Highlights One out of two children missed routine immunizations during COVID-19 lockdown in Sindh. COVID-19 lockdown disproportionately affected coverage rates across the districts. Drop in the number of immunizations was higher in rural areas followed by urban slums. Expanding pool of un-immunized children is bringing down herd immunity and raising the risk of vaccine-preventable disease outbreaks.

Laith Abu-Raddad and colleagues assess the current state of knowledge of the HIV epidemic among people who inject drugs in the Middle East and North Africa. Please see later in the article for the Editors' Summary

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Neu-Laxova syndrome (NLS) is a rare autosomal-recessive disorder characterized by a recognizable pattern of severe malformations leading to prenatal or early postnatal lethality. Homozygous mutations in PHGDH, a gene involved in the first and limiting step in L-serine biosynthesis, were recently identified as the cause of the disease in three families. By studying a cohort of 12 unrelated families affected by NLS, we provide evidence that NLS is genetically heterogeneous and can be caused by mutations in all three genes encoding enzymes of the L-serine biosynthesis pathway. Consistent with recently reported findings, we could identify PHGDH missense mutations in three unrelated families of our cohort. Furthermore, we mapped an overlapping homozygous chromosome 9 region containing PSAT1 in four consanguineous families. This gene encodes phosphoserine aminotransferase, the enzyme for the second step in L-serine biosynthesis. We identified six families with three different missense and frameshift PSAT1 mutations fully segregating with the disease. In another family, we discovered a homozygous frameshift mutation in PSPH, the gene encoding phosphoserine phosphatase, which catalyzes the last step of L-serine biosynthesis. Interestingly, all three identified genes have been previously implicated in serine-deficiency disorders, characterized by variable neurological manifestations. Our findings expand our understanding of NLS as a disorder of the L-serine biosynthesis pathway and suggest that NLS represents the severe end of serine-deficiency disorders, demonstrating that certain complex syndromes characterized by early lethality could indeed be the extreme end of the phenotypic spectrum of already known disorders.

Background Sustainable Development Goal (SDG) 3 aims to "ensure healthy lives and promote well-being for all at all ages". While a substantial effort has been made to quantify progress towards SDG3, less research has focused on tracking spending towards this goal. We used spending estimates to measure progress in financing the priority areas of SDG3, examine the association between outcomes and financing, and identify where resource gains are most needed to achieve the SDG3 indicators for which data are available. MethodsWe estimated domestic health spending, disaggregated by source (government, out-of-pocket, and prepaid private) from 1995 to 2017 for 195 countries and territories. For disease-specific health spending, we estimated spending for HIV/AIDS and tuberculosis for 135 low-income and middle-income countries, and malaria in 106 malaria-endemic countries, from 2000 to 2017. We also estimated development assistance for health (DAH) from 1990 to 2019, by source, disbursing development agency, recipient, and health focus area, including DAH for pandemic preparedness. Finally, we estimated future health spending for 195 countries and territories from 2018 until 2030. We report all spending estimates in inflation-adjusted 2019 US$, unless otherwise stated. FindingsSince the development and implementation of the SDGs in 2015, global health spending has increased, reaching $7•9 trillion (95% uncertainty interval 7•8-8•0) in 2017 and is expected to increase to $11•0 trillion (10•7-11•2) by 2030. In 2017, in low-income and middle-income countries spending on HIV/AIDS was $20•2 billion (17•0-25•0) and on tuberculosis it was $10•9 billion (10•3-11•8), and in malaria-endemic countries spending on malaria was $5•1 billion (4•9-5•4). Development assistance for health was $40•6 billion in 2019 and HIV/AIDS has been the health focus area to receive the highest contribution since 2004. In 2019, $374 million of DAH was provided for pandemic preparedness, less than 1% of DAH. Although spending has increased across HIV/AIDS, tuberculosis, and malaria since 2015, spending has not increased in all countries, and outcomes in terms of prevalence, incidence, and per-capita spending have been mixed. The proportion of health spending from pooled sources is expected to increase from 81•6% (81•6-81•7) in 2015 to 83•1% (82•8-83•3) in 2030.Interpretation Health spending on SDG3 priority areas has increased, but not in all countries, and progress towards meeting the SDG3 targets has been mixed and has varied by country and by target. The evidence on the scale-up of spending and improvements in health outcomes suggest a nuanced relationship, such that increases in spending do not always results in improvements in outcomes. Although countries will probably need more resources to achieve SDG3, other constraints in the broader health system such as inefficient allocation of resources across interventions and populations, weak governance systems, human resource shortages, and drug shortages, will also need to be addressed.Funding The Bill & ...