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Crimean-Congo Hemorrhagic Fever (CCHF) is endemic in Uganda, yet its epidemiology remains largely uncharacterized. To better understand its occurrence within Uganda, case reports of patients hospitalized with CCHF between 2013 and 2019 were reviewed. Further, genome sequences of CCHF-positive RNA obtained during this period were determined for phylogenetic comparisons. We found that a total of 32 cases (75% males; CFR, 31.2%), aged between 9 to 68 years, were reported during the study period. Most cases were detected during July to December of each outbreak year (81.2%; P < 0.01) and were located along the “cattle corridor” (68.7%, P = 0.03). The most common presenting symptoms were fever (93.8%), hemorrhage (81.3%), headache (78.1%), fatigue (68.8%), vomiting (68.8%), and myalgia (65.6%). In five patients for whom hematological data were available, varied abnormalities were observed including thrombocytopenia, leukopenia, anemia, lymphopenia, lymphocytosis, polycythemia, and microcytosis. About 56.3% (P = 0.47) of patients reported tick bites or exposure to livestock as their potential source of infection. Person-to-person transmission was suspected for two cases. Using unbiased metagenomics, we found that the viral S- and L- segments have remained conserved in Africa 2 clade since the 1950s. In contrast, the M segment split into two geographically interspersed clades; one that belongs to Africa 2 and another that is ancestral to Africa 1 and 2. Overall, this data summarizes information on the history and clinical presentation of human CCHF in Uganda. Importantly, it identifies vulnerable populations as well as temporal and geographic regions in Uganda where surveillance and control interventions could be focused.

Crimean-Congo hemorrhagic fever (CCHF) is endemic in Africa, but the epidemiology remains to be defined. Using a broad database search, we reviewed the literature to better define CCHF evidence in Africa. We used a One Health approach to define the impact of CCHF by reviewing case reports, human and animal serology, and records of CCHF virus (CCHFV) isolations (1956–mid-2020). In addition, published and unpublished collection data were used to estimate the geographic distribution of Hyalomma ticks and infection vectors. We implemented a previously proposed classification scheme for organizing countries into five categories by the level of evidence. From January 1, 1956 to July 25, 2020, 494 CCHF cases (115 lethal) were reported in Africa. Since 2000, nine countries (Kenya, Mali, Mozambique, Nigeria, Senegal, Sierra Leone, South Sudan, Sudan, and Tunisia) have reported their first CCHF cases. Nineteen countries reported CCHF cases and were assigned level 1 or level 2 based on maturity of their surveillance system. Thirty countries with evidence of CCHFV circulation in the absence of CCHF cases were assigned level 3 or level 4. Twelve countries for which no data were available were assigned level 5. The goal of this review is to inform international organizations, local governments, and healthcare professionals about shortcomings in CCHF surveillance in Africa to assist in a movement toward strengthening policy to improve CCHF surveillance.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease that can evolve into deadly hemorrhagic fever and that is endemic in many parts of Europe, Middle East, Central Asia, and Africa. Because of several reports about CCHF outbreaks in the south of Sudan during the last years, we examined in this study if unrecognized CCHF-V infections also occurred in the eastern and central parts of the country. The study examined the seroprevalence of CCHF virus infection in 464 sera from three regions of Sudan without previous reports of CCHF infection. The total CCHF virus seroprevalence was 2.6% (12 sera). The percentage was significantly elevated (7.5%) in sera from Khashm el Girba in eastern Sudan. The population in this area should be educated about the risk of disease transmission and how to avoid the infection. Health-care providers should be informed about the disease to identify possible cases and to prevent nosocomial transmission.

Crimean-Congo hemorrhagic fever virus (CCHFV; family Bunyaviridae, genus Nairovirus) infection of humans can result in a disease spectrum ranging from a nonspecific febrile illness to hemorrhagic fever manifestations with a mortality rate of 5%–30%.1 The relatively low rate of disease in seropositive populations has spurred research into potential host susceptibility factors,2–5 although the availability of appropriate supportive care may provide a more direct correlation with clinical outcomes. CCHFV is predominantly transmitted by ixodid ticks of the genus Hyalomma, and CCHFV has a wide geographic distribution with endemic foci in Eastern Europe, sub-Saharan and southern Africa, the Middle East, and Asia.6,7 Handling of tick-infested livestock and proximity to vegetated areas with high tick burdens are significant risk factors for CCHFV infection. In addition, nosocomial exposure to CCHFV-infected individuals in low resource facilities can result in severe disease among healthcare workers.1,7 CCHFV is an enveloped virus with a trisegmented, negative-sense RNA genome that encodes an RNA-dependent RNA polymerase (L), two major structural glycoproteins (GN and GC), and a nucleoprotein (N) on the L, M, and S genome segments, respectively. CCHFV has the largest genome of any bunyavirus at 19.1 kb total with 12.1, 5.4, and 1.6 kb in the three genome segments, respectively. To date, the National Institute of Allergy and Infectious Diseases (NIAID) Virus Pathogen Database and Analysis Resource (ViPR) lists complete genome sequences available for 54 (L), 75 (M), and 102 (S) genome segments of CCHFV strains.8 Pairwise alignments of these sequences indicate that their mean sequence identities are 89.4% (L), 80.0% (M), and 88.1% (S). Currently, there are no CCHFV vaccines or therapeutics approved for human use by the United States Food and Drug Administration, although immunoglobulin therapy and ribavirin have been used abroad with mixed results.9 In the absence of approved countermeasures, effective diagnostics remain an invaluable means to identify and control CCHFV outbreaks. A variety of assay platforms for CCHFV can detect viral nucleic acids to include low density macroarrays,10 high density resequencing arrays,11 padlock probes with colorimetric readout,12 loop-mediated isothermal amplification (LAMP),13 and polymerase chain reaction.14–18 Real-time reverse-transcription polymerase chain reaction (RT-PCR) remains the gold standard for quantitative, sensitive, and specific detection of CCHFV; however, these assays have sensitivity issues due to the genetic diversity of different CCHFV strains.19 Previously, Garrison et al.20 developed a TaqMan MGB real-time RT-PCR assay (Garrison assay) capable of detecting eighteen strains of CCHFV. Subsequent testing of this assay identified several additional strains which were undetectable by this assay.15 We suspected whether the inherent diversity of CCHFV genome contributed to inefficient primer/probe hybridization. To improve the assay performance, we sequenced these isolates and designed a set of degenerate primers and probes to take into account CCHFV diversity in the assay target region. This optimization increased assay sensitivity compared with the original Garrison assay and to a commonly used assay developed by Atkinson et al.15,21–26

Crimean Congo hemorrhagic fever (CCHF) is a viral zoonotic disease. During 1999–2011, 871 human cases of CCHF were diagnosed in Iran. A history of serologic conversion for CCHF virus was seen in 58.7% of 2,447 sheep samples, 25.0% of 1,091 cattle samples and 24.8% of 987 goat samples from different parts of Iran. Spatial analysis showed that the main foci of this disease in humans during these years were in eastern Iran (P < 0.01) and the second most common foci were in northeastern and central Iran. Two livestock foci were detected in the northeastern northwestern Iran. On the basis of the results of this study, infection likely entered Iran from eastern and western neighboring countries.

Minimal information is available on the incidence of Crimean–Congo hemorrhagic fever (CCHF) virus and hantavirus infections in Georgia. From 2008 to 2011, 537 patients with fever ≥ 38°C for ≥ 48 hours without a diagnosis were enrolled into a sentinel surveillance study to investigate the incidence of nine pathogens, including CCHF virus and hantavirus. Of 14 patients with a hemorrhagic fever syndrome, 3 patients tested positive for CCHF virus immunoglobulin M (IgM) antibodies. Two of the patients enrolled in the study had acute renal failure. These 2 of 537 enrolled patients were the only patients in the study positive for hantavirus IgM antibodies. These results suggest that CCHF virus and hantavirus are contributing causes of acute febrile syndromes of infectious origin in Georgia. These findings support introduction of critical diagnostic approaches and confirm the need for additional surveillance in Georgia.

WOS: 000329587200028, PubMed ID: 24166037, We investigated the possibility of transmission of Crimean-Congo hemorrhagic fever (CCHF) virus through respiratory and physical contact. In this prospective study, we traced 116 close relatives of confirmed CCHF cases who were in close contact with the patients during the acute phase of the infection and evaluated the type of contact between patients and their relatives. These relatives were followed for clinical signs or symptoms indicative of CCHF disease, blood samples of those with and without clinical signs were analyzed for CCHF virus immunoglobulin M and G (IgM and IgG, respectively) by enzyme-linked immunosorbent assay. No close relatives developed any signs or symptoms of CCHF and were negative for CCHF virus IgM and IgG. The results suggest that CCHF virus is not easily transmitted from person to person through respiratory or physical contact., Scientific Research Project Fund of Cumhuriyet University [T-438], This work was supported by the Scientific Research Project Fund of Cumhuriyet University (11.10.2010, T-438).

Crimean-Congo hemorrhagic fever (CCHF) is a viral disease with several different modes of transmission. We describe the manifestations, outcome, and likely modes of transmission for three nosocomial cases. All threee cases were healthcare workers (two men and one woman). They had fever, myalgia, and petechia. Disseminated intravascular coagulation resulted in the death occurred in the woman. Because this disease is manifested with non-specific influenza-like symptoms, diagnosis can be difficult. Data for these patients can be used to investigate airborne or sexual transmission of this virus, although neither route was substantiated for these patients. Use of universal precautions and early case detection are the most helpful strategy for preventing nosocomial transmission of CCHF.

Crimean–Congo hemorrhagic fever virus (CCHFV) and dengue virus (DENV) are endemic to Pakistan. Patients presenting with symptoms of fever, bleeding, and rash cannot be distinguished without appropriate testing. We report data on 354 samples tested for CCHFV at The Aga Khan University Hospital in Pakistan between 2007 and 2013. All samples were tested for the presence of CCHFV RNA. Some samples were also tested for DENV RNA, NS-1 antigen, and/or reactive immunoglobulin M antibodies. Of 354 clinical specimens screened for CCHFV, 52 specimens were positive, with 24 cases in 2013 alone. Most cases were from Sindh and Baluchistan, which border other CCHFV-endemic regions: Iran and Afghanistan. Among CCHFV-negative samples, 168 samples were tested for DENV, and 36% of these samples were found to be DENV-positive. Rapid differentiation of CCHFV and DENV can prevent nosocomial transmission and result in time and cost savings for patients and healthcare workers.

A multi-faceted investigation was conducted in the United Arab Emirates to characterize the epidemiologic and ecologic factors underlying an outbreak of Crimean-Congo hemorrhagic fever (CCHF) noted in November 1994 among abattoir workers. A chart review was conducted among hospitalized suspected cases of viral hemorrhagic fever with onset between January 1994 and March 1995 coupled with serologic testing of available specimens for the presence of virus antigen and IgG and IgM antibodies by ELISA. Livestock handlers and animal skin processors were interviewed and tested for the presence of IgG antibody. Sera from imported and domestic ruminants were examined for antibody for CCHF virus, and ticks collected from these animals were tested with an antigen-capture ELISA. Thirty-five suspected cases of CCHF were identified (case fatality = 62%). Livestock market employees, abattoir workers, and animal skin processors accounted for 16 (57%) of 28 cases with known occupational status. Serologic evidence of past asymptomatic infection was noted in 12 (4%) of 291 livestock and abattoir workers but in none of the controls. Nineteen (7%) of 268 animals were positive for CCHF virus antibodies by ELISA including 12 ruminants from Somalia and Iran and five indigenous camels. One Hyalomma impeltatum and two H. excavatum from Somali cattle and one H. anatolicum from a Somali goat were positive for CCHF virus antigen.

Viral hemorrhagic fever has re-emerged in the United Arab Emirates (UAE) since November 1993. Genomic RNA of Crimean-Congo hemorrhagic virus (C-CHFV) was detected by a newly developed, nested reverse transcriptase polymerase chain reaction (RT-PCR) in the sera of four (25.0%) of 16 suspected cases of viral hemorrhagic fever. The RT-PCR was based on oligonucleotide primers deducted from the small RNA segment encoding the nucleoprotein of the virus. By comparison with a nucleotide sequence of a C-CHFV isolate from a Chinese sheep, a divergence of 10.0-11.8% was detected in the C-CHFV variants causing the UAE outbreak. In the four positive sera, three phylogenetically distinct C-CHFV variants were amplified and confirmed by direct sequencing of the PCR fragments. These C-CHFV sequences were obtained directly from sera of infected humans without prior propagation in cell culture. The RT-PCR allows rapid detection of genomic C-CHFV RNA in clinical specimens and study of the molecular epidemiology of this infection.

Crimean-Congo hemorrhagic fever (CCHF) virus is widely distributed in wild and domestic mammals, birds, and ticks throughout many regions of Africa, Europe, and Asia. Interviews were conducted with 484 individuals from nine farms in the Republic of South Africa from which recent human CCHF cases had originated and with individuals from 27 farms without recognized cases. Serum samples were obtained from all consenting individuals. Blood was also drawn from 2,212 farm animals. Human infection with CCHF virus was uncommon (point prevalence 12.6/1,000). Antibody prevalence in humans on farms increased with age (P less than 0.001), and was correlated with handling lambs. Overall, a greater number of older animals were antibody positive than animals less than one year of age (P less than 0.001), but 12.7% of young animals on farms with human were antibody positive compared with 5.8% on those farms without human infection (P less than 0.05). Physical contact with ticks or tick bite was also found to be a risk factor, but contact with animal blood or fresh meat was not. The risk of CCHF virus infection in the community increased seven-fold following contact with a recognized CCHF case, even when other risk factors were taken into account (point prevalence rate 4.7%). In contrast, antibody prevalence was less than 1% (1 of 128) in the local hospital staff who had cared for patients with CCHF. Prevention is best achieved by education of the farming community and establishing and maintaining awareness in the hospital staff.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus of the genus Nairovirus and the family Bunyaviridae. It is a negative-strand RNA virus comprised of small (S), medium (M), and large (L) genome segments. The S segment encodes for nucleocapsid protein, the M segment codes for envelope glycoproteins (Gn and Gc), and the L segment codes for the RNA-dependent RNA polymerase. Currently, there are a limited number of methods for rapidly diagnosing CCHFV infections. We developed a real-time, reverse transcription-polymerase chain reaction assay for the rapid detection of CCHFV by using the TaqMan((R))-minor groove binding protein probe technology. The primers and probes were designed to amplify and detect a region in the S segment of CCHFV that is conserved across multiple strains. The limit of detection of the assay was 10 genome copies of RNA. This primer and probe set was specific to 18 strains of CCHFV tested and did not cross-react with either a DNA panel of 78 organisms or a panel of 28 diverse RNA viruses. This will rapidly and specifically detect CCHFV, and it has been used to detect CCHFV infection in samples from humans, animals, and ticks.

Crimean-Congo hemorrhagic fever (CCHF) has repeatedly caused nosocomial outbreaks among hospital staff. In the summer of 2003, we studied the seroprevalence of anti-CCHF IgG among health care workers who had come in contact with Crimean-Congo hemorrhagic fever patients from three referral hospitals in endemic regions of Iran. A total of 223 eligible staff were examined. Whereas 5 of 129 (3.87%) exposed health care workers tested positive, none of the 94 in the unexposed group did (P = 0.075). Seropositivity was more frequent among those whose intact skin had come in contact with nonsanguineous body fluids (9.52%) and those who had had percutaneous contacts (7.14%). Health care workers exposed to Crimean-Congo hemorrhagic fever patients, those who live in Systan-Baluchestan province, and older health care workers were more prone to seropositivity. Where introduction of high-risk modes of contact cannot be confined, we propose that health care workers take all the protective measures when handling Crimean-Congo hemorrhagic fever patients, particularly their blood and other body fluids.

We report a case of compartment syndrome of the left upper limb following hemorrhage due to Crimean-Congo hemorrhagic fever in a 45-year-old man. As far as we know, there is not such a report in the literature. We discuss clinical manifestations, electrophysiologic findings, differential diagnosis, and management of the patient. A high degree of awareness for an early diagnosis may participate to improve the poor prognosis.

A nosocomial outbreak of Crimean-Congo hemorrhagic fever occurred in Rawalpindi, Pakistan in February 2002. The identified index case died shortly after admission to a hospital. Two of the health care workers became secondary cases; one of them died on day 13 after coming in contact with the index case. The other secondary case was successfully treated with oral ribavirin.

During the investigation of an outbreak of Crimean-Congo hemorrhagic fever (CCHF) in the United Arab Emirates (UAE) between 1994 and 1995, blood samples from suspected CCHF cases and ticks collected from livestock were tested for CCHF virus by antigen-capture ELISA and by a reverse transcription-polymerase chain reaction. Phylogenetic analysis of partial small (S) segment nucleotide sequences from four ticks and five human samples showed that with one exception, all the human and tick viruses clustered along with samples from Pakistan and Madagascar in one distinct lineage. Within this lineage, sequences from the UAE patients were identical or closely related to those from three Hyalomma spp. ticks obtained from livestock recently imported from Somalia. Another sequence from a UAE patient was more closely related to a CCHF virus from Nigeria. These data indicate that the 1994-1995 CCHF epidemic in the UAE was a multisource outbreak possibly associated with importation of CCHF virus-infected livestock and ticks.

A repository of domestic animal sera collected in Niger between 1984 and 1988 was assayed for antibody against two zoonotic hemorrhagic fever viruses known to be present in the West African Sahel. A total of 2,540 serum samples from 2,324 cattle, sheep, goats, and camels were tested by an IgG-specific enzyme-linked immunosorbent assay (ELISA) and the 80% plaque reduction neutralization test (PRNT80) for Rift Valley fever (RVF) virus antibody. Of the 2,540 sera tested for RVF-specific IgG antibody, 1,676 sera from cattle, sheep, and goats were examined for RVF-specific IgM antibody by ELISA. A subset of 2,263 sera were examined for evidence of Crimean-Congo hemorrhagic fever (CCHF) virus antibody by an IgG-specific ELISA. Antibody against CCHF virus was found to be most prevalent in adult cattle (422 of 732 or 57.7% positive) sampled at nine locations in the Niamey area. The highest prevalence for RVF neutralizing antibodies was found in camels from the Agadez Department with 67 (47.5%) of 141 positive. The results indicate that both CCHF and RVF viruses are circulating in Niger and are potential zoonotic health risks.

Crimean-Congo hemorrhagic fever (CCHF) virus was transmitted from infected adult Hyalomma ticks to uninfected larval and nymphal Hyalomma ticks while cofeeding on a guinea pig host that did not have a detectable viremia. When tested after feeding with infected adults, three (0.8%) of 370 H. truncatum larvae contained detectable CCHF virus (mean virus titer 101.6 plaque-forming units [PFU]/tick). The virus was transmitted transstadially from infected larvae and was detected in 15 (1.2%) of 1,253 nymphs and 12 (0.1%) of 2,049 adults. Virus was recovered from 18 (1.9%) of 931 H. impeltatum nymphs, which originated from larvae that cofed with infected adults. After H. impeltatum nymphs cofed with infected adults, CCHF virus was detected in 21 (4.3%) of 449 (mean virus titer 101.7 PFU/tick) fed nymphs, but none of 886 adults tested after molt. Results of this study indicate that a small proportion of either larvae or nymphs may acquire CCHF infection while cofeeding on a host without a detectable viremia.

Eleven species of small African wild mammals, laboratory rabbits, guinea pigs, and Syrian hamsters were infected with Crimean-Congo hemorrhagic fever (CCHF) virus. Low-titered viremia followed by development of antibody was observed in scrub hares (Lepus saxatilis), Cape ground squirrels (Xerus inauris), red veld rats (Aethomys chrysophilus), white tailed rats (Mystromys albicaudatus), bushveld gerbils (Tatera leucogaster), striped mice (Rhabdomys pumilio), and guinea pigs. The maximum viremic titer in 4 scrub hares was 10(1.7-4.2) 50% mouse lethal doses/ml. Viremia was detected in 1/17 infected laboratory rabbits. Antibody response was only detected in South African hedgehogs (Atelerix frontalis), highveld gerbils (T. brantsii), Namaqua gerbils (Desmodillus auricularis), 2 species of multimammate mouse (Mastomys natalensis and M. coucha), and Syrian hamsters. The results of the study indicate that a proportion of infected scrub hares develop CCHF viremia of an intensity shown in the Soviet Union to be sufficient for infection of feeding immature ixodid ticks, but that South African hedgehogs and wild rodents are unlikely to be of importance as maintenance hosts of the virus in southern Africa.

Ribavirin was evaluated as a potential therapeutic for Crimean-Congo hemorrhagic fever (CCHF). Viral yields for strains of CCHF virus from Europe, Asia, and African in African green monkey kidney (Vero) cells were markedly reduced by this drug. Some CCHF viral strains appeared more sensitive than others, but in general, ribavirin doses as low as 5 ug/ml caused a transient reduction of viral yields. A further reduction in viral yields was induced by a dose of 25 ug/ml, and evidence of viral replication was not demonstrated in cells treated with 50 or 250 ug/ml. In contrast, a dose of ribavirin at least 9 times greater was required to induce a comparable inhibitory effect on the yields of Rift Valley fever virus, for which the drug has been shown to inhibit replication in monkeys and rodents. Keywords: Reprints; Therapy.

From 1974 through 1976, U.S. Naval Medical Research Unit No. 5 isolated 25 strain of tick-borne virus in infant mice from 410 pools containing over 6,000 ticks, and one strain from a bird and one strain from a rodent collected in central and southern Ethiopia. Of these, 17 were identified as known viruses previously found in West Central and East Africa. There were 8 strains of Jos virus from Amblyomma ticks; 7 strains of Dugbe virus from a bird, a rodent and from ticks; 1 strains of Crimean-Congo hemorrhagic fever virus and 1 strain of Thogoto virus from ticks.

Reversed passive hemagglutination (RPHA) tests were performed by coating glutaraldehyde-fixed and tannic acid-treated sheep erthrocytes with antibodies to Rift Valley fever (RVF) and Crimean-Congo hemorrhagic fever (CCHF) viruses. Cells coated with crude antibody, in the form of mouse immune ascitic fluid, reacted with high specificity and sensitivity in RPHA tests with live or inactivated virus antigens. In inhibition (RPHI) tests, RVF antibody titers in human and sheep sera were similar to those determined by hemagglutination inhibition test. RVF virus antigen could be detected in viremic sheep sera by the RPHA technique. RPHI antibody titers to CCHF virus in human and hare sera were similar to indirect immunofluorescence (IF) titers, but sheep and cattle sera with RPHI titers of 1:32 or less were negative in IF tests.

Strains of Crimean hemorrhagic fever-Congo (CHF-C) virus originating in widely separated points representing diverse zoogeograhiczl and ecological areas were compared by a neutralization of fluorescent foci of infection-test, in an attempt to determine whether antigenic differences could be detected among the strains. Minor differences were found which could be confirmed by reciprocal kinetic neutralization tests with one-injection immune sera if the results were analyzed by linear regression. However, CHF-C virus strains cannot be reliably subdivided into geographic variants on the basis of the minor antigenic variations observed. In this apparent paucity of antigenic diversity over its wide distribution, CHF-C virus differs from other arboviruses with similar or even lesser distribution.

Seven African tick species were studied as potential vectors of Crimean-Congo hemorrhagic fever (CCHF) virus. Engorged nymphae of 4 ixodid species, Hyalomma marginatum rufipes, H. truncatum, Rhipicephalus evertsi mimeticus, and Amblyomma hebraeum, were inoculated intracoelomically with CCHF virus and assayed for virus content at varying times post-inoculation. The virus replicated in all 4 species, reaching maximum titers of 4.6-5.5(10) fluorescence focus units per ml on days 5-9 post-inoculation. Virus titers declined up to the molt, but increased slightly on emergence of adult ticks. Thereafter, virus titers declined progressively, but infectivity could still be detected in adult ticks for up to 205 days post-inoculation. Groups of H. m. rufipes, H. truncatum, and R.e. mimeticus infected adults were fed on susceptible sheep and successfully transmitted CCHF infection. CCHF virus was not isolated from pools of the larval and nymphal progeny of the female ticks nor did the larvae transmit infection to guinea pigs by bite. CCHF virus failed to replicate in adults and nymphae of 3 argasid tick species, Argas walkerae, Ornithodorus porcinus porcinus, and O. savignyi, after intracoelomic inoculation and could be reisolated from the ticks no later than 1 day post-inoculation. The results suggest that all ixodid ticks are capable of transmitting CCHF virus but argasid ticks do not appear to be capable of serving as vectors.

Following the diagnosis in 1981 of the first case of Crimean-Congo hemorrhagic fever (CCHF) in South Africa, an antibody survey was undertaken on cattle sera to determine the distribution of the virus and specific diagnostic tests were routinely applied to specimens from suspected cases of hemorrhagic fever to establish the medical significance of its presence. Antibody to CCHF virus was demonstrated by reversed passive hemagglutination-inhibition technique in 2,460/8,667 (28%) cattle sera and in 140/180 herds tested in South Africa, as well as in 347/763 (45%) cattle sera and in 32/34 (94%) herds tested in Zimbabwe. The antibody was found in all major cattle farming areas, but was of low prevalence along the southern coast where 2 of the 3 species of Hyalomma tick which occur in South Africa are absent. From February 1981 to January 1986, inclusive, 29 indigenous cases of CCHF were diagnosed in 16 outbreaks which arose in various locations throughout South Africa. A further 2 imported cases of CCHF arose in Zaire and Tanzania. The clinical features of infection conformed to the classical descriptions of CCHF in the Soviet Union. The fatal outcome in 11/31 cases indicates that the African disease is no less severe than that which occurs in Eurasia. It is inferred that the virus is widespread in all countries in Africa and Eurasia which lie within the limits of world distribution of ticks of the genus Hyalomma.

Using the immunofluorescence test, a serosurvey for antibodies to five viral agents associated with hemorrhagic febrile infections was conducted with 1,677 human sera from different parts of Nigeria. Three hundred fifty-seven (21.3%) were positive for Lassa virus antibody, while antibodies to Rift Valley fever virus were detected in 42 (2.5%) of the sera. Testing for Rift Valley fever virus antibody was confirmed by plaque reduction neutralization test. Antibodies to Ebola and Marburg viruses were detected in 30 and 29 sera, respectively. Of the 357 Lassa virus antibody-positive sera, 297 (83.2%) were positive for Lassa only. In contrast, sera positive for Marburg were positive in combination with Lassa, Ebola, or Rift Valley fever viruses. Antibodies to Lassa and Rift Valley fever viruses were found in all locations in Nigeria, whereas Ebola and Marburg antibodies were found mainly in the northern Savanna zones of Benue and Gongola, but not in the rain forest area of Ondo.

Utilization of direct and indirect enzyme-linked immunosorbent assay (ELISA) and solid-phase radioimmunoassay (SPRIA) for the diagnosis of Crimean-Congo hemorrhagic fever (CCHF) allows the detection of low amounts of infectious virus (2 log LD50) or inactivated antigen and antibody to CCHF within 5-6 hours. These methods were shown to be more sensitive, specific, rapid, and reproducible than the complement-fixation test, immunofluorescence, hemagglutination, or radial diffusion in gel. The experimental design of ELISA and SPRIA developed for CCHF may be used successfully for the detection of the other members of the Bunyaviridae family.

Crimean-Congo hemorrhagic fever virus was isolated for the first time in South Africa in February 1981, from the blood of a 13-year-old boy who died in Johannesburg after attending a camp in a nature reserve in the western Transvaal. Virus was isolated from 21/120 pools of questing ticks from the nature reserve, the infected species being Hyalomma marginatum rufipes and H. truncatum. Virus was also isolated from 4/38 pools of partially engorged ticks and other ectoparasites collected off hosts, the infected species being H.m. rufipes, H. truncatum and Rhipicephalus evertsi. Antibodies were found in the sera of 5/74 humans, 8/26 wild vertebrates, 74/270 sheep, and 109/170 cattle from the reserve and surrounding farms. Antibodies were also found in 28/200 hares from various locations in the country. It was concluded that the virus is widely prevalent in South Africa, but the full medical and veterinary significance of its presence has yet to be determined.

Larval Hyalomma truncatum ticks were infected with Crimean-Congo hemorrhagic fever (CCHF) virus by allowing them to engorge on viremic newborn mice. The overall tick infection rate was 4.4% (24/542). Virus was detected in specimens for greater than or equal to 160 days postinfection. Transstadial transmission to the adult tick stage was observed and horizontal transmission to a mammalian host was demonstrated. Horizontal transmission of CCHF virus to uninfected adult ticks occurred while feeding with transstadially infected ticks on the same host. No evidence of transovarial virus transmission from infected female ticks to their 1st generation progeny was observed.

Sixty-five residents in a rural area of northern Greece were tested for circulating antibodies against Congo-Crimean hemorrhagic fever virus; antibodies were demonstrated in four by immunofluorescence and hemagglutination-inhibition tests. While the virus had been previously isolated in the area, this is the first time that evidence of human infection in nature has been observed in Greece.

Crimean-Congo hemorrhagic fever (CCHF) virus is becoming increasingly recognized as an important human pathogen in southern Africa. In order to determine the role of wild mammals in the natural ecology of the virus, sera from 3,772 wild mammals of 87 species and from 1,978 domestic dogs collected in South Africa and Zimbabwe between 1964 and 1985 were tested for antibody to CCHF virus by reversed passive hemagglutination inhibition (RPHI) and by indirect immunofluorescence (IF). Antibody was found to be highly prevalent in large mammals in the Orders Artiodactyla and Perissodactyla such as giraffe, Giraffa camelopardalis (3/3 positive), rhinoceros, Ceratotherium simium and Diceros bicornis (7/13), eland, Taurotragus oryx (59/127), buffalo, Syncerus caffer (56/287), kudu, Tragelaphus strepsiceros (17/78), and zebra, Equus burchelli (16/93). In small mammals antibody was found in the sera of 40/293 hares, 22/1,305 rodents, and 1/74 wild carnivores, but not in 522 primates, 176 insectivores, or 19 hyrax. Antibody was also found in the sera of 118/1,978 domestic dogs. The species of wild mammal in which antibody was distributed (with highest antibody prevalence in hares and large herbivores) reflects the feeding preference of immature and adult ticks of the genus Hyalomma, suggesting that Hyalomma sp. are the principal CCHF vectors in the wild.