Predictors of severity and prolonged hospital stay of viral acute respiratory infections (ARI) among children under five years in Burkina Faso, 2016-2019.

BACKGROUND: Viruses are the leading etiology of acute respiratory infections (ARI) in children. However, there is limited knowledge on drivers of severe acute respiratory infection (SARI) cases involving viruses. We aimed to identify factors associated with severity and prolonged hospitalization of viral SARI among children < 5 years in Burkina Faso. METHODS: Data were collected from four SARI sentinel surveillance sites during October 2016 through April 2019. A SARI case was a child < 5 years with an acute respiratory infection with history of fever or measured fever ≥ 38 °C and cough with onset within the last ten days, requiring hospitalization. Very severe ARI cases required intensive care or had at least one danger sign. Oropharyngeal/nasopharyngeal specimens were collected and analyzed by multiplex real-time reverse-transcription polymerase chain reaction (rRT-PCR) using FTD-33 Kit. For this analysis, we included only SARI cases with rRT-PCR positive test results for at least one respiratory virus. We used simple and multilevel logistic regression models to assess factors associated with very severe viral ARI and viral SARI with prolonged hospitalization. RESULTS: Overall, 1159 viral SARI cases were included in the analysis after excluding exclusively bacterial SARI cases (n = 273)very severe viral ARI cases were common among children living in urban areas (AdjOR = 1.3; 95% CI: 1.1-1.6), those < 3 months old (AdjOR = 1.5; 95% CI: 1.1-2.3), and those coinfected with Klebsiella pneumoniae (AdjOR = 1.9; 95% CI: 1.2-2.2). Malnutrition (AdjOR = 2.2; 95% CI: 1.1-4.2), hospitalization during the rainy season (AdjOR = 1.71; 95% CI: 1.2-2.5), and infection with human CoronavirusOC43 (AdjOR = 3; 95% CI: 1.2-8) were significantly associated with prolonged length of hospital stay (> 7 days). CONCLUSION: Younger age, malnutrition, codetection of Klebsiella pneumoniae, and illness during the rainy season were associated with very severe cases and prolonged hospitalization of SARI involving viruses in children under five years. These findings emphasize the need for preventive actions targeting these factors in young children.

Combining viral genetic and animal mobility network data to unravel peste des petits ruminants transmission dynamics in West Africa.

Peste des petits ruminants (PPR) is a deadly viral disease that mainly affects small domestic ruminants. This disease threaten global food security and rural economy but its control is complicated notably because of extensive, poorly monitored animal movements in infected regions. Here we combined the largest PPR virus genetic and animal mobility network data ever collected in a single region to improve our understanding of PPR endemic transmission dynamics in West African countries. Phylogenetic analyses identified the presence of multiple PPRV genetic clades that may be considered as part of different transmission networks evolving in parallel in West Africa. A strong correlation was found between virus genetic distance and network-related distances. Viruses sampled within the same mobility communities are significantly more likely to belong to the same genetic clade. These results provide evidence for the importance of animal mobility in PPR transmission in the region. Some nodes of the network were associated with PPRV sequences belonging to different clades, representing potential "hotspots" for PPR circulation. Our results suggest that combining genetic and mobility network data could help identifying sites that are key for virus entrance and spread in specific areas. Such information could enhance our capacity to develop locally adapted control and surveillance strategies, using among other risk factors, information on animal mobility.

Effectiveness of Trachomatous Trichiasis Case-identification Approaches in Ethiopia.

BACKGROUND: Trachoma control programs use multiple approaches to identify individuals with trachomatous trichiasis (TT). Evidence is limited regarding which approaches are most effective and cost-efficient. METHODS: We evaluated the effectiveness of two TT case-identification approaches in Ethiopia: community mobilization to encourage self-referral for centralized screening and house-to-house screenings conducted by case finders. We compared the number of true cases found per 1000 population and costs associated with case identification under each approach, stratified by villages that received one or multiple screening visits. RESULTS: We conducted screenings in 396 villages. In villages receiving one house-to-house visit, case finders identified 14,229 suspected cases, of whom 10,513 (73.9%) presented for TT confirmation. A median of 17.2% (interquartile range [IQR]: 9.1%-27.8%) of those presenting truly had TT (positive predictive value). In single-visit villages, the community mobilization approach yielded higher rates of confirmed cases than the house-to-house approach (1.5 [IQR: 1.1, 2.6] vs. 1.1 [IQR: 0.5, 1.9] cases per 1000 population), and the median cost of identifying a TT case was less ($5.59 vs. $31.18) using community mobilization than house-to-house. In multiple-visit villages, additional screening visits increased the median rate of confirmed cases to 2.5 per 1000 population in community mobilization villages, but the rate remained unchanged in house-to-house villages. CONCLUSIONS: Community mobilization-based TT case finding had a higher yield than house-to-house, at a substantially lower cost. Future research should examine whether additional tools to aid case finders in their diagnosis increases case-finding efficiency and accuracy and whether TT prevalence and surgical program duration impact case-finding success.

Estimated Effectiveness of JYNNEOS Vaccine in Preventing Mpox: A Multijurisdictional Case-Control Study - United States, August 19, 2022-March 31, 2023.

As of March 31, 2023, more than 30,000 monkeypox (mpox) cases had been reported in the United States in an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and transgender persons (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) was approved by the Food and Drug Administration (FDA) in 2019 for the prevention of smallpox and mpox via subcutaneous injection as a 2-dose series (0.5 mL per dose, administered 4 weeks apart) (2). To expand vaccine access, an Emergency Use Authorization was issued by FDA on August 9, 2022, for dose-sparing intradermal injection of JYNNEOS as a 2-dose series (0.1 mL per dose, administered 4 weeks apart) (3). Vaccination was available to persons with known or presumed exposure to a person with mpox (postexposure prophylaxis [PEP]), as well as persons at increased risk for mpox or who might benefit from vaccination (preexposure mpox prophylaxis [PrEP]) (4). Because information on JYNNEOS vaccine effectiveness (VE) is limited, a matched case-control study was conducted in 12 U.S. jurisdictions,† including nine Emerging Infections Program sites and three Epidemiology and Laboratory Capacity sites,§ to evaluate VE against mpox among MSM and transgender adults aged 18-49 years. During August 19, 2022-March 31, 2023, a total of 309 case-patients were matched to 608 control patients. Adjusted VE was 75.2% (95% CI = 61.2% to 84.2%) for partial vaccination (1 dose) and 85.9% (95% CI = 73.8% to 92.4%) for full vaccination (2 doses). Adjusted VE for full vaccination by subcutaneous, intradermal, and heterologous routes of administration was 88.9% (95% CI = 56.0% to 97.2%), 80.3% (95% CI = 22.9% to 95.0%), and 86.9% (95% CI = 69.1% to 94.5%), respectively. Adjusted VE for full vaccination among immunocompromised participants was 70.2% (95% CI = -37.9% to 93.6%) and among immunocompetent participants was 87.8% (95% CI = 57.5% to 96.5%). JYNNEOS is effective at reducing the risk for mpox. Because duration of protection of 1 versus 2 doses remains unknown, persons at increased risk for mpox exposure should receive the 2-dose series as recommended by the Advisory Committee on Immunization Practices (ACIP),¶ regardless of administration route or immunocompromise status.

Modeling Optimal Laboratory Testing Strategies for Bacterial Meningitis Surveillance in Africa.

Since 2010, the introduction of an effective serogroup A meningococcal conjugate vaccine has led to the near-elimination of invasive Neisseria meningitidis serogroup A disease in Africa's meningitis belt. However, a significant burden of disease and epidemics due to other bacterial meningitis pathogens remain in the region. High-quality surveillance data with laboratory confirmation is important to monitor circulating bacterial meningitis pathogens and design appropriate interventions, but complete testing of all reported cases is often infeasible. Here, we use case-based surveillance data from 5 countries in the meningitis belt to determine how accurately estimates of the distribution of causative pathogens would represent the true distribution under different laboratory testing strategies. Detailed case-based surveillance data was collected by the MenAfriNet surveillance consortium in up to 3 seasons from participating districts in 5 countries. For each unique country-season pair, we simulated the accuracy of laboratory surveillance by repeatedly drawing subsets of tested cases and calculating the margin of error of the estimated proportion of cases caused by each pathogen (the greatest pathogen-specific absolute error in proportions between the subset and the full set of cases). Across the 12 country-season pairs analyzed, the 95% credible intervals around estimates of the proportion of cases caused by each pathogen had median widths of ±0.13, ±0.07, and ±0.05, respectively, when random samples of 25%, 50%, and 75% of cases were selected for testing. The level of geographic stratification in the sampling process did not meaningfully affect accuracy estimates. These findings can inform testing thresholds for laboratory surveillance programs in the meningitis belt.

Health workers' perceptions and challenges in implementing meningococcal serogroup a conjugate vaccine in the routine childhood immunization schedule in Burkina Faso.

BACKGROUND: Meningococcal serogroup A conjugate vaccine (MACV) was introduced in 2017 into the routine childhood immunization schedule (at 15-18 months of age) in Burkina Faso to help reduce meningococcal meningitis burden. MACV was scheduled to be co-administered with the second dose of measles-containing vaccine (MCV2), a vaccine already in the national schedule. One year following the introduction of MACV, an assessment was conducted to qualitatively examine health workers' perceptions of MACV introduction, identify barriers to uptake, and explore opportunities to improve coverage. METHODS: Twelve in-depth interviews were conducted with different cadres of health workers in four purposively selected districts in Burkina Faso. Districts were selected to include urban and rural areas as well as high and low MCV2 coverage areas. Respondents included health workers at the following levels: regional health managers (n = 4), district health managers (n = 4), and frontline healthcare providers (n = 4). All interviews were recorded, transcribed, and thematically analyzed using qualitative content analysis. RESULTS: Four themes emerged around supply and health systems barriers, demand-related barriers, specific challenges related to MACV and MCV2 co-administration, and motivations and efforts to improve vaccination coverage. Supply and health systems barriers included aging cold chain equipment, staff shortages, overworked and poorly trained staff, insufficient supplies and financial resources, and challenges with implementing community outreach activities. Health workers largely viewed MACV introduction as a source of motivation for caregivers to bring their children for the 15- to 18-month visit. However, they also pointed to demand barriers, including cultural practices that sometimes discourage vaccination, misconceptions about vaccines, and religious beliefs. Challenges in co-administering MACV and MCV2 were mainly related to reluctance among health workers to open multi-dose vials unless enough children were present to avoid wastage. CONCLUSIONS: To improve effective administration of vaccines in the second-year of life, adequate operational and programmatic planning, training, communication, and monitoring are necessary. Moreover, clear policy communication is needed to help ensure that health workers do not refrain from opening multi-dose vials for small numbers of children.

Development and Implementation of a Cloud-Based Meningitis Surveillance and Specimen Tracking System in Burkina Faso, 2018.

Nationwide case-based meningitis surveillance was established in Burkina Faso following the introduction of meningococcal serogroup A conjugate vaccine in 2010. However, timely tracking and arrival of cerebrospinal fluid specimens for confirmation at national reference laboratories remained suboptimal. To better understand this gap and identify bottlenecks, the Burkina Faso Ministry of Health, along with key partners, developed and implemented a cloud-based System for Tracking Epidemiological Data and Laboratory Specimens (STELAB), allowing for timely nationwide data reporting and specimen tracking using barcodes. STELAB was adapted to Burkina Faso's infrastructure to ensure suitability, functionality, flexibility, and sustainability. We describe the design, development, and implementation of STELAB. In addition, we discuss strategies used to promote sustainability, lessons learned during the first year of implementation, and future directions. STELAB's novel design and country-driven approach has the potential to achieve sustainable real-time data reporting and specimen tracking for the first time in sub-Saharan Africa.

Implementation of Case-Based Surveillance and Real-time Polymerase Chain Reaction to Monitor Bacterial Meningitis Pathogens in Chad.

BACKGROUND: Meningococcal serogroup A conjugate vaccine (MACV) was introduced in Chad during 2011-2012. Meningitis surveillance has been conducted nationwide since 2003, with case-based surveillance (CBS) in select districts from 2012. In 2016, the MenAfriNet consortium supported Chad to implement CBS in 4 additional districts and real-time polymerase chain reaction (rt-PCR) at the national reference laboratory (NRL) to improve pathogen detection. We describe analysis of bacterial meningitis cases during 3 periods: pre-MACV (2010-2012), pre-MenAfriNet (2013-2015), and post-MenAfriNet (2016-2018). METHODS: National surveillance targeted meningitis cases caused by Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae. Cerebrospinal fluid specimens, inoculated trans-isolate media, and/or isolates from suspected meningitis cases were tested via culture, latex, and/or rt-PCR; confirmed bacterial meningitis was defined by a positive result on any test. We calculated proportion of suspected cases with a specimen received by period, and proportion of specimens with a bacterial meningitis pathogen identified, by period, pathogen, and test. RESULTS: The NRL received specimens for 6.8% (876/12813), 46.4% (316/681), and 79.1% (787/995) of suspected meningitis cases in 2010-2012, 2013-2015, and 2016-2018, respectively, with a bacterial meningitis pathogen detected in 33.6% (294/876), 27.8% (88/316), and 33.2% (261/787) of tested specimens. The number of N. meningitidis serogroup A (NmA) among confirmed bacterial meningitis cases decreased from 254 (86.4%) during 2010-2012 to 2 (2.3%) during 2013-2015, with zero NmA cases detected after 2014. In contrast, proportional and absolute increases were seen between 2010-2012, 2013-2015, and 2016-2018 in cases caused by S. pneumoniae (5.1% [15/294], 65.9% [58/88], and 52.1% [136/261]), NmX (0.7% [2/294], 1.1% [1/88], and 22.2% [58/261]), and Hib (0.3% [1/294], 11.4% [10/88], and 14.9% [39/261]). Of specimens received at the NRL, proportions tested during the 3 periods were 47.7% (418), 53.2% (168), and 9.0% (71) by latex; 81.4% (713), 98.4% (311), and 93.9% (739) by culture; and 0.0% (0), 0.0% (0), and 90.5% (712) by rt-PCR, respectively. During the post-MenAfriNet period (2016-2018), 86.1% (678) of confirmed cases were tested by both culture and rt-PCR, with 12.5% (85) and 32.4% (220) positive by culture and rt-PCR, respectively. CONCLUSIONS: CBS implementation was associated with increased specimen referral. Increased detection of non-NmA cases could reflect changes in incidence or increased sensitivity of case detection with rt-PCR. Continued surveillance with the use of rt-PCR to monitor changing epidemiology could inform the development of effective vaccination strategies.

Epidemiology of Bacterial Meningitis in the Nine Years Since Meningococcal Serogroup A Conjugate Vaccine Introduction, Niger, 2010-2018.

BACKGROUND: In 2010, Niger and other meningitis belt countries introduced a meningococcal serogroup A conjugate vaccine (MACV). We describe the epidemiology of bacterial meningitis in Niger from 2010 to 2018. METHODS: Suspected and confirmed meningitis cases from January 1, 2010 to July 15, 2018 were obtained from national aggregate and laboratory surveillance. Cerebrospinal fluid specimens were analyzed by culture and/or polymerase chain reaction. Annual incidence was calculated as cases per 100 000 population. Selected isolates obtained during 2016-2017 were characterized by whole-genome sequencing. RESULTS: Of the 21 142 suspected cases of meningitis, 5590 were confirmed: Neisseria meningitidis ([Nm] 85%), Streptococcus pneumoniae ([Sp] 13%), and Haemophilus influenzae ([Hi] 2%). No NmA cases occurred after 2011. Annual incidence per 100 000 population was more dynamic for Nm (0.06-7.71) than for Sp (0.18-0.70) and Hi (0.01-0.23). The predominant Nm serogroups varied over time (NmW in 2010-2011, NmC in 2015-2018, and both NmC and NmX in 2017-2018). Meningococcal meningitis incidence was highest in the regions of Niamey, Tillabery, Dosso, Tahoua, and Maradi. The NmW isolates were clonal complex (CC)11, NmX were CC181, and NmC were CC10217. CONCLUSIONS: After MACV introduction, we observed an absence of NmA, the emergence and continuing burden of NmC, and an increase in NmX. Niger's dynamic Nm serogroup distribution highlights the need for strong surveillance programs to inform vaccine policy.

Bacterial Meningitis Epidemiology in Five Countries in the Meningitis Belt of Sub-Saharan Africa, 2015-2017.

BACKGROUND: The MenAfriNet Consortium supports strategic implementation of case-based meningitis surveillance in key high-risk countries of the African meningitis belt: Burkina Faso, Chad, Mali, Niger, and Togo. We describe bacterial meningitis epidemiology in these 5 countries in 2015-2017. METHODS: Case-based meningitis surveillance collects case-level demographic and clinical information and cerebrospinal fluid (CSF) laboratory results. Neisseria meningitidis, Streptococcus pneumoniae, or Haemophilus influenzae cases were confirmed and N. meningitidis/H. influenzae were serogrouped/serotyped by real-time polymerase chain reaction, culture, or latex agglutination. We calculated annual incidence in participating districts in each country in cases/100 000 population. RESULTS: From 2015-2017, 18 262 suspected meningitis cases were reported; 92% had a CSF specimen available, of which 26% were confirmed as N. meningitidis (n = 2433; 56%), S. pneumoniae (n = 1758; 40%), or H. influenzae (n = 180; 4%). Average annual incidences for N. meningitidis, S. pneumoniae, and H. influenzae, respectively, were 7.5, 2.5, and 0.3. N. meningitidis incidence was 1.5 in Burkina Faso, 2.7 in Chad, 0.4 in Mali, 14.7 in Niger, and 12.5 in Togo. Several outbreaks occurred: NmC in Niger in 2015-2017, NmC in Mali in 2016, and NmW in Togo in 2016-2017. Of N. meningitidis cases, 53% were NmC, 30% NmW, and 13% NmX. Five NmA cases were reported (Burkina Faso, 2015). NmX increased from 0.6% of N. meningitidis cases in 2015 to 27% in 2017. CONCLUSIONS: Although bacterial meningitis epidemiology varied widely by country, NmC and NmW caused several outbreaks, NmX increased although was not associated with outbreaks, and overall NmA incidence remained low. An effective low-cost multivalent meningococcal conjugate vaccine could help further control meningococcal meningitis in the region.

Evaluation of the Impact of Meningococcal Serogroup A Conjugate Vaccine Introduction on Second-Year-of-Life Vaccination Coverage in Burkina Faso.

BACKGROUND: After successful meningococcal serogroup A conjugate vaccine (MACV) campaigns since 2010, Burkina Faso introduced MACV in March 2017 into the routine Expanded Programme for Immunization schedule at age 15-18 months, concomitantly with second-dose measles-containing vaccine (MCV2). We examined MCV2 coverage in pre- and post-MACV introduction cohorts to describe observed changes regionally and nationally. METHODS: A nationwide household cluster survey of children 18-41 months of age was conducted 1 year after MACV introduction. Coverage was assessed by verification of vaccination cards or recall. Two age groups were included to compare MCV2 coverage pre-MACV introduction (30-41 months) versus post-MACV introduction (18-26 months). RESULTS: In total, 15 925 households were surveyed; 7796 children were enrolled, including 3684 30-41 months of age and 3091 18-26 months of age. Vaccination documentation was observed for 86% of children. The MACV routine coverage was 58% (95% confidence interval [CI], 56%-61%) with variation by region (41%-76%). The MCV2 coverage was 62% (95% CI, 59%-65%) pre-MACV introduction and 67% (95% CI, 64%-69%) post-MACV introduction, an increase of 4.5% (95% CI, 1.3%-7.7%). Among children who received routine MACV and MCV2, 93% (95% CI, 91%-94%) received both at the same visit. Lack of caregiver awareness about the 15- to 18-month visit and vaccine unavailability were common reported barriers to vaccination. CONCLUSIONS: A small yet significant increase in national MCV2 coverage was observed 1 year post-MACV introduction. The MACV/MCV2 coadministration was common. Findings will help inform strategies to strengthen second-year-of-life immunization coverage, including to address the communication and vaccine availability barriers identified.

Improving Case-Based Meningitis Surveillance in 5 Countries in the Meningitis Belt of Sub-Saharan Africa, 2015-2017.

BACKGROUND: The MenAfriNet consortium was established in 2014 to support implementation of case-based meningitis surveillance in 5 countries in the meningitis belt of sub-Saharan Africa: Burkina Faso, Chad, Mali, Niger, and Togo. Assessing surveillance performance is critical for interpretation of the collected data and implementation of future surveillance-strengthening initiatives. METHODS: Detailed epidemiologic and laboratory data were collected on suspected meningitis cases through case-based meningitis surveillance in participating districts in 5 countries. Performance of case-based surveillance was evaluated through sensitivity of case ascertainment in case-based versus aggregate meningitis surveillance and an analysis of surveillance indicators. RESULTS: From 2015 to 2017, 18 262 suspected meningitis cases were identified through case-based surveillance and 16 262 were identified through aggregate surveillance, for a case ascertainment sensitivity of 112.3%. Among suspected cases, 16 885 (92.5%) had a cerebrospinal fluid (CSF) specimen collected, 13 625 (80.7%) of which were received at a national reference laboratory. Among these, 13 439 (98.6%) underwent confirmatory testing, and, of those tested, 4371 (32.5%) were confirmed for a bacterial pathogen. CONCLUSIONS: Overall strong performance for case ascertainment, CSF collection, and laboratory confirmation provide evidence for the quality of MenAfriNet case-based surveillance in evaluating epidemiologic trends and informing future vaccination strategies.

MenAfriNet: A Network Supporting Case-Based Meningitis Surveillance and Vaccine Evaluation in the Meningitis Belt of Africa.

Meningococcal meningitis remains a significant public health threat, especially in the African meningitis belt where Neisseria meningitidis serogroup A historically caused large-scale epidemics. With the rollout of a novel meningococcal serogroup A conjugate vaccine (MACV) in the belt, the World Health Organization recommended case-based meningitis surveillance to monitor MACV impact and meningitis epidemiology. In 2014, the MenAfriNet consortium was established to support strategic implementation of case-based meningitis surveillance in 5 key countries: Burkina Faso, Chad, Mali, Niger, and Togo. MenAfriNet aimed to develop a high-quality surveillance network using standardized laboratory and data collection protocols, develop sustainable systems for data management and analysis to monitor MACV impact, and leverage the surveillance platform to perform special studies. We describe the MenAfriNet consortium, its history, strategy, implementation, accomplishments, and challenges.

Human rabies post exposure prophylaxis at the Pasteur Institute of Dakar, Senegal: trends and risk factors.

BACKGROUND: Rabies remains a major public health problem in developing countries. Most fatal rabies cases, especially in children, result from dog bites and occur in low-income countries, such as those in Sub-Saharan Africa. Rabies can be controlled through mass dog vaccination and human deaths prevented through timely and appropriate post-exposure prophylaxis (PEP). As access to appropriate PEP remains a serious challenge for bite-victims, the aim of this study was to understand the use of PEP, to evaluate the knowledge, attitudes and practices with respect to rabies and to identify risk factors related to non-compliance with PEP to define recommendations for improving PEP in Senegal. METHODS: This study included patients with suspicion of rabies exposure who sought PEP at the Pasteur Institute of Dakar from April 2013 to March 2014. Patients with rabies clinical symptoms, those who had already started PEP and those with exposure outside Senegal or for more than 3 months were excluded. Data on risk factors and propensity to seek and complete PEP were collected using questionnaires and phone interviews. The association between acceptability and compliance with PEP and other independent variables were evaluated using multivariate regression analysis. RESULTS: Among the 905 patients enrolled into the study, 67% were male (sex ratio M/F, 2) and 46%, children under 15 years of age. Exposures by animal bites represented 87%, whereas the remainder were due to scratches or contact; 76% were classified as WHO category III and 88% were due to dogs. Among these patients, 7% refused to start PEP and 54.5% completed the full schedule. Main factors reported by non-compliant patients were vaccine costs and affordability, and knowledge on status of biting animal. CONCLUSION: This study shows that despite the awareness about rabies dangers and prevention, only half of the patients completed the full PEP schedule. The following recommendations, such as free of charge prophylaxis or intradermal regimens as an alternative to intramuscular regimens, should be considered to increase the adherence to PEP at the Pasteur Institute of Dakar and in Senegal.

Comparative evolutionary analyses of peste des petits ruminants virus genetic lineages.

Peste des petits ruminants virus (PPRV) causes a highly infectious disease affecting mainly goats and sheep in large parts of Africa, Asia, and the Middle East and has an important impact on the global economy and food security. Full genome sequencing of PPRV strains has proved to be critical to increasing our understanding of PPR epidemiology and to inform the ongoing global efforts for its eradication. However, the number of full PPRV genomes published is still limited and with a heavy bias towards recent samples and genetic Lineage IV (LIV), which is only one of the four existing PPRV lineages. Here, we generated genome sequences for twenty-five recent (2010-6) and seven historical (1972-99) PPRV samples, focusing mainly on Lineage II (LII) in West Africa. This provided the first opportunity to compare the evolutionary pressures and history between the globally dominant PPRV genetic LIV and LII, which is endemic in West Africa. Phylogenomic analysis showed that the relationship between PPRV LII strains was complex and supported the extensive transboundary circulation of the virus within West Africa. In contrast, LIV sequences were clearly separated per region, with strains from West and Central Africa branched as a sister clade to all other LIV sequences, suggesting that this lineage also has an African origin. Estimates of the time to the most recent common ancestor place the divergence of modern LII and LIV strains in the 1960s-80s, suggesting that this period was particularly important for the diversification and spread of PPRV globally. Phylogenetic relationships among historical samples from LI, LII, and LIII and with more recent samples point towards a high genetic diversity for all these lineages in Africa until the 1970s-80s and possible bottleneck events shaping PPRV's evolution during this period. Molecular evolution analyses show that strains belonging to LII and LIV have evolved under different selection pressures. Differences in codon usage and adaptative selection pressures were observed in all viral genes between the two lineages. Our results confirm that comparative genomic analyses can provide new insights into PPRV's evolutionary history and molecular epidemiology. However, PPRV genome sequencing efforts must be ramped up to increase the resolution of such studies for their use in the development of efficient PPR control and surveillance strategies.

Multiple cardiovascular risk factor care in 55 low- and middle-income countries: A cross-sectional analysis of nationally-representative, individual-level data from 280,783 adults.

The prevalence of multiple age-related cardiovascular disease (CVD) risk factors is high among individuals living in low- and middle-income countries. We described receipt of healthcare services for and management of hypertension and diabetes among individuals living with these conditions using individual-level data from 55 nationally representative population-based surveys (2009-2019) with measured blood pressure (BP) and diabetes biomarker. We restricted our analysis to non-pregnant individuals aged 40-69 years and defined three mutually exclusive groups (i.e., hypertension only, diabetes only, and both hypertension-diabetes) to compare individuals living with concurrent hypertension and diabetes to individuals with each condition separately. We included 90,086 individuals who lived with hypertension only, 11,975 with diabetes only, and 16,228 with hypertension-diabetes. We estimated the percentage of individuals who were aware of their diagnosis, used pharmacological therapy, or achieved appropriate hypertension and diabetes management. A greater percentage of individuals with hypertension-diabetes were fully diagnosed (64.1% [95% CI: 61.8-66.4]) than those with hypertension only (47.4% [45.3-49.6]) or diabetes only (46.7% [44.1-49.2]). Among the hypertension-diabetes group, pharmacological treatment was higher for individual conditions (38.3% [95% CI: 34.8-41.8] using antihypertensive and 42.3% [95% CI: 39.4-45.2] using glucose-lowering medications) than for both conditions jointly (24.6% [95% CI: 22.1-27.2]).The percentage of individuals achieving appropriate management was highest in the hypertension group (17.6% [16.4-18.8]), followed by diabetes (13.3% [10.7-15.8]) and hypertension-diabetes (6.6% [5.4-7.8]) groups. Although health systems in LMICs are reaching a larger share of individuals living with both hypertension and diabetes than those living with just one of these conditions, only seven percent achieved both BP and blood glucose treatment targets. Implementation of cost-effective population-level interventions that shift clinical care paradigm from disease-specific to comprehensive CVD care are urgently needed for all three groups, especially for those with multiple CVD risk factors.

Sequential Brain Perfusion Findings in a Case of Osmotic Demyelination Syndrome.

ABSTRACT: A 60-year-old man with chronic alcoholism for 30 years was admitted to the hospital for an acute alcoholic syndrome with global confusional state, cognitive disorders, and ataxia. MRI detected bilateral mamillary bodies T 2 hypersignal related to Wernicke encephalopathy. It was treated by oral thiamine supplementation with clinical improvement. Two months later, he was rehospitalized for rapidly progressive dementia symptoms. Brain perfusion scintigraphy revealed pontine hyperperfusion and right hippocampal hypoperfusion. One month after IV thiamine supplementation, brain perfusion scintigraphy showed normalization of perfusion abnormalities in the pons and right hippocampus, leading to the diagnosis of alcoholic-related osmotic demyelination syndrome.

Malignant hypercalcemia revealing a diffuse large B-cell lymphoma in a patient with a previous diagnosis of chronic myelomonocytic leukemia: An uncommon hematological coexistence.

A 76-year-old patient previously admitted to the cardiology department for replacement of a right ventricular lead on a double-chamber pacemaker was admitted to the internal medicine department 15 days after for bronchopneumopathy. His past medical history was relevant for Type 2 diabetes mellitus, heart failure due to dilated hypokinetic heart disease, transcatheter aortic valve implantation (TAVI), and chronic myelomonocytic leukemia (CMML-0) diagnosed in 2021. Twenty-four hours after admission, the patient's general condition deteriorated abruptly, with the onset of drowsiness and psychomotor retardation. Laboratory exams revealed hypercalcemia at 4.18 mmol/L. Intensive hydration, calcitonin, and zoledronic acid were initiated and the patient was transferred to the nephrology intensive care unit where he underwent two sessions of hemodialysis to normalize serum calcium levels before readmission to internal medicine. Laboratory exams revealed low parathyroid hormone, normal 1-25-OH vitamin D, and increased parathyroid hormone-related peptide. Thoracoabdominal and positron emission tomography (PET) scan showed diffuse abdominopelvic peritoneal carcinosis associated with low-grade pleural effusion and multiple supra- and sub-diaphragmatic adenopathies, leading to a search for a solid tumor. The patient's clinical condition worsened leading to a transfer to the intensive care unit. The biopsy of a peritoneal carcinosis nodule confirmed the diagnosis of diffuse large B-cell lymphoma. Specific treatments were unsuccessful and the patient expired.

Impact of malaria diagnostic choice on monitoring of Plasmodium falciparum prevalence estimates in the Democratic Republic of the Congo and relevance to control programs in high-burden countries.

Malaria programs rely upon a variety of diagnostic assays, including rapid diagnostic tests (RDTs), microscopy, polymerase chain reaction (PCR), and bead-based immunoassays (BBA), to monitor malaria prevalence and support control and elimination efforts. Data comparing these assays are limited, especially from high-burden countries like the Democratic Republic of the Congo (DRC). Using cross-sectional and routine data, we compared diagnostic performance and Plasmodium falciparum prevalence estimates across health areas of varying transmission intensity to illustrate the relevance of assay performance to malaria control programs. Data and samples were collected between March-June 2018 during a cross-sectional household survey across three health areas with low, moderate, and high transmission intensities within Kinshasa Province, DRC. Samples from 1,431 participants were evaluated using RDT, microscopy, PCR, and BBA. P. falciparum parasite prevalence varied between diagnostic methods across all health areas, with the highest prevalence estimates observed in Bu (57.4-72.4% across assays), followed by Kimpoko (32.6-53.2%), and Voix du Peuple (3.1-8.4%). Using latent class analysis to compare these diagnostic methods against an "alloyed gold standard," the most sensitive diagnostic method was BBA in Bu (high prevalence) and Voix du Peuple (low prevalence), while PCR diagnosis was most sensitive in Kimpoko (moderate prevalence). RDTs were consistently the most specific diagnostic method in all health areas. Among 9.0 million people residing in Kinshasa Province in 2018, the estimated P. falciparum prevalence by microscopy, PCR, and BBA were nearly double that of RDT. Comparison of malaria RDT, microscopy, PCR, and BBA results confirmed differences in sensitivity and specificity that varied by endemicity, with PCR and BBA performing best for detecting any P. falciparum infection. Prevalence estimates varied widely depending on assay type for parasite detection. Inherent differences in assay performance should be carefully considered when using community survey and surveillance data to guide policy decisions.

Diabetes risk and provision of diabetes prevention activities in 44 low-income and middle-income countries: a cross-sectional analysis of nationally representative, individual-level survey data.

BACKGROUND: The global burden of diabetes is rising rapidly, yet there is little evidence on individual-level diabetes prevention activities undertaken by health systems in low-income and middle-income countries (LMICs). Here we describe the population at high risk of developing diabetes, estimate diabetes prevention activities, and explore sociodemographic variation in these activities across LMICs. METHODS: We performed a pooled, cross-sectional analysis of individual-level data from nationally representative, population-based surveys conducted in 44 LMICs between October, 2009, and May, 2019. Our sample included all participants older than 25 years who did not have diabetes and were not pregnant. We defined the population at high risk of diabetes on the basis of either the presence of impaired fasting glucose (or prediabetes in countries with a haemoglobin A1c available) or overweight or obesity, consistent with the WHO Package of Essential Noncommunicable Disease Guidelines for type 2 diabetes management. We estimated the proportion of survey participants that were at high risk of developing diabetes based on this definition. We also estimated the proportion of the population at high risk that reported each of four fundamental diabetes prevention activities: physical activity counselling, weight loss counselling, dietary counselling, and blood glucose screening, overall and stratified by World Bank income group. Finally, we used multivariable Poisson regression models to evaluate associations between sociodemographic characteristics and these activities. FINDINGS: The final pooled sample included 145 739 adults (86 269 [59·2%] of whom were female and 59 468 [40·4%] of whom were male) across 44 LMICs, of whom 59 308 (40·6% [95% CI 38·5-42·8]) were considered at high risk of diabetes (20·6% [19·8-21·5] in low-income countries, 38·0% [37·2-38·9] in lower-middle-income countries, and 57·5% [54·3-60·6] in upper-middle-income countries). Overall, the reach of diabetes prevention activities was low at 40·0% (38·6-41·4) for physical activity counselling, 37·1% (35·9-38·4) for weight loss counselling, 42·7% (41·6-43·7) for dietary counselling, and 37·1% (34·7-39·6) for blood glucose screening. Diabetes prevention varied widely by national-level wealth: 68·1% (64·6-71·4) of people at high risk of diabetes in low-income countries reported none of these activities, whereas 49·0% (47·4-50·7) at high risk in upper-middle-income countries reported at least three activities. Educational attainment was associated with diabetes prevention, with estimated increases in the predicted probability of receipt ranging between 6·5 (3·6-9·4) percentage points for dietary fruit and vegetable counselling and 21·3 (19·5-23·2) percentage points for blood glucose screening, among people with some secondary schooling compared with people with no formal education. INTERPRETATION: A large proportion of individuals across LMICs are at high risk of diabetes but less than half reported receiving fundamental prevention activities overall, with the lowest receipt of these activities among people in low-income countries and with no formal education. These findings offer foundational evidence to inform future global targets for diabetes prevention and to strengthen policies and programmes to prevent continued increases in diabetes worldwide. FUNDING: Harvard T H Chan School of Public Health McLennan Fund: Dean's Challenge Grant Program and the EU's Research and Innovation programme Horizon 2020.