Lessons from scaling up urban sanitation development in Indonesia and Mozambique

Indonesia and Mozambique are very different in terms of geography, culture, income, population and the type of sanitation used – and other aspects of development. This paper looks at urban sanitation development over the last 10 years in both countries – and the similar aspects of their development. In particular it looks at what lead to achieving national leadership: the role played by gating solid data and evidence; sanitation development models and how the critical role of effective advocacy. It ends with an overview of unresolved shared challenges and asks if these important issues provide lessons learned for other countries too

Multidisciplinary Management of Disorders of Sex Development in Indonesia, a Prototype in Developing Country

Background : Disorder of sex development (DSD) patients require comprehensive management to improve quality of life. A standardized management protocol for patients in Indonesia is not yet available resulting in patients infrequently received a proper diagnosis. This study reported a multidisciplinary management DSD in Indonesia based on minimal diagnostic facilities and expertise in developing country.Objectives : The purpose of the study is to review the management of DSD patients in Indonesia relates to providing appropriate gender assignment and to improving patients quality of life.Methodology : We analyzed the records of DSD patient admitted to the division of Human Genetics Center for Biomedical Research (CEBIOR) Faculty of Medicine Diponegoro University, Semarang, Indonesia from May 2004 - December 2015. Data were collected and analyzed for physical examination, family pedigree karyotyping, hormonal assays and psychosocial. Other examination such as ultrasonography, Xray and Cytoscopy were also recorded for selected cases. Bimonthly, Sexual Adjustment Team (SAT) meeting was recorded.Results : From the total 617 DSD cases we found 426 cases (69,04 %) with 46, XY DSD, 117 cases (18,96%) with 46,XX DSD and 74 cases (12%) with sex chromosome DSD. Most of the patients in the group of 46, XY DSD are Unknown Male Undervirilization (UMU) with 256 cases (60.09%). As the majority cases of 46, XX DSD was Congenital Adrenal Hyperplasia with 81 cases (69.23%). The remaining cases were Androgen Action Disorder (AAD) with 140 cases (32.86%), 46, XY DSD Gonadal Dysgenesis with 30 cases (7.04%), Androgen Excess Disorders with 3 cases (2.56%), Defect of Mullerian Development with 19 cases (16,24%), 3 cases (2.56%) of Androgen Excess and 3 cases (2.56%) of 46, XX Gonadal Dysgenesis.Conclusion : Comprehensive management for DSD Patients help patient in diagnosis, gender assignment and support patient to improve quality of life. This multidisciplinary of DSD team is the only team in Indonesia that can be used as a model for other center in Indonesia as well as other developing countries with minimal diagnostic facilities

Safely Managed On-Site Sanitation: A National Assessment of Sanitation Services and Potential Fecal Exposure in Indonesia.

Sustainable Development Goal target 6.2 calls for universal access to adequate and equitable sanitation, setting a more ambitious standard for 'safely managed sanitation services'. On-site sanitation systems (e.g., septic tanks) are widely used in low- and middle-income countries (LMICs). However, the lack of indicators for assessing fecal exposure risks presents a barrier to monitoring safely managed services. Furthermore, geographic diversity and frequency of disasters require a more nuanced approach to risk-informed decision-making. Taking Indonesia as an example, the purpose of this paper is to provide insights into current status and practices for on-site sanitation services in the contexts of LMICs. Using a dataset from a national socio-economic survey (n = 295,155) coupled with village census (n = 83,931), we assessed (1) household sanitation practices across Indonesia stratified by city-level population density and meteorological factors, (2) factors associated with septic tank emptying practice, and (3) inequalities in potential fecal exposure as measured by population density and WASH access by wealth quintile. We found a high reliance on on-site sanitation facilities (80.0%), almost half of which are assumed to be 'uncontained' septic tanks and one in ten facilities discharging untreated waste directly into the environment. The most densely populated areas had the highest rates of septic tank emptying, though emptying rates were just 17.0%, while in the lowest population density group, emptying was rarely reported. Multivariate regression analysis demonstrated an association between flooding and drought occurrence and septic tank emptying practice. Higher groundwater usage for drinking among poorer households suggests unsafe sanitation may disproportionally affect the poor. Our study underscores the urgent need to strengthen the monitoring of on-site sanitation in LMICs by developing contextualized standards. Furthermore, the inequalities in potential fecal exposure require greater attention and tailored support mechanisms to ensure the poorest gain access to safely managed sanitation services

Co-developing evidence-informed adaptation actions for resilient citywide sanitation: Local government response to climate change in Indonesia

Already climate-related hazards are impacting sanitation systems in Indonesia and elsewhere, and climate models indicate these hazards are likely to increase in frequency and intensity. Without due attention, to maintain existing progress on Sustainable Development Goal 6’s target 6.2 and to increase it to meet ambitions for 2030 will be difficult. City governments need new forms of evidence to respond, as well as approaches to enable them to consider sufficient breadth of strategies to adapt effectively. This paper describes a co-production research process which engaged local governments in four cities in Indonesia experiencing different climate hazards. Local government engagement took place across three stages of (i) inception and design, (ii) participation as key informants and (iii) joint analysis and engagement on the findings. We adapted and simplified a risk prioritisation process based on current literature and employed a novel framework of a ‘climate resilient sanitation system’ to prompt articulation of current and proposed climate change adaptation response actions. In contrast to many current framings of climate resilience in sanitation that focus narrowly on technical responses, the results paint a rich picture of efforts needed by city governments across all domains, including planning, institutions, financing, infrastructure and management options, user awareness, water cycle management and monitoring and evaluation. Local government commitment and improved comprehension on the implications of climate change for sanitation service delivery were key outcomes arising from the co-production process. With strengthened policy and capacity building initiatives from national level, this foundation can be supported, and Indonesian city governments will be equipped to move forward with adaptation actions that protect on-going access to sanitation services, public health and the environment. </jats:p

Functional characterisation of novel NR5A1 variants reveals multiple complex roles in Disorders of Sex Development

Variants in the NR5A1 gene encoding SF1 have been described in a diverse spectrum of disorders of sex development (DSD). Recently, we reported the use of a targeted gene panel for DSD where we identified 15 individuals with a variant in NR5A1, nine of which are novel. Here, we examine the functional effect of these changes in relation to the patient phenotype. All novel variants tested had reduced trans-activational activity, while several had altered protein level, localization, or conformation. In addition, we found evidence of new roles for SF1 protein domains including a region within the ligand binding domain that appears to contribute to SF1 regulation of Mu¨llerian development. There was little correlation between the severity of the phenotype and the nature of the NR5A1 variant. We report two familial cases of NR5A1 deficiency with evidence of variable expressivity; we also report on individuals with oligogenic inheritance. Finally, we found that the nature of the NR5A1 variant does not inform patient outcomes (including pubertal androgenization and malignancy risk). This study adds nine novel pathogenic NR5A1 variants to the pool of diagnostic variants. It highlights a greater need for understanding the complexity of SF1 function and the additional factors that contribute

Meiotic genes in premature ovarian insufficiency: variants in HROB and REC8 as likely genetic causes

International audiencePremature ovarian insufficiency (POI), affecting 1 in 100 women, is characterised by loss of ovarian function associated with elevated gonadotropin, before the age of 40. In addition to infertility, patients face increased risk of comorbidities such as heart disease, osteoporosis, cancer and/or early mortality. We used whole exome sequencing to identify the genetic cause of POI in seven women. Each had biallelic candidate variants in genes with a primary role in DNA damage repair and/or meiosis. This includes two genes, REC8 and HROB, not previously associated with autosomal recessive POI. REC8 encodes a component of the cohesin complex and HROB encodes a factor that recruits MCM8/9 for DNA damage repair. In silico analyses, combined with concordant mouse model phenotypes support these as new genetic causes of POI. We also identified novel variants in MCM8, NUP107, STAG3 and HFM1 and a known variant in POF1B. Our study highlights the pivotal role of meiosis in ovarian function. We identify novel variants, consolidate the pathogenicity of variants previously considered of unknown significance, and propose HROB and REC8 variants as new genetic causes while exploring their link to pathogenesis

New insights into the genetic basis of premature ovarian insufficiency: Novel causative variants and candidate genes revealed by genomic sequencing

International audienceOvarian deficiency, including premature ovarian insufficiency (POI) and diminished ovarian reserve (DOR), represents one of the main causes of female infertility. POI is a genetically heterogeneous condition but current understanding of its genetic basis is far from complete, with the cause remaining unknown in the majority of patients. The genes that regulate DOR have been reported but the genetic basis of DOR has not been explored in depth. Both conditions are likely to lie along a continuum of degrees of decrease in ovarian reserve. We performed genomic analysis via whole exome sequencing (WES) followed by in silico analyses and functional experiments to investigate the genetic cause of ovarian deficiency in ten affected women. We achieved diagnoses for three of them, including the identification of novel variants in STAG3, GDF9, and FANCM. We identified potentially causative FSHR variants in another patient. This is the second report of biallelic GDF9 and FANCM variants, and, combined with functional support, validates these genes as bone fide autosomal recessive “POI genes”. We also identified new candidate genes, NRIP1, XPO1, and MACF1. These genes have been linked to ovarian function in mouse, pig, and zebrafish respectively, but never in humans. In the case of NRIP1, we provide functional support for the deleterious nature of the variant via SUMOylation and luciferase/β-galactosidase reporter assays. Our study provides multiple insights into the genetic basis of POI/DOR. We have further elucidated the involvement of GDF9, FANCM, STAG3 and FSHR in POI pathogenesis, and propose new candidate genes, NRIP1, XPO1, and MACF1, which should be the focus of future studies