Artemisinin resistance (delayed P. falciparum clearance following artemisinin-based combination therapy), is widespread across Southeast Asia but to date has not been reported in Africa
. Here we ...genotyped the P. falciparum K13 (Pfkelch13) propeller domain, mutations in which can mediate artemisinin resistance
, in pretreatment samples collected from recent dihydroarteminisin-piperaquine and artemether-lumefantrine efficacy trials in Rwanda
. While cure rates were >95% in both treatment arms, the Pfkelch13 R561H mutation was identified in 19 of 257 (7.4%) patients at Masaka. Phylogenetic analysis revealed the expansion of an indigenous R561H lineage. Gene editing confirmed that this mutation can drive artemisinin resistance in vitro. This study provides evidence for the de novo emergence of Pfkelch13-mediated artemisinin resistance in Rwanda, potentially compromising the continued success of antimalarial chemotherapy in Africa.
Antimicrobial resistance in neonatal sepsis is rising, yet mechanisms of resistance that often spread between species via mobile genetic elements, ultimately limiting treatments in low- and ...middle-income countries (LMICs), are poorly characterized. The Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) network was initiated to characterize the cause and burden of antimicrobial resistance in neonatal sepsis for seven LMICs in Africa and South Asia. A total of 36,285 neonates were enrolled in the BARNARDS study between November 2015 and December 2017, of whom 2,483 were diagnosed with culture-confirmed sepsis. Klebsiella pneumoniae (n = 258) was the main cause of neonatal sepsis, with Serratia marcescens (n = 151), Klebsiella michiganensis (n = 117), Escherichia coli (n = 75) and Enterobacter cloacae complex (n = 57) also detected. We present whole-genome sequencing, antimicrobial susceptibility and clinical data for 916 out of 1,038 neonatal sepsis isolates (97 isolates were not recovered from initial isolation at local sites). Enterobacterales (K. pneumoniae, E. coli and E. cloacae) harboured multiple cephalosporin and carbapenem resistance genes. All isolated pathogens were resistant to multiple antibiotic classes, including those used to treat neonatal sepsis. Intraspecies diversity of K. pneumoniae and E. coli indicated that multiple antibiotic-resistant lineages cause neonatal sepsis. Our results will underpin research towards better treatments for neonatal sepsis in LMICs.
Rwanda 20 years on: investing in life Binagwaho, Agnes, Dr; Farmer, Paul E, MD; Nsanzimana, Sabin, MD ...
The Lancet (British edition),
07/2014, Letnik:
384, Številka:
9940
Journal Article
Recenzirano
Odprti dostop
Summary Two decades ago, the genocide against the Tutsis in Rwanda led to the deaths of 1 million people, and the displacement of millions more. Injury and trauma were followed by the effects of a ...devastated health system and economy. In the years that followed, a new course set by a new government set into motion equity-oriented national policies focusing on social cohesion and people-centred development. Premature mortality rates have fallen precipitously in recent years, and life expectancy has doubled since the mid-1990s. Here we reflect on the lessons learned in rebuilding Rwanda's health sector during the past two decades, as the country now prepares itself to take on new challenges in health-care delivery.
Emerging artemisinin partial resistance and diagnostic resistance are a threat to malaria control in Africa. Plasmodium falciparum kelch13 (k13) propeller-domain mutations that confer artemisinin ...partial resistance have emerged in Africa. k13-561H was initially described at a frequency of 7.4% from Masaka in 2014-2015, but not present in nearby Rukara. By 2018, 19.6% of isolates in Masaka and 22% of isolates in Rukara contained the mutation. Longitudinal monitoring is essential to inform control efforts. In Rukara, an assessment was conducted to evaluate recent k13-561H prevalence changes, as well as other key mutations. Prevalence of hrp2/3 deletions was also assessed.
Samples collected in Rukara in 2021 were genotyped for key artemisinin and partner drug resistance mutations using molecular inversion probe assays and for hrp2/3 deletions using qPCR.
Clinically validated k13 artemisinin partial resistance mutations continue to increase in prevalence with the overall level of mutant infections reaching 32% in Rwanda. The increase appears to be due to the rapid emergence of k13-675V (6.4%, 6/94 infections), previously not observed, rather than continued expansion of 561H (23.5% 20/85). Mutations to partner drugs and other anti-malarials were variable, with high levels of multidrug resistance 1 (mdr1) N86 (95.5%) associated with lumefantrine decreased susceptibility and dihydrofolate reductase (dhfr) 164L (24.7%) associated with a high level of antifolate resistance, but low levels of amodiaquine resistance polymorphisms with chloroquine resistance transporter (crt) 76T: at 6.1% prevalence. No hrp2 or hrp3 gene deletions associated with diagnostic resistance were found.
Increasing prevalence of artemisinin partial resistance due to k13-561H and the rapid expansion of k13-675V is concerning for the longevity of artemisinin effectiveness in the region. False negative RDT results do not appear to be an issue with no hrp2 or hpr3 deletions detected. Continued molecular surveillance in this region and surrounding areas is needed to follow artemisinin partial resistance and provide early detection of partner drug resistance, which would likely compromise control and increase malaria morbidity and mortality in East Africa.
Abstract
Background
From 2019 to 2021, Rwandan residents of the border with the Democratic Republic of the Congo were offered the Ad26.ZEBOV (adenovirus type 26 vector vaccine encoding Ebola virus ...glycoprotein) and MVA-BN-Filo (modified vaccinia virus Ankara vector vaccine, encoding glycoproteins from Ebola, Sudan, Marburg, and nucleoprotein from Tai Forest viruses) Ebola vaccine regimen.
Methods
Nonpregnant persons aged ≥2 years were eligible. Unsolicited adverse events (UAEs) were reported through phone calls or visits, and serious adverse events (SAEs) were recorded per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines.
Results
Following Ad26.ZEBOV, UAEs were reported by 0.68% of 216 113 vaccinees and were more common in younger children (aged 2–8 years, 1.2%) compared with older children (aged 9–17 years, 0.4%) and adults (aged ≥18 years, 0.7%). Fever and headache were the most reported symptoms. All 17 SAEs related to vaccine were in children aged 2–8 years (10 postvaccination febrile convulsions ± gastroenteritis and 7 fever and/or gastroenteritis). The incidence of febrile seizures was 8 of 26 062 (0.031%) prior to initiation of routine acetaminophen in December 2020 and 2 of 15 897 (0.013%) thereafter. Nonobstetric SAEs were similar in males and females. All 20 deaths were unrelated to vaccination. Young girls and adult women with UAEs were less likely to receive the second dose than those without UAEs. Seven unrelated SAEs occurred in 203 267 MVA-BN-Filo recipients.
Conclusions
Postvaccination febrile convulsions in young children were rare but not previously described after Ad26.ZEBOV and were reduced with routine acetaminophen. The regimen was otherwise safe and well-tolerated.
UMURINZI, the largest campaign of the Ad26.ZEBOV/MVA-BN-Filo Ebola vaccination, confirmed previous trials’ safety conclusions. Notable findings were rare febrile seizures in young children, reduced second-dose retention in women with incident pregnancy, and more obstetric vs nonobstetric serious adverse events.
Hospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income countries (LMICs). During the ...BARNARDS study, hospital surfaces from neonatal wards were sampled to assess the degree of environmental surface and patient care equipment colonisation by Gram-negative bacteria (GNB) carrying antibiotic resistance genes (ARGs). Here, we perform PCR screening for extended-spectrum β-lactamases (bla
) and carbapenemases (bla
, bla
-like and bla
), MALDI-TOF MS identification of GNB carrying ARGs, and further analysis by whole genome sequencing of bacterial isolates. We determine presence of consistently dominant clones and their relatedness to strains causing neonatal sepsis. Higher prevalence of carbapenemases is observed in Pakistan, Bangladesh, and Ethiopia, compared to other countries, and are mostly found in surfaces near the sink drain. Klebsiella pneumoniae, Enterobacter hormaechei, Acinetobacter baumannii, Serratia marcescens and Leclercia adecarboxylata are dominant; ST15 K. pneumoniae is identified from the same ward on multiple occasions suggesting clonal persistence within the same environment, and is found to be identical to isolates causing neonatal sepsis in Pakistan over similar time periods. Our data suggests persistence of dominant clones across multiple time points, highlighting the need for assessment of Infection Prevention and Control guidelines.
Coordinated progress is urgently needed in four domains: redesigning the pharmaceutical innovation ecosystem and its policy environment to resolve the incoherence between market-driven approaches and ...public health needs; applying evidence-based and transparent prioritisation criteria in the national health systems; strengthening the regulatory and supply systems; and promoting financial health protection as part of universal health coverage. The inequitable access to COVID-19 vaccines uncovered multiple structural problems in the organisation, financing and governance of the medical research and development (R&D) and supply ecosystem,3 encompassing unclear demand, weak distribution systems, poor donation practices and corruption, historic inequalities in access to knowledge, training and technological capabilities, lack of technology sharing and transfer, limited local production, and the absence of public health perspective in intellectual property governance. ...efforts by the United Nations to come to a binding Research and Development treaty or convention to support collective public-health focused R&D and hold governments accountable regarding public funding of health-related R&D and commitments for access have not succeeded.11 In fact, equitable access to the latest generations of medicines is increasingly hampered by monopolies and high prices, even in wealthy countries (eg, cancer treatments and the newest gene-based and cell-based therapies), with governments unable (or unwilling) to leverage their power to negotiate or enforce fair pricing, alongside a lack of transparency on development and production costs.12 For example, the lack of transparency about the pricing of COVID-19 vaccines, and the associated power imbalance between governments seeking to procure vaccines for their population and pharmaceutical companies, has caused some blatant inequities, such as the South Africa government being charged more than some high-income countries.13 In the near future, this gap in access to essential medicines and vaccines could become even more pronounced, with the evolution to personalised medicine. The tension between control and access exacerbates the largely ignored North-South gap in access to adequate pain therapy for adults and children.16 Rabies vaccination is life-saving, and pre-exposure prophylaxis (PrEP) increases the likelihood of survival in bitten persons.
In the version of this article initially published, affiliation 2 (Malaria Genetics and Resistance Unit, Institut Pasteur, Paris, France) was incorrect. The correct affiliation is ‘Malaria Genetics ...and Resistance Unit–Institut Pasteur, INSERM U1201, CNRS ERL9195, Paris, France’. Also, in the first sentence in the first paragraph of the fifth subsection of Results (‘Origins of the Rwandan Pfkelch13 561H haplotype and its relationship to other P. falciparum populations’), the first part of the sample description (“350 samples, comprising 25 Rwandan sequences and 10 Eritrean P. falciparum sequences generated for this study”) was incorrect. The correct text is “...340 samples, comprising 25 Rwandan P. falciparum sequences generated for this study...”. Finally, Fig. 1 was incorrect, and the number of worldwide isolates in the legend title (325) was incorrect. The corrected figure is presented here, and the correct number of worldwide isolates is 315. The errors have been corrected in the HTML and PDF versions of the article
Background
During the last decades, a great interest was given to viral etiology of breast cancer. Indeed, due to recent technical improvements and some encouraging new results, it has been a ...resurgence of interest in the possibility that a substantial proportion of human breast cancers may be caused by viral infections. High-risk genotypes of human papillomavirus (HPV) have been found in breast cancer cases. In the present study, we aimed to assess the presence of HPV DNA in breast cancer cases from Rwanda and to evaluate the association between HPV infection and clinico-pathological features.
Methods
Therefore, a total of 47 archived formalin-fixed paraffin-embedded biopsies were collected and complete information was recorded. HPV detection and genotyping were done by PCR amplification and DNA sequencing.
Results
Overall, HPV DNA was found in 46.81% of cases, HPV16 being the most prevalent subtype (77.27%) followed by HPV33 (13.64%) and HPV31 (9.09%). Comparison of HPV with clinico-pathological features showed no significant difference between HPV infection and breast localization, histological subtype, clinical stage, tumor grade, and intrinsic molecular subtypes.
Conclusions
These findings provide evidence of high prevalence of high-risk HPV in Rwandese patients with breast cancer and suggest that high-risk HPV infections could be a risk factor associated with human breast cancer development.
Abstract
Background
Artemisinin resistance mutations in Plasmodium falciparum kelch13 (Pfk13) have begun to emerge in Africa, with Pfk13-R561H being the first reported in Rwanda in 2014, but limited ...sampling left questions about its early distribution and origin.
Methods
We genotyped P. falciparum positive dried blood spot (DBS) samples from a nationally representative 2014–2015 Rwanda Demographic Health Surveys (DHS) HIV study. DBS were subsampled from DHS sampling clusters with >15% P. falciparum prevalence, as determined by rapid testing or microscopy done during the DHS study (n clusters = 67, n samples = 1873).
Results
We detected 476 parasitemias among 1873 residual blood spots from a 2014–2015 Rwanda Demographic Health Survey. We sequenced 351 samples: 341/351 were wild-type (97.03% weighted), and 4 samples (1.34% weighted) harbored R561H that were significantly spatially clustered. Other nonsynonymous mutations found were V555A (3), C532W (1), and G533A (1).
Conclusions
Our study better defines the early distribution of R561H in Rwanda. Previous studies only observed the mutation in Masaka as of 2014, but our study indicates its presence in higher-transmission regions in the southeast of the country at that time.
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