assumed before conception and then for the first 3 months of pregnancy
reduces the risk of recurrence of neural tube defectsref,
and fortification of food has been proposed. The effects of long term exposure
to high concentrations of supplemental folate are unknown, and antimetabolite
effects are theoretically possibleref.
A large trial of folate supplementation in pregnancy was followed up from
the 1960sref.
In women randomised to high doses of supplemental folate, all cause mortality
was about a fifth greater, and the risk of deaths attributable to breast
cancer
was twice as great. This increased risk in deaths attributable to breast
cancer is unlikely to be due to competing causes as the number of deaths
was small and all cause mortality appeared to be greater. The increase
in mortality and in death from breast cancer with high doses of folate
could be a chance finding. The number of deaths was small, the confidence
intervals were wide, and we had no prespecified hypothesis that taking
folate supplements in pregnancy would increase the risk of cancer. As this
randomised trial was of high quality, bias and confounding are unlikely
explanations for these findingsref.
A recent study indicated that rats fed diets deficient in folate had increased
mammary tumorigenesis compared with rats fed diets with sufficient folate,
whereas rats fed a high dose folate diet had similar levels of tumorigenesis
to deficient ratsref.
: 1.5-2.5 fluoride
mg/die (0.05-0.07 mg/kg). Fluoride displaces -OH groups in hydroxyapatite
creating fluoroapatite, reducing caries by 80%. The fluoride only seems
to penetrate into the first few layers of atoms on a tooth's surface, so
the physical abrasion during chewing will probably remove it : this suggests
that repeated exposure to fluoride is necessary for a lasting protective
effect on tooth enamel. Some researchers have argued that fluoride has
to be incorporated into teeth as they form in young children to protect
the teeth for life, but more recent research shows that using fluoride
toothpaste as an adult is just as effective at strengthening teethref- systemic route (since pregnancy up to age 12-13 for > 260 days/yr). Plasma peak after 30'.
- fluorized water (different water drinking is a variable)
- fluoride caps
- fluoride drops (4 gtt = 0.25 mg)
- fluoride-fortified chewing gums = 0.50 mg (also local action)
- topical route after age 13
- sodium fluoride and orthophosphoric acid solution : a solution containing 90 to 110% of the labeled amount of fluoride ion; used as a dental caries prophylactic, applied topically to the teeth.
prophylaxis to prevent rickets
:- malnutrition rickets : from birth to age 2, suspended during summertime if the baby can be exposed to sunlight for enough time
- 200-400 IU 1a,25-(OH)2-vitamin D3/day p.o.
- 100,000 IU 1a,25-(OH)2-vitamin D3 every 2-3 months p.o.
- 200,000 IU 1a,25-(OH)2-vitamin D3 every 6 months i.m.
- intestinal malabsorption rickets : 2,000-4,000 IU 1a,25-(OH)2-vitamin D3/day p.o or 10-20 mg 25-OH-vitamin D3/day
- hepatobiliary rickets :
- 2,000-5,000 IU 1a,25-(OH)2-vitamin D3/day p.o. or 10 mg 25-OH-vitamin D3/kg/die
- 200,000 IU 1a,25-(OH)2-vitamin D3 every 3 months i.m. or 50 mg 25-OH-vitamin D3/day
- anticonvulsant rickets : 800-1,200 IU 1a,25-(OH)2-vitamin D3/day p.o. or 1,000-3,000 every week p.o.
(treatment : GR
agonists,
bisphosphonates,
hemodialysis)
prophylaxis : there is no evidence that calcium and vitamin D supplements
reduce the risk of fractures in older women living in the community. The
researchers identified 3,314 women aged 70 and over and at high risk of
hip fracture from primary care clinics. The women were randomly split into
two groups. Patients in the treatment group received advice from a practice
nurse on how to reduce the risk of fracture and were given calcium and
vitamin D tablets to take daily. The control group received only a leaflet
on diet and prevention of falls. All women were monitored for an average
of two years. Over the 25-year monitoring period, the fracture rate was
lower than expected but did not significantly differ between the groups
(4.0% in the intervention group and 3.7% in the control group; P =.97).
The adjusted odds ratio was 1.1. Time to fracture did not differ between
the groups. And the researchers found no evidence that supplements reduced
the risk of fractures or falling, or improved quality of life (0.98, 0.79
to 1.20). They also found no evidence that women who adhered to treatment
might have had a reduced fracture rate (1.03, 0.68 to 1.56). Putting this
study in the context of other trials suggests that calcium and vitamin
D supplementation may not be an effective intervention for reducing fractures
in primary care. Among healthy postmenopausal women, calcium with vitamin
D supplementation resulted in a small but significant improvement in hip
bone density, did not significantly reduce hip
fracture,
and increased the risk of kidney
stonesref
prophylaxis to prevent barbiturates
and phenytoin-
cranberry juice can prevent urinary
tract infections.
It turns out, this may hold up under scientific scrutiny. Cranberries produce
an unusual version of proanthocyanidin, a condensed tannin. Other
plant proanthocyanidins have a single interflavanoid bond that links the
compounds together. Cranberry proanthocyanidins have stronger double bonds
that may resist degradation when eaten and enable them to dock onto uropathogenic
Escherichia
coli (UPEC),
preventing the bacteria from attaching to the urinary tract lining. Bacteria,
when added to urine from women who had consumed cranberries, could not
adhere to cultured bladder cellsref
-
Alzheimer's disease
(AD)-model
mice that were fed blueberry anthocyanins have increased activity of MAP
kinases such as PKC and CREB, which are associated with learning and short-term
memory. Moreover, the AD mice perform cognitively on par with non-AD mice.
The equivalent of a cup of berries a day provided a beneficial dose. In
humans, blueberry anthocyanins may resensitize the age-dulled receptors
for neurotransmitter signals and revive the brain's flagging neuronal communication
system
-
individuals eating 3 or more servings of fruit daily had a 36% reduced
incidence of age-related
macular degeneration (ARMD),
compared to those eating less than 1.5 daily servingsref
)-
antioxidants : in assessing whether or
not a compound or food acts as an antioxidant in vivo, a conventional
approach is to monitor biological markers of oxidative damage in response
to the intervention. Another is to measure the change in total plasma antioxidant
capacity— however, it should not be assumed that the effect is necessarily
beneficial. The intake of 400-600 g/d of fruits and vegetables is associated
with reduced incidence of many common forms of cancer, and diets rich in
plant foods are also associated with a reduced risk of heart disease and
many chronic diseases of agingref.
- nutrients
-
calcium
: people at high risk of colon cancer appear to reduce the risk of developing
polyps while taking calcium supplements and continue to benefit for as
long as 5 years after they stop taking them. Participants who were randomized
to take 1200 mg of elemental calcium daily for 4 years had a "statistically
significant 19% reduction in polyp formation. The cohort of 822 patients
was followed another 5 years after the end of the study, and the patients
randomized to calcium achieved a 36% reduction in new adenoma polyp formation
: however this added benefit did not persist beyond 5 years. Calcium supplementation
did not appear to be of much help for patients with advanced adenoma formation.
Calcium supplementation reduces the risk of cancer, especially colon cancer,
but you would have to take it for a very long time to reduce colon cancer
-- perhaps 20 years or more. Some data suggest that calcium supplementation
may increase the risk of prostate cancer, so it should not be recommended
for men
- fiber
-
folate
-
vitamin B6
-
vitamin B12
-
Se
: after a 10-month intervention, neither selenomethionine nor celecoxib
inhibited esophageal
squamous carcinogenesis
for all high-risk subjects. However, among subjects with mild esophageal
squamous dysplasia at baseline, selenomethionine did have a protective
effectref.
-
vitamin A
-
vitamin C
-
vitamin D
: higher intake of calcium
and vitamin D has been associated with a reduced risk of colorectal cancer
in epidemiologic studies and polyp recurrence in polyp-prevention trials.
However, randomized-trial evidence that calcium with vitamin D supplementation
is beneficial in the primary prevention of colorectal cancer is lacking.
Daily supplementation of calcium with vitamin D for seven years had no
effect on the incidence of colorectal cancer among postmenopausal women.
The long latency associated with the development of colorectal cancer,
along with the 7-year duration of the trial, may have contributed to this
null finding. Ongoing follow-up will assess the longer-term effect of this
interventionref
-
vitamin E
: dietary administration of the pro-apoptotic vitamin E analog a-tocopheryloxyacetic
acid inhibits metastatic murine breast cancer (Akporiaye et al. Cancer
Research, 2006)
- nonclassical antioxidant agents
- phytochemicals
- carotenoids
- corcumin
- diallyl sulfides
- genistein
- indole-3-carbinol
- isoflavones
- L-perillyl alcohol
- saponins
- terpines
- ellagic acid
- green-tea and grape-derived polyphenols
-
epigallocatechin-3-gallate
(EGCG)
binds to 67-kDa laminin receptor (67LR). 67LR confers sensitivity to physiological
concentrations of EGCG (0.1 and 1.0 mM) - the levels of the compounds that
were effective in slowing cell proliferation are about the same concentration
found in plasma after a person drinks 2 or 3 cups of tea. Otther components
of green tea, such as caffeine and other tea polyphenols, are not found
to affect the growth of LR-expressing cells. 67LR has been shown to be
involved in retinal angiogenesis, and gene expression profiling studies
have shown that it is upregulated in malignant mesotheliomaref
- lycopene in tomato, Guava, apricots, watermelon, papaya and pink grapefruit (most lycopene in processed tomato products including paste, sauces and juice) reduces cell growth of prostate cancer within 6 weeks. Consumption of tomato powder, but not lycopene alone, inhibits prostate carcinogenesis in rats, indicating that other phytochemicals in tomatoes are required to prevent tumour preventionref.
- acylic retinoids
- inducers of carcinogen-detoxification pathways have a long pharmacodynamic half-life (upregulation of expression lasts for up to 1 week after treatment, thereby simplifying compliance and reducing costs)
- oltipraz / (5-[2-pyrazinyl]-4-methyl-1,2-3-thione)
- isothiocyanates exist in plants belonging to the family Cruciferae and to the genus Brassica (for example, 3-day-old broccoli sprouts, cauliflower and Brussel sprouts) as relatively stable b-thioglucoside N-hydroxysulphate precursor conjugates (known as glucosinolates). The enzyme myrosinase promotes the hydrolysis of glucosinolates to isothiocyanates. Myrosinase is normally physically segregated from its glucosinolate substrates, but it is released when plant cells are injured (for example, by chewing, food preparation, or insect predation). This reaction is responsible for the bitter taste of horseradish, mustard and wasabi. Side effects : primary hypothyroidism
-
resveratrol : the same mechanism that makes it an anti-inflammatory
agent also helps it fight cancer, reports Marty Mayo at the University
of Virginia Health System in Charlottesville. Resveratrol inhibits the
transcription factor NFkB
that stimulates genes responsible for cell survival, inflammation, and
the proliferation that runs rampant in cancer. When applied to cancer cells,
resveratrol sensitizes them to tumor necrosis factor-a, which initiates
apoptosis. As a future drug treatment, resveratrol could both enhance the
effectiveness of chemotherapy and relieve arthritis and atherosclerosis.
- N-acetylcysteine (NAC)
- linoleic acid : men who consume the highest amounts are 45% less likely to develop prostate cancer than their peers who consume the lowest amounts
-
quercetin : fresh apples have some of the highest levels when compared
to other fruits and vegetables and may be among the best food choices for
fighting Alzheimer's disease (AD).
Even though quercetin is relatively stable during cooking, fresh apples
are better sources of quercetin than cooked or processed apple products
because the compound is mainly concentrated in the skin of apples rather
than the flesh. Products such as apple juice and apple sauce do not contain
significant amounts of skin. In general, red apples tend to have more of
the antioxidant than green or yellow ones, although any apple variety is
a good source of quercetin. Other foods containing high levels of quercetin
include onions, which have some of the highest levels of quercetin among
vegetables, as well as berries, particularly blueberries and cranberries.
Like other antioxidants, quercetin has been associated with an increasing
number of potential health benefits, including protection against cancer.
-
people who like bananas, carrots and beets may have a lower risk of developing
adulthood
renal cancer.
Besides bananas and root vegetables, white cabbage (widely consumed in
Sweden) and salad vegetables including lettuce and cucumber, were linked
to a lower cancer risk. The study found that a high overall intake of fruits
and vegetables was related to a lower risk of kidney cancer. Women who
ate bananas 4-6 times a week, for example, had about half the risk of kidney
cancer as those who did not eat the fruit. Regular consumption of root
vegetables, including carrots and beets, was linked to a 50-65% decrease
in risk. Bananas contain an especially high amount of antioxidant compounds
called phenolics. For its part, white cabbage contains isothiocyanates
-
eflornithine
- pharmaceuticals
-
antiangiogenic
drugs
- chromatin modifiers
- nuclear receptor ligands
-
RAR agonists
: they are used in patients with head
and neck tumors.
9-cis-retinoic acid (RA) can restore expression of RARb,
whose loss is thought to be a biomarker of premalignancy, in the bronchi
of ex-smokers
-
ER
antagonists
: breast cancers
- letrozole
- tamoxifen reduces risk of contralateral tumor by 50% in affected females and by 40-50% in unaffected but genetically predisposed females
- raloxifene appears to substantially lower the risk of breast cancer in older women at relatively low risk of the disease. New, long-term follow-up data showed a 66% reduction after 8 years of use for osteoporosis. The Evista study also showed the drug doubled the risk of potentially hazardous blood clots.
-
COX-2
inhibitors
sensitize cancer cells to apoptosis
and prevent tumour
angioneogenesis,
lowering the risk of colorectal
cancer.
Some animal studies and human data have indicated that aspirin might also
inhibit pancreatic carcinogenesis, but analysis of cancer incidence as
part of a large prospective study into the risk factors for chronic disease
in women shows that aspiring users actually have a 1.20 RR of developing
pancreatic
cancer
compared with non-users. Increasing the duration of aspirin use is also
associated with a significantly increased risk: women who have taken aspirin
regularly for 20 years or more have a RR of 1.58. Women who have taken
> 14 aspirin tablets per week for > 4 years have a RR of 1.86. Other risk
factors include smoking and obesity, but taking these factors into account
does not alter the association of pancreatic cancer risk with aspirin use.
There is some evidence that regular aspirin use might cause pancreatitis
- inflammation of the pancreas that has been linked to an increased risk
of developing pancreatic cancer - so this connection is worth investigating
further. NSAIDs reduce half the risk oral cancer in active and moderate
cigarette smokers, but this reduction apparently did not translate into
increased overall survival. Results from the Women’s Health Study, a randomized
2 × 2 factorial trial evaluating the benefits and risks of taking
aspirin every other day (100 mg) and natural-source vitamin E (600 IU)
vs placebo in the primary prevention of cardiovascular disease (CVD) and
cancer, that compared with placebo, neither aspirin nor vitamin E was associated
with reductions in overall or site-specific cancer incidence, cancer mortality,
major cardiovascular events, or cardiovascular and total mortalityref1,
ref2.
-
NO-1886 and its derivatives suppress of serum
lipid levels by increasing LPL activity, contributing to a reduction of
intestinal polyp formation with Apc-deficiency, reducing the risk of colorectal
cancerref
-
5-fluorouracil
: topical applications to prevent sunlight-induced skin
cancer
-
HMG-CoA reductase inhibitors
: people who took them at least 5 years appeared to cut their risk of colon
cancer
by 50% : those who took other cholesterol drugs had no cancer protection.
Earlier work has shown reductions in risk of breast
cancer
and prostate
cancer
as well. One concern of suggesting statins to prevent cancer without definitive
proof of their worth is the risk of exposing people to possible side effects
(muscle and liver problems)
-
type
II 5a-reductase inhibitors
: for androgen-dependent prostate
cancers
: men who took finasteride daily for 7 years had 25% fewer prostate cancers
than men given dummy pills. But about 6.4% of finasteride patients were
diagnosed with high-grade tumors, compared with 5.1% of men given dummy
pills.
in the cytoplasm by binding to its amino-terminal regulatory domain. Once
in the nucleus, NRF2 forms heterodimers with small MAF-family proteins
to activate the expression of antioxidant response element (ARE)-containing
genes, including UDP-glucuronosyltransferases and glutathione-S-transferases
(GST).
.
chemoprevention-
pyridostigmine bromide (PB)
(sources : Roche and Solvay Duphar BV) :
- muscarinic effects (counteracted with i.v. atropine sulphate 1-2 mg) may include
-
abdominal cramps, increased peristalsis, diarrhoea,
nausea
and vomiting
-
sialorrhea,
hyperhidrosis
-
miosis
- increased bronchial secretions.
- nicotinic effects may include
Formulation : p.o. round, biconvex, white to off-white 30 mg tablets. Excipients : pregelatinized starch, marze starch, lactose, colloidal silicon dioxide, talc, magnesium stearate. Shelf-life : 48 months. They are presented in a blister pack containing 21 tablets (7 days supply, 1 every 8 hours; good protector is achieved within 2½ hours of the first dose).
Mechanism of action : nerve agent pre-treatment set (NAPS) greatly enhances the efficacy of nerve agents poisoning treatment with oximes
.
NAPS at the recommended dosage produces 20-40% carbamoxylation of RBC acetylcholinesterase
/ Yt blood group, protecting this proportion of the enzyme from attack
by nerve agents. Pyridostigmine does not cross the BBB and offers lithe
protection against the CNS effects. It is relatively ineffective against
tabun, sarin, and Vx, but highly effective against soman.
Contraindications : mechanical GI or urinary obstruction, hypersensitivity to bromides, bronchial asthma
Side effects : GI (50% : status, loose stools, nausea, abdominal cramps, salivation), urinary (5-30% : pollakiuria), headache, rhinorrhoea and paraesthesiae (< 5%). Overdosing causes 'cholinergic crisis' :
-
pentamidine
for Tripanosoma spp.
-
spiramycin for Toxoplasma
gondii
in newborns
-
malaria chemoprophylaxis
for Plasmodium spp.
in travelersref1,
ref2
- chemoprophylaxis schedule
- agents are started 1-2 weeks before travel
- agents are continued for 4-6 weeks after travel
- chemoprophylaxis: first line
- indications (areas of no chloroquine resistance)
- Mexico
- Caribbean
- Central America
- Argentina
- some areas in Middle East
- some areas of China
-
chloroquine
- adult: 500 mg (300 mg base) PO weekly
- child: 8.3 mg/kg (5 mg/kg of base) PO weekly
- chemoprophylaxis: 2nd line (if no mefloquine resistance)
- indications
- chloroquine resistance
- safe in pregnancy
- contraindications (relative)
- seizure disorder
- cardiac conduction abnormality
- psychosis
-
mefloquine
- adult: 250 mg (228 mg base) PO weekly
- child: see mefloquine for pediatric dosing
- chemoprophylaxis: third line
- indications
- short term travel to chloroquine resistance areas
- mefloquine resistance areas
- Thailand - Cambodia border
- Thailand - Myanmar (Burma) border
- contraindications
- lactating women
- children under age 8 years
-
doxycycline
- adult dosing: 100 mg PO qd
- pediatric dosing (may use if older than age 8)
- dose: 2 mg/kg/day up to 100 mg qd
- chemoprophylaxis: terminal prophylaxis
- indications (on leaving endemic area)
- prolonged exposure to P. vivax or P. ovale
- taken for 14 days on leaving endemic area
- contraindications
- pregnancy
- G6PD deficiency
- adult dose
-
primaquine
26.3 mg PO qd for 14 days
- chemoprophylaxis: Other agents (adult dosing)
-
atovaquone/proguanil
250/100 mg PO qd
-
azithromycin
250 mg PO qd
-
tafenoquine
250 mg PO weekly
-
pyrimethamine with sulfadoxine
- post-exposure prophylaxis (PEP) for infectious diseases :
- for bacteria :
-
anti-Neisseria
meningitidis
PEP : health care workers (HCWs) as an overall group are not at high
risk for secondary transmission of meningococcus, and chemoprophylaxis
with an antimicrobial agent such as ciprofloxacin
or rifampin
is not routinely recommended for the usual contact that a HCW, even an
emergency service person, has with an infected patient. The kinds of contact
that elicit the recommendation of chemoprophylaxis are those related to
direct exposure with the patient's oral secretions including mouth-to-mouth
resuscitation, endotracheal intubation, endotracheal tube management, or
other direct exposures (e.g. surgery)ref.
A risk assessment of HCWs from the UK found that the absolute risk in HCWs
was 0.8 per 100 000, about 25 times higher than the risk in the population
at largeref.
The risk among HCWs was 500 times lower than among household contacts (210
per 100 000) in endemic disease. The meningococcus is spread from person
to person through nasopharyngeal secretions or large-particle respiratory
droplets that are unlikely to remain in the air for distances beyond 3
feetref.
Chemoprophylaxis for household contacts can reduce their risk of infection
by 89% : compared with placebo, ciprofloxacin
(RR = 0.04), rifampin
(RR = 0.17), minocycline
(RR = 0.30), and penicillin
(RR = 0.47), proved effective at eradicating Neisseria meningitidis
1 week after treatment. After 1-2 weeks, only ciprofloxacin (RR = 0.03)
and rifampin (RR = 0.20) still proved significantly effective when compared
with placebo. No trials evaluated ceftriaxone against placebo. Ceftriaxone
was more effective than rifampin, after one to two weeks of follow up (RR
5.93; 95% CI 1.22 to 28.68). Rifampin continued to be effective (RR = 0.24)
compared with placebo until up to 4 weeks post treatment but resistant
isolates were seen following prophylactic treatment. Rifampin was the only
drug to which resistance developed. Given that the use of rifampin in an
outbreak setting might lead to the circulation of isolates resistant to
rifampin, the use of ciprofloxacin and ceftriaxone should be consideredref1,
ref2
-
anti-Mycobacterium
tuberculosis
PEP : for 9 months in children with TB infection but not disease
(latent tuberculosis). Early trials of tuberculosis chemoprevention were
carried out using isoniazid
daily for 9 months between 1955 and 1964. The studies were performed in
the USA as well as Denmark, Tunisia, Kenya, Japan, the Netherlands, and
the Philippines. An extensive monograph by Ferebee published in 1970ref
reviewed the data, which showed by treatment with isoniazid greatly reduced
-- but not completely prevented -- the incidence of clinically apparent
TB as compared with placebo. Its use is based on this reduction balanced
against the risk of hepatotoxicity, which can be severe enough to result
in the need for liver transplantationref.
Given the observations that the amount of use of this therapy in health
care workers is not substantial and the treatment is not completely preventative,
it is vitally important for the health care worker individually to seek
medical care and diagnosis for any respiratory illness lasting > 1-2 weeks
or so. Because of the risk of risk of TB and a variety of other respiratory
diseases, this should be the case whether the individual is known to be
tuberculin-reactive or not. In this case, the index case was symptomatic
for 8 weeks and even when seen with a history of a known reactive tuberculin
test, the diagnosis was not suspected. Even when a CT scan showed
upper lobe volume loss in a patient with a known reactive tuberculin test,
the diagnosis was not suspected. It is fortunate that the infants found
did not have progressive infection, although it is certainly possible that
morbidity and mortality occurred among the large number of infants and
mothers lost to follow-up. Because bronchoscopy is a cough-inducing procedure
that can result in increased transmission of M. tuberculosis, diagnosis
of TB disease and microscopic examination of sputum for AFB should be considered
before bronchoscopy. CDC recommends avoiding bronchoscopy if possible for
patients with suspected or confirmed TB disease or postponing the procedure
until the patient is determined to be noninfectious by confirmation of
3 negative AFB sputum smear results. If the patient cannot produce sputum,
CDC recommends considering sputum induction before bronchoscopy. HIV infection
is the greatest risk factor for progression from LTBI to TB diseaseref.
In 2002, the incidence of TB disease among foreign-born HCWs in the state
of New York was 17.5 per 100 000, compared with 2.0 among USA-born HCWsref.
During 1998-2002, among 297 HCWs (employed in hospitals, home health care,
nursing homes, and ambulatory care facilities) who were reported to have
TB disease, 221 (74%) had had LTBI diagnosed previously. Of these, 111
(50%) had met criteria for treatment for LTBI, but only 26 (23%) of these
received treatmentref.
Those data and the circumstances described in this report support the need
for effective LTBI testing and treatment programs among HCWs, particularly
those born outside the USA. Studies have demonstrated poor adherence to
LTBI treatment among HCWsref.
HCWs might attribute a positive TST result to BCG vaccinationref.
Compared with USA-born physicians, foreign-born physicians in one USA medical
residency program were less likely to recommend LTBI treatment for themselves,
their family members, or recent immigrants if they had received BCG vaccination
(Tsiouris S, Muttana H, Salazar-Schicchi J, et al:. Attitudes about BCG
vaccination and treatment for latent tuberculosis infection among international
and U.S. medical graduates. In: Proceedings of the 100th International
Conference of the American Thoracic Society, Orlando, FL; 21-26 May 2003).
However, in the absence of M. tuberculosis infection, tuberculin
reactivity caused by BCG vaccination wanes over time and is unlikely to
persist > 10 years after vaccinationref.
Current guidelines recommend considering treatment for HCWs who have a
TST result > 10 mm, especially if they emigrated from a country with high
TB prevalence during the preceding 5 years. A history of vaccination with
BCG should not influence the decision to treat LTBI. The proportion of
HCWs in the USA who were born outside the country is growing. Approximately
25% of all USA practicing physicians graduated from medical schools outside
of the country (American Medical Association. Physician characteristics.
In: Pasko T, Smart DR, eds. Physician characteristics and distribution
in the U.S. 25th ed. Chicago, IL: American Medical Association; 2005:1-44).
Moreover, the shortage of registered nurses in the USA is anticipated to
increase from 6% in 2000 to 29% by 2020, and foreign-born nurses likely
will increasingly be sought to fill this gapref.
All HCWs in the USA, particularly those foreign-born or foreign-trained,
should be encouraged to follow USA guidelines for LTBI treatment. Guidelines
for preventing transmission of M. tuberculosis in health care settings,
including baseline and periodic TB screening and effective LTBI treatment
programs for HCWs in high-risk settings, should be followed. In addition,
infection-control programs in health care settings should implement interventions
to increase adherence to treatment for infected HCWs working in high-risk
settings. On-site, directly observed preventive therapy is one such option.
A New York City maternity ward nurse who had infectious tuberculosis exposed
as many as 1500 patients to the disease over 2 months in 2003, and most
likely infected at least 4 infantsref
- for viruses :
-
anti-HAV
PEP : in post-exposure prophylaxis for hepatitis A virus, although
there have been no studies comparing the effectiveness of vaccination with
that of immunoglobin injections, it is at present proposed to provide only
vaccination. The target groups eligible for post-exposure prophylaxis are
evokedref.
-
anti-HBV
PEP : in the case of acute hepatitis B, antiviral treatment should
not be started, in view of the high percentage of spontaneous recoveries
and the potentially negative effect of treatment on the chances of spontaneous
recovery. Post-exposure prophylaxis by anti-HBV
immunoglobin
injections and/or vaccination should be considered after evaluation of
the hepatitis B surface antigen status of the source and of the vaccination
and vaccine-response status of the exposed person. The classic scheme for
selecting the most appropriate postexposure prophylaxis is remindedref
-
anti-HCV
PEP : screening for the HCC virus as early as the fifteenth day after
the potentially contaminating act and, in the case of virus transmission,
starting interferon treatment as soon as elevation of the transaminases
appears. No special precautions are to be taken by the person potentially
contaminated for avoiding possible secondary HCV transmission during the
follow-up periodref.
-
antiretroviral
PEP : antiretroviral drugs to be given to people who may have been
exposed to HIV through sexual intercourse, injection of drugs, or injury.
CDC gudelines recommend treatment with highly active antiretrovirals beginning
within 72 hours of exposure and continuing for 28 daysref.
Antiretroviral drugs reduced the rate of transmission of HIV after exposure
to the virus in animal studies, in trials looking at prevention of perinatal
transmission, in studies of health workers who received prophylactic treatment
after exposure at work, and in observational studies. There is an early
window of opportunity to interrupt or prevent transmission. Animal studies
of SIV showed that the virus first infects cells in the vaginal subepithelium,
is found in draining lymph nodes within 2 days, and spreads to the bloodstream
within 5 days. Early treatment with zidovudine
led to an 81% reduction in risk of acquiring HIV in healthcare workers
who had needlestick injuries, a case-control study showed. Several studies
cited in the guidelines show that early treatment with antiretrovirals
greatly reduced transmission of the virus in high-risk homosexual and bisexual
men, women who had been raped, and people who had been exposed to HIV through
sex or injection use. The study also noted 2 cases of high risk exposure
(transfusion of HIV contaminated blood and insemination from an HIV positive
man) followed by antiretroviral treatment; in neither case did the patient
become infected. Patients’ compliance was important for successful treatment
and to avoid development of resistant strains, so patients must be well
counselled. The preferred treatments are either a non-nucleoside reverse
transcriptase inhibitor regimen of efavirenz
with lamivudine
or emtricitabine
and zidovudine
or tenofovir
disoproxil,
or a protease inhibitor regimen of lopinavir
and ritonavir
(co-formulated as Kaletra) with lamivudine
or emtricitabine
and zidovudine.
Efavirenz should not be used in pregnant women or women of child bearing
potential. The guidelines also say that women who have been raped should
be told about emergency contraception—in contrast to recent US Department
of Justice guidelines, which did not mention itref.
When the HIV status of the source is unknown, and treatment is sought within
72 hours, exposed people and their doctors should evaluate the risks and
benefits of antiretroviral treatment. They should consider the risk that
the source is HIV positive and the risk of transmission if the source is
HIV positive. Treatment is not recommended for people whose exposure doesn’t
present a substantial risk or who do not seek treatment within 72 hours—but
the guidelines say it is unknown whether later treatment will be ineffective.
The guidelines suggest giving patients, who may be under emotional stress,
starter packs containing drugs for 3-5 days of treatment and scheduling
a follow up visit to review baseline HIV testing, offering counselling
and support and adjusting the treatment if necessary. Adherence to the
28 day regimen can be "challenging" and has been shown to be especially
poor among people who have been sexually assaulted, so simplifying the
regimen, treating side effects, and providing education and support will
increase the chances that the patient will complete treatment. However,
the drug combination would likely cost more than double the usual US$8
for a single dose of nevirapine
for mother and newborn. In the US, the complete 3-drug HIV cocktail has
cut mother-to-baby transmission rates to around 2%. But patients in the
US are given longer treatments, and drugs that are far more effective and
expensive than those tested in Africa. The African studies -- one in the
Ivory Coast, one in Botswana -- reduced rates at 4-6 weeks after birth
to about 5%, the lowest ever recorded in Africa. Nevirapine in single doses
typically reduces that rate from around 35% to 12%.
