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zinc. In zinc deficiency, the concentration in the cir-

culation declines. Unfortunately, it also declines for a

myriad of reasons from normal meal patterns to stress

and infection to prolonged fasting to use of contra-

ceptive hormones, etc. The zinc in the circulation at

any given moment, however, represents less than

0.01% of the total body supply. For the individual,

a normal zinc level is a reasonable indication of ad-

equate status, but an isolated low value is difficult to

interpret. For populations, however, the prevalence of

low zinc concentrations provides the best epidemi-

ological diagnostic assessment.

0050 The recent development of assays for circulating

metallothionein I suggests the possibility of a sub-

stance that is low when the body demand is high

and high when the demand is low. Newer tests (func-

tional, see below) that are based on the state of regu-

lation and expression of the metallothionein gene

may be more sensitive with fewer confounding

factors than any assay for the metallothionein protein

itself, and more reflective of an active zinc pool. (See

Nutritional Assessment: Importance of Measuring

Nutritional Status; Biochemical Tests for Vitamins

and Minerals.)

Tests that Assess Tissue Concentrations

0051 A series of accessible tissues can be biopsied and

assessed as indicators of zinc availability at peripheral

sites, including: platelet zinc, lymphocyte zinc, gran-

ulocyte zinc, red cell zinc, buccal mucosa zinc, hair

zinc, and nail zinc. The former three circulating cellu-

lar elements, in theory, represent tissue that is more

rapidly turning over, and hence would represent more

current peripheral availability. More than 50% of all

circulating red cells are over 60 days old. Studies in

experimental mild zinc deprivation in volunteers have

shown that levels of zinc decline much earlier in

platelets, lymphocytes, and granulocytes than in red

cells or plasma. Buccal mucosa is easy to obtain, but it

can be contaminated by other sources of zinc. The

final three options represent integumentary tissue in

which the zinc may be deposited in proportion to the

zinc that was mobilized to the underlying, active

dermal, or mucosal tissue. For hair and nails, how-

ever, the rate of outward growth operates independ-

ently of the deposition of the nutrient into the roots,

confounding the interpretation of zinc content and

concentration.

Tests that Assess the Intactness of Zinc-dependent

Functions

0052 The functional assessment of nutritional status

involves evaluating the intactness of zinc-dependent

physiological functions. For zinc, performance-related

tests include growth attainment, gustatory acuity,

immune functions, dark adaptation, serum thymulin

activity and reconstitution, and zinc metalloenzyme

activities, to mention some of the more readily avail-

able options. The ratios of specific CD markers on

T-lymphocytes represent a newer version of an

immune-function measure. When evaluated at a

single point in time, the values for these or other

functional test must be classified in terms of norma-

tive curves of standard populations. As healthy

individuals vary widely along these parameters, this

weakens their reliability for clinical assessment. A

substantial overlap in the distributions of perform-

ance results exists for truly deficient and truly suffi-

cient individuals. Moreover, deficits in most of these

functions are not specific to zinc deficiency and may

be caused by other nutritional or pathological factors.

(See Nutritional Assessment: Functional Tests.)

Tests that Assess the Homeostatic Regulation

of Zinc

0053More specific functional tests for zinc are found in

those that examine its regulation. When the metabol-

ism of a nutrient is homeostatically regulated to

achieve fairly constant total body content, as in the

case with zinc, functional assessment of nutritional

status can also involve evaluation of the operation or

regulation. Isotopic turnover, again with

Zn, is an

index. Urinary zinc output after a zinc load has been

used to determine the threshold when body needs

have been met, and the body is no longer in a strict

conservation mode. Zinc absorption tests have also

been used to gauge regulation, as high rates of uptake

will occur in the zinc-deficient state. The regulation of

zinc by assessment of the function of metal regulatory

elements in gene expression or of rapidly turning over

products of the homeostatic mechanism, such as the

messenger RNA for metallothionein I, is the most

modern and sophisticated candidate in this line.

Responses to Zinc Supplementation

0054It has been stated correctly that, given the limitations

and caveats in the interpretations of all of the classes

of zinc status tests, the surest approach to diagnosis of

zinc status is retrospective, after a therapeutic trial

with zinc. Static indices such as plasma zinc levels or

the concentrations in accessible tissues are of limited

interpretation in a zinc supplementation trial, as they

would be expected to rise passively with increased

availability. However, a positive response in func-

tional tests either of tests of zinc-dependent functions

or of tests of homeostatic regulation would be a sig-

nificant indication that a zinc-responsive deficit in

function or an upregulation state had existed at the

time of the original inquiry. Zinc doses should be in

the dietary range, as high-dose supplements raise the

6280 ZINC/Deficiency

specter of a pharmacological effect of zinc, unrelated

to underlying nutritional status.

Practical Recommendations for Zinc Status

Evaluation

0055 Despite the theoretical considerations that the major

response to zinc deficiency involves conservative and

adaptive mechanism of a nonspecific nature, total-

body zinc and zinc in various tissues and compart-

ments are influenced in most forms and etiologies of

human zinc deficiency. Given the pitfalls in the inter-

pretation of any given tests, a battery of tests, com-

bining circulating zinc level assay with several of the

other tissue assays and functional tests, is recom-

mended. When a short-term clinical supplementation

trial is possible, it can give the most definitive diagno-

sis short of isotopic studies.

Clinical Conditions Associated with Zinc

Deficiency

0056 It follows from the discussion of pathogenesis of zinc

deficiency that any disease or disorder that produces

decreased intake, decreased absorption, excess losses,

impaired utilization, or increased demand could pre-

dispose to zinc deficiency. The clinical conditions that

have been associated with human zinc deficiency are

as follows:

0057 protein–energy malnutrition;

0058 vegetarianism;

0059 zinc-poor diet;

0060 experimental depletion;

0061 psychogenic eating disorders (anorexia nervosa;

bulimia);

0062 high-fiber, high phytate diets;

0063 high-dose iron supplements;

0064 cancer cachexia;

0065 synthetic diets;

0066 zinc-poor total parenteral nutrition;

0067 acarodermatitis enteropathica;

0068 Crohn’s disease;

0069 jejuno-ileal bypass;

0070 chronic renal failure;

0071 ulcerative colitis;

0072 celiac disease;

0073 intestinal helminthiasis (ascariasis, trichuriasis);

0074 intestinal giardiasis;

0075 alcoholism;

0076 alcoholic hepatitis;

0077 viral hepatitis;

0078 alcoholic cirrhosis;

0079 acute alcoholic pancreatitis;

0080 primary biliary cirrhosis;

0081 infantile biliary atresia;

0082 cystic fibrosis;

0083Schwachman’s syndrome;

0084phenylketonuria;

0085sickle cell disease;

0086thalassemia;

0087porphyria;

0088muscular dystrophy;

0089acquired immunodeficiency syndrome;

0090hyperparathyroidism;

0091thermal burns;

0092short-gut syndrome;

0093exocrine pancreatic insufficiency;

0094thiazide diuretic use;

0095parenteral ethylene diamine tetraacetate chelation

therapy;

0096oral ethylene diamine pentaacetate chelation

therapy;

0097oral d() penicillamine therapy;

0098diabetes mellitus;

0099persistent diarrhea;

0100ileostomy fluid loss;

0101exfoliative dermatitis;

0102psoriasis;

0103prolonged lactation;

0104twin pregnancies;

0105very low birth weight;

0106rapidly proliferating malignancies;

0107synthetic growth hormone therapy.

Prevalence of Zinc Deficiency

0108When the parameter is zinc deficiency in a medical

and clinical context, the prevalence and incidence of

the diseases and conditions discussed in the preceding

section – and their management – would determine

the global prevalence of zinc deficiency. Viewed as a

public health problem on a population and epidemi-

ological basis, however, marginal and deficient zinc

status is emerging as a subject of great interest. In the

classical regions of endemic zinc deficiency, the rural

oases of Iran and Egypt, its occurrence has been

attributed to interference with zinc bioavailability

by the high-extraction, unrefined cereal diets. Char-

acteristics of the diet and the occurrence of adverse

health conditions would determine endemic zinc defi-

ciency. Brown and Wuehler have made a crude esti-

mate of risk of endemic zinc deficiency through an

assessment of zinc in the global food supply. This is

based on national food balance sheets and estimates

of the content of zinc and of major inhibitors of its

biological availability, primarily phytic acid. They

conclude that the daily rations provide 7–9mg of

absorbable zinc per capita in South and South-east

Asia, the Middle East, and throughout Africa, with

9–11 mg available in Latin America and China, and

11–12 ng in the affluent countries of North America,

Western Europe, and Oceania, placing the former

ZINC/Deficiency 6281

two geographic categories at risk of endemic zinc

deficiency. This has potentially important implica-

tions, as a recent population intervention trial with

oral zinc has suggested that the incidence of malarial

attacks, diarrheal episodes, and acute respiratory

infections may be reduced by daily zinc supplements.

0109 Within societies, social and economic deprivation

is a common denominator for the expression of zinc

deficiency or marginal zinc status in both industrial-

ized and nonindustrialized countries.

0110 As with other nutrients, it is believed that young

children, pregnant women, and the elderly would be

the most at risk for zinc deficiency. Infants who are

exclusively breast-fed are generally protected against

zinc deficiency, but formula-fed infants, especially

those with iron-fortified diets, could also share some

risk for zinc deficiency. Adolescence is associated

with a rapid growth spurt, and this could attenuate

the adequacy of zinc from a diet that was sufficient

when less of the nutrient was being deposited or

utilized for cell growth and replication. Zinc loss

resulting from recurrent infections, parasites, and

climatic conditions (heat, humidity) would also be

factors in the etiology of marginal zinc deficiency.

(See Elderly: Nutritional Status.)

0111 Despite these theoretical considerations, bolstered

by some experience in attempting to document the

zinc status of the various populations and subgroups

discussed above, the pitfalls and limitations of diag-

nostic indices for zinc status have limited both the

number of population-based surveys of human zinc

status that have been performed and the reliability of

the estimates of prevalence of deficiency. The most

reliable approach to assessing the prevalence of zinc

deficiency would alter that prevalence at the same

time, namely a therapeutic trial of zinc supplemen-

tation. The individuals who respond with a func-

tional improvement, i.e., accelerated growth, better

appetite, and improved physiological or cognitive

performance, could be classified retrospectively as

having been zinc-deficient.

Treatment of Zinc Deficiency

0112 The treatment of clinical or subclinical zinc deficiency

requires the restoration of adequate body pools and

tissue concentrations of zinc. It invariably involves

the administration of amounts of zinc in excess of

the daily requirements as zinc-rich foods or in the

form of zinc salts or chelates. Salts such as zinc sulfate

and chelates such as zinc gluconate are available

commercially as oral tablets; no convincing evidence

of improved bioavailability of chelates has been

forthcoming. The most efficient uptake of zinc from

supplements is achieved on an empty stomach, but

gastric irritation symptoms often move patients to

combining their zinc with meals, to the detriment of

its absorption rate.

0113When subjects cannot tolerate food or oral medi-

cations, the intravenous (parenteral) route can be

used. For parenteral administration, pharmacological

preparations of zinc chloride or zinc sulfate are avail-

able in single formulation or in combination with

trace elements. The daily dosage original guidelines

they put forth by expert panels of various North

American physicians groups have remained valid for

decades: they put forth the following guidelines for

daily parenteral administration of zinc: stable adults,

2–5-4.0 mg; adults with disease-related, enteral

losses, 12–17 mg; term infants, 150 mgkg

1

; pre-

mature, low-birthweight infants, > 300 mgkg

1

.To

avoid the toxicity reported with excessively rapid

dosing, parenteral zinc should never be given as a

bolus. Zinc chloride and zinc sulfate are compatible

in solution with most other intravenous forms of

essential micronutrients.

Prevention of Zinc Deficiency

0114Prevention of zinc deficiency can be considered at

the level of the healthy individual adult or child,

at the level of the zinc deficiency or a predisposing

medical condition, or at the level of public health of

nutritionally vulnerable populations or subgroups.

Prevention in Healthy, Normal Individuals

0115Spontaneous clinical zinc deficiency is unlikely to

occur in healthy individuals on a dietary basis, but

they are at risk of marginal deficits. The US Institute

of Medicine’s Food and Nutrition Board in its Dietary

Reference Intakes has revised the recommendations

for dietary intakes that would keep most healthy

individuals replete, as has an expert panel for the

UN agencies of the World Health Organization and

International Atomic Energy Agencies. In a departure

from the approach of the past, in which the safe and

adequate level for the individual (recommended diet-

ary allowance, safe dietary intake) was the focus of

recommendations, the new approach is focused more

on the normative distribution of zinc intakes within a

population that would be considered to be at low risk

for endemic zinc deficiency. For the US population,

this is based on the estimated average requirement

derived from actual normative zinc intake data. For

the world at large, the UN still used a factorial ap-

proach to determine the requirement for uptake of

zinc, and then added assumptions for different levels

of bioavailability in different regional cuisines (high

(45–55%), medium (30–35%), and low (10–15%)),

and finally adjusted for a standard population vari-

ance. For instance, for an infant, 6–12 months of age,

6282 ZINC/Deficiency

the WHO/IAEA recommended population daily zinc

intake for a diet of medium bioavailability is 5.6 mg.

For children aged 6–10 years, this figure is 7.5 mg,

rising to 13.1 mg in late adolescence; for men above

18 years, 9.4 mg; for women above 18 years, 6.5 mg;

for pregnant women, 10 mg; and for lactating

women, 12.2 in the first 6 months of breast-feeding.

To calculate the intake that would cover 97.5% of the

population, a 50% overage is added to these values

for the respective individual protective intakes. (See

Dietary Requirements of Adults.)

0116 Sources of highly available zinc include oysters,

herring, lean beef, and lean pork. Increasingly, ready-

to-eat breakfast cereals and breakfast snack bars

are zinc-fortified. Almost all multivitamin-mineral

supplements currently contain zinc. Although breast

milk has relatively low zinc concentrations, its zinc is

highly absorbable. Exclusive breast-feeding should be

protective for the infant, although an occasional case

of zinc deficiency from an idiopathic abnormal milk

supply has led to infantile zinc deficiency.

Prevention in Persons Predisposed to Deficiency

0117 If an individual has a history of zinc deficiency, or has

one of the conditions listed above (see Section Physio-

logical and Metabolic Consequences), more attention

to primary prevention, or to avoiding recurrence, is

required. Eliminating or ameliorating the primary

medical or psychological condition should reduce

the tendency to underconsumption and/or malutiliza-

tion of the nutrient. If the underlying disorder cannot

be addressed, chronic use of some multiple – two or

three times – of the usual recommended level may be

necessary.

Prevention in Vulnerable Populations

0118 If epidemiology suggests that a population is prone to

zinc deficiency or marginal zinc status, some public

health measures are warranted. The classical popula-

tions in which zinc deficiency on a dietary basis was

described were juveniles in rural areas of Iran and

Egypt with a common factor of total zinc intakes in

the acceptable range but a consumption of inhibitors

of bioavailability (dietary fiber, phytic acid) that re-

duced its absorption. For such a population, changes

in dietary practices to introduce sources of highly

absorbable zinc or to adopt alternative processing of

traditional cereal grains (germination, fermentation,

phytase treatment) might be a solution. Possibilities

in plant genetics and plant breeding to reduce inhibi-

tors such as phytic acid or to increase the affinity of

the leaves and other tissue to hold divalent cations are

under exploration. The final approach is fortification

of a staple food with zinc. Hence, the strategies for

ensuring a generous intake of zinc in underprivileged

populations include popular nutrition education for

better food choices, and fortification of some

common food-stuffs with additional zinc. As growing

children are the usual victims of endemic marginal

zinc status, a food vehicle targeted to this age group

can provide more effective coverage. Confectionary,

breakfast cereals and soft drinks are among the

options for reaching the vulnerable population with

fortification of zinc. (See Food Fortification.)

0119In underprivileged groups in both developed and

developing countries, subsections of the population

of children who respond to zinc supplementation

with improved growth have been identified. Whether

or not the additional burden of zinc loss owing to

recurrent infections combines with poor appetite and

restricted variety of foods to generate a subclass of

zinc marginal individuals is worth considering. Once

again, increased loss of zinc can be overcome by

compensatory increased intakes of the mineral.

Chronic supplementation with zinc is likely to be

unsustainable and poses a potential risk to copper

nutriture and immune function in at least a subseg-

ment of a long-term supplemented population.

See also: Adolescents; Bioavailability of Nutrients;

Children: Nutritional Requirements; Nutritional

Problems; Coenzymes; Dietary Requirements of

Adults; Elderly: Nutritional Status; Food Fortification;

Infants: Nutritional Requirements; Nutritional

Assessment: Importance of Measuring Nutritional

Status; Biochemical Tests for Vitamins and Minerals;

Functional Tests

Further Reading

Black RE (1998) Zinc deficiency and child development.

American Journal of Clinical Nutrition 68(supplement):

464S–469S.

Brown KH and Wuehler S (2000) Zinc and Human Health:

Results of Recent Trials and Implication for Program

Interventions and Research. Ottawa: Micronutrient

Initiative.

Gibson RS (1994) Zinc nutrition in developing countries.

Nutrition Research Reviews 7: 151–173.

Hambidge KM (2000) Zinc and human health: current

status and future directions. Journal of Nutrition 130:

1341S–1343S.

Prasad AS (1990) Discovery of human zinc deficiency and

marginal deficiency of zinc. In: Tomita H (ed.) Trace

Elements in Clinical Medicine, pp. 3–14. Tokyo:

Springer-Verlag.

Sandstro

m BM (2001) Diagnosis of zinc deficiency and

excess in individuals and populations. Food and Nutri-

tion Bulletin 22: 133–137.

World Health Organization/International Atomic Energy

Agency (1996) Trace Elements in Human Nutrition

and Health. Geneva: WHO.

ZINC/Deficiency 6283

ZOONOSES

R Cichon, A Platt-Samoraj and J Uradzin

ski,

Warmia and Masuria University in Olsztyn, Poland

Introduction

0001 Zoonoses are defined as ‘those diseases and infections

which are naturally transmitted between vertebrate

animals and man.’ In an obligate zoonotic disease,

such as anthrax, transmission occurs only from animal

to human, whereas in facultative zoonoses, infections

are mostly transmitted among humans. Animal-based

food may harbor the etiological agent which has

infected its living host.

0002 None of these zoonotic diseases is transmitted to

humans exclusively by means of food. Food is only

occasionally the vehicle of transmission. Since the

oral route represents only one of several possible

ways of infection, zoonoses are not then foodborne

diseases in the general meaning.

0003 It is impossible to give here a complete survey of all

zoonoses potentially transmitted to humans via food.

This article highlights three of the most important:

brucellosis, Q fever, and leptospirosis.

Brucellosis

0004 Brucellosis is an acute febrile disease, or a chronic

disease with a wide variety of symptoms. It is a true

(an obligate) zoonosis transmitted to humans gener-

ally by domestic animals, especially cattle, pigs, and

goats. Brucellosis is variously known as undulant

fever, Malta fever, Mediterranean fever, or mimic

fever.

Occurrence and Prevalence of Disease

0005 This disease is caused by pleomorphic organisms of

the genus Brucella, which also includes the organisms

that are responsible for infectious abortion (Bang’s

disease) in cattle and swine. Brucellae are highly

infectious, even in very small numbers. The organ-

isms can appear as a coccus, a bacillus, or with char-

acteristics of both (a coccobacillus). They may appear

singly and, less frequently, in pairs, short chains, or

small groups. The brucellae are nonmotile and

nonsporing, and they possess neither capsules nor

flagellae. Resting stages are not known.

0006 The genus Brucella contains six species of bacteria.

Important causes of human disease are the three main

species: Brucella melitensis of goats and sheep, bio-

types 1–3; B. abortus of cattle, biotypes 1–9; and

B. suis of pigs, European hares, and reindeer, biotypes

1–4, with the possible exception of biovar 2. Of the

others, B. ovis causes disease only in sheep, mainly

rams; B. canis affects dogs, but is occasionally trans-

mitted to humans, causing a mild type of brucellosis;

and B. neatomae has been isolated from the desert

wood rat. Brucellae have also been isolated from

many other animal species, both wild and domestic,

e.g., poultry, rabbits, rodents, foxes, hares, elk, deer,

moose, polecats, hedgehogs, and insects (flies, mos-

quitoes, ticks, and bedbugs). It seems, therefore, that

there are many types of animal reservoir of brucellae.

The extent of the role of insects and wild animals

in the transmission of brucellosis to humans is not

known. The fact that B. ovis and B. canis were

not discovered until 1953 and 1967, respectively,

has led to speculation that the genus Brucella may

be in a phase of rapid evolution and that new species

may be emerging.

0007Brucellosis is distributed everywhere throughout

the world. The following groups of people whose

occupation brings them into contact with animals

are especially endangered: farmers, veterinarians,

workers in slaughterhouses and meat-packing and

-processing plants, as well as laboratory personnel.

It is particularly common in areas where goats, sheep,

cattle, and swine are raised. B. melitensis infection is

prevalent in the Mediterranean area, central Asia,

and some parts of Latin America, especially Mexico

and Peru; it does not occur in northern Europe, the

USA, Canada, South-east Asia, or Australia. Bovine

brucellosis (B. abortus infection) is moderately preva-

lent in most parts of the world, with the exception of

many developed countries, although it persists in

some southern areas of the USA. Porcine brucellosis

(B. suis infection) is still fairly widespread in Latin

America, South-east Asia, and the Pacific region.

Canine brucellosis due to B. canis occurs in many

countries, but poses only a minimal threat to human

health.

Mechanism of Entry into Food and Transfer to

Human

0008In the more susceptible species of domestic animal

(cattle, goats, sheep, and pigs), enormous multipli-

cation of brucellae occurs in the uterus in the latter

part of pregnancy and, to a lesser extent, in the

mammary glands during lactation. Abortion, and

sometimes parturition at the normal time, leads to

6284 ZOONOSES

massive contamination of the environment. On the

other hand, excretion of brucellae in the milk, usually

in much smaller numbers, may continue for years.

Thus, milk and dairy products are frequently the

source of foodborne brucellosis. Moreover, brucellae

are intracellular parasites of the reticuloendothelial

system and penetrate the whole body of the infected

host.

0009 B. melitensis and B. suis transmit more easily to

humans then B. abortus. The usual portal of entry in

humans is by the mouth, either directly by consuming

infected dairy and meat products, or indirectly

through contact with hands contaminated during

work. Less commonly infection may occur via con-

junctiva or by inhalation. An outbreak of brucellosis

from consumption of wild greens contaminated by

sheep and goat urine and feces has also been reported.

Detection in Foods

0010 The detection of Brucella species involves cultivation,

various serological methods, animal tests and, occa-

sionally, microscopic examination.

0011 There is a simple and sensitive method of detecting

Brucella contamination in milk, known as the milk

ring test. In this test, a Brucella antigen stained with

hematoxylin is added to milk. Any agglutinins in the

milk, which are carried by the cream as it rises to the

surface, react with the antigen. Clumping follows,

and a blue ring, indicative of the presence of brucel-

lae, is formed. This test can be used to detect contam-

inated cows’ milk but a similar ring test is available

for goats’ milk. Milk ring tests are unreadable with

sheep milk. Recently, a rapid polymerase chain reac-

tion (PCR) method has been developed for detection

of Brucella species in milk and in milk products.

There is also an immunoenzymatic assay (milk

enzyme-linked immunosorbent assay (ELISA)),

which is more sensitive then the milk ring test and it

is a better screening test then PCR.

Fate of Bacteria During Processing of Storage

0012 Brucellae in milk and meat are readily destroyed by

conventional pasteurization methods properly used in

dairy or meat processing. They are very sensitive to

sunlight, being killed in a few hours, and also quite

sensitive to acid conditions (pH 4 or below). How-

ever, highly relevant to the transmission of brucellae

by food products is the extent of survival of these

organisms in food. The organisms survive for only a

few hours in raw milk at 37



C, and for 48 h at 8



At ordinary room temperature the organism will sur-

vive, according to another report, for several days

until souring of the milk kills them. It is possible

that other organisms may influence the survival of

brucellae since, in sterile milk, they may survive for

17 days. Moreover, they can survive in tapwater for

10 days at 25



C or 57 days at 8



C, but in the pres-

ence of organic matter, such as cattle urine and feces,

soil, and even lake water at 25



C, they can survive for

more than 2 years.

0013It appears that the brucellae are a group of sturdy

organisms, which can survive prolonged periods in

milk and dairy products as well as in meat products.

0014Methods of processing milk products, e.g., cheese-

making from raw milk, generally do not destroy

them. Survival of Brucella in unpasteurized soft

cheese is discussed. If present in cheese, the organism

will survive from 38 days to more than 180 days,

but aging of cheese tends to destroy the bacteria. In

Cheddar cheese, no brucellae survived after 1 year.

However, the European Union veterinary advisory

committee in 1995 concluded that a ripening time

or cheese age of 60 days is sufficient to eliminate a

potential brucellosis risk to the consumer. Brucellae in

naturally contaminated milk have been shown to sur-

vive during the processing of the milk to butter, but-

termilk, and icecream. The organism has also been

shown to survive in icecream stored below freezing

for more than 1 month. Brucellae may survive in ham

during pickling in brine for 21 days, and in salted and

otherwise cured meats for 150 days, but not after

the smoking process. B. suis has also been shown to

survive for 21 days in pork under refrigeration and

B. abortus in sausages for 175 days.

Symptoms of Illness and Treatment

0015Brucellosis in humans provides serious diagnostic

problems, partly because the clinical symptoms are

variable and often ill-defined and the complications

can affect many systems. The incubation period

ranges from 10 to 14 days. The onset is influenza-

like with recurrent or undulating fever reaching tem-

peratures up to 40–41



C in the evening, falling to

normal each morning. Limb and back pains are un-

usually severe. Sweating, headache, muscle ache, mal-

aise, and fatigue, as well as anorexia and weight loss

are the other symptoms. If untreated, symptoms may

persist for months and complications may enter an

ill-defined chronic syndrome, involving several body

systems and organs.

0016For reasons which are not known, children, who

are the main milk drinkers, seem to be less susceptible

to brucellosis than adults. Evidence suggests that in

humans, natural infection and complete recovery

produce some resistance to reinfection.

0017Tetracycline alone or in several drug combinations

may determine the effective treatment of acute bru-

cellosis in humans if the treatment is prolonged for

ZOONOSES 6285

6 weeks. Patients with chronic brucellosis frequently

need symptomatic treatment in addition to antibiot-

ics, and their response to antibiotic treatment is often

disappointing.

Prevention of Brucellosis

0018 Vaccination of animals, particularly when young, and

testing animals and slaughtering reactors are prob-

ably the best means of controlling brucellosis. Occu-

pationally exposed workers can be protected by

wearing impermeable clothing, rubber boots, gloves

and face masks, and by practicing good personal

hygiene.

0019 Since food and water are not the only modes of

transmission, control in these aspects only will not

minimize the occurrence of the disease. Nevertheless,

removal of these sources of infection will do much to

minimize human brucellosis. Thus, meat of all kinds,

especially from unknown sources or from contamin-

ated areas, must be cooked thoroughly. Raw milk

should never be drunk without pasteurization, no

matter what the source. Milk products, such as

cheese, butter, and icecream, should be prepared

from pasteurized milk. It must be emphasized that,

in countries in which brucellosis has been eradicated,

individuals can acquire the disease by consuming

imported dairy products or by visiting countries in

which the disease is endemic.

Q Fever

0020 The Q (for ‘query’) fever infection was observed for

the first time in Queensland, Australia, in 1935,

during an outbreak of the febrile illness among abat-

toir workers. The disease also occurs in the USA,

Canada, and Europe. Although a number of animals

are susceptible, it is not certain that infection results

in overt disease, except in the guinea-pig and in

humans.

Occurrence and Prevalence of the Disease

0021 The disease is transmitted generally by tick bites from

wild animals (the natural reservoir) to domestic

animals, especially ruminants. The infection is fre-

quently symptomless in animals; the mammary gland,

parenchymatous organs, muscles, lymph nodes, and

uterus of infected slaughter cattle may harbor the

organism. The microorganisms grow particularly

well in the placenta of these animals, where they

may reach a titer value of 10

viable organisms per

gram of tissue. Transmission of disease from ticks to

humans is uncommon. Sporadic cases or outbreaks of

the human disease, Q fever, occur primarily among

individuals involved in the transport of infected do-

mestic animals and in the meat and dairy industries.

Mechanism of Entry into Food and Transfer to

Humans

0022The main source of infection is highly infectious dust

from tick feces deposited on the hides of animals or

from dried placenta following parturition. The dis-

ease is usually transmitted to humans in three ways:

by airborne dissemination in aerosols or dust contam-

inated with organisms; by processing of animal

products, usually wool and hides; or by ingestion of

infected food, especially raw milk. It seems to be well

established that the infection may be transmitted by

drinking infected milk. Milk may contain up to 10

infective doses per gram, even when serologically

negative.

Detection in Food

0023Coxiella burnetii, the infectious agent of Q fever,

differs sufficiently from other organisms of the genus

Rickettsia to be classified in a separate genus, Cox-

iella, in the family Rickettsiaceae. Attempts to isolate

C. burnetii in the laboratory are hazardous and should

be avoided. The diagnosis of Q fever can be con-

firmed serologically by significant increases in com-

plement fixation, agglutination, or direct fluorescent

antibody levels to phase I or II antigens. The comple-

ment fixation test (CFT) is widely used and regarded

as reliable. However, some cows excrete coxiellae

without positive CFT titers. The agglutination test is

the method of choice for epidemiological survey

work. Additionally, the capillary agglutination test

(CAT) requires very small amounts of reagents; it is

performed similarly to the Brucella ring test by over-

laying serum, milk, or whey with a partially purified

phase I C. burnetii antigen. Positive results are indi-

cated by a colored ring (cream layer) and/or agglutin-

ation throughout the serum or milk column. Also,

ELISA, PCR, and PCR-ELISA techniques are avail-

able. PCR technique is more sensitive than standard

culture techniques for retrospective diagnosis with

frozen samples.

Fate of Bacteria During Processing or Storage

0024C. burnetii has a high degree of resistance to physical

and chemical agents, comparable to that of sporo-

genic bacteria. This resistance might be attributable

to the endospore-like forms. At 4



C, viability is

retained for over 1 year in dried form such as tick

feces or wool, as well as in sterile skim milk or

unchlorinated water. Meats remain infected for at

least 1 month. Whether common dairy pasteurization

will kill the organism depends on the procedure

applied. Complete inactivation is not always

accomplished by exposure to 63



C for 30 min or

85–90



C for a few seconds. However, with the

6286 ZOONOSES

high-temperature, short-time method, no viable cox-

iellae have been demonstrated as yet in naturally

infected milk.

Symptoms of Illness and Treatment

0025 Q fever usually becomes apparent 2–4 weeks after

exposure to the causative agent. In most cases

Q fever may resemble a mild type of influenza. How-

ever, the severity of illness ranges from a subclinical

infection to a febrile flu-like illness accompanied by

respiratory symptoms, severe headache, arthralgia,

and myalgia. Interstitial pneumonia, resembling a

viral or primary atypical pneumonia, occurs in

about 50% of patients. The characteristic rash of

other rickettsial diseases does not occur. Usually,

Q fever is a self-limited disease which lasts for 2–3

weeks, but fulminating pneumonia and chronic infec-

tions in the form of lipogranulomatous liver disease

and endocarditis may complicate its course. To pre-

vent complications, all patients with acute Q fever

should be treated with tetracycline and chloram-

phenicol. Prolonged therapy with tetracycline, usu-

ally in combination with a rickettsiacidal drug, is

required. C. burnetii is also inhibited by rifampicin,

and only to a very limited extent by penicillin,

streptomycin, or erythromycin.

Prevention of Disease

0026 Persons at risk, such as abattoir workers, dairy and

farm workers, veterinary personnel, woolsorters,

tanners, and some laboratory research workers,

should be monitored serologically at regular intervals

and during respiratory or influenza-like illnesses.

Also an effective vaccination as a preventive measure

should be considered for such groups of population. If

Q fever is diagnosed, treatment should be instituted

promptly to prevent the serious complications that

can develop after the illness.

Leptospirosis

0027 Leptospirosis is a zoonosis that is worldwide in

distribution and encompasses a broad spectrum of

animal hosts. The primary reservoir hosts are wild

animals. Domestic animals, especially dogs, cattle,

and swine, may also be an important source of

human infection.

Occurrence and Prevalence of the Disease

0028 Leptospires, the causative agents of leptospirosis,

have been isolated from approximately 160 mamma-

lian species in the temperate zone. The disease is more

widespread in tropical countries where the infectious

agent may be one of some 150 pathogenic serotypes

of Leptospira interrogans, carried by a large variety

of hosts. The most important reservoirs or carriers are

various rodents, particularly the common Norway rat

(Rattus norvegicus), which is the principal carrier of

the often very virulent serotype L. interrogans serovar

icterohaemorrhagiae. In animals, particularly rodents

and dogs, pathogens may colonize the kidneys

following infection, which may or may not be symp-

tomatic. Pathogenic leptospires, multiplying in the

convoluted tubules, are shed in the urine of infected

animals, and susceptible hosts become infected

through contact with urine or urine-contaminated

environs such as moist soil and surface water.

Humans are accidental hosts. In general, infections

in humans occur through broken skin and mucous

membranes. Thus, persons who work in foul, watery

places such as sewers, rice fields, and poorly built

mines are exposed to the causative agent.

Mechanisms of Entry into Food and Transfer to

Humans

0029There are two sources of leptospires which may be

involved in contamination of food: (1) urine of

infected animals, especially rats; and (2) infected

soil, dust, and water. However, the possibility of

leptospirosis transmitted by contaminated food or

water is rare. This is understandable in view of the

extreme sensitivity of the organism to acidity. Thus,

the stomach serves as a protective barrier. Neverthe-

less, one case of foodborne leptospirosis has been

reported: 8 days previously, the patient had consumed

ham which appeared to have been gnawed by rats,

and presumably have been urinated on by the rodents.

While leptospires may be shed into the milk from

infected animals, there are no proven cases of milk-

borne leptospirosis in humans. However, milk has a

leptospiricidal property which is not destroyed by

pasteurization.

Fate of Bacteria During Processing or Storage

0030Leptospires are very sensitive to heat. They are killed

within 10 s at 60



C and 2 h at 32



C. Therefore, any

pasteurization method used should be effective in

killing the organism during food processing.

0031Leptospires are quite sensitive to many chemical

and environmental factors. They are killed by long-

chain fatty acids as well as by detergents. These sub-

stances, however, have no effect in the presence of

albumin or other serum proteins which combine

with these chemicals. The organisms are also killed

by sea water, chlorine in the water supply, and ultra-

violet light. They are killed at varying rates (a few

minutes or hours) in liquids at pH values below 5 and

above 8.5.

ZOONOSES 6287

0032 Moisture may play an important role in their sur-

vival. Thus, leptospires have been shown to survive

for 279 days during the winter in soils with 70%

moisture and only 3 days with 10% moisture. Lep-

tospires have also shown a remarkable ability to

survive at extremely low temperatures. Thus, when

quick-frozen to 70



C, they survive for many years

with no loss in virulence.

0033 In milk, stored at 40



C for 2 months, pasteurized

or heated at 80



C for 5 min, leptospires are killed

within 3 h. This leptospiricidal property of raw or

pasteurized milk is destroyed by boiling. Dilution of

the milk also decreases the leptospiricidal property.

Thus, it has been shown that 1:20 to 1:80 dilutions

allow the organisms to survive in milk for 60 days.

Leptospires have been shown to survive for 33 h at



C in refrigerated bovine meats. Survival of the

organism from 3 to 12 days in muscle, liver, kidney,

and spleen at 3–5



C has also been reported.

Symptoms of Illness and Treatment

0034 Leptospirosis may appear in either a mild or severe

form, and both types have similar incubation periods

– 7–14 days. Most leptospiral infections are mild

and virtually all pathogenic serotypes cause febrile

illness in humans. The most prominent symptom is

continuous fluctuating fever with temperatures of

38.9–41.9



C for 2–12 days or more, severe headache,

muscle pain, and nausea that persists for approxi-

mately 7 days. Jaundice occurs during this phase in

more severe infections. The different forms of lepto-

spirosis are known by other names which are suggest-

ive of the causative serotype, duration of symptoms,

or the mode or place of transmission or original dis-

covery. Thus, the disease is also known as Fort Bragg

fever, canicola fever, 7 days’ fever, mud or swamp

fever, canecutter’s disease, pea picker’s disease, and

swineherd disease. In the severe form of leptospirosis,

also known as Weil’s disease, these symptoms are

more intense, particularly gastrointestinal bleeding,

renal failure, and central nervous system symptoms

such as anorexia, nausea, and vomiting.

0035 Clinical manifestations of leptospirosis, however,

are not sufficiently characteristic for a specific diag-

nosis of leptospirosis. As a result, the disease is often

initially misdiagnosed as meningitis or hepatitis.

Thus, microscopic demonstration of the organisms,

serological tests, or both, is necessary for diagnosis.

The microscopic agglutination test is more frequently

used for serodiagnosis of this disease. Highly sensitive

immunoenzymatic assays (ELISA) have recently been

used for the detection of leptospiral antibodies in

serum. Although leptospires are sensitive to penicillin

and tetracycline in vitro, use of these drugs in the

treatment of leptospirosis is controversial. If treat-

ment is initiated within the first week of disease

onset, the general belief is that it can be effective.

Later in the disease, immunological damage may al-

ready have begun, rendering antimicrobial therapy

ineffective.

Prevention of the Disease

0036Human leptospirosis may be controlled by reducing

its prevalence in wild and domestic animals. Al-

though little can be done about controlling the disease

in wild animals, leptospirosis in domestic animals can

be reduced through vaccination. Doxycycline is a

valued preventive drug. Administration of 200 mg

weekly may be effective prevention against lepto-

spirosis in endangered people. This group of persons

should wear impermeable clothes and boots. An

awareness of the possible contamination of, for

example, soil, mud, stagnant water, ponds, and

streams, and avoiding polluted food or water, along

with control of rat populations, is essential to the

prevention of the infection. Even though transmission

of the disease by ingestion is very rare, there remains

the hazard of foodborne transmission. Heating and

cooking food and avoiding unchlorinated water

would still be a safe rule to follow, particularly if the

source of drinking water may be contaminated by

animal discharges.

See also: Contamination of Food; Escherichia coli:

Food Poisoning by Species other than Escherichia coli;

Infection, Fever, and Nutrition; Milk: Processing of

Liquid Milk