Neglected tropical diseases in Australia: a narrative review.

•Neglected tropical diseases (NTDs) represent a threat to the health, wellbeing and economic prosperity of billions of people worldwide, often causing serious disease or death. •Commonly considered diseases of low and middle-income nations, the presence of NTDs in high income countries such as Australia is often overlooked. •Seven of the 20 recognised NTDs are endemic in Australia: scabies, soil-transmitted helminths and strongyloidiasis, echinococcosis, Buruli ulcer, leprosy, trachoma, and snakebite envenoming. •Dengue, while not currently endemic, poses a risk of establishment in Australia. There are occasional outbreaks of dengue fever, with local transmission, due to introductions in travellers from endemic regions. •Similarly, the risk of introduction of other NTDs from neighbouring countries is a concern. Many NTDs are only seen in Australia in individuals travelling from endemic areas, but they need to be recognised in health settings as the potential consequences of infection can be severe. •In this review, we consider the status of NTDs in Australia, explore the risk of introducing and contracting these infections, and emphasise the negative impact they have on the health of Australians, especially Aboriginal and Torres Strait Islander peoples.

Impact of hookworm infection and preventive chemotherapy on haemoglobin in non-pregnant populations.

OBJECTIVE: To assess the impact of hookworm infection and preventive chemotherapy on haemoglobin levels in non-pregnant populations in endemic areas. METHOD: Systematic review and meta-analysis searching PubMed and Web of Science for articles published since 2010 reporting either hookworm prevalence and Hb concentration (cross-sectional studies) or Hb concentration before and after the implementation of preventive chemotherapy (before-after studies and randomised controlled trials [RCTs]). For papers published before 2010, data were extracted from a previously published systematic review. Random effects meta-analyses were conducted to examine the relationship between Hb concentration and hookworm infection intensity (from cross-sectional studies) and the effect of preventive chemotherapy on Hb concentration (from before-after studies and RCTs). Sensitivity analyses investigated the impact of malaria endemicity and combined interventions for schistosomiasis and nutrition status on Hb concentration. RESULTS: Among cross-sectional studies, both light- and heavy-intensity hookworm infections were associated with lower Hb in school-aged children. School-aged children with heavy hookworm infection in settings of high malaria endemicity had lower mean Hb than those in settings of low malaria endemicity. In non-pregnant populations, deworming with albendazole was associated with an increase in Hb of 3.02 g/L (95% CI 0.1, 6.0 g/L). No additional benefit was seen with deworming using albendazole co-administered with praziquantel for schistosomiasis infection or iron supplementation for nutrition status. CONCLUSION: Our findings confirm the benefits of preventive chemotherapy as a public health intervention.

Efficacy of Anthelminthic Drugs and Drug Combinations Against Soil-transmitted Helminths: A Systematic Review and Network Meta-analysis.

Background: Periodic mass distribution of benzimidazole anthelminthic drugs is the key strategy to control soil-transmitted helminths (STHs) globally. However, benzimidazoles have low efficacy against Trichuris trichiura, and there are concerns about benzimidazole resistance potentially emerging in humans. Therefore, identifying alternative drug regimens is a pressing priority. We present a systematic review and network meta-analysis comparing the efficacy of 21 different anthelminthic drug regimens, including standard, novel, and combination treatments. Methods: We searched PubMed, Medline, Embase, Web of Science, and Cochrane databases and identified studies comparing anthelminthic treatments to each other or placebo. The outcomes calculated were relative risk (RR) of cure and difference in egg reduction rates (dERR). We used an automated generalized pairwise modeling framework to generate mixed treatment effects against a common comparator, the current standard treatment (single-dose albendazole). Results: Our search identified 4876 studies, of which 114 were included in the meta-analysis. Results identified several drug combinations with higher efficacy than single-dose albendazole for T. trichiura, including albendazole-ivermectin (RR of cure, 3.22 [95% confidence interval {CI}, 1.84-5.63]; dERR, 0.97 [95% CI, .21-1.74]), albendazole-oxantel pamoate (RR, 5.07 [95% CI, 1.65-15.59]; dERR, 0.51 [95% CI, .50-.52]), mebendazole-ivermectin (RR, 3.37 [95% CI, 2.20-5.16]), and tribendimidine-oxantel pamoate (RR, 4.06 [95% CI, 1.30-12.64]). Conclusions: There are several promising drug combinations that may enhance the impact of STH control programs on T. trichiura, without compromising efficacy against Ascaris lumbricoides and hookworm. We suggest further, large-scale trials of these drug combinations and consideration of their use in STH control programs where T. trichiura is present. International Prospective Register of Systematic Reviews Registration: CRD42016050739.

Tobacco smoking and risk of 36 cardiovascular disease subtypes: fatal and non-fatal outcomes in a large prospective Australian study.

BACKGROUND: Tobacco smoking is a leading cause of cardiovascular disease (CVD) morbidity and mortality. Evidence on the relation of smoking to different subtypes of CVD, across fatal and non-fatal outcomes, is limited. METHODS: A prospective study of 188,167 CVD- and cancer-free individuals aged ≥ 45 years from the Australian general population joining the 45 and Up Study from 2006 to 2009, with linked questionnaire, hospitalisation and death data up to the end of 2015. Hazard ratios (HRs) for hospitalisation with or mortality from CVD among current and past versus never smokers were estimated, including according to intensity and recency of smoking, using Cox regression, adjusting for age, sex, urban/rural residence, alcohol consumption, income and education. Population-attributable fractions were estimated. RESULTS: During a mean 7.2 years follow-up (1.35 million person-years), 27,511 (crude rate 20.4/1000 person-years) incident fatal and non-fatal major CVD events occurred, including 4548 (3.2) acute myocardial infarction (AMI), 3991 (2.8) cerebrovascular disease, 3874 (2.7) heart failure and 2311 (1.6) peripheral arterial disease (PAD) events. At baseline, 8% of participants were current and 34% were past smokers. Of the 36 most common specific CVD subtypes, event rates for 29 were increased significantly in current smokers. Adjusted HRs in current versus never smokers were as follows: 1.63 (95%CI 1.56-1.71) for any major CVD, 2.45 (2.22-2.70) for AMI, 2.16 (1.93-2.42) for cerebrovascular disease, 2.23 (1.96-2.53) for heart failure, 5.06 (4.47-5.74) for PAD, 1.50 (1.24-1.80) for paroxysmal tachycardia, 1.31 (1.20-1.44) for atrial fibrillation/flutter, 1.41 (1.17-1.70) for pulmonary embolism, 2.79 (2.04-3.80) for AMI mortality, 2.26 (1.65-3.10) for cerebrovascular disease mortality and 2.75 (2.37-3.19) for total CVD mortality. CVD risks were elevated at almost all levels of current smoking intensity examined and increased with smoking intensity, with HRs for total CVD mortality in current versus never smokers of 1.92 (1.11-3.32) and 4.90 (3.79-6.34) for 4-6 and ≥ 25 cigarettes/day, respectively. Risks diminished with quitting, with excess risks largely avoided by quitting before age 45. Over one third of CVD deaths and one quarter of acute coronary syndrome hospitalisations in Australia aged < 65 can be attributed to smoking. CONCLUSIONS: Current smoking increases the risk of virtually all CVD subtypes, at least doubling the risk of many, including AMI, cerebrovascular disease and heart failure. Paroxysmal tachycardia is a newly identified smoking-related risk. Where comparisons are possible, smoking-associated relative risks for fatal and non-fatal outcomes are similar. Quitting reduces the risk substantially. In an established smoking epidemic, with declining and low current smoking prevalence, smoking accounts for a substantial proportion of premature CVD events.

A cluster-randomised controlled trial comparing school and community-based deworming for soil transmitted helminth control in school-age children: the CoDe-STH trial protocol.

BACKGROUND: Current guidelines and targets for soil-transmitted helminth (STH) control focus on school-based deworming for school-age children, given the high risk of associated morbidity in this age group. However, expanding deworming to all age groups may achieve improved STH control among both the community in general and school-age children, by reducing their risk of reinfection. This trial aims to compare school-based targeted deworming with community-wide mass deworming in terms of impact on STH infections among school-age children. METHODS: The CoDe-STH (Community Deworming against STH) trial is a cluster-randomised controlled trial (RCT) in 64 primary schools in Dak Lak province, Vietnam. The control arm will receive one round of school-based targeted deworming with albendazole, while in the intervention arm, community-wide mass deworming with albendazole will be implemented alongside school-based deworming. Prevalence of STH infections will be measured in school-age children at baseline and 12 months following deworming. The primary outcome is hookworm prevalence in school-age children at 12 months, by quantitative PCR. Analysis will be intention-to-treat, with outcomes compared between study arms using generalised linear and non-linear mixed models. Additionally, cost-effectiveness of mass and targeted deworming will be calculated and compared, and focus group discussions and interviews will be used to assess acceptability and feasibility of deworming approaches. Individual based stochastic models will be used to predict the impact of mass and targeted deworming strategies beyond the RCT timeframe to assess the likelihood of parasite population 'bounce-back' if deworming is ceased due to low STH prevalence. DISCUSSION: The first large-scale trial comparing mass and targeted deworming for STH control in South East Asia will provide key information for policy makers regarding the optimal design of STH control programs. TRIAL REGISTRATION: ACTRN12619000309189 .

Differential effect of mass deworming and targeted deworming for soil-transmitted helminth control in children: a systematic review and meta-analysis.

BACKGROUND: Soil-transmitted helminth infections are a major global health issue, causing substantial morbidity in the world's poorest populations. Regular delivery of anthelmintic drugs is the mainstay for global soil-transmitted helminth control. Deworming campaigns are often targeted to school-aged children, who are at high risk of soil-transmitted-helminth-associated morbidity. However, findings from modelling studies suggest that deworming campaigns should be expanded community-wide for effective control of soil-transmitted helminth transmission. We aimed to do a systematic review and meta-analysis to compare the effect of mass (community-wide) and targeted (children only) anthelmintic delivery strategies on soil-transmitted helminth prevalence in school-aged children. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, and Web of Science for articles published on or before Nov 5, 2015, reporting soil-transmitted helminth prevalence before and after distribution of albendazole or mebendazole, either targeted to children or delivered to the whole community. We excluded studies in which drug delivery was restricted to infected individuals or to a subset of the community or school, or if follow-up time was less than 3 months or greater than 18 months after drug delivery. We extracted data on study year, country, drug administration strategy, drug dose, number of deworming rounds, treatment coverage, diagnostic method, follow-up interval, and soil-transmitted helminth prevalence before and after treatment. We used inverse variance weighted generalised linear models, with prevalence reduction as the outcome variable, to examine the effect of mass versus targeted drug administration, as well as baseline prevalence, number of drug doses, and follow-up time. This study is registered with PROSPERO, number CRD42016026929. FINDINGS: Of 10 538 studies identified, 56 studies were eligible for the systematic review and 38 of these were included in meta-analysis. Results of the regression models showed that mass deworming led to a significantly greater reduction in prevalence in children than targeted deworming, for both hookworm (odds ratio 4·6, 95% CI 1·8-11·6; p=0·0020) and Ascaris lumbricoides (16·4, 2·1-125·8; p=0·0092), with no effect seen for Trichuris trichiura. There was significant heterogeneity across studies; for targeted studies I2 was 97% for A lumbricoides and hookworm, and 96% for T trichiura, and for mass studies, I2 was 89% for A lumbricoides, 49% for hookworm, and 66% for T trichiura. INTERPRETATION: The results of this meta-analysis suggest that expanding deworming programmes community-wide is likely to reduce the prevalence of soil-transmitted helminths in the high-risk group of school-aged children, which could lead to improved morbidity outcomes. These findings are in support of recent calls for re-evaluation of global soil-transmitted helminth control guidelines. FUNDING: None.

Fulminant liver failure in a neonate.

Neonatal acute liver disease is relatively rare, with multiple different aetiologies including congenital infections, metabolic disorders, gestational alloimmune liver disease, haemophagocytic lymphohistiocytosis, and ischaemic injury. We report a case of neonatal liver failure in a preterm, growth-restricted infant, who underwent extensive investigation and was clinically diagnosed with gestational alloimmune liver disease, which was confirmed on post-mortem examination. We then discuss management of neonatal liver failure and gestational alloimmune liver disease, including maternal management in future pregnancies.

Effectiveness of ivermectin mass drug administration in the control of soil-transmitted helminth infections in endemic populations: a systematic review and meta-analysis.

BACKGROUND: Current soil-transmitted helminth (STH) control guidelines endorse the use of albendazole or mebendazole for school-based targeted preventive chemotherapy (PC), yet their reduced efficacy against Strongyloides stercoralis and Trichuris trichiura presents significant limitations. Emerging evidence indicates that community-wide PC [or mass drug administration (MDA)] using ivermectin, commonly used in other neglected tropical disease (NTD) control programs, may play an important role in controlling these parasites. We conducted a systematic review and meta-analysis to evaluate the effectiveness of ivermectin PC in reducing STH prevalence in endemic populations. METHODS: We searched Pubmed, EMBASE, and Web of Science on February 14, 2023, for studies that investigated the effectiveness of ivermectin PC, either alone or in combination with other anthelmintic drugs, on STH infections, and provided a measure of STH prevalence before and after PC. We calculated pooled prevalence reductions for each STH using random-effects meta-analyses. Our protocol is available on PROSPERO (registration number CRD42023401219). RESULTS: A total of 21 were eligible for the systematic review, of which 15 were eligible for meta-analysis. All studies delivered ivermectin through MDA. The pooled prevalence reduction of S. stercoralis following MDA with ivermectin alone was 84.49% (95% CI 54.96-94.66) across five studies and 81.37% (95% CI 61.62-90.96) across seven studies with or without albendazole. The prevalence reduction of T. trichiura was 49.93% (95% CI 18.23-69.34) across five studies with ivermectin alone, and 89.40% (95% CI 73.66-95.73) across three studies with the addition of albendazole. There was high heterogeneity for all syntheses (I2 > 65%). CONCLUSIONS: This study underscores the key role of ivermectin-based MDA in addressing limitations in current global STH guidelines in terms of limited efficacy against S. stercoralis and T. trichiura. Based on these findings, revising international STH guidelines to include ivermectin is a promising option to progress the control and eventual elimination of STHs and other NTDs.

Vein of Galen Aneurysmal Malformation: A Case Report.

Vein of Galen aneurysmal malformation is a relatively rare disease in which failure of the median prosencephalic vein of Markowski to involute early in gestation leads to a grossly dilated deep cerebral vein with multiple arterial feeders, causing a large arteriovenous shunt which leads to high-output cardiac failure. We describe a case of a term neonate who presented to a tertiary neonatal centre on day one of life with history, symptoms, and signs consistent with perinatal asphyxia; however, in the context of worsening multi-organ dysfunction and cardiomegaly, the infant was found to have a severe vein of Galen aneurysmal dilatation leading to high-output cardiac failure. The patient was transferred to a tertiary paediatric hospital and underwent a total of four coiling procedures to embolise the multiple feeder arteries supplying the aneurysmal malformation. This case highlights the difficulties in diagnosing this relatively uncommon condition, particularly in the context of a possible perinatal insult.

Use of targeted SMS messaging to encourage COVID-19 oral antiviral uptake in South West Victoria.

OBJECTIVES: During winter 2022, as part of a multifaceted approach to optimise oral antiviral uptake in the Barwon South West region in Victoria, Australia, the Barwon South West Public Health Unit (BSWPHU) implemented an innovative, targeted SMS messaging program that encouraged people with coronavirus disease 2019 (COVID-19) to be assessed for antiviral treatment. In this study, we investigated patterns of antiviral uptake, identified barriers and facilitators to accessing antivirals, and examined the potential impact of targeted SMS messaging on oral antiviral uptake. METHODS: We conducted a cross-sectional study of notified COVID-19 cases aged 50 years and older, and Aboriginal and Torres Strait Islander people aged 30-49 years, in the BSWPHU catchment area over a 6-week period commencing 21 July 2022. We analysed survey data using descriptive statistics and generalised linear models. RESULTS: Of the 3829 survey respondents, 36.7% (95% confidence interval (CI) 35.2, 38.2) reported being prescribed oral antivirals, with 75.4% (95% CI 72.8, 77.9) of these aged ≥70. Antiviral prescriptions increased significantly over the 6-week survey period. Most prescriptions (87.5%; 95% CI 85.7, 89.2) were provided by the respondents' usual general practitioners (GPs). Barriers to receiving antivirals included respondents being unable to get a medical appointment in time (3.7%; 95% CI 3.1, 4.2), testing too late in their illness (2.3%; 95% CI 1.8, 2.8) and being unable to access medications in time after receiving a prescription (0.2%; 95% CI 0.1, 0.6). Facilitators to receiving antivirals included respondents first hearing about antivirals from a trusted source such as a family member, friend or usual doctor. Nearly one in eight people who were prescribed antivirals reported first hearing about them from the SMS message sent by BSWPHU. CONCLUSIONS: Oral antiviral treatment uptake in south-west Victoria in July-August 2022 was high among survey respondents and increased over time. GPs were the key prescribers in the community. Targeted SMS messaging to COVID-19 cases is a simple, low-cost intervention that potentially increases antiviral uptake.

Effectiveness of one and two doses of ivermectin mass drug administration in reducing the prevalence and intensity of soil-transmitted helminth (STH) infections in Western Province, Solomon Islands: a cluster-randomised, before-after analysis.

Background: Ivermectin mass drug administration (MDA) is effective for controlling onchocerciasis and scabies, with evidence supporting its role in some species of soil-transmitted helminth (STH) infections. In the context of RISE, a cluster-randomised trial for scabies, this study evaluated the effectiveness of ivermectin MDA in reducing STH burden in the Western Province of Solomon Islands. Methods: Twenty villages were randomised 1:1 to receive ivermectin MDA as one dose (IVM-1) or two doses (IVM-2) for scabies. The effectiveness of one and two doses in reducing STH prevalence and intensity was evaluated before (May 2019) and 21 months after (February 2021) MDA in May 2019. All residents aged 12 months or older in the study villages were eligible to participate and provide stool specimens. Species-specific STH infection and intensity were assessed using quantitative PCR. We compared prevalence and intensity of infection between baseline and 21 months in each intervention arm individually using cluster-level analysis (adjusted for clustering) and individual-level analysis (adjusted for sex, age, and clustering). The primary outcomes were the prevalence risk difference (RD) from the cluster-level analysis, and the change in adjusted odds of infection from the individual-level analysis. Secondary outcomes included change in incident rates of mean eggs per gram (epg) of stool from baseline to 21 months, relative risk difference in prevalence and relative change in odds of infection between arms at 21 months. Sex data (male/female) were self-reported. Findings: Overall, STH infection was assessed in 830 participants from 18 villages at baseline and 1172 from 20 villages at follow-up. Females represented 58% (n = 478) of the sample at baseline and 59% (n = 690) at follow-up. We observed a reduction in Strongyloides spp. prevalence following two doses of ivermectin MDA in the cluster-level analysis from 7.0% (32/458 participants) to 1.2% (8/674 participants), corresponding to a RD of -0.07 (95% CI -0.14 to -0.01, p = 0.036), and in the individual-level analysis (OR 0.11, 95% CI 0.04-0.33, p < 0.001). T. trichiura prevalence decreased following one dose from 19.4% (74/372 participants) to 11.7% (56/505 participants) (OR 0.44, 95% CI 0.26-0.73, p = 0.0040), while egg count reduced in both arms (IVM-1: IRR 0.28, 95% CI 0.11-0.70, p = 0.0070; IVM-2: IRR 0.18, 95% CI 0.08-0.40, p < 0.001), in the individual-level analysis. We did not detect a significant difference in effect measures between the one- and two-dose arms for any species after 21 months. Interpretation: Our study highlights the long-term benefits of ivermectin MDA in reducing the burden of Strongyloides spp. and T. trichiura. STH control programs should leverage the geographical overlap of NTDs, existing drug distribution channels, and broad-spectrum agents. Funding: The National Health and Medical Research Council of Australia.

Epidemiology of soil-transmitted helminths using quantitative PCR and risk factors for hookworm and Necator americanus infection in school children in Dak Lak province, Vietnam.

BACKGROUND: Soil-transmitted helminth (STH) infection is driven by a complex interaction of demographic, socioeconomic and behavioural factors, including those related to water, sanitation and hygiene (WASH). Epidemiological studies that measure both infection and potential risk factors associated with infection help to understand the drivers of transmission in a population and therefore can provide information to optimise STH control programmes. METHODS: During October and November 2019, we conducted a cross-sectional survey of the prevalence and intensity of STH infection and associated risk factors among 7710 primary-school-age children from 64 primary schools across 13 districts in Dak Lak province, Vietnam. Quantitative PCR (qPCR) was used to detect and quantify STH infections. RESULTS: The predominant STH species was the hookworm Necator americanus (overall cluster-adjusted prevalence of 13.7%), and its prevalence was heterogeneously distributed across surveyed schools (0% to 56.3%). All other STH species had a prevalence of less than 1%. Using mixed-effects logistic regression, we found that the adjusted odds ratio (aOR) was significantly higher for both infection and moderate-to-heavy-intensity infection with N. americanus among children from multiple ethnic minority groups, compared to children from the majority group (Kinh). Adjusted odds of infection with N. americanus were also higher in children who reported practising open defecation at school (aOR 1.42, 95% CI 1.05, 1.93, P = 0.02) and in those who had an unimproved household water supply (aOR 1.28, 95% CI 1.04, 1.57, P = 0.02). Conversely, children with a flushing household toilet had a reduced risk of infection (aOR 0.58, 95% CI 0.47, 0.70, P < 0.01), as did those whose primary female carer attended secondary (aOR 0.65, 95% CI 0.51, 0.84, P < 0.01) or tertiary education (aOR 0.39, 95% CI 0.24, 0.63, P < 0.01). CONCLUSIONS: This study is the largest reported prevalence survey of STH infections conducted using qPCR as a diagnostic technique. The findings of higher adjusted odds of infection amongst ethnic minority children highlight that STH control programmes may not be reaching certain population groups and that additional culturally appropriate approaches may be required. Additionally, the associations between specific WASH factors and infection indicate potential programmatic targets to complement preventive chemotherapy programmes.

The impact of ivermectin, diethylcarbamazine citrate, and albendazole mass drug administration on the prevalence of scabies and soil-transmitted helminths in school-aged children in three municipalities in Timor-Leste: a before-after assessment.

BACKGROUND: Integrated programmes that use combination mass drug administration (MDA) might improve control of multiple neglected tropical diseases simultaneously. We investigated the impact of Timor-Leste's national ivermectin, diethylcarbamazine citrate, and albendazole MDA, for lymphatic filariasis elimination and soil-transmitted helminth (STH) control, on scabies, impetigo, and STH infections. METHODS: We did a before-after study in six primary schools across three municipalities in Timor-Leste (urban [Dili], semi-urban [Ermera], and rural [Manufahi]) before (April 23 to May 11, 2019) and 18 months after (Nov 9 to Nov 27, 2020) MDA delivery between May 17 and June 1, 2019. Study participants included schoolchildren, as well as infants, children, and adolescents who were incidentally present at school on study days. All schoolchildren whose parents provided consent were eligible to participate in the study. Infants, children, and adolescents younger than 19 years who were not enrolled in the school but were incidentally present at schools on study days were also eligible to participate if their parents consented. Ivermectin, diethylcarbamazine citrate, and albendazole MDA was implemented nationally, with single doses of oral ivermectin (200 µg/kg), diethylcarbamazine citrate (6 mg/kg), and albendazole (400 mg) administered by the Ministry of Health. Scabies and impetigo were assessed by clinical skin examinations, and STHs using quantitative PCR. The primary (cluster-level) analysis adjusted for clustering while the secondary (individual-level) analysis adjusted for sex, age, and clustering. The primary outcomes of the study were prevalence ratios for scabies, impetigo, and STHs (Trichuris trichiura, Ascaris lumbricoides, Necator americanus, and moderate-to-heavy A lumbricoides infections) between baseline and 18 months from the cluster-level analysis. FINDINGS: At baseline, 1043 (87·7%) of 1190 children registered for the study underwent clinical assessment for scabies and impetigo. The mean age of those who completed skin examinations was 9·4 years (SD 2·4) and 514 (53·8%) of 956 were female (87 participants with missing sex data were excluded from this percentage calculation). Stool samples were received for 541 (45·5%) of 1190 children. The mean age of those for whom stool samples were received was 9·8 years (SD 2·2) and 300 (55·5%) were female. At baseline, 348 (33·4%) of 1043 participants had scabies, and 18 months after MDA, 133 (11·1%) of 1196 participants had scabies (prevalence ratio 0·38, 95% CI 0·18-0·88; p=0·020) in the cluster-level analysis. At baseline, 130 (12·5%) of 1043 participants had impetigo, compared with 27 (2·3%) of 1196 participants at follow-up (prevalence ratio 0·14, 95% CI 0·07-0·27; p<0·0001). There was a significant reduction in T trichiura prevalence from baseline (26 [4·8%] of 541 participants) to 18-month follow-up (four [0·6%] of 623 participants; prevalence ratio 0·16, 95% CI 0·04-0·66; p<0·0001). In the individual-level analysis, moderate-to-heavy A lumbricoides infections reduced from 54 (10·0%; 95% CI 0·7-19·6) of 541 participants to 28 (4·5%, 1·2-8·4) of 623 participants (relative reduction 53·6%; 95% CI 9·1-98·1; p=0·018). INTERPRETATION: Ivermectin, diethylcarbamazine citrate, and albendazole MDA was associated with substantial reductions in prevalence of scabies, impetigo, and T trichiura, and of moderate-to-heavy intensity A lumbricoides infections. Combination MDA could be used to support integrated control programmes to target multiple NTDs. FUNDING: National Health and Medical Research Council of Australia and the Department of Foreign Affairs and Trade Indo-Pacific Centre for Health Security. TRANSLATION: For the Tetum translation of the abstract see Supplementary Materials section.

Community-wide versus school-based targeted deworming for soil-transmitted helminth control in school-aged children in Vietnam: the CoDe-STH cluster-randomised controlled trial.

Background: Soil-transmitted helminth (STH) infection control programs typically consist of school-based preventive chemotherapy (PC) targeted to school-aged children. STH reservoirs in untreated community members contribute to ongoing transmission in children. The CoDe-STH (Community Deworming against STH) trial, conducted in Dak Lak province, Vietnam, between October 2019 and November 2020, aimed to determine whether community-wide mass drug administration (MDA) is more effective than school-based targeted PC in reducing STH prevalence and intensity in children. Methods: In this two-arm cluster randomised controlled trial, 64 primary schools were randomly assigned 1:1 to receive either school-based targeted PC ("school arm") or community-wide MDA ("community arm"). A single dose of albendazole 400 mg was used for deworming. The primary outcome was hookworm prevalence in schoolchildren, measured using quantitative real-time PCR. We also measured infection intensity for Necator americanus only, using qPCR cycle threshold (Ct) values converted into eggs per gram of faeces (EPG). Analysis was by intention to treat. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000309189). Findings: The analysis included 4955 children in the school arm and 5093 children in the community arm. N. americanus was the dominant STH species. The relative reduction in hookworm prevalence was not significantly different between the school arm (30.1%, 95% confidence interval [CI] 20.5-36.9) and the community arm (34.6%, 95% CI 19.9-49.4). Due to lower baseline prevalence than expected, the study was underpowered to detect a difference in prevalence reduction between the study arms. The community arm showed significantly greater relative reduction in N. americanus infection intensity (56.0%, 95% CI 39.9-72.1) compared to the school arm (3.4%, 95% CI -24.7 to 31.4). The community arm also showed greater relative reduction in prevalence of moderate-to-heavy intensity (≥2000 EPG) N. americanus infections (81.1%; 95% CI 69.7-92.6) compared to the school arm (39.0%, 95% CI 13.7-64.2). Interpretation: Although no impact was seen on overall prevalence, community-wide MDA was more effective in lowering N. americanus infection intensity in schoolchildren compared to school-based targeted PC, measured 12 months after one round of albendazole deworming with high coverage. Funding: National Health and Medical Research Council, Australia (APP1139561).

Assessing the efficacy of albendazole against hookworm in Vietnam using quantitative PCR and sodium nitrate flotation.

Preventive chemotherapy (PC), consisting of the regular distribution of anthelmintics to populations or groups of populations at risk, is the primary tool used to control soil-transmitted helminth (STH) infections. This strategy, whilst cost-effective, raises the concern of potential emergence of drug resistance. The efficacy of anthelmintics against STH infections is measured using cure rate (CR) and egg reduction rate (ERR), using microscopy-based techniques such as the Kato-Katz thick smear. However, Kato-Katz has low sensitivity, especially for low-intensity infections, and requires fresh samples that need to be processed quickly. Realtime quantitative PCR (qPCR), which is more sensitive, is emerging as a "gold standard" for STH diagnostics given its higher sensitivity (important in low prevalence settings) and ability to differentiate hookworm species, while sodium nitrate flotation (SNF) may provide a low-cost more sensitive and practical alternative to Kato-Katz in the field. In this study, we examined the efficacy of a locally manufactured brand of albendazole 400 mg ("Alzental") against hookworm in Dak Lak province, Vietnam, using both qPCR and SNF. For qPCR, formulae to convert qPCR cycle threshold (Ct) values into eggs per gram of faeces (EPG) were utilised to determine efficacy calculations, and these values directly compared with efficacy values generated using SNF. Factors associated with CR and ERR were examined, and Alzental tablet quality was assessed by comparing with an Australian TGA-approved equivalent "Eskazole" tablet. We observed a CR and ERR of 64.9% and 87.5% respectively using qPCR, and 68.4% and 67.6% respectively using SNF. The tablet composition of Alzental was comparable to Eskazole in terms of active albendazole drug concentration with no evidence of impurities. This study demonstrates that the efficacy of Alzental against hookworm is within the range of previously reported studies for albendazole 400 mg. The study also demonstrates the value of qPCR and SNF as alternatives to standard Kato-Katz methodology for assessment of anthelmintic efficacy.

Improving Uptake and Sustainability of Sanitation Interventions in Timor-Leste: A Case Study.

Open defecation (OD) is still a significant public health challenge worldwide. In Timor-Leste, where an estimated 20% of the population practiced OD in 2017, increasing access and use of improved sanitation facilities is a government priority. Community-led total sanitation (CLTS) has become a popular strategy to end OD since its inception in 2000, but evidence on the uptake of CLTS and related interventions and the long-term sustainability of OD-free (ODF) communities is limited. This study utilized a mixed-methods approach, encompassing quantitative monitoring and evaluation data from water, sanitation, and hygiene (WASH) agencies, and semi-structured interviews with staff working for these organizations and the government Department of Environmental Health, to examine sanitation interventions in Timor-Leste. Recommendations from WASH practitioners on how sanitation strategies can be optimized to ensure ODF sustainability are presented. Whilst uptake of interventions is generally good in Timor-Leste, lack of consistent monitoring and evaluation following intervention delivery may contribute to the observed slippage back to OD practices. Stakeholder views suggest that long-term support and monitoring after ODF certification are needed to sustain ODF communities.

The prevalence of tuberculosis, malaria and soil-transmitted helminth infection in minority indigenous people of Southeast Asia and the Western Pacific: protocol for a systematic review and meta-analysis.

BACKGROUND: Infectious diseases such as tuberculosis (TB), malaria and soil-transmitted helminthiasis continue to impose a significant global health burden and socio-economic impact. Globally, minority indigenous people are disproportionately affected by poverty and are shown to experience a disparate burden of disease and poorer health outcomes than the comparative majority population. Despite these inequalities, countries rarely systematically compile epidemiological data disaggregated by ethnicity to enable the extent of the differential to be quantified. METHODS: The systematic review will be reported in accordance with The Preferred Reporting Items for Systematic Review and Meta- Analyses (PRISMA) guidelines. Systematic searches will be conducted in EMBASE, Medline, Scopus and Web of Science for studies reporting data which enable the prevalence of TB, malaria, and/or soil-transmitted helminth (STH) infections amongst minority indigenous populations within the Southeast Asia Region (SEAR) and Western Pacific Region (WPR) to be calculated. Where studies provide data on disease prevalence for both minority indigenous and other populations within the same study, a comparative analysis will be undertaken. In addition to a narrative synthesis, where sufficient data are available, a random-effects meta-analysis will be conducted to obtain a pooled estimate value for each disease/infection by country and mortality stratum. Heterogeneity between studies will be examined using the Cochran's Q test and quantitatively measured by the index of heterogeneity squared (I2) statistics. The methodological quality of the included studies will be assessed using a modified Newcastle-Ottawa Scale. DISCUSSION: This systematic review aims to analyse the available data on the prevalence of TB, malaria and STH infections within minority indigenous populations of the SEAR and WPR. REGISTRATION: Open Science Framework registration: osf.io/m6sqc.

Novel statistical approaches to identify risk factors for soil-transmitted helminth infection in Timor-Leste.

Soil-transmitted helminths (STHs) are parasitic intestinal worms that infect almost a fifth of the global population. Sustainable control of STHs requires understanding the complex interaction of factors contributing to transmission. Identifying risk factors has mainly relied on logistic regression models where the underlying assumption of independence between variables is not always satisfied. Previously demonstrated risk factors including water, sanitation and hygiene (WASH) access and behaviours, and socioeconomic status are intrinsically linked. Similarly, environmental factors including climate, soil and land attributes are often strongly correlated. Alternative methods such as recursive partitioning and Bayesian networks can handle correlated variables, but there are no published studies comparing these methods with logistic regression in the context of STH risk factor analysis. Baseline cross-sectional data from school-aged children in the (S)WASH-D for Worms study were used to compare risk factors identified from modelling the same data using three different statistical techniques. Outcomes of interest were infection with Ascaris spp. and any hookworm species (Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum). Mixed-effects logistic regression identified the fewest risk factors. Recursive partitioning identified the most WASH and demographic risk factors, while Bayesian networks identified the most environmental risk factors. Recursive partitioning produced classification trees that visualised potentially at-risk population sub-groups. Bayesian networks helped visualise relationships between variables and enabled interactive modelling of outcomes based on different scenarios for the predictor variables of interest. Model performance was similar across all techniques. Risk factors identified across all techniques were vegetation for Ascaris spp., and cleaning oneself with water after defecating for hookworm. This study adds to the limited body of evidence exploring alternative data modelling approaches in identifying risk factors for STH infections. Our findings suggest these approaches can provide novel insights for more robust interpretation.

Gender differences in the psychosocial experience of parents of children with cancer: a review of the literature.

OBJECTIVE: To build a descriptive literature base of investigated and identified gender differences in the psychosocial experience of parents of children with cancer, in order to guide future research in this area. METHODS: An extensive literature search was conducted using Medline, PsycINFO, CINAHL and EMBASE databases. Thirty papers were included in the review. Themes from these papers were identified, and on this basis, the review findings were grouped according to five main outcome categories: role perceptions, illness beliefs, psychological distress, coping strategies and perceptions of marital, family and child functioning. RESULTS: Few gender differences were found in perceptions of marital, family and child functioning. There was a tendency toward traditional gender roles in the division of parental tasks. Findings in relation to parent psychological distress and preferred coping strategies were mixed, with trends toward increased distress, more emotion-focused coping and greater social support-seeking in mothers. CONCLUSIONS: Further studies using longitudinal designs with solid theoretical groundings will provide valuable information on the unique psychosocial experiences of mothers and fathers throughout the child's illness, which may in turn guide the development of evidence-based interventions.