Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 14, Issue 3, 2014

Influenza is an acute respiratory illness that remains an important cause of excessive morbidity and mortality with substantial economic cost to the population. Influenza, being a virus that frequently mutates, is not amenable to elimination. Vaccination remains the most effective preventive measure. This review summarises the latest developments in the fields of biology and epidemiology relating to clinical and economic impacts of influenza disease, and vaccination. We suggest that future efforts should focus on developing safer, more effective, and cost-effective prophylactic vaccines for influenza.

The numerous protozoa that can inhabit the human gastro-intestinal tract are known, yet little is understood of the viruses which infect these protozoa. The discovery, morphologic details, purification methods of virus-like particles, genome and proteome of the parasitic viruses, Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, and the Eimeria sp. are described in this review. The protozoan viruses share many common features: most of them are RNA or double-stranded RNA viruses, ranging between 5 and 8 kilobases, and are spherical or icosahedral in shape with an average diameter of 30-40 nm. These viruses may influence the function and pathogenicity of the protozoa which they infect, and may be important to investigate from a clinical perspective. The viruses may be used as specific genetic transfection vectors for the parasites and may represent a research tool. This review provides an overview on recent advances in the field of protozoan viruses.

Mycobacterium fortuitum complex skin infection is described in a previously healthy adolescent girl in Sydney, Australia. Mycobacterium fortuitum typically causes superficial skin infections following trauma to the skin and in our patient may have been related to prior leg “waxing”. This case highlights common causes for a delay in diagnosis: lack of clinician awareness and inadequate microbiological and histopathological investigations of tissue samples. Due to the size and number of lesions, surgical excision was felt to be a less desirable therapeutic option due to the potential risk of poor cosmetic outcome for our patient. The standard chemotherapeutic approach to M. fortuitum infections involves the use of a combination of at least two antimicrobial agents to which the isolate is susceptible. Despite in vitro susceptibility testing that suggested that the isolate from our patient was resistant to most oral anti-microbial agents, our patient was treated successfully with a 10-week course of oral trimethoprim-sulfamethoxazole and moxifloxacin.

Objective: There is strong evidence of a link between parental substance use and/or mental health problems and adverse outcomes in children. We wanted to know the impact of these early childhood adversities on the health and social outcomes of children. We also wanted to determine whether early identification of these risks made a difference to the child’s outcome and what effective strategies and interventions are available that will ensure the safety of children, provide support for them and improve their long-term outcomes. Method: This was a retrospective analysis of children attending a specialized Pediatric (“Branches”) clinic in South West Sydney; set up for children exposed to perinatal risks including parental substance use and/or mental health problems. Total of 124 children attended the Branches clinic from January 2006 to December 2009. Data recorded included health, developmental and social outcomes. Result: Mean age of first presentation to the clinic was 3.95 years, majority (63%) were in foster care. Parental substance abuse was identified in 73% of the cases while parental mental health disorder was documented in 48% cases. A range of infection and other health related problems were identified, including the risk of hepatitis C transmission. Almost one third of children had incomplete immunization (29%) and over 90% of children needed referrals to services. We did not find any difference in outcomes or age of first presentation to the clinic between children identified in the perinatal period, compared to those not identified early. Conclusion: Our study found significant health problems in children exposed to perinatal risks. Early or perinatal identification of these risks did not affect outcomes in our setting. Better coordination between maternity, pediatrics, hospital and community services may improve child outcomes through earlier identification of health concerns.

Hajj attendance increases the risk of respiratory infections including pneumonia. Streptococcus pneumoniae is a frequently identified pathogen, found in about 10% of respiratory tract samples of symptomatic Hajj pilgrims; and at least 20% of these isolates are penicillin resistant. However, the burden of pneumococcal disease at Hajj is not precisely defined at serotypic level, and it is postulated that due to intense mixing of pilgrims the distribution of pneumococcal serotypes at Hajj could be different from pilgrims’ country of origin or of Saudi Arabia. In Saudi Arabia, the most prevalent pneumococcal serotypes are 23F, 6B, 19F, 18C, 4, 14, and 19A, and 90% of the serotypes are covered by 13-valent pneumococcal conjugate vaccine (PCV-13) as well as 23-valent pneumococcal polysaccharide vaccine (PPV-23). However, due to lack of Hajj-specific data, the Saudi Arabian Ministry of Health has not yet recommended pneumococcal vaccine for pilgrims, and the immunisation recommendation and uptake vary greatly across countries. As at least one third of Hajj pilgrims are ‘at risk’ of pneumococcal disease either by virtue of age or pre-existing medical conditions, consideration should be given to vaccinating high risk pilgrims against pneumococcal disease. Other preventive measures such as smoking cessation, pollution reduction and vaccinations against influenza and pertussis should also be considered. Precisely defining the epidemiology of pneumococcal disease to identify an optimum vaccination schedule for Hajj pilgrims is a current research priority.

Congenital cytomegalovirus (cCMV) is a contributing cause of neurodevelopmental disabilities including cerebral palsy (CP). In this case series we reviewed the neuroimaging findings of children with CP and cCMV infection in the context of the children’s clinical profile. Participants: Children with CP and laboratory confirmed cCMV (n=12) reported to the Australian CP Register, born in South Australia and Victoria, 1993-2006, with magnetic resonance imaging (MRI) and/or computerized tomography (CT) report available. Clinical details and neuroimaging findings were tabulated and compared to published literature. Children in this series were mostly born at term (n=8), with symptoms or signs of cCMV (n=10) and had spastic quadriplegia (n=9), epilepsy (n=8), intellectual deficit (n=12), communication (n=10) and hearing impairments (n=9). All but one had abnormal neuroimaging findings reported on MRI or CT (n=11): most commonly brain malformations including disorders of neuronal migration (n=10), such as lissencephaly, pachygyria and polymicrogyria, and cerebellar hypoplasia (n=5). Other findings included ventricular dilatation (n=8), calcifications (n=7) and white matter abnormalities (n=6). This study suggests that brain malformations, calcifications, ventricular dilatation and cerebellar hypoplasia are common neuroimaging patterns in children with CP and cCMV infection. The presence of these findings should prompt investigations for congenital cytomegalovirus.

The medication management pathway (MMP) outlines the medication journey from the decision to prescribe through to monitoring the outcomes. Medication errors (MEs) can occur at any point of the pathway. MEs in children may result in poor health outcomes; and as children are more vulnerable to dose calculation and administration errors especially in the ambulatory setting, this cohort may be at a higher risk of adverse outcomes. This review aimed to identify MEs in children and attribute them to the steps within the MMP for paediatric ambulatory patients. A systematic search of studies related to MEs in children was performed using MEDLINE, EMBASE and International Pharmaceutical Abstracts in the period from Jan 1991 to June 2011, using keywords pertaining to children, medication errors and ambulatory settings. Thirty articles met the review inclusion criteria and the findings of these studies were reported. Based on the MMP, 26 studies reported prescribing errors, 7 dispensing errors, and 12 administration errors. Twelve studies reported errors at more than one time point within the MMP; four studies at 2 stages and 8 studies at 3 stages. The most common types of the errors identified were dose errors which commonly occurred during prescribing, dispensing, or administration. Studies have highlighted that MEs occurring in children, with most of the errors reported at the prescribing stage. This could be a reflection of the studies’ focus, and further work is needed to review errors occurring at other time points during the medication management cycle. Identifying where errors occur will contribute to the development of novel strategies to detect and prevent these errors in ambulatory settings.

This systematic review evaluates the prevalence of long-term complications of serogroup B meningococcal disease (MD) in light of the recent licensure of a vaccine against meningococcal B disease. Twelve appropriate studies were identified by searching available databases from 1946 to July 2014. The average prevalence of hearing impairment was 4.2% among serogroup B MD survivors; 2.3% suffered amputation and 2.3% developed seizures. When compared with complications due to non-meningococcal B bacterial meningitis, physical impairment and seizures were more common in survivors of meningococcal B disease but hearing impairment had similar prevalence. Few studies quantified less frequent complications such as visual impairment and cognitive dysfunction. Better comprehensive reporting of the complications and costs of serogroup B MD in survivors and their families is needed to inform vaccination policy.

Travellers attending mass gathering events like Hajj are at high risk of acquisition of respiratory viral infection, especially influenza. Following the official recommendation from the Saudi Ministry of Health in 2005, the coverage rate of influenza vaccine rose to 100% by the year 2009, and thereafter remained above 80% in pilgrims from resource-rich countries. In a meta-analysis of observational studies, influenza vaccine was found to be significantly effective against laboratory-confirmed influenza; therefore, it is interesting to determine whether there has been any change in the prevalence of influenza. Over the last few decades a score of studies have been undertaken to establish the prevalence of influenza among Hajj pilgrims. The studies varied greatly in their designs; most notably, two separate endpoints were used: ‘point prevalence’ and ‘attack rate’. The attack rate of influenza among Hajj pilgrims has remained stable between 4% and 15%, as did its point prevalence between 1.3% and 10%. However, the prevalence of influenza-like illness (ILI) varied widely between 8% and 63%, depending on how ILI was defined. It is therefore sensible to assume that the prevalence of influenza at Hajj has not declined considerably, and vaccine and other preventive measures may have contributed to keep the epidemiology stable. More studies are needed to understand the epidemiology of influenza at Hajj, particularly by assessing the efficacy of influenza vaccine against laboratory-proven influenza in pilgrims.

Trachoma is one of the major causes of preventable blindness worldwide. In Australia it is solely a disease of Aboriginal people. Trachoma in non-indigenous Australians has been eradicated earlier this century, however, is still prevalent among Aboriginal communities. Poor living condition, lack of access to water supply and sanitation, living in a crowded and unhealthy environment are the main causes of trachoma in Indigenous Australians. The World Health Organization (WHO) has initiated Global Alliance for the Elimination of Trachoma by the year 2020 (GET2020). The alliance has adopted the “SAFE” (Surgery, Antibiotic distribution, Facial cleanliness and Environmental improvements) strategy to eliminate trachoma in endemic countries. In Australia, the National Trachoma Surveillance and Reporting Unit (NTSRU) was established in 2006 and ever since has been providing high quality surveillance data on national trachoma burden. In 2009, the Australian Government made a commitment investment of $16 million over a 4-year period to eliminate trachoma from Australia. Today, promising success has been achieved in surveillance and management of trachoma using the SAFE strategy. But the ultimate elimination of the disease would require a long-term political commitment founded, inter alia, on multi-sectoral collaboration, targeted research, and community engagement.