Genomic surveillance and antimicrobial resistance determinants in Neisseria gonorrhoeae isolates from Uganda, Malawi and South Africa, 2015-20.

OBJECTIVES: Global antimicrobial resistance (AMR) surveillance in Neisseria gonorrhoeae is essential. In 2017-18, only five (10.6%) countries in the WHO African Region reported to the WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO GASP). Genomics enhances our understanding of gonococcal populations nationally and internationally, including AMR strain transmission; however, genomic studies from Africa are extremely scarce. We describe the gonococcal genomic lineages/sublineages, including AMR determinants, and baseline genomic diversity among strains in Uganda, Malawi and South Africa, 2015-20, and compare with sequences from Kenya and Burkina Faso. METHODS: Gonococcal isolates cultured in Uganda (n = 433), Malawi (n = 154) and South Africa (n = 99) in 2015-20 were genome-sequenced. MICs were determined using ETEST. Sequences of isolates from Kenya (n = 159), Burkina Faso (n = 52) and the 2016 WHO reference strains (n = 14) were included in the analysis. RESULTS: Resistance to ciprofloxacin was high in all countries (57.1%-100%). All isolates were susceptible to ceftriaxone, cefixime and spectinomycin, and 99.9% were susceptible to azithromycin. AMR determinants for ciprofloxacin, benzylpenicillin and tetracycline were common, but rare for cephalosporins and azithromycin. Most isolates belonged to the more antimicrobial-susceptible lineage B (n = 780) compared with the AMR lineage A (n = 141), and limited geographical phylogenomic signal was observed. CONCLUSIONS: We report the first multi-country gonococcal genomic comparison from Africa, which will support the WHO GASP and WHO enhanced GASP (EGASP). The high prevalence of resistance to ciprofloxacin (and empirical use continues), tetracycline and benzylpenicillin, and the emerging resistance determinants for azithromycin show it is imperative to strengthen the gonococcal AMR surveillance, ideally including genomics, in African countries.

Cellular immune activation in cerebrospinal fluid from ugandans with cryptococcal meningitis and immune reconstitution inflammatory syndrome.

BACKGROUND: Human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is characterized by high fungal burden and limited leukocyte trafficking to cerebrospinal fluid (CSF). The immunopathogenesis of CM immune reconstitution inflammatory syndrome (IRIS) after initiation of antiretroviral therapy at the site of infection is poorly understood. METHODS: We characterized the lineage and activation status of mononuclear cells in blood and CSF of HIV-infected patients with noncryptococcal meningitis (NCM) (n = 10), those with CM at day 0 (n = 40) or day 14 (n = 21) of antifungal therapy, and those with CM-IRIS (n = 10). RESULTS: At diagnosis, highly activated CD8(+) T cells predominated in CSF in both CM and NCM. CM-IRIS was associated with an increasing frequency of CSF CD4(+) T cells (increased from 2.2% to 23%; P = .06), a shift in monocyte phenotype from classic to an intermediate/proinflammatory, and increased programmed death ligand 1 expression on natural killer cells (increased from 11.9% to 61.6%, P = .03). CSF cellular responses were distinct from responses in peripheral blood. CONCLUSIONS: After CM, T cells in CSF tend to evolve with the development of IRIS, with increasing proportions of activated CD4(+) T cells, migration of intermediate monocytes to the CSF, and declining fungal burden. These changes provide insight into IRIS pathogenesis and could be exploited to more effectively treat CM and prevent CM-IRIS.

A randomized controlled trial to evaluate the effectiveness of a board game on patients' knowledge uptake of HIV and sexually transmitted diseases at the Infectious Diseases Institute, Kampala, Uganda.

BACKGROUND: As the number of HIV infections continues to rise, the search for effective health education strategies must intensify. A new educational board game was developed to increase HIV peoples' attention and knowledge to HIV and sexually transmitted infections (STIs) information. The object of this study was to assess the effect of this educational board game on the uptake of knowledge. METHODS: A randomized controlled trial where patients attending the Infectious Diseases Clinic, Kampala, Uganda were randomized to either play the board game (intervention arm) or to attend a health talk (standard of care arm). Participants' knowledge was assessed before and after the education sessions through a questionnaire. RESULTS: One hundred eighty HIV-positive participants were enrolled, 90 for each study arm. The pretest scores were similar for each arm. There was a statistically significant increase in uptake of knowledge of HIV and STIs in both study arms. Compared with patients in the standard of care arm, participants randomized to the intervention arm had higher uptake of knowledge (4.7 points, 95% confidence interval: 3.9 to 5.4) than the controls (1.5 points, 95% confidence interval: 0.9 to 2.1) with a difference in knowledge uptake between arms of 3.2 points (P < 0.001). Additionally, both participants and facilitators preferred the board game to the health talk as education method. CONCLUSIONS: The educational game significantly resulted in higher uptake of knowledge of HIV and STIs. Further evaluation of the impact of this educational game on behavioral change in the short and long term is warranted.