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An outbreak of Rift Valley fever in Northeastern Kenya, 1997-98. (Research).


In December 1997, 170 hemorrhagic Hemorrhagic
A condition resulting in massive, difficult-to-control bleeding.

Mentioned in: Hantavirus Infections


hemorrhagic

pertaining to or characterized by hemorrhage.
 fever-associated deaths were reported in Garissa District, Kenya. Laboratory testing identified evidence of acute Rift Valley fever Rift Valley fever

An arthropod-borne (primarily mosquito), acute, febrile, viral disease of humans and numerous species of animals. Rift Valley fever is caused by a ribonucleic acid (RNA) virus in the genus Phlebovirus of the family Bunyaviridae.
 virus (RVFV RVFV Rift Valley Fever Virus ). Of the 171 persons enrolled in a cross-sectional study cross-sectional study
n.
See synchronic study.


cross-sectional study,
n the scientific method for the analysis of data gathered from two or more samples at one point in time.
, 31(18%)were anti-RVFV immunoglobulin (Ig) M positive. An age-adjusted IgM antibody prevalence of 14% was estimated for the district. We estimate approximately 27,500 infections occurred in Garissa District, making this the largest recorded outbreak of RVFV in East Africa. In multivariable analysis, contact with sheep body fluids and sheltering livestock in one's home were significantly associated with infection. Direct contact with animals, particularly contact with sheep body fluids, was the most important modifiable risk factor for RVFV infection. Public education during epizootics may reduce human illness and deaths associated with future outbreaks.

**********

Rift Valley fever virus (RVFV) is a zoonosis Zoonosis Definition

Zoonosis, also called zoonotic disease refers to diseases that can be passed from animals, whether wild or domesticated, to humans.
 that can cause epizootics and associated human epidemics in Africa (1). RVFV is a member of the family Bunyaviridae, genus Phlebovirus. Epizootics of RVFV occur periodically after heavy rains that flood natural depressions in the grasslands of sub-Saharan Africa (2). Flooding allows for the hatching of the primary vector and reservoir, multiple species of mosquitoes known as floodwater flood·wa·ter  
n.
The water of a flood. Often used in the plural.

floodwater naguas fpl (de la inundación)

floodwater n
 Aedes, which feed on nearby mammals (3,4). High levels of viremia viremia /vi·re·mia/ (vi-re´me-ah) the presence of viruses in the blood.

vi·re·mi·a
n.
The presence of viruses in the bloodstream.
 in these animals lead to infection of secondary arthropod arthropod

Any member of the largest phylum, Arthropoda, in the animal kingdom. Arthropoda consists of more than one million known invertebrate species in four subphyla: Uniramia (five classes, including insects), Chelicerata (three classes, including arachnids and horseshoe
 vector species and to subsequent infection of other mammals and livestock, in which it causes abortions and death in susceptible animals (5-7).

Human infection with RVFV was first reported soon after Daubney and colleagues isolated the virus in 1930 (8). Extensive human disease outbreaks were not reported until 1951, however, when an estimated 20,000 persons were infected during an epizootic ep·i·zo·ot·ic
adj.
Affecting a large number of animals at the same time within a particular region or geographic area. Used of a disease.



ep
 of cattle and sheep in South Africa (9). Outbreaks were reported exclusively from sub-Saharan Africa until 1977-78, when 18,000 persons were infected and 598 deaths were reported in Egypt (10). Transmission of the virus to humans is thought to occur by arthropod vectors, aerosols of blood or amniotic fluid amniotic fluid
n.
The fluid within the amnion that surrounds the fetus and protects it from injury.


Amniotic fluid
The liquid that surrounds the baby within the amniotic sac.
, or other direct contact with infected animals. RVFV in humans manifests a broad spectrum of disease, from asymptomatic infection to a benign febrile febrile /feb·rile/ (feb´ril) pertaining to or characterized by fever.

feb·rile
adj.
Of, relating to, or characterized by fever; feverish.
 illness, to a severe illness in approximately 1%-3% of cases that can include retinitis retinitis /ret·i·ni·tis/ (ret?i-ni´tis) inflammation of the retina.

retinitis circina´ta , circinate retinitis circinate retinopathy.
, encephalitis encephalitis (ĕnsĕf'əlī`təs), general term used to describe a diffuse inflammation of the brain and spinal cord, usually of viral origin, often transmitted by mosquitoes, in contrast to a bacterial infection of the meninges , and hemorrhagic fever hemorrhagic fever (hĕm'ərăj`ĭk), any of a group of viral diseases characterized by sudden onset, muscle and joint pain, fever, bleeding, and shock from loss of blood.  (11,12). In addition to the human illness, disability, and suffering, RVFV outbreaks can result in devastating dev·as·tate  
tr.v. dev·as·tat·ed, dev·as·tat·ing, dev·as·tates
1. To lay waste; destroy.

2. To overwhelm; confound; stun: was devastated by the rude remark.
 economic losses when livestock in an agricultural society are affected (13,14).

The normalized difference vegetation index The Normalized Difference Vegetation Index (NDVI) is a simple numerical indicator that can be used to analyze remote sensing measurements, typically but not necessarily from a space platform, and assess whether the target being observed contains live green vegetation or not.  has a linear relationship to rainfall in semiarid semiarid

said of regions of the earth which have dry climates but not as dry as those of arid climates.
 regions such as East Africa. Figure 1 depicts the vegetation development (as sensed by orbiting satellites) in late 1997, indicating elevated rainfall and the potential for RVFV outbreaks (15). In December 1997, the Kenyan Ministry of Health (MOH See modem on hold. ) and the World Health Organization (WHO) in Nairobi received reports of unexplained deaths in the North Eastern Province of Kenya and southern Somalia. Clinical features included an acute onset of fever and headache often associated with hemorrhage (hematochezia, hematemesis hematemesis /he·ma·tem·e·sis/ (he?mah-tem´e-sis) the vomiting of blood.

he·ma·tem·e·sis
n.
The vomiting of blood.
, and bleeding from other mucosal sites). Farmers and local veterinary health officials also reported high rates of spontaneous abortion spon·ta·ne·ous abortion
n.
A naturally occurring termination of a pregnancy. Also called miscarriage.


spontaneous abortion 
 and death among domestic livestock. Active surveillance conducted by the WHO, the Kenya MOH, and international relief organizations during December 22 to 28 in 18 villages in Garissa District (population 231,022), North Eastern Province, Kenya, identified 170 human deaths, reportedly from a hemorrhagic fever. No clinical specimens were available from the persons who had died. However, of 36 blood samples obtained from other ill persons in these villages that were tested at the National Institute for Virology virology, study of viruses and their role in disease. Many viruses, such as animal RNA viruses and viruses that infect bacteria, or bacteriophages, have become useful laboratory tools in genetic studies and in work on the cellular metabolic control of gene expression  and at the Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center.  (CDC See Control Data, century date change and Back Orifice.

CDC - Control Data Corporation
), 17 (47%) had evidence of acute infection with RVFV by detection of IgM antibodies, virus isolation, or reverse-transcriptase-polymerase chain reaction (RT-PCR RT-PCR

reverse transcriptase-polymerase chain reaction. See PCR1.
) for viral nucleic acid nucleic acid, any of a group of organic substances found in the chromosomes of living cells and viruses that play a central role in the storage and replication of hereditary information and in the expression of this information through protein synthesis. .

[FIGURE 1 OMITTED]

After RVFV was identified as the primary cause of this outbreak, an international task force led by the Kenya MOH established surveillance for hemorrhagic fever and other severe manifestations of infection. Because the surveillance system identified only those with severe symptoms, the task force also conducted a cross-sectional study in the human population of the Garissa District to determine the incidence of recent infection with RVFV and to evaluate risk factors for infection.

Methods

Site and Population

The investigation was conducted in the Garissa District of the North Eastern Province of Kenya, which borders southern Somalia. In 1998, an estimated 231,022 residents living in Garissa District were distributed among 12 divisions and 84 sublocations (Office of the President, Garissa District Development Plan: 1997-2001, unpub. data). In addition to the Kenyan residents, 120,000 Somali refugees lived in the district in 1998. Garissa has an arid climate with a predominantly flat and grassy landscape. Precipitation in the district averages 250 mm to 500 mm annually, varies considerably from year to year, and occurs in a bimodal bi·mod·al  
adj.
1. Having or exhibiting two contrasting modes or forms: "American supermarket shopping shows bimodal behavior
 pattern with two peaks, in March through May and October through December. Although a number of settled towns are dispersed throughout the region, the rural population is principally composed of nomadic herdsmen.

Two events hampered surveillance. By January 1998, floodwater had damaged or covered most of the already poor roadways in the Garissa District, making them impassable. Investigators required air transportation to perform surveillance. Additionally, a nationwide nurses' strike in December and January greatly decreased the medical personnel in hospitals and clinics, which contributed to the difficulties in providing patient care and collecting data.

Hemorrhagic Fever Surveillance

Case Definition

A probable case was defined as someone presenting with fever and bleeding from their gums, nose, eyes, rectum, lungs, or gastrointestinal tract gastrointestinal tract
n.
The part of the digestive system consisting of the stomach, small intestine, and large intestine.


Gastrointestinal tract 
, between October 1997 (the onset of flooding) and February 8, 1998. If specimens were available, diagnostic laboratory tests for RVFV were performed.

Case Ascertainment

In Garissa, active case-finding for hemorrhagic fever was performed by members of local law enforcement, village chiefs, and other government officials. Periodic reports were provided to the district health officers and the task force. We disseminated a case-report form to all district medical officers and international relief agencies involved in medical care in the area. When possible, reports of possible cases were investigated to obtain demographic and clinical information, as well as blood, stool, or tissue specimens. The WHO Hemorrhagic Fever Task Force was conducting similar surveillance throughout Kenya and in southern Somalia and northern Tanzania.

Laboratory

Initially, specimens were transported to the Africa Medical Research Foundation in Nairobi, where serum specimens were centrifuged, divided into aliquots, and forwarded to the Viral Research Center/Kenyan Medical Research Institute. Subsequently, a laboratory operated by Medecins du Monde n. 1. The world; a globe as an ensign of royalty.
Le beau monde
fashionable society. See Beau monde.
Demi monde
See Demimonde.
 was established in Garissa to process clinical samples. Within 12 hours of collection, serum specimens were stored at 4 [degrees] C until packed and shipped to National Institute for Virology and CDC for RVFV-specific IgG and IgM antibody enzyme-linked immunosorbent assay enzyme-linked immunosorbent assay
n.
ELISA.


Enzyme-linked immunosorbent assay (ELISA)
A diagnostic blood test used to screen patients for AIDS or other viruses.
 (ELISA ELISA (e-li´sah) Enzyme-Linked Immuno-Sorbent Assay; any enzyme immunoassay using an enzyme-labeled immunoreactant and an immunosorbent.

ELISA
n.
), virus isolation, RT-PCR, and sequencing of the DNA DNA: see nucleic acid.
DNA
 or deoxyribonucleic acid

One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes.
 product, or immunohistochemistry using previously described methods (16-19).

Cross-Sectional Survey

Case Definition

For the cross-sectional survey, a laboratory-confirmed case definition was used. A case of recent infection was defined as presence of RVFV-specific IgM antibodies by ELISA. Persons with RVFV-specific IgG antibodies by ELISA and no IgM antibody were considered to have been infected before this outbreak. In our initial calculations, we considered persons with only anti-RVFV IgG antibodies to be protected against infection. The background prevalence of past RVFV infection in Kenya is not known, but IgG positivity as high as 40% has been shown in populations at high risk after epizootics (20). In contrast, a 1983 study for serologic se·rol·o·gy  
n. pl. se·rol·o·gies
1. The science that deals with the properties and reactions of serums, especially blood serum.

2.
 prevalence of hemorrhagic fever viruses in Kenya demonstrated that <1% of persons sampled had anti-RVFV IgG, but a less sensitive immunofluorescent immunofluorescent

having the characteristic of immunofluorescence.


immunofluorescent antibody test
see fluorescence microscopy.

immunofluorescent microscopy
see fluorescence microscopy.
 antibody test was used (21). This study did not include the North Eastern Province. Additionally, the duration of IgM antibodies is not well documented. Therefore, a second analysis included persons with either anti-RVFV IgG or IgM antibodies.

Sampling

We selected participants for the cross-sectional survey from the non-refugee population of Garissa District using a modified multistage mul·ti·stage  
adj.
1. Functioning in more than one stage: a multistage design project.

2. Relating to or composed of two or more propulsion units.
 cluster design (22). In Kenya, each province is divided into divisions that are made up of locations and then sublocations. We used sublocations as the units for choosing clusters. Thirty clusters (sublocations) were selected from 12 divisions. The number of clusters per division was weighted to represent population density. Clusters were then chosen randomly. Seven households were chosen in each cluster by systematic random sampling for a total sample size of 210 persons. The investigating team identified one person in each household for recruitment into the study. To reflect the age distribution of the RVFV infection and hemorrhagic fever cases already identified in the outbreak, we included one child between 2 and 9 years old, five persons between 10 and 49 years old, and one person [greater than or equal to] 50 years in each cluster. Between February 8 and 14, 1998, three field teams interviewed and obtained samples from 202 persons from 29 clusters. Three of the selected cluster sites had been destroyed by the flood and could not be located. Replacement sublocations were sampled for two of the three destroyed clusters. In one cluster, only six persons were sampled. In four clusters, children <10 years of age were not sampled and were replaced by adults.

Data Collection

After informed consent was obtained, a blood specimen was collected and each participant was interviewed. We used a standardized questionnaire that included demographic characteristics (age, gender, family size), exposure information (e.g., slaughtering practices, butchering, consuming raw meat and milk), environmental factors (displacement by flood, type of settlement, loss of livestock), and history of illness between the start of the floods and the date of the interview. Exposure to mosquitoes was evaluated through questions about attempts to reduce bites (i.e., mosquito nets, fires, other methods). Otherwise, all persons were assumed to share a similar risk for insect bites. Local health workers fluent in English, Kiswahili, and Somali were trained to administer the questionnaire and were supervised by an epidemiologist. Interviewers recorded information in English.

Laboratory

Blood specimens were kept at ambient temperature for <6 hours. Specimens were processed at the Medecins du Monde laboratory as noted above. RVFV-specific IgG ELISA IgG ELISA,
n.pr a diagnostic test for identifying reactive substances that provoke delayed hypersensitivity of the immune system. A solid-phase immunoassay that uses enzymes to test for IgG subclass reactions.
, as well as IgM ELISA, was performed on all blood specimens. At the time of the cross-sectional survey, there were no reports of severe manifestations of illness and we believed that virus transmission was not ongoing. Therefore, virus isolation and PCR PCR polymerase chain reaction.

PCR
abbr.
polymerase chain reaction


Polymerase chain reaction (PCR) 
 were not performed on these specimens.

Data Management and Analysis

Data from completed questionnaires were double-entered into databases by using Epi Info version 6.0 (CDC, Atlanta, GA). Univariate and multivariable analyses were performed by using SAS (1) (SAS Institute Inc., Cary, NC, www.sas.com) A software company that specializes in data warehousing and decision support software based on the SAS System. Founded in 1976, SAS is one of the world's largest privately held software companies. See SAS System.  (version 6.12, Cary, NC). Poisson regression was used with a generalized estimating equations algorithm and controlled for the clustered nature of the data (23).

Results

Hemorrhagic Fever Surveillance

The hemorrhagic fever surveillance system identified 77 persons with severe febrile illness in Garissa District whose onset of fever was between November 10, 1997, and February 8, 1998. Fifty-three persons (57% male; median age 28 years, from 3 to 85 years) met the case definition for hemorrhagic fever (Figure 2). Of these 53 patients, 10 (19%) had evidence of acute RVFV infection (Table 1), and another 10 were positive by the anti-RVFV IgG ELISA. Because few cases were available for follow-up, case-fatality proportions were not calculated. Of the 24 persons whose illness did not meet the case definition for hemorrhagic fever, six (25%) had evidence of acute RVFV infection; one of these six had encephalitis and another had retinitis. The limited surveillance system also confirmed human disease in Tanzania and in Somalia (Figure 3).

[FIGURE 2-3 OMITTED]

Cross-Sectional Survey

Antibody Prevalence

Of the 202 persons enrolled in the cross-sectional study, 31 (15%) were positive only for anti-RVFV IgG (i.e., previously infected). Although persons having only IgG antibody were widely dispersed geographically, the highest prevalence was found in the Hulugho Division (32%) and the Masalani Division (29%). The highest percentage of previous infection by age group was for persons [greater than or equal to] 65 years of age (Table 2). Characteristics of the sampled population are provided in Table 2.

Of the 171 susceptible persons in the sample, 31 (18%) were positive for anti-RVFV IgM. The percentage of those with detectable IgM antibody varied with age; this antibody was detected in 5% of children <15 years of age, 23% of persons 15 to 65 years of age, and 13% of persons >65 (Table 2). The age-adjusted prevalence of IgM antibody positivity standardized to the population of Garissa District was 14% (95% CI 11-16). Sixteen clusters, representing all 12 of the administrative divisions in Garissa District, had persons with anti-RVFV IgM antibody, indicating recent viral transmission. Of the 31 persons with serologic evidence of recent infection, 30 (97%) reported having a recent illness, compared with 116 (83%) of the antibody-negative persons (p=0.06); no symptoms distinguished recent RVFV-associated illness from other illness.

Assuming an age-adjusted IgM antibody prevalence of 14% in the susceptible population, we estimate that approximately 27,500 persons were infected with RVFV during this outbreak in Garissa District alone. If the presence of IgG antibody were included in the case definition for recent infection, then the standardized prevalence would increase to 23% (95% CI 20-26) and would represent approximately 53,000 infected residents.

Risk Factor Assessment

Certain demographic characteristics (Table 2) were associated with higher rates of infection as determined by IgM ELISA, including rural habitation (p=0.02) and household size of less than four persons (p=0.001). Age <15 years was associated with a lower rate of recent infection (p=0.05). A large number of animal contact activities, including herding, milking, slaughtering, and sheltering animals in the home, were statistically associated with recent RVFV infection (Table 3). The association was greatest with sheep-related activities, especially for those resulting in contact with sheep blood or body fluids.

Many of the animal contact variables were highly associated with infection in univariate analysis, but were also highly correlated. Multivariable analysis of composite variables for species-specific activities that resulted in similar exposures and potential confounders demonstrated a significant association between recent RVFV infection and persons who had contact with sheep blood, amniotic fluid, or milk (not including milk consumption; RR 3.0, 95% CI 1.3-6.7) (Table 4). Sheltering any domestic livestock (mostly sheep and goats) in one's home during the flood also remained independently and significantly associated with infection in the multivariable analysis (RR 3.5, 95% CI 1.3-9.1). Although not significant in univariate analysis, being male also was significantly associated with infection (RR 1.6, 95% CI 1.0-2.8). Age <15 years was associated with a reduced risk for infection when controlling for the other risk factors (RR 0.3, 95% CI 0.06-1.0). Drinking raw sheep milk was independently associated with infection, but did not reach statistical significance (RR 1.6, 95% CI 0.9-2.9).

When the analysis was repeated using detection of either anti-RVFV IgM or IgG as the outcome variable, which effectively doubled the number of cases of RVFV, only contact with sheep blood or body fluids and sheltering animals in the home remained significantly associated with illness in the multivariable model (data not shown).

Discussion

After heavy rainfall in late 1997, an epidemic of Rift Valley fever among humans accompanied an epizootic among ungulates ungulates, ungulata

animals with hooves; cattle, sheep, goat, pig, horse and many wild and other domesticated species.
 in East Africa. From the cross-sectional investigation in the Garissa District of Kenya, we estimated 27,500 recent human infections with the virus occurred during this period, making this the largest outbreak of RVFV infection ever recorded in sub-Saharan Africa. In addition to Garissa District in the North Eastern Province, we identified recent human infection associated with hemorrhagic fever or encephalitis in four of Kenya's six provinces during the 1997-1998 outbreak (CDC, unpub. data). Surveillance also confirmed human disease in Tanzania, and, for the first time, in Somalia. Risk factors for human infection identified by this study included a broad array of activities associated with animal exposures, but most significantly, contact with sheep (particularly contact with sheep blood or other body fluids), male gender, and housing animals indoors with household members. Children <15 years of age were significantly less likely to have had recent RVFV infection.

Persons identified by the surveillance system did not undergo thorough clinical and laboratory investigations, and most persons who reported hemorrhaging were not directly observed by a clinician. Laboratory testing also found evidence of infection with other viral agents (Dengue dengue
 or breakbone fever or dandy fever

Infectious, disabling mosquito-borne fever. Other symptoms include extreme joint pain and stiffness, intense pain behind the eyes, a return of fever after brief pause, and a characteristic rash.
 and Bunyamwera viruses), malaria, shigella shigella

Any of the rod-shaped bacteria that make up the genus Shigella, which are normal inhabitants of the human intestinal tract and can cause dysentery, or shigellosis. Shigellae are gram-negative (see gram stain), non-spore-forming, stationary bacteria. S.
 dysentery dysentery (dĭs`əntĕr'ē), inflammation of the intestine characterized by the frequent passage of feces, usually with blood and mucus. , and leptospirosis leptospirosis (lĕp'təspīrō`sĭs), febrile disease caused by bacteria of the genus Leptospirae. The disease occurs in dogs, cattle, pigs, sheep, goats, and horses and is transmissible to humans.  as explanations for some of the persons whose illness met the hemorrhagic fever case definition, but who were negative for RVFV infection (CDC, unpub. data). Additionally, the epidemic appears to have preceded a large outbreak of malaria reported from the same region (24). Other possible explanations for the persons with fever and hemorrhage who had no laboratory evidence of RVFV infection include an overly sensitive case definition; improper collection, labeling, handling, and transport of samples; other pathogens or toxins; and complications of malnutrition.

In the cross-sectional study, the case definition for recent infection was based on the detection of IgM antibody. Unfortunately, the kinetics of the IgM response to RVFV are not well described. After natural infection, domestic animals lose a detectable amount of IgM antibody within 6 months of infection (25). In a large percentage of humans, experimental inoculation with a killed vaccine killed vaccine

see dead vaccine.

killed vaccine A vaccine consisting of dead but antigenically active viruses or bacteria, which evokes production of protective antibodies without causing disease. Cf Live attenuated vaccine.
 results in an early IgM response that wanes and is undetectable by 4 to 6 weeks, but this is not a model for natural infection (26). Of the few clinical infections that have been followed closely for serologic conversion, IgM antibody appears around day 5, is absent in 50% by day 45, and is undetectable 4 months later (12), whereas IgG appears about day 4 and may persist indefinitely at high titer.

All blood specimens for our cross-sectional study were obtained within 12 weeks of the first reported case of hemorrhagic fever in Garissa District. Therefore, the IgM antibodies probably represent recent infection related to the outbreak. If the IgM antibodies disappear quickly, however, the persons in whom we detected only IgG antibody may actually have been infected recently. If we include those persons in the analysis, the incidence of infection could be as high as 23%, representing an additional 25,000 infected persons in Garissa District alone.

Human suffering from RVFV is compounded by the loss of domestic animals. Livestock owners reported losses of approximately 70% of their animals, with the greatest losses among sheep and goats. Other infections thought to contribute to illness among livestock during the flooding included nonspecific nonspecific /non·spe·cif·ic/ (non?spi-sif´ik)
1. not due to any single known cause.

2. not directed against a particular agent, but rather having a general effect.


nonspecific

1.
 pneumonia, pasteurellosis Pasteurellosis

A variety of infectious diseases caused by the coccobacilli Pasteurella multocida and P. haemolytica; the term also applies to diseases caused by any Pasteurella species.
, contagious caprine cap·rine
n.
See norleucine.



caprine

pertaining to or emanating from goats.


caprine arthritis-encephalitis (CAE)
 pleuropneumonia pleuropneumonia /pleu·ro·pneu·mo·nia/ (-ndbobr-mo´ne-ah) pleurisy complicated by pneumonia.

pleu·ro·pneu·mo·nia
n.
Inflammation of the pleura and lungs; pneumonia aggravated by pleurisy.
, contagious pustular pus·tu·lar
adj.
Of, relating to, or consisting of pustules.



pustular

pertaining to or of the nature of a pustule; consisting of pustules.
 dermatitis, bluetongue bluetongue

an infectious, non-contagious disease of sheep and occasionally cattle, transmitted by Culicoides spp. Caused by an Orbivirus with at least 24 serotypes worldwide. Cattle are the reservoir and amplification hosts.
, foot rot, and complications of mange mange (mānj), contagious skin disease of domestic and wild animals. The several types of mange, including follicular and sarcoptic mange, are caused by various minute parasitic mites that burrow into skin, hair follicles, or sweat glands.  (Field Mission of the Food and Agriculture Organization of the United Nations Noun 1. Food and Agriculture Organization of the United Nations - the United Nations agency concerned with the international organization of food and agriculture
FAO, Food and Agriculture Organization
, unpub. data).

Because direct contact with blood or body fluids from viremic animals is an important risk factor for human infection identified by this study, the high number of domestic animal abortions and deaths may have increased the risk for humans developing illness. Many of the early cases were in persons who had recently been involved in the dissection, slaughter, or care of sick animals (12,27). A high attack rate has been demonstrated for abattoir abattoir (ăb'ətwär`) [Fr.], building for butchering. The abattoir houses facilities to slaughter animals; dress, cut and inspect meats; and refrigerate, cure, and manufacture byproducts.  workers (28), herdsmen (19), and veterinary personnel (9), all of whom have extensive contact with animal blood or other body fluids in the course of their work. In a retrospective investigation in Senegal based on IgG antibody positivity, men who assisted with animal births or abortions, and women who treated ill animals were found to be at increased risk for infection (29). Additionally, the virus has been isolated from raw milk, and ingestion ingestion /in·ges·tion/ (-chun) the taking of food, drugs, etc., into the body by mouth.

in·ges·tion
n.
1. The act of taking food and drink into the body by the mouth.

2.
 of raw milk has been suggested as a risk factor in previous studies (30,31).

Although any animal that develops a high level of viremia can pose a certain risk for animal-to-human transmission of virus, we found the greatest association with sheep. In past RVFV epizootics, sheep have been the most susceptible domestic animals (1,9,32). After a 2- to 4-day incubation period incubation period
n.
1. See latent period.

2. See incubative stage.


Incubation period 
, young lambs become listless, and fever and bloody diarrhea occur; the case-fatality of 90% to 100% is attributed to hepatic liquefaction liquefaction, change of a substance from the solid or the gaseous state to the liquid state. Since the different states of matter correspond to different amounts of energy of the molecules making up the substance, energy in the form of heat must either be supplied to  (33,34). The disease manifests similarly in adult sheep, although the case-fatality rate is much lower (20%-30%). As many as 80% of pregnant ewes abort after infection (9). The more severe manifestations in sheep are possibly the result of higher levels of viremia ([10.sup.10] suckling suckling

In mammals, the drawing of milk into the mouth from the nipple of a mammary gland. In human beings, it is referred to as nursing or breast-feeding. The word also denotes an animal that has not yet been weaned—that is, whose access to milk has not yet been
 mouse intra-cerebral [SMIC SMIC Salaire Minimum Interprofessionnel de Croissance (French: guaranteed minimum wage)
SMIC Semiconductor Manufacturing International Corp (Shanghai)
SMIC Side Mount Intercooler
] 50% lethal dose/mL), which can exceed those documented in cows and goats ([10.sup.8-10] SMIC 50% lethal dose/mL) (14). Higher levels of viremia with a high rate of abortion and deaths result in an increased likelihood of human contact with an infectious inoculum inoculum /in·oc·u·lum/ (-ok´u-lum) pl. inoc´ula   material used in inoculation.

in·oc·u·lum
n. pl.
. If the animal survives acute illness, the virus can be isolated in lower titers for as long as 3 weeks after illness, making it potentially dangerous to slaughter an animal, even after the epizootic appears to be over (33,35).

From this study it is not possible to identify which cases were infected by mosquitoes and which through direct contact with animals because we did not gather data on the numbers, species, prevalence of RVFV infection, or biting rates of mosquitos at the time of the outbreak. During February 1998, however, 3,180 mosquitoes were collected from three trapping sites in Garissa District. Of the nine captured species, three have been previously implicated im·pli·cate  
tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates
1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot.

2.
 in RVFV transmission to humans (Anopheles Anopheles: see mosquito.  coustani, Mansonia africana, and M. uniformis). In our multivariable model, we assumed that the high mosquito density led to an equal mosquito exposure rate for the entire population. The association of infection with being male and > 15 years indicates that persons who are more likely than other groups to perform high-risk behaviors (i.e., adult men) are more likely to be exposed to the virus. All but one (97%) of the persons with acute RVFV infection, as identified by IgM antibody, had recent exposure to either blood, milk, or abortive materials of a sheep or goat. Most of these people (87%) also sheltered animals in their home.

The probability of recurring outbreaks in East Africa and the potential for spread, by either natural or intentional means, to non-disease-endemic areas emphasize the necessity of developing and validating methods to predict, prevent, detect, and treat Rift Valley fever. Remote sensing satellite technology, which can predict rainfall patterns likely to result in disease emergence, has been suggested as a means to monitor RVFV activity (15,36). Longitudinal studies longitudinal studies,
n.pl the epidemiologic studies that record data from a respresentative sample at repeated intervals over an extended span of time rather than at a single or limited number over a short period.
 using satellite data to target areas for animal vaccination, enhance surveillance activities for RVFV in animals and humans, and conduct prospective entomologic en·to·mol·o·gy  
n.
The scientific study of insects.



ento·mo·log
 studies are in progress. However, until these methods are validated, simple public health interventions may greatly reduce transmission of the virus. Control programs aimed at protecting persons during epizootics should include education about the risks of having contact with infected animal body fluids. Although this report highlights the importance of direct animal contact in the transmission of RVFV to humans, the role of arthropod vectors, particularly in the virus life cycle in epizootics, cannot be discounted. Control of mosquito populations during or after heavy rains should be pursued to prevent animal and human infection.
Table 1. Results of testing for laboratory-confirmed cases of
Rift Valley fever, Garissa District, Kenya, 1997-98

              Collection     Virus                  IgM      IgG
Onset date       date      isolation     RT-PCR    ELISA    ELISA

12/9/97        12/23/97        +           +         -        -
12/18/97       12/25/97        +           +         +        -
12/18/97       12/26/97        -        Not done     +        +
12/19/97       12/26/97        +           +         +        +
12/21/97       12/26/97        +           +         +        -
12/22/97       01/22/98     Not done    Not done     +        +
12/30/97       01/23/98     Not done       +         +        +
1/18/98        01/22/98     Not done       -         +        +
1/28/98        02/02/98     Not done    Not done     +        +
2/7/98         02/09/98     Not done    Not done     +        -

RT-PCR = reverse transcription-polymerase chain reaction;
IG = immunoglobulin; ELISA = enzyme-linked immunosorbent assay.
Table 2. Demographic characteristics of persons enrolled in Rift
Valley fever cross-sectional survey, Garissa District, Kenya,
1997-98

                                   Prior (a)
                                   infection
                     Total (%)    (% of total)
Characteristic        n = 202         n = 31

Age group (years)

  < 15                 40 (20)       2 (5)
  15 to 65            150 (74)      25 (17)
  > 65                 12 (6)        4 (33)

Sex

  Male                103 (51)      16 (16)
  Female               99 (49)      15 (15)

Rural                 161 (80)      25 (16)
habitation

Household > 4          74 (37)      10 (14)
persons

                                       Acute (c)
                                       infection
                                         (% of
                    Susceptible (b)   susceptible)
Characteristic          n = 171           n = 31

Age group (years)

  < 15                    38             2 (5)
  15 to 65               125            28 (22)
  > 65                     8             1 (13)

Sex

  Male                    87            18 (21)
  Female                  84            13 (15)

Rural                    136            30 (22)
habitation

Household > 4             64            21 (33)
persons

(a) Anti-RVF IgG antibody-positive (no immunoglobulin M [IgM]).

(b) Total screened minus those with prior infection.

(c) Anti-Rift Valley fever virus IgM antibody-positive.
Table 3. Exposures during previous 90 days, Rift Valley fever (RVF)
cross-sectional survey, Garissa District, Kenya, 1997-98

                      Acute (a)      No       Relative   95% CI
                      infection   infection     risk
                         (%)         (%)
                       n = 31      n = 140

Animal exposures

  Sheltered            27 (87)     63 (45)      5.3      2.3-12.6
  livestock in home
  after flood

  Killed an animal     20 (64)     47 (34)      2.4      1.3-4.3

  Butchered an         14 (45)     33 (24)      2.0      1.1-3.6
  animal

  Skinned an animal    20 (65)     38 (27)      2.4      1.6-3.5

  Cooked with meat     20 (65)     48 (34)      2.3      1.1-4.9

  Milked animals       25 (80)     59 (42)      3.8      1.9-7.7

  Drank raw animal     30 (97)     89 (64)      8.6      2.0-36.0
  milk

  Care of animal       21 (68)     46 (33)      2.6      1.4-4.9
  during birth

  Disposal of          19 (61)     36 (26)      2.8      1.5-5.5
  aborted fetus

  Sheep contact (b)    25 (81)     48 (29)      6.3      2.9-14.0

  Goat contact (b)     28 (90)     91 (65)      3.1      1.6-6.4

  Cow contact (b)      20 (65)     49 (35)      2.4      1.3-4.5

  Camel contact (b)     5 (16)     17 (12)      1.3      0.5-3.8

Non-animal
exposures

  Home flooded         25 (81)    103 (73)      1.3      0.8-2.1
  since November
  1997

  Ill family member     7 (23)     20 (14)      1.6      0.8-3.1

  Contact with a        6 (21)     10 (7)       2.2      1.0-4.6
  dead human body

  Use mosquito nets    19 (61)    102 (73)      0.7      0.3-1.4

(a) Anti-Rift valley fever virus immunoglobulin M
antibody-positive.

(b) Contact includes herding, cooking, slaughtering or other body
fluid contact (except consumption), drinking raw milk.
Table 4. Multivariable risk factor analysis--cross-sectional
survey, Garissa District, Kenya, 1997-98

Exposure                       Relative risk     95% CI

Contact with sheep blood or         3.0          1.3-6.7
body fluids

Sheltering animals in the           3.5          1.3-9.1
home

Male gender                         1.6          1.0-2.8

Age < 15 years                      0.3         0.06-1.0

Drinking raw sheep milk             1.6          0.9-2.9


Acknowledgments

This manuscript is dedicated to the memory of Louise Martin and all those who died or suffered in the U.S. Embassy bombing in Nairobi Kenya, July 1998. The authors thank Kent Wagoner for technical assistance.

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Infections of humans caused by the transmission of disease agents that naturally live in animals. People become infected when they unwittingly intrude into the life cycle of the disease agent and become unnatural hosts.
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Prevalent among or restricted to animals of a specific geographic area. Used of a disease.

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An enzootic disease.



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peculiar to or present constantly in a location. See also endemic.
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Study of bacteria. Modern understanding of bacterial forms dates from Ferdinand Cohn's classifications. Other researchers, such as Louis Pasteur, established the connection between bacteria and fermentation and disease.
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DJJ Division of Juvenile Justice
DJJ David J Joseph Company
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JHS Jefferson High School
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JHS Journal of Hellenic Studies
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An antigen with multiple antigenicities that is protein in nature, strain-specific, and closely associated with the virus particle.
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Address for correspondence: Christopher W. Woods, Clinical Microbiology Laboratory, Duke University Medical Center, Box 3824, Durham, NC 27710, USA; fax: 919-684-8519; e-mail: Woods004@mc.duke.edu

Christopher W. Woods, * Adam M. Karpati, * Thomas Grein, ([dagger]) Noel McCarthy, ([double dagger]) Peter Gaturuku, ([section]) Eric Muchiri, ([section] Lee Dunster, ([paragraph]) Alden Henderson, * Ali S. Khan, * Robert Swanepoel, # Isabelle Bonmarin, ([double dagger]) Louise Martin, ** Philip Mann, ([double dagger]) Bonnie L. Smoak, ([double dagger]) Michael Ryan, ** Thomas G. Ksiazek, * Ray R. Arthur, ** Andre Ndikuyeze, ** Naphtali N. Agata, ** Clarence J. Peters, * and the World Health Organization Hemorrhagic Fever Task Force 1

* Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ([dagger]) European Program for Intervention Epidemiology Training (EPIET EPIET European Programme for Intervention Epidemiology Training ), European Union, Saint-Maurice, France; ([double dagger]) EPICENTRE epicentre

Point on the surface of the Earth that is directly above the source (or focus) of an earthquake. There the effects of the earthquake usually are most severe. See also seismology.
, Paris, France; ([section] Kenya Ministry of Health, Nairobi, Kenya; ([paragraph]) Kenyan Medical Research Institute, Nairobi, Kenya; # National Institutes of Virology (NIV NIV New International Version (of the Bible)
NIV Non-Immigrant Visa
NIV No Income Verification (loan)
NIV Non Invasive Ventilation
NIV No Innocent Victim (band) 
), Sandringham, South Africa; ** World Health Organization, African Regional Office, Harare, Zimbabwe; ([double dagger]) Medecins Sans Frontieres, Paris, France; and ([double dagger] United States Army United States Army

Major branch of the U.S. military forces, charged with preserving peace and security and defending the nation. The first regular U.S. fighting force, the Continental Army, was organized by the Continental Congress on June 14, 1775, to supplement local
 Medical Research Unit, Kenya the World Health Organization Hemorrhagic Fever Task Force(1)

(1) Members of the World Health Organization (WHO) Hemorrhagic Fever Task Force, in addition to the listed authors, included Paul Arguin, David Ashford, Julianna Grant, Stuart Nichol, and Brian Plikaytis, Centers for Disease Control and Prevention; Marta Valenciano, European Program for Intervention Epidemiology Training, European Union; James N. Mwanzia, Philip Kangethe, Stephen A. Mileso, and Quinto Maloba, Kenya Ministry of Health; Manuela Dunster, Kenyan Medical Research Institute; Alan Kemp and Koos Coetzer, National Institutes of Virology, Sandringham, South Africa; Jean-Jacques Muyembe, Philip M. Mothoka, Gregory C. Gottlieb, John H. Bierke, and Glyn Davies, WHO, Geneva Geneva, canton and city, Switzerland
Geneva (jənē`və), Fr. Genève, canton (1990 pop. 373,019), 109 sq mi (282 sq km), SW Switzerland, surrounding the southwest tip of the Lake of Geneva.
 and African Regional Office; Saade Abdallah, International Federation of the Red Cross and Red Crescent; Elizabeth Nicore and Olivier West, Medecins du Monde; and Christine Grace Adhiambo, Africa Medical Research Foundation.

Dr. Woods is an Infectious Diseases and Medical Microbiology Fellow at Duke University. His interests include infectious disease outbreak investigations and diagnostic tests for emerging pathogens.
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