Mohamud Sheikh

The epidemiology of health conditions of newly arrived refugee children: A review of patients attending a specialist health clinic in Sydney

Aim:  To determine the prevalence of common diseases in newly arrived refugee children, resettled in Sydney, by region of birth. To identify health needs of refugee children in Australia.

Passive immunization for influenza through antibody therapies, a review of the pipeline, challenges and potential applications.

The Global Action Plan for influenza vaccines (GAP) aims to increase the production capacity of vaccines so that in the event of a pandemic there is an adequate supply to meet global needs. However, it has been estimated that even in the best case scenario there would be a considerable delay of at least five to six months for the first supplies of vaccine to become available after the isolation of the strain and availability of the candidate vaccine virus to vaccine manufacturers. By this time, the virus is likely to have already infected millions of people worldwide, causing significant mortality, morbidity and economic loss. Passive immunization through broadly neutralizing antibodies which bind to multiple, structurally diverse strains of influenza could be a promising solution to address the immediate health threat of an influenza pandemic while vaccines are being developed. These products may also have a role in seasonal influenza as an alternative to other options such as antivirals for the treatment of severe acute respiratory illness due to influenza. This article provides an overview of the current clinical pipeline of anti-influenza antibodies and discusses potential uses and the challenges to product development.

Therapeutic antibodies for infectious diseases

Passive immunization is the transfer of antibodies and occurs naturally during pregnancy. The transplacental transfer of maternal antibodies to the fetus can protect the infant from many infectious diseases for the first vulnerable months of its life. Passive immunization has been used in the global effort to eliminate maternal and neonatal tetanus. Researchers have estimated that vaccinating pregnant women with two or more doses of tetanus-containing vaccine has reduced neonatal mortality from tetanus by 94%.1 In addition, clinicians have used passive immunization, to prevent or to treat various infections for over a century for diseases such as rabies, diphtheria, tetanus, hepatitis B, respiratory syncytial virus and botulism. Passive immunization is also used in immunocompromised individuals and to manage complications after vaccination. Most of the antibody preparations administered to patients, containing polyclonal antibodies, have been derived from sera of immunized animals, immunized humans, and for some rarer diseases, from sera of convalescent patients.2–4 Box 1 presents blood-derived polyclonal antibodies currently in use.5–7 The production and use of polyclonal antibodies have revealed several challenges, including standardization, patient safety, supply and access. These challenges have led researchers to explore the possibility of replacing polyclonal antibodies with monoclonal antibodies (mAbs), which can be produced through recombinant deoxyribonucleic acid technologies. In the past, producing mAbs was difficult and expensive. However, the increasing use of mAbs as therapeutics for cancer, autoimmune diseases and other chronic diseases has led to increased production capacities and improved manufacturing processes.8 These advancements have made mAbs potentially cost-competitive with blood-derived polyclonal antibodies, while at the same time contributing towards an improved supply at a global level. Over 40 therapeutic mAbs are currently in use, targeting a range of noncommunicable diseases. In addition to potentially addressing the patient safety and supply limitations of polyclonal antibodies, antiinfective mAbs may offer prophylactic or therapeutic interventions for infectious diseases where drugs or vaccines are not available or are poorly efficacious. For example, the use of broadly crossreactive mAbs to prevent influenza or neutralizing mAbs against Ebola and Middle East respiratory syndrome coronavirus (MERS-CoV). Furthermore, anti-infective mAbs could be used to target multidrug resistant pathogens, such as Staphylococcus aureus, to reduce the incidence of hospital-acquired infections and may help to prevent the emergence of antimicrobial resistance. Although passive immunization produces a short-lived protection against infections, mAbs have some advantages over vaccines for active immunization. First, protection from vaccination takes longer and often requires several doses to elicit a protective immune response, whereas passive immunization provides a much quicker protection. Second, passive immunization can provide protection in immunosuppressed individuals, who are often at a high risk of acquiring infections. Third, since the mAb manufacturing process is generic, a manufacturer can start production of mAbs with minimal lead-time. Therefore, mAbs could become available faster than vaccines during an emergency. The 2013–2016 Ebola virus disease outbreak in West Africa demonstrated the need for mAb research and development. In August 2014, two American health-care workers infected with Ebola were treated with ZmappTM, an experimental drug containing three mAbs against Ebola.9 Unfortunately, the drug supply was only sufficient to treat seven patients and efforts had to be made to increase production before clinical evaluation could take place.10 Efficacy trials in Ebola infected patients in West Africa were completed in January 2016. However, due to the waning epidemic, the trial could only enroll 72 patients out of the planned 200. The outcomes showed that out of the 36 patients who received ZmappTM, eight died, which was less than in the group receiving only standard care (13 of 35 patients died). However, the trial sample size was too low to draw any conclusions.11 Despite this setback, anti-Ebola mAb development – which has been ongoing for several years and the first neutralizing mAb reported in 199912 – continues towards the goal of licensure under alternative pathways to standard randomized controlled clinical trials. While there are numerous mAb products under development for a range of infectious diseases, currently only three have been licensed: palivizumab for prevention of respiratory syncytial virus in high-risk infants; and raxibacumab and obiltoxaximab for prophylaxis and treatment of anthrax. Numerous mAbs have shown the potential to treat infectious diseases in preclinical evaluation, both in vitro and in animal models. However, not many of these mAbs have reached clinical trials.13–16 A review of the WHO International Clinical Trials Registry Platform17 and ClinicalTrials.gov, found that as of November 2016, there were at least 38 mAb products in active clinical development for 14 infectious diseases: Anthrax, Clostridium botulinum (botulinum neurotoxin A), C difficile, Ebola virus disease, hepatitis B, hepatitis C, Hendra virus, herpes simplex virus, human immunodeficiency virus, influenza, rabies, respiratory syncytial virus, S aureus and S epidermidis. While mAbs have great potential to address health threats, their developTherapeutic antibodies for infectious diseases Erin Sparrow, Martin Friede, Mohamud Sheikh & Siranda Torvaldsen

The impact of intensive health promotion to a targeted refugee population on utilisation of a new refugee paediatric clinic at the children's hospital at Westmead

Objective. To evaluate the impact of intensive promotion of a new health service to a targeted refugee population, recently resettled in Sydney, and the role of early social connection and membership of social group in promoting health service utilisation of refugees. Design. Descriptive epidemiological study and survey. Settings. A paediatric refugee clinic at a childrens hospital in Sydney. Participants. Newly resettled refugee parents of children seen at the clinic. Interventions. An intensive health promotion and education campaign using ethnic media and social networks to increase awareness of and encourage utilisation of a new clinical service for refugee children (above and beyond the standard promotion that accompanied the start of the new refugee clinic) to a targeted group of refugees from Sub-Saharan Africa. Main outcome measure(s). Rates of attendance and utilisation of the new service in targeted versus non-targeted refugee parents; changes in health beliefs, health-seeking behaviour and utilisation of services following clinic attendance. Results. We interviewed 34 Sub-Saharan African refugee parents (intervention) and 12 non-African refugee parents (non-intervention) attending a paediatric refugee clinic, between June 2005 and May 2006, with a total number of 112 children. The mean ages of the children were 12 and 10 years for the Africans and non-Africans, respectively. Our targeted health promotion campaign appeared to be effective in increasing attendance for target communities compared to the non-targeted communities (OR for African families attending clinic 3.0, 95% CI=1.5–6.2, p<0.001). We observed a significant change in parental knowledge, attitudes and beliefs about infectious diseases after attending the clinic, including decreased stigma around tuberculosis, more awareness of the seriousness of some infections, and increased awareness of the role of immunisation in prevention of infectious diseases. Conclusion. Our study shows that targeted promotion of service to refugee parents is effective. Such efforts may improve access to care for refugees and may constructively change knowledge, attitudes and beliefs about infectious diseases.

Australian Hajj pilgrims' infection control beliefs and practices: Insight with implications for public health approaches

BACKGROUND Hajj is one of the largest annual mass gatherings around the world. Although the Saudi Arabian health authority recommends vaccination and other infection control measures, studies identified variable uptake of these measures among pilgrims, and the reasons behind this variability remain unclear. This qualitative study aimed to addresses this knowledge gap. METHODS In-depth interviews were conducted with pilgrims over 18 years of age. RESULTS A total of 10 participants took part in the study. There was low perception of the potential severity of respiratory conditions and the need for influenza vaccination during Hajj. Different attitudes were found by age group with elderly participants believing that they were under Allahs protection, and were fatalistic about the risk of illness. While younger participants described the impact infections would have on their worship. Facemask use was infrequent with discomfort; difficulty in breathing and a feeling of isolation were commonly cited barriers to use of facemasks. Participants accepted and trusted preventative health advice from travel agents and friends who had previously undertaken the Hajj more so than primary care practitioners. CONCLUSIONS This study extended our understanding of how health beliefs influence uptake of preventive measures during the Hajj, and the gaps in the provision of Hajj-specific health information to pilgrims.

Improving access to immunisation for migrants and refugees: recommendations from a stakeholder workshop

Australian and New Zealand Journal of Public Health 2017 vol. 41 no. 2

Management of old world cutaneous leishmaniasis in refugee children.

The optimal treatment of cutaneous leishmaniasis is controversial. We report our experience managing Old World cutaneous leishmaniasis in a pediatric refugee clinic. Conventional amphotericin B therapy caused reversible renal failure in 2 of 3 children treated. The choice of treatment for cutaneous leishmaniasis needs to balance the risks of treatment against the likely cosmetic benefits of therapy.

Does Zika Virus Cause Microcephaly - Applying the Bradford Hill Viewpoints

Introduction: Zika virus has been documented since 1952, but been associated with mild, self-limiting disease. Zika virus is classified as an arbovirus from a family of Flaviviridae and primarily spread by Aedes Aegypti mosquitos. However, in a large outbreak in Brazil in 2015, Zika virus has been associated with microcephaly. Methods: In this review we applied the Bradford-Hill viewpoints to investigate the association between Zika virus and microcephaly. We examined historical studies, available data and also compared historical rates of microcephaly prior to the Zika virus outbreak. The available evidence was reviewed against the Bradford Hill viewpoints. Results: All the nine criteria were met to varying degrees: strength of association, consistency of the association, specificity, temporality, plausibility, coherence, experimental evidence, biological gradient and analogy. Conclusion: Using the Bradford Hill Viewpoints as an evaluation framework for causation is highly suggestive that the association between Zika virus and microcephaly is causal. Further studies using animal models on the viewpoints which were not as strongly fulfilled would be helpful.

Preventive detention: the ethical ground where politics and health meet. Focus on asylum seekers in Australia

Australia has a history of migration, especially during the wars in Europe, but many have forgotten the difficulties underlying asylum and wars endured by their forefathers. Preventive, indefinite detention of asylum seekers, most of whom are found to be genuine refugees, impinges on their human rights. The mental and physical health consequences of detention in this already traumatised group are significant, particularly in children. There are abundant studies to support this but, even as these studies continue to be done, asylum seekers languish in detention centres. To be fully addressed, the health implications of detention cannot be considered in isolation, but must be considered frankly and openly by health professionals in the broader historical and political context within which they occur. If we do not do this, we risk turning a blind eye to, or even condoning, human rights abuses.

Risk activities and pre-travel health seeking practices of notified cases of imported infectious diseases in Australia

Background Travellers are at risk of acquiring infectious diseases during travel, with risks differing by destination, travel and traveller characteristics. A pre-travel health consultation may minimize this risk. However, uptake of pre-travel health advice remains low. We investigated pre-travel health preparations and disease-specific risk behaviours among notified cases of selected travel-associated infectious diseases imported into Australia. Methods Prospective enhanced surveillance of notified cases of typhoid, paratyphoid, measles, hepatitis A, hepatitis E, malaria and chikungunya was conducted in two Australian states between February 2013 and January 2014. Details of pre-travel health preparation and disease-specific risk behaviours were collected. Results Among 180 cases associated with international travel, 28% were <18 years, 65% were VFR travellers and 22% were frequent travellers, having travelled ≥5 times in the past 5 years. 25% had sought pre-travel advice from a healthcare provider, and 16% reported a pre-travel vaccine. Seeking pre-travel health advice did not differ by immigrant status ( P  = 0.22) or by reason for travel ( P  = 0.13) but was more commonly sought by first time travellers ( P  = 0.03). Travellers visiting friends and relatives were more likely to report at-risk activities of brushing teeth with tap water ( P  < 0.001) and eating uncooked food ( P  = 0.03) during travel compared to other travellers. Conclusions Pre-travel health advice seeking practices and vaccine uptake was suboptimal among cases of notified disease. The results of this study highlight the need for a better understanding of barriers to pre-travel health seeking, particularly among high risk travellers, to reduce the importation of infectious diseases into Australia.