Protocol for integrated solutions for healthy birth, growth and development: a cluster-randomised controlled trial to evaluate the effectiveness of a mixed nutrition intervention package in reducing child undernutrition in Lao People's Democratic Republic.

INTRODUCTION: While Lao People's Democratic Republic has seen economic gains in recent years, one-third of children aged 5 years and under are stunted. There is a need for evidence around clinically effective and cost-effective integrated nutrition-specific and nutrition-sensitive interventions in the local context. METHODS AND ANALYSIS: We aim to conduct a cluster-randomised control trial to test the effectiveness of an integrated package of community-based nutrition-specific and nutrition-sensitive interventions compared with the standard government package of nutrition actions. The trial will be in six districts within the province of Vientiane. We will recruit pregnant women in their third trimester and follow the children born to them every 6 months until 18 months of age. A total of 256 villages (serviced by 34 health centres) will be randomised to a control arm or an intervention arm using a minimisation algorithm. The primary outcome is the prevalence of stunting among children aged 6, 12 and 18 months. The secondary outcomes include prevalence of low birth weight and wasting among children aged 6, 12 and 18 months. Analyses for the primary and secondary outcomes will be conducted at the mother-infant dyad level and adjusted for the cluster randomisation. The difference in prevalence of low birth weight, wasting and stunting between control and intervention groups will be assessed using Pearson's χ2 tests and 95% CIs for the group difference, adjusted for clustering. ETHICS AND DISSEMINATION: The trial protocol was approved by the Alfred Human Research Ethic Committee (Ref: 227/16) and the Lao National Ethics Committee for Health Research (Ref: 81). The trial was registered with the Australian New Zealand Clinical Trials Registry on 28 April 2020 (ACTRN12620000520932). The results will be disseminated at different levels: study participants; the local community; other Lao stakeholders including policymakers; and an international audience. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trials Registry: ACTRN12620000520932.

Added socioeconomic burden of non-communicable disease on HIV/AIDS affected households in the Asia Pacific region: A systematic review.

BACKGROUND: HIV/AIDS causes significant socioeconomic burden to affected households and individuals, which is exacerbated by non-communicable diseases (NCDs). The Asia Pacific Region (APR) comprises about 60% of the global population and has been significantly affected by HIV/AIDS with 5.8 million after Sub-Saharan Africa in 2019. We investigated socioeconomic impacts of HIV/AIDS alone and the added burden of NCDs on HIV-affected households (HIV-HHs) and individuals in the APR. METHOD: We searched multiple databases for studies published in English over 30 years on socioeconomic impact of HIV/AIDS alone and HIV/AIDS with NCDs on affected households or individuals in APR. Findings were synthesised across six domains: employment, health-related expenditure, non-health expenditure, strategies for coping with household liabilities, food security, and social protection. FINDINGS: HIV-HHs had a significantly higher socioeconomic burden compared to Non-HIV households. Total household expenditure was lower in HIV-HHs but with higher expenditure on health services. HIV-HHs experienced more absenteeism, lower wages, higher unemployment, and higher food insecurity. There is a paucity of evidence on the added burden of NCDs on HIV-HHs with only a single study from Myanmar. INTERPRETATION: Understanding the socioeconomic impact of HIV/AIDS with and without NCD is important. The evidence indicates that HIV-HHs in APR suffer from a significantly higher socioeconomic burden than Non-HIV-HHs. However, evidence on the additional burden of NCDs remains scarce and more studies are needed to understand the joint socioeconomic impact of HIV/AIDS and NCDs on affected households. FUNDING: Deakin University School of Health and Social Development grant and Career Continuity grant.

Antimicrobial resistance in the Pacific Island countries and territories.

Antimicrobial resistance (AMR) is a critical global health threat with a disproportionate impact on low-income and middle-income countries (LMICs) due to their higher burden of infections, reduced laboratory surveillance infrastructure and fewer regulations governing antimicrobial use among humans or animals. While there have been increasing descriptions of AMR within many LMICs in WHO's Western Pacific and South East Asian regions, there remains a paucity of data from Pacific Island countries and territories (PICTs). The PICTs represent 22 predominantly middle-income countries and territories with a combined population of 12 million people and 20 official languages, spread over hundreds of separate islands spanning an area corresponding to more than 15% of the earth's surface. Our paper outlines the present state of the evidence regarding AMR in PICTs-discussing the present estimates of AMR and their accompanying limitations, important drivers of AMR, as well as outlining key priorities and potential solutions for tackling AMR in this region. Significant areas for action include developing National Action Plans, strengthening laboratory surveillance systems and educational activities targeted at both healthcare workers and the wider community. Ensuring adequate funding for AMR activities in PICTs is challenging given competing health and environmental priorities, in this context global or regional funding initiatives such as the Fleming Fund can play a key role.

Adverse effects of amphotericin B in children; a retrospective comparison of conventional and liposomal formulations.

AIMS: Lipid formulations of amphotericin B, rather than conventional amphotericin (c-amB), are increasingly used despite limited data comparing these preparations in children. Data on the incidence of adverse effects with amphotericin B at standard doses are scarce. This study aimed to compare the adverse effects associated with standard doses of c-amB and liposomal amphotericin (l-amB) in children. METHODS: Children admitted to the Royal Children's Hospital Melbourne and treated with c-amB or l-amB between January 2010 and September 2013 were included. Clinical and laboratory data were retrospectively extracted from medical records to compare amphotericin-related infusion reactions, nephrotoxicity (glomerulotoxicity and tubulopathy) and hepatotoxicity. RESULTS: Seventy-six children received c-amB and 39 received l-amB. Standard drug administration (recommended dose and infusion time) occurred in 74% (56/76) of patients on c-amB and 85% (33/39) on l-amB. In these 89 children, infusion-related reactions were similar for both c-amB and l-amB (23% (13/56) vs. 9% (3/33); P = 0.15); none occurred in children aged <90 days. There was no difference in amphotericin-associated glomerulotoxicity (c-amB 14% (8/56) vs. l-amB 21% (7/33); P = 0.40) or in the median maximum potassium requirements (c-amB 3.1 vs. l-amB 2.3 mmol kg-1  d-1 ; P = 0.29). Hepatotoxicity occurred more frequently with l-amB than c-amB (83% (24/29) vs. 56% (20/36); P = 0.032). CONCLUSIONS: When appropriately administered, l-amB was associated with more hepatotoxicity than c-amB, with no difference in infusion-related reactions or nephrotoxicity. Differences in adverse effects between the preparations is not as marked in children as reported in adults.

The development of One Health approaches in the Western Pacific.

The Western Pacific Region, the most populous of six regional groupings of World Health Organization (WHO) member states, has seen the emergence of a series of novel zoonotic infections in the last decade. This has focused attention on addressing underlying risks and vulnerabilities in the complex interactions among people, animals, and environments as a better way to counter emerging diseases. This "One Health" approach is pertinent to the region because, it is a "hot spot" for the emergence of novel diseases from wildlife, because unexpected epidemics of re-emerging zoonotic diseases have caused morbidity and mortality in urban and periurban communities, and because it remains a sanctuary for well-known zoonotic infections. In this chapter, selected regional, multicountry, and national steps to operationalize One Health are discussed. While the region is well positioned to exploit the opportunities that have come with outbreaks of new diseases, the array of disconnected and overlapping initiatives from various consortia, donors, research institutes, and UN agencies is to some extent impeding the development of better ways of managing both new and old infections for the local, regional, and global good.

Are hard-to-reach populations being reached with immunization services? Findings from the 2005 Papua New Guinea national immunization coverage survey.

OBJECTIVE: To measure immunization coverage among children aged 12-23 months in Papua New Guinea (PNG) and to assess if and why there are differences between hard-to-reach and more accessible communities. METHODS: WHO cluster sampling methodology was employed to measure immunization coverage in PNG's four regions. Survey data were re-analyzed according to a local assessment of geographical accessibility indicated by census unit type: urban, rural and hard-to-reach. Census units were designated as hard-to-reach if they were five or more km from a health centre. FINDINGS: Nationwide coverage for most antigens falls below the national target of 80% although there are regional differences with Islands performing the best. Late doses are a major concern: just 4% were fully immunized with valid ("on time") doses by 1 year of age. Coverage was lower in both rural and remote communities: at 6 months 48% of children from urban units had received three valid doses of DTP-3 but only 16% in rural areas and 13% in hard-to-reach communities. Reasons for failure to immunize varied: 21% of mothers said their child was not immunized because distance, travel conditions or cost of transportation prevented access to local health centres; 27% cited a lack of knowledge or misconceptions about immunization; while 29% believed it was because of an issue with the health system. CONCLUSIONS: Throughout PNG there is an urgent need to increase immunization coverage and to ensure that children are immunized on time according to the schedule. Both coverage and timeliness of doses are worse for children living in hard-to-reach and rural areas. Achieving national immunization targets requires improvements in health service delivery, including outreach, especially for remote and rural communities, as well as greater community education and social mobilisation in support of immunization services.

Global control of hepatitis B virus: does treatment-induced antigenic change affect immunization?

Since its widespread introduction, the hepatitis B vaccine has become an essential part of infant immunization programmes globally. The vaccine has been particularly important for countries where the incidence of hepatitis B virus-related hepatocellular carcinoma is high. Effective treatment options for individuals with chronic hepatitis B infection were limited until 1998 when lamivudine, the first nucleoside analogue drug, was introduced. As a single treatment agent, however, lamivudine has a significant drawback: it induces lamivudine-resistant hepatitis B virus strains that may pose a risk to the global hepatitis B immunization programme. Mutations associated with drug treatment can cause changes to the surface antigen protein, the precise part of the virus that the hepatitis B vaccine mimics. However, the emergence of antiviral drug-associated potential vaccine escape mutants (ADAP-VEMs) in treated patients does not necessarily pose a significant, imminent threat to the global hepatitis B immunization programme. Nonetheless, there is already evidence that current treatment regimens have resulted in the selection of stable ADAP-VEMs. Treatment is currently intended to prevent the long-term complications of hepatitis B virus infection, with little consideration given to potential adverse public health impacts. To address individual and public health concerns, trials are urgently needed to find the optimal combination of existing drugs that are effective but do not induce the emergence of ADAP-VEMs. This paper examines the mechanism of antiviral drug-selected changes in the portion of the viral genome that also affects the surface antigen, and explores their potential impact on current hepatitis B immunization programmes.