Resistance of Common Circulating Enteric Bacterial Pathogens to Prescribed Antibiotics Among Under Five Years in Selected Public Hospitals in Kenya

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The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Performance of Ziehl-Neelsen Microscopy, Light Emitting Diode – FM and Xpert MTB/RIF in the Diagnosis of Tuberculosis in People with Presumptive TB from EAPHLNP study sites in Kenya

In Kenya, sputum smear microscopy, especially Ziehl-Neelsen (ZN) method has been the cornerstone for tuberculosis (TB) diagnosis at  most public health facilities. Recently, Led Emitted Diode (LED) fluorescent microscopy (FM) and Xpert MTB/ RIF (GeneXpert), have been introduced in selected health facilities for diagnosis of TB and Drug Resistant TB. This study was undertaken to determine and compare the performance (sensitivity, specificity, positive and negative predictive test values) of these two new TB diagnostics with ZN microscopy as a benchmark, LED/FM and GeneXpert using either LJ or MGIT culture, whichever was available or if one was positive while the other negative, as a gold standard. Methodology: A cross-sectional study was conducted between February 2013 and August 2014 in nine selected public health, facilities in Kenya. People with presumptive TB aged 18 years and above, both new and re-treatment cases attending the facilities with symptoms suggestive of TB (including cough of two or more weeks) were eligible for the study and consecutively recruited. Two sputum specimens (spot and early morning) were collected over two consecutive days. A total of 3073 sputum samples were collected from 1891 people with presumptive TB. The specimens from the study sites were appropriately packaged and shipped to the TB research laboratory in KEMRI, Nairobi, whereby samples were received and processed for ZN, LED, GeneXpert, LJ and MGIT culture in accordance with standard  procedures. Culture was used as a gold standard. The study was approved by the Ethical Review Committee of KEMRI. Results: A total of 639 specimens from 390 patients with culture results were included in the analysis. GeneXpert showed significantly  higher sensitivity (83.7% (95%CI: 76.6-90.8)) than ZN  6 African Journal of Health Sciences Volume 32, Issue No. 6, November - December, 2019 (65.4% (95% CI: 56.3-74.5)) and FM (68.3% (95% CI: 59.4-77.2)) microscopy methods in the diagnosis of TB. On the contrary, specificity of GeneXpert (87.9% (95% CI: 85.1-90.7)) was significantly lower than that of ZN (93.5% (95% CI: 91.4-95.6)) and FM (93.3% (95% CI: 91.295.4)) microscopy. GeneXpert sensitivity in smear positive culture positive was (95.6% (95% CI: 90.7-100.0)) and (97.2% (95% CI: 93.4-100.0)) for ZN and FM, respectively, it was significantly lower in smear negative culture positive specimens with (61.1% (95% CI: 45.2-77.0)) and (54.5% (95%CI: 37.5-71.5)) for ZN and FM, respectively. Sensitivity rate was significantly higher in specimens from non-previously treated with presumptive TB (71.1% (95%CI: 61.4-80.9)) for ZN, (73.5% (95% CI: 64.0-83.0)) for FM and (89.2% (95% CI: 82.5-95.9)) for GeneXpert than those from retreatment cases (42.9% (95% CI: 21.7-64.1)), (47.6% (95% CI: 26.2-69.0)) and (61.9% (95%CI: 41.1-82.7)), respectively. Overall, HIV status did not affect the performance of GeneXpert. However, Sensitivity of GeneXpert (84.4% (95% CI: 71.8-97.0)) was significantly higher in HIV positive than that of ZN (53.1% (95% CI: 35.8-70.4)) and FM (56.3% (95% CI: 39.1-73.5)) microscopy. There were no significant differences in sensitivity of ZN (70.8% (95% CI: 60.3-81.3)) and FM (73.6% (95% CI: 63.4-83.8)) in HIV negative specimens compared to sensitivity of ZN (53.1% (95% CI: 35.8-70.4)) and FM (56.3% (95% CI: 39.1-73.5)) in HIV positive specimens. A small proportion (6.2%) of specimens with ZN and culture negative results was positive by GeneXpert. Conclusions: Performance of GeneXpert was higher than both ZN and FM microscopy for diagnosis of TB in Kenya and is comparable with performance indicated in a few previous studies in Africa. Despite the low sensitivity in smear negative culture positive specimens, GeneXpert has potential to increase diagnostic yield in smear and culture negative specimens, especially from HIV positive people with presumptive TB. Further studies are required to ascertain its specificity and application in specific patient population. This will be possible when patients' clinical details are linked with respective laboratory data as a result of combination of tests to improve diagnostic yield. Key words: ZN, LED-FM; GeneXpert: Performance; Tuberculosis Diagnosis

Emerging Antimicrobial Resistance Patterns of Enteric Pathogens Isolated from Children under 5 years in EAPHLNP Satellite Sites in Kenya

Introduction: The emergence of resistance to antimicrobial agents in bacterial pathogens is a worldwideproblem that has been associated with inappropriate use in human and veterinary medicine.Epidemiological studies from several African countries by the year 2001 established that, diarrhoeawas the most common illness reported by the United States military service members deployed toAfrica for strategic training and contingency operations. Out of 15,000 US military personnel whoparticipated, more than 500 service members were affected by acute diarrhoea [7]. Objective: To determine the susceptibility of common circulating enteric bacterial pathogens to antimicrobials. Methodology: Between 12th February 2013 and 30th July 2014, a total of 420 children under 5 years of age with diarrhea were analyzed for bacterial enteric pathogens of which E. coli isolates were characterized by Polymerase Chain Reaction for the presence of virulence genes. Results:  Patients from whom bacterial enteric pathogens were isolated and identified from the 5 satellite sites were= 145, Wajir = 21, Malindi= 42, Kitale = 34, Machakos = 18 and Busia = 30 County Referral Hospitals. Antibiotic susceptibility testing was done on all isolates: pathogenic E. coli = 55, Salmonella =23 and Shigella =72 using disk-diffussion methods containing Ampicillin, Cefotaxime, Tetracycline, Erythromycin Gentamicin, Chloramphenicol, Trimethoprim / Sulphamethoxazole, Ciprofloxacin, Furasolidine and Nalidixic acid. E. coli, Shigella and Salmonella isolates showed up to 100% level of resistance to ampicillin, trimethoprin / sulphamethoxazole and erythromycin.Furthermore, pathogenic E. coli revealed tetracycline resistance ranging from 67% to 76% in all sites. Emerging resistance to ciprofloxacin ranged from 14.3% in Wajir to 50.0% in Machakos and gentamycin resistance ranged from 20% in Kitale to 100% in Wajir. Salmonella isolates showed levels of resistance ranging from 25% to 100% in Busia and 14% to 100% in Wajir for all the antimicrobials tested.Conclusion: Our findings on diarrhea due to enteric bacteria show that a high percentage is caused by antimicrobial-resistant strains, thus illustrating the effect of long-standing unregulated antimicrobial use. Most enteric pathogens easily share genes for antimicrobial  resistance. There was emerging resistance to newly prescribed antibiotics. This may have policy implications on the use of antibiotics in Keny