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Measles is a highly contagious disease that results from infection with measles virus and is still responsible for more than 100 000 deaths every year, down from more than 2 million deaths annually before the introduction and widespread use of measles vaccine. Measles virus is transmitted by the respiratory route and illness begins with fever, cough, coryza, and conjunctivitis followed by a characteristic rash. Complications of measles affect most organ systems, with pneumonia accounting for most measles-associated morbidity and mortality. The management of patients with measles includes provision of vitamin A. Measles is best prevented through vaccination, and the major reductions in measles incidence and mortality have renewed interest in regional elimination and global eradication. However, urgent efforts are needed to increase stagnating global coverage with two doses of measles vaccine through advocacy, education, and the strengthening of routine immunisation systems. Use of combined measles-rubella vaccines provides an opportunity to eliminate rubella and congenital rubella syndrome. Ongoing research efforts, including the development of point-of-care diagnostics and microneedle patches, will facilitate progress towards measles elimination and eradication.

Measles is a highly contagious disease caused by measles virus and is one of the most devastating infectious diseases of man—measles was responsible for millions of deaths annually worldwide before the introduction of the measles vaccines. Remarkable progress in reducing the number of people dying from measles has been made through measles vaccination, with an estimated 164 000 deaths attributed to measles in 2008. This achievement attests to the enormous importance of measles vaccination to public health. However, this progress is threatened by failure to maintain high levels of measles vaccine coverage. Recent measles outbreaks in sub-Saharan Africa, Europe, and the USA show the ease with which measles virus can re-enter communities if high levels of population immunity are not sustained. The major challenges for continued measles control and eventual eradication will be logistical, financial, and the garnering of sufficient political will. These challenges need to be met to ensure that future generations of children do not die of measles.

The Ebola epidemic in West Africa has caused substantial morbidity and mortality. The outbreak has also disrupted health care services, including childhood vaccinations, creating a second public health crisis. We project that after 6 to 18 months of disruptions, a large connected cluster of children unvaccinated for measles will accumulate across Guinea, Liberia, and Sierra Leone. This pool of susceptibility increases the expected size of a regional measles outbreak from 127,000 to 227,000 cases after 18 months, resulting in 2000 to 16,000 additional deaths (comparable to the numbers of Ebola deaths reported thus far). There is a clear path to avoiding outbreaks of childhood vaccine-preventable diseases once the threat of Ebola begins to recede: an aggressive regional vaccination campaign aimed at age groups left unprotected because of health care disruptions.

Approximately 62,000 Zambian children are living with HIV. HIV care and treatment is generally more limited in rural areas, where a heavy reliance on rain-fed subsistence agriculture also places households at risk of food and water insecurity. We nested a mixed methods study with an explanatory sequential design in a clinical cohort of children and adolescents living with HIV (CHIV) in rural Zambia. We used validated questionnaires to assess household food and water insecurity and examined associations between indicators derived from those scales, household characteristics, and HIV treatment adherence and outcomes using log-binomial regression. We identified caregivers and older CHIV from food insecure households for in-depth interviews. Of 186 participants completing assessments, 72% lived in moderately or severely food insecure households and 2% in water insecure households. Food insecurity was more prevalent in households of lower socioeconomic status (80% vs. 59% for higher scores; p = 0.02) and where caregivers had completed primary (79%) vs. secondary school or higher (62%; p = 0.01). No other characteristics or outcomes were associated with food insecurity. Parents limited both the quality and quantity of foods they consumed to ensure food availability for their CHIV. Coping strategies included taking on piecework or gathering wild foods; livestock ownership was a potential buffer. Accessing sufficient clean water was less of a concern. During periods of drought or service interruption, participants travelled further for drinking water and accessed water for other purposes from alternative sources or reduced water use. Community contributions afforded some protection against service interruptions. Overall, while food insecurity was prevalent, strategies used by parents may have protected children from a measurable impact on HIV care or treatment outcomes. Reinforcing social protection programs by integrating livestock ownership and strengthening water infrastructure may further protect CHIV in the case of more extreme food or water system shocks.

Background As countries move towards or achieve measles elimination status, serosurveillance is an important public health tool. However, a major challenge of serosurveillance is finding a feasible, accurate, cost-effective, and high throughput assay to measure measles antibody concentrations and estimate susceptibility in a population. We conducted a systematic review to assess, characterize, and – to the extent possible – quantify the performance of measles IgG enzyme-linked assays (EIAs) compared to the gold standard, plaque reduction neutralization tests (PRNT). Methods We followed the PRISMA statement for a systematic literature search and methods for conducting and reporting systematic reviews and meta-analyses recommended by the Cochrane Screening and Diagnostic Tests Methods Group. We identified studies through PubMed and Embase electronic databases and included serologic studies detecting measles virus IgG antibodies among participants of any age from the same source population that reported an index (any EIA or multiple bead-based assays, MBA) and reference test (PRNT) using sera, whole blood, or plasma. Measures of diagnostic accuracy with 95% confidence intervals (CI) were abstracted for each study result, where reported. Results We identified 550 unique publications and identified 36 eligible studies for analysis. We classified studies as high, medium, or low quality; results from high quality studies are reported. Because most high quality studies used the Siemens Enzygnost EIA kit, we generate individual and pooled diagnostic accuracy estimates for this assay separately. Median sensitivity of the Enzygnost EIA was 92.1% [IQR = 82.3, 95.7]; median specificity was 96.9 [93.0, 100.0]. Pooled sensitivity and specificity from studies using the Enzygnost kit were 91.6 (95%CI: 80.7,96.6) and 96.0 (95%CI: 90.9,98.3), respectively. The sensitivity of all other EIA kits across high quality studies ranged from 0% to 98.9% with median (IQR) = 90.6 [86.6, 95.2]; specificity ranged from 58.8% to 100.0% with median (IQR) = 100.0 [88.7, 100.0]. Conclusions Evidence on the diagnostic accuracy of currently available measles IgG EIAs is variable, insufficient, and may not be fit for purpose for serosurveillance goals. Additional studies evaluating the diagnostic accuracy of measles EIAs, including MBAs, should be conducted among diverse populations and settings (e.g., vaccination status, elimination/endemic status, age groups).

Assessment of antiretroviral treatment programmes for HIV-infected children in sub-Saharan Africa is important to enable the development of effective care and improve treatment outcomes. We review the effectiveness of paediatric antiretroviral treatment programmes in sub-Saharan Africa and discuss the implications of these findings for the care and treatment of HIV-infected children in this region. Available reports indicate that programmes in sub-Saharan Africa achieve treatment outcomes similar to those in North America and Europe. However, progress in several areas is required to improve the care of HIV-infected children in sub-Saharan Africa. The findings emphasise the need for low-cost diagnostic tests that allow for earlier identification of HIV infection in infants living in sub-Saharan Africa, improved access to antiretroviral treatment programmes, including expansion of care into rural areas, and the integration of antiretroviral treatment programmes with other health-care services, such as nutritional support.

The Seeds of IgnoranceConsumption of betel nut, a carcinogen, has increased throughout the Asia–Pacific region. Many users begin chewing betel nut in adolescence and are unaware of its adverse effects.

Apicomplexa encompasses a large number of intracellular parasites infecting a wide range of animals. Cyclic nucleotide signaling is crucial for a variety of apicomplexan life stages and cellular processes. The cyclases and kinases that synthesize and respond to cyclic nucleotides (i.e., 3',5'-cyclic guanosine monophosphate and 3',5'-cyclic adenosine monophosphate) are highly conserved and essential throughout the parasite phylum. Growing evidence indicates that phosphodiesterases (PDEs) are also critical for regulating cyclic nucleotide signaling via cyclic nucleotide hydrolysis. Here, we discuss recent advances in apicomplexan PDE biology and opportunities for therapeutic interventions, with special emphasis on the major human apicomplexan parasite genera , , , and . In particular, we show a highly flexible repertoire of apicomplexan PDEs associated with a wide range of cellular requirements across parasites and lifecycle stages. Despite this phylogenetic diversity, cellular requirements of apicomplexan PDEs for motility, host cell egress, or invasion are conserved. However, the molecular wiring of associated PDEs is extremely malleable suggesting that PDE diversity and redundancy are key for the optimization of cyclic nucleotide turnover to respond to the various environments encountered by each parasite and life stage. Understanding how apicomplexan PDEs are regulated and integrating multiple signaling systems into a unified response represent an untapped avenue for future exploration.

Background Understanding temporal and spatial dynamics of malaria transmission will help to inform effective interventions and strategies in regions approaching elimination. Parasite genomics are increasingly used to monitor epidemiologic trends, including assessing residual transmission across seasons and importation of malaria into these regions. Methods In a low and seasonal transmission setting of southern Zambia, a total of 441 Plasmodium falciparum samples collected from 8 neighbouring health centres between 2012 and 2018 were genotyped using molecular inversion probes (MIPs n = 1793) targeting a total of 1832 neutral and geographically informative SNPs distributed across the parasite genome. After filtering for quality and missingness, 302 samples and 1410 SNPs were retained and used for downstream population genomic analyses. Results The analyses revealed most (67%, n = 202) infections harboured one clone (monogenomic) with some variation at local level suggesting low, but heterogenous malaria transmission. Relatedness identity-by-descent (IBD) analysis revealed variable distribution of IBD segments across the genome and 6% of pairs were highly-related (IBD ≥ 0.25). Some of the highly-related parasite populations persisted across multiple seasons, suggesting that persistence of malaria in this low-transmission region is fueled by parasites “seeding” across the dry season. For recent years, clusters of clonal parasites were identified that were dissimilar to the general parasite population, suggesting parasite populations were increasingly fragmented at small spatial scales due to intensified control efforts. Clustering analysis using PCA and t-SNE showed a lack of substantial parasite population structure. Conclusion Leveraging both genomic and epidemiological data provided comprehensive picture of fluctuations in parasite populations in this pre-elimination setting of southern Zambia over 7 years.

Measles is an infectious disease in humans caused by the measles virus (MeV). Before the introduction of an effective measles vaccine, virtually everyone experienced measles during childhood. Symptoms of measles include fever and maculopapular skin rash accompanied by cough, coryza and/or conjunctivitis. MeV causes immunosuppression, and severe sequelae of measles include pneumonia, gastroenteritis, blindness, measles inclusion body encephalitis and subacute sclerosing panencephalitis. Case confirmation depends on clinical presentation and results of laboratory tests, including the detection of anti-MeV IgM antibodies and/or viral RNA. All current measles vaccines contain a live attenuated strain of MeV, and great progress has been made to increase global vaccination coverage to drive down the incidence of measles. However, endemic transmission continues in many parts of the world. Measles remains a considerable cause of childhood mortality worldwide, with estimates that >100,000 fatal cases occur each year. Case fatality ratio estimates vary from <0.01% in industrialized countries to >5% in developing countries. All six WHO regions have set goals to eliminate endemic transmission of MeV by achieving and maintaining high levels of vaccination coverage accompanied by a sensitive surveillance system. Because of the availability of a highly effective and relatively inexpensive vaccine, the monotypic nature of the virus and the lack of an animal reservoir, measles is considered a candidate for eradication. Measles is an infectious disease caused by the measles virus. In this Primer, Rota et al. cover the pathophysiology and management options, with a focus on the strategies to eliminate endemic transmission of the measles virus by achieving a high level of vaccination coverage