction may occur in the spleen or by antibodies against malaria, while bone marrow suppression and disseminated intravascular coagulation (DIC) consume platelets. Although thrombocytopenia is a hallmark of Plasmodium falciparum species [10], an effect on platelet counts is frequently documented even with non-Plasmodium falciparum malaria [11]. The present trial aimed to study thrombocytopenia due to Plasmodium falciparum infection in Wad Medani Teaching Hospital and to identify its association with clinical symptoms, sociodemographics, and degree of parasitemia.
Materials and Methods
Study Settings and Population
The study followed a hospital-based cross-sectional design and was conducted at Wad Medani Teaching Hospital, the central hospital in Gezira State. The hospital has a capacity of about 200 beds and a frequency of about 150–300 patients per day. The State is densely populated with a high incidence of malaria in Sudan. The study period was from August 2020 to April 2021. Enrolled participants were patients with malaria diagnosed with Plasmodium falciparum infection. The study recruited adult inpatients who had no other causes of thrombocytopenia and agreed to participate. Patients with thrombocytopenia due to other causes than malaria were excluded from this study.
Sampling
Sampling followed a simple random method. The size was determined using the following formula:
n=z2p(1−p)d2
where:
n is sample size,
z is the level of confidence according to standard normal distribution (95%) = (1.96),
p is the proportion of thrombocytopenia in malaria patients (85%) = (0.85),
d is the tolerated marginal error (0.05).
According to the mentioned formula, the target sample size was 295 participants. Venous blood specimens were collected from suspected admitted patients. Blood samples were obtained with EDTA anticoagulant and sent immediately to the Central Laboratory of Wad Medani Teaching Hospital.
Laboratory Diagnosis
Malaria was diagnosed using a thick and thin film of Giemsa staining preparation. Parasitaemia was estimated from thick films, while thin films allowed parasite species to be identified. Platelet count, WBC count, and hemoglobin level were measured by an automated blood analyzer (Sysmex). Platelet count was categorized into normal, mild thrombocytopenia, moderate thrombocytopenia, and severe thrombocytopenia, while WBCs were classified into normal, low, and high counts. Parasitemia is calculated according to plus criteria as (+), (++), (+++), and (++++).
Data Collection and Analysis
A detailed, close-ended structured questionnaire collected sociodemographics and clinical information about the study subject. Observed symptoms were fever, headache, vomiting, joint pain, skin pallor, and jaundice. Malaria complications documented in this study were convulsion, splenomegaly, and hepatomegaly. Collected data was analyzed by a computer utilizing the program Statistical Package for Social Sciences (SPSS) v22. The analyzed data was presented in tables and figures. The histograms were created using a Python program through Matplotlib (2024). Chi-square was used as a significant test for categorical data. The P-value was considered significant if <0.05.
Results
The total number of malaria patients participating was 200. The age group of 18 to 30 years was the most frequent 28.5% (57/200), followed by 60 to 75 years 21.5% (43/200), 45–60 years 21% (42/200), 30–45 years 19.5% (39/200) and >75 years 9.5% (19/200). The percentage of residents in Gezira State reached 74% (148/200), while the percentage of residents from outside the State reached 26% (52/200). The proportion of malaria patients from rural areas was 78.5% (157/200), and 21.5% (43/200) from urban areas. In terms of occupations, 45.5% (91/200) of the participants were housewives, 20% (4/200) were workers, 11.5% (23/200) were farmers, and 2% (4/200) were employees (Fig. 1).
Fig. 1. Distribution of some sociodemographics of Plasmodium falciparum infection participants.
Most cases were accompanied by fever, headache, and vomiting, with rates of 94% (188/200), 76% (152/200), and 60.5% (121/200), respectively. Less frequent symptoms were joint pain, skin pallor, and jaundice. The most common complication associated with malaria is convulsions, which have been documented in 7.5% (15/200) of current patients (Fig. 2).
Fig. 2. Observed clinical symptoms and complications of Plasmodium falciparum infection among study subjects.
The degree of parasitemia was estimated based on the WHO Plus system. Most cases 80.5% (161/200) were classified as (+), followed by (++) 8.5% (17/200), (+++) 7.5% (15/200) and (++++) 3.5% (7/200) (Fig. 3).
Fig. 3. Parasitological and hematological findings of Plasmodium falciparum-infected subjects.
Regarding hematological changes, decreased hemoglobin levels were detected in 22% (44/200) cases. Leucopenia and leucocytosis were found in 8% (16/200) and 20% (40/200) of patients, respectively. Thrombocytopenia was observed among 51% (102/200) of the patients studied and categorized as mild 29.5 (59/200), moderate 14% (28/200), and severe 7.5% (15/200) (Fig. 3). No association was observed between platelet count and sociodemographic characteristics of the participants (Table I). Thrombocytopenia was significantly associated with joint pain and skin pallor (Table II). Also, platelet count was significantly associated with TWBC count, while no association was observed between platelet count and degree of parasitemia (Table III).
Variable | Platelet count | Total | p | ||||
---|---|---|---|---|---|---|---|
>150 | 100–150 | 100–50 | <50 | ||||
Gender | Male | 38 | 28 | 15 | 10 | 91 | 0.150 |
Female | 60 | 31 | 13 | 5 | 109 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
Age group | 18–30 | 21 | 25 | 9 | 2 | 57 | 0.254 |
30–45 | 23 | 7 | 7 | 2 | 39 | ||
45–60 | 22 | 11 | 4 | 5 | 42 | ||
60–75 | 22 | 12 | 6 | 3 | 43 | ||
>75 | 10 | 4 | 2 | 3 | 19 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
Residence | Urban | 22 | 9 | 9 | 3 | 43 | 0.261 |
Rural | 76 | 50 | 19 | 12 | 157 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
Occupation | Labor | 15 | 14 | 8 | 3 | 40 | 0.209 |
Employee | 1 | 1 | 2 | 0 | 4 | ||
Housewife | 56 | 22 | 8 | 5 | 91 | ||
Farmer | 11 | 5 | 4 | 3 | 23 | ||
Student | 5 | 8 | 2 | 2 | 17 | ||
Others | 10 | 9 | 4 | 2 | 25 | ||
Total | 98 | 59 | 28 | 15 | 200 |
Variable | Platelet count | Total | p | ||||
---|---|---|---|---|---|---|---|
>150 | 100–150 | 100–50 | <50 | ||||
Fever | Yes | 89 | 58 | 27 | 14 | 188 | 0.261 |
No | 9 | 1 | 1 | 1 | 12 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
Headache | Yes | 76 | 47 | 18 | 11 | 152 | 0.436 |
No | 22 | 12 | 10 | 4 | 48 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
Vomiting | Yes | 53 | 41 | 17 | 10 | 121 | 0.270 |
No | 45 | 18 | 11 | 5 | 79 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
Joints pain | Yes | 44 | 28 | 22 | 8 | 102 | 0.016 |
No | 54 | 31 | 6 | 7 | 98 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
Skin pallor | Yes | 8 | 6 | 5 | 5 | 24 | 0.030 |
No | 90 | 53 | 23 | 10 | 176 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
Jaundice | Yes | 3 | 3 | 3 | 0 | 9 | 0.291 |
No | 95 | 56 | 25 | 15 | 191 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
Convulsion | Yes | 7 | 4 | 2 | 2 | 15 | 0.849 |
No | 91 | 55 | 26 | 13 | 185 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
Splenomegaly | Yes | 0 | 0 | 0 | 1 | 1 | 0.006 |
No | 98 | 59 | 28 | 14 | 199 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
Hepatomegaly | Yes | 0 | 0 | 2 | 1 | 3 | 0.036 |
No | 98 | 59 | 26 | 14 | 197 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
Others | Yes | 43 | 16 | 6 | 1 | 66 | 0.006 |
No | 55 | 43 | 22 | 14 | 134 | ||
Total | 98 | 59 | 28 | 15 | 200 |
Variable | Platelets count | Total | P | ||||
---|---|---|---|---|---|---|---|
>150 | 100–150 | 100–50 | <50 | ||||
Degree of parasitemia | + | 80 | 48 | 20 | 13 | 161 | 0.442 |
++ | 10 | 3 | 2 | 2 | 17 | ||
+++ | 5 | 5 | 5 | 0 | 15 | ||
++++ | 3 | 3 | 1 | 0 | 7 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
Hemoglobin levels | Normal | 82 | 42 | 23 | 9 | 156 | 0.088 |
Abnormal | 16 | 17 | 5 | 6 | 44 | ||
Total | 98 | 59 | 28 | 15 | 200 | ||
TWBCs | <4 low | 3 | 4 | 7 | 2 | 16 | 0.001 |
4–11 normal | 70 | 50 | 16 | 8 | 144 | ||
>11 high | 25 | 5 | 5 | 5 | 40 | ||
Total | 98 | 59 | 28 | 15 | 200 |
Discussion
Malaria remains the biggest health threat in Sudan for decades until today. It is endemic in most parts of the country, and cases of infection increase during the fall months and through the beginning of winter. Plasmodium falciparum alone accounts for about 87.6% of all malaria cases [4].
In this study, out of 200 patients, there was a predominance of young females at a rate of 54.5% (109/200), mostly from rural areas, due to the increased number of mosquito breeding sites and, thus, the abundance of vectors.
The severity and progression of Plasmodium falciparum infection in the body can lead to the possibility of many clinical complications. Acute kidney injury and neurological manifestations of cerebral malaria are common complications of severe falciparum malaria infection [12]. Furthermore, It has been estimated that cerebral malaria is responsible for 13% of malaria deaths [13]. This study included patients with two or more malaria symptoms, so asymptomatic cases were absent. Fever, the most common symptom of malaria, was not present in 6% of studied patients, and those who did not develop fever were mainly from the (+) parasitemia group. While all cases in the (+++) and (++++) parasitemia groups manifested with fever. This study indicated that 4.5% (9/200) of the malaria patients included in the study suffered from jaundice, line jaundice, and hyperbilirubinemia in malaria usually occur in association with other complications and may occur in up to 40% of cases [14].
Anaemia is one of the most common complications of malaria infection, especially in areas with high transmission. The cause of anemia during malaria infection is thought to result from the parasite's primary target, the red blood cells, which leads to the destruction of the red blood cells, accelerated removal of both parasitized and non-parasitized cells, bone marrow dysfunction, and the level of parasitemia [15] It is well documented that anemia can arise from severe malaria, primarily as a result of the destruction of infected red blood cells [16], [17]. In this context, the present study found a significant proportion of Plasmodium falciparum infected patients with abnormal hemoglobin levels. To explain the severity of anemia due to malaria, more factors can be considered, such as the parasite's virulence, its resistance to medications, and the host's immune condition [18].
The present study regarding white blood cell count shows that the number of malaria patients with leukocytosis is significantly greater than those with leukopenia. The number of neutrophils increases during the blood phase of malaria, and this change was not observed while the parasite was in the liver [19]. Although some studies have documented a decrease in white blood cell count due to malaria or suggest variation in their numbers, severe malaria is associated with an increase in the white blood cell count [20].
The study showed that the frequency of thrombocytopenia among malaria patients included in the study was 51%, which is also close to the study conducted by Shiraz Jamal in India, which estimated an infection rate of 53% [21]. In a systematic literature review, platelet counts under 150.000 platelets per microliter of blood ranged from 24% to 94% [22]. The study noted that thrombocytopenia occurred more commonly in males than females, consistent with published data [23].
The study revealed a significant association between thrombocytopenia, joint pain, and skin pallor. Other studies have confirmed that joint pain strongly indicates malaria infection [24]. The pallor of the palms due to malaria has been studied previously with Plasmodium falciparum parasitemia in children [25] and malarial anemia; however, no association with thrombocytopenia has been studied. This result encourages further research to confirm the relationship between thrombocytopenia and joint pain on the one hand and skin pallor on the other hand [15]. As documented in other findings, this study is consistent with the conclusion that no significant association was found between thrombocytopenia and the degree of parasitemia. In contrast, a study conducted in India mentioned the association between the severity of malaria and thrombocytopenia [23]. Genetic variation of host and Plasmodium strain characteristics may have an explanatory role for such data. In the current study, only one case presented severe thrombocytopenia accompanied by bruising and nosebleeds, which agreed with what was found in the literature. Fortunately, thrombocytopenia is rarely accompanied by clinical bleeding or biochemical evidence of disseminated intravascular coagulation (DIC), and platelet counts rise rapidly with recovery.
Conclusion
Two hundred patients with malaria were included in the trial; most of them were young, rural women. Thrombocytopenia was seen in 51% of patients, and common symptoms of a Plasmodium falciparum infection were fever (94%) and headache (76%). There were no discernible correlations between thrombocytopenia and age, gender, or place of residence in the sociodemographic domain. Nevertheless, thrombocytopenia was shown to be significantly correlated with symptoms including hepatomegaly, splenomegaly, joint pain, and skin pallor, all of which were indicative of the infection's severity. No discernible association was found between the amount of parasitemia and platelet count; however, a drop in total white blood cell counts was linked to a decrease in platelet count, indicating possible immune system participation.
Study Limitations
1. The study was limited to a single hospital, which may have limited the applicability of the results to other areas.
2. The cross-sectional design was limited to capturing a single moment in time, making it unable to see changes in the illness over time or the long-term effects of thrombocytopenia.
3. Even though the sample size is sufficient to provide preliminary findings, it might not be enough to thoroughly investigate more complex connections between the severity of malaria and thrombocytopenia.
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