Recent increase in low complexity polygenomic infections and sialic acid-independent invasion pathways in Plasmodium falciparum from Western Gambia.

BACKGROUND: The malaria parasite Plasmodium falciparum utilizes multiple alternative receptor-ligand interactions for the invasion of human erythrocytes. While some P. falciparum clones make use of sialic acid (SA) residues on the surface of the human glycophorin receptors to invade the erythrocyte, others use alternative receptors independent of sialic acid residues. We hypothesized that over the years, intensified malaria control interventions and declining prevalence in The Gambia have resulted in a selection of parasites with a dominant invasion pathways and ligand expression profiles. METHODS: Blood samples were collected from 65 malaria-infected participants with uncomplicated malaria across 3 years (2015, 2016, and 2021). Genetic diversity was determined by genotyping the merozoite surface protein 2 (msp2) polymorphic gene of P. falciparum. Erythrocyte invasion phenotypes were determined using neuraminidase, trypsin, and chymotrypsin enzymes, known to cleave different receptors from the surface of the erythrocyte. Schizont-stage transcript levels were obtained for a panel of 6 P. falciparum invasion ligand genes (eba175, eba181, Rh2b, Rh4, Rh5, and clag2) using 48 successfully cultured isolates. RESULTS: Though the allelic heterozygosity of msp2 repeat region decreased as expected with reduced transmission, there was an increase in infections with more than a single msp2 allelotype from 2015 to 2021. The invasion phenotypes of these isolates were mostly SA independent with a continuous increase from 2015 to 2021. Isolates from 2021 were highly inhibited by chymotrypsin treatment compared to isolates from 2015 and 2016. Higher invasion inhibition for 2021 isolates was further obtained following erythrocyte treatment with a combination of chymotrypsin and trypsin. The transcript levels of invasion ligand genes varied across years. However, levels of clag2, a rhoptry-associated protein, were higher in 2015 and 2016 isolates than in 2021 isolates, while Rh5 levels were higher in 2021 compared to other years. CONCLUSIONS: Overall, these findings suggest increasing mixed infections with an increase in the use of sialic-acid independent invasion pathways by P. falciparum clinical isolates in the Western part of Gambia.

Longitudinal Analysis of the Impacts of Urogenital Schistosomiasis on the Gut microbiota of Adolescents in Nigeria.

The gut microbiome is important for many host physiological processes and helminths and these interactions may lead to microbial changes. We carried out a longitudinal study of the impacts of S. haematobium infection on the gut microbiome of adolescents (11-15 years) in northern Nigeria pre and post praziquantel treatment. Using 16S sequencing a total of 267 DNA from faecal samples of infected versus uninfected adolescents were amplified and sequenced on an Illumina Miseq. We assessed the diversity of the taxa using alpha diversity metrices and observed that using Shannon index we obtained significant differences when we compared infected samples at 3, 9 and 12 months to baseline uninfected controls (P= <0.0001, P=0.0342 and P=0.0003 respectively). Microbial community composition analysis revealed that there were only significant differences at 3, 9 and 12 months (P=0.001, P=0.001, P=0.001 and P=0.001, respectively). We also demonstrated that the effects of the infection on the gut was more significant than praziquantel. Overall, our data suggests that S. haematobium, a non-gut resident parasite has indirect interactions with the gut. The bacterial taxa changes we have identified opens up the opportunity to investigate their role in human health, especially in urogenital schistosomiasis endemic communities.

Molecular detection of drug resistant polymorphisms in Plasmodium falciparum isolates from Southwest, Nigeria.

OBJECTIVE: Nigeria bears 25% of global malaria burden despite concerted efforts towards its control and elimination. The emergence of drug resistance to first line drugs, artemisinin combination therapies (ACTs), indicates an urgent need for continuous molecular surveillance of drug resistance especially in high burden countries where drug interventions are heavily relied on. This study describes mutations in Plasmodium falciparum genes associated with drug resistance in malaria; Pfk13, Pfmdr1, PfATPase6 and Pfcrt in isolates obtained from 83 symptomatic malaria patients collected in August 2014, aged 1-61 years old from South-west Nigeria. RESULTS: Two Pfmdr1, N86 and Y184 variants were present at a prevalence of 56% and 13.25% of isolates respectively. There was one synonymous (S679S) and two non-synonymous (M699V, S769M) mutations in the PATPase6 gene, while Pfcrt genotype (CVIET), had a prevalence of 45%. The Pfk13 C580Y mutant allele was suspected by allelic discrimination in two samples with mixed genotypes although this could not be validated with independent isolation or additional methods. Our findings call for robust molecular surveillance of antimalarial drug resistance markers in west Africa especially with increased use of antimalarial drugs as prophylaxis for Covid-19.

Beyond SARS-CoV-2: Lessons That African Governments Can Apply in Preparation for Possible Future Epidemics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has placed unprecedented pressure on healthcare systems, even in advanced economies. While the number of cases of SARS-CoV-2 in Africa compared to other continents has so far been low, there are concerns about under-reporting, inadequate diagnostic tools, and insufficient treatment facilities. Moreover, proactiveness on the part of African governments has been under scrutiny. For instance, issues have emerged regarding the responsiveness of African countries in closing international borders to limit trans-continental transmission of the virus. Overdependence on imported products and outsourced services could have contributed to African governments' hesitation to shut down international air and seaports. In this era of emerging and re-emerging pathogens, we recommend that African nations should consider self-sufficiency in the health sector as an urgent priority, as this will not be the last outbreak to occur. In addition to the Regional Disease Surveillance Systems Enhancement fund (US$600 million) provided by the World Bank for strengthening health systems and disease surveillance, each country should further establish an epidemic emergency fund for epidemic preparedness and response. We also recommend that epidemic surveillance units should create a secure database of previous and ongoing pandemics in terms of aetiology, spread, and treatment, as well as financial management records. Strategic collection and analysis of data should also be a central focus of these units to facilitate studies of disease trends and to estimate the scale of requirements in preparation and response to any future pandemic or epidemic.

Translation of genomic epidemiology of infectious pathogens: Enhancing African genomics hubs for outbreaks.

BACKGROUND: Deadly emerging infectious pathogens pose an unprecedented challenge to health systems and economies, especially across Africa, where health care infrastructure is weak, and poverty rates remain high. Genomic technologies are vital for enhancing the understanding and development of intervention approaches against these pathogens, including Ebola and the novel coronavirus disease 2019 (COVID-19). DISCUSSION: Africa has contributed few genomes of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) to the global pool in growing open access repositories. To bridge this gap, the Africa Centre for Disease Control and Prevention (ACDC) is coordinating continent-wide initiatives to establish genomic hubs in selected well-resourced African centres of excellence. This will allow for standardisation and efficient and rapid data generation and curation. However, the strategy to ensure capacity for high-throughput genomics at selected hubs should not overshadow the deployment of portable, field-friendly and technically less demanding genomics technologies in all affected countries. This will enhance small-scale local genomic surveillance in outbreaks, leaving validation and large-scale approaches to be taken at central genomic hubs. CONCLUSION: The ACDC needs to scale-up its campaign for government support across African Union countries to ensure the sustainable financing of its strategy for increased pathogen genomic intelligence and other interventions in current and inevitable future epidemics in Africa.

Sustainable Elimination (Zero Cases) of Sleeping Sickness: How Far Are We from Achieving This Goal?

The recent massive reduction in the numbers of fresh Human African Trypanosomiasis (HAT) infection has presented an opportunity for the global elimination of this disease. To prevent a possible resurgence, as was the case after the reduced transmission of the 1960s, surveillance needs to be sustained and the necessary tools for detection and treatment of cases need to be made available at the points of care. In this review, we examine the available resources and make recommendations for improvement to ensure the sustenance of the already achieved gains to keep the trend moving towards elimination.

Urogenital schistosomiasis is associated with signatures of microbiome dysbiosis in Nigerian adolescents.

Urogenital schistosomiasis is a neglected tropical disease caused by the parasite Schistosoma haematobium, which resides in the vasculature surrounding the urogenital system. Previous work has suggested that helminthic infections can affect the intestinal microbiome, and we hypothesized that S. haematobium infection could result in an alteration of immune system-microbiota homeostasis and impact the composition of the gut microbiota. To address this question, we compared the fecal microbiomes of infected and uninfected schoolchildren from the Argungu Local Government Area of Kebbi State, Nigeria, detecting significant differences in community composition between the two groups. Most remarkably, we observed a decreased abundance of Firmicutes and increased abundance of Proteobacteria - a shift in community structure which has been previously associated with dysbiosis. More specifically, we detected a number of changes in lower taxa reminiscent of inflammation-associated dysbiosis, including decreases in Clostridiales and increases in Moraxellaceae, Veillonellaceae, Pasteurellaceae, and Desulfovibrionaceae. Functional potential analysis also revealed an enrichment in orthologs of urease, which has been linked to dysbiosis and inflammation. Overall, our analysis indicates that S. haematobium infection is associated with perturbations in the gut microbiota and may point to microbiome disruption as an additional consequence of schistosome infection.

Effects of host-derived chemokines on the motility and viability of Trypanosoma brucei.

African trypanosomes (Trypanosoma brucei spp.) are extracellular, hemoflagellate, protozoan parasites. Mammalian infection begins when the tsetse fly vector injects trypanosomes into the skin during blood feeding. The trypanosomes then reach the draining lymph nodes before disseminating systemically. Intravital imaging of the skin post-tsetse fly bite revealed that trypanosomes were observed both extravascularly and intravascularly in the lymphatic vessels. Whether host-derived cues play a role in the attraction of the trypanosomes towards the lymphatic vessels to aid their dissemination from the site of infection is not known. Since chemokines can mediate the attraction of leucocytes towards the lymphatics, in vitro chemotaxis assays were used to determine whether chemokines might also act as chemoattractants for trypanosomes. Although microarray data suggested that the chemokines CCL8, CCL19, CCL21, CCL27 and CXCL12 were highly expressed in mouse skin, they did not stimulate the chemotaxis of T brucei. Certain chemokines also possess potent antimicrobial properties. However, none of the chemokines tested exerted any parasiticidal effects on T brucei. Thus, our data suggest that host-derived chemokines do not act as chemoattractants for T brucei. Identification of the mechanisms used by trypanosomes to establish host infection will aid the development of novel approaches to block disease transmission.

Typhoid Fever Diagnosis in Endemic Countries: A Clog in the Wheel of Progress?

Typhoid fever causes significant morbidity and mortality in developing countries, with inaccurate estimates in some countries affected, especially those situated in Sub-Saharan Africa. Disease burden assessment is limited by lack of a high degree of sensitivity and specificity by many current rapid diagnostic tests. Some of the new technologies, such as PCR and proteomics, may also be useful but are difficult for low-resource settings to apply as point-of-care diagnostics. Weak laboratory surveillance systems may also contribute to the spread of multidrug resistant Salmonella serovar Typhi across endemic areas. In addition, most typhoid-endemic countries employ serological tests that have low sensitivity and specificity making diagnosis unreliable. Here we review currently available typhoid fever diagnostics, and advances in serodiagnosis of S. Typhi.

Tools for Detection of Schistosomiasis in Resource Limited Settings.

Schistosomiasis is a debilitating disease affecting over 200 million people, with the highest burden of morbidity and mortality in African countries. Despite its huge impact on the health and socio-economic burden of the society, it remains a neglected tropical disease, with limited attention from governments and stakeholders in healthcare. One of the critical areas that is hugely under-developed is the development of accurate diagnostics for both intestinal and urogenital schistosomiasis. Diagnosis of schistosomiasis is important for the detection and treatment of disease in endemic and non-endemic settings. A conclusive detection method is also an indispensable part of treatment, both in the clinic and during mass drug administration (MDA), for the monitoring efficacy of treatment. Here, we review the available diagnostic methods and discuss the challenges encountered in diagnosis in resource limited settings. We also present the available diagnostics and cost implications for deployment in resource limited settings. Lastly, we emphasize the need for more funding directed towards the development of affordable diagnostic tools that is affordable for endemic countries as we work towards the elimination of the disease.

Self-Medication with Antibiotics, Attitude and Knowledge of Antibiotic Resistance among Community Residents and Undergraduate Students in Northwest Nigeria.

This study set out to evaluate self-medicated antibiotics and knowledge of antibiotic resistance among undergraduate students and community members in northern Nigeria. Antibiotic consumption pattern, source of prescription, illnesses commonly treated, attitude towards antibiotics, and knowledge of antibiotic resistance were explored using a structured questionnaire. Responses were analyzed and summarized using descriptive statistics. Of the 1230 respondents from undergraduate students and community members, prescription of antibiotics by a physician was 33% and 57%, respectively, amongst undergraduate students and community members. We tested the respondents’ knowledge of antibiotic resistance (ABR) and found that undergraduate students displayed less knowledge that self-medication could lead to ABR (32.6% and 42.2% respectively). Self-medication with antibiotics is highly prevalent in Northwest Nigeria, with most medicines being purchased from un-licensed stores without prescription from a physician. We also observed a significant gap in respondents’ knowledge of ABR. There is an urgent need for public health authorities in Nigeria to enforce existing laws on antibiotics sales and enlighten the people on the dangers of ABR.

Current status of cerebrospinal meningitis and impact of the 2015 meningococcal C vaccination in Kebbi, Northwest Nigeria.

INTRODUCTION: Following the significant reduction of Neisseria meningitidis A (NmA) in most parts of northern Nigeria, a new strain of Neisseria meningitidis C (NmC) emerged in 2013 causing outbreaks in the north and recently spreading to southern parts of the Nigeria. This study provides detailed epidemiological investigation in the last four years. METHODS: Analysis of confirmed and suspected cases of meningitis in Kebbi, Nigeria from 2014 to June 2017 detected through Integrated Disease Surveillance and Response. RESULTS: Of the 2776 cases, 1568 were males, and 1208 females. The median age of males and females was 10 and 11 years (Interquartile range of ages is 9 years) respectively. The attack rate (AR) per 100,000 in the state between 2014 and 2017 was 13.2, 46.7, 2.2 and 3.2 respectively. Case fatality rate (CFR) in 2014 was highest in the 4 years analysed at 13.8%. Binary logistic regression analysis suggests that the odds of confirmation of meningitis was 3.6 (Odds ratio, OR 3.60, 95% CI 1.58-8.2; p = 0.002) times as high in the age group 6-10 years and 2.4 times in the age group 11-19 years compared to the age group 0-5 years (OR 2.44, 95% CI 1.09-5.48; p = 0.03). An epidemic of NmC in 2015, led to a reactive vaccination campaign in selected wards in Aliero and Jega targeting age groups 1-29 years old, with a coverage of 72% and 51% respectively. In 2016-2017 Aliero and Jega local government areas (LGA) had no recorded deaths due to meningitis, a significant improvement over 2015 mortality rates (MR) per 100,000 of 33.4 and 12.2 respectively. CONCLUSION: The CFR in the state is still very high, suggesting the need for a more coordinated approach aimed at improving disease notification and early treatment. Vaccination in Aliero and Jega LGAs have demonstrated the usefulness of meningococcal C vaccine in reduction of morbidity and mortality.