In addition, the antibody responses against the surface antigen protein elicited by the recombinant yeast-derived vaccine now in use are weaker and more specific than those achieved with the previous plasma-derived surface antigen vaccine. Each of these nucleoside analogue drugs has an excellent safety and efficacy profile.
Effective long-term suppression of HBV replication by these agents is associated with histological and clinical improvement.
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However, compared with lamivudine monotherapy, this combination was more effective in preventing the emergence of lamivudine-resistant HBV. The HBV genome is circular and organized into four open reading frames that overlap with each other. Although drug-driven changes in the S protein have been well described, the effect of these changes on the antigenicity of the surface antigen has been little studied. For instance, some ADAP-VEMs selected by lamivudine have been shown to be less fit virologically; that is, they are rapidly replaced when the drug is removed and are unlikely to be a dominant or co-dominant viral population in terms of virus transmission.
Of these four characteristics, to date we have evidence that three have been fulfilled, although we do not know if ADAP-VEMs have the same propensity to cause disease as do strains of HBV that are already circulating. The first feature of such programmes that can increase the risk is the type of antiviral agent. Lamivudine, although it is relatively inexpensive, has been shown to rapidly result in the selection of primary antiviral drug-resistant polymerase variants. These variants in turn also select for compensatory mutations, some of which may have altered surface antigens.
The second potentially problematic feature of current treatment programmes is the way patients are selected. Because of the strong correlation between HBV viral load and the likelihood of developing cirrhosis and hepatocellular carcinoma, reducing viral replication as early as possible after infection is likely to be beneficial. In addition to being costly, this approach may generate antiviral drug resistance since current agents never lead to eradication of the virus, but only to control of replication. Treatment in industrialized countries is therefore usually reserved for patients likely to respond to therapy and those who have advanced disease.
Inappropriate inclusion criteria, improper application of these criteria or lack of compliance with treatment could greatly influence the emergence of both drug resistance and ADAP-VEMs. The public health risk of treatment programmes in different populations may also depend upon features of the circulating viral genotype. There is evidence that the genotype of the virus influences the speed and frequency of development of resistance to treatment, which may in turn influence the likelihood that ADAP-VEMs will emerge.
For example, genotype A-1 common in north-western Europe and North America more frequently develops surface protein changes with lamivudine therapy than genotype D-1 concentrated in Mediterranean countries but distributed globally. The disease process can also be more active and more rapidly progressive in HBeAg-positive individuals, 43 although disease progression may also be influenced more by the underlying HBV genotype than by HBeAg status alone.
Given these features, the likelihood that escape mutants will emerge as a result of HBV treatment programmes is probably greatest in settings of high HBV prevalence, where treatment is widely available and where regimens are inappropriate or adherence is uneven.
Within these settings there may be subgroups of particular interest. To this end, official and unofficial treatment programmes that already record the type of antiviral treatment, treatment criteria and the extent of substandard medications could be combined with descriptive epidemiology e. Although the threat is theoretical, there is already evidence that current treatment regimens have resulted in the selection of stable ADAP-VEMs.
Knowing this, what should our response be now? At the very least, we must learn more about ADAP-VEMs, their transmissibility and their potential to cause infection and disease in immunized individuals. This will require virological surveillance and clinical follow-up of infected individuals and those undergoing treatment, and also, possibly, surveillance of their close contacts. The initial focus of these activities should be high-risk settings until the level of risk is defined and understood better.
Follow-up of such cases of HBV, however, would depend on the availability of testing, and currently no suitable commercial tests are available. At present, treatment aims to prevent the long-term complications of HBV infection, with little consideration given to potential adverse public health impacts.
The number of potent antiviral agents is limited, their development by manufacturers is episodic and trials that have evaluated combination therapies are lacking. Because of these factors, monotherapy remains the usual practice in most settings. Those who are seronegative for CMV should be counselled regarding the small risk of primary maternal CMV infection that can cause damage to the fetus.
Increased risk of infections
They should be advised that attention to hand washing, and not caring for children under three years of age can reduce the risk of CMV acquisition. Human enteric bacteria 25 and viruses 26 can be easily isolated from the hands of children and staff, and from surfaces and toys in child care centres during gastroenteritis outbreaks. Pathogenic viruses including hepatitis A virus, 27 rotavirus, 28 rhinovirus 29 and respiratory syncytial virus RSV 30 can survive on the hands for many hours.
Hand contact is important in the transmission of viral respiratory infections caused by rhinovirus 31 and RSV 30 as well as diarrhoeal infections. Hand washing, using soap and warm running water, is the principal means of reducing transmission. The effectiveness of hand washing has been illustrated by a study 32 which showed that the incidence of diarrhoeal episodes among young children in child care centres was markedly reduced after the introduction of an intensive hand washing program for carers. Carers washed their hands after arrival at the centre, before handling food, and after using the toilet or changing children's nappies.
Carers should wash their hands on these occasions as well as after wiping their own or a child's nose, after cleaning up body fluids such as blood, faeces, vomit or urine and before going home. Nappy change areas must be located close to a hand basin. Where a hand basin is not available, alcohol-based hand rinses, shown to reduce the bacterial skin flora, 33 can be used. Staff may prefer to use disposable gloves when changing dirty nappies, but their use is optional and does not replace the need for hand washing. Disposable gloves should be worn when cleaning up spills of blood or body fluids, and when handling food.
Cuts and open lesions on carers' hands should be kept covered with water resistant occlusive dressings. Contaminated fomites, surfaces, toys and utensils in the child care environment may also be vehicles for the spread of infection. Influenza virus, 34 RSV, 30 rhinovirus, parainfluenza virus 29 and CMV 35 may survive on non-porous objects for many hours. Rotavirus, 28 hepatitis A virus 36 and parasites such as Cryptosporidium 37 may remain viable for days or weeks outside the body. All surfaces and articles should be chosen for their ease of cleaning. Daily vigorous physical cleaning of toys and surfaces using water and a neutral detergent is generally all that is required to remove pathogens from contaminated articles.
The use of disinfectants should be left to a supplementary role in the control of outbreaks of enteric infection; in such instances a disinfectant should be chosen to suit the pathogen. Specific advice should be sought from a hospital microbiologist or infection surveillance practitioner. Nappy change areas should use a non-absorbent change mat which is cleaned after each use.
Nappies and other items contaminated with body substances should be handled as little as possible. If they are to be laundered at the centre, they should be sluiced with care and machine washed in either hot or cold water using a recommended detergent. Ideally, they should be placed in bins for cleaning by a commercial laundry service.
Most child care related infections are more common in infants and toddlers than among older children. A study of bacterial contamination in centres found that the prevalence of faecal coliforms on hands, surfaces and in air samples was inversely related to the age of the children.
The likelihood of faecal contamination was greatest on the hands of infants and carers, and least on those of the older children. Two prospective studies of risk factors for diarrhoeal illness found that centres with non-toilet trained infants, and those in which food-handling staff also changed nappies, had higher diarrhoeal rates.
Prevention of the spread of enteric infections is best achieved by ensuring that wherever possible, carers have not been involved in nappy changing prior to handling food on the same shift, that minimal contact occurs between children in nappies and older children, and that the same members of staff do not look after both age groups at the same time. Antibiotics are generally prescribed when clinical indications are present. Their prescription is influenced by the wish for the child to return to care promptly, as is the case with bacterial conjunctivitis, streptococcal pharyngitis and impetigo.
In other infections, the use of antibiotics beyond the first few days of illness has no clear benefit for the patient, but may reduce the likelihood of transmission to contacts. Examples include gastroenteritis caused by Shigella 43 or Campylobacter. However, treatment of individual children found to be excreting Giardia cysts should remain a clinical decision.
In pertussis, a ten day course of erythromycin should be administered to the case if it is within three weeks of onset of the cough, to reduce the infectious period. Within child care centres, antibiotic prophylaxis should be limited to contacts under one year of age and children not up to date with pertussis vaccinations. If there is more than one case within a child care centre, prophylaxis should be extended to include all attendees and staff in contact with the case.
Roxithromycin may be a suitable alternative to erythromycin for the treatment of cases and contacts, however, it has not been approved for that purpose. When a case of meningococcal or Hib infection occurs in a centre, the public health authority should arrange for dispensing of prophylactic rifampicin to child care contacts, both children and staff, in accordance with current guidelines 49, Post-exposure prophylaxis with normal human immunoglobulin NHIG is indicated in a limited number of infections.
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If given within seven days of exposure in a dose of 0. Mass administration of immunoglobulin has been used successfully to terminate hepatitis A outbreaks in child care centres. During measles outbreaks, vaccination with MMR vaccine is recommended for all susceptible contacts from nine months of age unless there are medical contraindications or NHIG has been given. Infants who are vaccinated against measles prior to 12 months of age should be revaccinated in three months time or after the age of 12 months whichever is the later to avoid interference by maternal antibody. Recent guidelines suggest the consideration of vaccination when two or more cases of invasive meningococcal infection with the same serogroup occur in a child care centre within a three month period.
It could be speculated that there might also be a place for the use of hepatitis A vaccine a new formulation for year olds , or varicella and pertussis-only vaccines when they become available in the near future. Child care regulations in each State and Territory require exclusion of children and employees from the centre whilst infectious with a significant, acute illness.
Children with mild illnesses, for example the common cold, or with chronic infections such as HIV, hepatitis B or CMV infection are generally not excluded. Exclusion policies are time-honoured but have a number of drawbacks. Parents may have difficulty in finding alternative care for mildly unwell children.
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As a result, they may be tempted to place the children in other centres, thereby increasing the chance of the spread of infection into the wider community. The childhood exanthemata are most infectious during the prodrome, before the illness is recognised and the child excluded. Persons with erythema infectiosum fifth disease or slapped-cheek syndrome , caused by infection with parvovirus B19, are no longer infectious once the rash appears, so that exclusion is generally not warranted.
If appropriate staffing and space are available, cohorting of children during outbreaks may reduce the need for exclusion. Cohorting would involve separating affected and unaffected children, and also ensuring that staff who care for one of these groups do not care for the other group for the course of the outbreak. During shigellosis outbreaks in child care, asymptomatic carrier children were successfully cohorted after initiation of specific antibiotic therapy, until the organism was eradicated from the faeces.
Child care workers need to be supported with formal in-service training which covers modes of spread of infection, immunisation, hygiene in particular frequent hand washing , reporting requirements and the local public health infrastructure. Such personnel may encourage the development of practical case definitions, and use of appropriate confirmatory testing as a basis for formal or informal surveillance networks. Surveillance which actively involves child care staff is likely to promote the early seeking of expert advice and recognition of outbreaks, and would serve to enhance preventative approaches to communicable disease in the child care setting.
Australian Bureau of Statistics. Child care, Australia, March Canberra: ABS, Catalogue no. Frequency and severity of infections in day care.
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J Pediatr ; Rasmussen F, Sundelin C. Use of medical care and antibiotics among preschool children in different day care settings. Acta Paediatr Scand ; Form of day care and respiratory infections among Finnish children. Am J Public Health ; Child care arrangements and repeated ear infections in young children.
Department of Health | Infection control in child care settings
Acute respiratory illness in Adelaide children - the influence of child care. Med J Aust ; Longitudinal study of occurrence of diarrheal disease in day care centers. A longitudinal study of rotavirus infection in childcare centres. J Paediatr Child Health ; Cryptosporidium and coxsackievirus B5 causing epidemic diarrhoea in a child-care centre. Giardia carriage in Aboriginal and non-Aboriginal children attending urban day-care centres in South Australia. Aust Paediatr J ; Hepatitis A outbreak in a preschool in Eastern Sydney. Commun Dis Intell ; Hepatitis A in day-care centers.
NEJM ; Haemophilus influenzae type b infections in Victoria, Australia, J Infect Dis ; suppl 1 :S Meningococcal disease in Belgium. Secondary attack rate among household, day-care nursery and pre-elementary school contacts. J Infect ; suppl 1 Impact of child day care on infectious diseases in adults. Infect Dis Clin N Amer ; The occupational risk of cytomegalovirus infection among day-care providers.
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JAMA ; Occupational risk of human parvovirus B19 infection for school and day-care personnel during an outbreak of erythema infectiosum. JAMA ; Staying healthy in child care. Canberra: Australian Government Publishing Service, National Health and Medical Research Council.