Infectious Disease Control in Different Scenarios

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Introduction

With the ever-growing incidence of Healthcare-associated Infections (HAI), re-emergence of several previously eradicated organisms and the emergence of multi-drug resistant organisms, vigilant monitoring of any possible outbreaks and adequate and timely implementation of stringent infection control practices is imperative. While implementing such measures, a variety of factors need to be kept in mind. These include host factors, characteristics of the pathogenic organism implicated, type of exposure and also environmental factors, amongst others, as these differ amongst different groups of populations such as in pediatric and adult populations (Wongsawat, 2008). The following paper discusses measures that need to be undertaken promptly in order to control the spread of infections in different health care settings.

The pertussis index case in the neonatal nursery

Pertussis is a disease involving the respiratory tract which is highly contagious and is known to be caused by the organism Bordetella pertussis (Crameri & Heininger, 2008), which is an aerobic, gram-negative coccobacillus (Crowcroft & Pebody, 2006). The spread of this organism is via droplets secreted from infected persons. The incidence of this disease was high prior to the introduction and use of vaccinations but decreased considerably in the post-immunization era. For example, in the UK the annual incidence was greater than 100,000 cases prior to the vaccination era but decreased to less than 100 per year as a result of >90% immunization coverage (Alexander, et al., 2008). However, more recently, a rising trend is again being observed in the number of pertussis cases. Moreover, although pertussis is a disease that primarily affects infants and children, recently, an increasing number of cases of this disease are being observed in adolescents and adults, since the efficacy of the vaccine in providing immunity against the organism has been found to wane after a period of several years (Alexander, et al., 2008). In the year 2005, more than 25,000 pertussis cases were reported to the Centers for Disease Control and Prevention (CDC) and amongst these, 34% were found to be affecting individuals in the 11-18 years age group while another 29% were found to be adults aged 19 years or more (Edwards & Talbot, 2006). The changing trends in the incidence of pertussis have important implications in the recognition and control of the spread of this disease. Firstly, adolescents and adults may present with atypical symptoms and thus, may remain undiagnosed (Alexander, et al., 2008). Secondly, these infected adults, in particular, the health care workers, are a potential source for the spread of infection to infants and children who are non-immunized, partially immunized and at times even those who have received full immunization against pertussis (Crameri & Heininger, 2008). Thirdly, the increased incidence amongst adults raises concerns regarding the duration of efficacy of the vaccine and has led to the contemplation of the administration of booster doses in adults.

The symptoms of pertussis include recurrent, paroxysmal bouts of cough ending with and an inspiratory “whoop”, often followed by post-tussive vomiting and is associated with respiratory distress. The onset of typical symptoms is usually preceded by a non-specific prodromal coryzal phase which might have symptoms identical to common upper respiratory infections such as runny nose and sneezing and may be variably accompanied by low-grade fever (Crowcroft & Pebody, 2006). The catarrhal phase is important because it is during this phase that the illness is unrecognized and thus inadvertent transmission of disease might occur. The infectious period of pertussis begins with the onset of the catarrhal phase and persists for at least three weeks after the onset of typical symptoms (Crowcroft & Pebody, 2006). Studies have shown that after the acquisition of the organism from an infected individual, the incubation period of pertussis varies between 5-21 days after which catarrhal phase symptoms of the disease begin to manifest (Crowcroft & Pebody, 2006).

In a neonatal nursery, there are three potential sources of pertussis infection that can trigger an outbreak, viz. pediatric patients, their attendants including parents or other visitors and the health care workers (HCW) involved in their care (Bryant, et al., 2006). Once an index case of pertussis is identified in a neonatal nursery, it is imperative to eradicate the pathogen as soon as possible and launch infection control measures to prevent the spread of disease in a highly prone population. It is also important to keep in mind that infection might already have spread beyond the index case to other people, including health care workers and other neonates. There are several different methods that have been developed for the diagnosis of pertussis in individuals suspected of being infected and these include bacterial culture, serology, or use of a molecular method such as PCR (Crowcroft & Pebody, 2006). Bacterial culture is considered to be the gold standard for the diagnosis of pertussis and although it has a high specificity, it has a low sensitivity and factors such as the use of specimens other than nasopharyngeal aspirate, delays in specimen transportation and prior antibiotic use have been shown to decrease the sensitivity further (Crowcroft & Pebody, 2006).On the other hand, PCR has been shown to have sensitivities ranging from 73% to 100% and a specificity approaching 100% and is thus preferred over culture. However, one limitation of the use of PCR is the occurrence of false-positive results (Crowcroft & Pebody, 2006). Despite this limitation, the timely use of PCR to diagnose index cases and individuals who are suspected of being infected is of extreme importance (Alexander, et al., 2008). Similarly, serology has been shown to be beneficial in diagnosing pertussis in later stages of the illness. Moreover, in the acute stage, studies have shown that a single high titer of anti-pertussis toxin IgG has a sensitivity of 76% and a specificity of 99% (Crowcroft & Pebody, 2006). A review of the literature concludes that PCR is the preferred diagnostic method for infants, who present in the acute stage of the illness and in the screening and diagnosis of close contacts of infected individuals, while serology is most useful in older children and adults who usually present after a prolonged period of illness and may have atypical symptoms (Crowcroft & Pebody, 2006).

Once diagnosed, the treatment of pertussis includes the early administration of antibiotics and the provision of supportive care. The antibiotics of choice include macrolides, amongst which erythromycin was the one that was being commonly used previously (Crowcroft & Pebody, 2006). The recommended dose of erythromycin for use against pertussis in children is 40 to 50 mg/kg per day and in adults 1 to 2 g/day orally in 4 divided doses for 14 days (maximum 2 g/day) (Centers for Disease Control, 1991). However, this drug has been shown to be associated with the development of idiopathic infantile hypertrophic pyloric stenosis in neonates (Bryant, et al., 2006) and thus, newer macrolides such as azithromycin and clarithromycin are now used (Crowcroft & Pebody, 2006). Antibiotic therapy should be initiated as early as possible since initiation of therapy after more than 1 week after onset of illness has been shown to have no effect on the course of illness (Crowcroft & Pebody, 2006). Duration of antibiotic treatment varies amongst different centers and continuation of therapy for 7 days has been shown to be equally effective as 14-day use of antibiotics (Crowcroft & Pebody, 2006).

In addition, identified cases need to be isolated and droplet precautions are taken. The recommended precautions include the use of droplet precautions for a minimal period of at least five days after antimicrobial therapy has been initiated. For individuals who have not received any form of antimicrobial therapy, droplet precautions need to be taken for a period of almost 3 weeks from the onset of symptoms (Floret, et al., 2005).

With regard to prophylaxis, early treatment of close contacts, which include HCW involved in patient management and patient’s family members, with macrolides has been proven to be effective in reducing the nasopharyngeal carriage of organisms and limiting the spread of the disease (Bryant, et al., 2006). Prophylactic therapy should be initiated within three weeks of the onset of the index case (Crowcroft & Pebody, 2006). During outbreaks, it is recommended to administer the TDaP vaccine in infants as young as those who are 6 weeks of age with the two subsequent primary doses given at four-weekly intervals (Bryant, et al., 2006). Moreover, as of 2005, the US Food and Drug Administration approved the use of tetanus and diphtheria toxoids and acellular pertussis vaccine (TDaP) in adolescents and adults. The administration of this vaccine in HCWs who have had direct contact with pertussis patients and for adults who are suspected of having close contact with infants less than one year of age is recommended (MMWR, 2008). Similar recommendations exist in the Global Pertussis Initiative (Alexander, et al., 2008). The effectiveness of selective immunization of high-risk groups such as parents of young infants and HCWs, which is termed as the ‘cocoon strategy’ has been proven to be effective by several studies (Crameri & Heininger, 2008).

Moreover, apart from prompt treatment of cases, ensuring isolation and droplet precautions and use of prophylactic antibiotics and immunization in close contacts, education regarding the importance of recognition of early symptoms of pertussis and prompt reporting of any suspected case to the appropriate health care authorities is imperative (Crameri & Heininger, 2008).

Two concurrent pseudomonas infections in the burn’s unit

One of the most important causes of morbidity and mortality in burns patients are infections since these individuals due to the loss of the protective function of the skin are highly susceptible to the entry of several pathogenic organisms into the body. Burns patients are particularly susceptible to developing Pseudomonas infections due to their immunodeficient state. The transmission of this infection can occur via various modes including direct contact, droplet and airborne infections. One of the most important routes of infection is direct or indirect contact which can occur through the hands of health care personnel or via contaminated equipment. There can be a multitude of sources of infection and the most frequent sources implicated are contaminated humidifiers and ventilator equipment but other fomites have also been found to be contaminated (Lari, Honar, & Alaghehbandan, 1998). Another important consideration in burns patients is the propensity of burns patients in the dispersal of pathogenic organisms into the surrounding and the volume of organisms shed is directly proportional to the area of the burnt surface (Weber & McManus, 2004).

Once a case of pseudomonas is identified in the burn’s unit, prompt infection controls measures should be undertaken. These include isolation of the patients and use of barrier techniques such as appropriate barrier garb including gloves and gown. Klein et al. in their study of patients in the pediatric ICU demonstrated the effectiveness of stringent infection control practices (Weber & McManus, 2004). Proper handwashing is also integral in limiting the spread of infection. In addition, contaminated equipment and surfaces should be decontaminated before concomitant use in other patients (Weber & McManus, 2004). Moreover, the emerging resistance to antibiotics amongst various pseudomonas species makes it imperative to isolate any individuals from each other so that the spread of resistant organisms is kept under check (Weber & McManus, 2004).

For the treatment of the identified cases, prompt diagnosis and identification of the infectious agent involved should be undertaken. Studies have found that species of pseudomonas acquired in the hospital are resistant to most of the commonly available antibiotics including gentamicin, ceftizoxime, carbenicillin, cephalothin and ceftazidime (Estahbanati, Kashani, & Ghanaatpisheh, 2002). Estahbanati et al. found that in the burns unit in Tehran the only antibiotics to which the pseudomonas species were sensitive were Amikacin and tetracycline (Estahbanati, Kashani, & Ghanaatpisheh, 2002). However, sensitivities vary from hospital to hospital and thus culture and sensitivity testing should be undertaken before prescribing antibiotics. Moreover, cautious use of antibiotics in the hospitals is necessary to prevent further development of resistance since the rate of development of resistance for pseudomonas species is very rapid (Estahbanati, Kashani, & Ghanaatpisheh, 2002). In order to prevent the emergence of resistant species, prophylactic use of antibiotics in close contact is not recommended (Estahbanati, Kashani, & Ghanaatpisheh, 2002).

An effective measure for the prevention of infections in susceptible individuals and in the control of infections is the use of antiserum vaccination (Estahbanati, Kashani, & Ghanaatpisheh, 2002). The use of this vaccine in burns patients has been shown to be efficacious in the reduction of mortality associated with pseudomonas (Alexander, Fisher, & MacMillan).

The varicella index case in the oncology ward

Varicella infections in childhood are fairly common and most follow a benign course. However, in immunocompromised patients, this disease can have severe manifestations and can cause significant morbidity and mortality. Morgan et al in their review of 600 children receiving immunosuppressive therapy discovered that almost 50% of the individuals developed life-threatening complications with visceral involvement (Chan, Ha, Peiris, Chiu, Lim, & Lau, 1994). In identified cases, early administration of acyclovir has been shown to help in the reduction of severity of symptoms (Chan, Ha, Peiris, Chiu, Lim, & Lau, 1994).

In order to limit the spread of infection, once a case of Varicella is identified, prompt discharge of that patient from the hospital should be undertaken (Hayden GF, 1979). Patients who cannot be discharged should be isolated. Isolation measures include placement of the patients in separate rooms, ensuring that there is no cross circulation of air, and the use of barrier methods such as gowns, gloves and masks by visitors. Susceptible patients who have been exposed should also be discharged if possible (Hayden GF, 1979). Patients in the oncology ward are immunocompromised and if exposed, should be given an exogenous antibody against the varicella-zoster virus as soon as possible after exposure, preferably within 72 hours (Hayden GF, 1979). The prophylactic agents which are preferred for use nowadays include zoster immune globulin and varicella-zoster immune globulin. Other alternative agents include zoster immune plasma and pooled, standard immunoglobulin (Hayden GF, 1979). More recently, the use of live attenuated varicella vaccination in immunocompromised patients, such as those undergoing chemotherapy, has been proposed (Chan, Ha, Peiris, Chiu, Lim, & Lau, 1994).

A concern with vaccine administration in immunocompromised patients especially those undergoing chemotherapy an interruption of the chemotherapy schedule during the active infection phase, which may make an individual susceptible to disease recurrence (Chan, Ha, Peiris, Chiu, Lim, & Lau, 1994). Studies conducted in leukemia patients have concluded that in order to mount an adequate response to the administered vaccine, cessation of chemotherapy for 1 week prior to and 1-week post-vaccination should be undertaken. Moreover, the patient’s lymphocyte count should be greater than 500/mm (Chan, Ha, Peiris, Chiu, Lim, & Lau, 1994). However, some studies have also produced contradicting results and propose the continuation of chemotherapy, except prednisolone, in the immediate pre and post-vaccine period in order to minimize discontinuation of treatment (Chan, Ha, Peiris, Chiu, Lim, & Lau, 1994).

Respiratory syncytial virus index case who is ventilated and in the neonatal nursery

One of the most common respiratory infections amongst children worldwide is Respiratory Syncytial Virus (RSV) which affects almost every child at least once in the initial years of life (Goldmann, 2001). RSV is the most common cause of bronchiolitis and almost 1% of the children who are infected need hospitalization for the provision of supportive care (Langley, et al., 1997). The most common route of spread of RSV is via the infected respiratory secretions which may be transferred via droplets suspended in the air or may be carried on the hands or fomites (Langley, et al., 1997). It has been found that infected infants secrete greater than 10⁷/mL of nasal discharge (Goldmann, 2001). Once an outbreak occurs, almost 45% of the contacts of the infected individuals acquire the infection (Langley, et al., 1997).

Once infected, infants and children develop the initial symptoms of runny nose, decreased appetite and lethargy within 4 to 6 days. Over the period of the next 1 to 3 days, other symptoms such as cough, sneezing and fever develop. It is important to note that in very young infants, irritability, jitteriness, lethargy, and respiratory distress may be the only symptoms of infection (Centers for Disease Control and Prevention (CDC), 2008). Most children will recover in 1 to 2 weeks, but complications are common in infants with severe RSV bronchiolitis such as electrolyte disturbances, apnea, hypoxemia, and cardiopulmonary abnormalities. These complications are more common in pre-term infants, and those with immune deficiencies and congenital anomalies (Mlinaric´-Galinovic´ & Varda-Brkic, 2000). In the most severe cases of the disease, infants may require supplemental oxygen, suctioning of secretions from the airways, or intubation with mechanical ventilation (Centers for Disease Control and Prevention (CDC), 2008).

The diagnosis of RSV bronchiolitis is mainly clinical. However, several different tests can be used for the confirmation of diagnosis and are of particular use in the event of an outbreak where close contacts need to be screened to rule out the presence of infection. These tests include rapid diagnostic assays including enzyme-linked immunosorbent assay (ELISA) and fluorescent antibody techniques for detection of the viral antigen which can be performed on respiratory specimens, antigen detection tests and culture. The latter two are ideal for use in young infants and are less useful in adolescents and adults (Centers for Disease Control and Prevention (CDC), 2008). More recently, RT-PCR has been made commercially available and is of extreme importance in the diagnosis of adults. Serologic tests are also available for RSV but are of limited use in clinical practice since the presence of paired sera is required and thus the timely diagnosis of patients is not possible (Centers for Disease Control and Prevention (CDC), 2008).

Once an index case is identified, the initiation of strict infection control measures becomes imperative. The need to be on a ventilator signifies severe disease and so after isolation, prompt supportive therapy is required. By definition, RSV is a self-limited disease and thus, only supportive management, including ensuring optimal oxygen saturation by supplying humidified oxygen and adequate fluid replacement, is required (Fitzgerald & Kilham, 2004). In regard to the use of specific therapies for the index case and other infected individuals, different studies have demonstrated conflicting results regarding the use of ribavirin in the management of RSV bronchiolitis. Ribavirin is delivered in the form of the aerosol delivered via a mist generator or mask for a period of about three days. Analysis of the trials conducted so far reveals the length of hospital stay and the duration of the requirement of mechanical ventilation may be reduced with the use of Ribavirin. Moreover, in the long term, Ribavirin has been shown to have the added benefit of decreasing the recurrences of wheezing episodes (Purcell & Fergie, 2004). However, there is still a paucity of data regarding the use of Ribavirin in complicated cases and in infants requiring mechanical ventilation. Thus, further research in this regard is implicated and should be undertaken. Similarly, the routine uses of nebulised adrenaline, inhaled and systemic corticosteroids, and inhaled bronchodilators has not been shown to be efficacious in the management of bronchiolitis (Fitzgerald & Kilham, 2004).

To date, no effective vaccine for the prevention of RSV infections in high-risk individuals and close contacts of infected individuals has been developed. However, a human recombinant monoclonal antibody named Palivizumab is available for prophylaxis in high-risk groups. This antibody is directed against a surface glycoprotein of RSV and is administered on a monthly basis for a period of almost six months in high-risk infants such as those who are premature or immunocompromised. The use of Palivizumab has been shown to reduce hospitalization and ICU admission rates in these individuals but has not been shown to be effective in reducing the incidence of mechanical ventilation (Fitzgerald & Kilham, 2004). Similarly, an antibody preparation derived from the human serum RSV-IGIV (Respigam) has been discovered which is administered intravenously at monthly intervals. This preparation has been found to be as effective as Palivizumab in reduction of hospitalization rates but has the limitations of being expensive and administered via IV route (Fitzgerald & Kilham, 2004).

The infection control practices which are recommended in the control of an outbreak of RSV and limiting the spread of the disease from the index case to other individuals include the isolation of the patients into separate rooms, use of barrier methods such as gowns, gloves, masks and goggles for the eyes and nose (Langley, et al., 1997). Moreover, cohorting of nurses, screening of patients at the time of admission, and visitor restrictions are also helpful in limiting the spread of infection (Langley, et al., 1997). A study conducted at the Children’s Hospital, Boston revealed that the implementation of such practices led to a reduction in the infection rate from 6.4 to 3.1 cases per 1,000 patient days (Goldmann, 2001). Another important measure to reduce the spread of infections is proper handwashing. Studies have shown that the use of a hand antisepsis agent which contains detergents or alcohol as opposed to aqueous chlorhexidine only is effective in reducing transmission of infection (Goldmann, 2001).

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