Update: chikungunya fever diagnosed among international travelers--United States, 2006

Chikungunya virus (CHIKV) is a mosquitoborne alphavirus indigenous to tropical Africa and Asia, where it causes endemic and epidemic chikungunya (CHIK) fever, an acute illness characterized by fever, arthralgias, and sometimes arthritis, commonly accompanied by conjunctivitis and rash. Although symptoms of CHIKV infection usually last days to weeks, joint symptoms and signs usually last for months and occasionally for 1 year or longer; deaths from CHIKV infection are rare. No specific antiviral treatment exists for CHIKV infection; treatment consists of supportive care, including analgesics and anti-inflammatory medication for joint symptoms. During 2005-2006, an epidemic of CHIK fever occurred on islands in the Indian Ocean and in India, resulting in millions of clinically suspected cases, mainly in southern India. In the United States, CHIK fever has been diagnosed in travelers from abroad. CDC previously reported 12 imported cases of CHIK fever diagnosed in the United States from 2005 through late September 2006, including 11 with illness onset in 2006. This report of 26 additional imported cases with onset in 2006 underscores the importance of recognizing such cases among travelers. Health-care providers are encouraged to suspect CHIKV infection in travelers with fever and arthralgias who have recently returned from areas with CHIKV transmission. Acute- and convalescent-phase serum specimens can be submitted to CDC for testing through state health departments. Public health officials and health-care providers are encouraged to be vigilant for the possibility of indigenous CHIKV transmission in areas of the United States where CHIKV mosquito vectors are prevalent.     

An outbreak of yellow fever with concurrent chikungunya virus transmission in South Kordofan, Sudan, 2005

From September through December 2005, an outbreak of hemorrhagic fever occurred in South Kordofan, Sudan. Initial laboratory test results identified IgM antibodies against yellow fever (YF) virus in patient samples, and a YF outbreak was declared on 14 November. To control the outbreak, a YF mass vaccination campaign was conducted and vector control implemented in parts of South Kordofan. Surveillance data were obtained from the Sudan Federal Ministry of Health. Clinical information and serum samples were obtained from a subset of patients with illness during the outbreak. Nomads, health personnel and village chiefs were interviewed about the outbreak. Mosquitoes were collected in 11 villages and towns in North and South Kordofan. From 10 September to 9 December 2005 a total of 605 cases of outbreak-related illness were reported, of which 45% were in nomads. Twenty-nine percent of 177 patients seen at clinics in Julud and Abu Jubaiyah had illness consistent with YF. Five of 18 unvaccinated persons with recent illness and 4 of 16 unvaccinated asymptomatic persons had IgM antibodies to YF virus. IgM antibodies to chikungunya virus were detected in five (27%) ill persons and three (19%) asymptomatic persons. These results indicate that both chikungunya and YF occurred during the outbreak.     

A yellow fever epizootic in Zika Forest, Uganda, during 1972: Part 2: Monkey serology.

During the 1972 yellow fever epizootic in Zika Forest, Uganda, sera from 21 monkeys shot in a number of forests around the Entebbe area were tested for the presence of a number of arbovirus antibodies. All sera were tested for antibodies against Chikungunya (CHIK), O'nyong-nyong (ONN), Zika, yellow fever (YF) West Nile (WN) and Wesselsbron (WESS) by the haemagglutination-inhibition (HI) test. Because of the crossreaction within the flaviviruses (group B arboviruses) mouse protection test (PT) was also carried out on the sera against YF, WESS and Zika viruses. Serological studies carried out on monkey sera from different parts of Uganda, including the Entebbe area, during 1968 gave results which reflected a surprisingly low rate of YF immune monkeys (3%) throughout the country compared with the rate of over 40% immune monkeys obtained by Haddow et al. in 1951. 40% of the monkey sera collected during 1972 were immune to YF by the PT. Since no YF virus had been isolated between 1968 and 1972 the results indicate strongly that the monkeys in the Entebbe area were involved in the epizootic of 1972. No sick or dead monkeys were found in all the forests checked around Entebbe area during the epizootic. This indicates that the animal-to-animal cycle of the equatorial African forests involved the mild endemic infection characteristic of a virus in its natural habitat and infecting its natural host.     

我国基孔肯雅热的流行状况

2010年10月,广东省东莞市暴发了我国首起基孔肯雅热社区聚集性疫情,打破了其长期以来以散在输入性病例为特征的流行现状。基孔肯雅热是一种由基孔肯雅病毒引起的急性传染病,伊蚊是其主要传播媒介。而我国大多数地区拥有其主要传播媒介埃及伊蚊和白纹伊蚊,一旦病原体侵入,可能暴发基孔肯雅热疫情。如何控制该疫情,防止疫情的进一步扩散,是摆在我们面前的当务之急。现就基孔肯雅病毒的病原学特征以及基孔肯雅热在我国历年的流行状况做一概述,以便更好地认识基孔肯雅热,为有效地监测和防治提供科学依据。     

Vector competence of Brazilian Aedes aegypti and Ae. albopictus for a Brazilian yellow fever virus isolate

Because the potential urban yellow fever (YF) mosquito vectors Aedes aegypti and Ae. albopictus are at historical highs in Brazil, both in terms of density and geographical range, we assessed the risk of an urban YF epidemic in Brazil. We evaluated and confirmed in a laboratory setting the vector competence of Brazilian Ae. aegypti for a currently circulating strain of YF virus, and investigated the potential for Brazilian Ae. albopictus to transmit YF.     

Clinical progression of chikungunya fever during acute and chronic arthritic stages and the changes in joint morphology as revealed by imaging

This longitudinal follow-up study of 203 patients with serologically confirmed chikungunya (CHIK) virus infection describes the clinical features of CHIK fever during the first and tenth months of illness. During the acute stage CHIK fever presents with a wide array of symptoms. The foremost chronic symptoms at the end of a month were rheumatism (75%) and fatigue (30%). During the tenth month of follow-up the symptoms/signs observed were joint pain/swelling (46%), fatigue (13%) and neuritis (6%). The cure rate at the end of 9 months was 51%. Among the patients who had joint pain, 36% (34/94) met the American College of Rheumatology criteria to classify them as having rheumatoid arthritis. A subpopulation of the patients with joint pain (20/94) was tested for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody, and the joints were imaged by X-ray and magnetic resonance imaging (MRI). All tested negative for RF and one tested positive for anti-CCP. A radiolucent lesion in the X-ray was seen in the bones of five patients. The MRI findings were joint effusion, bony erosion, marrow oedema, synovial thickening, tendinitis and tenosynovitis. The study proves with relative certainty that CHIK arthritis is chronic inflammatory erosive arthritis, which has implications for management of the infection.     

Japanese encephalitis virus/yellow fever virus chimera is safe and confers full protection against yellow fever virus in intracerebrally challenged mice

Yellow fever (YF) is an acute viral haemorrhagic disease caused by the yellow fever virus (YFV), which remains a potential threat to public health. The live-attenuated YF vaccine (17D strain) is a safe and highly effective measure against YF. However, increasing adverse events have been associated with YF vaccinations in recent years; thus, safer, alternative vaccines are needed. In this study, using the Japanese encephalitis live vaccine strain SA14-14–2 as a backbone, a novel chimeric virus was constructed by replacing the pre-membrane (prM) and envelope (E) genes with their YFV 17D counterparts.The chimeric virus exhibited a reduced growth rate and a much smaller plaque morphology than did either parental virus. Furthermore, the chimera was much less neurovirulent than was YF17D and protected mice that were challenged with a lethal dose of the YF virus. These results suggest that this chimera has potential as a novel attenuated YF vaccine.     

Effect of administration of sodium aurothiomalate on the virulence of yellow fever viruses in adult mice

Administration of sodium aurothiomalate (SATM) to adult mice results in a reduction of their average survival time (AST) following intracerebral challenge with the wild-type strains, Asibi and French viscerotropic virus (FVV), of yellow fever (YF) virus. Most attenuated 17D YF vaccines, derived by passage of the wild-type Asibi strain in chick tissue, showed no reduction in AST following intracerebral challenge and administration of SATM. In contrast, challenge with the majority of live attenuated French neurotropic vaccines, derived by passage of FVV in mouse brain, still resulted in SATM reducing the AST of mice. SATM also changed some YF viruses from non-lethal to lethal following intraperitoneal challenge and negated the ability of a monoclonal antibody to elicit passive protection of mice challenged intracerebrally with YF virus.     

Chikungunya fever as a risk factor for endemic Burkitt's lymphoma in Malawi

The geographical and age distributions of endemic Burkitt's lymphoma (eBL), in Africa, parallel those of certain arboviruses, which include chikungunya fever. Increased incidences of antibodies to assorted arboviruses, including chikungunya, have been found in eBL sera compared to controls. An increased incidence and space-time case-clusters of eBL occurred during a chikungunya fever epidemic which were confirmed by serology and clinical observation. The present study, conducted in 1987-89, involved 108 eBL patients, and 97 local and 111 hospital controls. We examined, as hospital controls, patients with afebrile, non-malignant conditions admitted to Kamuzu Central Hospital, Malawi, during the eBL patients' first admission there. Analyses were for hospital controls and eBL patients at the end of their first admission and for local controls and eBL patients at the beginning of their third admission, about 8 weeks after the day of first admission, because of the local controls' temporal bias. Patients in case-clusters were among those seropositive for chikungunya virus, with a history compatible with arbovirus infection preceding the lymphoma, suggesting involvement of chikungunya virus in the case-clusters and a possible association between recent infection with this virus and development of the lymphoma. eBL patients were significantly more likely to be seropositive for chikungunya virus antibody (68x5%) than either hospital controls (46.8%) or local controls (50x5%) (P = 0x002 and 0x009, respectively), raising the possibility of an association between infection with an arbovirus and developing eBL in children already primed by holoendemic malaria and Epstein-Barr virus infection.     

Urban yellow fever epidemic in western Nigeria, 1987

A large epidemic of urban yellow fever occurred in April and May 1987 in Oyo State, western Nigeria. The principal vector was Aedes aegypti, breeding in domestic water containers. The 1987 outbreak followed an epidemic of sylvatic yellow fever in eastern Nigeria the previous year, and probably resulted from introduction of the virus by viraemic travellers. The outbreak in Oyo State ended in early July, by which time 805 cases and 416 deaths had been officially notified. However, surveys of 3 villages in the epicentre, a region with over 4 million inhabitants, indicated an infection rate of approximately 20%, a clinical attack rate of 2.9% and a mortality rate of 0.6%, suggesting that the true incidence of cases and deaths far exceeded the official reports. Yellow fever virus was isolated from persons with fully developed yellow fever as well as mild febrile illness. One virus isolate was made from blood of an individual with mild illness, who had received 17D vaccine 5 d earlier; monoclonal antibody analysis showed that the isolate was a wild-type virus. Larval indices of Ae. aegypti were very high; however, low vector competence of the Ae aegypti population may have provided a constraint on spread of the epidemic. In late 1987 a third epidemic appeared in Niger State, northern Nigeria, with 644 reported cases and 149 deaths. The vector(s) involved is (are) unknown.     

Vector competence of Aedes albopictus from Houston, Texas, for dengue serotypes 1 to 4, yellow fever and Ross River viruses

A combination of virus infection and transmission experiments showed that a Houston, Texas strain of Aedes albopictus is a competent vector for dengue (DEN), yellow fever (YF) and Ross River (RR) viruses. However, at 14 days incubation, DEN virus infection rates in a Puerto Rican strain of Aedes aegypti were significantly higher for each of the four DEN serotypes, except DEN-1, than in Houston Ae. albopictus fed simultaneously on the same virus suspensions. The degree of correlation between disseminated DEN infection rates in Houston Ae. albopictus and transmission to an in vitro system ranged from 42 to 88% for the four DEN serotypes. No significant difference was noted in YF virus infection rates or transmission rates in the two mosquito species fed on the same virus suspensions and incubated for the same time period. Also, RR virus infection and transmission rates in Houston and Hawaiian strains of Ae. albopictus were generally comparable.     

The risk of yellow fever in travellers

Yellow fever is a tropical virus disease characterised by high fever, jaundice, heart and kidney failure, and haemorrhagic diathesis. The causative Flavivirus is endemic in parts of tropical Africa and South America and is transmitted among humans and primates by mosquitoes. The chance that an unvaccinated traveller to West Africa will die of yellow fever is estimated at 1:650 to 1:5000 visitors per month of stay, depending on whether an epidemic occurs. Vaccination with the attenuated yellow fever Asibi 17D virus results in limited virus replication in the body and long-term protection due to the formation of neutralising antibodies. Vaccination is contraindicated in immunocompromised persons. Serious disseminated disease and encephalitis due to infection with the vaccine virus strain are seen more often in the elderly. One should therefore refrain from vaccination in persons over 60 years of age when the risk of infection is negligible. In recent years, the number of yellow fever epidemics has risen substantially, particularly in West Africa and the Amazon region. Reintroduction of yellow fever vaccination in childhood vaccination programmes is necessary in endemic areas to turn the tide of increasing outbreaks of yellow fever.     

Chikungunya epidemic-related mortality

Port Blair, the capital city of the Union Territory of Andaman and Nicobar Islands in the republic of India, witnessed an outbreak of chikungunya (CHIK) fever in 2006. Although no deaths attributable to CHIK fever were registered, thousands of people were affected. In view of evidence from other parts of the world indicating that CHIK fever does cause death we studied the mortality trend in Port Blair from 2002 to 2008 in order to verify if there was increased mortality during the CHIK fever epidemic. The expected number of monthly deaths in 2006 was calculated by multiplying the average monthly mortality rate from 2002 to 2008 (with the exception of 2006) with the monthly population in 2006. The results indicated that there was a significant increase in expected deaths during some months of 2006, which coincided with the peak in the CHIK fever epidemic in Port Blair.     

Persistence of neutralizing antibody 30-35 years after immunization with 17D yellow fever vaccine

Previous studies on the duration of antibody following vaccination with 17D yellow fever (17D YF) virus vaccine have indicated that immunity persists for at least 17 years and suggest that the vaccine may provide lifelong immunity. We studied sera obtained from 149 veterans of the Second World War, 30 - 35 years after military service during which YF vaccination was required for defined groups. A significantly high proportion of ”vaccinated” subjects was found to be seropositive to 17D YF virus. The highest proportion of seropositive ”vaccinated” veterans (97%) was among navy and air corps personnel, while only 60% of ”vaccinated” army personnel and 19% of ”unvaccinated” personnel were seropositive. This study suggests that (i) antibody to 17D YF virus, as measured by the plaque-reduction neutralization test (PRNT), persists for 30 years or more following administration of a potent vaccine; (ii) army personnel often had not received potent vaccine, even though their service history indicated that they should have been vaccinated; (iii) some personnel were vaccinated, although their service did not include vaccination-designated areas; and (iv) 88% of veterans with persistent PRNT antibody to 17D YF virus also had mouse-protective antibody against French neurotropic YF virus.     

A yellow fever epizootic in Zika forest, Uganda, during 1972: Part 1: Virus isolation and sentinel monkeys.

The results of the yellow fever immunity survey of Central and East Africa reported by SAWYER & WHITMAN in 1936 prompted scientists to undertake well-planned epidemiological studies on yellow fever in eastern Africa. A Yellow Fever Research Institute (the present East African Virus Research Institute) was established at Entebbe in 1936 for this purpose. One of the areas where much work has been carried out is a strip of typical tropical forest, the Zika Forest, 12 kilometres from the Institute. Routine surveillance work, particularly on the biting activity of the yellow fever vector mosquitoes, has been going on since 1946. It was during one of these studies in 1972 that the first yellow fever virus strain was isolated from Aedes africanus collected from the Zika and Sisa forests and one strain was isolated from Coquillettidia fuscopennata, also from the Zika Forest. Three sentinel rhesus monkeys, nomimmune to YF, which were kept in the Zika Forest during the time of the epizootic died of YF disease. The present observations indicate that YF is still present in Africa, and as such it still remains a potential menace to the human population. The epidemiological implications are discussed.     

Outbreak of Chikungunya fever in Mayotte, Comoros archipelago, 2005-2006

In 2005-2006, a large outbreak of Chikungunya (CHIK) fever occurred on the western Indian Ocean Islands. In Mayotte, concurrent with an enhanced passive case notification system, we carried out two surveys. A seroprevalence survey designed to document recent CHIK infection was conducted on serum samples collected from pregnant women in October 2005 (n=316) and in March-April 2006 (n=629). A cross-sectional clinical community survey carried out from 2 to 10 May 2006 among 2235 individuals was designed to determine the cumulative incidence of presumptive CHIK fever cases. The seroprevalence of recent infection among pregnant women was 1.6% in October 2005 and rose to 26% in April 2006. The clinical community survey showed that nearly 26% of respondents had experienced presumptive CHIK fever between January and May 2006. Extrapolated to the overall population of Mayotte, these figures lead to an estimated attack rate of 249.5 cases per 1000 population as of early May 2006. Nine patients with the maternofetal form and six subjects with the severe form were recorded. This first emergence of CHIK fever in Mayotte lead to a very large outbreak. Efforts to strengthen surveillance and prevention of arbovirus infection are needed at country and regional levels.     

Development of an attenuated strain of chikungunya virus for use in vaccine production

An attenuated chikungunya (CHIK) virus clone was developed for production of a live vaccine for human use. CHIK strain 15561 was subjected to 18 plaque-to-plaque passages in MRC-5 cultures before CHIK 181/clone 25 was selected as vaccine seed based on homogeneous small plaque size, suckling mouse avirulence, reduced monkey viraemia and genetic stability. Oligonucleotide mapping demonstrated differences between parent and clone. Vaccine (pilot-lot production) elicited neutralizing antibody and protected mice and rhesus monkeys against challenge. After challenge, viraemias were absent in vaccinated monkeys. Vaccine was then produced and tested in accordance with governmental regulatory requirements of human use.     

Examination of the envelope glycoprotein of yellow fever vaccine viruses with monoclonal antibodies

Two panels of envelope glycoprotein reactive monoclonal antibodies (mAbs) were prepared against yellow fever (YF) 17D vaccine viruses. Five mAbs were prepared against the World Health Organization 17D-204 avian leukosis virus-free secondary seed virus and eight mAbs against 17DD vaccine manufactured in Brazil. The majority of these mAbs were type-specific and displayed differing reactions in neutralization tests. One, B14, would only neutralize YF vaccine virus grown in invertebrate cells. Others would differentiate 17D-204 and 17DD vaccines, from different manufacturers, in neutralization tests when the viruses were grown in vertebrate cells. The data indicate that heterogeneity exists between the epitopes that elicit neutralizing antibody on YF vaccine from different manufacturers.