Bilateral macular retinitis in patients with presumed rift valley fever from Sudan: A case series.

BACKGROUND: Epidemic retinitis occurs seasonally following febrile infections in endemic regions. Rift valley fever (RVF) is endemic to Sudan, with a recent outbreak starting in 2019. METHODS: Retrospective case series of 3 patients travelling from Sudan with post-febrile retinitis, and with a history and clinical picture suggestive of RVF retinitis. RESULTS: The three patients were adult males with underlying medical conditions and underwent fundus fluorescein angiography that confirmed bilateral retinitis and occlusive vasculitis involving the posterior pole. Optical coherence tomography showed distortion of the macular layers. Case 2 presented 1 month following febrile illness and had retinal thinning, with optical coherence tomography angiography showing marked reduction in vessel density. CONCLUSION: We present multimodal imaging data of three cases with presumed RVF retinitis from a recent outbreak in Sudan. The unavailability of standardized methods of testing for RVF, as is the case for most epidemic retinitis-causing pathogens, makes the diagnosis challenging.

Multimodal Imaging of Rift Valley Fever Outer Retinitis.

PURPOSE: To report a case of Rift Valley Fever retinitis studied with multimodal imaging. METHOD: A 50-years-old man from Sudan, diagnosed with Rift Valley fever, presented with complete loss of vision in the right eye and visual impairment in the left. Multimodal imaging was performed at baseline and follow-up. RESULTS: Upon examination, the right eye showed complete optic nerve atrophy, diffuse dot-blot hemorrhages and patches of retinitis. The left eye had a visual acuity of 20/40 with no anterior chamber nor vitreous inflammatory cells. Fundus examination of the left eye showed diffuse patches of retinitis that on SD-OCT were confined to the outer retina, with a retinal pigment epithelium reactive thickening. These areas of active retinitis where hypofluorescent on fluorescein angiography (blockage) and the RPE hypertrophy cause hyperautofluorescence. The patient was treated empirically with oral and intravitreal steroid to stabilize the course of the retina infection. On the 3 months follow up the areas of retinitis had consolidated with RPE sub-atrophy that cause hypoautofluorescence. The left eye visual acuity was stable. CONCLUSION: Rift Valley Fever etina lesions seem to be confined to the outer retina, and optic nerve involvement with RNFL loss seems to be the main cause of vision loss when the macula is spared.

Rift Valley Fever Virus Infection Causes Acute Encephalitis in the Ferret.

Rift Valley fever virus (RVFV) is a pathogen of both humans and livestock in Africa and the Middle East. Severe human disease is associated with hepatitis and/or encephalitis. Current pathogenesis studies rely on rodents and nonhuman primates, which have advantages and disadvantages. We evaluated disease progression in Mustela putorius furo (the ferret) following intradermal (i.d.) or intranasal (i.n.) infection. Infected ferrets developed hyperpyrexia, weight loss, lymphopenia, and hypoalbuminemia. Three of four ferrets inoculated intranasally with RVFV developed central nervous system (CNS) disease that manifested as seizure, ataxia, and/or hind limb weakness at 8 to 11 days postinfection (dpi). Animals with clinical CNS disease had transient viral RNAemia, high viral RNA loads in the brain, and histopathological evidence of encephalitis. The ferret model will facilitate our understanding of how RVFV accesses the CNS and has utility for the evaluation of vaccines and/or therapeutics in preventing RVFV CNS disease.IMPORTANCE Animal models of viral disease are very important for understanding how viruses make people sick and for testing out drugs and vaccines to see if they can prevent disease. In this study, we identify the ferret as a model of encephalitis caused by Rift Valley fever virus (RVFV). This novel model will allow researchers to evaluate ways to prevent RVFV encephalitis.

Genetic dissection of Rift Valley fever pathogenesis: Rvfs2 locus on mouse chromosome 11 enables survival to early-onset hepatitis.

Infection of mice with Rift Valley fever virus (RVFV) reproduces major pathological features of severe human disease, notably the early-onset hepatitis and delayed-onset encephalitis. We previously reported that the Rvfs2 locus from the susceptible MBT/Pas strain reduces survival time after RVFV infection. Here, we used BALB/cByJ (BALB) mice congenic for Rvfs2 (C.MBT-Rvfs2) to investigate the pathophysiological mechanisms impacted by Rvfs2. Clinical, biochemical and histopathological features indicated similar liver damage in BALB and C.MBT-Rvfs2 mice until day 5 after infection. However, while C.MBT-Rvfs2 mice succumbed from acute liver injury, most BALB mice recovered and died later of encephalitis. Hepatocytes of BALB infected liver proliferated actively on day 6, promoting organ regeneration and recovery from liver damage. By comparison with C.MBT-Rvfs2, BALB mice had up to 100-fold lower production of infectious virions in the peripheral blood and liver, strongly decreased RVFV protein in liver and reduced viral replication in primary cultured hepatocytes, suggesting that the BALB Rvfs2 haplotype limits RVFV pathogenicity through decreased virus replication. Moreover, bone marrow chimera experiments showed that both hematopoietic and non-hematopoietic cells are required for the protective effect of the BALB Rvfs2 haplotype. Altogether, these results indicate that Rvfs2 controls critical events which allow survival to RVFV-induced hepatitis.

Rift Valley fever virus induces fetal demise in Sprague-Dawley rats through direct placental infection.

Rift Valley fever virus (RVFV) infections in pregnant livestock cause high rates of fetal demise; miscarriage in pregnant women has also been associated with RVFV infection. To address how RVFV infection during pregnancy causes detrimental effects on the fetus, we developed a pregnant rodent model of RVFV infection. We found that pregnant rats were more susceptible to RVFV-induced death than their nonpregnant counterparts and that RVFV infection resulted in intrauterine fetal death and severe congenital abnormalities, even in pups from infected asymptomatic pregnant rats. Virus distribution in infected dams was widespread, with a previously unrecognized preference for infection, replication, and tissue damage in the placenta. In human mid-gestation placental tissue, RVFV directly infected placental chorionic villi, with replication detected in the outermost syncytial layer. Our work identifies direct placental infection by RVFV as a mechanism for vertical transmission. This is the first study to show vertical transmission of RVFV with a lethal outcome in a species other than livestock. This study highlights the potential impact of a future epidemic of this emerging mosquito-borne virus.

Global research trends of World Health Organization's top eight emerging pathogens.

BACKGROUND: On December 8th, 2015, World Health Organization published a priority list of eight pathogens expected to cause severe outbreaks in the near future. To better understand global research trends and characteristics of publications on these emerging pathogens, we carried out this bibliometric study hoping to contribute to global awareness and preparedness toward this topic. METHOD: Scopus database was searched for the following pathogens/infectious diseases: Ebola, Marburg, Lassa, Rift valley, Crimean-Congo, Nipah, Middle Eastern Respiratory Syndrome (MERS), and Severe Respiratory Acute Syndrome (SARS). Retrieved articles were analyzed to obtain standard bibliometric indicators. RESULTS: A total of 8619 journal articles were retrieved. Authors from 154 different countries contributed to publishing these articles. Two peaks of publications, an early one for SARS and a late one for Ebola, were observed. Retrieved articles received a total of 221,606 citations with a mean ± standard deviation of 25.7 ± 65.4 citations per article and an h-index of 173. International collaboration was as high as 86.9%. The Centers for Disease Control and Prevention had the highest share (344; 5.0%) followed by the University of Hong Kong with 305 (4.5%). The top leading journal was Journal of Virology with 572 (6.6%) articles while Feldmann, Heinz R. was the most productive researcher with 197 (2.3%) articles. China ranked first on SARS, Turkey ranked first on Crimean-Congo fever, while the United States of America ranked first on the remaining six diseases. Of retrieved articles, 472 (5.5%) were on vaccine - related research with Ebola vaccine being most studied. CONCLUSION: Number of publications on studied pathogens showed sudden dramatic rise in the past two decades representing severe global outbreaks. Contribution of a large number of different countries and the relatively high h-index are indicative of how international collaboration can create common health agenda among distant different countries.

Association of Rift Valley fever virus infection with miscarriage in Sudanese women: a cross-sectional study.

BACKGROUND: Rift Valley fever virus is an emerging mosquito-borne virus that causes infections in animals and human beings in Africa and the Arabian Peninsula. Outbreaks of Rift Valley fever lead to mass abortions in livestock, but such abortions have not been identified in human beings. Our aim was to investigate the cause of miscarriages in febrile pregnant women in an area endemic for Rift Valley fever. METHODS: Pregnant women with fever of unknown origin who attended the governmental hospital of Port Sudan, Sudan, between June 30, 2011, and Nov 17, 2012, were sampled at admission and included in this cross-sectional study. Medical records were retrieved and haematological tests were done on patient samples. Presence of viral RNA as well as antibodies against a variety of viruses were analysed. Any association of viral infections, symptoms, and laboratory parameters to pregnancy outcome was investigated using Pearson's χ2 test. FINDINGS: Of 130 pregnant women with febrile disease, 28 were infected with Rift Valley fever virus and 31 with chikungunya virus, with typical clinical and laboratory findings for the infection in question. 15 (54%) of 28 women with an acute Rift Valley fever virus infection had miscarriages compared with 12 (12%) of 102 women negative for Rift Valley fever virus (p<0·0001). In a multiple logistic regression analysis, adjusting for age, haemorrhagic disease, and chikungunya virus infection, an acute Rift Valley fever virus infection was an independent predictor of having a miscarriage (odds ratio 7·4, 95% CI 2·7-20·1; p<0·0001). INTERPRETATION: This study is the first to show an association between infection with Rift Valley fever virus and miscarriage in pregnant women. Further studies are warranted to investigate the possible mechanisms. Our findings have implications for implementation of preventive measures, and evidence-based information to the public in endemic countries should be strongly recommended during Rift Valley fever outbreaks. FUNDING: Schlumberger Faculty for the Future, CRDF Global (31141), the Swedish International Development Cooperation Agency, the County Council of Västerbotten, and the Faculty of Medicine, Umeå University.

[Severe hemorrhagic forms of Rift Valley fever: about 5 cases]. / Formes hémorragiques graves de la fièvre de la vallée du Rift: à propos de 5 cas.

Rift Valley fever (RVF) is an arbovirus caused by an RNA virus belonging to family Bunyaviridae (genus phlebovirus). It is a zoonosis that primarily affects animals but it also has the capacity to infect humans, either by handling meat, runts of sick animals or, indirectly, by the bite of infected mosquitoes (Aedes sp, Anopheles sp, Culex sp). In most cases, RVF infection in humans is asymptomatic, but it can also manifest as moderate febrile syndrome with a favorable outcome. However, some patients may develop hemorrhagic syndrome and/or neurological damages with a fatal evolution. We present a case study of the development of 5 patients with RVF associated with hemorrhagic fever syndrome admitted to the internal medicine department at National Hospital Center in Nouakchott (Mauritania), in October 2015. The outcome was favorable for two of the five patients. The other 3 died, two of hemorrhagic shock and one of septic shock.

[Severe hemorrhagic form of Rift Valley Fever in Mauritania]. / Forme hémorragique grave de la fièvre de la Vallée du Rift en Mauritanie.

We report three severe cases of hemorrhagic form of Rift Valley Fever which have been observed in the Hospital of Aïoun (two cases) and in the regional hospital of Tidjikdja (one case). The disease manifested itself by an infectious syndrome, an early infectious syndrome (on the second day) with onset of hemorrhagic complications and disorder of consciousness ranging from an agitation to deep coma. The biological examinations showed a severe anemia. Multiple organ failures were also observed. Of the three patients treated one died. Therefore, the management of both suspected and confirmed cases must be initiated as soon as possible in order to control organ damages and prevent fatality. There is no specific treatment. The importance of the epidemiological survey must be emphasized to avoid outbreaks and control any epidemic due to this virus.

[Rift Valley fever]. / Fièvre de la vallée du Rift.

Rift Valley Fever (RVF) is a zoonotic arbovirosis. Among animals, it mainly affects ruminants, causing abortions in gravid females and mortality among young animals. In humans, RVF virus infection is usually asymptomatic or characterized by a moderate fever. However, in 1 to 3% of cases, more severe forms of the disease (hepatitis, encephalitis, retinitis, hemorrhagic fever) can lead to the death of infected individuals or to major sequels. The RVF virus (Bunyaviridae, genus Phlebovirus) was identified for the first time in the 1930s in Kenya. It then spread over almost all African countries, sometimes causing major epizootics/epidemics. In 2000, the virus was carried out of Africa, in the Middle East Arabian Peninsula. In 2007-2008, Eastern-African countries, including Madagascar, reported significant episodes of RVF virus, this was also the case for the Comoros archipelago and the French island of Mayotte. This ability to spread associated with many vectors, including in Europe, and high viral loads in infected animals led the health authorities worldwide to warn about the potential emergence of RVF virus in areas with a temperate climate. The awareness has increased in recent years with climate changes, which may possibly modify the vector distribution and competence, and prompted many RVF virus-free countries to better prepare for a potential implantation of RVF.

[Severe presentations of Rift Valley Fever in Madagascar]. / Les formes graves de la fièvre de la vallée de Rift pendant l'épidémie à Madagascar.

OBJECTIVE: The authors describe clinical and epidemiologic characteristics of severe presentations of Rift valley fever (RVF) during the 2008 epidemic in Madagascar. METHODOLOGY: The diagnosis was confirmed by RVF virus polymerase chain reaction (PCR), or detection of specifics antibodies by Elisa. RESULTS: Sixteen cases of severe RVF were recorded. The sex-ratio was 7/1 and median age was 32 years (20/59 years). The risk factors of infection were: contact with infected animals or their meat (n=8), and travelling to a risk area (n=2). Hemorrhagic, neurological, and ocular manifestations were observed respectively in 87.5%, 43.8% and 6.3% of cases. All patients who died (n=4) presented with a hemorrhagic form of the disease. CONCLUSION: The hemorrhagic form was the most frequent presentation of RVF and was responsible for a high level of mortality. Epidemiologic surveillance must be implemented.

Novel infectious agents causing uveitis.

In any patient with uveitis, an infectious cause should be ruled out first. The differential diagnosis includes multiple well-known diseases including herpes, syphilis, toxoplasmosis, tuberculosis, bartonellosis, Lyme disease, and others. However, clinician should be aware of emerging infectious agents as potential causes of systemic illness and also intraocular inflammation. Air travel, immigration, and globalization of business have overturned traditional pattern of geographic distribution of infectious diseases, and therefore one should work locally but think globally. This review recapitulates the systemic and ocular manifestations of several emergent infectious diseases relevant to the ophthalmologist including Rickettsioses, West Nile virus infection, Rift valley fever, Dengue fever, and Chikungunya. Retinitis, chorioretinitis, retinal vasculitis, and optic nerve involvement have been associated with these emergent infectious diseases. The diagnosis of any of these infections is usually based on pattern of uveitis, systemic symptoms and signs, and specific epidemiological data and confirmed by detection of specific antibody in serum. A systematic ocular examination, showing fairly typical fundus findings, may help establish an early clinical diagnosis, which allows prompt, appropriate management.

Acute renal failure associated with the Rift Valley fever: a single center study.

Renal impairment is a frequent occurrence among patients with the Rift Valley fever (RVF), and is probably the result of hypovolemia and multiple organ dysfunctions in the majority of cases. This study was conducted to estimate the incidence of renal impairment in patients with RVF as well as to determine the associated mortality. Data of all patients admitted with renal impairment to the Gezira Hospital for Renal Diseases, Sudan, during the epidemic of RVF between September 2007 and January 2008 were analyzed. The total number of patients with RVF was 392 of whom, 194 were admitted to the Medani Teaching Hospital. Renal impairment was detected in 60% of the admitted patients; 90% of them needed dialysis treatment. The mortality rate was 31% in patients with acute renal failure, 25% in those with the hepatorenal syndrome and 31% in patients with primary hepatic involvement and mild renal impairment. The overall mortality was 40%. Our study suggests that RVF remains a major cause of acute renal failure with considerable mortality, although progression to chronic renal failure was not seen. Early renal substitution therapy fosters the best hope for survival.

Clinical demodicosis in African buffalo (Syncerus caffer) in the Kruger National Park.

We investigated the relationship between prevalence and severity of clinical signs of Demodex cafferi infection in free-ranging African buffalo (Syncerus caffer) and other factors such as age, sex, pregnancy status, and concomitant infections with bovine tuberculosis (BTB), Rift Valley fever (RVF), and brucellosis (BA). Approximately half of 203 buffalo examined in this study had clinical signs of demodicosis (cutaneous nodules); younger age classes had the highest prevalence and severity of lesions (chi(2)=21.4, df=6, P=0.0015). Nodules were generally limited to the head and neck region, but in severe cases were present over the entire animal. We found no significant association between clinical severity of the Demodex infection and gender, pregnancy status, or infection with BTB, RVF, or BA.

Forme hemorragique grave de la fievre de la vallee du Rift observee chez un jeune Malgache

La fievre de la vallee du Rift (FVR) est une zoonose virale qui touche principalement les animaux mais elle peut contaminer l'homme. La forme hemorragique constitue une complication grave et mortelle de la FVR; elle ne s'observe que dans 1des cas mais gravement mortelle dans 50des cas. Notre etude rapporte un cas grave de forme hemorragique de FVR qui est observe dans le service de reanimation du CHU Antananarivo (Hopital Joseph Raseta Befelatanana) chez un eleveur de 22 ans. La maladie se manifeste par un syndrome infectieux et une apparition precoce (des le 2e jour) des complications hemorragiques. Ce sont des hemorragies diffuses (hematemese; gingivorragie; petechies; hematurie; hemorragie au point de ponction veineuse..). Cette complication hemorragique a entraine le deces de ce patient des le 4e jour du debut de symptome malgre la reanimation. Le bilan biologique a montre des alterations de la fonction hepatique et des troubles de la coagulation. Des defaillances multi viscerales ont ete egalement observees

Fatal outcome of hepatitis A virus (HAV) infection in a traveler with incomplete HAV vaccination and evidence of Rift Valley Fever virus infection.

Hepatitis A virus (HAV) infection is rarely fatal except in patients with chronic liver disease. In the case reported here, an elderly women died of HAV infection 12 years after incomplete HAV vaccination. The possible role of a concordant Rift Valley fever virus infection acquired in Kenya is discussed.

Ocular complications of Rift Valley fever outbreak in Saudi Arabia.

OBJECTIVE: To report ocular complications of Rift Valley fever (RVF) during its first reported outbreak in southwest Saudi Arabia in autumn 2000. DESIGN: Cross-sectional study of patients in a referral hospital. PARTICIPANTS: One hundred forty-three consecutive patients with confirmed RVF serologic test results and ocular lesions were enrolled in the study. METHODS: Hospitalized patients (n = 30) and outpatients (n = 113) with clinical symptoms consistent with RVF, positive RVF serologic test results, and ocular abnormalities were studied. Ophthalmologic examinations, including fundus photography and fluorescein angiography, were performed. Patients were followed up at regular intervals to determine the prognosis and outcome of identified ocular abnormalities. MAIN OUTCOME MEASURES: Visual acuity at initial presentation and course of anterior and posterior segment complications. RESULTS: Among 143 patients (78% males; mean age, 53.2 years), 212 eyes were affected, comprising 47 eyes in 30 inpatients and 165 eyes in 113 outpatients. The mean interval between the onset of RVF and visual symptoms ranged from 4 to 15 days (mean, 8.8 days). Macular or paramacular retinitis was identified in all the affected eyes (n = 212) at the time of initial assessment. Lesions included retinal hemorrhages (40%), vitreous reactions (26%), optic disc edema (15%), and retinal vasculitis (7%). Anterior uveitis was present in 31% of outpatients. Fluorescein angiography of the retinitis showed early hypofluorescence with late staining of retinal lesions and blood vessels. Initial visual acuity was less than 20/200 in 80% of eyes in the outpatient group; their vision improved, deteriorated, or remained the same in 13%, 15%, or 72%, respectively. Evaluation at the last follow-up showed macular (60%) or paramacular (9%) scarring, vascular occlusion (23%), and optic atrophy (20%) in the outpatient group. CONCLUSIONS: Rift Valley fever was associated with major ocular morbidity. Ocular manifestations of RVF occurred with a relatively higher frequency than reported up to now and were not limited to severe infections. Rift Valley fever affects the uvea and posterior chorioretinal area and is associated with permanent visual loss resulting from macular and paramacular scarring, vascular occlusion, and optic atrophy. The study demonstrated for the first time that transient nongranulomatous anterior uveitis is associated with RVF.

Rift Valley fever: a sero-epidemiological survey among pregnant women in Mozambique.

Rift Valley fever (RVF) causes abortion in sheep and cattle. However, the teratogenic and abortogenic potential of RVF in humans is not known. Sera from a total of 1163 pregnant women in Mozambique were tested for RVF virus antibodies by ELISA and 28 (2%) were found to be positive. Mothers experiencing fetal death or miscarriage (155) had the same RVF virus antibody prevalence as those with normal deliveries. Analysis of maternity histories showed some indication of increased fetal wastage among women positive for RVF virus antibody. The ELISA used in this study was compared with a plaque reduction neutralization test and found to be equally sensitive and specific for the detection of RVF virus IgG antibodies.