Heterozygous NOTCH1 Variants Cause CNS Immune Activation and Microangiopathy.

NOTCH1 belongs to the NOTCH family of proteins that regulate cell fate and inflammatory responses. Somatic and germline NOTCH1 variants have been implicated in cancer, Adams-Oliver syndrome, and cardiovascular defects. We describe 7 unrelated patients grouped by the presence of leukoencephalopathy with calcifications and heterozygous de novo gain-of-function variants in NOTCH1. Immunologic profiling showed upregulated CSF IP-10, a cytokine secreted downstream of NOTCH1 signaling. Autopsy revealed extensive leukoencephalopathy and microangiopathy with vascular calcifications. This evidence implicates that heterozygous gain-of-function variants in NOTCH1 lead to a chronic central nervous system (CNS) inflammatory response resulting in a calcifying microangiopathy with leukoencephalopathy. ANN NEUROL 2022;92:895-901.

Clinical seizure semiology is subtle and identification of seizures by parents is unreliable in infants with tuberous sclerosis complex.

OBJECTIVE: The objectives of this study were to assess the accuracy of parental seizure detection in infants with antenatally diagnosed tuberous sclerosis complex (TSC), and to document the total seizure burden (clinical and subclinical) in those patients who met criteria for prolonged electroencephalography (EEG) recording. METHODS: Consecutive infants at a single institution with antenatally diagnosed TSC who met criteria for prolonged video-EEG (vEEG) were recruited to this study. The vEEG data were reviewed and when a seizure was identified on EEG, the video and audio recording was assessed for evidence of clinical seizure and, if present, whether there was evidence of parent seizure identification. RESULTS: Nine infants were enrolled, for whom 674 focal seizures were identified in eight of nine patients across 24 prolonged vEEG recordings, with vEEG total duration of 634 h 49 min (average seizure frequency of 1 focal seizure/h). Only 220 of 674 (32.6%) were clinical seizures, 395 of 674 (58.6%) were subclinical seizures, and 59 of 674 seizures could not be classified. Only 63 of 220 clinical seizures (28.6%) were identified by parents, with 157 of 220 (71.4%) not identified. Thirty clusters of epileptic spasms were detected in one patient. At least one clinical epileptic spasm occurred in 2 of 30 clusters (6.7%), 24 of 30 clusters of epileptic spasms (80%) were electrographic only, and classification was uncertain for 4 of 30 clusters (13.3%). No clinical epileptic spasms were detected by parents. Clinical seizure frequency was significantly underestimated by parents for all patients. SIGNIFICANCE: This study demonstrates that in infants with TSC who met criteria for prolonged vEEG, (1) parents significantly under recognize total clinical seizure count, (2) parents fail to identify epileptic spasms, and (3) seizure frequency is high. This highlights that epilepsy treatment decisions should not be based solely on parental clinical seizure identification. Prolonged vEEG monitoring may have an important role in the routine epilepsy care of infants with TSC, as demonstrating undetected high clinical seizure frequency may allow improved epilepsy management decisions.

Extensive subcutaneous needle fragment retention due to injecting drug use.

Deaths in those with a history of injecting drug use commonly come to the attention of forensic pathologists, and therefore, one must have knowledge of possible findings and hazards of performing autopsies in these cases. This case demonstrates the finding of extensive retained broken needles in the subcutis of the arms and femoral region in a man with a long history of injecting drug use. While few or single broken needles are not uncommonly encountered, the multiplicity of needles in this case is noteworthy. We have demonstrated the findings both radiologically with PMCT and by conventional autopsy.

Lethal hemorrhage from iliac vein rupture complicating inferior vena cava thrombosis demonstrated by post-mortem CT angiography.

Spontaneous iliac vein rupture is a rare cause of retroperitoneal hemorrhage that may present to the forensic pathologist. It has been reported in association with venous thrombosis, anatomical variants such as May-Thurner syndrome, and as a complication of a long-term indwelling IVC filter. It has a female predominance and most often occurs due to rupture of the left iliac vein. This is the first report of the use of post-mortem computed tomography (PMCT) and post-mortem computed tomography angiography (PMCTA) as an adjunct to a conventional autopsy to diagnose rupture of the left iliac vein causing retroperitoneal hemorrhage arising as a complication of an inferior vena cava (IVC) thrombus. We discuss the use of PMCTA as a useful tool in the diagnosis of vascular injury and how it can be used to assist the forensic pathologist. The use of PMCT with PMCTA is an invaluable adjunct to conventional autopsy to diagnose the site of vascular rupture.

ANCA-Associated Vasculitis Following Pfizer-BioNTech COVID-19 Vaccine.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread around the world. As of the end of June 2021, there were approximately 181 million confirmed cases and more than 3.9 million deaths across the globe. The colossal impact of coronavirus disease 2019 (COVID-19) is driving the biggest vaccination campaign in human history. All 3 vaccines authorized for emergency use by the US Food and Drug Administration (Pfizer-BioNTech, Moderna, and Janssen/Johnson & Johnson) have been thoroughly studied and found to be safe and effective in preventing severe COVID-19 cases. While short-term side effects of COVID-19 vaccine resemble those of other vaccines, long-term side effects remain unknown. Rare side effects continue to surface as millions of people receive COVID-19 vaccines around the world, as compared with the thousands enrolled in the clinical trials. We report a case of new-onset renal-limited ANCA-associated vasculitis (AAV) in a 78-year-old woman with previously normal kidney function after receiving the Pfizer-BioNTech COVID-19 vaccine. The patient developed acute kidney injury with proteinuria and microscopic hematuria with many dysmorphic red blood cells in the urine. Anti-myeloperoxidase antibody titer was elevated. Kidney biopsy showed pauci-immune crescentic necrotizing glomerulonephritis. Kidney function improved after treatment with steroids and rituximab. Our patient had normal routine laboratory testing before the vaccination. Although this case cannot demonstrate a causal relationship between COVID-19 vaccination and AAV, ongoing surveillance for similar complications would be prudent as worldwide vaccination efforts continue.

Willingness-to-pay for long-lasting insecticide-treated bed nets: a discrete choice experiment with real payment in Ghana.

BACKGROUND: Expanding access to long-lasting insecticidal nets (LLINs) is difficult if one is limited to government and donor financial resources. Private commercial markets could play a larger role in the continuous distribution of LLINs by offering differentiated LLINs to middle-class Ghanaians. This population segment has disposable income and may be willing to pay for LLINs that meet their preferences. Measuring the willingness-to-pay (WTP) for LLINs with specialty features that appeal to middle-class Ghanaians could help malaria control programmes understand what is the potential for private markets to work alongside fully subsidized LLIN distribution channels to assist in spreading this commodity. METHODS: This study conducted a discrete choice experiment (DCE) including a real payment choice among a representative sample of 628 middle-income households living in Ashanti, Greater Accra, and Western regions in Ghana. The DCE presented 18 paired combinations of LLIN features and various prices. Respondents indicated which LLIN of each pair they preferred and whether they would purchase it. To validate stated willingness-to-pay, each participant was given a cash payment of $14.30 (GHS 65) that they could either keep or immediately spend on one of the LLIN products. RESULTS: The households' average probability of purchasing a LLIN with specialty features was 43.8% (S.D. 0.07) and WTP was $7.48 (GHS34.0). The preferred LLIN features were conical or rectangular one-point-hang shape, queen size, and zipper entry. The average WTP for a LLIN with all the preferred features was $18.48 (GHS 84). In a scenario with the private LLIN market, the public sector outlay could be reduced by 39% and private LLIN sales would generate $8.1 million ($311 per every 100 households) in revenue in the study area that would support jobs for Ghanaian retailers, distributors, and importers of LLINs. CONCLUSION: Results support a scenario in which commercial markets for LLINs could play a significant role in improving access to LLINs for middle-income Ghanaians. Manufacturers interested could offer LLIN designs with features that are most highly valued among middle-income households in Ghana and maintain a retail price that could yield sufficient economic returns.

A Prospective Study of Sudden Cardiac Death among Children and Young Adults.

BACKGROUND: Sudden cardiac death among children and young adults is a devastating event. We performed a prospective, population-based, clinical and genetic study of sudden cardiac death among children and young adults. METHODS: We prospectively collected clinical, demographic, and autopsy information on all cases of sudden cardiac death among children and young adults 1 to 35 years of age in Australia and New Zealand from 2010 through 2012. In cases that had no cause identified after a comprehensive autopsy that included toxicologic and histologic studies (unexplained sudden cardiac death), at least 59 cardiac genes were analyzed for a clinically relevant cardiac gene mutation. RESULTS: A total of 490 cases of sudden cardiac death were identified. The annual incidence was 1.3 cases per 100,000 persons 1 to 35 years of age; 72% of the cases involved boys or young men. Persons 31 to 35 years of age had the highest incidence of sudden cardiac death (3.2 cases per 100,000 persons per year), and persons 16 to 20 years of age had the highest incidence of unexplained sudden cardiac death (0.8 cases per 100,000 persons per year). The most common explained causes of sudden cardiac death were coronary artery disease (24% of cases) and inherited cardiomyopathies (16% of cases). Unexplained sudden cardiac death (40% of cases) was the predominant finding among persons in all age groups, except for those 31 to 35 years of age, for whom coronary artery disease was the most common finding. Younger age and death at night were independently associated with unexplained sudden cardiac death as compared with explained sudden cardiac death. A clinically relevant cardiac gene mutation was identified in 31 of 113 cases (27%) of unexplained sudden cardiac death in which genetic testing was performed. During follow-up, a clinical diagnosis of an inherited cardiovascular disease was identified in 13% of the families in which an unexplained sudden cardiac death occurred. CONCLUSIONS: The addition of genetic testing to autopsy investigation substantially increased the identification of a possible cause of sudden cardiac death among children and young adults. (Funded by the National Health and Medical Research Council of Australia and others.).

Measuring and characterizing night time human behaviour as it relates to residual malaria transmission in sub-Saharan Africa: a review of the published literature.

BACKGROUND: Malaria cases and deaths decreased dramatically in recent years, largely due to effective vector control interventions. Persistence of transmission after good coverage has been achieved with high-quality vector control interventions, namely insecticide-treated nets or indoor residual spraying, poses a significant challenge to malaria elimination efforts. To understand when and where remaining transmission is occurring, it is necessary to look at vector and human behaviour, and where they overlap. To date, a review of human behaviour related to residual malaria transmission has not been conducted. METHODS: Studies were identified through PubMed and Google Scholar. Hand searches were conducted for all references cited in articles identified through the initial search. The review was limited to English language articles published between 2000 and 2017. Publications with primary data from a malaria endemic setting in sub-Saharan Africa and a description of night time human behaviours were included. RESULTS: Twenty-six publications were identified that met inclusion criteria. Study results fit into two broad categories: when and where people are exposed to malaria vectors and what people are doing at night that may increase their contact with malaria vectors. Among studies that quantified human-vector interaction, a majority of exposure occurred indoors during sleeping hours for unprotected individuals, with some variation across time, contexts, and vector species. Common night time activities across settings included household chores and entertainment during evening hours, as well as livelihood and large-scale socio-cultural events that can last throughout the night. Shifting sleeping patterns associated with travel, visitors, illness, farming practices, and outdoor sleeping, which can impact exposure and use of prevention measures, were described in some locations. CONCLUSIONS: While the importance of understanding human-vector interaction is well-established, relatively few studies have included human behaviour when measuring exposure to malaria vectors. Broader application of a standardized approach to measuring human-vector interaction could provide critical information on exposure across settings and over time. In-depth understanding of night time activities that occur during times when malaria vectors are active and barriers to prevention practices in different contexts should also be considered. This information is essential for targeting existing interventions and development and deployment of appropriate complementary prevention tools.

Poverty and food security: drivers of insecticide-treated mosquito net misuse in Malawi.

BACKGROUND: Over the past decade, food insecurity, connected to erratic rains and reduced agricultural outputs, has plagued Malawi. Many households are turning to fishing to seek additional sources of income and food. There is anecdotal evidence that insecticide-treated net (ITN) recipients in Malawi are using their nets for purposes other than sleeping, such as for fishing, protecting crops, and displaying merchandise, among others. The objective of this qualitative study was to explore the factors leading residents of waterside communities in Malawi to use ITNs for fishing. METHODS: This study used qualitative and observational methods. Five waterside communities were identified, two each in the North, Central and Southern regions, representing a mix of lakeside and riverside settings. Fifteen focus group discussions were conducted with a total of 146 participants, including men, women, and community leaders. RESULTS: Respondents stated that they knew that ITNs should be slept under to protect from malaria. Respondents discussed financial hardships their communities were facing due to droughts, poverty, food scarcity, unemployment, and devaluation of the Malawian currency, the kwacha. Many described selling household goods, including clothes and cooking pots, to generate short-term income for their family. Though no respondents admitted to selling an ITN themselves, the practice was commonly known. Participants said that food shortages were forcing them to make difficult choices. Fishing with ITNs was reported to be common in the study sites, as a response to food insecurity, and was widely understood to be harmful over the longer term. Respondents felt that it was everyone's responsibility to cut down on this practice, but that efforts to confiscate or burn nets and boats of those caught fishing with ITNs were counter-productive since boats, especially, were a required resource for a productive livelihood. Respondents feared that if the health workers, government officials and donors continued to see ITNs being misused for fishing, the distribution of free ITNs would end, which would worsen malaria in their communities. CONCLUSIONS: Faced with economic hardships and food security crises, participants reported being forced to look for alternative incomes to feed their families. This sometimes included selling or repurposing their belongings, including ITNs, for income. This issue is complex and will require a community-led multisectoral response to preserve health, fisheries, and livelihoods.

Who buys nets? Factors associated with ownership and use of purchased mosquito nets in sub-Saharan Africa.

BACKGROUND: Public sector strategies to promote insecticide-treated net (ITN) access have resulted in increased ITN ownership across sub-Saharan Africa. However, the current status of the private sector distribution channel for nets has not been fully explored. This multi-country study explored the prevalence of net purchases and the characteristics of households that had purchased nets and used such nets in sub-Saharan Africa. METHODS: Data from recent Malaria Indicator Survey (MIS) or Demographic and Health Survey (DHS) in 16 countries were analysed to explore the prevalence of purchased nets. Purchased nets were defined as nets obtained from shops/markets or pharmacies. Additional sub-analysis of factors associated with ownership and use of purchased nets was conducted in seven countries with over 10% of nets reported as purchased. Key outcomes included: prevalence of purchased nets out of all nets, household ownership of a purchased net, and whether a purchased net was used the previous night. Analytical methods included country level tests of association and multivariable logistic regressions. RESULTS: Among all nets, the proportion of purchased nets in the study countries ranged from 0.8 to 32.7% and most (median = 77%) of these purchased nets were ITNs. Although the private nets are presumed to be from the retail, non-public sector, the prevalence of treated purchased nets suggests that some purchased nets may be "leaked" ITNs from public sector distributions, and thus, may be an informal sector rather than part of the formal "private sector". Urban, wealthier households as well as those with educated heads were more likely to own purchased nets. Use of such nets was, however, lower in wealthier households. In addition, net use was higher in households owning insufficient nets for their family size, and when the nets were newer than 24 months. CONCLUSION: The formal and informal private sector have played a role in bolstering net access rates in some settings. Study findings can help relevant malaria control stakeholders gain insight on the contribution of purchased nets on their overall ITN strategy, identify potential target populations for private sector nets as well as inform the design and distribution of private sector insecticide-treated nets that appeal to their target groups.

Human behaviour and residual malaria transmission in Zanzibar: findings from in-depth interviews and direct observation of community events.

BACKGROUND: Zanzibar has maintained malaria prevalence below 1% for the past decade, yet elimination remains elusive despite high coverage of core vector control interventions. As part of a study investigating the magnitude and drivers of residual transmission in Zanzibar, qualitative methods were utilized to better understand night time activities and sleeping patterns, individual and community-level risk perceptions, and malaria prevention practices. METHODS: A total of 62 in-depth interviews were conducted with community members and local leaders across six sites on Unguja Island, Zanzibar. Twenty semi-structured community observations of night-time activities and special events were conducted to complement interview findings. Data were transcribed verbatim, coded, and analysed using a thematic approach. RESULTS: Participants reported high levels of ITN use, but noted gaps in protection, particularly when outdoors or away from home. Routine household and community activities were common in evenings before bed and early mornings, while livelihood activities and special events lasted all or most of the night. Gender variation was reported, with men routinely spending more time away from home than women and children. Outdoor sleeping was reported during special events, such as weddings, funerals, and religious ceremonies. Participants described having difficulty preventing mosquito bites while outdoors, travelling, or away from home, and perceived higher risk of malaria infection during these times. Travel and migration emerged as a crucial issue and participants viewed seasonal workers coming from mainland Tanzania as more likely to have a malaria infection and less likely to be connected to prevention and treatment services in Zanzibar. Some community leaders reported taking the initiative to register seasonal workers coming into their community and linking them to testing and treatment services. CONCLUSIONS: Targeting malaria interventions effectively is critical and should be informed by a clear understanding of relevant human behaviour. These findings highlight malaria prevention gaps in Zanzibar, and the importance of identifying new approaches to complement current interventions and accelerate the final phases of malaria elimination. Development and deployment of complementary interventions should consider human behaviour, including gender norms, that can influence exposure to malaria vectors and prevention practices. Expansion of community-level programmes targeting travellers and seasonal workers should also be explored.

Joint European Society of Paediatric Radiology (ESPR) and International Society for Forensic Radiology and Imaging (ISFRI) guidelines: paediatric postmortem computed tomography imaging protocol.

Postmortem CT for investigating childhood deaths is increasingly utilised as a noninvasive adjunct or alternative to standard autopsy; however there are no standardised published imaging protocols. This article describes a standardised imaging protocol that has been developed based on current practices of international postmortem imaging practitioners and experts. This recommendation is expected to be useful for postmortem imaging centres wishing to update their existing practices and for those starting paediatric postmortem CT as a new service.

Reviewing the cost-effectiveness of long-acting reversible contraceptive methods in an Australian context.

BACKGROUND: Relative to the oral contraceptive pill, uptake of long-acting reversible contraceptive methods (LARCs) in Australia continues to be lower than might be suggested by the evidence on their clinical and economic benefits. AIM: To undertake a critical appraisal of published economic evaluations of LARCs to assess the generalisability of their results to the Australian healthcare context. MATERIALS AND METHODS: A search of the literature was conducted to identify studies of economic evaluations of LARCs using the Medline, Embase and PubMed databases. The quality of the studies was evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: A total of 1009 citations were screened, from which 20 papers, typically reporting the cost per pregnancy avoided, were reviewed. The overall quality of the studies varied but was generally poor (average score of 62/100). To aid comparisons, results have been grouped under the headings IUS (all hormonal intrauterine systems), IUDs (all non-hormonal intrauterine devices), injectables (all contraceptive injections) and implants (all subdermal contraceptive implants). Overall, the results indicated that LARCs were more effective and less costly than oral contraceptives. CONCLUSIONS: Despite evidence that LARCs represent value for money, limitations in study quality and approaches must be taken into account when applying these results to Australia. Differences in healthcare settings aside, LARCs may also have benefits beyond their effect on pregnancy that might be captured in broader analyses, such as cost-benefit analyses using willingness to pay methods. These would capture benefits beyond health, which seem to be particularly relevant to contraception.

PGC1α in the kidney.

Acute kidney injury (AKI) arising from diverse etiologies is characterized by mitochondrial dysfunction. The peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC1α), a master regulator of mitochondrial biogenesis, has been shown to be protective in AKI. Interestingly, reduction of PGC1α has also been implicated in the development of diabetic kidney disease and renal fibrosis. The beneficial renal effects of PGC1α make it a prime target for therapeutics aimed at ameliorating AKI, forms of chronic kidney disease (CKD), and their intersection. This review summarizes the current literature on the relationship between renal health and PGC1α and proposes areas of future interest.

Age and gender trends in insecticide-treated net use in sub-Saharan Africa: a multi-country analysis.

BACKGROUND: The degree to which insecticide-treated net (ITN) supply accounts for age and gender disparities in ITN use among household members is unknown. This study explores the role of household ITN supply in the variation in ITN use among household members in sub-Saharan Africa. METHODS: Data was from Malaria Indicator Surveys or Demographic and Health Surveys collected between 2011 and 2016 from 29 countries in sub-Saharan Africa. The main outcome was ITN use the previous night. Other key variables included ITN supply (nets/household members), age and gender of household members. Analytical methods included logistic regressions and meta-regression. RESULTS: Across countries, the median (range) of the percentage of households with enough ITNs was 30.7% (8.5-62.0%). Crude analysis showed a sinusoidal pattern in ITN use across age groups of household members, peaking at 0-4 years and again around 30-40 years and dipping among people between 5-14 and 50+ years. This sinusoidal pattern was more pronounced in households with not enough ITNs compared to those with enough ITNs. ITN use tended to be higher in females than males in households with not enough ITNs while use was comparable among females and males in households with enough ITNs. After adjusting for wealth quintile, residence and region, among households with not enough ITNs in all countries, the odds of ITN use were consistently higher among children under 5 years and non-pregnant women 15-49 years. Meta-regressions showed that across all countries, the mean adjusted odds ratio (aOR) of ITN use among children under 5 years, pregnant and non-pregnant women aged 15-49 years and people 50 years and above was significantly higher than among men aged 15-49 years. Among these household members, the relationship was attenuated when there were enough ITNs in the household (dropping 0.26-0.59 points) after adjusting for geographical zone, household ITN supply, population ITN access, and ITN use:access ratio. There was no significant difference in mean aOR of ITN use among school-aged children compared to men aged 15-49 years, regardless of household ITN supply. CONCLUSIONS: This study demonstrated that having enough ITNs in the household increases level of use and decreases existing disparities between age and gender groups. ITN distribution via mass campaigns and continuous distribution channels should be enhanced as needed to ensure that households have enough ITNs for all members, including men and school-aged children.

Assessing whether universal coverage with insecticide-treated nets has been achieved: is the right indicator being used?

BACKGROUND/METHODS: Insecticide-treated nets (ITNs) are the primary tool for malaria vector control in sub-Saharan Africa, and have been responsible for an estimated two-thirds of the reduction in the global burden of malaria in recent years. While the ultimate goal is high levels of ITN use to confer protection against infected mosquitoes, it is widely accepted that ITN use must be understood in the context of ITN availability. However, despite nearly a decade of universal coverage campaigns, no country has achieved a measured level of 80% of households owning 1 ITN for 2 people in a national survey. Eighty-six public datasets from 33 countries in sub-Saharan Africa (2005-2017) were used to explore the causes of failure to achieve universal coverage at the household level, understand the relationships between the various ITN indicators, and further define their respective programmatic utility. RESULTS: The proportion of households owning 1 ITN for 2 people did not exceed 60% at the national level in any survey, except in Uganda's 2014 Malaria Indicator Survey (MIS). At 80% population ITN access, the expected proportion of households with 1 ITN for 2 people is only 60% (p = 0.003 R2 = 0.92), because individuals in households with some but not enough ITNs are captured as having access, but the household does not qualify as having 1 ITN for 2 people. Among households with 7-9 people, mean population ITN access was 41.0% (95% CI 36.5-45.6), whereas only 6.2% (95% CI 4.0-8.3) of these same households owned at least 1 ITN for 2 people. On average, 60% of the individual protection measured by the population access indicator is obscured when focus is put on the household "universal coverage" indicator. The practice of limiting households to a maximum number of ITNs in mass campaigns severely restricts the ability of large households to obtain enough ITNs for their entire family. CONCLUSIONS: The two household-level indicators-one representing minimal coverage, the other only 'universal' coverage-provide an incomplete and potentially misleading picture of personal protection and the success of an ITN distribution programme. Under current ITN distribution strategies, the global malaria community cannot expect countries to reach 80% of households owning 1 ITN for 2 people at a national level. When programmes assess the success of ITN distribution activities, population access to ITNs should be considered as the better indicator of "universal coverage," because it is based on people as the unit of analysis.

Effectiveness and equity of the Tanzania National Voucher Scheme for mosquito nets over 10 years of implementation.

BACKGROUND: The Tanzania National Voucher Scheme (TNVS) was a public private partnership managed by the Ministry of Health that provided pregnant women and infants with highly subsidized (long-lasting) insecticide-treated nets between 2004 and 2014. It was implemented in the context of the National Insecticide Treated Nets (NATNETS) Programme and was the main keep up strategy for vulnerable populations. CASE DESCRIPTION: The programme design was adjusted considerably over time to incorporate new evidence, shifting public health policies, and changing donor priorities. Three TNVS models can be distinguished: (1) the fixed discount; (2) the fixed top-up; (3) the hybrid voucher model. The changes improved equity and effectiveness, but also had a profound effect on how the programme was managed and implemented. RESULTS: The TNVS reached the majority of beneficiaries with vouchers, and significantly increased household ownership and use of LLINs. While two mass distribution campaigns implemented between 2009 and 2011 achieved universal coverage and equity, the TNVS ensured continuous protection of the vulnerable populations before, during and after the campaigns. The TNVS stimulated and maintained a large national retail network which managed the LLIN supply chain. DISCUSSION AND LESSONS LEARNED: The effectiveness of the TNVS was a function of several interdependent factors, including the supply chain of vouchers through the public health system; the supply chain of nets in the commercial sector; the demand for nets from voucher recipients; management and risk mitigation measures; and the influence of global and donor objectives. CONCLUSION: The TNVS was a highly innovative and globally influential programme, which stimulated the thinking around effectively and equitably distributing ITNs, and contributed directly to the evolution of global policy. It was a fundamental component of the NATNETS programme which protected a malaria-vulnerable population for over a decade.

Evaluation of community-based continuous distribution of long-lasting insecticide-treated nets in Toamasina II District, Madagascar.

BACKGROUND: Continuous distribution of insecticide-treated nets (ITNs) is thought to be an effective mechanism to maintain ITN ownership and access between or in the absence of mass campaigns, but evidence is limited. A community-based ITN distribution pilot was implemented and evaluated in Toamasina II District, Madagascar, to assess this new channel for continuous ITN distribution. METHODS: Beginning 9 months after the December 2012 mass campaign, a community-based distribution pilot ran for an additional 9 months, from September 2013 to June 2014. Households requested ITN coupons from community agents in their village. After verification by the agents, households exchanged the coupon for an ITN at a distribution point. The evaluation was a two-stage cluster survey with a sample size of 1125 households. Counterfactual ITN ownership and access were calculated by excluding ITNs received through the community pilot. RESULTS: At the end of the pilot, household ownership of any ITN was 96.5%, population access to ITN was 81.5 and 61.5% of households owned at least 1 ITN for every 2 people. Without the ITNs provided through the community channel, household ownership of any ITN was estimated at 74.6%, population access to an ITN at 55.5%, and households that owned at least 1 ITN for 2 people at only 34.7%, 18 months after the 2012 campaign. Ownership of community-distributed ITNs was higher among the poorest wealth quintiles. Over 80% of respondents felt the community scheme was fair and simple to use. CONCLUSIONS: Household ITN ownership and population ITN access exceeded RBM targets after the 9-month community distribution pilot. The pilot successfully provided coupons and ITNs to households requesting them, particularly for the least poor wealth quintiles, and the scheme was well-perceived by communities. Further research is needed to determine whether community-based distribution can sustain ITN ownership and access over the long term, how continuous availability of ITNs affects household net replacement behaviour, and whether community-based distribution is cost-effective when combined with mass campaigns, or if used with other continuous channels instead of mass campaigns.