Hemorrhagic Fever with Renal Syndrome Associated with Acute Pancreatitis

Hemorrhagic fever with renal syndrome (HFRS) is a systemic infectious disease caused by Hantaviruses and characterized by fevers, bleeding tendencies, gastrointestinal symptoms and renal failure. It encompasses a broad spectrum of clinical presentations, ranging from unapparent or mild illnesses to fulminant hemorrhagic processes. Among the various complications of HFRS, acute pancreatitis is a rare find. In this report, based on clinical data, laboratory and radiologic examination findings, we describe a clinical case, with HFRS from Dobrava virus, associated with acute pancreatitis. The patient was successfully treated by supportive management. Clinicians should be alert to the possibility of HFRS when examining patients with epidemiological data and symptoms of acute pancreatitis.

Hemorrhagic fever with renal syndrome complicated with aortic dissection:A case report

BACKGROUND Hemorrhagic fever with renal syndrome is caused by hantaviruses presenting with high fever,hemorrhage,and acute kidney injury.Microvascular injury and hemorrhage in mucus were often observed in patients with hantavirus infection.Infection with bacterial and virus related aortic aneurysm or dissection occurs sporadically.Here,we report a previously unreported case of hemorrhagic fever with concurrent aortic dissection.CASE SUMMARY A 56-year-old man complained of high fever and generalized body ache,with decreased platelet counts of 10×10^9/L and acute kidney injury.The enzymelinked immunosorbent assays test for immunoglobulin M and immunoglobulin G hantavirus-specific antibodies were both positive.During the convalescent period,he complained sudden onset acute chest pain radiating to the back,and the computed tomography angiography revealed an aortic dissection of the descending aorta extending to iliac artery.He was diagnosed with hemorrhagic fever with renal syndrome and Stanford B aortic dissection.The patient recovered completely after surgery with other support treatments.CONCLUSION Hemorrhagic fever with renal syndrome complicated with aortic dissection is rare and a difficult clinical condition.Hantavirus infection not only causes microvascular damage presenting with hemorrhage but may be risk factor for acute macrovascular detriment.A causal relationship has yet to be confirmed.

DETERMINATION OF URINE TUMOR NECROSIS FACTOR, IL-6, IL-8 AND SERUM IL-6 IN PATIENTS WITH HEMORRHAGIC FEVERS WITH RENAL SYNDROME

Objective To explore the roles of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome(HFRS). Methods Double-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6 and IL-8 levels in 56 patients with HFRS. Results Serum IL-6, urine TNF, IL-6 and IL-8 concentrations in HFRS patients were significantly higher than those in control group, respectively (P<0.001). The concentrations increased at fever stage, then continued to increase during hypotension stage and peaked at oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6 and IL-8 increased in accord with the severity of the disease and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β_2-microglobulin (β_2-MG), blood ureanitrogen (BUN) and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r=0.5768, P<0.05; r=0.3760, P<0.01). Conclusion TNF, IL-6 and IL-8 activated during the course of the disease. IL-6 is associated with the immunopathological lesions caused by the hyperfunction of humoral immune response. IL-6, IL-8 and TNF are involved in the renal immune impairment. Determining them might, in certain extent, be used in predicting the prognosis and outcome of patients with HFRS.

A Retrospective Study of Continuous Renal Therapy and Anticoagulation in Patients with Hemorrhagic Fever with Renal Syndrome

Objective To observe the application of continuous renal replacement therapy(CRRT) and heparin anticoagulation in patients with HFRS, and to explore a more suitable anticoagulant strategy. Methods Eighty-five severe-type patients(severe group) and 71 critical-type patients(critical group) were enrolled in this study. The frequency of CRRT was compared between the two groups; the frequency of CRRT treated with and without heparin anticoagulation and the frequency of hemorrhage and channel blood clotting induced by the two anticoagulant strategies were observed. Results The frequency of CRRT in the critical group was higher than that in the severe group(P < 0.001). The frequency of CRRT initiated during the overlapping phases in the critical group was significantly higher than that of the severe group(P = 0.032). The total times of CRRT was 103, and 70 of them were treated with heparin anticoagulation. The frequencies of hemorrhage induced by heparin anticoagulation and no heparinization were 16 and 0, respectively, and the frequencies of channel blood clotting were 2 and 4, respectively. Conclusions CRRT has been used extensively in the critical-type patients with HFRS. The heparin anticoagulation and no anticoagulant strategies should be used more rationally in patients treated with CRRT, according to the clinical characteristics of the disease.

Determination of CD_(30) Expression on Peripheral Blood T Lymphocyte Subsets in Patients with Hemorrhagic Fever with Renal Syndrome by FCM

To determine the CD 30 expression on peripheral blood T lymphocyte subsets in patients with hemorrhagic fever with renal syndrome (HFRS) and its clinical implications, double immunofluorescence technique and flow cytometry were used. There was no significant difference among the severe group, mild-moderate group and normal control group in the CD + 4CD - 30 T lymphocyte subset. While the CD + 4CD + 30 T cells of HFRS patients were increased and the difference between severe group and mild-moderate group or normal control group were very significant (P<0.01) and the difference between the mild-moderate group and normal control group was also significant (P<0.05). The CD + 8CD - 30 T cells were increased while the CD + 8CD + 30 T cells decreased obviously in HFRS patients, and the differences among three groups in both subsets were very significant (P<0.01). The results showed that the humoral immunity and cellular immunity are overactive in HFRS patients during acute phase. The loss of balance between T lymphocyte subsets may play an important role in the pathophysiology of HFRS and is closely correlated with the severity of the HFRS.

STUDIES ON DYNAMIC CHANGES AND COMPARISONS OF SERUM SPECIFIC IGM AND IGG ANTIBODIES IN PATIENTS WITH HEMORRHAGIC FEVER WITH RENAL SYNDROME

The speciric IgM and IgG antibodies in serum samples from patients with hemorrhagic fever with renal syndrome (HFRS) were sequentially and simultaneously determined during the course of the disease. The results showed that the detectable days and the days reaching 100% positive rate after onset of illness in specific IgM antibodies were earlier than those in specific IgG antibodies. No significant differences were observed between the titers of specific IgM antibodies on different days after onset of the disease while the titers of specific IgG antibodies differed, significantly on different days after onset of illness (F'= 11. 72,P< 0. 01 ). The titers of specific IgM antibodies in different clinical types were not significantly different at the same illness day but the titers of specific IgG antibodies in various clinical types were significantly different from day 7 to day 8 after onset of disease (F' = 4. 004, P< 0. 05). The levels of specific IgM and IgG antibodies were more stable and the crossings of the IgM and IgG antibody curves presented later in patients with mild and middle clinical types than those in patients with severe and gravis types. These results suggest that the detection of specific IgM antibodies may be useful for the early laboratory diagnosis of HFRS,the excess Production of specific IgG antibodies may play a role in the formation of immune complexes and the exacerbation of pathologic damage in patients with severe and gravis types and the observations of the dynamic changes of specific IgM and IgG antibody curves may have some implications in evaluating the seventies of the disease and the prognosis of the patients with HFRS.

Effect of High-Quality Nursing on Patients with Hemorrhagic Fever with Renal Syndrome

Objective:To explore and analyze the effect of high-quality nursing on patients with epidemic hemorrhagic fever with renal syndrome.Methods:Ninety patients with epidemic hemorrhagic fever with renal syndrome treated in Huyi District People’s Hospital from October 2021 to January 2022 were randomly divided into an experimental group and a control group,with 45 cases in each group.The control group received routine nursing and the experimental group received high-quality nursing.The effect of routine nursing and high-quality nursing were compared and analyzed based on the Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS),the degree of satisfaction with nursing care,and the patients’quality of life.Results:Before nursing,there was no significant difference in the patients’psychological state between the two groups(P>0.05);after nursing,there was significant difference in the patients’psychological state between the two groups(P<0.05);the degree of satisfaction with nursing care of the experimental group was significantly higher than that of the control group(P<0.05);comparing the quality of life of the two groups,the quality-of-life score of the control group was significantly lower than that of the experimental group(P<0.05).Conclusion:For patients with epidemic hemorrhagic fever with renal syndrome,high-quality nursing can significantly and effectively improve their psychological state,level of satisfaction with nursing care,and quality of life.

Study on the Cytotoxic T Lymphocytes Clone Specific for the Nucleocapsid Protein of Hantaan Virus from Peripheral Blood in Patients with Hemorrhagic Fever with Renal Syndrome

In order to elucidate the molecular and immunological mechanisms as well as the pathogenesis of hemorrhagic fever with renal syndrome (HFRS), the CD8 + cytotoxic T lymphocytes (CTL) clone was established directly from peripheral blood mononuclear cells (PBMC) of patients with HFRS. The activities of CTL were detected as usual with EBV-transformed lymphoblastoid cell line (BLCL) as target cells. The results showed that the CTL clone could recognized and killed the target cells with specificity of nucleocapsid protein of Hantaan virus (HTNVNP) with the cytotoxicity percentages of 50.2%, 25.4% and 39.0% respectively. These results demonstrated that the antigenic epitopes of HTNVNP mainly located on the C-terminal of the viral nucleocapsid protein.

CLINICAL SIGNIFICANCE OF DETECTING SERUM ANTIBODIES TO NUCLEOPROTEIN AND GLYCOPROTEIN G_2 OF HANTAAN VIRUS IN PATIENTS WITH HEMORRHAGIC FEVER WITH RENAL SYNDROME

Antibody blocking enzyme linked immunosorbent assays, respectively detecting antibodies to Hantaan virus nucleoprotein (NPAb) and glycoprotein GZ (G,Ab), were developed using monoclonal antibody L133, L13r3, LV48A and LVZB28B NPAb and GZAb in 291 serum samples from 65 patientswith kemorrkagic fever with renal syudrome (HFRS) were detfrmlned by these methods. The positive rates or NPAb were 90N on day 2-3 and 100 % on day 8-9 arter onset of disease, respectively.NPAb titers Increased during fever period and reached Peak levels during kypotensive and oliguric periods of HFRS. It was suggested that NPAb might be an important component Involved in the immunopathogenlc lin'alrmeut of HFRS and the detection of NPAb might be useful for the early diagnosis or HFRS. The I,osltlve rates and titers of GZAh were very low during the rirst three periods,namely rever, hypoteuslve and ollgurlc periods, and reached high levels during the convalescent period. GRAb titers were negatively related to the I,rotelnurla levels during the course of HFRS. It wasIndicated that GZAb might be the main component or neutralizing autlhodles to Hantaan virus Infection and the efrlclent production or GZAb was a good marker ror predicting the recovery and betterprognosis of HFRS.

HLA-E-restricted Hantaan virus-specific CD8^(+)T cell responses enhance the control of infection in hemorrhagic fever with renal syndrome

Infection with the Hantaan virus(HTNV)may result in severe hemorrhagic fever with renal syndrome(HFRS).The functions of HLA-E-restricted CD8^(+)T lymphocytes in virus control and vaccine development have recently received increased attention.The purpose of this research is to discover HLA-E-restricted CD8^(+)T cell epitopes on HTNV as well as the features of these epitope-specific CD8^(+)T cells in HFRS patients.To anticipate HLA-Erestricted HTNV epitopes,the NetMHCpan servers were utilized.The K562/HLA-E cell binding test and the enzyme-linked immunospot assay were used to confirm epitope binding to HLA-E.The number and features of HLA-E-restricted epitope-specific CD8^(+)T lymphocytes in HFRS patients were investigated using tetramer staining,intracellular cytokine labeling,proliferation,and cytotoxicity assays.Six HTNV-derived HLA-Erestricted CD8^(+)T cell epitopes were found in this study.In mild/moderate HFRS patients,the frequency of HLA-E-restricted epitope-specific CD8^(+)T cells was greater than in severe/critical patients.CD38+HLA-DR+HLA-E-restricted CD8^(+)T cells were identified.Meanwhile,CD45RA^(+)CCR7^(-)effector memory-re-expressing CD45RA T cells with early and intermediate maturation and differentiation characteristics predominated.Notably,CD8^(+)T cells from milder HFRS patients produced more interferon-γ,interleukin-2,and granzyme B,had a stronger proliferative potential,and were inversely linked with the amount of plasma HTNV virus load.Furthermore,HLA-E-restricted epitope-specific CD8^(+)T cells demonstrated improved cytotoxic activity in vitro during the acute stage of HFRS.Taken together,the findings demonstrate the protective effects of HLA-E-restricted CD8^(+)T cells during HTNV infection,suggesting that HLA-E-targeted vaccines against HTNV might be developed for HLA-diverse populations.

Epidemic Characteristics and Spatio-Temporal Patterns of HFRS in Qingdao City,China,2010-2022

Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome(HFRS)in Qingdao City,China.Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022.Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed.Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52%.The male:female ratio was 2.8:1.75.3%of patients were aged between 16 and 60 years old,75.3%of patients were farmers,and 11.6%had both“three red”and“three pain”symptoms.The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak.The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou.The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak.Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity.The typical symptoms of“three red”and“three pain”in patients with HFRS were not obvious.

Epidemiological progresses of hemorhagic fever with renal syndrome in China

Purpose To summarize the major achievements of Chinese work on the epid emiology and prevention of hemorrhagic fever with renal syndrome (HFRS) in recen t years, and to give a general review on the present situation of HFRS in China.Data sources Reviews and papers published in Chinese journals, relevant to the objectives, written or collected by the author; and the research work of the author.Study selection An outline was drafted according to the purpose given a bove, and the relevant materials and data were grouped together into different i tems outlined.Data extraction All the materials and data extracted were published or specially assessed.Results HFRS was first recognized in the northeastern China in 1931. It has been found prevalent also in many other parts of China since 1955, and p resently, 28 out of 31 provinces (autonomous regions, or municipalities) have b een proved to be its endemic areas. The total number of cases is 1?256?431 from 1950 to 1997, with 44?304 death (3.53%). 50-100 thousands of cases co uld be registered annually since 1981 when the presence of the Rattus type HFRS wa s first identified serologically in China, with the highest peak in 1986 ( 115 ?985 cases). Three types of endemicity have been differentiated: the Apodemus type, the Rattus type and the mixed type of the two, by their peculiar season al distributions of cases and by methods of serotyping (HI, MAbs serotyping kits ). The epidemiologic features of the Rattus type HFRS are quite different from that of the Apodemus type. 67 species of vertebrates were found to harbor hanta virus antigen or antibodies, but the chief or primary reservoir hosts are A podemus agrarius and Rattus norveg icus only. Besides the commonly recognized enzootic mode of transmission (via co ntact s with the reservoir rodents or their excreta), mite transmission (including cer tain species of gamasid mites, and chigger mites) has been identified as the po tential vectors and reservoir hosts with HFRS. Vertical transmission had been fo un d in pregnant patients with HFRS, and in all three chief host rodents (Apodemus agr arius, Rattus norvegicus, the laboratory rats). The relatively high inapparent i nfection rates in the population of endemic areas of the Rattus type HFRS afte r big outbreaks (8%-20%) are suggested to play a significant role in the gradual decl ine of the incidence of HFRS in that areas. Three kinds of inactivated vaccines ag ainst HFRS (the golden hamster kidney cell vaccine, the Mongolian gerbil kidney cell vaccine and the purified suckling mouse brain vaccine) have been successive ly developed and proved highly effective in the prevention of HFRS. Conclusion Chinese workers on the epidemiology and prevention of HFRS i n China have accomplished great achievements since 1981. As the relatively high annu al incidence of HFRS sustained in recent years, control measures have to be reen forced. Many problems of HFRS and hantavirus infections are still not well under stood or unclear, such as the poly host nature, and the multi modes of transmi ssion, the natural history of hantaviruses and their genetic variation occurred in nature etc. The task for effective control of HFRS and the research on its ep idemiology in China should be held on a high priority.

STUDY ON AEROSOL TRANSMISSION ROUTES OF HEMORRHAGIC FEVER WITH RENAL SYNDROME (HFRS)

The present paper reviews our studies on transmission routes and prophylactic measures of Hemorrhagic Fever with Renal Syndrome (HFRS), including aerosol inhalation, skin injury/mucosa, insect vectors, peroral infection and vertical transmission. The results show that HFRS is transmitted by Hantaan virus via multi-routes. One of them, the aerosol transmission, is perhaps the main route transmitting HFRS from mouse to human beings. The injury and mu-cosa is the main transmission route from mouse to mouse and also an important agent from mouse to human beings. The peroral infection may occur in very serious pollution of foods. The insect vectors may play an important role in the focus of HFRS and in the transmission of HFRS from mouse to human. The epidemiological significance of vertical transmission is yet uncertain. According to the results, four proposals should be emphasized including killing insects and mice, long lasting and combined prophylactics, intensive studies on prophylactic measures on viral aerosols and the blocking of transmission of HFRS from mouse to human via aerosols.

Lack of association between integrin αvβ3 gene polymorphisms and hemorrhagic fever with renal syndrome in Han Chinese from Hubei, China

Hantaviruses belong to the family Bunyaviridae and cause hemorrhagic fever with renal syndrome （HFRS） in humans. 133 integrins, including αvβ3 and αⅡbβ3 integrins, act as receptors on endothelial cells and play key roles in cellular entry during the pathogenesis of hantaviruses. Previous study demonstrated that the polymorphisms of integrin αⅡbβ3 are associated with susceptibility to hantavirus infection and the disease severity of HFRS in Shaanxi Province of China, rather than in Finland. However, the polymorphisms of integrin av133 in patients with HFRS was incompletely understood. Here, we aimed to investigate the associations between polymorphisms in human integrin αvβ3 and HFRS in Han Chinese individuals. Ninety patients with HFRS and 101 healthy controls were enrolled in this study. Analysis of five single nucleotide polymorphism （SNP） sites （rs3768777 and rs3738919 on ITGAV; rs13306487, rs5921, and rs5918 on ITGB3） was performed by TaqMan SNP genotyping assays and bi-directional PCR allele-specific amplification method. No significant differences were observed between the HFRS group and controls regarding the genotype and allele frequency distributions of any of the five SNP sites, and no associations were found between ITGAV polymorphisms/genotypes and disease severity. In conclusion, our results implied that these five SNPs in the integrin αvβ3 gene were not associated with HFRS susceptibility or severity in Han Chinese individuals in Hubei Province.

STUDIES ON THE ENVIRONMENT STRUCTURE OF NATURAL NIDI AND EPIDEMIC AREAS OF HEMORRHAGIC FEVER WITH RENAL SYNDROME IN CHINA

The environment structure of natural nidi and epidemic areas of hemorrhagic fever with renal syndrome (HFRS) possesses characteristics of topography, hydrology, climate, soil, vegetation, and animals. The natural nidi and epidemic areas of HFRS are distributed mainly in plain and hilly regions under 500 meters above the sea level; in plentiful-water zones and transitional zones; in temperate zone and subtropical zone of the eastern monsoon region; in the abundant-aluminum soil region and the sial soil region; in the eastern China damp forest region (agricultural districts and northeast forest districts); in the eastern Asia dampness-prefering animal geographic region. Apodemus agrarius and Rattus norvegicus are the thriving animal population, predominant species or common species as well as the main reservoir hosts and sources of infection in the natural nidi and epidemic areas of HFRS.

Epidemic Prediction of Hemorrhagic Fever with Renal Syndrome Using Grey Multivariable Model

In this paper,we set up a grey multivtriable model to predict the HFRS morbidity.Forecasting test results show that this new model is of general use in the prediction Of the disease.It is particularly appropriate for HFRS investigations and controls.

Research Progress on the Pathogenesis of Hemorrhagic Fever with Renal Syndrome

Hemorrhagic fever with renal syndrome(HFRS)is an acute natural focus epidemic disease characterized by fever,shock,hemorrhage and kidney injury caused by hantavirus infection.Hantavirus mainly infects human vascular endothelial cells,and induces extensive damage to small blood vessels and capillaries.Increased vascular permeability is the pathological basis for clinical manifestations of HFRS.Although domestic and foreign scholars have carried out many studies on the hantavirus pathogenesis,such as the immune pathological response induced by hantavirus,host genetics and apoptosis,thrombocytopenia,coagulation and fibrinolysis dysfunction,and the vascular endothelial damage,the pathogenesis of HFRS has not been fully elucidated and there is no effective drug yet.In-depth discussion of the molecular mechanism of HFRS and finding effective therapeutic drugs are still the research hotspots on the field of hantavirus/HFRS.This review will elaborate the research progress on the pathogenesis of HFRS in recent years.

Expert Consensus on the Prevention and Treatment of Hemorrhagic Fever with Renal Syndrome

Hemorrhagic fever with renal syndrome(HFRS)is an acute zoonosis with a global distribution.China is one of the countries with a high incidence of HFRS,which has long endangered the lives and health of the Chinese people.The Infectious Disease Branch of the Chinese Preventive Medicine Association and the Infectious Diseases Branch of the Chinese Medical Association organized national multidisciplinary experts,based on domestic and international research results combined with experts’practical experiences,to reach this consensus after thorough discussion.This consensus contains 17 recommendations aimed at prevention and identification of important clinical issues to further standardize the prevention,diagnosis,and treatment of HFRS.

Detection of Hantavirus gene from peripheral blood of patients with HFRS in Heilongjiang province and the epidemiological significance

The aim of this study is to further understand the genotype of Hantavirus （HV） from peripheral blood of patients with hemorrhagic fever with renal syndrome （HFRS） and the epidemiological significance of this disease in Heilongjiang province in recent years. Thirty-one serum samples of clinically diagnosed patients with HFRS were examined by RT-PCR to decide the genetic subtype. On the basis of infection season, the serum samples were divided into two groups： winter （Nov, 2003--Feb, 2004）, spring and summer （April, 200d--Sep, 2004）. Further analysis was performed in combination with clinical symptoms. It was found that among the total 31 samples, 22 were sero-positive. Among 14 serum samples in winter, 8 were sero-positive, of which 5 cases were of type Ⅰ （Hantaan virus, HTNV） and 3 of type Ⅱ （Seoul virus, SEOV）. Among 17 samples in spring and summer, 14 were sero-positive, of which 5 cases were of type Ⅰ and 9 of type Ⅱ . So it concludes that both of the two types of Hantavirus exist in Heilongjiang. The type Ⅰ is the main pathogen of HFRS in winter, and typeⅡ is the main in spring and summer.

Spatio-temporal Evolution on Geographic Boundaries of HFRS Endemic Areas in Shandong Province, China

Objective To take effective strategies and measures for the prevention and control of hemorrhagic fever with renal syndrome （HFRS） endemic areas by investigating its dynamic geographical boundaries in Shandong Province, China. Methods The incidence of HFRS from 1982 to 2008 in Shandong Prvince, China, was detected with inverse distance weighting （IDW） interpolation based on geographical information system （GIS）. Dynamic geographical boundaries of HFRS endemic areas in Shandong Province, China, were analyzed by geographical boundary analysis. Results The HTN-type endemic areas of HFRS were located in Linyi City in phase 1 （1982-1986）, the SEO-type endemic areas of HFRS were located in Jining City in phase 2 （1987-2003）, and the endemic areas of HFRS in Jining City gradually disappeared and the endemic areas of HFRS with mixed-types of reservoir rodents were located in Linyi City in phase 3 （2004-2008）. Meanwhile, new endemic areas emerged in the northwestern Shandong province, China. Conclusion The SEO-type endemic areas of HFRS are located in western Shandong Province, China, and the HTN-type endemic areas of HFRS are located eastern Shandong Province, Chin, indicating that the endemic areas of HFRS should be vaccinated and rodents should be controlled.