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This study investigated the mediators of the association between socioeconomic position (SEP) and Plasmodium falciparum (Pf) infection in Southern region of Malawi. We utilized data from the 2014 International Center of Excellence for Malaria Research (ICEMR) surveys from Malawi in which blood samples of all individuals from selected households in Blantyre, Thyolo and Chikhwawa were tested for Pf parasitemia. We assessed household SEP and potential mediators - housing quality, food security, education status of household heads, and use of long-lasting Insecticide-treated nets (LLINs) and nutritional status. We conducted causal mediation analyses to assess the proportion of SEP effect that is attributed to each mediator and combination of mediators. The mediation analysis shows that during the rainy season, improved housing and educational attainment explained 39.4% and 17.0% of the SEP effect on Pf infection, respectively, and collectively 66.4%. In the dry season, housing, educational attainment, and LLIN usage collectively mediated 33.4% of SEP's effect with individual contributions of 15.6%, 11.2%, and 3.8%, respectively. Nutrition also played a role, particularly for children, mediating 9.2% of SEP's effect in the rainy season and 3.7% in the dry season. The study concluded that multifaceted interventions targeting housing, education, LLIN usage, and nutrition are vital to reducing socioeconomic disparities in Pf infection risk in the Southern region of Malawi., (© 2024. The Author(s).)

Reduced susceptibility to ART, the first-line treatment against malaria, is common in South East Asia (SEA). It is associated with point mutations, mostly in kelch13 ( k13 ) but also in other genes, like ubp1 . K13 and its compartment neighbors (KICs), including UBP1, are involved in endocytosis of host cell cytosol. We tested 135 mutations in KICs but none conferred ART resistance. Double mutations of k13 C580Y with k13 R539T or k13 C580Y with ubp1 R3138H, did also not increase resistance. In contrast, k13 C580Y parasites subjected to consecutive RSAs did, but the k13 sequence was not altered. Using isogenic parasites with different k13 mutations, we found correlations between K13 protein amount, resistance, and fitness cost. Titration of K13 and KIC7 indicated that the cellular levels of these proteins determined resistance through the rate of endocytosis. While fitness cost of k13 mutations correlated with ART resistance, ubp1 R3138H caused a disproportionately higher fitness cost., Importance: Parasites with lowered sensitivity to artemisinin-based drugs are becoming widespread. However, even in these "resistant" parasites not all parasites survive treatment. We found that the proportion of surviving parasites correlates with the fitness cost of resistance-inducing mutations which might indicate that the growth disadvantages prevents resistance levels where all parasites survive treatment. We also found that combining two common resistance mutations did not increase resistance levels. However, selection through repeated ART-exposure did, even-though the known resistance genes, including k13 , were not further altered, suggesting other causes of increased resistance. We also observed a disproportionally high fitness cost of a resistance mutation in resistance gene ubp1 . Such high fitness costs may explain why mutations in ubp1 and other genes functioning in the same pathway as k13 are rare. This highlights that k13 mutations are unique in their ability to cause resistance at a comparably low fitness cost., Competing Interests: The authors declare no conflict of interest.

Background: Healthcare resources are often limited in areas of sub-Saharan Africa. This makes accurate and timely diagnoses challenging and delays treatment of childhood febrile illness. We explored longitudinal characteristics related to symptoms, diagnosis and treatment of hospitalised febrile children in a rural area of Ghana highly endemic for malaria., Methods: Febrile children under 15 years, admitted to the study hospital paediatric ward, were recruited to the study and clinical data were collected throughout hospitalisation. Descriptive statistics were reported for all cases; for longitudinal analyses, a subset of visits with limited missing data was used., Results: There were 801 hospitalised children included in longitudinal analyses. Malaria (n = 581, 73%) and sepsis (n = 373, 47%) were the most prevalent suspected diagnoses on admission. One-third of malaria suspected diagnoses (n = 192, 33%) were changed on the discharge diagnosis, compared to 84% (n = 315) of sepsis suspected diagnoses. Among malaria-only discharge diagnoses, 98% (n/N = 202/207) received an antimalarial and 33% (n/N = 69/207) an antibiotic; among discharge diagnoses without malaria, 28% (n/N = 108/389) received an antimalarial and 83% (n/N = 324/389) an antibiotic., Conclusions: Suspected diagnoses were largely based on clinical presentation and were frequently changed; changed diagnoses were associated with lingering symptoms, underscoring the need for faster and more accurate diagnostics. Medications were over-prescribed regardless of diagnosis stability, possibly because of a lack of confidence in suspected diagnoses. Thus, better diagnostic tools are needed for childhood febrile illnesses to enhance the accuracy of and confidence in diagnoses, and to cut down unjustified medication use, reducing the risk of antimicrobial and malaria resistance., (© 2023 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

In spite of ongoing eradication programs, helminth infections are still a medical issue in Ghana. For follow-up assessments on the decline of regional helminth infections, historic baseline prevalence values obtained with standardized diagnostic procedures can be helpful. In this retrospective cross-sectional study, real-time PCR targeting the nematodes Ancylostoma spp. (ITS2), Ascaris lumbricoides (ITS1), Enterobius vermicularis (ITS1), Necator americanus (ITS2), Strongyloides stercoralis (18S rRNA) and Trichuris trichiura (18S rRNA), the trematodes Schistosoma spp. (ITS2) as well as the cestodes Hymenolepis nana (ITS1), Taenia saginata (ITS1) and Taenia solium (ITS1) was applied with 2046 DNA eluates from stool samples of Ghanaian children from the Ashanti region collected between 2007 and 2008 in order to retrospectively define prevalence values. The overall prevalence was low with 3.8% ( n = 77) and only 0.1% ( n = 2) double infections with helminths were recorded. The three most frequently detected enteric helminth species comprised 2% S. stercoralis ( n = 41), 0.8% H. nana ( n = 16), and 0.7% N. americanus ( n = 14), while only sporadic infection events were recorded for other helminth species comprising 0.1% E. vermicularis ( n = 2), 0.1% Schistosoma spp. ( n = 2), 0.1% T. saginata ( n = 1) and 0.1% T. trichiura ( n = 1). A. lumbricoides , Ancylostoma spp. and T. solium were not detected at all. In conclusion, the retrospective assessment suggests a low prevalence of enteric helminth infections in Ghanaian children from the Ashanti Region within the assessment period between 2007 and 2008.

It is evident that all the countries surrounding Ghana have experienced epidemics of key arboviruses of medical importance, such as the recent dengue fever epidemic in Burkina Faso. Therefore, Ghana is considered a ripe zone for epidemics of arboviruses, mainly dengue. Surprisingly, Ghana never experienced the propounded deadly dengue epidemic. Indeed, it is mysterious because the mosquito vectors capable of transmitting the dengue virus, such as Aedes aegypti , were identified in Ghana through entomological investigations. Additionally, cases may be missed, as the diagnostic and surveillance capacities of the country are weak. Therefore, we review the arbovirus situation and outline probable reasons for the epidemic mystery in the country. Most of the recorded cases of arbovirus infections were usually investigated via serology by detecting IgM and IgG immunoglobulins in clinical samples, which is indicative of prior exposure but not an active case. This led to the identification of yellow fever virus and dengue virus as the main circulating arboviruses among the Ghanaian population. However, major yellow fever epidemics were reported for over a decade. It is important to note that the reviewed arboviruses were not frequently detected in the vectors. The data highlight the necessity of strengthening the diagnostics and the need for continuous arbovirus and vector surveillance to provide an early warning system for future arbovirus epidemics.

Little information is available on the local epidemiology of mobile genetic elements such as plasmids harboring acquired beta-lactamase genes in Western African Ghana. In the present study, we screened for plasmids in three Escherichia coli and four Klebsiella pneumoniae isolates expressing extended spectrum beta-lactamases (ESBL) mediated by the bla CTX-M-15 gene from chronically infected wounds of Ghanaian patients. Bacterial isolates were subjected to combined short-read and long-read sequencing to obtain the sequences of their respective plasmids. In the bla CTX-M-15 -gene-carrying plasmids of the four ESBL-positive K. pneumoniae isolates, IncFIB/IncFII ( n = 3) and FIA ( n = 1) sequences were detected, while in the bla CTX-M-15 -gene-carrying plasmids of the three ESBL-positive E. coli isolates, IncFIA/IncFIB ( n = 2) and IncFIB ( n = 1) sequences were found. The three IncFIB/IncFII sequence-containing plasmids were almost identical to a K. pneumoniae plasmid reported from France. They belonged to the clonal lineages ST17, ST36 and ST39 of K. pneumoniae , suggesting transversal spread of this obviously evolutionary successful plasmid in Ghana. Other resistance gene-encoding plasmids observed in the assessed Enterobacterales harbored IncFIA/IncR and IncFII sequences. International spread was confirmed by the high genetic similarity to resistance-mediating plasmids published from Asia, Australia, Europe and Northern America, including a bla CTX-M-15 -gene-carrying plasmid isolated from a wild bird in Germany. In conclusion, the study contributed to the scarcely available information on the epidemiology of third-generation cephalosporine resistance-mediating plasmids in Ghana. Furthermore, the global spread of resistance-mediating plasmids provided hints on the evolutionary success of individual resistance-harboring plasmids by transversal spread among K. pneumoniae lineages in Ghana.

Prior to the implementation of new diagnostic techniques, a thorough evaluation is mandatory in order to ensure diagnostic reliability. If positive samples are scarcely available, however, such evaluations can be difficult to perform. Here, we evaluated four SeeGene Allplex real-time PCR assays amplifying a total of 28 bacteria, microsporidal and parasitic nucleic acid sequence targets in human stool samples in a multicentric approach. In the assessments with strongly positive samples, sensitivity values ranging between 13% and 100% were recorded for bacteria, between 0% and 100% for protozoa and between 7% and 100% for helminths and microsporidia; for the weakly positive samples, the recorded sensitivity values for bacteria ranged from 0% to 100%; for protozoa, from 0% to 40%; and for helminths and microsporidia, from 0% to 53%. For bacteria, the recorded specificity was in the range between 87% and 100%, while a specificity of 100% was recorded for all assessed PCRs targeting parasites and microsporidia. The intra- and inter-assay variations were generally low. Specifically for some helminth species, the sensitivity could be drastically increased by applying manual nucleic acid extraction instead of the manufacturer-recommended automatic procedure, while such effects were less obvious for the bacteria and protozoa. In summary, the testing with the chosen positive control samples showed varying degrees of discordance between the evaluated Allplex assays and the applied in-house reference assays associated with higher cycle threshold values in the Allplex assays, suggesting that samples with very low pathogen densities might be missed. As the targeted species can occur as harmless colonizers in the gut of individuals in high-endemicity settings as well, future studies should aim at assessing the clinical relevance of the latter hint.

Typhoidal and para-typhoidal Salmonella are major causes of bacteraemia in resource-limited countries. Diagnostic alternatives to laborious and resource-demanding serotyping are essential. Fourier transform infrared spectroscopy (FTIRS) is a rapidly developing and simple bacterial typing technology. In this study, we assessed the discriminatory power of the FTIRS-based IR Biotyper (Bruker Daltonik GmbH, Bremen, Germany), for the rapid and reliable identification of biochemically confirmed typhoid and paratyphoid fever-associated Salmonella isolates. In total, 359 isolates, comprising 30 S . Typhi, 23 S . Paratyphi A, 23 S . Paratyphi B, and 7 S . Paratyphi C, respectively and other phylogenetically closely related Salmonella serovars belonging to the serogroups O:2, O:4, O:7 and O:9 were tested. The strains were derived from clinical, environmental and food samples collected at different European sites. Applying artificial neural networks, specific automated classifiers were built to discriminate typhoidal serovars from non-typhoidal serovars within each of the four serogroups. The accuracy of the classifiers was 99.9%, 87.0%, 99.5% and 99.0% for Salmonella Typhi, Salmonella Paratyphi A, B and Salmonella Paratyphi C, respectively. The IR Biotyper is a promising tool for fast and reliable detection of typhoidal Salmonella . Hence, IR biotyping may serve as a suitable alternative to conventional approaches for surveillance and diagnostic purposes.

Wound infections are common medical problems in sub-Saharan Africa but data on the molecular epidemiology are rare. Within this study we assessed the clonal lineages, resistance genes and virulence factors of Gram-negative bacteria isolated from Ghanaian patients with chronic wounds. From a previous study, 49 Pseudomonas aeruginosa , 21 Klebsiella pneumoniae complex members and 12 Escherichia coli were subjected to whole genome sequencing. Sequence analysis indicated high clonal diversity with only nine P. aeruginosa clusters comprising two strains each and one E. coli cluster comprising three strains with high phylogenetic relationship suggesting nosocomial transmission. Acquired beta-lactamase genes were observed in some isolates next to a broad spectrum of additional genetic resistance determinants. Phenotypical expression of extended-spectrum beta-lactamase activity in the Enterobacterales was associated with bla CTX-M-15 genes, which are frequent in Ghana. Frequently recorded virulence genes comprised genes related to invasion and iron-uptake in E. coli , genes related to adherence, iron-uptake, secretion systems and antiphagocytosis in P. aeruginosa and genes related to adherence, biofilm formation, immune evasion, iron-uptake and secretion systems in K. pneumonia complex. In summary, the study provides a piece in the puzzle of the molecular epidemiology of Gram-negative bacteria in chronic wounds in rural Ghana.

Risk communication during pandemics is an element of utmost importance. Understanding the level of public attention-a prerequisite for effective communication-implicates expensive and time-consuming surveys. We hypothesise that the relative search volume from Google Trends could be used as an indicator of public attention of a disease and its prevention measures. The search terms 'RKI' (Robert Koch Institute, national public health authority in Germany), 'corona' and 'protective mask' in German language were shortlisted. Cross-correlations between these terms and the reported cases from 15 February to 27 April were conducted for each German federal state. The findings were contrasted against a timeline of official communications concerning COVID-19. The highest correlations of the term 'RKI' with reported COVID-19 cases were found between lags of - 2 and - 12 days, meaning web searches were already performed from 2 to 12 days before case numbers increased. A similar pattern was seen for the term 'corona'. Cross-correlations indicated that most searches on 'protective mask' were performed from 6 to 12 days after the peak of cases. The results for the term 'protective mask' indicate a degree of confusion in the population. This is supported by conflicting recommendations to wear face masks during the first wave. The relative search volumes could be a useful tool to provide timely and location-specific information on public attention for risk communication.

This study aimed to assess standard and harsher nucleic acid extraction schemes for diagnostic helminth real-time PCR approaches from stool samples. A standard procedure for nucleic acid extraction from stool and a procedure including bead-beating as well as proteinase K digestion were compared with group-, genus-, and species-specific real-time PCR assays targeting helminths and nonhelminth pathogens in human stool samples. From 25 different in-house and commercial helminth real-time PCR assays applied to 77 stool samples comprising 67 historic samples and 10 external quality assessment scheme samples positively tested for helminths, higher numbers of positive test results were observed after bead-beating-based nucleic acid extraction for 5/25 (20%) real-time PCR assays irrespective of specificity issues. Lower cycle threshold values were observed for one real-time PCR assay after the standard extraction scheme, and for four assays after the bead-beating-based scheme. Agreement between real-time PCR results after both nucleic acid extraction strategies according to Cohen's kappa ranged from poor to almost perfect for the different assays. Varying agreement was observed in eight nonhelminth real-time PCR assays applied to 67 historic stool samples. The study indicates highly variable effects of harsh nucleic acid extraction approaches depending on the real-time PCR assay used.

Although infection with the human enteropathogen Giardia lamblia causes self-limited diarrhea in adults, infant populations in endemic areas experience persistent pathogen carriage in the absence of diarrhea. The persistence of this protozoan parasite in infants has been associated with reduced weight gain and linear growth (height-for-age). The mechanisms that support persistent infection and determine the different disease outcomes in the infant host are incompletely understood. Using a neonatal mouse model of persistent G. lamblia infection, we demonstrate that G. lamblia induced bile secretion and used the bile constituent phosphatidylcholine as a substrate for parasite growth. In addition, we show that G. lamblia infection altered the enteric microbiota composition, leading to enhanced bile acid deconjugation and increased expression of fibroblast growth factor 15. This resulted in elevated energy expenditure and dysregulated lipid metabolism with reduced adipose tissue, body weight gain, and growth in the infected mice. Our results indicate that this enteropathogen's modulation of bile acid metabolism and lipid metabolism in the neonatal mouse host led to an altered body composition, suggesting how G. lamblia infection could contribute to growth restriction in infants in endemic areas., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The cause of acute encephalitis/meningoencephalitis in pediatric patients remains often unexplained despite extensive investigations for large panel of pathogens. To explore a possible viral implication, we investigated the virome of cerebrospinal fluid specimens of 70 febrile pediatric inpatients with clinical compatible encephalitis/meningoencephalitis. Using viral metagenomics, we detected and genetically characterized three novel human Torque teno mini virus (TTMV) species (TTMV-G1-3). Phylogenetically, TTMV-G1-3 clustered in three novel monophyletic lineages within genus Betatorquevirus of the Anelloviridae family. TTMV-G1-3 were highly prevalent in diseased children, but absent in the healthy cohort which may indicate an association of TTMV species with febrile illness. With 2/3 detected malaria co-infection, it remains unclear if these novel anellovirus species are causative agents or increase disease severity by interaction with malaria parasites. The presence of the viruses 28 days after initiating antimalarial and/or antibiotic treatment suggests a still active viral infection likely as effect of parasitic and/or bacterial co-infection that may have initiated a modulated immune system environment for viral replication or a defective virus clearance. This study increases the current knowledge on the genetic diversity of TTMV and strengthens that human anelloviruses can be considered as biomarkers for strong perturbations of the immune system in certain pathological conditions.

Melioidosis is an often fatal infectious disease with a protean clinical spectrum, caused by the environmental bacterial pathogen Burkholderia pseudomallei . Although the disease has been reported from some African countries in the past, the present epidemiology of melioidosis in Africa is almost entirely unknown. Therefore, the common view that melioidosis is rare in Africa is not evidence-based. A recent study concludes that large parts of Africa are environmentally suitable for B. pseudomallei . Twenty-four African countries and three countries in the Middle East were predicted to be endemic, but no cases of melioidosis have been reported yet. In this study, we summarize the present fragmentary knowledge on human and animal melioidosis and environmental B. pseudomallei in Africa and the Middle East. We propose that systematic serological studies in man and animals together with environmental investigations on potential B. pseudomallei habitats are needed to identify risk areas for melioidosis. This information can subsequently be used to target raising clinical awareness and the implementation of simple laboratory algorithms for the isolation of B. pseudomallei from clinical specimens. B. pseudomallei was most likely transferred from Asia to the Americas via Africa, which is shown by phylogenetic analyses. More data on the virulence and genomic characteristics of African B. pseudomallei isolates will contribute to a better understanding of the global evolution of the pathogen and will also help to assess potential differences in disease prevalence and outcome.