Viral hemorrhagic fevers

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The region consists of low hillocks adjoining the north—south Sarawat mountain chain and includes valleys that emerge from the mountains [ 14 ]. Each region is divided into a number of governorates and districts, many of them are vastly interconnected with other adjoining regions. In Yemen, three main governorates are within the Tihamah region, which includes small parts of both Hajah and Taiz and the whole city of Hodiedah.

Each governorate is divided into different districts Table 1. Hodeidah is the largest Tihami part and it includes 26 districts. Due to the availability of water sources for cultivation over the last three centuries, the Tihamah ecological habitat has undergone extensive agricultural development. The current methods of irrigation in the region depend mainly on the spate flow, and together with the rainfall, this results in many large and small water pools suitable as breeding sites for certain mosquito species and increases the transmission of viral agents [ 14 ].

The climate of the Tihamah region is hot, windy, and tropical arid to semiarid. The population of Tihamah is one of the highest regions in the Arabian Peninsula, with population density reaching to The total population of the Tihamah part in Saudi Arabia is around 8,,, according to the reports of the census of the General Authority for Statistics in Saudi Arabia; however, the population density varies in the main five regions Table 1. In Yemen, the population of Tihamah is estimated by the Central Statistical Organization of Yemen to be 4,, in , and its population density is the highest among all the other regions of Tihamah [ 12 , 13 ].

The region also has different seaports: Jeddah in the region of Mecca , Jizan, and Hodeidah. Tihamah is an important trade route from Asia to Africa and there is a remarkable African influence in the region. The rural economy depends mainly on agriculture and pastoralism, which represent the potential food security in both countries [ 15 ]. The lawlessness on Yemeni borders increased the number of African refugees coming from African horn countries.

Moreover, the current war in Yemen raised the number of Yemeni refugees from other regions. Several cases and outbreaks caused by viruses of the families Flaviviridae and Bunyaviridae have been recorded in the Arabian Peninsula, but there is no evidence for the presence of Arenaviridae and Filoviridae species in this region. In Yemen, the only described viruses are dengue and Rift Valley fever viruses. Here, we highlight the documented viruses in Tihamah.

Dengue is the most common arbovirus infection that belongs to the family Flaviviridae, genus Flavivirus , and can be transmitted by the bite of infective female mosquitoes of the species Aedes aegypti and, to a lesser extent, A. There are four serotypes dengue virus DENV1—4 , but infection with one of them does not provide cross-protective immunity against the other serotypes [ 17 — 19 ].

After an incubation period of two to five days, dengue virus may cause a mild flu-like illness or quickly progresses to serious dengue hemorrhagic fever—dengue shock syndrome [ 20 , 21 ]. Alarmingly, the incidence of dengue fever increased dramatically between and , from 8. The history of dengue-like virus in Arabian peninsula dates back to — during an outbreak in Tanzania when the diseases known as dinga, dyenga, or dengue, then spread to several countries in East Africa, Saudi Arabia Jeddah, Mecca, and Medina , and Yemen Aden [ 8 ].

A new pandemic was recorded in Yemen from to and from to in Aden [ 8 , 23 ]. The first serological confirmation from Hodeidah was in , when a traveler returning from Yemen to the United States was serologically diagnosed with dengue [ 24 ]. Currently, dengue outbreaks have been documented in Saudi Arabia, mainly in Jeddah — and Mecca and in Yemen — [ 20 , 25 — 28 ].

Most recently, an Italian patient who had returned from Yemen to Italy in was confirmed to have dengue virus infection due to serotype DENV3 [ 29 ]. The endemicity of this disease is also confirmed in the south-western part of Saudi Arabia, mainly in Jizan and Asir [ 30 , 31 ]. In , an outbreak reported the cocirculation of dengue virus and Chikungunya virus CHIKV in different districts of Hodeidah governorate. The predominant serotype was DENV2 [ 10 , 32 ]. Dengue fever and dengue hemorrhagic fever are frequent public health problems in both countries and the most frequently isolated serotypes in the region are DENV1—3 [ 9 , 26 ].

Alkhurma hemorrhagic fever virus AHFV is a tick-borne encephalitis Flavivirus family: Flaviviridae that can be transmitted by the bite of soft Ornithodoros savigni and hard Hyalomma dromedarii ticks collected from camels and sheep [ 33 ]. It was first isolated in Saudi Arabia and described as a unique viral agent of Arabian Peninsula [ 6 , 34 ].

Viral Hemorrhagic Fevers

After an incubation period of two to four days, the disease presents initially with nonspecific influenza like symptoms, including fever, anorexia, malaise, diarrhea, and vomiting. A second phase includes neurologic and hemorrhagic symptoms in severe form. Multiorgan failure leads to fatal outcomes. AHF is a zoonotic disease and clinical cases have been attributed to exposure to livestock camels and sheep , but AHFV is not isolated yet from such animals [ 34 ]. It was isolated in in Jeddah from six patients in Alkhurma district [ 36 ]. Since its first description, several hundred cases of AHF have been reported in different western Saudi governorates with cases peaking in spring and summer [ 35 ].

Consequently, several sporadic cases were recorded in Najran from to [ 38 ]. A recent retrospective study in Saudi Arabia of all laboratory confirmed cases of AHF collected from to showed a high percentage of cases in the Najran region. Najran is an agricultural zone with emphasis on livestock farming, suggesting that cases may have arisen from contact with animals [ 33 ]. A second possibility could be the improved surveillance in this region compared to other regions such as Mecca, Jizan, Taif, and Asir, which have similar agricultural conditions [ 33 ].

There are no reported cases of AHF in Yemen, but due to the large geographic range of the tick vector, it is expected that the distribution of the virus is expanding, with likely undetected human cases in Yemen [ 35 ]. In , the virus was detected in two Italian travelers coming from the southern part of Egypt, which affirms an overseas expansion of geographic distribution of AHFV [ 39 ]. CCHFV causes a subclinical disease in most livestock species and is maintained in the herds through the bite of ixodid ticks of the genus Hyalomma [ 40 ].

The length of the incubation period depends on the mode of transmission of the virus. If the infection is influenced by a tick bite, the incubation period is usually one to five days. The incubation period following contact with infected blood or tissues is usually 5—7 days, with a documented maximum of 13 days [ 40 , 41 ]. The first signs of disease are not specific prehemorrhagic phase.

Viral hemorrhagic fever - Wikipedia

The hemorrhagic phase is characterized by a petechial rash of the skin, conjunctiva, and other mucous membranes, which progresses to bleeding from the gastrointestinal and urinary tracts. Hepato- and splenomegaly are common. As a result of hemorrhage, multiorgan failure and shock can occur [ 40 ]. CCHF virus was first recognized in Crimea in southeastern Europe on the northern coast of the Black Sea after the Nazi invasion in the mids and named Crimean hemorrhagic fever [ 41 , 42 ].

Then, it was isolated in Congo present Democratic Republic of the Congo in , thus resulting in the name of the disease. It was suspected that the CCHF virus was introduced to Saudi Arabia by infected ticks on imported livestock camels, cattle, sheep, goats, and buffaloes , arriving to the Jeddah seaport. The main risk factor was the exposure to the blood or tissue of livestock in abattoirs, but not tick bites [ 44 ].

In , a serosurvey for CCHF antibody was conducted on humans and imported livestock in Saudi Arabia and clearly showed that Sudanese small ruminants exhibited the highest antibody prevalence among all imported livestock 4. An isolation trails from ticks on Sudanese sheep arrived to Jeddah via the seaport in demonstrated the presence of CCHF virus in some of those ticks [ 46 ].

The CCHF is related to the scarification during the Eid-al-Adha feast with lack of controlling livestock movements in and between countries [ 47 ]. RVF is a vector-borne zoonotic disease caused by a Phlebovirus family Bunyaviridae [ 48 ]. RVF virus is transmitted by Culex and A. Humans are incidentally infected when they are bitten by infected mosquitoes, come into contact with aborted or infected animal tissues, or drink unpasteurized milk. It is also a potential bioterrorism agent [ 49 ]. Humans suffering from RVF experience influenza-like symptoms that after the initial febrile stage, in some cases, can develop into hemorrhagic fever, encephalitis, and death [ 49 ].

RVF was historically restricted to the African continent, but a recent outbreak occurred on the Arabian Peninsula [ 43 , 49 — 53 ]. Saudi Arabia reported human cases and deaths. In Yemen, 1, cases and deaths were reported [ 20 , 51 ]. The viruses from Saudi Arabia and Yemen were almost identical to those associated with earlier RVF epidemics in East Africa, and RNA sequences analysis showed similar phylogenetic relationships among these viruses [ 55 ].

Recurrence of outbreaks is now documented in Egypt and the Arabian Peninsula [ 50 ]. This finding suggests the transmission of the virus was from imported mosquitos or livestock from East Africa [ 52 , 56 ]. A recent seroepidemiological study in the southwestern regions of Saudi Arabia Jizan, Asir, and Al-Qunfuda revealed the lack of recent RVF activity among humans in the study areas since the outbreak of [ 57 ].

Through the limited numbers of published data about the outbreaks of VHFs that occurred in the Tihamah region, this review addressed the real threat of those illnesses in the community, especially in the Arabian Peninsula. The first description of VHFs in Tihamah was in the last 19th century, and after the mids, the outbreaks of several VHFs appeared and drew special attention of health care providers from the entire world. Most of those epidemics and epizootics were well characterized before their last introduction in the Arabian Peninsula except the Alkhurma virus, which is the only hemorrhagic fever virus isolated for the first time in the Arabian Peninsula.

Most of those outbreaks were in the African continent and mainly in the neighboring African horn countries Somalia, Ethiopia, Djibouti, and Eritrea and Sudan Fig 1. Furthermore, the southern part of the Arabian Peninsula Bab el Mandeb has a very close position to the African horn and a long story of animal trade and human movements. Tihamah is an entry gate for animal trade heading towards the other parts of the Arabian Peninsula [ 15 ]. Significantly, the recorded VHFs were arthropod-borne disease and mainly mosquito-borne diseases rather than tick-borne diseases, especially in Yemen.

Therefore, the early detection and diagnosis are mandatory to the control of hemorrhagic fever diseases in Tihamah. Encompassing the spread of such diseases in a consistent community requires an active observation for signs of an outbreak, rapid declaration of its frequency, diagnosis, and identification of the causal agent, in addition to strategies and resources for an appropriate and efficient response. Although the responses are often observed in terms of human and animal public health, there are also challenges limiting the control of these diseases in the region of Tihamah, especially, with the lack of vaccine and treatment.

Diagnosis may be delayed due to clinicians' unfamiliarity with these diseases and lack of widely available diagnostic tests, or even differential diagnosis reagents, in some health care institutions. Moreover, the clinical microbiology and public health laboratories in Yemen are not currently equipped to make a rapid diagnosis of these viruses, and clinical specimens in a new outbreak need to be sent to the regional WHO office and the CDC. Indeed, this is not enough for the detection of viral genome and makes the isolation of new viruses either ambiguous or underestimated, like the case of Alkhurma virus.

Additionally, Tihamah is an endemic area for several tropical illnesses, and the contributing symptoms may lead to misdiagnosis in complicated cases. For VHFs that are spread by arthropod vectors, prevention efforts should focus on community-wide arthropod control, which poses a great challenge in Tihamah. In addition to poverty, political conflict in Yemen and associated breakdowns in public health and livestock control have contributed to the emergence of these infections.

Furthermore, the most affected region Tihamah lies on the Red Sea coast with movement of refugees from and to the African horn [ 10 ]. Moreover, the water insufficiency and lack of infrastructure in urban and rural areas require storage of water in water containers and tanks, which create a good environment for mosquitos [ 10 , 32 ].

The sewers overflow in the port city of Hodeidah and electrical outages have aggravated the situation during the current war. Owing to all those factors, breeding sites of mosquitoes have increased, making the region a favorable habitat for their reproduction.


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Worldwide, fumigation campaigns are very useful for controlling vectors; however, the most accessible mitigation in almost all Yemeni governorates is still based on mass spraying, while the distribution of vectors can be disturbingly more heterogeneous. Indoor residual spray IRS has been increasingly used and considered to be a potential alternative to mass spraying. The use of the IRS should be an essential part of the vector control strategies where this intervention is appropriate.

According to the latest reports from the eDEWS in Yemen, residual fumigation campaigns have been recently adopted in some regions, including Hodeidah, but an extension of response is needed for a good prevention program [ 59 ]. Likewise, in southwestern Saudi Arabia, several factors could lead to human infection with these viruses, including the lack of electricity, having livestock in the house, slaughtering animals, and contact with or transporting aborted and dead animals [ 57 ].

Saudi Arabia annually hosts 2—3 million people from across the world for the pilgrimage Hajj. The Hajj rituals require sacrifice of livestock more than 10—15 million small ruminants annually , and their importation from other countries may contribute to the global spread of those pathogens [ 6 , 11 ]. All these factors are thought to be the reasons for the emergence of VHFs in the region, threatening the new adjoining ecozones like Najran, Taiz, and other southern parts of the Arabian Peninsula, mainly in Yemen [ 14 ].

Patients infected with VHF should receive supportive therapy, with special attention to maintaining fluid and electrolyte balance, circulatory volume, blood pressure, and treatment for complicating infections. This is not always possible in Yemen due to the inadequate health care infrastructure, especially in rural areas. Additionally, reporting of cases to health authorities is not always accurate and could be misleading. The lack of community awareness due to illiteracy or inadequate education also represents a great problem in the affected region.

Thus, emphasis on educating and empowering individuals and communities should be the first action considered in the fight against VHFs. The dissemination of information among health care professionals and within communities is also a critical for the achievement of these goals. Better management of VHFs in Tihamah depends on the implementation of general strategies and policies at different levels. At the individual level, scientists, researchers, and health care providers should build strong competencies to assess the needs of the community, find suitable solutions, and develop strategies for better response and control of VHF epidemics.

Increasing the awareness and interactivity within the society and providing training on clinical management, diagnosis, and vector control at the local level with different collaborative centers are essential activities for the effective management and preventive action. At the national level, there is an urgent need to reinforce the disease surveillance and notification system in collaboration with public health authorities to stimulate prompt public health action. The setup of sentinel surveillance centers could provide timely information on the disease situation, which serves as an indicator of the quality of the local preventive or therapeutic measures.

At the international level, health care agencies, organizations, and governments should strive for a deep understanding of those diseases. Collaboration between nations is the most effective strategy for overcoming challenges and enhancing public health surveillance in and between countries. Abstract Viral hemorrhagic fever VHF refers to a group of diseases characterized by an acute febrile syndrome with hemorrhagic manifestations and high mortality rates caused by several families of viruses that affect humans and animals.

Funding: The authors received no specific funding for this work. Background Viral hemorrhagic fever VHF refers to a group of emerging diseases characterized by acute febrile syndromes with vascular damages, hemorrhagic manifestations, and high mortality rates [ 1 ]. Geographic, climatic and demographic features of Tihamah Tihamah or Tihama refers to the Red Sea coastal plain of the Arabian Peninsula.

Download: PPT. Fig 1. Hemorrhagic fever viruses circulating in Tihamah Several cases and outbreaks caused by viruses of the families Flaviviridae and Bunyaviridae have been recorded in the Arabian Peninsula, but there is no evidence for the presence of Arenaviridae and Filoviridae species in this region. Deafness, thought to be an immune-mediated injury, may develop suddenly or gradually over a few hours during convalescence [ 27 ]. Marburg virus disease and Ebola hemorrhagic fever have very similar clinical features. After an incubation period that usually ranges from 5 to 14 days, there is sudden onset of illness with fever, headache, malaise, myalgia, arthralgia, abdominal pain, nausea, conjunctival injection, and a relative bradycardia.

Other common symptoms include diarrhea, which may be bloody, vomiting, and anorexia. Despite severe hepatic involvement, overt jaundice is not common until the terminal stage of illness [ 28 ]. A prominent feature is a severe sore throat associated with marked edematous swelling of the soft tissues at the back of the throat, dysphagia, and, in more severe cases, dyspnea.

A short-lived, profuse, nonitchy maculopapular rash against an intensely erythematous background, which blanches on pressure, is often seen in white-skinned patients around the fifth day of illness. It is followed by desquamation of the affected skin during the early convalescent phase. On dark skins, the appearance of desquamation without a prior rash may be the only visible indication of skin involvement.

Late eye complications in the form of a unilateral uveitis have been noted in one case of MVD, in which viable virus was isolated from the anterior chamber of the eye 1 week after onset of ocular symptoms 87 days after onset of MVD [ 29 ], and in 1 patients with EHF, in 1 of whom the presence of Ebola virus in a conjunctival swab specimen was suggested by reverse-transcriptase—PCR 22 days after onset of EHF [ 30 ]. The differential diagnosis of the VHFs is extensive and based on other infections associated with features such as fever, rash, jaundice or other evidence of hepatic and renal involvement , hemorrhage from multiple sites including needle puncture wounds , leukopenia, and thrombocytopenia.

Infections such as falciparum malaria, the acute form of African trypanosomiasis, typhoid fever, leptospirosis, relapsing fever, meningococcal infections, septicemic and pneumonic plague, rickettsial infections, viral hepatitis, other bacterial septicemia, dengue fever, and other arboviral infections must therefore be considered.

Samples to be submitted for laboratory confirmation include blood, throat washings, urine, and various postmortem tissue specimens, especially of the liver. Laboratory confirmation of a VHF is usually based on electron microscopy, virus isolation, and serological demonstration of viral antigens and antibody in the form of specific IgM and IgG. An immunohistochemical assay was recently developed to detect Ebola virus in formalin-fixed skin biopsy samples and provided a simple, safe, and sensitive method for laboratory confirmation of Ebola virus disease [ 31 ].

Confirmatory investigations should be carried out in a specialized virology laboratory with maximum containment facilities biosafety level 4. Available evidence indicates that the majority of nosocomial VHF cases have been acquired by inoculation with virus-contaminated instruments or by direct contact with blood or body fluids from infected patients. Isolation of VHF patients whenever possible is strongly recommended.

Strict barrier nursing and universal precautions with blood, body fluids, and potentially contaminated objects are highly effective. These measures must be activated as soon as a diagnosis of a VHF is suspected. The use of a facial shield or mask and goggles is useful in avoiding entry of virus-contaminated blood or secretions through conjunctivae, nose, or mouth when a patient suddenly vomits, coughs, or sneezes.

These measures should never be delayed until laboratory confirmation of a VHF is obtained, as secondary virus transmission is most likely to occur in the interim, when appropriate precautions are not practiced. Nonimmune YF contacts should be immunized without delay. Preventive measures should apply to doctors, nurses, and anyone else such as visitors, technicians, clerks, cleaners, messengers, and laboratory personnel who may come into contact with a patient infected with a VHF or with potentially infectious blood or body fluids. Healthy persons who have already been in contact with the patient when a VHF diagnosis is being considered should be subject to daily medical surveillance, but without quarantine or isolation, for a period of 21 days from the date of last contact.

All samples for laboratory investigations should be clearly labeled, securely packaged, and forwarded by trained messengers. The receiving virology laboratory, as a matter of routine, is likely to practice all necessary containment measures during specimen processing. However, the same is not necessarily the case with all clinical pathology laboratories where regular monitoring of the patient's microbiological, hematologic, and chemical parameters may be performed.

Such laboratories should be fully informed about the patient's diagnosis and its implications at the earliest opportunity.

Community and Environment

Treatment of most VHFs is mainly supportive, and availability or lack of facilities for regular monitoring and support of vital functions may affect the course and outcome of illness. Treatment with ribavirin has significantly reduced the mortality rate associated with Lassa fever, with best results obtained when the drug is started early in the course of illness [ 33 ].

For C-CHF, because of its relative rarity and high mortality rate, placebo-controlled trials with ribavirin have not been appropriate. Although iv ribavirin is the preferred formulation, this has not always been readily available. However, the use of oral ribavirin early in the course of this disease appeared to result in a higher survival rate than had been observed among untreated patients [ 34 ].

Ribavirin is ineffective against filoviruses.

Viral hemorrhagic fever

The results of administration of immunoglobulin to laboratory animals infected with Ebola virus generally have been disappointing, as have results with IFN [ 35 ]. In a small, noncontrolled trial, transfusion of blood from patients convalescing from Ebola virus infection resulted in a markedly lower case-fatality rate However, these patients generally received better care than the nontreated patients who had presented earlier during the course of the outbreak.

In addition, they were transfused late in the course of illness, when they probably were already on the way to recovery [ 37 ]. Recent studies suggest that certain nucleoside analog inhibitors of S-adenosylhomocysteine hydrolase inhibited replication of Ebola virus. One of these compounds, carbocyclic 3-deazaadenosine Ado, John Montgomery, Southern Research Institute , conferred significant protection on laboratory mice when they were treated by the second day after experimental Ebola virus infection [ 38 ].

This is the first compound capable of protecting animals infected with Ebola virus from this otherwise lethal infection. Although much more work is needed, these results may herald the advent of a much-needed specific therapeutic drug for filovirus infections. In terms of the International Health Regulations, YF remains the only disease subject to control by compulsory vaccination of international travelers from areas of endemicity or infection.

The YF vaccine consists of a live attenuated 17D strain of the virus and has proved to be very safe and effective. However, infants, pregnant women, and immunocompromised persons are generally excepted from this regulation, provided they are issued a medical certificate specifying the reasons for nonvaccination. Nevertheless, when the risk of YF exposure is significant, vaccination may be the less harmful option. Vaccination certificates must be issued 10 days before arrival in a YF-affected area and remain valid for 10 years [ 39 ].

RVF vaccination is not recommended for the average traveler, but although it is not generally available, it may be indicated for those who are traveling to participate in international RVF-outbreak investigations or are otherwise at high risk of exposure. Mosquito-avoidance measures should be routinely practiced by travelers to prevent not only YF and RVF but also malaria, dengue, and other mosquito-borne infections.

Such measures include the wearing of long sleeves and long trousers, as well as the use of mosquito repellents, bed nets ideally impregnated with a residual insecticide, such as permethrin , insecticide-spraying of sleeping quarters unless air conditioned , and screening of windows and doors. Tick-avoidance measures are important in the prevention of C-CHF, especially for backpackers and hikers, and include the use of protective clothing, with trousers tucked into socks and boots, and tick repellents.

Frequent body searches should be made to find and remove ticks. No specific measures are needed by the average traveler to prevent LF. Avoiding contact with rodents and avoiding sleeping in potentially rodent-infested premises in rural areas are recommended. Contact with nonhuman primates, the only immediate animal source of filovirus infections implicated thus far, should be avoided. Expatriate health care workers in African clinics or hospitals should, in addition, practice barrier precautions when in doubt about a patient's diagnosis.

Standard precautions should be practiced at all times and with all patients. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents. Epidemiology of Viral Hemorrhagic Fevers in Africa.

Clinical Features.


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    Cite Citation. Permissions Icon Permissions. Abstract This short review covers 6 viral hemorrhagic fevers VHFs that are known to occur in Africa: yellow fever, Rift Valley fever, Crimean-Congo hemorrhagic fever, Lassa fever, Marburg virus disease, and Ebola hemorrhagic fever. Search ADS. World Health Organization. Google Preview. Potential importation of dangerous exotic arbovirus diseases.

    A case report of Rift Valley fever with retinopathy. Antigenic similarity between the virus causing Crimean haemorrhagic fever and Congo virus Epidemiologic and clinical features of Crimean-Congo hemorrhagic fever in southern Africa. Lassa fever, a new virus disease of man from West Africa. Isolation and characterization of the virus.

    Outbreak news. Epidemic Rift Valley fever in Egypt: observations of the spectrum of human illness. Late ophthalmologic manifestations in survivors of the Ebola virus epidemic in Kikwit, Democratic Republic of the Congo.

    Severe Hemorrhagic fevers: Ebola and Marburg

    A novel immunohistochemical assay for the detection of Ebola virus in skin: implications for diagnosis, spread, and surveillance of Ebola hemorrhagic fever. Physicochemical inactivation of Lassa, Ebola, and Marburg virus disease viruses and effect on clinical laboratory analyses. Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. Ebola hemorrhagic fever, Democratic Republic of the Congo, determinants of survival. Antiviral drug therapy of filovirus infections: S-adenosylhomocysteine hydrolase inhibitors inhibit Ebola virus in vitro and in a lethal mouse model.

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