BACKGROUND
In low-resource settings, limited laboratory capacity adds to the burden of central nervous system (CNS) infections in children and spurs overuse of antibiotics. The commercially available BioFire® FilmArray® Meningitis/Encephalitis Panel (FA-ME) with its capability to simultaneously detect 14 pathogens in cerebrospinal fluid (CSF), could potentially narrow such a diagnostic gap.
METHODS
In Mbarara, Uganda, we compared clinical utility (clinical turnaround time [cTAT], microbial yield, and influence on patient outcome and antibiotic exposure) of FA-ME with bacterial culture, in children 0–12 years with suspected CNS infection.
RESULTS
Of 212 enrolled children, CSF was sampled from 194. All samples underwent bacterial culture, of which 193 also underwent FA-ME analyses. FA-ME analyses prospectively influenced care for 169 of the 193 patients, and they constituted an ‘Index group’. The remaining 43/212 patients constituted a ‘Reference group’. Of all 194 CSF-sampled patients, 87% (168) had received antibiotics before lumbar puncture. Median cTAT for FA-ME was 4.2 h, vs. two days for culture. Bacterial yield was 12% (24/193) and 1.5% (3/194) for FA-ME and culture, respectively. FA-ME viral yield was 12% (23/193). Fatality rate was 14% in the Index group vs. 19% in the Reference group (P = 0.20). From clinician receival of FA-ME results, median antibiotic exposure was 6 days for bacteria-negative vs. 13 days for bacteria-positive patients (P = 0.03). Median hospitalization duration was 7 vs. 12 days for FA-ME negative and positive patients, respectively (P < 0.01).
CONCLUSIONS
In this setting, clinical FA-ME utility was found in a higher and faster microbial yield and shortened hospitalization and antibiotic exposure of patients without CSF pathology. More epidemiologically customized pathogen panels may increase FA-ME utility locally, although its use in similar settings would require major cost reductions.
BACKGROUND
While the relationship between conflict-associated injuries and antimicrobial resistance is increasingly being elucidated, data concerning civilian casualties is sparse. This systematic review assesses literature focused on Global Antimicrobial Resistance Surveillance System (GLASS) Priority Pathogens causing infections in civilian wounds and burns in conflict-affected countries within the World Health Organisation's Eastern Mediterranean Region Office (EMRO)
METHODS
A systematic literature review was conducted following Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Five databases and grey literature were searched, identifying studies published from January 2010 to June 2024. Search terms included "wounds", "burns," "antimicrobial resistance", and the twelve countries of interest. Included studies reported resistance of GLASS pathogens. Two reviewers used Covidence to assess papers for inclusion. Data were extracted into a spreadsheet for analysis. Where quantitative data were available, medians, interquartile ranges and percentages were calculated by pathogen and country.
RESULTS
621 records were identified; 19 studies met inclusion criteria. Nine of the papers were from Iraq, three from Libya, three from Lebanon, one each from Yemen and Gaza; two reported on conflict affected refugees in Jordan. A total of 1,942 distinct microbiological isolates were reported, representing all four critical and high priority GLASS pathogen categories. Among the isolates, Staphylococcus aureus was the most prevalent (36.3%). Median resistances identified: Methicillin resistant Staphylococcus aureus (n = 680): 55.6% (IQR:49.65-90.3%); carbapenem resistant Pseudomonas aeruginosa (n = 372): 22.14% (7.43-52.22%); carbapenem resistant Acinetobacter baumannii (n = 366): 60.3% (32.1-85%); carbapenem resistant Klebsiella pneumoniae (n = 75): 12.65% (9.73-34.25%); ceftriaxone resistant Escherichia coli (n = 63): 76% (69-84.65%); ceftriaxone resistant Klebsiella pneumoniae (n = 40): 81.45% (76.73-86.18%). Only three studies had a low risk of bias.
DISCUSSION
Findings imply high rates of GLASS priority pathogens among wounded civilians in conflict-affected EMRO countries. However, evidence was heterogeneous, low quality and sparse in certain countries, highlighting the necessity of effective surveillance including standardised data collection. Improving primary data will facilitate the production of large, high-quality studies throughout the EMRO, including under-represented countries.
Conclusion: Laboratory diagnostic capacity building and improved surveillance in conflict-affected settings in the Eastern Mediterranean Region are required to assess the burden of GLASS priority pathogens in vulnerable non-combatant populations.
BACKGROUND
Hepatitis C virus (HCV) antibody self-testing (HCVST) may help expand screening access and support HCV elimination efforts. Despite potential benefits, HCVST is not currently implemented in Pakistan. This study aimed to assess the usability and acceptability of HCVST in a high HCV prevalence informal settlement in Karachi, Pakistan.
METHODS
We performed a cross-sectional study in a hepatitis C clinic from April through June 2023. Participants were invited to perform a saliva-based HCVST (OraSure Technologies, USA) while following pictorial instructions. A study member evaluated test performance using a standardized checklist and provided verbal support if a step could not be completed. Perceived usability and acceptability were assessed using a semi-structured questionnaire. The HCVST was considered successful if the participant was able to complete all steps and correctly interpret test results. Overall concordance and positive and negative agreement were estimated in comparison with the HCVST result read by the study member (inter-reader concordance and agreement) and result of a second rapid HCV test (Abbott Diagnostics Korea Inc, South Korea) performed by a trained user (inter-operator concordance and agreement).
RESULTS
The study included 295 participants of which 97 (32%) were illiterate. In total, 280 (95%, 95% CI 92–97%) HCVSTs were successful. Overall, 38 (13%) people performed the HCVST without verbal assistance, 67 (23%) needed verbal assistance in one step, 190 (64%) in two or more. Assistance was most often needed in managing the test buffer and test reading times. The inter-reader concordance was 96% and inter-operator concordance 93%. Inter-reader and inter-operator positive percent agreement were 84 and 70%, respectively. All participants reported they would use HCVST again and would recommend it to friends and family.
CONCLUSION
Saliva-based HCVST was very well accepted in this clinic-based setting. However, many people requested verbal support in several steps, highlighting the need for clear instructions for use and test devices that are simple to use, particularly in low literacy settings. Moderately low positive percent agreement with the results of a rapid test performed by a trained user highlights potential uncertainty in the accuracy of HCVST in the hands of lay users.
BACKGROUND
Improving treatment success rates among multi drug-resistant tuberculosis (MDR-TB) patients is critical to reducing its incidence and mortality, but adherence poses an important challenge. Video-based direct observed therapy (vDOT) may provide adherence benefits, while addressing the time and cost burden associated with community treatment supporter (CTS)-DOT. This study explored experiences of patients, family members and healthcare workers with different DOT modalities for adherence support in Eswatini.
METHODS
Between April 2021 and May 2022, thirteen men and five women with MDR-TB, ten healthcare workers, and nine caregivers were purposively sampled to include a range of characteristics and experiences with DOT modalities. Data were generated through individual in-depth interviews and a smartphone messaging application (WhatsApp). Data coding was undertaken iteratively, and thematic analysis undertaken, supported by Nvivo.
RESULTS
Four themes emerged that reflected participants’ experiences with different DOT modalities, including stigma, efficiency, perceived risks of TB acquisition, and patient autonomy. vDOT was appreciated by patients for providing them with privacy and shielding them from stigmatisation associated with being seen in TB clinics or with community treatment supporters. vDOT was also seen as more efficient than CTS-DOT. Health workers acknowledged that it saved time, allowing them to attend to more patients, while many patients found vDOT more convenient and less expensive by removing the need to travel for in-person consultations. Health workers also appreciated vDOT because it reduced risks of TB acquisition by minimising exposure through virtual patient monitoring. Although many patients appreciated greater autonomy in managing their illness through vDOT, others preferred human contact or struggled with making video recordings. Most family members appreciated vDOT, although some resented feeling removed from the process of supporting loved ones.
CONCLUSIONS
vDOT was generally appreciated by MDR-TB patients, their family members and health workers as it addressed barriers to adherence which could contribute to improved treatment completion rates and reduced workplace exposure. However, patients should be offered an alternative to vDOT such as CTS-DOT if this modality does not suit their circumstances or preferences.
In 2022, a Sudan virus disease (SVD) outbreak occurred in Uganda, resulting in 142 confirmed cases, most in Mubende and Kassanda districts. We determined risk factors for Sudan virus (SUDV) infection among household members (HHM) of cases.
METHODS
We conducted a case-control and retrospective cohort study in January 2023. Cases were RT-PCR-confirmed SUDV infection in residents of Mubende or Kassanda districts during the outbreak. Case-households housed a symptomatic, primary case-patient for ≥24 hours and had ≥1 secondary case-patient with onset <2 weeks after their last exposure to the primary case-patient. Control households housed a case-patient and other HHM but no secondary cases. A risk factor questionnaire was administered to the primary case-patient or another adult who lived at home while the primary case-patient was ill. We conducted a retrospective cohort study among case-household members and categorized their interactions with primary case-patients during their illnesses as none, minimal, indirect, and direct contact. We conducted logistic regression to explore associations between exposures and case-household status, and Poisson regression to identify risk factors for SUDV infection among HHM.
RESULTS
Case- and control-households had similar median sizes. Among 19 case-households and 51 control households, primary case-patient death (adjusted odds ratio [ORadj]=7.6, 95% CI 1.4-41) and ≥2 household bedrooms (ORadj=0.19, 95% CI 0.056-0.71) were associated with case-household status. In the cohort of 76 case-HHM, 44 (58%) were tested for SUDV <2 weeks from their last contact with the primary case-patient; 29 (38%) were positive. Being aged ≥18 years (adjusted risk ratio [aRRadj]=1.9, 95%CI: 1.01-3.7) and having direct or indirect contact with the primary case-patient (aRRadj=3.2, 95%CI: 1.1-9.7) compared to minimal or no contact increased risk of SVD. Access to a handwashing facility decreased risk (aRRadj=0.52, 95%CI: 0.31-0.88).
CONCLUSION
Direct contact, particularly providing nursing care for and sharing sleeping space with SVD patients, increased infection risk among HHM. Risk assessments during contact tracing may provide evidence to justify closer monitoring of some HHM. Health messaging should highlight the risk of sharing sleeping spaces and providing nursing care for persons with Ebola disease symptoms and emphasize hand hygiene to aid early case identification and reduce transmission.
In 2018, the World Health Organization commenced a multi-country validation study of the Cepheid GeneXpert for a range of molecular-based point-of-care (POC) tests in primary care settings. One study arm focused on the evaluation of POC tests for screening ‘women at risk’ for chlamydia (CT), gonorrhoea (NG) and trichomonas (TV) in four countries – Australia, Guatemala, Morocco and South Africa.
METHODS
Study participants completed a pre-test questionnaire which included demographics, clinical information and general questions on POC testing (POCT). Two vaginal swab samples (either self-collected or clinician collected) from each patient were tested on the GeneXpert at the POC and at a reference laboratory using quality-assured nucleic acid amplification tests (NAATs).
RESULTS
One thousand three hundred and eighty-three women were enrolled: 58.6% from South Africa, 29.2% from Morocco, 6.2% from Guatemala, and 6.0% from Australia. 1,296 samples for CT/NG and 1,380 samples for TV were tested by the GeneXpert and the reference NAAT. The rate of unsuccessful tests on the GeneXpert was 1.9% for CT, 1.5% for NG and 0.96% for TV. The prevalence of CT, NG and TV was 31%, 13% and 23%, respectively. 1.5% of samples were positive for all three infections; 7.8% were positive for CT and NG; 2.4% were positive for NG and TV; and 7.3% were positive for CT and TV. Compared to reference NAATs, pooled estimates of sensitivity for the GeneXpert tests were 83.7% (95% confidence intervals 69.2-92.1) for CT, 90.5% (85.1-94.1) for NG and 64.7% (58.1-70.7) for TV (although estimates varied considerably between countries). Estimates for specificity were ≥96% for all three tests both within- and between-countries. Pooled positive and negative likelihood ratios were: 32.7 ([CI] 21.2-50.5) and 0.17 (0.08-0.33) for CT; 95.3 (36.9-245.7) and 0.10 (0.06-0.15) for NG; and 56.5 (31.6-101.1) and 0.35 (0.27-0.47) for TV.
CONCLUSION
This multi-country evaluation is the first of its kind world-wide. Positive likelihood ratios, as well as specificity estimates, indicate the GeneXpert POC test results for CT, NG and TV were clinically acceptable for ruling in the presence of disease. However, negative likelihood ratios and variable sensitivity estimates from this study were poorer than expected for ruling out these infections, particularly for TV.
Adolescents living with HIV/AIDS (ALHIV) are a particularly vulnerable but often overlooked group in the HIV response despite additional disease management challenges.
METHODS:
All ALHIV (10-19 years), on ART for ≥6 months, presenting to care at a Médecins Sans Frontières (MSF) clinic in Myanmar from January-April 2016 were eligible for the quantitative study component (clinical history, medical examination, laboratory investigation). A subset of these respondents were invited to participate in qualitative interviews. Interviews and focus groups were also conducted with other key informants (care givers, clinicians).
RESULTS:
Of 177 ALHIV, 56% (100) were aged 9-13 years and 77 (44%) were 14-19. 49% (86) had been orphaned by one parent, and 19% (33) by both. 59% (104) were severely underweight (BMI < 16). 47% presented with advanced HIV (WHO stage III/IV). 93% were virally supressed (< 250 copies/mL). 38 (21%) of ALHIV were on a second-line ART after first-line virological failure. Qualitative interviewing highlighted factors limiting adherence and the central role that HIV counsellors play for both ALHIV patients and caregivers.
CONCLUSIONS:
Our study shows good clinical, immunological, and virological outcomes for a cohort of Myanmar adolescents living with HIV, despite a majority being severely underweight, presenting with Stage III or IV illness, and the prevalence of comorbid infections (TB). Many treatment and adherence challenges were articulated in qualitative interviewing but emphasized the importance of actively engaging adolescents in their treatment. Comprehensive HIV care for this population must include routine viral load testing and social support programs.
