Comparing the Trends of Vector-Borne Diseases (VBDs) before and after the COVID-19 Pandemic and Their Spatial Distribution in Southern Iran

Objectives We aimed to model and predict the changes in the trend of vector-borne diseases (VBDs) before and after the COVID-19 pandemic in a high-risk area of Iran. Methods This case-series study was conducted in Fars province, south of Iran, between April 2016 and July 2021. All referred cases of VBDs were considered during the five years to investigate the effect of the lockdown on the epidemiological profile of these diseases. We used time-series autoregressive integrated moving average (ARIMA) and seasonal ARIMA (SARIMA) models. Results Pediculosis incidence trend was rising with a peak of 1,146 per 100,000 in 2018, followed by a dramatic decrease reached to the minimum amount of 157.8 per 100,000 in 2021. In contrast, malaria and scabies had a smooth decreasing trend ranging from 2.2 per 100,000 and 7.3 per 100,000 in 2016 to a minimum of 0.2 per 100,000 in 2021, respectively. Likewise, leishmaniasis had a falling trend, with a maximum rate of 82.9 per 100,000 in 2016 to the lowest rate of 9.4 per 100,000 in 2021. However, the difference between observed and expected values revealed that the consequences of the COVID-19 pandemic had increased the number of leishmaniasis cases. Conclusion Tropical regions of Iran, including Fars province, are the favorite destinations for travelers. During COVID-19 outbreaks, some reasons, such as quarantine, movement restrictions, and social distancing, reduced human-vector contact and finally led to the reduction of VBDs in this area.


Introduction
Vector-borne diseases (VBDs) are health issues caused by disease agents and parasites in human populations that Arthropoda transmits.VBDs infect more than one billion people annually.Moreover, more than one million people die from these important diseases including malaria, dengue, trypanosomiasis, leishmaniasis, chagas disease, yellow fever, and other VBDs especially in tropical areas [1].
Factors such as climate change, global warming, the growing trend of international trade, traveling, the overuse of pesticides, the resistance of vectors to common insecticides, and the human population afect the prevalence of vector-borne diseases [2,3].In late 2019, pneumonia cases of unknown cause were reported in the Wuhan (China), and epidemiological surveys showed they were linked to the Wuhan Seafoods and live animals vendors market [4].In less than fve months, COVID-19 (coronavirus disease 2019) has grown from a limited area in Wuhan to more than 5 million people in almost all countries [5].
Some eforts have been made to control this unknown and invasive disease, such as quarantine limitations, which have afected human contacts and the environment.Terefore, it is expected that reports of vector-borne infections would change during the pandemic.A study was performed in Malaysia to determine the impact of COVID-19 lockdown on dengue transmission.Te results showed the incidence trend of this VBD in the frst two weeks of restrictions (the frst stage of quarantine) was signifcantly reduced, while in the second stage, the incidence of dengue increased exponentially [6].
In Iran, however, the prevalence of VBDs is diferent because of the climatic diversity and various geographical regions.According to recent research, malaria transmission still exists in some areas of southern and southeastern Iran, especially in spring and autumn [7].Malaria parasites are microorganisms that belong to the genus Plasmodium that it is transmitted through the bite of some female Anopheles mosquito [8].
Tere were estimated 241 million malaria cases worldwide in 85 malaria-endemic countries in 2020 [9].Leishmaniasis is a VBD afecting the populations of high-risk areas in over 90 countries throughout Asia, Africa, the Middle East, and Central and South America.Leishmania parasites are transmitted through the bite of phlebotomine sand fies [10].In recent decades, the prevalence of leishmaniasis has been rising in Iran because of drastic changes in some demographic factors and climate conditions [11].
According to previous studies, the scabies infestation rate ranges between 1.3% and 57% [12].Sarcoptes scabiei, also called itch mite, is an ectoparasite that burrows canals into the skin and causes scabies.Pruritus is a common symptom of this parasitic disease resulting from an allergic hypersensitivity reaction to the mites, eggs, and fecal pellets [13,14].Lice are blood-feeder parasites that infest the body and head of human beings (pediculosis), especially in people with poor health conditions.In addition, school students, especially girls, are another susceptible population to the disease.Overall, 52,342 students (from primary and secondary schools) and around 20,000 adult persons were infested with Pediculus capitis in Iran for three decades (1990-2020) [15].
Recent studies showed that the world has changed since the beginning of the COVID-19 pandemic, and human interventions have accelerated these changes.Terefore, we expect to see dramatic changes in the pattern of vector-borne diseases, but there is no study has been carried out in this regard.In the present study, we aimed to model and predict the amount of change in the trend of main vector-borne diseases (leishmaniasis, pediculosis, malaria, and scabies) before and after the occurrence of the COVID-19 pandemic.Ten, we decided to address this phenomenon in a critical high-risk area for VBDs in Iran.

Materials and Methods
Tis case-series study was conducted in Fars province between April 2016 and July 2021.Fars province, with an area of 122,400 km 2 , is located in the southwest of Iran with geographical locations 29 °37′30″N, 52 °31′54″E.Information on main reported cases of vector-borne disease was collected from the data registry designed by Iran's Ministry of Health and Medical Education.During these years, 153,550 cases of pediculosis, 10,686 cases of leishmaniasis, 296 cases of malaria, and 820 cases of scabies were reported in the studied area.Te study region was all cities of Fars province except Fasa, Jahrom, Lar, and Gerash (these cities are not covered by Shiraz University of Medical Sciences and have a separate registry system).

Data Analysis.
All referred cases of the main VBDs were considered during the fve years (before and after the COVID-19 pandemic) to investigate the efect of lockdown on the frequency of these diseases.We used time-series autoregressive integrated moving average (ARIMA (p, d, q)) and seasonal ARIMA (SARIMA (p, d, q)(P, D, Q) s) models, where"AR (p)" represents the number ofautoregressive terms, "I (d)" is the diference in the nonseasonal observations, and "MA (q)" shows the size of the moving average.Also, the "P," "D," and "Q" parameters are similar to the "p," "d," and "q" parameters, but for the seasonal component of the data, the "s" parameter represents the length of the seasonal cycle.Te monthly number of reported cases before the pandemic (from April 2016 to January 2020) was modeled to predict how the trend was if there was no COVID-19 pandemic (expected values).Ten, the observed and expected values of 2020 and 2021 (during the COVID-19 pandemic) were compared with independent sample T-tests to fnd the efect of lockdown.To assess the time-series model, ITSM (interactive time series modeling) software (v.2000) was used.Tis software is interactive Windows-based menu-driven software for time-series modeling and forecasting [16].To assess the goodness of ft in SARIMA models, we chose the model with minimum Akaike information criterion (AIC), and after ftting the model, we checked the normality of residuals.All models were ftted appropriately, and residuals were normal.Also, after predicting the trend of each vector-borne disease, we considered the Arc Gis software to map the 5-year cumulative incidence rate of infections to fnd the high-risk regions in Fars province.Te high-risk regions were determined using geometrical interval method.Tis algorithm creates geometric intervals by minimizing the sum of squares of the number of elements in each class.For calculating incidence rate, the denominators (people at risk) were estimated based on Iranian census in the site of statistical center of Iran.Te confdence level for all statistical tests was considered as 0.95% in this study.

Results
Te annual incidence of vector-borne diseases is reported in Table 1.As can be seen, the incidence of pediculosis (head lice) in the population increased over time, peaking in 2018 with 1,146 cases per 100,000 people.After 2018, there was a sharp decline in pediculosis, dropping to just 157.8 cases per 100,000 in 2021.In contrast, malaria and scabies infections showed a gradual yet consistent decreasing trend between 2016 and 2021.Malaria dropped from 2.2 cases to 0.2 cases per 100,000, and scabies declined from 7.3 to a minimum of 0.2 cases per 100,000 during the 2016-2021 periods.Similarly, the incidence of leishmaniasis infections exhibited an overall downward trend, reaching a high of 82.9 cases per 100,000 people in 2016 and then decreasing to a low of 9.4 cases per 100,000 by 2021.
Generally, the incidence of vector-borne diseases was high in the south and southwest of Fars province.Te 5-year incidence of pediculosis had a maximum rate of 21,641 per 100,000 in Qir-Karzin and 20,055 per 100,000 in Zarindasht (Figure 1).Leishmaniasis was in the second stage, with an incidence of 1,915 per 100,000 in Zarindasht and 1,131 per 100,000 in Farashband (Figure 2).Zarindasht, with a scabies incidence of 101.1 per 100,000 (Figure 3), and Shiraz, with a malaria incidence of 13.2 per 100,000 (Figure 4), were the high-risk cities.
According to the time-series results, the linear trend of pediculosis was not signifcant (P � 0.985).Still, there was a signifcant diference (P < 0.001) between observed and expected values before and after the COVID-19 lockdown.
In other words, the ARIMA (1, 1, 1) model, which was ftted to the pediculusis data, showed that lockdown has decreased the number of reported pediculosis (Figure 5).Likewise, there was a signifcant decreasing trend for the data on malaria (P < 0.001), and the comparison of expected values of the SARIMA (0, 1, 5) (1, 1, 0) 12 model with observed values indicated that lockdown had reduced the number of malaria cases (Figure 6).

Discussion
VBDs are illnesses caused by pathogens that are transmitted to humans through the bites of infected vectors, such as mosquitoes, ticks, feas, or fies.Tese diseases pose a signifcant global health threat, afecting millions of people each year.Te transmission of these diseases is infuenced by various factors including climate change, urbanization, and globalization, making them a growing concern in many parts of the world.Preventive measures such as vector control, vaccination, and public awareness campaigns are crucial in reducing the burden of vector-borne diseases and protecting vulnerable populations [2].
Tis study surveyed the change in the epidemiological profle of VBDs before and after the COVID-19 outbreak in Fars province, south of Iran.Te present study was designed to evaluate the efects of COVID-19-related quarantine/ isolation outcomes on the prevalence of some main ectoparasitic diseases including pediculosis and scabies in Fars province.As shown in Figure 1, Zarrin Dasht, Qirokarzin, and Mohr cities showed the highest incidence rate for pediculosis before COVID-19 outbreak among all studied areas.Tis phenomenon can be attributed to some epidemiological and meteorological factors, including being located in the tropical regions of the country as well as unsuitable socioeconomic and health conditions of the inhabitants of these areas.
Contrary to our prediction analysis results, after the onset of the COVID-19 pandemic, the trend of pediculosis has drastically declined in 2021 (Figure 5).Some probable factors that might afect the incidence of pediculosis are the closure of schools, limited population movements, and reduction of physical contact of people, especially among students as the high-risk group during lock down.
Pediculosis is a worldwide parasitic disease afecting school-aged children, primarily girls [15].For the frst time in the country, we investigated the efects of the COVID-19 pandemic on the infestation trend of the studied population to head lice in one of the most populated provinces of Iran.
Our statistical analysis showed that the average annual incidence rate in the two years before the COVID-19 (2018-2019) decreased from 1019.3% to 322.25% two years after the COVID-19 (2020-2021).Similarly, a signifcant decline in pediculosis prevalence was also reported in Argentina (Buenos Aires), from before (69.6%) to during (43.9%)COVID-19 lockdown in 1,118 children [17].Possible reasons for this decline could be people's fear of catching the coronavirus and not going to health centers.Consequently, the number of registered cases of the disease has been reduced.Another explanation was to minimize physical contact with lockdown and implement a social distancing program [18].Human movement restrictions of the COVID-19 lockdown signifcantly infuenced pediculosis, fewer people available outdoors, limited human contact, and school closures and therefore diminished vector-host contact [17].Fars province is now one of the main endemic foci of leishmaniasis in Iran due to the high spread of the disease in almost all parts of the province.Te incidence of leishmaniasis has increased during the last decade [19].Among all studied areas, Farashband and Zarrin Dasht had the highest incidence rate for leishmaniasis (Figure 2).Although the cities of Mohr and Khonj are located in the vicinity of the mentioned cities (Farashband and Zarrin Dasht), they showed a lesser number of leishmaniasis cases.Socioeconomic and educational factors difer in these two regions and can afect the epidemiology of the disease.
Leishmaniasis revealed an increasing trend during the last decade in Iran because of some reasons.In the past, when the prevalence of malaria was high in Iran, insecticides massively were applied to control diferent stages of anopheline mosquitoes, which consequently reduced the population of sandfies and also afected the prevalence of leishmaniasis [20].Given that our country is in the phase of malaria elimination, malaria control operations are no longer performed, which can lead to an increase in the population of sandfies [21].
Other factor infuencing the increase of the disease in recent years is the phenomenon of uncontrolled and nonstandard urban planning.Increased unprincipled urbanization is another infuencing factor on transmission cycle of the disease.Almost all new settlements are being built on the margin areas of cities that are near or on the colonies of rodents.Tese regions usually are suitable habitats for rodents and sandfies, which can make a new focus for leishmaniasis [22].
After the coronavirus pandemic, people's desire to go to medical centers decreased sharply.Disease cases did not go to diagnostic/treatment centers, and this increased parasite reservoir hosts, especially for anthroponotic cutaneous leishmaniasis.
Iran is also one of the countries that have been severely afected by these changes, and some VBDs including leishmaniasis have also been afected by this global phenomenon [23].Fars province is one of the main endemic foci for leishmaniasis in Iran.Tree clinical forms of leishmaniasis existed in this province including zoonotic cutaneous leishmaniasis, anthroponotic cutaneous leishmaniasis, and visceral leishmaniasis.Most cases of the disease are cutaneous form [24].People from Afghanistan and Pakistan have migrated to Iran due to facing war and economic issues, and Fars province is one of the desired destinations for refugees.Tese individuals can act as potential reservoirs of the disease and Journal of Tropical Medicine create the possibility of an epidemic in vulnerable parts of the province [25].
Zarrin Dasht, Qirokarzin, and Darab showed the highest 5-year incidence rate of scabies among all surveyed cities (Figure 3), which may be attributed to the health condition of the residents in these areas.Most scabies disease cases in Iran are reported from military barracks, prisons, and addiction rehabilitation centers [26].Based on our results, the incidence rate of scabies has not signifcantly changed in the observed and predicted value before and after occurrence of COVID-19 pandemic (Figure 7).Scabies is an ectoparasitic disease often reported in places which have not become less crowded since the outbreak of COVID-19.Social distancing and reducing the number of people in such sites are impractical.
Because of various equipped medical centers, Shiraz is an ideal destination for all patients in south Iran.Journal of Tropical Medicine Accordingly, most malaria patients refer to Shiraz for treatment, so most of the reported malaria cases in Shiraz are imported (Figure 4).Te results of this study depicted that malaria in diferent regions of Fars province has a signifcantly lower prevalence than years before the COVID-19 pandemic (Figure 6).Malaria and COVID-19 can have similar clinical manifestations, including fever, sweats and chills, headaches, loss of appetite, muscle pains, sore throat, cough, and difculty breathing.Tese common symptoms may lead to misdiagnosis of malaria and COVID-19, especially when the doctors only pay attention to disease symptoms [27].In Taiwan, a study by Lai et al. investigated the efect of the coronavirus disease epidemic on notifable infectious diseases.Seven routine VBDs showed an overall reduction of 557 (−54.8%)cases from 2019 to 2020.Similar trends were observed for the changes in incidence, which were 2.4 (−55.0%) per 100,000 people for vector-borne diseases [28].
Since the tropical regions of Iran are considered recreational and touristic areas, during COVID-19 outbreaks, some reasons such as the restrictions on travelers' movement and the implementation of general quarantine, caused people to receive fewer bites from mosquitoes and other blood-sucking arthropods in these areas.
Another research considered the efect of coronavirus disinfectants "sodium hypochlorite" on mosquito populations in southwestern Iran (Abadan and Khorramshahr city).Tey showed that excessive use of disinfectants releases large amounts of chlorine gas into the environment, which may disrupt the natural balance of ecosystems.Tey indicated that the decrease in the mosquito population is related to the entry of sodium hypochlorite into the environment [29].
In addition, quarantine, movement restrictions, obligatory isolation, and reduction in night movement reduced the contact between mosquitoes and the residents of the area.It may be another possible reason for the decrease in malaria cases in Fars province [6].

Conclusion
Te pandemic of COVID-19 caused tremendous changes in human lifestyle and the epidemiological pattern of many diseases.Some of the consequences of the COVID-19 can occur in the long term and afect populations after many years.Since the transmission of vector-borne diseases is very complex and many parameters afect them, the epidemiological profle of VBDs should also be discussed and investigated in the post-COVID-19 era.

Figure 6 :Figure 4 : 5 -
Figure 6: Number of reported malaria in Fars province and its prediction during the COVID-19 pandemic.

Figure 7 :Figure 8 :
Figure 7: Number of reported scabies in Fars province and its prediction during the COVID-19 pandemic.

Table 1 :
Annual incidence rate (no. of cases per 100,000) of main vector-borne disease.