Novel Z-DNA binding domains in giant viruses.

Z-nucleic acid structures play vital roles in cellular processes and have implications in innate immunity due to their recognition by Zα domains containing proteins (Z-DNA/Z-RNA binding proteins, ZBPs). Although Zα domains have been identified in six proteins, including viral E3L, ORF112, and I73R, as well as, cellular ADAR1, ZBP1, and PKZ, their prevalence across living organisms remains largely unexplored. In this study, we introduce a computational approach to predict Zα domains, leading to the revelation of previously unidentified Zα domain-containing proteins in eukaryotic organisms, including non-metazoan species. Our findings encompass the discovery of new ZBPs in previously unexplored giant viruses, members of the Nucleocytoviricota phylum. Through experimental validation, we confirm the Zα functionality of select proteins, establishing their capability to induce the B-to-Z conversion. Additionally, we identify Zα-like domains within bacterial proteins. While these domains share certain features with Zα domains, they lack the ability to bind to Z-nucleic acids or facilitate the B-to-Z DNA conversion. Our findings significantly expand the ZBP family across a wide spectrum of organisms and raise intriguing questions about the evolutionary origins of Zα-containing proteins. Moreover, our study offers fresh perspectives on the functional significance of Zα domains in virus sensing and innate immunity and opens avenues for exploring hitherto undiscovered functions of ZBPs.

A fish herpesvirus highlights functional diversities among Zα domains related to phase separation induction and A-to-Z conversion.

Zalpha (Zα) domains bind to left-handed Z-DNA and Z-RNA. The Zα domain protein family includes cellular (ADAR1, ZBP1 and PKZ) and viral (vaccinia virus E3 and cyprinid herpesvirus 3 (CyHV-3) ORF112) proteins. We studied CyHV-3 ORF112, which contains an intrinsically disordered region and a Zα domain. Genome editing of CyHV-3 indicated that the expression of only the Zα domain of ORF112 was sufficient for normal viral replication in cell culture and virulence in carp. In contrast, its deletion was lethal for the virus. These observations revealed the potential of the CyHV-3 model as a unique platform to compare the exchangeability of Zα domains expressed alone in living cells. Attempts to rescue the ORF112 deletion by a broad spectrum of cellular, viral, and artificial Zα domains showed that only those expressing Z-binding activity, the capacity to induce liquid-liquid phase separation (LLPS), and A-to-Z conversion, could rescue viral replication. For the first time, this study reports the ability of some Zα domains to induce LLPS and supports the biological relevance of dsRNA A-to-Z conversion mediated by Zα domains. This study expands the functional diversity of Zα domains and stimulates new hypotheses concerning the mechanisms of action of proteins containing Zα domains.

PASQUALE - A long-term partnership to improve hand hygiene and capacity building in infection prevention and control in the Faranah region of Guinea.

Across the globe, hand hygiene (HH) is promoted to fight the spread of healthcare associated infections. Despite multiple ongoing HH campaigns and projects, the healthcare associated infection rates remain high especially in low- and middle-income countries. In the narrative overview presented here, we aim to share objectives, framework, successes and challenges of our long-term partnership in Guinea to offer guidance for other projects aiming to sustainably improve HH.

Evaluating the performance of Plasmodium falciparum genetic metrics for inferring National Malaria Control Programme reported incidence in Senegal.

BACKGROUND: Genetic surveillance of the Plasmodium falciparum parasite shows great promise for helping National Malaria Control Programmes (NMCPs) assess parasite transmission. Genetic metrics such as the frequency of polygenomic (multiple strain) infections, genetic clones, and the complexity of infection (COI, number of strains per infection) are correlated with transmission intensity. However, despite these correlations, it is unclear whether genetic metrics alone are sufficient to estimate clinical incidence. METHODS: This study examined parasites from 3147 clinical infections sampled between the years 2012-2020 through passive case detection (PCD) across 16 clinic sites spread throughout Senegal. Samples were genotyped with a 24 single nucleotide polymorphism (SNP) molecular barcode that detects parasite strains, distinguishes polygenomic (multiple strain) from monogenomic (single strain) infections, and identifies clonal infections. To determine whether genetic signals can predict incidence, a series of Poisson generalized linear mixed-effects models were constructed to predict the incidence level at each clinical site from a set of genetic metrics designed to measure parasite clonality, superinfection, and co-transmission rates. RESULTS: Model-predicted incidence was compared with the reported standard incidence data determined by the NMCP for each clinic and found that parasite genetic metrics generally correlated with reported incidence, with departures from expected values at very low annual incidence (< 10/1000/annual [‰]). CONCLUSIONS: When transmission is greater than 10 cases per 1000 annual parasite incidence (annual incidence > 10‰), parasite genetics can be used to accurately infer incidence and is consistent with superinfection-based hypotheses of malaria transmission. When transmission was < 10‰, many of the correlations between parasite genetics and incidence were reversed, which may reflect the disproportionate impact of importation and focal transmission on parasite genetics when local transmission levels are low.

Two decades of molecular surveillance in Senegal reveal rapid changes in known drug resistance mutations over time.

BACKGROUND: Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. Pathogen genomic surveillance could be invaluable for monitoring current and emerging parasite drug resistance. METHODS: Data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasites from Senegal were retrospectively examined to assess historical changes in malaria drug resistance mutations. Several known drug resistance markers and their surrounding haplotypes were profiled using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole genome sequence based population genomics. RESULTS: This dataset was used to track temporal changes in drug resistance markers whose timing correspond to historically significant events such as the withdrawal of chloroquine (CQ) and the introduction of sulfadoxine-pyrimethamine (SP) in 2003. Changes in the mutation frequency at Pfcrt K76T and Pfdhps A437G coinciding with the 2014 introduction of seasonal malaria chemoprevention (SMC) in Senegal were observed. In 2014, the frequency of Pfcrt K76T increased while the frequency of Pfdhps A437G declined. Haplotype-based analyses of Pfcrt K76T showed that this rapid increase was due to a recent selective sweep that started after 2014. DISCUSSION (CONCLUSION): The rapid increase in Pfcrt K76T is troubling and could be a sign of emerging amodiaquine (AQ) resistance in Senegal. Emerging AQ resistance may threaten the future clinical efficacy of artesunate-amodiaquine (ASAQ) and AQ-dependent SMC chemoprevention. These results highlight the potential of molecular surveillance for detecting rapid changes in parasite populations and stress the need to monitor the effectiveness of AQ as a partner drug for artemisinin-based combination therapy (ACT) and for chemoprevention.

Perspectives and experiences of healthcare providers on the response to the COVID-19 pandemic in three maternal and neonatal referral hospitals in Guinea in 2020: a qualitative study.

BACKGROUND: The COVID-19 pandemic has adversely affected access to essential healthcare services. This study aimed to explore healthcare providers' perceptions and experiences of the response to the COVID-19 pandemic in three referral maternal and neonatal hospitals in Guinea. METHODS: We conducted a longitudinal qualitative study between June and December 2020 in two maternities and one neonatology referral ward in Conakry and Mamou. Participants were purposively recruited to capture diversity of professional cadres, seniority, and gender. Four rounds of in-depth interviews (46 in-depth interviews with 18 respondents) were conducted in each study site, using a semi-structured interview guide that was iteratively adapted. We used both deductive and inductive approaches and an iterative process for content analysis. RESULTS: We identified four themes and related sub-themes presented according to whether they were common or specific to the study sites, namely: 1) coping strategies & care reorganization, which include reducing staffing levels, maintaining essential healthcare services, suspension of staff daily meetings, insertion of a new information system for providers, and co-management with COVID-19 treatment center for caesarean section cases among women who tested positive for COVID-19; 2) healthcare providers' behavior adaptations during the response, including infection prevention and control measures on the wards and how COVID-19-related information influenced providers' daily work; 3) difficulties encountered by providers, in particular unavailability of personal protective equipment (PPE), lack of financial motivation, and difficulties reducing crowding in the wards; 4) providers perceptions of healthcare service use, for instance their fear during COVID-19 response and perceived increase in severity of complications received and COVID-19 cases among providers and parents of newborns. CONCLUSION: This study provides insights needed to be considered to improve the preparedness and response of healthcare facilities and care providers to future health emergencies in similar contexts.

Shifting Patterns of Influenza Circulation during the COVID-19 Pandemic, Senegal.

Historically low levels of seasonal influenza circulation were reported during the first years of the COVID-19 pandemic and were mainly attributed to implementation of nonpharmaceutical interventions. In tropical regions, influenza's seasonality differs largely, and data on this topic are scarce. We analyzed data from Senegal's sentinel syndromic surveillance network before and after the start of the COVID-19 pandemic to assess changes in influenza circulation. We found that influenza shows year-round circulation in Senegal and has 2 distinct epidemic peaks: during January-March and during the rainy season in August-October. During 2021-2022, the expected January-March influenza peak completely disappeared, corresponding to periods of active SARS-CoV-2 circulation. We noted an unexpected influenza epidemic peak during May-July 2022. The observed reciprocal circulation of SARS-CoV-2 and influenza suggests that factors such as viral interference might be at play and should be further investigated in tropical settings.

Ex vivo RSA and pfkelch13 targeted-amplicon deep sequencing reveal parasites susceptibility to artemisinin in Senegal, 2017.

BACKGROUND: Malaria control is highly dependent on the effectiveness of artemisinin-based combination therapy (ACT), the current frontline malaria curative treatment. Unfortunately, the emergence and spread of parasites resistant to artemisinin (ART) derivatives in Southeast Asia and South America, and more recently in Rwanda and Uganda (East Africa), compromise their long-term use in sub-Saharan Africa, where most malaria deaths occur. METHODS: Here, ex vivo susceptibility to dihydroartemisinin (DHA) was evaluated from 38 Plasmodium falciparum isolates collected in 2017 in Thiès (Senegal) expressed in the Ring-stage Survival Assay (RSA). Both major and minor variants were explored in the three conserved-encoding domains of the pfkelch13 gene, the main determinant of ART resistance using a targeted-amplicon deep sequencing (TADS) approach. RESULTS: All samples tested in the ex vivo RSA were found to be susceptible to DHA (parasite survival rate < 1%). The non-synonymous mutations K189T and K248R in pfkelch13 were observed each in one isolate, as major (99%) or minor (5%) variants, respectively. CONCLUSION: The results suggest that ART is still fully effective in the Thiès region of Senegal in 2017. Investigations combining ex vivo RSA and TADS are a useful approach for monitoring ART resistance in Africa.

FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial.

BACKGROUND: Vascular leakage is a major feature of acute respiratory distress syndrome (ARDS). We aimed to evaluate the efficacy of FX06, a drug under development that stabilizes interendothelial cell junctions, at reducing vascular leakage during SARS-CoV-2-induced ARDS. METHODS: This multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for < 5 days and were randomized to receive either intravenous FX06 (400 mg/d, for 5 days) or its vehicle as placebo. The primary endpoint was the lowering-from day 1 to day 7-of the transpulmonary thermodilution-derived extravascular lung-water index (EVLWi). RESULTS: Twenty-five patients were randomized to receive FX06 and 24 the placebo. Although EVLWi was elevated at baseline (median [IQR] 15.6 mL/kg [13.5; 18.5]), its declines from day 1 to day 7 were comparable for FX06 recipients and controls (respectively, - 1.9 [- 3.3; - 0.5] vs. - 0.8 [- 5.5; - 1.1] mL/kg; estimated effect - 0.8 [- 3.1; + 2.4], p = 0.51). Cardiac indexes, pulmonary vascular permeability indexes, and fluid balances were also comparable, as were PaO2/FiO2 ratios and durations of mechanical ventilation. Adverse event rates were similar for the 2 groups, although more FX06 recipients developed ventilator-associated pneumonia (16/25 (64%) vs. 6/24 (24%), p = 0.009). CONCLUSIONS: In this unique-dosing-regimen study, FX06 did not lower SARS-CoV-2-induced pulmonary vascular leakage. Future investigations will need to evaluate its efficacy at earlier times during the disease or using other regimens. Trial registration NCT04618042. Registered 5 November 2020.

Effect of the COVID-19 pandemic on maternal and neonatal health services in three referral hospitals in Guinea: an interrupted time-series analysis.

INTRODUCTION: In sub-Saharan Africa, there is limited evidence on the COVID-19 health-related effect from front-line health provision settings. Therefore, this study aimed to analyse the effect of the COVID-19 pandemic on routine maternal and neonatal health services in three referral hospitals. MATERIALS AND METHODS: We conducted an observational study using aggregate monthly maternal and neonatal health services routine data for two years (March 2019-February 2021) in three referral hospitals including two maternities: Hôpital National Ignace Deen (HNID) in Conakry and Hôpital Regional de Mamou (HRM) in Mamou and one neonatology ward: Institut de Nutrition et de Santé de l'Enfant (INSE) in Conakry. We compared indicators of health service utilisation, provision and health outcomes before and during the COVID-19 pandemic periods. An interrupted time-series analysis (ITSA) was performed to assess the relationship between changes in maternal and neonatal health indicators and COVID-19 through cross-correlation. RESULTS: During COVID-19, the mean monthly number (MMN) of deliveries decreased significantly in HNID (p = 0.039) and slightly increased in HRM. In the two maternities, the change in the MMN of deliveries were significantly associated with COVID-19. The ITSA confirmed the association between the increase in the MMN of deliveries and COVID-19 in HRM (bootstrapped F-value = 1.46, 95%CI [0.036-8.047], p < 0.01). We observed an increasing trend in obstetric complications in HNID, while the trend declined in HRM. The MMN of maternal deaths increased significantly (p = 0.011) in HNID, while it slightly increased in HRM. In INSE, the MMN of neonatal admissions significantly declined (p < 0.001) and this decline was associated with COVID-19. The MMN of neonatal deaths significantly decreased (p = 0.009) in INSE and this decrease was related to COVID-19. CONCLUSION: The pandemic negatively affected the maternal and neonatal care provision, health service utilisation and health outcomes in two referral hospitals located in Conakry, the COVID-19 most-affected region.

Effect of women's literacy on maternal and child health: Evidence from demographic Health Survey data in Senegal.

BACKGROUND: Senegal has certainly made significant efforts in adult literacy and in the fight against maternal and infant mortality. However, a large proportion of the female population is illiterate, and the country's maternal and infant mortality rates are still higher than WHO recommendations. This article examined the effect of women's literacy on maternal and child health in Senegal. METHODS: Data were extracted from the last Senegal Demographic and Health Surveys (DHS) collected in 2019. A binary logistic model was performed to assess the effect of women's literacy on ten outcomes of maternal and child health indicators. RESULTS: Results indicate that women's literacy has a positive and significant effect on nine of key indicators outcomes. For instance, women's literacy increases the odds of contraceptive use by 1.29 (95% Confidence Interval [CI], 1.13-1.48; p < 0.01), compliance with the number of prenatal visits by 1.57 (95% CI, 1.35-1.83; p < 0.01) and consultation in the first trimester of pregnancy by 1.52 (95% CI, 1.31-1.78; p < 0.01). Literacy is associated with increased odds of breastfeeding up to six months (Odds Ratio [OR], 1.17; 95% CI, 0.97-1.42; p < 0.1) and healthy birth interval (OR, 1.18; 95% CI, 0.97-1.44; p < 0.1) only in rural areas. Women literacy reduces the risk of stunting by 0.81 (95% CI, 0.68-0.96; p < 0.05) and the risk of underweight by 0.72 (95% CI, 0.59-0.87; p < 0.01) among children under five years. The mother's ability to read and write favors compliance with the increase of odds of DPT vaccination record of her children, especially in rural areas (OR, 1.69; 95% CI, 1.05-2.74; p < 0.05). Moreover, there are serval other factors influencing positively the maternal and child health, like health insurance access, media exposure, and clean water and improved sanitation facilities access. CONCLUSIONS: This study emphasizes on the need to strengthen adult literacy programs, especially for women in rural areas. Indeed, this could help generalize health insurance by income-sensitive premiums or exemptions for the poor as well as increased awareness campaigns to promote reproductive and maternal health benefits, via the radio or television. Furthermore, improving access to clean water supply and improved sanitation facilities would greatly ameliorate maternal and child health.

Rapid Increase of Community SARS-CoV-2 Seroprevalence during Second Wave of COVID-19, Yaoundé, Cameroon.

We conducted 2 independent population-based SARS-CoV-2 serosurveys in Yaoundé, Cameroon, during January 27-February 6 and April 24-May 19, 2021. Overall age-standardized SARS-CoV-2 IgG seroprevalence increased from 18.6% in the first survey to 51.3% in the second (p<0.001). This finding illustrates high community transmission during the second wave of COVID-19.

Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced acute respiratory distress syndrome (ARDS) causes high mortality. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have potentially relevant immune-modulatory properties, whose place in ARDS treatment is not established. This phase 2b trial was undertaken to assess the efficacy of UC-MSCs in patients with SARS-CoV-2-induced ARDS. METHODS: This multicentre, double-blind, randomized, placebo-controlled trial (STROMA-CoV-2) recruited adults (≥ 18 years) with SARS-CoV-2-induced early (< 96 h) mild-to-severe ARDS in 10 French centres. Patients were randomly assigned to receive three intravenous infusions of 106 UC-MSCs/kg or placebo (0.9% NaCl) over 5 days after recruitment. For the modified intention-to-treat population, the primary endpoint was the partial pressure of oxygen to fractional inspired oxygen (PaO2/FiO2)-ratio change between baseline (day (D) 0) and D7. RESULTS: Among the 107 patients screened for eligibility from April 6, 2020, to October 29, 2020, 45 were enrolled, randomized and analyzed. PaO2/FiO2 changes between D0 and D7 did not differ significantly between the UC-MSCs and placebo groups (medians [IQR] 54.3 [- 15.5 to 93.3] vs 25.3 [- 33.3 to 104.6], respectively; ANCOVA estimated treatment effect 7.4, 95% CI - 44.7 to 59.7; P = 0.77). Six (28.6%) of the 21 UC-MSCs recipients and six of 24 (25%) placebo-group patients experienced serious adverse events, none of which were related to UC-MSCs treatment. CONCLUSIONS: D0-to-D7 PaO2/FiO2 changes for intravenous UC-MSCs-versus placebo-treated adults with SARS-CoV-2-induced ARDS did not differ significantly. Repeated UC-MSCs infusions were not associated with any serious adverse events during treatment or thereafter (until D28). Larger trials enrolling patients earlier during the course of their ARDS are needed to further assess UC-MSCs efficacy in this context. TRIAL REGISTRATION: NCT04333368. Registered 01 April 2020, https://clinicaltrials.gov/ct2/history/NCT04333368 .

Assessment of Comamonas testosteroni strain PT9 as a rapid phthalic acid degrader for industrial wastewaters.

In this study, characterization of industry-borne Comamonas testosteroni strain PT9 isolate was performed by determining degradation ability on phthalic acid (PA). High-performance liquid chromatography analyses showed that strain PT9 completely degraded 102.94 mg/L of PA within 6 h. Viability polymerase chain reaction (vPCR) was performed with propidium monoazide treatment. vPCR showed that the PA has positively stimulated the cell growth during degradation. To consider the fate of PA, the proposed catalytic genes (ophA2, iphA2, tphA2, tphA3, pmdA, and pmdB) for the degradation pathways of PA isomers for C. testosteroni were screened in strain PT9. All genes except iphA2 were detected in strain PT9, and expression levels of related genes were analyzed by Real-Time PCR (qPCR).

Electric-Field-Based Guidance for Percutaneous Catheter Vessel Crossing.

Percutaneous procedures to divert blood flow from one blood vessel to another can be performed with intravascular catheters but demand a method to align a crossing needle from one vessel to another. Fluoroscopic imaging alone is not adequate, and it is preferable to have a sensor on one catheter that detects the correct alignment of an incoming needle. This can be implemented by generating dipole electric fields from the crossing catheter which are detected by a receiving catheter in the target vessel and, thus, can calculate and display the degree of alignment, permitting the operator to rotate the crossing catheter to guarantee alignment when deploying a crossing needle. Catheters were built using this concept and evaluated in vitro. The results show that accurate alignment is achieved, and a successful crossing can be made. The concept is being further developed for further clinical evaluation.

Intracellular Signaling Pathways Mediating Tyrosine Kinase Inhibitor Cardiotoxicity.

Tyrosine kinase inhibitors (TKIs) are used to treat several cancers; however, a myriad of adverse cardiotoxic effects remain a primary concern. Although hypertension (HTN) is the most common adverse effect reported with TKI therapy, incidents of arrhythmias (eg, QT prolongation, atrial fibrillation) and heart failure are also prevalent. These complications warrant further research toward understanding the mechanisms of TKI-induced cardiotoxicity. Recent literature has given some insight into the intracellular signaling pathways that may mediate TKI-induced cardiac dysfunction. In this article, we discuss the cardiotoxic effects of TKIs on cardiomyocyte function, signaling, and possible treatments.

Understanding Long-term Evolution and Predictors of Sequelae of Ebola Virus Disease Survivors in Guinea: A 48-Month Prospective, Longitudinal Cohort Study (PostEboGui).

BACKGROUND: Longitudinal analyses are needed to better understand long-term Ebola virus disease (EVD) sequelae. We aimed to estimate the prevalence, incidence, and duration of sequelae and to identify risk factors associated with symptom occurrence among EVD survivors in Guinea. METHODS: We followed 802 EVD survivors over 48 months and recorded clinical symptoms with their start/end dates. Prevalence, incidence, and duration of sequelae were calculated. Risk factors associated with symptom occurrence were assessed using an extended Cox model for recurrent events. RESULTS: Overall, the prevalence and incidence of all symptoms decreased significantly over time, but sequelae remained present 48 months after Ebola treatment center discharge with a prevalence of 30.68% (95% confidence interval [CI] 21.40-39.96) for abdominal, 30.55% (95% CI 20.68-40.41) for neurologic, 5.80% (95% CI 1.96-9.65) for musculoskeletal, and 4.24% (95% CI 2.26-6.23) for ocular sequelae. Half of all patients (50.70%; 95% CI 47.26-54.14) complained of general symptoms 2 years' postdischarge and 25.35% (95% CI 23.63-27.07) 4 years' post-discharge. Hemorrhage (hazard ratio [HR], 2.70; P = .007), neurologic (HR 2.63; P = .021), and general symptoms (HR 0.34; P = .003) in the EVD acute phase were significantly associated with the further occurrence of ocular sequelae, whereas hemorrhage (HR 1.91; P = .046) and abdominal (HR 2.21; P = .033) symptoms were significantly associated with musculoskeletal sequelae. CONCLUSIONS: Our findings provide new insight into the long-term clinical complications of EVD and their significant association with symptoms in the acute phase, thus reinforcing the importance of regular, long-term follow-up for EVD survivors.

High expression of ring-hydroxylating dioxygenase genes ensure efficient degradation of p-toluate, phthalate, and terephthalate by Comamonas testosteroni strain 3a2.

Para-toluic acid, a major pollutant in industrial wastewater, is hazardous to human health. It has been demonstrated that Gram-negative bacteria are among the most effective degraders of para-toluic acid. In this study, the ability of Comamonas testosteroni strain 3a2, isolated from a petrochemical industry wastewater, to degrade para-toluic acid was investigated. The effect of different carbon (glucose and ethylene glycol) and nitrogen sources (urea, yeast extract, peptone, NaNO3, NH4NO3) on the biodegradation of para-toluic acid by the isolate 3a2 was evaluated. Furthermore, ring hydroxylating dioxygenase genes were amplified by PCR and their expression was evaluated during the biodegradation of para-toluic acid. The results indicated that strain 3a2 was able to degrade up to 1000 mg/L of para-toluic acid after 14 h. The highest degradation yield was recorded in the presence of yeast extract as nitrogen source. However, the formation of terephthalic acid and phthalic acid was noted during para-toluic acid degradation by the isolate 3a2. Toluate 1,2-dioxygenase, terephthalate 1,2 dioxygenase, and phthalate 4,5 dioxygenase genes were detected in the genomic DNA of 3a2. The induction of ring hydroxylating dioxygenase genes was proportional to the concentration of each hydrocarbon. This study showed that the isolate 3a2 can produce terephthalate and phthalate during the para-toluic acid biodegradation, which were also degraded after 24 h.

Routine Vaccination Coverage - Worldwide, 2020.

Endorsed by the World Health Assembly in 2020, the Immunization Agenda 2030 (IA2030) strives to reduce morbidity and mortality from vaccine-preventable diseases across the life course (1). This report, which updates a previous report (2), presents global, regional,* and national vaccination coverage estimates and trends as of 2020. Changes are described in vaccination coverage and the numbers of unvaccinated and undervaccinated children as measured by receipt of the first and third doses of diphtheria, tetanus, and pertussis-containing vaccine (DTP) in 2020, when the COVID-19 pandemic began, compared with 2019. Global estimates of coverage with the third dose of DTP (DTP3) and a polio vaccine (Pol3) decreased from 86% in 2019 to 83% in 2020. Similarly, coverage with the first dose of measles-containing vaccine (MCV1) dropped from 86% in 2019 to 84% in 2020. The last year that coverage estimates were at 2020 levels was 2009 for DTP3 and 2014 for both MCV1 and Pol3. Worldwide, 22.7 million children (17% of the target population) were not vaccinated with DTP3 in 2020 compared with 19.0 million (14%) in 2019. Children who did not receive the first DTP dose (DTP1) by age 12 months (zero-dose children) accounted for 95% of the increased number. Among those who did not receive DTP3 in 2020, approximately 17.1 million (75%) were zero-dose children. Global coverage decreased in 2020 compared with 2019 estimates for the completed series of Haemophilus influenzae type b (Hib), hepatitis B vaccine (HepB), human papillomavirus vaccine (HPV), and rubella-containing vaccine (RCV). Full recovery from COVID-19-associated disruptions will require targeted, context-specific strategies to identify and catch up zero-dose and undervaccinated children, introduce interventions to minimize missed vaccinations, monitor coverage, and respond to program setbacks (3).

Malaria epidemiology and anti-malarial drug efficacy in Guinea: a review of clinical and molecular studies.

Malaria is one of the leading causes of mortality and morbidity in Guinea. The entire country is considered at risk of the disease. Transmission occurs all year round with peaks occurring from July through October with Plasmodium falciparum as the primary parasite species. Chloroquine (CQ) was the first-line drug against uncomplicated P. falciparum in Guinea until 2005, prior to the adoption of artemisinin-based combination therapy (ACT). In this review, data on therapeutic efficacy of CQ and artemisinin-based combinations reported in published literature is summarized. Against CQ, a failure rate of 27% (12/44) was reported in a study in 1992; a median failure rate of 15.6% [range: 7.7-28.3; 8 studies] was observed during 1996-2001, and 81% (17/21) of the patients failed to clear parasitaemia in a study conducted in 2007. For artemisinin-based combinations, three published studies were identified (1495 patients; 2004-2016); all three studies demonstrated day 28 polymerase chain reaction corrected efficacy > 95%. One study characterized kelch-13 mutations (389 tested; samples collected in 2016) with no evidence of mutations currently known to be associated with artemisinin resistance. The impact of the ongoing COVID-19 pandemic and widespread usage of counterfeit medicines are immediate challenges to malaria control activities in Guinea.