Level of Activity Limitation Due to Joints Pain among Hemophilia Patients

Level of Activity Limitation Due to Joints Pain among Hemophilia Patients

Introduction
Hemophilia is an inherited type of disease in which clotting factor VIII cannot produce properly in the body. These diseases can lead to prolonged bleeding after injury or surgery and sometimes bleeding in the joint [1]. The first time hemophilia was discovered in the 2nd century AD and a full description of hemophilia was written in the 19thcentury.The ant hemophilic factor was discovered in the middle of 20 century [2]. Approximately 40,000 peoples are affected by hemophilia worldwide and it is the most complicated disease in the world [3]. Hemophilia is the type of X-linked group disease in which blood coagulation factor VIII cannot produce. Based on clotting factor hemophilia has two types. The deficiency of clotting factor VIII is called hemophilia A and the deficiency of clotting factor IX is also called hemophilia B [4]. Hemophilia A is the most common genetic disorder about 80 % of people have hemophilia A in the overall population of hemophilia diseases. The prevalence of hemophilia A (HA) 1 per 5000 in the general population and the prevalence of hemophilia B (HB) is 1 per 30,000 in overall general papulation .Hemophilia is mainly present in the male population .on based on coagulation factor activity hemophilia is also divided into three further groups .Clotting activity less than 1 percent is severe if 1-5 % is moderate and if clotting greater than 5-30 %. The intensity of bleeding is depending on hemophilia severity. If the intensity of hemophilia is severe, the spontaneous bleeding occurs in soft tissues, joints, nose, and other parts of the body, and if the intensity of diseases is moderate or mild the prolonged bleeding occurs after injury or surgery [5].

Bleeding in joints is more common in hemophilia patients due to a lack of clotting factors. The bleeding in the joint produces more complications in joint. Inflammatory reactions start due to hem arthrosis. Hemophilic arthropathy starts due to repeated episodes of bleeding in joints. The inflammation of the synovial membrane in a joint can lead to a breakdown of articular cartilage of the joint. The articular breakdown starts in early childhood in hemophilic patients. Chronic pain starts in hemophilic joints due to the breakdown of articular cartilage. Chronic hemophilic arthropathy can various effects on bone health, it can cause chronic pain in joints, swelling, limit the daily activities of life, decrease the range of motion of joints and also decrease the quality of life in hemophilic patients. The most common joints which are affected by hemophilia are ankle, knee, hip, elbow, and shoulder joints. There are usually weight-bearing joints that have a bad impact on physical movements. The bleeding the joints cause hypertrophy of physics which lead to valgus deformity in hemophilia patient [6].
Joint illness linked with recurrent joint bleeding causes discomfort and functional impairment in people with hemophilia (PWH) (hemarthroses). Discomfort is common in PWH, according to many studies [7,8] and pain associated with hemophilia has been linked to a worse health-related quality of life (HRQoL). PWH also has mental health problems [9,10]. According to the EQ-5D- 3L, depression affects around one-third of PWH, and the Patient Health Questionnaire (PHQ-9), a scale used to evaluate the severity of depressive symptoms in adults, 37 percent of PWH fulfilled the criteria for depression in another research [11]. The influence of hemophilia on emotional well-being, like other elements of HRQoL, is rarely studied in the therapeutic context. In the comprehensive care environment or to individualize hemophilia therapy, neither general nor disease-specific patient-reported outcome (PRO) tools are routinely employed [12]. Greater expertise with and validation of PRO instruments in PWH may expand their usage for clinical outcome monitoring, as well as provide possibilities to improve patient dialog and treatment of specific outcomes.
The repeated episode of bleeding in joints can start the inflammatory reaction in joints. This inflammatory reaction starts the breakdown process in joints. The breakdown has a serious impact on bone and joint health it can lead to osteoporosis of bone, articular cartilage damage, and bony osteophytes formation in joints, decrease the range of motion of joints and also decrease the daily activity of life. Hemophilia patients have a great risk of depression. The main reason for depression in hemophilia patients is a decrease in the activity of life [13]. Swelling, heat, and immobility are all symptoms of joint bleeding. Furthermore, acute bleeding produces significant discomfort in the affected joint, a symptom that has received little attention in prior research. The bulk of studies in this area focused on the management of pain in general and the use of analgesics [14]. The hemophilia patient faced many psychosocial problems. This problem related to their education and jobs and is also a problem for the caregiver of children with hemophilia and barrier for happy living the people with hemophilia because they cannot perform the daily activity due to pain in joints and difficulty to concentrate his work [15].
Recurrent bleeding, in addition to the acute discomfort, triggers a persistent process that results in synovitis, increased cartilage degradation, and bone deterioration, eventually leading to hemophilic arthropathy. Despite the existence of numerous potential pathophysiological ideas, the actual underlying processes for either blood-induced arthropathy or, more specifically, joint bleedinginduced pain are yet unknown. Similar to other inflammatory joint diseases, the associated inflammatory response might be addressed as one possible source of pain complaints [16,17]. All of these mechanisms, on the other hand, contribute to hemophilia’s reported joint discomfort. As a result, current research is focusing on the causes and effects of persistent pain caused by hemophilic arthropathy. Because pain therapy is often ineffective, and many analgesic and anti-inflammatory medications are prohibited due to their clotting-inhibitory effects, a deeper pathophysiology understanding of pain in persons with hemophilia (PWH) is vitally necessary [18]. Hemophilic patients faced many problems in our society. They face social, mental, and physical problems. The reason for study in hemophilia to find out the activity limitation due to pain or hemarthrosis.

Literature Review

J Michael soucie (2015) et al. Conduct a cross-sectional study in a hemophilic treatment center in the USA. The study sample size was 4343 males aged 2-19 years with hemophilia diseases. They collect the data to assess the joint range of motion. They concluded that the range of motion limitation in hemophilia patients depends on the severity of disease and damage of articular cartilage due to bleeding in joints [19]. M. Witkop (2017) et al. Purpose a crosssectional study to find the prevalence and joint pain due to bleeding joint in people with hemophilia. Their study sample size was 381 whose age is middle to 37. They found that 71 % of people have a severe type of hemophilia and pain in the joint more common the people with hemophilia. In this study, they concluded that the functional activity limitation and quality of life decrease in people with hemophilia are due to chronic pain in the joint [7]. Tyler and W Buckner (2018) conducted a study in which they find the prevalence of functional limitation or living quality in hemophilia patients. The study sample size was 381 adult patients with hemophilia whose age was medial to 34 old. They use the visual analogs scale and brief pain inventory v2 short form to collect the data. They found that patients present severe pain in joints and functional limitation and also decrease the quality of life due to pain in joints. They concluded that early asses of joints bleeding and proper history improve the quality 0f life and activity of daily life [20]. Heng Zhang (2019) et al purpose a cohort study in China to identify the health-related quality of life in children. The study sample size was 42 children and the data was collected from kid’s life assessment tools. The conclusion of that study was health-related quality of life decrease in the children with hemophilia which depend on the severity of hemophilia or joint bleeding and bleeding joint decrease the activity of limitation [21].
MjidDavari and Zahra Gheribnaseri (2019) et al. conducted a cross-sectional study to determine the joints health status and living quality in hemophilia patients. The data was collected from the HR-QO2 questioner and joint health is to collect from hemophilic joint health score the study sample size was 38 people with hemophilia. They concluded that health-related quality of life in hemophilia patients was very low and many joints problems are found due to bleeding in joints [22]. Merel A and timmer (2020) purpose a study to determine the movement or behavior pattern in hemophilia patients. The study sample size was 107 people who have hemophilia. They collect the data from the Kruskal wall test and HJHS TOOLS. They found that runner and bike person with hemophilia is a few limitations in their life and they also concluded that sitting or standing was better for joint health [23]. In 2019 Dr. Edward Nguyo Maina purpose a cross-sectional study to find the prevalence of musculoskeletal problems in people with hemophilia. His study sample size was 37 people with hemophilia. He was data collected from the gilbert joint scoring system. He found that 86.5 % recurrent bleeding in joint, 75.7% of people have limited range of motion, and 70% have flexion contracture formation in joint with hemophilia. They found that musculoskeletal problems was linked with the severity of diseases [24].

Objective

The objective of this study was to determine the: “Level of activity limitation due to joint pain among hemophilia patients.”

Rationale

Hemophilia causes activity limitation or other health disorders in children. The Research gap exist to determine the level of activity limitation occur in hemophilia patients due to pain in joints. This study may also helpful for physiotherapy field to find the best physiotherapy treatment for hemophilia patients regarding their activity limitation. The main rationale of my study to find advance prevention and eliminates the activity limitation risk factor in further studies.

Operational Definitions

Outcome measure tools that was used in the study is Activilm Questionnaire.
The ACTIVILM Questionnaire focus on assessing the basic knowledge of activity limitation by different question their correct answer [25].
Variables:
a) Dependent variable: Activity limitation & pain
b) Independent variable: Hemophilia patient are independent variable.
Value of sensitivity/ specificity/validity/ reliability=0.95.

Materials and Methods

A. Study Design: Design of study was Cross-Sectional.
B. Study Settings: Data for this research was gathered from hemophilic center in Lahore.
C. Duration of Study: 06 months.
D. Sample Size: Sample size is calculated using following formula and parameters.

Here Z _1−α/2 = is standard normal variate (at 5% type 1 error (P<0.05) it is 1.96 and at 1% type 1 error (P<0.01) it is 2.58). As a majority of studies P values are considered significant below 0.05 hence 1.96 is used in formula.
p = Expected proportion in population based on previous studies or pilot studies.
d= Absolute error or precision − Has to be decide by researcher Using 75.7% proportion of the condition sample size is 152 (Table 1).

Table 1: Antibody characterics used for immunohistochemistry.

Nguyo, E.M., Prevalence of musculoskeletal complications among hemophilia patients as seen at Kenyatta National Hospital. 2020, University of Nairobi.

E. Sample Technique: Non-probability convenient sampling was used.
F. Criteria of Sample Selection:
a) Inclusion Criteria:
i. Hemophilia patients.
ii. Age between 5-19 years.
b) Exclusion Criteria: The people who have joint bleeding due to hematoma or other joint disorder such as juvenile arthritis.

Data Collection Procedure

The data was collected after approval from the ethical board of concerned institute. The study design for the study was a descriptive cross-sectional study. The data collected from only people with hemophilia diseases. A convenience non-probability is used as a sampling technique for a minimum sample size of 152 and father data was added according to study requirement to minimum choice of error. The duration of the study was of 6 months and eligibility criteria for participants include volunteers. The data was collected from the ACTIVLIM questionnaire that including the activity limitation assessment and knowledge. The data was collected in the different hemophilic centers in Lahore city. The data collected in the form of a hard copy. And distribute to hemophilia patients. Hemophilia patient was filled the form.

Ethical Consideration

The data was collected after the approval of the ethical board. The participant was provided with information regarding the study and informed consent was signed by the participant. Volunteers were preferred. The identity of participants kept confidential and the participant was allowed to withdraw from the study.

Statistical Analysis

Data was analyzed by using SPSS software for the questionnaire.

Results

a) Among 152 participants, male were 146(96.1%) and female were 6(3.9%) (Table 2 & Figure 1).

Table 2: Frequency distribution of Difficulty in gender.

Figure 1: Frequency distribution of Difficulty in gender

b) Among 152 participants, Putting on a T Shirt was difficult among 27(17.8%) and Easy among s125 (82.2%) (Table 3 & Figure 2).

Table 3: Frequency distribution of Difficulty in Putting on a T shirt.

Figure 2: Frequency distribution of Difficulty in Putting on a T shirt.

c) Among 152 participants, Washing ones upper body was difficult among 35(23.0%) and Easy among 117(77.0%) (Table 4 & Figure 3).

Table 4: Frequency distribution of Difficulty in Washing Ones Upper Body.

Figure 3: Frequency distribution of Difficulty in Washing Ones Upper Body.

d) Among 152 participants, Dressing ones lower body was difficult among 83(54.6%) and Easy among 69(45.4%) (Table 5 & Figure 4).

Table 5: Frequency distribution of Difficulty in Dressing Ones Lower Body.

Figure 4: Frequency distribution of Difficulty in Dressing Ones Lower Body.

e) Among 152 participants, Taking a Shower was Impossible among 2(1.3%), difficult among 87(57.2%) and Easy among 63(45.4%) (Table 6 & Figure 5).

Table 6: Frequency distribution of Difficulty in Taking a Shower.

Figure 5: Frequency distribution of Difficulty in Taking a Shower.

f) Among 152 participants, Sitting on the toilet was Impossible among 12(7.9%), difficult among 91(59.9%) and Easy among 49(32.2%) (Table 7 & Figure 6).

Table 7: Frequency distribution of Difficulty in Sitting on the Toilet.

Figure 6: Frequency distribution of Difficulty in Sitting on the Toilet.

g) Among 152 participants, Taking a bath was Impossible among 4(2.6%), difficult among 85(55.9%) and Easy among 63(41.4%) (Table 8 & Figure 7).

Table 8: Frequency distribution of Difficulty in taking a bath.

Figure 7: Frequency distribution of Difficulty in taking a bath.

h) Among 152 participants, Walking Upstairs was Impossible among 9(5.9%), difficult among 96(63.2%) and Easy among 47(30.9%) (Table 9 & Figure 8).

Table 9: Frequency distribution of Difficulty in walking downstairs.

Figure 8: Frequency distribution of Difficulty in walking downstairs.

i) Among 152 participants, Stepping out of a bath tub was Impossible among 1(0.7%), difficult among 53(34.9%) and Easy among 98(64.5%) (Table 10 & Figure 9).

Table 10: Frequency distribution of Difficulty in Stepping out of a bathtub.

Figure 9: Frequency distribution of Difficulty in Stepping out of a bath tub.

j) Among 152 participants, Opening a door was difficult among 12(7.9%) and Easy among 140(92.1%) (Table 11 & Figure 10).

Table 11: Frequency distribution of Difficulty in opening a door.

Figure 10: Frequency distribution of Difficulty in opening a door.

k) Among 152 participants, Walking outdoor on level ground was Impossible among 4(2.6%), difficult among 52(34.2%) and Easy among 96(63.2%) (Table 12 & Figure 11).

Table 12: Frequency distribution of Difficulty in walking outdoors on level ground.

Figure 11: Frequency distribution of Difficulty in walking outdoors on level ground.

l) Among 152 participants, Washing ones face was difficult among 25(16.4%) and Easy among 127(83.6%) (Table 13 & Figure 12).

Table 13: Frequency distribution of Difficulty in washing ones face.

Figure 12: Frequency distribution of Difficulty in washing ones face.

m) Among 152 participants, hanging up a jacket on a hat stand was difficult among 67(44.1%) and Easy among 85(55.9%) (Table 14 & Figure 13).

Table 14: Frequency distribution of Difficulty in Hanging up a jacket on a hat stand.

Figure 13: Frequency distribution of Difficulty in Hanging up a jacket on a hat stand.

n) Among 152 participants, Wiping ones upper body was Impossible among 1(0.7%), difficult among 52(34.2%) and Easy among 99(65.1%) (Table 15 & Figure 14).

Table 15: Frequency distribution of Difficulty in wipes ones upper body.

Figure 14: Frequency distribution of Difficulty in wipes ones upper body.

o) Among 152 participants, walking upstairs was Impossible among 6(3.9%), difficult among 134(88.2%) and Easy among 12(7.9%) (Table 16 & Figure 15).

Table 16: Frequency distribution of Difficulty in walking upstairs.

Figure 15: Frequency distribution of Difficulty in walking upstairs.

p) Among 152 participants, Carrying a heavy load was Impossible among 13(8.6%), difficult among 133(87.5%) and Easy among 6(3.9%) (Table 17 & Figure 16).

Table 17: Frequency distribution of Difficulty in carrying a heavy load.

Figure 16: Frequency distribution of Difficulty in carrying a heavy load.

q) Among 152 participants, Getting in to a car was difficult among 24(15.8%) and Easy among 128(84.2%) (Table 18 & Figure 17).

Table 18: Frequency distribution of Difficulty in getting into a car.

Figure 17: Frequency distribution of Difficulty in getting into a car.

r) Among 152 participants, Standing for a long time was Impossible among 12(7.9%), difficult among 117(77.0%) and Easy among 23(15.1%) (Table 19 & Figure 18).

Table 19: Frequency distribution of Difficulty in Standing for a long time.

Figure 18: Frequency distribution of Difficulty in Standing for a long time.

s) Among 152 participants, Walking more than 1 km was Impossible among 23(15.1%), difficult among 117(77.0%) and Easy among 12(7.9%) (Table 20 & Figure 19).

Table 20: Frequency distribution of Difficulty in walking more than 1 km.

Figure 19: Frequency distribution of Difficulty in walking more than 1 km.

t) Among 152 participants, Closing a door was difficult among 8(5.3%) and Easy among 144(94.7%) (Table 21 & Figure 20).

Table 21: Frequency distribution of Difficulty in closing a door.

Figure 20: Frequency distribution of Difficulty in closing a door.

u) Among 152 participants, Hopping on one foot was Impossible among 5(3.3%), difficult among 97(63.8%) and Easy among 50(32.9%) (Table 22 & Figure 21).

Table 22: Frequency distribution of Difficulty in Hopping on one foot.

Figure 21: Frequency distribution of Difficulty in Hopping on one foot.

v) Among 152 participants, Putting on a backpack was Impossible among 3(2.0%), difficult among 105(69.1%) and Easy among 44(28.9%) (Table 23 & Figure 22).

Table 23: Frequency distribution of Difficulty in putting on a backpack.

Figure 22: Frequency distribution of Difficulty in putting on a back pack.

w) Among 152 participants, Running was Impossible among 17(11.2%), difficult among 134(88.2%) and Easy among 1(0.7%) (Table 24 & Figure 23).

Table 24: Frequency distribution of D.

Figure 23: Frequency distribution of Difficulty in Running.

Discussion

A study conducted by Buckner, Tyler Win 2018, Study aimed to determine the Assessments of pain, functional impairment, anxiety and depression in US adults with hemophilia. According to this study, participants reported feeling tired (93 percent), worn out (86 percent), very nervous (68 percent), downhearted and depressed (55 percent) and so down in the dumps that nothing could cheer them up (41 percent). According to our study Among 152 participants, male were 146(96.1%) and female were 6(3.9%). Putting on a T Shirt was difficult among 27(17.8%) and Easy among 125(82.2%).Washing ones upper body was difficult among 35(23.0%) and Easy among 117(77.0%).Dressing ones lower body was difficult among 83(54.6%) and Easy among 69(45.4%). Taking a Shower was Impossible among 2(1.3%), difficult among 87(57.2%) and Easy among 63(45.4%).Sitting on the toilet was Impossible among 12(7.9%), difficult among 91(59.9%) and Easy among 49(32.2%).Taking a bath was Impossible among 4(2.6%), difficult among 85(55.9%) and Easy among 63(41.4%) [25].
A study revealed patient was unable to perform the activity, or need complete assistance to perform the activity like transfers/ squatting and running. Some need partial assistance/aids/ modified instruments/modified environment to perform the activity like eating, bathing, dressing going up a stairs, walking running. The other group able to perform the activities without aids or assistance, but with slight discomfort, unable to perform the activities similar to their healthy peers like eating, bathing, dressing going up a stairs, walking and running. A few subjects were able to perform the activities without any difficulty similar to their healthy peer. According to our study among 152 participants, walking upstairs was Impossible among 9(5.9%), difficult among 96(63.2%) and Easy among 47(30.9%). Stepping out of a bath tub was impossible among 1(0.7%), difficult among 53(34.9%) and Easy among 98(64.5%).Opening a door was difficult among 12(7.9%) and Easy among 140(92.1%).Walking outdoor on level ground was Impossible among 4(2.6%), difficult among 52(34.2%) and Easy among 96(63.2%). Washing ones face was difficult among 25(16.4%) and Easy among 127(83.6%). Hanging up a jacket on a hat stand was difficult among 67(44.1%) and Easy among 85(55.9%). Wiping ones upper body was Impossible among 1(0.7%), difficult among 52(34.2%) and Easy among 99(65.1%). walking upstairs was Impossible among 6(3.9%), difficult among 134(88.2%) and Easy among 12(7.9%) [26].
According to another study knees (23.7 percent), elbows (23.7 percent) and ankles (37.4 percent) were the most often reported sore joints (18.9 percent) among hemophilia patients. On the International Physical Activity Questionnaire, 51% said they had done nothing in the previous week. The median sub scores for four physical health domains were lower than the median sub scores for four mental health domains on the SF-36v2 health survey. Leg functions (median, 66.7) and lying/sitting/kneeling/standing (median, 67.5) were the most impacted Hemophilia Activities List domains (range 0 (worst)-100 (best)), whereas self-care was the least impacted (median, 100.0). Ankle scores (median, 6.0; range, 0-40) on the HJHS were lower than elbow/knee scores (median, 4.0/4.0).and according to our study Among 152 participants, Carrying a heavy load was Impossible among 13(8.6%), difficult among 133(87.5%) and Easy among 6(3.9%). Getting in to a car was difficult among 24(15.8%) and Easy among 128(84.2%). Standing for a long time was Impossible among 12(7.9%), difficult among 117(77.0%) and Easy among 23(15.1%). Walking more than 1 km was Impossible among 23(15.1%), difficult among 117(77.0%) and Easy among 12(7.9%). Closing a door was difficult among 8(5.3%) and Easy among 144(94.7%). Hopping on one foot was Impossible among 5(3.3%), difficult among 97(63.8%) and Easy among 50(32.9%). Putting on a backpack was Impossible among 3(2.0%), difficult among 105(69.1%) and Easy among 44(28.9%). Running was Impossible among 17(11.2%), difficult among 134(88.2%) and Easy among 1(0.7%) [27].

Conclusion
Pain was observed most common problem that affected daily activities and quality of life among hemophilia patients. Respondents reported functional impairment that limit the daily routine work and activities they participated in especially with activities involving the lower extremities.

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Health Risks of Simulium (Boophthora) erythrocephalum (De Geer, 1776) in the Valencian Autonomous Region, Eastern Spain

Health Risks of Simulium (Boophthora) erythrocephalum (De Geer, 1776) in the Valencian Autonomous Region, Eastern Spain

Introduction
Black flies (Diptera: Simuliidae) constitute a harmful group of arthropods due to their bites, allergic reactions, and parasitic diseases. In some places, such as Spain, they do not act as disease transmitters, though it is important not to forget their vector role in the transmission of the parasitic agent triggering human onchocerciasis. Climate change and global warming can contribute to the displacement of Simuliidae from their endemic places (Central Africa, South America, Central America, and Yemen) to the European continent. Simulium erythrocephalum (De Geer, 1776) is significant because of its possible action as a vector vehicle and transmitter of disease-causing agents, and because it is a telmophagus insect that lacerates the skin and blood capillaries. In addition, it inoculates saliva whose anesthetic, vasodilator, anticoagulant, and antithrombin substances prevent the host from perceiving the pain of the bite, prevent blood clotting and contribute to increased blood flow in the area, facilitating its intake [1-3]. These components can cause allergic reactions such as dermatitis (which can persist for several days), poisoning such as simuliotoxicosis [4,5], and even asphyxia due to airway obstruction [6]. This species can cause “Black Fly Fever”, a medically recognized syndrome consisting of headache, feverish sweating, chills, swollen lymph glands, joint pain, nausea, lack of energy, laziness, feeling tired and psychological depression [7]. These symptoms are due to the reaction to compounds secreted by the salivary glands [8]. This syndrome can have a significant economic impact due to sick leave, disability compensation, prolonged treatment, hospitalization, and even job loss [7]. The bites of this species can cause intoxication of the blood flow, the symptoms of which consist of accelerated circulation, dyspnea, hyperthermia, hypothermia, nervous disorders and, in extreme cases, death [9].

However, they not only affect man directly but also indirectly, negatively impacting tourist and recreational activities located in rivers and nearby areas, creating economic losses in the tourism sector [1,5]. Therefore, suffering the bites of these Diptera is a brake on the well-being of people and their sources of economic livelihood. Historically, the study of these nematocerous dipterans in Spain was not approached from a health perspective, due to the low significance of their bites in the past. However, from 1995 to the present, the situation has changed considerably. This dipteran is acquiring great relevance in certain regions of the national territory, among which the Valencian Autonomous Region stands out [10,11] where they are colonizing river basins and water channels due to the improvement of the water quality of the rivers, the expansion of the distribution area of plant species used by larvae and pupae as adhesion support, and by the effects on local climatology due to climate change and global warming. All these causes are favoring the increase in simuliid populations, their dispersal, settlement, and colonization in areas where their presence was not perceived in the past. These factors are leading to an exponential increase in the nuisance to human populations close to the breeding, growth, and development areas of the flies. Females of S. erythrocephalum cause discomfort to humans both in Spain [3,12-15] and European countries [16-18]. The simultaneous hatching of adults raises the population level to the status of a plague, causing outbreaks such as those that occurred in the Danube [7] and Ebro [19,20] rivers. Indeed, evidence shows that on certain occasions, administrations have had to resort to the mechanical removal of hydrophytes and helophytes from riverbeds manually or with the aid of an amphibious vehicle to reduce the populations of S. erythrocephalum and other hematophagous species. Land and air treatments with formulations based on the use of Bacillus thuringiensis variety israeliensis have been used in areas that required it, such as La Ribera (Figure 1). Of this species, its anthropophilic preference is recognized [18,21], as well as the tendency of females to form swarms and attack in masse [18]. For these reasons, S. erythrocephalum can act as a potential transmitter of Onchocerca volvulus in Europe. In fact, laboratory studies have already shown that it is a competent vector for the transmission of this filaria [22].

The main objective of this work focused on knowing the distribution of S. erythrocephalum, and on graphically representing the range of air displacement of adults and the municipalities subject to their range of displacement, to highlight the localities whose citizens are at low risk of being bitten. In this regard, it should be noted that the Valencian health system is organized in 24 public health departments (PHD) according to DECREE 205/2018, of November 16, of the Consell, which approved the health map of the Valencian Autonomous Region. These departments are equivalent to the health areas contained in the General Health Law (14/1986 of April 25). The health departments are the fundamental structures of the Valencian health system, being the geographical demarcations into which the territory of the Valencian Autonomous Region is divided for health purposes.

Materials and Methods

From 2013 to the present, a field study has been carried out in which samples were taken from the 14 hydrographic basins and their main tributaries that flow through the Valencian Autonomous Region: Cenia, Cérvol, and Mijares in the province of Castellón; Palancia, Turia, Júcar, and Serpis in the province of Valencia; and Girona, Jalón, Algar, Amadorio, Monnegre, Vinalopó, and Segura in the province of Alicante. For this, a direct sampling was used in each of the points studied, which consisted of an active search for 15 min to detect the presence of the black fly in any substrate of the river. The environmental and physicochemical parameters of the water were also georeferenced and measured. Subsequently, the collected preimaginal individuals were transported under refrigerated conditions to the laboratory where they were processed. Subsequently, taxonomics were identified and classified using dichotomous keys [23,24] and a Leica brand MZ APO stereoscopic microscope assisted with a Leica brand model CLS 100 X cold light source as described in [14,25]. Ultimately, the classified specimens were deposited in the Entomology Collection of the University of Valencia (General Study). Finally, a geographic information system (GIS) was used to prepare the risk map. In addition, note that the bite data provided by the Conselleria de Sanitat Universal i Salut Pública of the Generalitat Valenciana were analyzed using ArcMapTM, ESRI’s ArcGIS® software. Through this program, the cartography referring to the DPH of the Valencian Autonomous Region was elaborated, as well as the relation of the population density and incidence of stings by municipality based on the flight range of the adults represented by buffers. To obtain these results, cartography in vector format provided by the National Center for Geographic Information was used regarding the geographic location of the population areas and the delimitation of the municipal boundaries. The information regarding population density was obtained from the municipal data bank of the ARGOS information portal of the Generalitat Valenciana. The integration of all these factors, providing them with a range of color, allows us to observe the differences in incidences in the studied area.

Figure 1: Departments of Health affected, breeding sites, and flight ranges of S. erythrocephalum.

Results

Of the 137 samplings carried out in the study area, the presence of S. erythrocephalum was verified in four sampling stations. Two were located in the middle (SER1) and upper (SER2) section of the Serpis river, and the other two were in the lower section of the Júcar river basin, one in its tributary the Albaida river (JUR1) and another in the insertion from another of its tributaries, the Magro River (JUR2) (Figure 2). From these breeding areas, and knowing that the flight range of the adults of this species is between 20 and 30 km [7, 8,17], three zones of influence were configured around each of the points where the identified species were found.In the maps, a maximum distance of 15 km was considered as the furthest dispersion range. This decision was made considering that some authors confirmed females of the species traveling up to 5 km in search of hosts from which to obtain blood [19]. At greater distances, it is assumed that the females tend to reduce their movements and therefore their bites, although they are capable of traveling greater distances if required (Figure 2). In this manner, three risk zones were delimited around each of the points where the presence of the species was corroborated. The first zone, with a radius of 5 km, is represented in maroon and indicative of high risk; the second, with a 10-km radius, is represented in orange and indicative of medium risk. The third zone, with a 15-km radius, is represented in yellow and indicative of low risk.

Figure 2: Risk map according to the flight range of S. erythrocephalum females, and information regarding the positive sampling points. SER1 (Villalonga, province of Valencia, 96 meter (m) altitude, 37.6% relative humidity, 17.9°C, coordinates N 38° 52′ 54.7ʺ W 00° 14′ 12.6ʺ), SER2 (Cocentaina, province of Alicante, 372 m altitude, 21% relative humidity, 15.3°C, coordinates N 38° 45′ 10.2ʺ W 00º 25′ 29.8ʺ), JUR1 (Genovés, province of Valencia, 88 m altitude, 79.3% relative humidity, 14.3ºC, coordinates N 38° 59′ 6.2ʺ W 00º 29′ 6.0ʺ) and JUR2 (Algemesí, province of Valencia, −7 m altitude, 64.4 % relative humidity, 31.2°C, coordinates N 39° 11′ 12.7ʺ W 00° 24′ 39.4

The variable population density of the municipalities located in any of the three risk areas varies between 2 and 4,039 inhabitants/ km2, which means that the risk reaches different magnitudes between localities that are under the influence of the same risk area. The measure of the population density of the municipalities involved is provided in quintiles according to the number of inhabitants per km² (Figure 3a). This population density can affect the behavior of the females of the species, inciting them to move to a greater or lesser distance in search of their mandatory nutritional requirement. In this way, females of the four populations detected may exhibit different displacement behaviors. As mentioned, the location of the urban nuclei of the municipalities can mark the pattern of flight distance exhibited by the females of S. erythrocephalum. Therefore, it can be seen that municipalities with a lower population density (0–25 and 25–79) are at low risk (yellow halo, 10 to 15 km), while municipalities with a medium population density (79–206 and 206–894) are in greater numbers and intermediate risk (orange halo from 5 to 10 km). Finally, most of the municipalities with the highest population density (894–12,592) fall within the low-risk halo (15 km away from the breeding place), although they also represent the largest number of municipalities located at high risk (red halo 0 to 5 km) (Figure 3b). Therefore, although a priori it would be expected that the closer the municipality is to the breeding place the greater the number of recorded bites, the data show that these occur more frequently in population centers with the highest density of inhabitants per km2. This conclusion is met repeatedly throughout the twelve months of the four years studied (2015, 2016, 2017, and 2018) without major alterations. In addition, the General Directorate of Public Health and the Valencian Autonomous Region Health Department were contacted to collect data regarding the number of citizens treated in health centers and hospitals as a result of bites caused by insects. The results of interest provided were relevant. Similarly, significant conclusions are provided when analyzing data provided on the number of consultations attended for insect bites during the years 2015, 2016, 2017, and 2018 of the seven health departments involved (PHD9 Valencia-Hospital General, PHD11 La Ribera, PHD12 Gandía, PHD13 Dénia, PHD14 Xàtiva-Ontinyent, PHD15 Alcoi, PHD17 Alicante-San Juan), whose domains coincide with the flight areas specified in the four breeding foci (Figure 1).

Figure 3: a) Total number of bites by municipality considering population density. b) Situation of the municipalities with respect to the flight ranges of S. erythrocephalum and incidence of bites by municipality.

In the first place, and as a consequence of the proximity between the health departments and the breeding centers of S. erythrocephalum, it is assumed that the consultations of citizens affected by insect bites were due to the eating habits of this family of Diptera. Second, and considering the data provided from the records of the 12 months of the last 4 years by the aforementioned health departments, it is corroborated that the number of cases treated for bites has increased in general from 2015 to 2018 (Figure 4). Although most health departments experienced a notable increase in the numbers of patients requiring medical care, in others, there has been a decrease. For example, PHD10 declined from 117 medical assistances in July 2015 to 95 in July 2017. PHD13 reduced from 188 in August 2015 to 111 in July 2018; and PHD12, with 2,233 consultations in August 2015, lowered to 1,360 in the same month of 2018. Likewise, and jointly analyzing the computation of PHD care, a general trend of an increasing the number of cases is observed year after year (Figure 5a & 5b).

Figure 4: Number of cases of bites treated in health departments of the Valencian Autonomous Region close to breeding sites of S. erythrocephalum.

Figure 5: Total number of bite cases treated during the years 2015, 2016, 2017, and 2018 in health departments of the Valencian Autonomous Region close to S. erythrocephalum breeding sites. a) stings per year; and b) stings per month.

Lastly, it is found that the months in which the highest number of cases have been registered coincide with the annual seasons with favorable physicochemical characteristics for the reproduction, development, and growth of this species. The highest peaks are in the months of June, July, and August and, eventually, in September and October (Table 1). However, analyzing the sum of the data for each year, the months in which the most cases were registered were August 2015 and 2016, and July in 2017 and 2018. Although it is still necessary to deepen the study of the bioecology of this species of sanitary importance, the results of this work reveal the need to consider the ethology of this dipteran when implementing surveillance and control plans to reduce its effects on citizen health.

Table 1: Months in which the highest number of health care for bites has been registered.

Discussion

The presence of S. erythrocephalum in the studied areas, together with the proximity of urban centers along the indicated river channels, entails an incidence on humans. The incidence of bites has increased in recent years in the Valencian Autonomous Region, which has taken measures to reduce its repercussions [10,11, 14]. This same effect is reflected in other areas of Spain, such as the Aragonese Autonomous Region [26]. In this work, the risk areas to which the municipalities are subjected are identified, establishing different ranges based on distances and population densities. In this regard, it is not possible to correlate these data with other data from Spain given the lack of knowledge of it.

In conclusion, and in clear harmony with other authors [16,17,19], it is stated that S. erythrocephalum is one of the simuliid species with the greatest impact on the human population. Fortunately, its current vector potential in Spain is zero. As a result of all the above, it is necessary to acquire a global and integrative perspective to understand the phenological, ethological, and bioecological dynamics of this species. This knowledge facilitates implementation of both the necessary surveillance strategies and the most effective and appropriate control actions in each case as quickly as possible. In addition, the growing and numerous citizen complaints, as well as the innumerable medical treatments shown in this article and other regions of the national territory [26], should encourage health professionals to develop a greater knowledge of the characteristics of the pathologies due to this dipteran. This awareness correctly prepares health practitioners to face this type of clinical picture when manifested in citizens and helps predict expected areas of higher incidence resulting from living near the aforementioned hematophagus. Increased knowledge allows for discerning between types of bites of various arthropodsmore specifically, insects-identifying whether they are due to mosquitoes, simuliids, or others. In this way, the data collected in the health consultations of citizens due to these hematophagous and anthropophilic organisms would be of higher quality and reliability, thus being able to infer and analyze these data with greater scientific rigor. Finally, it is necessary to inform and educate the population of how this dipteran can impact their daily life.

Finally, simuliid species with obligate hematophagy of biomedical and veterinary importance [27] such as S. erythrocephalum are generalist species regarding the type of habitat in which they develop, Therefore, these species are capable of tolerating a wide range of ecological conditions. Under this premise and given the current climate change scenario in which certain authors and institutions predict a decrease in coldwater river habitats and greater environmental variability [28], it would be expected that the resulting conditions would favor the distribution and colonization of S. erythrocephalum to new geographic areas, increasing its harm to the well-being of citizens. Therefore, it is recommended to deepen the study of the ecological requirements of the breeding places of black fly species that, like S. erythrocephalum, can be considered a plague negatively affecting public health as a consequence of increased temperatures from climate change [29]. In this way, the knowledge of the bioecology of the species will play a crucial role when it comes to implementing treatment plans for preimaginal states, minimizing the sizes of their populations and reducing their incidences in public health. In the case of S. erythrocephalum, it is important to know that it is a species whose preimaginal development optimum is 20°C, tolerates values higher than 25°C, shows a narrow range of altitudinal tolerance with its optimum around 75 meters above sea level (masl), so that its distribution in the Valencian Autonomous Region is restricted to elevations between 5 and 240 masl [27]. Likewise, some authors ecologically described this species as preferring lentic and warm waters typical of the middle and lower sections of rivers [30].

In addition, the results provided offer useful information on the location of S. erythrocephalum, which will help in the development and execution of surveillance and control programs.

Conclusions
Simulium erythrocephalum is one of the main black fly species that threatens public health in Spain. In recent years, there have been frequent events of massive hatchings of this simuliid, whose nutritional habits have serious repercussions on health care systems. For this reason, it has been pertinent to carry out the present study. This work provides relevant information on the distribution of the species, risk areas, population density, and incidence of bites per municipality according to the flight range of adult specimens, which is useful. The results obtained can be implemented by researchers, public health practitioners, and policy makers as well as companies specializing in the control of noxious species to minimize the magnitude of the problem of black fly bites in the Spanish health system.

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